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Adkins, Jordan M. "Anterior Cingulate Cortex and Dorsal Hippocampal Glutamate Receptors Mediate Generalized Fear in Female Rats." Kent State University / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=kent1544527648769848.
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Siegel-Ramsay, Jennifer Eileen. "Dorsal anterior cingulate cortex glutamate concentrations and their relationships in adults with autism spectrum disorder." Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/33096.
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Previous studies have reported altered glutamate (Glu) concentrations in the blood and brain of individuals with autism spectrum disorder (ASD) compared to neurotypical controls (NC), but the direction (increased or decreased) of metabolite differences is still unclear. Moreover, the relationship between Glu and both brain function and clinical manifestations of the disorder require further investigation. Within this study, we investigated metabolite concentrations within the dorsal anterior cingulate cortex (dACC), a brain region functionally associated with inhibitory executive control tasks and also part of the salience network. There were 19 participants with ASD and 20 NCs between the ages of 23 and 58 years who participated in this study. A study clinician administered the Autism Diagnostic Observation Schedule (ADOS) to individuals with ASD to further confirm their diagnosis. In addition, all participants in this study completed assessments of general intelligence and attention, which included an inhibitory executive control task. Researchers also acquired in vivo single-voxel proton magnetic resonance spectroscopy (1H-MRS) in the dACC to quantify both Glu and combined Glu and glutamine (Glx) concentrations. We hypothesised that these metabolite concentrations would be altered (decreased or increased) in adult participants with ASD compared to NCs and would correlate with inhibitory performance and ASD severity in individuals with ASD. Participants also underwent a resting-state functional magnetic resonance imaging (fMRI) scan to assess the relationship between functional connectivity and Glu and Glx concentrations. We also hypothesised that there would be an altered relationship between local Glu and Glx concentrations and seed-based functional connectivity in adults with ASD compared to NCs. There were no significant group differences in Glu or Glx concentrations between individuals with ASD and NCs. Furthermore, we did not find any relationship between metabolite concentrations and either inhibitory performance or clinical symptoms of the disorder. This evidence suggests that increased or decreased Glu and Glx concentrations were not a core marker of altered brain function in the dACC in this group of adult individuals with ASD. When individuals taking psychotropic medications were excluded from the analysis, there was a significant interaction between age and group for Glx concentrations. This evidence weakly suggests disease-specific variations in Glx concentrations over the lifespan of an individual with ASD. Nevertheless, this result did not survive correction for multiple comparisons and requires further replication. In our final experiment, we reported that Glu concentrations were negatively correlated with right and left dACC seed-based resting-state functional connectivity to the left medial temporal lobe only in individuals with ASD. We also reported an interaction between groups in the association between Glx concentrations and both left and right dACC functional connectivity to other salience network regions including the insular cortex. This evidence suggests that local Glu and Glx concentrations were incongruent with long-distance functional connectivity in individuals with ASD. This analysis was largely exploratory, but further investigation and replication of these relationships may further explain the pathophysiology of the disorder as well as provide a useful marker for therapeutic intervention.
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Rahman, Sufia Saburan. "Differential contributions of subregions of the dorsal anterior cingulate cortex to negative emotion in the common marmoset." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/277913.
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The dorsal anterior cingulate cortex (dACC) has been implicated in a broad range of cognitive and emotional functions, including the processing of negative emotion. Furthermore, abnormalities in dACC activity have been associated with anxiety and depression, disorders in which negative emotion is dysregulated. Thus, a better understanding of the precise contributions of the dACC to negative emotion could give us important insights into the neurobiological mechanisms underlying these debilitating neuropsychiatric disorders. However, despite extensive study of the dACC, its precise role in negative emotion is unclear. Instead there is mounting evidence that rather than being one functionally homogeneous region, subregions of the dACC may have distinct functional roles. This evidence is largely correlational, and interventional studies in experimental animals are required to address this. Accordingly, the work in this thesis causally assessed the contributions of two spatially distinct subregions of the dACC (rostral and caudal) to the regulation of the behavioural and cardiovascular correlates of negative emotion in the common marmoset (Callithrix jacchus). These dACC subregions were targeted with indwelling cannulae to enable pharmacological manipulations to be carried out in a range of tasks, used to assess distinct components of negative emotion, such as conditioned fear and anxiety. The findings suggest that the rostral dACC and the caudal dACC do indeed have distinct contributions to the expression of negative emotion and the regulation of anxiety, respectively. Furthermore, an assessment of the anterograde projections of these subregions provides anatomical support for the observed functional differences.
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Hussain, Muhammad Zubair. "Molecular Adaptations in the Endogenous Opioid System in Human and Rodent Brain." Doctoral thesis, Uppsala universitet, Institutionen för farmaceutisk biovetenskap, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-205133.
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The aims of the thesis were to examine i) whether the endogenous opioid system (EOS) is lateralized in human brain areas involved in processing of emotions and pain; ii) whether EOS responses to unilateral brain injury depend on side of lesion, and iii) whether in human alcoholics, this system is involved in molecular adaptations in brain areas relevant for cognitive control of addictive behavior and habit formation. The main findings were that (1) opioid peptides but not opioid receptors and classic neurotransmitters are markedly lateralized in the anterior cingulate cortex involved in processing of positive and negative emotions and affective component of pain. The region-specific lateralization of neuronal networks expressing opioid peptides may underlie in part lateralization of higher functions in the human brain including emotions and pain. (2) Analysis of the effects of traumatic brain injury (TBI) demonstrated predominant alteration of dynorphin levels in the hippocampus ipsilateral to the injury, while injury to the right hemisphere affected dynorphin levels in the striatum and frontal cortex to a greater extent than that to the left hemisphere. Thus, trauma reveals a lateralization in the mechanisms mediating the response of dynorphin expressing neuronal networks in the brain. These networks may differentially mediate effects of left or right brain injury on lateralized brain functions. (3) In human alcoholics, the enkephalin and dynorphin systems were found to be downregulated in the caudate nucleus and / or putamen that may underlie in part changes in goal directed behavior and formation of a compulsive habit in alcoholics. In contrast to downregulation in these areas, PDYN mRNA and dynorphins in dorsolateral prefrontal cortex, k-opioid receptor mRNA in orbitofrontal cortex, and dynorphins in hippocampus were upregulated in alcoholics. Activation of the k-opioid receptor by upregulated dynorphins may underlie in part neurocognitive dysfunctions relevant for addiction and disrupted inhibitory control. We conclude that the EOS exhibits region-specific lateralization in human brain and brain-area specific lateralized response after unilateral TBI in mice; and that the EOS is involved in adaptive processes associated with specific aspects of alcohol dependence.
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Feroz, Farah Shahnaz [Verfasser], and Christoph [Akademischer Betreuer] Mulert. "Time Course of the Dorsal and Rostral-Ventral Anterior Cingulate Cortex Reveals the Influence of Emotional Valence and Arousal on Cognitive Control in Healthy Subjects and Patients With Schizophrenia / Farah Shahnaz Feroz ; Betreuer: Christoph Mulert." Hamburg : Staats- und Universitätsbibliothek Hamburg, 2018. http://d-nb.info/1168380928/34.
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Syme, Catriona. "Cardiovascular reactivity and the anterior cingulate cortex." Thesis, McGill University, 2005. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=98504.
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Relationships between cardiovascular and neural activities were explored in 11 patients with intractable epilepsy. Using depth electrodes, we examined the cardiovascular response to direct electrical stimulation, and monitored EEG activity during simple physical and mental challenges known to elicit a cardiovascular response. Stimulation was most commonly performed in four regions: the hippocampus, amygdala, and the supra- and sub-callosal anterior cingulate cortex (ACC). While increases in systolic blood pressure (SBP) in response to electrical stimulation of these brain regions were observed with equal frequency, a striking cardiovascular response was observed in one patient when stimulating the supracallosal ACC (an increase in SBP of almost 50 mmHg). Cross-correlation analysis revealed significant relationships between EEG power and SBP during physical but not mental challenges, and the pattern of these relationships was only observed for power of EEG data recorded from the ACC. The observed relative timing of the correlations was consistent in the three patients whose SBP increased upon ACC stimulation. These results support the role of the ACC in cardiovascular regulation, as revealed in previous studies in experimental animals.
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Apps, Matthew. "Anterior cingulate cortex : contributions to social cognition." Thesis, Royal Holloway, University of London, 2012. http://repository.royalholloway.ac.uk/items/ed1f2ffb-d93b-e7fa-1121-846d7f34efd8/9/.
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It has been suggested that the Anterior Cingulate Cortex (ACC) plays an important role in decision-making. Activity in this area reflects processing related to two principles of Reinforcement Learning Theory (RLT): (i) signalling the predicted value of actions at the time they are instructed and (ii) signalling prediction errors at the time of the outcomes of actions. It has been suggested that neurons in the gyrus of the ACC (ACCg) process information about others' decisions and not one's own. An important aim of this thesis is to investigate whether the ACCg processes others' decisions in a manner that conforms to the principles of RLT. Four fMRI experiments investigate activity in the ACCg at the time of cues that signal either the predicted value of others' actions or that signal another's predictions are erroneous. • Experiment 1: Activity in the ACCg occurred when the outcome of another's decision was unexpectedly positive. • Experiment 2: Activity in the ACCg varied parametrically with the discrepancy between another's prediction of an outcome and the actual outcome known by the subject, in a manner that conformed to the computational principles of RLT. • Experiment 3: Activity in the ACCg varied with the predicted value of a reward, discounted by the amount of effort required to obtain it. • Experiment 4: Activity in the ACCg varied with the value of delayed rewards that were discounted in a manner that conformed to a social norm. These results support the hypothesis that the ACCg processes the predicted value of others' actions and also signals when others' predictions about the value of their actions are erroneous, in a manner that conforms to the principles of RLT.
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Ma, Liya. "Coding of sequential behaviors by anterior cingulate cortex ensembles." Thesis, University of British Columbia, 2014. http://hdl.handle.net/2429/48442.
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The anterior cingulate cortex (ACC) has been implicated in a myriad of different functions. Converging evidence suggests that the ACC continuously monitors and evaluates actions and their consequences. Such functions are essential in representing action sequences which are the building blocks of all complex behaviors. This dissertation seeks to delineate how ACC neuronal ensembles represent different types of information with special emphasis on action sequences.
