Academic literature on the topic 'Cortico-Striatal networks'

Abstract Aberrant dopamine function in the dorsal striatum and aberrant intrinsic functional connectivity (iFC) between distinct cortical networks and thalamic nuclei are among the most consistent large-scale brain imaging findings in schizophrenia. A pathophysiological link between these two alterations is suggested by theoretical models based on striatal dopamine’s topographic modulation of cortico-thalamic connectivity within cortico-basal-ganglia-thalamic circuits. We hypothesized that aberrant striatal dopamine links topographically with aberrant cortico-thalamic iFC, i.e. aberrant associative striatum dopamine is associated with aberrant iFC between the salience network and thalamus, and aberrant sensorimotor striatum dopamine with aberrant iFC between the auditory-sensorimotor network and thalamus. Nineteen patients with schizophrenia during remission of psychotic symptoms and 19 age- and sex-comparable control subjects underwent simultaneous fluorodihydroxyphenyl-l-alanine PET (18F-DOPA-PET) and resting state functional MRI (rs-fMRI). The influx constant kicer based on 18F-DOPA-PET was used to measure striatal dopamine synthesis capacity; correlation coefficients between rs-fMRI time series of cortical networks and thalamic regions of interest were used to measure iFC. In the salience network-centred system, patients had reduced associative striatum dopamine synthesis capacity, which correlated positively with decreased salience network-mediodorsal-thalamus iFC. This correlation was present in both patients and healthy controls. In the auditory-sensorimotor network-centred system, patients had reduced sensorimotor striatum dopamine synthesis capacity, which correlated positively with increased auditory-sensorimotor network-ventrolateral-thalamus iFC. This correlation was present in patients only. Results demonstrate that reduced striatal dopamine synthesis capacity links topographically with cortico-thalamic intrinsic dysconnectivity in schizophrenia. Data suggest that aberrant striatal dopamine and cortico-thalamic dysconnectivity are pathophysiologically related within dopamine-modulated cortico-basal ganglia-thalamic circuits in schizophrenia.

Abstract Background In schizophrenia, among the most consistent brain changes are both aberrant dopamine function in the dorsal striatum and aberrant intrinsic functional connectivity (iFC) between distinct cortical networks and thalamic nuclei; however, it is unknown whether these changes are pathophysiologically related. Such a relationship is expected because cortico-thalamic-connectivity is modulated by striatal dopamine within topographically distinct, parallel but interacting cortico-basal-ganglia-thalamic circuits. We hypothesized: (1) Within-circuits, aberrant striatal dopamine contributes to aberrant cortico-thalamic-iFC, specifically, associative-striatum dopamine contributes to salience-network-thalamic-iFC, and sensorimotor-striatum dopamine to auditory-sensorimotor-network-thalamic-iFC. (2) Due to between-circuits interactions following an anterior-to-posterior gradient, salience-network-centered-system changes contribute to auditory-sensorimotor-network-centered-system changes. Methods To test these hypotheses, 19 patients with schizophrenia during symptomatic remission of positive symptoms and 19 age- and sex-comparable controls underwent simultaneous fluorodihydroxyphenyl-L-alanine positron emission tomography (18F-DOPA-PET) and resting-state functional magnetic resonance imaging (rs-fMRI). The influx constant kicer based on 18F-DOPA-PET was used to measure dopamine synthesis capacity (DSC), indicating striatal dopamine function; correlation coefficients between rs-fMRI time-series of cortical networks and thalamic regions-of-interest were used to measure iFC. Results In the salience-network(SAL)-centered-system, patients had reduced associative-striatum-DSC, which correlated positively with SAL-mediodorsal-thalamus-iFC and mediated the reduction of SAL-thalamic-iFC in patients. In the auditory-sensorimotor-network(ASM)-centered-system, patients had reduced sensorimotor-striatum-DSC, which correlated positively with ASM-ventrolateral-thalamus-iFC, but did not mediate increased ASM-thalamic-iFC in patients. Finally, aberrant DSC and iFC of the SAL-centered-system mediated corresponding changes in the ASM-centered-system. Discussion Results demonstrate that cortico-thalamic-dysconnectivity links with aberrant striatal dopamine in schizophrenia - in a topographically distinct way, with an anterior-to-posterior gradient, and primary changes in the SAL-centered system.

