Littérature scientifique sur le sujet « Whole brain mapping »

Butterfly larvae display intricate cognitive capacities and behaviors, but relatively little is known about how those behaviors alter their brains at the molecular level. Here, we optimized a hybridization chain reaction 3.0 (HCR v3.0) protocol to visualize the expression of multiple RNA molecules in fixed larval brains of the African butterfly Bicyclus anynana. We optimized the polyacrylamide gel mounting, fixation, and sample permeabilization steps, and mapped the expression domains of ten genes in whole larval brain tissue at single-cell resolution. The genes included optomotor blind (omb), yellow-like, zinc finger protein SNAI2-like (SNAI2), weary (wry), extradenticle (exd), Synapsin, Distal-less (Dll), bric-à-brac 1 (bab1), dachshund (dac), and acetyl coenzyme A acetyltransferase B (AcatB). This method can be used alongside single-cell sequencing to visualize the spatial location of brain cells that change in gene expression or splicing patterns in response to specific behaviors or cognitive experiences.

Functional connectivity MRI (fcMRI) based on the blood oxygen level dependent (BOLD) contrast has become a widely used modality for mapping the brain's functional architecture. In recent years, applications of fcMRI have led to numerous breakthroughs in both clinical research and basic sciences. However, there are a number of unresolved issues associated with fcMRI relating to both the modality itself, and to methods used to analyse fcMRI data. The aim of this thesis was twofold: to develop novel data analysis procedures, and to demonstrate their feasibility in dedicated neuroimaging studies. Subject head movement can act as a significant confound in fcMRI. Investigating this issue, it was found that subject motion can induce significant increases and decreases in functional connectivity across the brain. A novel motion correction method was developed, which proved more effective than standard procedures in the removal of motion induced connectivity changes. The BOLD contrast is not a direct measure of neural activity, it measures the hemodynamic response caused by changes in neural activity, which varies across the brain. The hypercapnic state is often used to calibrate the BOLD signal. This calibration crucially relies on the assumption that hypercapnia does not affect neuronal activity. An investigation into the hypercapnic state revealed that it is associated with both increases and decreases in functional connectivity. Whilst carrying out this investigation, a number of limitations, such as the need for a hypothesis and information loss, were identified in standard data analysis procedures. Three novel methods were developed to address these limitations. The efficacy of these methods was demonstrated in four different neuroimaging studies, which investigated functional connectivity changes induced by hypercapnia, aerobic exercise, hormonal changes across the menstrual cycle, and electroconvulsive therapy treatment in depression.

Les comportements sont codés par des circuits neuronaux, englobant le cerveau, qui changent avec l'âge et l'expérience. L'immunodétection du gène c-Fos est utilisée depuis des décennies pour révéler les circuits neuronaux activés lors de tâches ou de conditions spécifiques. La méthode c-Fos présente cependant deux limites : 1) L'expression du c-Fos est limitée dans le temps. 2) Les quantifications sont chronophages et souvent limitées à une seule région cérébrale. Le premier objectif de ma thèse consistait à relever les défis actuels liés à l’étude de l'activité neuronale impliquée dans différents comportements à l’échelle du cerveau entier. Ainsi, j'ai développé un workflow contournant les limitations temporelles et spatiales associées à c-Fos. La combinaison de l’expression c-Fos avec celle de tdTomato, Cre-dépendante du c-Fos (souris TRAP2), m’a permis de visualiser et d'effectuer une comparaison directe des circuits neuronaux activés à différents moments ou au cours de différentes tâches. En utilisant des logiciels libres d’acces (QuPath et ABBA), j'ai établi un workflow qui optimise et automatise la détection des cellules, leur classification (c-Fos vs. c-Fos/tdTomato) et l'enregistrement du cerveau entier. Ce workflow automatique, basé sur des scripts entièrement automatisés, permet une quantification précise du nombre de cellules avec une variabilité interindividuelle minimale. De plus, l'interrogation d’atlas cérébraux à différentes échelles (de simplifiée à détaillée) a été réalisée, permettant un zoom progressif sur des régions cérébrales définies afin d'explorer la distribution spatiale des cellules activées. Enfin, j'ai illustré le potentiel de cette approche