Chapter 2 shows that the ACC ensembles represents different action sequences via unique activity patterns that change if the order of the actions are altered or if the locations of the actions is changed. Interestingly such shifts are achieved when overall levels of activity remain fixed.
Chapter 3 reveals a very different arrangement in which progression through a sequence of actions towards a goal is associated with a change in the overall level of neural activity without a significant change in the patterns of activity. Specifically, ACC ensembles display a smooth progressive change in overall activity over three lever press actions that culminate in a reward. In contrast, the dorsal striatal (DS) ensembles recorded simultaneously from the same animals display fluctuations in activity level that are tightly linked to each action. Together these two chapters show that the ACC may use two different firing rate-related codes to convey categorical versus continuous forms of information.
Chapter 4 provides a further examination of the mechanisms which allows the ACC ensembles to encode multiple types of categorical information. While the DS neurons encode both the sequence and the location of the levers in a somewhat synchronized fashion, ACC neurons encoded both of these types of information but kept them functionally segregated. As a result, even though ACC single neurons were no better than the DS in sequence decoding, sequence decoding by ACC ensembles was far superior to DS ensembles.
The last chapter attempts to produce a unified theory of ACC function based on its coding properties. I will argue that the ACC monitors many aspects of experience while evaluating the current state with reference to a goal. Its multiple coding schemes efficiently serve both monitoring and evaluating functions.Medicine, Faculty of
Graduate
9
Shinozaki, Jun. "Heterospecific and conspecific social cognition in the anterior cingulate cortex." Kyoto University, 2008. http://hdl.handle.net/2433/135801.
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Walton, Mark. "The role of the anterior cingulate cortex in making and changing decisions." Thesis, University of Oxford, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.400291.
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Holec, Victoria, and University of Lethbridge Faculty of Arts and Science. "Role of rat anterior cingulate cortex in effort- and courage-based decision making." Thesis, Lethbridge, Alta. : University of Lethbridge, [Dept. of] Neuroscience, c2013, 2013. http://hdl.handle.net/10133/3433.
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When given a choice between getting a high reward that requires climbing a high ramp or
pressing a lever multiple times, versus freely obtaining a low reward, healthy rats prefer
the former, while rats with lesions to the anterior cingulate cortex (ACC) prefer the latter.
We developed two novel effort tasks to examine if ACC mediates other types of physical
effort (weight-lifting) as well as emotional effort (courage). We replicated previous
findings on a modified version of the ramp-climbing task, showing that ACC lesions
impair these decisions. Lesions of ACC did not impair weight-lifting effort, even when
higher levels of effort were used and training on the task was eliminated. Initially,
lesions of ACC did not impair courage effort. When the task effort was subsequently
increased, rats with ACC lesions showed a failure to adapt to novelty throughout testing.
This research indicated that not all effort is mediated by ACC.xii, 177 leaves : ill. ; 29 cm
12
Golden, Caroline. "Neuronal dynamics of the anterior cingulate cortex during working memory and serotonergic manipulation." Thesis, Imperial College London, 2016. http://hdl.handle.net/10044/1/45527.
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The prefrontal cortex (PFC) plays a strong role in the execution of executive tasks such as working memory. It is thought to exert top-down control over sensory regions, and integrate information from both external stimuli, and internal computation, such as choice and expectation (1-3). The anterior cingulate cortex (ACC) is a region of the PFC known to receive strong projections from serotonergic neurons of the raphe nuclei (4). In the work presented here, the influence of the hallucinogenic compound, and serotonergic agonist, psilocybin, was investigated in the neural circuits of the ACC of awake, head-fixed mice. Extracellular, multi-unit recordings were performed to examine the effects of the systemic administration of psilocybin. Psilocybin was found to transition the network into a desynchronised state, reminiscent of REM sleep. This state was characterised by an increase in activation in the network, combined with a reduction in power of low frequency LFP oscillations in the delta, theta and alpha band, coupled with a moderate increase in power in the gamma frequency band. The encoding mechanisms in the ACC in working memory were examined by conducting similar recordings in mice performing a delayed response task. The neuronal dynamics revealed strong encoding of low-level (stimulus information) and high-level (choice, reward anticipation) information on both a single cell and population level. The population code appeared to have strong predictive properties of task outcome that surpassed the speed at which the behavioural information could correctly classify the upcoming behavioural response. An effective method to test these hypotheses was provided in the optogenetics experiments, which perturbed the neuronal activity during the delay period of the task using channel-rhodopsin 2 (ChR2). This method proved effective and versatile in inducing a behavioural response and perturbing the neural response profiles of cells encoding information key to working memory.
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Macaulay, Katherine. "The influence of self-reported ethnic origin and mood on elicited emotion and brain reactivity to happy and sad social films." Thesis, Brunel University, 2011. http://bura.brunel.ac.uk/handle/2438/6563.
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In recent years Social Neuroscience has started to investigate how mood and culture influence social and emotional situations. In the present study differences in elicited emotion and neural activation were investigated when participants viewed films depicting social interactions. Film clips are preferred stimuli for elicitation of emotion in laboratory studies, but given the lack of standardised film sets in the literature, two behavioural studies were conducted prior to imaging. The first study (147 females, 30 males; 98.8% 18 to 24 years) identified a set of clips that elicited emotion profiles in which the target emotion (happy, sad) was strongest, as well as neutral clips, and demonstrated an effect of participants’ stable mood. The second study (143 females, 19 males; mean age 19.2 years) optimised the stimulus set and demonstrated effects of self-reported ethnic origin, mood and interest on profiles of elicited emotion. In the fMRI investigation 33 female and 8 male participants (mean age 19.2 years) viewed film clips in a block design experiment with loose and tight t-contrasts and retrospective ratings of elicited emotion. Across all-participants, social interaction depicting sadness activated key emotion-related structures such as left amygdala and insula, and medial frontal cortex that were not significantly activated with social interaction depicting happiness. However, greater activation was observed for Europeans than for non-Europeans in orbitofrontal cortex, anterior and posterior cingulate for happy social interaction and in hippocampus, precuneus and retrosplenial cortex for sad social interaction. Individual differences in trait emotions and stable mood were measured with PANAS-X. For high fatigue participants greater activation was observed in the left amgydala for happy social interaction. For participants with high positive stable mood greater activation was observed in the insula for happy and sad social interaction. The research described here indicates that self-reported ethnic origin and mood are potentially significant influences on elicited emotion and brain reactivity to positive and negative social and emotional situations.
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Hercher, Christa. "Examining potential cellular alterations within the anterior cingulate cortex in major depression and suicide." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=112634.
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Representing a major public health concern, suicide is a leading cause of death worldwide. Generally regarded as a behavior with a multitude of state and trait dependent risk factors (e.g. psychiatric disorders, substance abuse, genetics), explanations as to why certain individuals commit suicide while others do not are complex. Of interest is in studying potential trait dependent variables involved in the neurobiology of suicide, particularly at the cellular level. Knowledge of the cellular integrity may aid in explaining the observed macroscopic alterations and ultimately the behavioral correlates associated with suicidality. Therefore we set out to summarize extant knowledge of the cellular alterations occurring in the brains of major depressive and suicide individuals. Following this, we conducted our own cellular investigation in a region known to be altered in major depression and suicide, a supracallosal area of BA24a. Neuronal and glial cell densities as well as neuronal cell sizes were assessed in upper and lower cortical layers between sudden-death controls and MDD suicide subjects. Secondary analyses were also conducted to examine the effect of alcohol on depressed suicides. Analyses of cell densities and neuronal soma sizes between controls and MDD suicide subjects did not reveal any significant differences. Further analyses showed increased glial cell densities in alcoholic depressed suicides. Future studies are necessary to examine explicit changes in the cellular compositions occurring in alcoholic dependent individuals. Staining techniques aimed at targeting specific subtypes of neurons and glial cells will help determine if these cell populations do in fact have an influential role in suicide and MDD.
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Morrison, Catherine India. "Investigations of the role of the human anterior cingulate cortex in observing others' pain." Thesis, Bangor University, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.433692.
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Gittins, Rebecca. "The cytoarchitecture of the human anterior cingulate cortex and its involvement in mood disorder." Thesis, University of Oxford, 2003. http://ora.ox.ac.uk/objects/uuid:8ca079f0-6133-4f6d-a470-3a590789d8bb.
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The biological mechanisms proposed to underlie primary mood disorder do not usually include a neuropathological component. Over recent years, a significant imaging literature attests to structural abnormalities in various brain regions in mood disorder, and has encouraged neuropathological investigations. Although the neuropathological understanding of mood disorder is still rudimentary, structural correlates have begun to emerge. The studies described in this thesis investigate the neuropathology of the anterior cingulate cortex in mood disorder. The anterior cingulate cortex is extremely diverse and complex, particularly in respect to its cytoarchitecture and functional organisation. These details are important when considering the precise localisation and clinical correlates of the neuropathological changes of this region in disease. Accordingly, I performed a detailed analysis of the cytoarchitecture of the human anterior cingulate cortex, as a prelude to investigations of this region in mood disorder. I measured several morphometric parameters within different anatomical levels and both hemispheres of the anterior cingulate cortex. Overall I found a clear distinction in the cellular composition of the supragenual and subgenual regions of the anterior cingulate cortex. The subgenual region demonstrated a lower glial density and smaller neurons in comparison to the supragenual region. A modest difference in neuronal density was also observed, with a higher density in the deep layers of the subgenual cortex compared to the deep layers of the supragenual cortex. Total cortical depth was also thinner in the subgenual region. This work may have important implications for the interpretation of imaging and pathological data in mood disorder. To assess the cytoarchitecture of this brain region in mood disorder, I examined several morphometric indices in addition to various parameters of gene expression in post mortem brains. I found a range of cytoarchitectural abnormalities in the supragenual anterior cingulate cortex in mood disorder. The most prominent change included a reduction in glial density, which was evident in all layers of the cortex. Glial fibrillary acidic protein was also reduced, providing some evidence for astrocyte involvement. Various neuronal changes were also observed in the mood disorder group. These included layer-specific reductions in pyramidal neuron density and a modest change in the density of cairetinin-immunoreactive neurons. I did not find any evidence supporting synaptic pathology in the anterior cingulate cortex in mood disorder. These findings extend previous evidence of cytoarchitectural alterations in the anterior cingulate cortex in mood disorder and in particular emphasise the prominent involvement of glial cells in the neuropathology of this disease. The origins of the glial (and neuronal) deficits in mood disorder remain to be established, but they are likely to have pathophysiological consequences.