BackgroundThe efficient organization and communication of brain networks underlie cognitive processing and their disruption can lead to pathological behaviours. Few studies have focused on whole-brain networks in obesity and binge eating disorder (BED). Here we used multi-echo resting-state functional magnetic resonance imaging (rsfMRI) along with a data-driven graph theory approach to assess brain network characteristics in obesity and BED.MethodMulti-echo rsfMRI scans were collected from 40 obese subjects (including 20 BED patients) and 40 healthy controls and denoised using multi-echo independent component analysis (ME-ICA). We constructed a whole-brain functional connectivity matrix with normalized correlation coefficients between regional mean blood oxygenation level-dependent (BOLD) signals from 90 brain regions in the Automated Anatomical Labeling atlas. We computed global and regional network properties in the binarized connectivity matrices with an edge density of 5%–25%. We also verified our findings using a separate parcellation, the Harvard–Oxford atlas parcellated into 470 regions.ResultsObese subjects exhibited significantly reduced global and local network efficiency as well as decreased modularity compared with healthy controls, showing disruption in small-world and modular network structures. In regional metrics, the putamen, pallidum and thalamus exhibited significantly decreased nodal degree and efficiency in obese subjects. Obese subjects also showed decreased connectivity of cortico-striatal/cortico-thalamic networks associated with putaminal and cortical motor regions. These findings were significant with ME-ICA with limited group differences observed with conventional denoising or single-echo analysis.ConclusionsUsing this data-driven analysis of multi-echo rsfMRI data, we found disruption in global network properties and motor cortico-striatal networks in obesity consistent with habit formation theories. Our findings highlight the role of network properties in pathological food misuse as possible biomarkers and therapeutic targets.

Over the past decade advances in tracing and imaging techniques have spurred the development of increasingly detailed maps of brain connectivity. Broadly termed ‘connectomes’, these maps provide a powerful tool for systems neuroscience. As with most ‘maps’, connectomes offer a static spatial description of the brain’s circuits, whereas timing and temporal processing are inherently dynamic processes; nevertheless, the timing field stands to be a major beneficiary of these large-scale mapping projects. The recently reported ‘projectome’ of mouse cortico-striatal sub-networks is of particular interest because theoretical developments such as the striatal beat-frequency model emphasize the role of the striatum in temporal processing. The cortico-striatal projectome confirms that the dorsal striatum is ideally situated to sample patterns of activity throughout most of the cortex, but that it also contains a level of modularity previously not considered by integrative models of interval timing. Furthermore, the striatal projectome will allow for targeted studies of whether specific subdivisions of the dorsal striatum are differentially involved in timing and time perception as a function of task, stimulus modality, intensity, and valence.

The basal ganglia (BG) promote complex sequential movements by helping to select elementary motor gestures appropriate to a given behavioral context. Indeed, Huntington’s disease (HD), which causes striatal atrophy in the BG, is characterized by hyperkinesia and chorea. How striatal cell loss alters activity in the BG and downstream motor cortical regions to cause these disorganized movements remains unknown. Here, we show that expressing the genetic mutation that causes HD in a song-related region of the songbird BG destabilizes syllable sequences and increases overall vocal activity, but leave the structure of individual syllables intact. These behavioral changes are paralleled by the selective loss of striatal neurons and reduction of inhibitory synapses on pallidal neurons that serve as the BG output. Chronic recordings in singing birds revealed disrupted temporal patterns of activity in pallidal neurons and downstream cortical neurons. Moreover, reversible inactivation of the cortical neurons rescued the disorganized vocal sequences in transfected birds. These findings shed light on a key role of temporal patterns of cortico-BG activity in the regulation of complex motor sequences and show how a genetic mutation alters cortico-BG networks to cause disorganized movements.