en comparant les schémas d'activation neuronale dans divers contextes (états de vigilance, comportement social) dans des groupes d'animaux distincts ainsi qu'au sein des mêmes animaux. Enfin, BrainRender a été utilisé pour la représentation intuitive des résultats obtenus. Ainsi ce workflow automatisé et accessible à tous les laboratoires ayant une expérience en histologie permet une analyse impartiale, rapide et précise de l'ensemble du modèle d'activité cérébrale au niveau cellulaire, dans différents contextes. Mon deuxième objectif consistait à étudier l'interdépendance de comportements spécifiques par l’étude des effets de la privation de sommeil paradoxal sur l'apprentissage perceptif olfactif. Cette tâche d'apprentissage est définie comme une capacité à discriminer entre deux odorants perceptivement similaires après une exposition passive à celles-ci pendant 10 jours, un processus partiellement dépendant de la neurogenèse adulte. c-Fos, en combinaison avec l’expression de tdTomato (souris TRAP2), m’a permis de visualiser l'activité neuronale avant et après l'apprentissage perceptif. Une privation de sommeil paradoxal automatisée pendant 4 heures par jour après cet apprentissage à permis d’observer une absence de discrimination olfactive. Ainsi sont posées des bases solides pour de futures études, impliquant notre workflow automatisé pour évaluer l'activité neuronale dans le bulbe olfactif et les centres olfactifs supérieurs du cerveau. En outre, le rôle des nouveaux neurones et l'impact de la privation de sommeil paradoxal sur leurs schémas d'activité seront explorés ultérieurement. En conclusion, le travail présenté dans ma thèse apporte des avancées méthodologiques significatives en développant un workflow automatisé sur l'ensemble du cerveau pour visualiser et comparer les circuits neuronaux activés dans différents comportements. Ainsi, l'exploration de l'impact de la privation de sommeil paradoxal sur l’apprentissage perceptif olfactif met en évidence la relation complexe entre le sommeil et le traitement sensoriel, posant les bases de futures recherches sur les mécanismes neuronaux qui sous-tendent ces processus
Behaviors are encoded by widespread neural circuits within the brain which change with age and experience. Immunodetection of the immediate early gene c-Fos has been used for decades to reveal neural circuits activated during specific tasks or conditions. While successful, c-Fos method presents two limitations: 1) c-Fos expression is restricted in time, and cannot be used to follow up the same neurons activation over time or in response to different stimuli. 2) Quantifications are time consuming and often performed for a single brain region which restricts spatial information. A first objective of my thesis consisted in addressing challenges associated with whole brain probing of neuronal activity involved in higher sensory information processing. To this end, I developed and benchmarked a workflow that circumvents temporal and spatial limitations associated with c-Fos quantification. I combined c-Fos with c-Fos driven Cre-dependent tdTomato expression (i.e. TRAP2 mice), to perform a direct comparison of neural circuits activated at different times or during different tasks. Using open-source softwares (i.e. QuPath and ABBA), I established a workflow that optimize and automate cell detection, cell classification (e.g. c-Fos vs. c-Fos/tdTomato) and whole brain registration. This automatic workflow, based on fully automatic scripts, allows accurate quantification with minimal interindividual variability. Further, interrogation of brain atlases at different scales (from simplified to detailed) was performed, allowing a gradual zoom on defined brain regions to explore the spatial distribution of activated cells. I finally illustrated the potential of this approach by comparing patterns of neuronal activation in various contexts, i.e. wakefulness, paradoxical sleep and social interaction tasks, in distinct animal groups as well as within the same animals. Finally, BrainRender was used for intuitive representation of obtained results. Altogether, this automated workflow accessible to all labs with some experience in histology, allows an unbiased, fast and accurate analysis of the whole brain activity pattern at the cellular level, in various contexts. As an extension of this work, the second objective of my PhD focused on investigating the interdependence of specific behaviours. To this end, I studied effects of paradoxical sleep deprivation on olfactory perceptual learning. This learning task is defined as an enhanced ability to discriminate between two perceptually similar odorants following passive exposure to these 2 odorants for 10 days, a process