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Crawford, Jessica D. "Cellular-based Brain Pathology in the Anterior Cingulate Cortex of Males with Autism Spectrum Disorder." Digital Commons @ East Tennessee State University, 2014. https://dc.etsu.edu/etd/2443.
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Autism spectrum disorder (ASD) now affects 1 in 68 children in the United States. Disorders within this spectrum share hallmark deficits in verbal and nonverbal communication, repetitive behavior, and social interaction. The cause of ASD is still unknown. Even though hundreds of genetic abnormalities have been identified in ASD, these markers account for less than 1% of all ASD cases. Researchers continue to search for pathological markers common to all or most cases of ASD. The research presented in this dissertation used a novel combination of state-of-the-art methods to investigate brain pathology in ASD. Postmortem anterior cingulate cortex (ACC) from ASD and typically developing brain donors was obtained from 2 national brain banks. The ACC was chosen for study because of its documented role in influencing behaviors characteristically disrupted in ASD. An initial study revealed elevated glial fibrillary acidic protein (GFAP) in ACC white matter from ASD brain donors compared to typically developing control donors. Laser capture microdissection was then employed to isolate specific cell populations from the ACC from ASD and control brain donors. Captured cells were used to interrogate potential gene expression abnormalities that may underlie biological mechanisms that contribute behavioral abnormalities of ASD. The expression of 4 genes associated with synaptic function, NTRK2, GRM8, SLC1A1, and GRIP1, were found to be significantly lower in ACC pyramidal neurons from ASD donors when compared to control donors. These expression abnormalities were not observed in ACC glia. Given robust evidence of neuronal and glial pathology in the ACC in ASD, a novel method for whole transcriptome analysis in single cell populations was developed to permit an unbiased analysis of brain cellular pathology in ASD. A list of genes that were differentially expressed, comparing ASD to control donors, was produced for both white matter and pyramidal neuron samples. By examining the ASD brain at the level of its most basic component, the cell, methods were developed that should allow future research to identify common cellular-based pathology of the ASD brain. Such research will increase the likelihood of future development of novel pharmacotherapy for ASD patients.
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Chandley, Michelle J., Jessica D. Crawford, Katalin Szebeni, Attila Szebeni, Jessica D. Crawford, and Gregory A. Ordway. "Gene Expression Deficits in Pyramidal Neurons From the Anterior Cingulate Cortex in Males With Autism." Digital Commons @ East Tennessee State University, 2014. https://dc.etsu.edu/etsu-works/8636.
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Background: Altered brain morphology was one of the first pathobiological findings associated with autism spectrum disorder. These gross abnormalities, documented in both white and gray matter areas in autistic brains, are postulated to contribute to disrupted neuronal communication. For example, glutamatergic pyramidal neurons in the anterior cingulate cortex (ACC) have decreased size and increased cell density in autism.
Objectives: We sought to determine whether autism-related gene expression abnormalities exist in the ACC that might underlie previously observed cell morphological alterations found in this brain region. Specifically, levels of expression of genes associated with glutamatergic neurotransmission were measured in pyramidal neurons and surrounding astrocytes in the ACC of postmortem brain tissues from autism donors and matched developmentally normal control donors.
Methods: Postmortem brain tissues were obtained from 6-8 age-matched pairs of male subjects who had autism and developmentally normal control males (age range 6-37). Laser-guided microdissection was used to capture pure populations of pyramidal neurons and astrocytes from layer III of the ACC. The expression of glutamate-related genes was measured in RNA isolates by reverse transcription followed by end-point PCR using three stable reference genes to normalize expression levels.
Results: ACC pyramidal neurons from autism subjects demonstrated significantly reduced gene expressions of the obligatory glutamatergic NMDA receptor subunit NR1, a glutamate transporter SLC1A1, and the glutamate receptor anchoring protein GRIP1. There was also a robust reduction in the gene expression of the brain-derived neurotrophic factor (BDNF) receptor NTRK2 in autism pyramidal neurons, with gene expression levels of BDNF itself unaffected. No gene expression abnormalities were observed in ACC astrocytes surrounding the pyramidal neurons from autistic subjects.
Conclusions: Autism spectrum disorder is associated with a reduction in the expression of genes associated with glutamatergic neurotransmission and downstream BDNF signaling in pyramidal neurons of the ACC. These findings suggest that glutamatergic signaling is compromised in these excitatory neurons in autism and raise hope that drugs or other treatments may be developed to overcome these pathobiological deficits.
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Ortiz, Samantha. "Anterior cingulate cortex and ventral hippocampus inputs to the basolateral amygdala selectively control generalized fear." Kent State University / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=kent1540975191665517.
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Weiss, Alexander R. "Novel approaches to studying the role of the anterior cingulate cortex in cognition and Parkinson's disease." Thesis, University of Oxford, 2017. https://ora.ox.ac.uk/objects/uuid:c827764b-af3b-4397-90cc-039f40fab460.
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The motor symptoms of Parkinson's disease (PD) have been linked to the emergence of exaggerated oscillatory activity in the 13 - 35 Hz beta range in recordings of the basal ganglia (BG) thalamocortical circuit of PD patients and animal models. PD patients and animal models also express dopamine-dependent cognitive impairments, implying effects of dopamine loss on the function of the anterior cingulate cortex (ACC). This thesis examines the electrophysiological behavior of the BG thalamocortical circuit in PD and dopamine-normal states during cognitive and motor activity. In vivo recordings in the BG of PD and dystonic patients were used to study the influence of dopamine during a test of executive function. Normal executive function was also investigated in the dopamine-healthy ACC of chronic pain patients. Both the BG and ACC exhibited lateralized electrophysiological responses to feedback valence. The BG also exhibited dopamine-sensitive event-related behavior. In additional experiments, chronically implanted recording electrodes in awake, behaving hemiparkinsonian rats were used to examine the transmission of synchronized oscillatory activity from the BG, through the ventral medial (VM) thalamus, to the ACC. Modulation of subthalamic nucleus, VM thalamus, and ACC activity during a simple cognitive/movement task was also investigated in hemiparkinsonian rats. Findings in the rat model suggest that ACC-mediated executive function is dopamine-sensitive and is reflected in the region's electrophysiology. These results may provide further insight into the significance of excessive oscillatory activity in PD and its influence on cognitive systems.
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Einarsson, Einar. "The anterior cingulate cortex in contextual fear memory: from formation, consolidation, and reconsolidation, to mediating context generalization." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=107666.
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To persist, new memories must undergo a consolidation process, during which they are sensitive to disruption. This process, referred to as cellular consolidation, is posited to be completed within the first hours following learning and involves stabilization of changes in synaptic connectivity. Memories can also consolidate at the level of brain systems. Systems-consolidation is a more prolonged process involving gradual reorganization of brain systems that support memory expression, where memories that initially depend on the hippocampus increasingly come to depend on specific cortical structures. A number of recent studies have suggested that the anterior cingulate cortex (ACC) is one such cortical structure that is not required for the expression of recent memory, but becomes critical for the expression of remote memory. In addition to reorganization of the anatomical substrates of memory, memories are known to change in other ways over time. Contextual memory, initially hippocampus-dependent, can become less specific over time, whereby animals generalize conditioned responding to novel contexts. However, a number of recent studies have described how following retrieval, memories can return to a labile state, a process referred to as cellular reconsolidation. Similarly, retrieval has been found to transiently return a hippocampus-independent remote memory to a hippocampus-dependent state, a process of systems reconsolidation. Moreover, memory retrieval reactivating the hippocampus has been found to renew memory precision with reduced behavioural generalization.To date, little is known about how retrieval affects the involvement of the ACC, more specifically: (1) whether memory undergoes cellular consolidation and reconsolidation in the ACC, and if so, if this is the case for recent as well as remote memories; (2) whether ACC-dependent remote memory transiently becomes ACC-independent following retrieval; and (3) whether increased context memory generalization is mediated by the ACC. This thesis aims to answer these questions in the following two manuscripts. In all experiments, rats underwent contextual fear conditioning. The first manuscript addresses the first two questions. To answer the first question, protein-synthesis inhibitor was infused into the ACC immediately following conditioning or memory retrieval. The results indicate that the ACC is involved in cellular consolidation and reconsolidation of recent and remote contextual fear memory. To answer the second question, the ACC was pharmacologically inactivated at different time-points before testing at time-points after a reactivation trial. The results suggest that at 6 hours following memory retrieval, memory expression can be supported by either the ACC or the dorsal hippocampus (DH), whereas at 24 hours after the retrieval, the memory is once more ACC-dependent. The second manuscript examines the third question, examining the effects of memory retrieval on subsequent context generalization. The results indicate that following memory retrieval, context discrimination is renewed at 24 hours, but not at 6 or 48 hours. Furthermore, pharmacological inactivation of the ACC before testing at 6 hours restores context discrimination, suggesting that the ACC mediates context generalization. In summary, research presented in this thesis suggests that the ACC plays an important role in the brain networks consolidating and reconsolidating contextual fear memory, and becomes more critical for memory retrieval with time as memory expression becomes more generalized.Afin d'être préservés, les nouveaux souvenirs doivent être soumis au processus de la consolidation, pendant lequel ces souvenirs sont sensibles à toute modification. Ce processus nommé consolidation cellulaire, a lieu pendant les premières heures suivant un apprentissage, et implique la stabilisation de certains changements au niveau des connections synaptiques. Les souvenirs peuvent également être consolidés au niveau des réseaux neuronaux, lors de la consolidation systémique. La consolidation systémique est un processus prolongé qui implique une réorganisation graduelle des réseaux neuronaux qui sous-tendent l'expression de la mémoire. Ainsi, un souvenir dépend initialement de l'hippocampe mais devient progressivement dépendant de structures corticales spécifiques. Plusieurs études récentes ont suggéré que le cortex cingulaire antérieur (CCA) est l'une de ces structures qui n'est pas requise pour l'expression de souvenirs récents, mais devient nécessaire pour l'expression de souvenirs anciens. En plus de la réorganisation des substrats anatomiques d'un souvenir, les souvenirs peuvent êtres modifiés autrement avec le temps. Les souvenirs contextuels, initialement dépendants de l'hippocampe, peuvent devenir moins spécifiques avec le temps, et les animaux vont généraliser leur réponse conditionnée à de nouveaux contextes. Cependant, selon plusieurs études récentes, suite au rappel, les souvenirs peuvent revenir à un état instable par un processus appelé la reconsolidation cellulaire. Il a également été montré qu'un souvenir ancien, et donc indépendant de l'hippocampe, peut de nouveau dépendre de cette structure suite au rappel, par un processus de reconsolidation systémique. De plus, il a été démontré que la réactivation de l'hippocampe suite au rappel d'un souvenir ancien peut renouveler la précision des souvenirs, et donc diminuer la généralisation comportementale normalement observée avec les souvenirs anciens. À l'heure actuelle, la façon dont le rappel affecte l'implication du CCA est assez méconnue. Plus spécifiquement, plusieurs questions se posent: (1) le souvenir est-il sujet à la consolidation et à la reconsolidation cellulaire au niveau du CCA, et si oui, est-ce le cas pour les souvenirs récents et anciens; (2) les souvenirs anciens dépendants du CCA deviennent-ils momentanément indépendants de cette structure après le rappel; et (3) la généralisation accrue des souvenirs contextuels est-elle gérée par le CCA? Cette thèse a pour but de répondre à ces questions dans les deux manuscrits suivants. Pour toutes les expériences, les rats ont été entrainés dans une tache de conditionnement de peur au contexte. Le premier manuscrit porte sur les deux premières questions. Pour répondre à la première question, un inhibiteur de synthèse protéique a été infusé dans le CCA immédiatement après le conditionnement ou le rappel. Les résultats montrent que le CCA est impliqué dans la consolidation et reconsolidation cellulaire des souvenirs de peur contextuels à la fois récents et anciens. Pour répondre à la deuxième question, le CCA a été pharmacologiquement inactivé à différents temps avant le test et après le rappel. Les résultats suggèrent que l'expression de la mémoire peut être sous-tendue par le CCA ou l'hippocampe dorsal 6 heures après le rappel. Néanmoins, le souvenir est de nouveau dépendant du CCA 24 heures après le rappel. Le second manuscrit examine la troisième question : étudier les effets du rappel sur la généralisation de contextes. Les résultats indiquent que suite au rappel d'un souvenir ancien, la discrimination des contextes est observée à 24 heures, mais pas à 6 ou 48 heures. De plus, l'inactivation pharmacologique du CCA avant le test à 6 heures rétablit la discrimination des contextes. Ceci suggère que le CCA gère la généralisation des contextes.