Neuroimaging research has highlighted maladaptive thalamo-cortico-striatal interactions in obsessive-compulsive disorder as well as a more general deficit in prefrontal functioning linked with compromised executive functioning. More specifically, dysfunction in the ventromedial prefrontal cortex, a central hub in coordinating flexible behaviour, is thought to be central to obsessive-compulsive disorder symptomatology. We sought to determine the intrinsic alterations of the ventromedial prefrontal cortex in obsessive-compulsive disorder employing resting-state functional connectivity magnetic resonance imaging analyses with a ventromedial prefrontal cortex seed region of interest. A total of 38 obsessive-compulsive disorder patients and 33 matched controls were included in our analyses. We found widespread ventromedial prefrontal cortex hyperconnectivity during rest in patients with obsessive-compulsive disorder, displaying increased connectivity with its own surrounding region in addition to hyperconnectivity with several areas along the thalamo-cortico-striatal loop: thalamus, caudate and frontal gyrus. Obsessive-compulsive disorder patients also exhibited increased functional connectivity from the ventromedial prefrontal cortex to temporal and occipital lobes, cerebellum and the motor cortex, reflecting ventromedial prefrontal cortex hyperconnectivity in large-scale brain networks. Furthermore, hyperconnectivity of the ventromedial prefrontal cortex and caudate correlated with obsessive-compulsive disorder symptomatology. Additionally, we used three key thalamo-cortico-striatal regions that were hyperconnected with our ventromedial prefrontal cortex seed as supplementary seed regions, revealing hypoconnectivity along the orbito- and lateral prefrontal cortex-striatal pathway. Taken together, these results confirm a central role of a hyperconnected ventromedial prefrontal cortex in obsessive-compulsive disorder, with a special role for maladaptive crosstalk with the caudate, and indications for hypoconnectivity along the lateral and orbito pathways.

The formation of new perceptual categories involves learning to extract that information from a wide range of often noisy sensory inputs, which is critical for selecting between a limited number of responses. To identify brain regions involved in visual classification learning under noisy conditions, we developed a task on the basis of the classical dot pattern prototype distortion task [M. I. Posner, Journal of Experimental Psychology, 68, 113–118, 1964]. Twenty-seven healthy young adults were required to assign distorted patterns of dots into one of two categories, each defined by its prototype. Categorization uncertainty was modulated parametrically by means of Shannon's entropy formula and set to the levels of 3, 7, and 8.5 bits/dot within subsets of the stimuli. Feedback was presented after each trial, and two parallel versions of the task were developed to contrast practiced and unpracticed performance within a single session. Using event-related fMRI, areas showing increasing activation with categorization uncertainty and decreasing activation with training were identified. Both networks largely overlapped and included areas involved in visuospatial processing (inferior temporal and posterior parietal areas), areas involved in cognitive processes requiring a high amount of cognitive control (posterior medial wall), and a cortico-striatal–thalamic loop through the body of the caudate nucleus. Activity in the medial prefrontal wall was increased when subjects received negative as compared with positive feedback, providing further evidence for its important role in mediating the error signal. This study characterizes the cortico-striatal network underlying the classification of distorted visual patterns that is directly related to decision uncertainty.