partially reliant on adult neurogenesis. I used c-Fos immunohistochemistry in combination with tdTomato expression (TRAP2 mice), to visualize neuronal activity before and after perceptual learning. I have implemented a chronic automated paradoxical sleep deprivation for 4 hours per days following the olfactory perceptual learning protocol. Our behavioural data revealed that paradoxical sleep deprivation altered the improvement of odour discrimination. This work lays a solid foundation for future studies, which will extend the automated workflow I developed to evaluate neuronal activity within the olfactory bulb, as well as in higher olfactory centres in the brain. Additionally, the role of adult-born neurons and the potential impact of paradoxical sleep deprivation on their activity patterns will be explored further. In conclusion, the work presented in my thesis provides significant advancements in addressing the limitations of traditional c-Fos quantification methods by developing an automated, whole-brain workflow to visualize and compare neural circuits activated under different conditions. Furthermore, the exploration of the impact of paradoxical sleep deprivation on perceptual learning highlights the intricate relationship between sleep and sensory processing, laying the groundwork for future investigations into the neural mechanisms underlying these processes

The neuronal and molecular mechanisms underlying behavioral responses triggered by fear have received wide interest in the last few years, and various preclinical studies have addressed potential treatments for fear-related disorders. The central histaminergic system is an important modulator of memory related to adverse events and the integrity of the brain histamine system is necessary for the consolidation of this type of memory. Therefore, the use of antihistaminic drugs could be useful for the treatments of conditions such as obsessive-compulsive disorders, post-traumatic stress disorders and generalized anxiety. In this context, it is essential to understand the neuronal circuits involved in behavioral responses associated with adverse events. During my PhD, I developed a pipeline for mapping neuronal activation at micron resolution, combining transgenic approach, clearing protocol, high-resolution imaging, atlas registration, and automated 3D image analysis. The combination of high-resolution imaging and 3D analysis for processing sub-cellular information became the key point of this pipeline, enabling high performance. This pipeline was validated using a classical paradigm, as step-through passive inhibitory avoidance, to analyze neuronal activation patterns across the entire brain of male and female mice, at selected time points. This approach highlighted a strong sexual dimorphism, during fear learning and recall, which was not evident from the behavioral task. Further, it identified brain regions whose degree of activity correlated to specific behavioral features. Finally, micron-scale 3D resolution was exploited to investigate histaminergic subpopulations elicited by aversive events. The combination of behavioral, transgenic, optical and computational methods presented here represents an important tool to quantitatively characterize the neuronal pathways involved in fear memories.

Tese de mestrado integrado em Engenharia Biomédica e Biofísica (Sinais e Imagens Médicas), Universidade de Lisboa, Faculdade de Ciências, 2021
O líquido cefalorraquidiano (LCR) tem um papel essencial na drenagem dos resíduos resultantes do metabolismo cerebral e o constante movimento a que este fluido está sujeito é vital para manter a homeostasia do cérebro. Com feito, alterações neste movimento, geralmente associadas com o envelhecimento ou com doença, levam a perturbações fisiológicas, como a doença de Alzheimer ou a hidrocefalia. Por esta razão, é fundamental consolidar e aprofundar o conhecimento referente a este fluido, nomeadamente perceber como varia a sua velocidade e deslocamento, pois só desta forma será possível desenvolver e aperfeiçoar a prevenção e tratamento destas perturbações. Com efeito, este fluido está em constante movimento e o seu comportamento está intimamente ligado ao ciclo cardíaco. Apesar de estudos anteriores sobre a velocidade e o deslocamento do líquido cefalorraquidiano através de métodos de Ressonância Magnética (RM), ainda não existe uma descrição completa sobre o comportamento deste fluido. O objetivo principal deste estudo, consistiu em obter uma descrição detalhada da velocidade e do deslocamento do LCR através da aquisição de imagens de ressonância magnética obtidas com contraste de fase, um método de referência no que toca ao estudo da velocidade de fluidos No entanto, utilizar