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Sciara, Aubrey N. "Characterization of Pro-inflammatory and Anti-inflammatory Microglia in the Anterior Cingulate Cortex in Autism Spectrum Disorder." Digital Commons @ East Tennessee State University, 2016. https://dc.etsu.edu/etd/3109.
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Autism spectrum disorder (ASD) is associated with functional abnormalities of the anterior cingulate cortex (ACC), a brain area that mediates social behavior. Given evidence of a role of inflammation in ASD, markers of pro-inflammatory and anti-inflammatory microglia were studied using postmortem ACC tissues from ASD and age-matched typically developed control donors. Gene expression levels of pro-inflammatory (CD68, HLA-DRA, IL1B, NOS2, PTGS2) and anti-inflammatory (ARG1, IGF1, MRC1, PPARG) microglial genes were measured using quantitative real-time PCR. Additionally, brain sections were immunohistochemically stained for a microglial marker. Expression levels of IGF1 were modestly higher, while the expression of MRC1 was modestly lower in ASD donors when compared to control donors. No other differences in gene expression levels between the two groups of donors were observed. Statistical significance for changes in expression levels IGF1 and MRC1 did not survive correction for multiple comparisons. Further research on anti-inflammatory microglial involvement in ASD is warranted.
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Andrew, Gethien. "GABAergic-Related Pathology in the Anterior Cingulate Cortex of Postmortem Human Brain Tissue in Autism Spectrum Disorder." Digital Commons @ East Tennessee State University, 2021. https://dc.etsu.edu/etd/3967.
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The anterior cingulate cortex (ACC) is part of the cognitive and emotional brain circuitry that mediates social interaction. Imbalances between inhibitory, GABAergic neurons, and excitatory, glutamatergic neurons, in this region are essential to brain circuity during social responses and are thought to be involved with behaviors associated with autism spectrum disorder (ASD). Enriched cell populations of glutamatergic neurons, obtained through laser capture microdissection, were used for gene expression studies of GABAergic receptors (GABRA1, GABRA4, and GABBR1). Additionally, proteins that impact GABAergic synapses (Spinophilin, CPLX1, mTOR, IGF1R, PSD95, PARP1) were investigated using Western Blotting with punchdissected homogenate brain tissue from ACC and frontal cortical brain regions. No significant differences in gene expression nor protein were identified between ASD and control brain donors. Evidence of GABAergic synaptic pathology was not found; however, future studies of alternative GABAergic markers and increased study numbers are needed to confirm these findings in ASD human tissue.
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Kiddoo, Cynthia E. "Selective attention and the visual representation of object attributes in the ventrolateral prefrontal cortex and anterior cingulate cortex of the rhesus monkey." Thesis, Massachusetts Institute of Technology, 2005. http://hdl.handle.net/1721.1/33674.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2005.Includes bibliographical references (p. 52-56).
The effects of attending to one or another of an object's attributes on neuronal representations of that object were investigated using extracellular recordings. A female rhesus monkey performed a delayed match to object attribute (DMSA) task, in which she alternately matched object orientations and object colors. In half of the task conditions, only one attribute matched the sample, forcing the animal to apply the current matching rule and ignore the irrelevant-attribute. Multiple simultaneous single-unit extracellular recordings were made in the ventrolateral prefrontal cortex (VLPFC) and anterior cingulate cortex (ACC) while the monkey performed the task. Neuronal selectivity for matching rule, object attributes, attribute relevance, response choice, and congruency were assessed using multi-factor ANOVAs. Attribute-selective responses were common in both cortical areas during the sample and delay periods, but were not significantly modulated by attribute relevance. There were few interactions between color-selective and orientation-selective responses according to the ANOVAs, suggesting that these attributes were represented independently.
(cont.) Significant effects of attribute relevance, response choice, and congruency appeared in both areas after the delay period, when the probe appeared onscreen. VLPFC cells were more active during incongruent and non-match conditions, when responses had to be suppressed. ACC cells were more active during congruent and match conditions, when active response suppression was not required. The results indicate that although prefrontal cortex often shows a bias for relevant information (Rainer et al, 1998), it may not do so if the task requires frequent alternation of attentional sets or active suppression of conflicting responses. The data also indicate that the VLPFC's role in managing attentional 'set' (Banich et al, 2000; Milham et al, 2001) is performed in conjunction with active stimulus comparison and response selection (e.g., Rushworth et al, 1997), not during working memory maintenance. The ACC may facilitate the reactivation of response tendencies that had been actively suppressed, possibly as part of a larger role in managing response conflict (Botvinick et al, 2004).
by Cynthia E. Kiddoo.
Ph.D.
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Boschin, Erica. "Dynamics of cognitive control and flexibility in the anterior cingulate and prefrontal cortices." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:31cdb9f1-8107-4431-bc7a-2e0dbb9885a1.
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The body of work hereby presented aims at better defining the specific mechanisms underlying cognitive control and flexibility, and to investigate the neural substrates that might support these dynamics. More specifically, the anterior cingulate (ACC), dorsolateral prefrontal (dlPFC) and frontopolar (FPC) cortices have been proposed to play a fundamental role in monitoring and detecting the presence of environmental contingencies that require the recruitment of cognitive control (such as competition between responses in the presence of conflicting information), implementing cognitive control, and supporting higher-order cognitive processing, respectively. This thesis investigates the effects of damage to these regions, and of interference with their activity, on these processes. It also argues for the importance of dissociating possible separate cognitive control components that might differently contribute to behavioural adjustments (such as caution and attention/task-relevant processing), and provides one of the first attempts to quantify them within the parameters of a mathematical model of choice response-time, the Linear Ballistic Accumulator (LBA). The results confirm the crucial role of the dlPFC in modulating behavioural adjustments, as both damage and interference with this region’s activity significantly affect measures of conflict-induced behavioural adaptation. It is hypothesized that dlPFC might drive behavioural adjustments by encoding recent conflict history and/or supporting the automatization of a newly advantageous behavioural strategy during the early stages after a change in conflict levels. When a task does not involve competition between a habit and instructed behaviour, lesions or interference with ACC’s activity do not appear to affect behaviour in a manner that is consistent with the classic conflict-monitoring framework. It is suggested that its role might be better described as a more general monitoring and confirmatory mechanism that evaluates both actual and potential outcomes of an action, in order to proactively guide adjustments away from contextually disadvantageous responses. Finally, lesions to the FPC do not affect abstract-rule integration, but do impair the early stages of acquisition of a new abstract rule, when a previously rewarded rule stops being rewarded, and specifically when acquisition is dependent on self-initiated exploration. This suggests a role for FPC in the evaluation of multiple concurrent options in order to aid the development of new behavioural strategies.
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Rundström, Alexandra. "Central neural correlates of generalized anxiety disorder : A systematic review." Thesis, Högskolan i Skövde, Institutionen för biovetenskap, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-20172.
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Generalized anxiety disorder (GAD) is a prevalent anxiety disorder that is characterized by persistent excessive worrying that is often difficult to control. The pathology of GAD has been associated with abnormal neural activity and functional connectivity. This systematic review has examined the central neural correlates of GAD which are the prefrontal cortex (PFC), the anterior cingulate cortex (ACC) and the amygdala and how activation and functional connectivity in these brain areas differ between patients with GAD and healthy controls. This review also investigated how abnormal functional connectivity and activation in these brain regions relates to worry which is the most prominent psychological symptom in patients with GAD. A systematic review was conducted and seven original functional magnetic resonance imaging (fMRI) studies were included after a literature search on PubMed, Scopus and, Web of Science. The main findings from this review revealed decreased activation in the PFC and ACC and enhanced activation in the amygdala during the viewing of negative stimuli in patients with GAD. Identifying the neural correlates of GAD and how it relates to worry may provide improved treatment in the future such as developing more effective psychotropic drugs or improved psychotherapy. GAD has been associated with lower well-being and life satisfaction and may even be a risk factor for suicidal thoughts. One of the limitations from this review is that several of the included studies recruited patients with comorbidities and for that reason results from these studies cannot be generalized and applied to individuals with GAD.