La mémoire procédurale est la mémoire des habitudes motrices. Les ganglions de la base (GB), un groupe de structures impliqué dans les fonctions motrices et cognitives, sont responsables de la formation de cette mémoire. Le striatum, principale structure d’entrée des GB, joue un rôle central dans le transfert de l’information entre le cortex et les autres structures sous-corticales, assurant ainsi la sélection et l’intégration de l’information corticale au sein de boucles fonctionnelles parallèles. Lors d’un apprentissage procédural, le comportement est tout d’abord dirigé vers un but, impliquant les boucles associatives et le striatum dorsomédial (DMS), pour ensuite évoluer vers un comportement habituel automatique, impliquant les boucles sensorimotrices et le striatum dorsolatéral (DLS). L’anatomie des circuits et la dynamique des réseaux striataux au cours de l’apprentissage procédural ont été bien décrites. Cependant, comment la mémoire procédurale est précisément encodée au niveau des réseaux corticostriataux (CS) reste inconnu.Dans mon travail de thèse, nous nous sommes intéressés à la caractérisation des dynamiques des réseaux CS impliqués dans l’apprentissage procédural et nous avons exploré l’existence de substrats neuronaux responsables de la formation de cette mémoire. Grâce à l’imagerie calcique ex vivo nous avons monitoré l’activité des réseaux CS durant les différentes phases d’apprentissage. Nous avons extrait et analysé les signaux calciques des neurones épineux moyens (MSN), les neurones de sortie du striatum. Afin de distinguer les MSNs des autres neurones striataux, nous avons développé un classifieur basé sur les réponses calciques des neurones et leur morphologie. Nous avons montré qu’il existe une réorganisation spécifique des réseaux DMS pendant la 1ère phase d’apprentissage moteur. L’activité dans le DMS est diminuée après un entraînement léger, avec une forte activité (HA) maintenue dans un petit groupe de cellules, et retournant à un niveau basal après un entrainement intense. Dans le DLS, la réorganisation est graduelle et localisée dans des ‘clusters’ d’activité (HA) après un entrainement intense. L’existence des cellules et clusters HA est directement corrélée à la qualité de l’apprentissage. Nous avons ensuite exploré les mécanismes sous-tendant cette réorganisation. Grâce à des enregistrements en patch-clamp nous avons examiné les propriétés des cellules et clusters HA et montré une augmentation du poids synaptique des afférences du cortex cingulaire sur les cellules HA dans le DMS après un entrainement léger. Des études de traçage anatomique ont montré des changements plus robustes dans le DLS avec une augmentation du nombre de projections du cortex somatosensoriel après entrainement intense. Une stratégie cFos-TRAP couplée à la chimiogénétique nous a permis d’inhiber spécifiquement les cellules et clusters HA, et montrer que cela affecte l’apprentissage moteur. Ceci montre la nécessité de ces cellules dans les premières et dernières phases de l’apprentissage moteur respectivement.Ensuite, notre but était d’explorer s’il existe des déficits d’apprentissage moteur dans une phase présymptomatique dans un modèle murin de la maladie de Huntington, et d’examiner l’association de ces déficits à des altérations au niveau des réseaux CS. Nous avons d’abord montré qu’il existait des déficits dans la dernière phase d’apprentissage dans ce modèle murin. Grâce à l’imagerie calcique ex vivo, nous avons observé une altération des réseaux du DMS et du DLS dans des conditions naïve ainsi qu’une absence de réorganisation des réseaux après l’apprentissage. Ainsi, ces résultats confirment l’importance de la réorganisation des réseaux pour l’apprentissage moteur.L’ensemble de ce travail offre de nouvelles perspectives quant au rôle des réseaux CS et leur réorganisation dans l’apprentissage moteur. La nécessité des cellules HA et des clusters ouvrent les portes du monde de l’engramme dans les réseaux striataux
Procedural memory is the memory of habits, involved in the acquisition and maintenance of new motor skills. The neural substrates underlying this memory are the basal ganglia (BG), a group of structures involved in motor and cognitive functions. The input nucleus of the BG is the striatum, earning it a central role in relaying information between the cortex and other subcortical structures, thus ensuring the selection and integration of cortical information within parallel functional loops. Procedural learning first follows a goal-directed behavior mediated by the associative loops, including the dorsomedial striatum (DMS), which is then transferred to an automatic behavior where habit is formed and mediated by the sensorimotor loops including the dorsolateral striatum (DLS). The anatomy and the evolution of the dynamics of the striatal networks has been well described during procedural learning, and the involvement of each striatal territory in a specific phase of learning established. However, how procedural learning is encoded at the level of the corticostriatal networks remains unknown.During my PhD work, we were interested in characterizing the dynamics of the corticostriatal networks involved in motor skill learning and determining the neural correlates responsible for the formation of this memory. We first used two-photon ex vivo calcium imaging to monitor the activity of the networks during the different phases of procedural learning. First we extracted the calcium responses of only medium spiny neurons (MSNs), the striatal output neurons. To distinguish MSNs from other striatal neurons, we developed a cell-sorting classifier based on the calcium responses of neurons and their morphology. We showed a specific reorganization of the DMS networks during the early phase, and the DLS during the late phase of motor skill learning. In DMS, the activity of the networks decreased after early training and returned to a basal level after late training. The main activity of the DMS networks was held by a group of highly active (HA) cells. In DLS, the reorganization of the activity was gradual and localized in small clusters of activity after late training. We then examined the properties of the HA cells in DMS and clusters in DLS. The existence of HA cells and clusters are directly correlated to the performance of the animals. Whole-cell patch-clamp recordings allowed us to characterize electrophysiological properties of HA bells and determine an increase of the synaptic weight of cingulate cortex inputs to HA cells in DMS after early learning. Anatomical tracing showed more robust changes in the DLS with an increase of the number of somatosensory projections to the DLS after late training. Using an AAV cFos-TRAP strategy coupled to chemogenetics, we inhibited HA and cluster cells, leading to impaired motor learning. These experiments thus highlighted the necessity of these cells in early and late phases of motor skill learning respectively.Next we wanted to explore if deficits in motor skill learning occur in a premotor-symptomatic phase of a mouse model of Huntington’s disease (HD), and if they would be associated to dysfunctions in the corticostriatal networks. We first showed deficits in the late phase of motor skill learning in a mouse model of HD. Using ex vivo two-photon calcium imaging, we explored the DMS and DLS networks and we observed an alteration of both networks in naïve HD animals and in addition, an absence of reorganization upon motor skill learning. These results confirm the importance of the reorganization of the networks in motor skill learning.Altogether, this work provides a new insight on the role of the corticostriatal networks and their reorganization in motor skill learning. The necessity of HA and cluster cells opens the door of the ‘engram’ world to the striatal networks