RM de contraste de fase para adquirir velocidades mais baixas, como as do LCR, requer tempos de aquisição mais longos e, consequentemente, as imagens obtidas estão mais sujeitas a distorções. Assim, a segunda parte deste projecto partiu dos resultados de deslocamento obtidos através da RM com contraste de fase para otimizar os parâmetros de uma segunda sequência de MR. Esta sequência é relativamente recente e possibilita o estudo do deslocamento sub-milimétrico do LCR associado ao movimento do cérebro através da aplicação de gradientes sucessivos (DENSE). Porém, é necessária uma escolha rigorosa dos parâmetros utilizados de forma a obter resultados que retratem o deslocamento do LCR de uma forma rigorosa e exata. Na primeira parte deste projecto, quatro voluntários foram estudados utilizando RM com contraste de fase, entre outubro de 2019 e fevereiro de 2020, em concordância com as diretrizes éticas da University Medical Center em Utrecth, Países Baixos. As aquisições foram realizadas utilizando um scanner de RM Philips 7 T e dois tipos de contraste foram utilizados: contraste de fase com 1mm de resolução isotrópica e com uma codificação de velocidade de 5m/s, e imagens 3D com ponderação em T1 com 1mm de resolução isotrópica. As imagens foram obtidas para três orientações distintas: anterior posterior, inferior-superior, e direita-esquerda. Na segunda parte deste projecto, dois voluntários foram estudados, de janeiro a fevereiro de 2020, utilizando seis contrastes: contraste de fase com 1mm de resolução isotrópica, e imagens 3D com ponderação em T1 com 1mm de resolução isotrópica, uma sequência básica DENSE com 2mm de resolução isotrópica, uma sequência básica DENSE com 3mm de resolução isotrópica, uma sequência DENSE com uma preparação T2 com 3mm de resolução isotrópica e, finalmente, uma sequência DENSE com tempo de eco prolongado com 3mm de resolução isotrópica. No entanto, e ao contrário das imagens adquiridas na primeira parte deste projecto, as imagens da segunda parte foram obtidas apenas para a orientação inferior-superior. Todas as imagens adquiridas no decorrer desta dissertação foram obtidas com gating cardíaco. O gating cardíaco foi realizado através da utilização de um eletrocardiograma e de um oxímetro de pulso de modo a relacionar o evolução da velocidade e do deslocamento com o ciclo cardíaco. Neste projecto foi também desenvolvida uma pipeline que permite que a partir das imagens adquiridas seja possível estudar a velocidade e o deslocamento do LCR. Esta pipeline inclui diversos passos. O primeiro passo consistiu em realinhar e co-registar as imagens obtidas de forma a permitir uma análise voxel a voxel. Seguidamente, as imagens foram segmentas em três tipos de tecidos: LCR, substância cinzenta, e substância branca. Adicionalmente, as primeiras etapas foram realizadas através da utilização de toolboxs disponíveis no MATLAB como o SPM e o CAT12. Posteriormente, os artefactos presentes nas imagens, tais como as correntes-eddy, foram corrigidos. No decorrer deste projecto diversas regiões foram analisadas e foram divididas em dois grupos: regiões do sistema ventricular, nas quais se incluíram os ventrículos laterais, o terceiro e quarto ventrículo, o aqueduto de Sylvius e a Cisterna Magna; e regiões mais abrangentes, como a região anterior e posterior do cérebro. Estas áreas do cérebro foram selecionadas através da segmentação das imagens anatómicas. Finalmente, a velocidade de cada uma destas regiões foi extraída e integrada ao longo do ciclo cardíaco de maneira a calcular o deslocamento do LCR. Os resultados obtidos relativamente à velocidade mostraram consistência para os quatro voluntários deste projecto. Verificou-se que as regiões do sistema ventricular demonstram valores de velocidade consideravelmente mais elevados do que as regiões mais abrangentes. Com efeito, a região que apresentou valores absolutos de velocidade mais elevados foi o aqueducto de Sylvius. Adicionalmente, verificou-se que as velocidades são superiores na orientação caudal-cranial e inferiores na orientação direita-esquerda. Concluiu-se também que o valor de velocidade escolhido não foi o mais indicado para as regiões mais abrangentes pois a velocidade destas regiões é significativamente inferior e, desta forma, poderá ter existido perda de sinal do LCR. Posteriormente, ao integrar a velocidade obtida através da RM com contraste fase obtiveram-se mapas de deslocamento para as mesmas regiões cerebrais. Estes resultados mostraram-se consistentes e, tal como anteriormente observado, o deslocamento é consideravelmente superior para as regiões do sistema ventricular. A região inferior do cérebro foi a que apresentou valores de deslocamento mais elevados, o que pode ser justificado