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Belanger, Annie. "Brain Basis of the Placebo Effect: A Proposed Integrative Model Implicating the Rostral Anterior Cingulate." Scholarship @ Claremont, 2013. http://scholarship.claremont.edu/scripps_theses/272.
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How is the brain capable of mediating pain relief via the mind alone? Placebo analgesia is just such a case, wherein an inert substance yields relief from a number of pain inducing stimuli. Scholars typically separate several factors thought to contribute to the placebo effect into psychological and neurobiological influences. Psychological mechanisms include expectation and conditioning of analgesic effects, while neurobiological mechanisms implicate the opioidergic descending pain system. The current paper proposes an integrative model in which the rostral anterior cingulate cortex (rACC), implicated in cognitive-affective modulation, receives goal-directed input (i.e., expected pain relief) from the prefrontal cortex. As the rACC processes the cognitive difference between expected and actual pain, it recruits a critical descending pain pathway by means of modulating the periaqueductal gray area (PAG). The PAG is a key relay station that connects to other endogenous subsystems of opioidergic pain relief. Whether the rACC and its connection to the PAG are necessary for the placebo effect is a question future research will have to address.
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Barrett, Jennifer Anne. "Linking brain structures with symptoms : the role of the anterior cingulate cortex and a frontocingulate circuit in affective states." Thesis, McGill University, 2004. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=84986.
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Linking brain regions or neural circuits to specific affective symptoms could help elucidate the neural mechanisms of affective states as well as antidepressant treatment effects. Much research has implicated the anterior cingulate cortex (ACC), mid-dorsolateral frontal cortex (MDLFC), and a "frontocingulate" (i.e., MDLFC-ACC) circuit in sad affect and depression as well as the mood response to antidepressant treatment, including 10-Hz repetitive transcranial magnetic stimulation (rTMS) applied over the MDLFC. While the empirical support for a direct role of the MDLFC in affect is unclear, a wealth of research supports the ACC as an interface between action and emotion (Paus, 2001). In a series of experiments using behavioural, brain imaging and brain stimulation techniques we investigated the involvement of the ACC and an MDLFC-ACC (i.e., frontocingulate) circuit in an "action and emotion" relevant behaviour, namely, paralinguistic aspects of speech production. (e.g., speech pitch and loudness). In Experiment 1, we examined the relationship between affect and paralinguistic aspects of speech and in Experiment 2 we investigated the role of the ACC in mediating this phenomenon. Next, applying our knowledge of the role of the ACC in affect-relevant behaviour, we combined rTMS with a speech task (Experiment 3) and with PET (Experiment 4) in order investigate further the possibility that influencing brain activity in a frontocingulate circuit may contribute to the known mood effects of rTMS applied over the MDLFC. Taken together, our results demonstrated a role for the ACC in pitch variation during affective states and suggested that changes in affect and pitch variation following 10-Hz rTMS applied over the left MDLFC may involve changes in neural activity in a network of brain regions widely implicated in affect, including a frontocingulate circuit. The findings of this collection of studies take us a step further toward understanding the r
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Schweimer, Judith. "Die Rolle des Anterioren Cingulären Cortex bei Entscheidungsprozessen und instrumentellen Lernvorgängen The role of the Anterior Cingulate Cortex in decision making and in instrumental behaviour /." [S.l. : s.n.], 2006. http://nbn-resolving.de/urn:nbn:de:bsz:93-opus-27629.
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Chandley, Michelle J., Jessica D. Crawford, Attila Szebeni, Katalin Szebeni, and Gregory A. Ordway. "NTRK2 Expression Levels Are Reduced in Laser Captured Pyramidal Neurons From the Anterior Cingulate Cortex in Males With Autism Spectrum Disorder." Digital Commons @ East Tennessee State University, 2015. https://dc.etsu.edu/etsu-works/8596.
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Background: The anterior cingulate cortex (ACC) is a brain area involved in modulating behavior associated with social interaction, disruption of which is a core feature of autism spectrum disorder (ASD). Functional brain imaging studies demonstrate abnormalities of the ACC in ASD as compared to typically developing control patients. However, little is known regarding the cellular basis of these functional deficits in ASD. Pyramidal neurons in the ACC are excitatory glutamatergic neurons and key cellular mediators of the neural output of the ACC. This study was designed to investigate the potential role of ACC pyramidal neurons in ASD brain pathology.
Methods: Postmortem ACC tissue from carefully matched ASD and typically developing control donors was obtained from two national brain collections. Pyramidal neurons and surrounding astrocytes were separately collected from layer III of the ACC by laser capture microdissection. Isolated RNA was subjected to reverse transcription and endpoint PCR to determine gene expression levels for 16 synaptic genes relevant to glutamatergic neurotransmission. Cells were also collected from the prefrontal cortex (Brodmann area 10) to examine those genes demonstrating differences in expression in the ACC comparing typically developing and ASD donors.
Results: The level of NTRK2 expression was robustly and significantly lower in pyramidal neurons from ASD donors as compared to typically developing donors. Levels of expression of GRIN1, GRM8, SLC1A1, and GRIP1 were modestly lower in pyramidal neurons from ASD donors, but statistical significance for these latter genes did not survive correction for multiple comparisons. No significant expression differences of any genes were found in astrocytes laser captured from the same neocortical area. In addition, expression levels of NTRK2 and other synaptic genes were normal in pyramidal neurons laser captured from the prefrontal cortex.
Conclusions: These studies demonstrate a unique pathology of neocortical pyramidal neurons of the ACC in ASD. NTRK2 encodes the tropomyosin receptor kinase B (TrkB), transmission through which neurotrophic factors modify differentiation, plasticity, and synaptic transmission. Reduced pyramidal neuron NTRK2 expression in the ACC could thereby contribute to abnormal neuronal activity and disrupt social behavior mediated by this brain region.
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Lawless, Caroline. "The Role of Basal Forebrain Cholinergic Projections to the Anterior Cingulate Cortex in Cued and Contextual Fear Conditioned Suppression Paradigms." Thesis, University of Delaware, 2018. http://pqdtopen.proquest.com/#viewpdf?dispub=10744544.
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Basal forebrain corticopetal cholinergic neurons are critical for contextual and cued fear memory in the conditioned suppression paradigm, but neural mechanisms that alter these neurons in fear memory remain unknown. Interestingly, basal forebrain cholinergic lesions have no effect on behavioral performance in commonly-studied fear conditioning paradigms like Pavlovian conditioned freezing or fear-potentiated startle, yet impair fear memory in the conditioned suppression paradigm. Many studies conducted have experimented with lesions of cell bodies of corticopetal cholinergic neurons in the nucleus basalis magnocellularis (NBM), but there is a void in the literature defining which specific projections may be responsible for their discrepant role in different fear memory paradigms. The basal forebrain projects to the anterior cingulate cortex (ACC), a subregion of the medial prefrontal cortex. The ACC is a well-established portion of the fear circuit across all fear conditioning paradigms and has a clear role in decision-making in the conditioned suppression paradigm. Given the role in choice conflict that the ACC plays in operant tasks involved in the conditioned suppression paradigm, it is plausible that it may be a region that allows basal forebrain cholinergic neurons to alter a fear memory in the conditioned suppression paradigm. The goal of this study is to examine the specific roles that basal forebrain cholinergic projections to the ACC play in fear memory, specifically in the conditioned suppression paradigm. These lesions may target specific cholinergic input to the ACC from the NBM in the basal forebrain and this may isolate a specific fear circuit involved in fear memory in the conditioned suppression paradigm. Data have suggested that ACC lesioned animals demonstrate less fear-conditioned suppression over sham animals, but further experiments and cohorts of animals are required. If ACC cholinergic lesions are shown to produce deficits in fear memory in the conditioned suppression paradigm, it may suggest that the presence of the appetitive task, which only occurs in the conditioned suppression paradigm and not in any of the other commonly studied fear paradigms, may be able to elicit changes in functional connectivity to incorporate this projection from the NBM to the ACC to the fear circuit. Discrepancies in fear memory between fear conditioning paradigms demand to be addressed because assumptions about functional connectivity across different paradigms are assumed to be similar in the literature. If the notion of paradigmdependent functional connectivity presented here is true, deductions about this functional connectivity may only be made in the context of one fear paradigm and may not necessarily be applicable across paradigms. In other words, to say that Pavlovian fear conditioning and fear-potentiated startle are indicative of the broad neurobiology of fear memory would only be looking at a fraction of the reality behind how fear circuitry operates. In order to further the literature to propose holistic circuits, molecular processes and constructs that apply to all fear memory regardless of protocol or paradigm, it is necessary to investigate neural involvement across alternative fear paradigms, like conditioned suppression. This study supports the novel idea that neural circuitry that supports fear can expand with new learning tasks or events and therefore, may be more susceptible to change than previously considered, but future studies are required
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Cavalcanti, João Zugaib. "Córtex cingulado anterior e respostas nociceptivas em cobaias: modulação GABAérgica, colinérgica e opioidérgica." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/17/17134/tde-31082016-103903/.