Studies using functional neuroimaging have played a critical role in the current understanding of the neurobiology of obsessive-compulsive disorder (OCD). Early studies using positron emission tomography (PET) identified a core cortico-striatal-thalamo-cortical circuit that is dysfunctional in OCD. Subsequent studies using behavioral paradigms in conjunction with functional magnetic resonance imaging (fMRI) have provided additional information about the neural substrates underlying specific psychological processes relevant to OCD. More recently, studies utilizing resting state fMRI have identified abnormal functional connectivity within intrinsic brain networks including the default mode and frontoparietal networks in OCD patients. Although these studies, as a whole, clearly substantiate the model of cortico-striatal-thalamo-cortical circuit dysfunction in OCD and support the continued investigation of neuromodulatory treatments targeting these brain regions, there is also growing evidence that brain regions outside this core circuit, particularly frontoparietal regions involved in cognitive control processes, may also play a significant role in the pathophysiology of OCD.

Work in animal models has great potential to shed light on the neural circuit perturbations that lead to OCD-related behaviors. Circuit-specific manipulations allow testing of the causal role of the brain network abnormalities observed in clinical imaging studies, with a precision that is not possible in investigations in humans. In recent years, circuit-specific manipulations in animals using a range of technologies have confirmed that abnormalities in the cortico-striatal circuitry can produce repetitive behaviors, such as excessive grooming. This chapter summarizes these advances. Refining our understanding of the contribution of particular neural circuits to OCD-relevant behaviors can inform the development of anatomically targeted treatments, such as deep brain stimulation.

Obsessive-compulsive disorder (OCD) is associated with abnormalities in the cortico-striatal–thalamic–cortical (CSTC) circuitry, and may be associated with dysregulation of neurotransmitters within this network. The major neurotransmitters of the CSTC are serotonin, dopamine, glutamate and γ‎-aminobutyric acid (GABA. This chapter reviews evidence of the involvement of these neurotransmitters in OCD from pharmaocological, genetic, and imaging studies. yielding an integrated neurotransmitter model of OCD. It concludes that the neurotransmitter model of OCD involves dopaminergic and glutamatergic overactivity in frontostriatal pathways, along with diminished serotonergic and GABAergic neurotransmission in frontolimbic systems. These neurotransmitter imbalances may explain frontostriatal hyperactivity and impaired frontolimbic emotion regulation. Advancing our understanding of neurotransmitter abnormalities in OCD, and how abnormalities in different transmitter systems relate to one another, holds promise for the development of new pharmacotherapies.

Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS), along with other tic disorders, involve pathophysiological alterations in the cortico-striatal circuitry. Both are neurodevelopmental conditions, although OCD can also have adult onset. They are frequently comorbid and often run together in families. Recent genetic studies suggest shared risk factors, especially in the case of early-onset OCD. Because of these shared characteristics, they are treated together here. Structural and functional neuroimaging studies are refining our understanding of the abnormalities in corticostriatal connectivity that accompany symptomatology; in the case of TS, these have been accompanied by exciting observations in postmortem tissue that are beginning to connect observed anatomical and network abnormalities to underlying cellular substrates. Finally, recent advances in animal modeling of pathophysiology have allowed testing of specific etiological hypotheses and have established several systems in which more precise mechanistic studies of pathophysiology are now proceeding.