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A dor é um fenômeno multidimensional, que geralmente desencadeia reações emocionais desconfortáveis quando identificada. Sua relação com injúria tecidual pode ser interpretado como um mecanismo adaptativo de defesa à integridade do organismo, tendo em vista sua preservação evolutiva. Porém, o substrato neurobiológico do organismo parece determinar a complexificação do repertório comportamental em diferentes espécies. Nesse sentido, o córtex cingulado anterior (CCA) tem sido amplamente descrito em mamíferos modulando diferentes aspectos da dor. O presente trabalho utilizou os testes algesimétricos de vocalização e da formalina em cobaias, para se avaliar o decurso temporal do efeito da microinjeção de agonistas e antagonistas GABAérgico (muscimol e bicuculina); colinérgico (carbacol e atropina) e opioidérgico (morfina e naloxona). A microinjeção de bicuculina (1 nmol / 0,2 µl) exacerbou as respostas nociceptivas em ambos os testes, porém diferentes doses de muscimol (0,5, 1 e 2 nmol / 0,2 µl), não modificaram as respostas. O efeito da bicuculina foi bloqueado em ambos os testes pela microinjeção prévia de muscimol (1 nmol/ 0,2 µl) no CCA. A microinjeção de carbacol (2,7 nmol /0,2 µl) neste substrato promoveu antinocicepção, evidenciada por meio da atenuação da amplitude das vocalizações, mas não pelo teste da formalina. Esse efeito foi bloqueado pela administração prévia de atropina (0,7 nmol /0,2 µl) e de naloxona (2,7 nmol /0,2 µl). A microinjeção de morfina (4,4 nmol /0,2 µl) promoveu antinocicepção em ambos os testes. Concluímos que a inibição do tônus GABAérgico no CCA exacerba os comportamentos nociceptivos e que a antinocicepção promovida por carbacol pode ter sido mediada pelo sistema de opióides endógenos, tendo em 9 vista o bloqueio do seu efeito com naloxona. Além disso, a estimulação opióide promove uma contundente antinocicepção.Pain is a multidimensional phenomenon which usually triggers uncomfortable emotional reactions when identified. Its relation injury can be interpreted as an adaptive mechanism to defend the integrity of the body given its evolutionary conservation. However the neurobiological substrate of the body seems to determine the complexification of behavioral repertoire in different species. Thus, the anterior cingulated cortex (ACC) has been widely described in mammals by modulating different cognitive aspects of pain. This study used algesimetric tests of vocalization and formalin in guinea pigs to evaluate the time course of the effect of microinjection of GABA agonists and antagonists (bicuculline and muscimol) and cholinergic (carbachol and atropine) beyond the opioid antagonist naloxone. The microinjection of bicuculline (1 nmol / 0,2 µl) exacerbated the nociceptive behavior in both tests but different doses of muscimol (0,5; 1 e 2 nmol / 0,2 µl) did not change the responses. The effect of bicuculline was blocked in both tests by prior microinjection of muscimol (1 nmol / 0,2 µl) in the ACC. The microinjection of carbachol (2,7 nmol / 0,2 µl) on this substrate promoted antinociception as evidenced by attenuation of the amplitude of the vocalizations, but not by the formalin test. This effect was blocked by prior administration of atropine (0,7 / 0,2 µl) and naloxone (0,7 nmol / 0, 2 µl). The microinjection of morphine (4,4 nmol / 0,2 µl) promoted antinociception in both tests. We conclude that inhibition of GABAergic tone in the ACC exacerbates nociceptive behaviors and that the antinociception promoted by carbachol may 11 have been mediated by endogenous opioid system in order blocking its effect with naloxone. In addition opioid stimulation promotes a striking antinociception.
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Corbo, Vincent. "Size does not matter, but shape does : a structural neuroimaging study of the anterior cingulate cortex in acute post-traumatic stress disorder." Thesis, McGill University, 2004. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=82209.
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The neurobiological model of Post-Traumatic Stress Disorder, based upon the neurobiological model of fear-conditioning, states that the amygdala is hyperactivated, while other, inhibiting structures, like the Anterior Cingulate Cortex (ACC), are hypoactivated, therefore not fully inhibiting the amygdala. Two structural neuroimaging studies have examined the ACC volume to try to comprehend the hypoactivation of the ACC observed in subjects suffering from PTSD. Yamasue et al. (2003) found a lower grey matter density in the ACC of subjects with PTSD. Rauch et al. (2003) found a lower volume of the affective division of the ACC in subjects with PTSD compared to subjects exposed to trauma who did not suffer from PTSD. Comparing 14 subjects with Acute PTSD to 14 healthy control subjects, we replicated the results of Yamasue et al. (2003), but failed to observe any volumetric differences. Further analyses allowed us to be the first study to show that the nature of the difference observed in grey matter density was a shape difference of the ACC. Thus ACC volume does not seem to be related to Acute PTSD. Furthermore, this difference in shape raises questions as to the validity of the results of functional neuroimaging studies and of the neurobiological model of PTSD.
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Ash, Elizabeth Sarah. "An investigation of the neurochemical mechanisms underlying the contrasting effects of d-amphetamine in two subregions of the rat anterior cingulate cortex." Thesis, University College London (University of London), 2007. http://discovery.ucl.ac.uk/1444065/.
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d-Amphetamine inhibits neuronal uptake, and causes impulse-independent release of monoamines. There are several reports that d-amphetamine increases glutamate efflux in the rat cerebral cortex, but this has not been investigated systematically. It is unclear whether this is direct or secondary to its effects on dopamine transmission. These experiments aimed to compare regulation of extracellular glutamate in two adjacent subregions of the rat anterior cingulate cortex using in vivo microdialysis: the rostral anterior cingulate cortex (rACC) and caudal anterior cingulate cortex (cACC), which are innervated by dopaminergic projections from different brainstem nuclei. The first finding was that the glutamate response to d-amphetamine depended on subregion and route of administration. Glutamate in the cACC but not the rACC was increased by systemic d-amphetamine. Conversely, glutamate in the rACC but not the cACC was increased by local d-amphetamine. Local infusion of dopamine in the rACC mimicked the effect of d-amphetamine, suggesting the glutamate response is mediated by dopamine. This was confirmed by experiments where the glutamate response to local d-amphetamine in the rACC was blocked by the Di-like receptor antagonist SCH23390 but not the D2-like receptor antagonist haloperidol. Local infusion of dihydrokainate (DHK), which inhibits the glial GLT-1 glutamate transporter, did not affect spontaneous efflux of glutamate in either subregion. However, DHK increased glutamate efflux during local infusion of d-amphetamine in the cACC, indicating that GLT-1 normally contributes to clearance of glutamate released by d-amphetamine. In contrast, infusion of DHK reduced glutamate efflux in the rACC of rats given systemic d-amphetamine, suggesting that impairment of GLT-1 function leads to reduced glutamate release (possibly through activation of inhibitory autoreceptors). Such striking neurochemical asymmetries enable spatial focussing of the response to d-amphetamine in the ACC and could contribute to demarcation of the role of each of its subregions in regulation of mood and behaviour.
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Owens, Misty. "BDNF-Related Gene Expression of Laser Capture Microdissected Glutamate Neurons from the Anterior Cingulate Cortex in Mouse Models of Autism Spectrum Disorder." Digital Commons @ East Tennessee State University, 2008. https://dc.etsu.edu/etd/3805.
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Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting social behaviors. ASD affects 1 in 59 children with males affected more frequently. ASD is postulated to result from excitatory and inhibitory neurotransmission imbalances. Brain-derived neurotrophic factor (BDNF) signaling affects ASD by influencing synaptogenesis, plasticity, and survival. Studying early in-utero neuropathological changes within ASD requires the use of animal models. Expression of BDNF-associated genes were analyzed within laser capture microdissected pyramidal neurons from the anterior cingulate cortex of male and female BTBR and valproic acid mouse models. No expression differences were found in any gene comparing the three groups. Gender comparisons did identify differences in NTRK2 and EFNB2. Significant correlations of gene expression were identified for male NTRK2 with EFNB2 and GRIN1 and EFNB2 with GRIN1 and female BDNF with GRIN1 expressions (p
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Owens, Misty. "BDNF-Related Gene Expression of Laser Capture Microdissected Glutamate Neurons from the Anterior Cingulate Cortex in Mouse Models of Autism Spectrum Disorder." Digital Commons @ East Tennessee State University, 2020. https://dc.etsu.edu/etd/3805.
Full textAbstract:
Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting social behaviors. ASD affects 1 in 59 children with males affected more frequently. ASD is postulated to result from excitatory and inhibitory neurotransmission imbalances. Brain-derived neurotrophic factor (BDNF) signaling affects ASD by influencing synaptogenesis, plasticity, and survival. Studying early in-utero neuropathological changes within ASD requires the use of animal models. Expression of BDNF-associated genes were analyzed within laser capture microdissected pyramidal neurons from the anterior cingulate cortex of male and female BTBR and valproic acid mouse models. No expression differences were found in any gene comparing the three groups. Gender comparisons did identify differences in NTRK2 and EFNB2. Significant correlations of gene expression were identified for male NTRK2 with EFNB2 and GRIN1 and EFNB2 with GRIN1 and female BDNF with GRIN1 expressions (p
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Edwards, Kristin S. "Effects of Acute Ethanol on Memory Encoding, Retrieval, and the Theta Rhythm." The Ohio State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=osu1300300541.
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Hallin, Nathalie. "Cognitive Dissonance : Neural Correlates and New Theoretical Approaches." Thesis, Högskolan i Skövde, Institutionen för kommunikation och information, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-7173.
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Cognitive dissonance has traditionally been defined as the negative affective state which accompanies inconsistent cognitions and motivates one to make the cognitions consistent. This thesis critically evaluates two theories about cognitive dissonance. The action-based model of dissonance argues that inconsistent cognitions have the potential to interfere with effective and unconflicted action. The new look model of dissonance, contradicting the traditional definition of dissonance, argues that it is aversive consequences rather than inconsistent cognitions that cause dissonance. Recent studies investigating the neural correlates of dissonance show that parts of anterior cingulate cortex and prefrontal cortex seem to be involved in the dissonance process. One of the major predictions of the new look model of dissonance has been undermined by recent evidence. In contrast, the action-based model of dissonance is supported by recent studies.
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Alexander, Laith. "Primate ventromedial prefrontal cortex and the physiological and behavioural dysfunction characteristic of mood and anxiety disorders." Thesis, University of Cambridge, 2019. https://www.repository.cam.ac.uk/handle/1810/288429.
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The heterogeneity intrinsic to the ventromedial prefrontal cortex (vmPFC) is evidenced in both its anatomy and implicated function: vmPFC subregions have roles in positive affect, negative affect and autonomic/endocrine regulation. Whether different subregions serve fundamentally different functions, or whether they perform similar computations on different inputs, remains unclear. Nevertheless, the role of the vmPFC in psychopathology is widely appreciated - in mood and anxiety disorders, over-activity within constituent regions of the vmPFC is consistently implicated in symptomatology, together with its normalisation following successful treatment. However, the precise locus of change varies between studies. The work presented in this thesis investigates the causal contributions of over-activity within two key subregions of the vmPFC - the subgenual anterior cingulate cortex (sgACC, area 25) and perigenual anterior cingulate cortex (pgACC, area 32) - in discrete dimensions of behaviour and physiology affected in psychiatric disorders. Specifically, the impact of over-activity is assessed on (i) baseline physiological function; (ii) the regulation of anticipatory, motivational and consummatory aspects of reward-related behaviour; and (iii) negative affect including fear learning, stress recovery and the intolerance of uncertainty. To provide further insight into the mechanism of action of antidepressants, the efficacy of selected treatments is tested on changes induced by over-activity of these regions. Beyond the direct relevance of the results presented here to psychiatric disorders and their treatment, the thesis aims to emphasise the importance of broader themes associated with the measurement and quantification of emotion in preclinical animal studies. First, a multi-faceted approach is utilised enabling quantification of both the autonomic and behavioural aspects of emotion. In so doing, the experiments maintain relevance to studies which assess these correlates in isolation, both in humans (which typically measure subjective responses and physiology) and in rodents (which frequently assess behaviour in isolation). The assessment of more than one dimension of emotion confers these studies with improved power to detect maladaptive changes. Second, the experiments described were conducted in the marmoset, a new-world primate. The extensive anatomical homology between marmoset and human prefrontal cortex facilitates the forward-translation of functional results. In combination with the appropriate assays, this renders marmosets as an invaluable species to study the causal contributions of vmPFC subregions to symptoms of psychiatric disorders. I believe that the results of these experiments provide important insights into the causal role primate vmPFC has in relation to the behavioural and physiological aspects of psychiatric symptomatology. Most importantly, I hope that they serve as the foundation for future work to further elucidate the neuropathological processes underlying mental disorders.
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Costa, Vinícius Pelarin do Nascimento. "Empatia em camundongos: avaliação do papel da amídala, insula e córtex cingulado anterior na nocicepção em camundongos expostos ao teste de contorções abdominais." Universidade Federal de São Carlos, 2014. https://repositorio.ufscar.br/handle/ufscar/1376.
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Previous issue date: 2014-05-09Universidade Federal de Minas Gerais
Empathy can be defined as the capacity for perceive emotional signals from others. Among these signals, the ability to perceive pain has clear adaptive and evolutionary value. Pain can be defined as a subjective experience that includes sensorial, emotional and cognitive components. Evidence has emphasized the role of amygdala, anterior cingulate cortex (ACC) and insula in modulation of pain and empathy. Research indicates the capacity of rodents to express empathy to a conspecific in pain or suffering. Works from literature and finds from our laboratory demonstrated that living together with a cagemate is able to alter the nociceptive behavior in mice. However, there are no works evidencing if occur alterations in nociception by living together with a cagemate with chronic pain and which encephalic structures would be involved in this modulation. To overcome this, male Swiss-albino mice were housed in groups or in pairs. The role of amygdala, ACC and insula are accessed by non-selective inactivation with cobalt chloride (CoCl2). Mice housed in groups (Experiment 1), aging 6-8 weeks, underwent a stereotaxic surgery. 4 to 5 days after surgery, these animals received saline or CoCl2 microinjection, and, after 10 minutes, they were submitted to the writhing test during 5 minutes (acetic acid 0.6%, i.p., nociceptive stimulus). On the dyads (Experiment 2), animals lived together for 28 days since weaning. On the 14th day, one animal of each pair were submitted to a sciatic nerve constriction (SNC animal) or not (sham animal). On the 24th day, the cagemate underwent a stereotaxic surgery, and, on the 28th day, they were submitted to the writhing test after microinjection of saline or CoCl2, like the procedure described to Experiment 1. To Experiment 1 were utilized Student s t test to independent samples; to Experiment 2 were utilized two-way analysis of variance (ANOVA; living together x treatment). Duncan s multiple range tests were utilized as post hoc. A p value of 0.05 or less was required for significance in both experiments. In Experiment 1, inactivation of the amygdala increased the number of writhing, while inactivation of ACC and insula did not alter this measure, suggesting a distinct modulatory role of these structures on the sensorial compound of pain. Our results demonstrated that for the mice that lived in groups, while inactivation of the ACC and insula did not change writhing, inactivation of amygdala increased it, suggesting a distinct modulatory role of these structures on sensory component of pain in the writhing test. In Experiment 2, living together with a SNC-cagemate increased writhing on the pair, suggesting that this experience activates the circuitry of neural representation of pain on the observer mouse (state of priming ). Thus, when this animal experienced nociception, its response was exacerbated. In this condition, inactivation of insula and amygdala produces opposite results, i.e., decreased and increased in contortions in those animals that lived together with a SNC animal, respectively. ACC inactivation did not alter writhing behavior. In this sense, our results suggest a different modulatory role of these structures on cognitive, affective-emotional and sensorial components of pain, and on empathy for pain.
Sob uma perspectiva evolucionista, a empatia é expressa pela capacidade de captar sinais emocionais nos outros. Neste sentido, a habilidade em perceber a dor também possui valor claramente adaptativo e evolutivo. A dor pode ser definida como uma experiência subjetiva que inclui componentes sensoriais, afetivo-emocionais e cognitivos. Evidencias apontam para o papel da amídala, córtex cingulado anterior (CCA) e insula na modulação da dor e da empatia. Estudos indicam para a capacidade de roedores em apresentarem empatia frente à dor ou ao sofrimento de seus coespecíficos. Trabalhos da literatura e do nosso grupo demonstram que a convivência em pares é capaz de alterar bidirecionalmente a resposta nociceptiva em camundongos. Entretanto, nenhum estudo havia ainda evidenciado se ocorrem alterações nociceptivas devido à convivência com um coespecífico em quadro de dor crônica, e quais estruturas encefálicas estariam envolvidas nessa modulação. Neste sentido, camundongos machos Suiço-albinos foram alojados em grupos ou em duplas para avaliação do papel da amídala, insula e córtex cingulado anterior por meio de inativação com cloreto de cobalto (CoCl2). Os animais alojados em grupo (Experimento 1), ao atingirem idade entre 6-8 semanas, passaram por cirurgia estereotáxica. De 4 à 5 dias após a cirurgia, esses animais receberam microinjeção de salina ou CoCl2 e, após 10 minutos, foram submetidos ao teste de contorções abdominais (ácido acético 0,6%, i.p., estímulo nociceptivo) durante 5 minutos. Nas duplas (Experimento 2), os animais conviveram por um período de 28 dias após o desmame. No 14º dia, um animal de cada par foi submetido à cirurgia de constrição do nervo ciático (animal CNC) ou não (animal sham). No 24º dia, o camundongo que conviveu com o animal CNC ou animal sham passou por uma cirurgia estereotáxica, e, no 28º dia, foi submetido ao teste de contorções abdominais, após microinjeção de salina ou CoCl2, conforme Experimento 1. Para o Experimento 1 foi utilizado o teste t de Student para amostras independentes; no Experimento 2 foi utilizada a análise de variância (ANOVA) de dois fatores (convívio x tratamento). O post hoc utilizado foi o teste de comparações múltiplas de Duncan. Os valores de p menores ou iguais a 0,05 foram considerados como significativos nos dois experimentos. No Experimento 1, a inativação da amídala aumentou o número de contorções, enquanto a inativação do CCA e da insula não alterou esse parâmetro, sugerindo um papel modulatório distinto dessas estruturas no componente sensorial da dor para o teste de contorções. No experimento 2, o convívio com um animal CNC aumentou o número de contorções no parceiro, sugerindo que essa convivência causou ativação dos circuitos de representatividade neural da dor no camundongo observador (state of priming ). Dessa forma, quando esse animal experiencia nocicepção, sua resposta é exacerbada. Nessa condição, a inativação da insula e amídala produziu resultados opostos, ou seja, diminuição e aumento das contorções naqueles animais que conviveram com o animal CNC, respectivamente. A inativação do CCA não alterou o número de contorções. Nesse sentido, nossos resultados sugerem um papel modulatório distinto dessas estruturas nos componentes cognitivo, afetivo-emocional e sensorial da dor, e na empatia para a dor.
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Shaw, Lynda Joan. "Emotional processing of natural visual images in brief exposures and compound stimuli : fMRI and behavioural studies." Thesis, Brunel University, 2009. http://bura.brunel.ac.uk/handle/2438/3203.
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Can the brain register the emotional valence of brief exposures of complex natural stimuli under conditions of forward and backward masking, and under conditions of attentional competition between foveal and peripheral stimuli? To address this question, three experiments were conducted. The first, a behavioural experiment, measured subjective valence of response (pleasant vs unpleasant) to test the perception of the valence of natural images in brief, masked exposures in a forward and backward masking paradigm. Images were chosen from the International Affective Picture System (IAPS) series. After correction for response bias, responses to the majority of target stimuli were concordant with the IAPS ratings at better than chance, even when the presence of the target was undetected. Using functional magnetic resonance imaging (fMRI), the effects of IAPS valence and stimulus category were objectively measured on nine regions of interest (ROIs) using the same strict temporal restrictions in a similar masking design. Evidence of affective processing close to or below conscious threshold was apparent in some of the ROIs. To further this line of enquiry, a second fMRI experiment mapping the same ROIs and using the same stimuli were presented in a foveal (‘attended’) peripheral (‘to-be-ignored’) paradigm (small image superimposed in the centre of a large image of the same category, but opposite valence) to investigate spatial parameters and limitations of attention. Results are interpreted as showing both valence and category specific effects of ‘to-be-ignored’ images in the periphery. These results are discussed in light of theories of the limitations of attentional capacity and the speed in which we process natural images, providing new evidence of the breadth of variety in the types of affective visual stimuli we are able to process close to the threshold of conscious perception.
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Demircapa, Idil [Verfasser], and Kristina [Akademischer Betreuer] Hennig-Fast. "Creating a new tool for Post-Traumatic Disorder treatment : real-time functional magnetic resonance imaging neurofeedback of rostral anterior cingulate cortex / Idil Demircapa ; Betreuer: Kristina Hennig-Fast." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2020. http://d-nb.info/1230754490/34.
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Sawamoto, Nobukatsu. "Expectation of pain enhances responses to nonpainful somatosensory stimulation in the anterior cingulate cortex and parietal operculum/posterior insula : an event-related functional magnetic resonance imaging study." Kyoto University, 2001. http://hdl.handle.net/2433/150507.
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Dutta, Arpan. "The effect of NMDA receptor antagonists and antidepressants on resting state in major depressive disorder." Thesis, University of Manchester, 2015. https://www.research.manchester.ac.uk/portal/en/theses/the-effect-of-nmda-receptor-antagonists-and-antidepressants-on-resting-state-in-major-depressive-disorder(0c1dd1fc-ff39-43fb-92c0-7b108e4f6230).html.
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Introduction: The aim of the project was to investigate the effects of antidepressants on brain networks whilst at rest. My hypothesis was that antidepressants work by reversing persistent activity in the brain’s default mode network (DMN). The DMN is implicated in self-reflection and rumination in MDD. The methodologies and results of studies of resting state networks in MDD and the effects of antidepressants are reviewed in the thesis. Increasing evidence implicates glutamate in the action of antidepressant drugs. Whether there are illness related changes in glutamate function is unresolved, largely because of the lack of techniques for assessing it. Ketamine and other NMDA antagonists have improved MDD symptoms within 24 hours though the effects are short lasting. The molecular neural networks involved in ketamine’s putative antidepressant effects are unclear. The thesis reviews the evidence. Much evidence implicates ACC as a site of action of antidepressant effects but whether this is through its regulation of the DMN or other networks is not known. This thesis compares the effect of ketamine and citalopram on ACC-related systems. Method: The thesis combines two systematic reviews of the effects of MDD and antidepressant drugs on i) resting state networks (53 studies) and ii) glutamate neurotransmission (45 studies of clinical efficacy of ketamine). There are two experimental chapters. The first describes investigation into two rapid acting antidepressant drugs acting via glutamate mechanisms. 54 unmedicated cMDD were scanned across two centres on 3T MRI scanners while being infused with placebo (0.5% saline), 0.5mg/kg ketamine or 100mg AZD6765 over 1 hour. fMRI resting state data between drug treatments was compared for the final 25 minutes of the drug infusion and for a 25 minute resting state scan a day later. The second experimental chapter examines whether these effects were shared by citalopram, a standard antidepressant. 67 unmedicated cMDD, rMDD and HC were administered citalopram 7.5mg i.v. and scanned on a 1.5T MRI scanner. In a second study 63 cMDD and HC were administered i.v. citalopram 7.5mg or placebo (0.5% saline). fMRI resting state data for the final 12 ½ minutes following drug infusion was compared. Independent Component Analysis was performed using the Group ICA for fMRI toolbox. The resting component with the highest spatial correlation to the ACC was used. Brain maps of the intensity of the selected component were constructed for each individual. Group averages were calculated and compared using SPM. Regional analysis was performed using Marseille Boite a Regions d'interet. Results: On day 1 AZD6765 significantly increased mean intensity of ACC resting component in the right insula, right IPL and left cingulate gyrus greater than ketamine or placebo. Ketamine increased mean intensity of ACC resting component greater than placebo in the right lentiform nucleus and left mFG. Significantly decreased mean intensity of ACC resting component in the left insula in the AZD6765 group compared to placebo was noted. On day 2 AZD6765 increased mean intensity of ACC resting component greater than ketamine and placebo in the left and right lentiform nuclei. AZD6765 reduced mean intensity of the ACC resting component in the left and right MFG. The first citalopram study revealed reduced mean intensity of ACC resting component in cMDD compared to rMDD and HC in PCC. rMDD had reduced mean intensity of ACC resting component in the precuneus compared to HC. In the second study, citalopram had no effect in HC but normalised precuneus activity in cMDD producing a significant drug x group interaction. Conclusions: The acute antidepressant effects of citalopram are modulated by changes in the bilateral precuneus. The precuneus is central to connectivity with other regions in MDD. It has a prominent role in the DMN and is linked to rumination. The mechanism of the antidepressant effects of AZD6765 is different from those of ketamine and citalopram. The insula, IPL, MFG, cingulate gyrus and lentiform nuclei are all regions implicated in MDD suggesting antidepressant effects. The rapid antidepressant effects of AZD6765 are possibly due to a resetting of the interface between DMN and salience networks.
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Endres, Ralph Julian Verfasser], Ulrike [Gutachter] Lüken, and Marcel [Gutachter] [Romanos. "Networks of fear: Functional connectivity of the amygdala, the insula and the anterior cingulate cortex in two subtypes of specific phobia / Ralph Julian Endres ; Gutachter: Ulrike Lüken, Marcel Romanos." Würzburg : Universität Würzburg, 2019. http://d-nb.info/1187140546/34.
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Okun, Alec. "Mechanistic Evaluation of Affective Dimensions of Pain in Rats." Diss., The University of Arizona, 2012. http://hdl.handle.net/10150/243095.
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Pain is the primary reason why patients seek medical care and there is a great unmet need for the development of pain relieving medications. The treatments that are currently available either have limited efficacy or are accompanied by a multitude of unwanted side effects. However, discovering novel therapeutics for the treatment of pain has been challenging. Part of the reason for this may be that that the ways in which pain is assessed in the preclinical setting are different from the way that it is evaluated clinically in human trials. The most common method for evaluating pain in preclinical models is to measure responses to evoked stimuli. However, a change in the threshold of response to evoked pain likely does not measure whether the unpleasant component of pain has actually been reduced. The most clinically relevant question for pain is whether the treatment actually makes the patients "feel better". Here, we demonstrate that the aversiveness of pain can be captured using motivated behavior to seek pain relief. We used conditioned place preference (CPP) to establish that animals with ongoing pain will seek a context that has been paired with effective pain relief, likely as a result of negative reinforcement. These studies allowed for mechanistic investigation. Our results show that: 1) effective pain relief can be achieved by either blocking noxious peripheral input or by directly attenuating pain related unpleasantness in the brain, and 2) pain relief is rewarding and activates the reward circuitry. These studies provide a basis for development of a future platform for drug discovery for pain.
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Zhang, Suyi. "Encoding and decoding of pain relief in the human brain." Thesis, University of Cambridge, 2019. https://www.repository.cam.ac.uk/handle/1810/286332.
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The studies in this thesis explored how pain and its relief are represented in the human brain. Pain and relief are important survival signals that motivate escape from danger and search for safety, however, they are often evaluated by subjective descriptions only. Studying how humans learn and adapt to pain and relief allows objective investigation of the information processing and neural circuitry underlying these internal experiences. My research set out to use computational learning models to provide mechanistic explanations for the behavioural and functional neuroimaging data collected in pain/relief learning experiments with independent groups of healthy human participants. With a Pavlovian acute pain conditioning task in Experiment 1, I found that 'associability' (a form of uncertainty signal) had a crucial role in controlling the learning rates of different conditioned responses, and can be used to anatomically dissociate underlying neural systems. Experiment 2 focused on relief learning of terminating a tonic pain stimulus, in which the priority for relief-seeking is in conflict with the general suppression of cognition and attention. I showed that associability during active learning not only controls the relief learning rate, but also correlates with endogenously modulated (reduced) ongoing pain. This finding was confirmed in Experiment 3 using an independent active relief learning paradigm in a complex dynamic environment. Critically, both experiments showed that associability was correlated with responses in the pregenual anterior cingulate cortex (pgACC), a brain region previously implicated in aspects of endogenous pain control related to attention and controllability. This provided a potential computational account of an information-sensitive endogenous analgesic mechanism. In Experiment 4, I explored the implications of endogenous controllability for technology-based pain therapeutics. I designed an adaptive closed-loop system that learned to control pain stimulation using decoded real-time pain representations from the brain. Subjects were shown to actively enhance the discriminability of pain only in the pgACC, and uncertainty during learning again correlated with endogenously modulated pain and were associated with pgACC responses. Together, these studies (i) show the importance of uncertainty in controlling learning during both acute and tonic pain, (ii) describe how uncertainty also flexibly modulates pain to maximise the impact of learning, (iii) illustrate a central role for the pgACC in this process, and (iv) reveal the implications for future technology-based therapeutic systems.
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Pasley, Maria Imelda Noblejas [Verfasser], Frank W. [Akademischer Betreuer] Ohl, and Markus [Akademischer Betreuer] Ullsperger. "The role of the anterior cingulate cortex in extinction learning of avoidance behavior and in the retrieval of its extinction memory / Maria Imelda Noblejas Pasley. Betreuer: Frank W. Ohl ; Markus Ullsperger." Magdeburg : Universitätsbibliothek, 2011. http://d-nb.info/1047596237/34.
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Pasley, Maria Imelda Noblejas Verfasser], Frank W. [Akademischer Betreuer] Ohl, and Markus [Akademischer Betreuer] [Ullsperger. "The role of the anterior cingulate cortex in extinction learning of avoidance behavior and in the retrieval of its extinction memory / Maria Imelda Noblejas Pasley. Betreuer: Frank W. Ohl ; Markus Ullsperger." Magdeburg : Universitätsbibliothek, 2011. http://nbn-resolving.de/urn:nbn:de:gbv:ma9:1-771.
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Fillinger, Clémentine. "Identification du connectome de l'aire 24 du cortex cingulaire antérieur dans le contexte du développement de phénotypes de type anxio-dépressif chez la souris : implication de la voie amygdalo-cingulaire." Thesis, Strasbourg, 2017. http://www.theses.fr/2017STRAJ029/document.
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Le cortex cingulaire antérieur (CCA) est une région préfrontale située au centre d’un réseau permettant l’échange d’informations cognitives, motrices, limbiques et viscérales, la plaçant ainsi comme un sujet incontournable dans l’étude de pathologies complexes telles que les troubles anxio-dépressifs. Afin de pouvoir aborder ces pathologies chez la souris, nous avons établi par traçage neuronal le connectome complet des différentes aires composant le CCA. Nous avons ainsi montré qu’une grande majorité des structures de ce connectome communique de manière réciproque avec cette région et que, selon les aires cingulaires, des spécificités de densité d'innervation et de topographie peuvent exister. Ceci suggère des fonctions partagées mais également des rôles plus spécifiques à chaque aire. A partir de ce connectome, nous avons ensuite montré, par une approche optogénétique associée à des tests comportementaux, que l'activation répétée de la projection de l’amygdale au CCA est susceptible d'induire des comportements de type anxio-dépressif chez des souris naïves. Ce travail met donc en évidence le rôle d'une partie du connectome du CCA dans l'établissement des troubles de l'humeurThe anterior cingulate cortex (ACC) is a prefrontal region located at the center of a network allowing the sharing of cognitive, motor, limbic and visceral information, placing it as an interesting target for the study of complex pathologies like mood disorders. To investigate these diseases in mice, we provided the complete connectome of each ACC areas by a tract-tracing approach. We demonstrated that the majority of structures constituting this connectome are reciprocally connected with the ACC and that some density and topographical connection specificities were observed among cingulate areas. These results potentially suggest some shared functions between cingulate areas, also completed by specific roles inherent to each area. Using this connectome, we demonstrated that the repeated activation of the amygdala projection to the ACC was able to induce anxiodepressive-like behaviors in naïve mice, by using optogenetics combined with behavioral tests. This study highlights for the first time the implication of a portion of the ACC connectome in the establishment of mood disorders