pelo facto desta região se encontrar mais próxima do coração e, desta maneira, o LCR ser ejetado das regiões que ocupa com maior velocidade. Adicionalmente, verificou-se que as maiores alterações do deslocamento ocorrem imediatamente após a sístole cardíaca. Seguidamente, foi possível, a partir dos valores de deslocamento obtidos, determinar um valor ótimo para a sensibilidade, relativamente ao deslocamento, da sequência DENSE. Contrariamente à primeira parte deste projecto, os resultados obtidos utilizando as sequências DENSE dizem respeito exclusivamente às regiões mais abrangentes. De facto, esta exclusão das regiões do sistema ventricular foi causada pela baixa resolução das imagens obtidas que, desta forma, não permitiram uma segmentação de áreas tão reduzidas com fiabilidade razoável. Os resultados desta análise mostram que a sequência utilizada cujos resultados de deslocamento se assemelham mais aos resultados obtidos através do contraste de fase foi a sequência que utilizou a preparação T2. Por oposição, as sequências básicas utilizadas mostraram semelhança reduzida com o método de comparação. Esta diferença observada foi justifica pela baixa resolução das imagens adquiridas, o que contribui para que não fosse possível eliminar o efeito de volume parcial. Adicionalmente, concluiu-se que o valor de sensibilidade para o deslocamento utilizado não foi o correto para estas regiões e, desta forma, houve perda de sinal adquirido justificando assim às diferenças encontradas entre os dois métodos. Concluindo, esta dissertação cumpriu o objetivo principal proposto, nomeadamente fazer uma descrição completa e quantificar a evolução da velocidade e do deslocamento do líquido cefalorraquidiano ao longo do ciclo cardíaco. Adicionalmente, o método de RM com contraste de fase mostrou ser um método fiável para o estudo do comportamento do LCR mesmo em regiões com velocidades mais lentas. Os resultados de deslocamento obtidos através da utilização do método DENSE permitiram confirmar o potencial desta técnica para medir deslocamentos sub-milimétricos. No entanto, este método ainda necessita de ser otimizado de forma a ser uma alternativa viável ao contraste de fase. Finalmente, os resultados obtidos neste estudo permitem que estudos futuros utilizem os valores máximos de cada região obtida de forma a otimizar futuras sequências.
Cerebrospinal fluid (CSF) plays an essential role in the drainage of cerebral waste, and its continuous motion is vital to maintain the brain’s homeostasis. Variations in this motion, associated with aging and disease, are observed in physical and physiological disorders, such as Alzheimer’s Disease. Therefore, a deep understating of this fluid motion, such as its velocity and displacement, is fundamental to strengthen our knowledge of these diseases and might be vital to their prevention and treatment. Despite previous studies reporting CSF velocity and displacement using magnetic resonance imaging techniques, a complete picture of this fluid motion has not yet been obtained. The aim of this study was to, first and foremost, obtain a general picture of CSF velocity and displacement using Phase Contrast (PC) MRI, a method of reference for velocity acquisition. Furthermore, this sequence was also used to optimize the parameters for an MRI technique called Displacement Encoding with Stimulated Echoes (DENSE), a sequence that was modified in order to be capable of measuring small displacements. Four healthy subjects were studied using whole-brain ultra-high field (UHF) MRI at 7 Tesla (T). The volunteers were scanned using two different MRI imaging sequences: Phase Contrast MRI at 1 mm isotropic resolution and 3D T1-weighted (T1w) at 1 mm isotropic resolution. Additionally, two healthy subjects were scanned using PC and four different DENSE acquisitions. Firstly, two basic DENSE sequences with 2mm and 3mm isotropic resolution were acquired. Next, a DENSE acquisition with a T2 prepared magnetization, and a DENSE sequence with a long echo time were acquired to avoid confounding effects from partial volume between tissue and CSF. The image processing pipeline included coregistration, segmentation, eddy current correction. Moreover, mean velocity and displacement maps were calculated for regions of interest previously selected. The results in this study obtained from the PC acquisitions show consistent velocity and displacement values across all subjects. Furthermore, CSF shows higher values for the ventricular regions, such as the aqueduct, and predominant motion in the anterior and feet direction. Comparatively, regions in the periphery of the brain display slower velocities and smaller displacements. The displacement values obtained with PC were used to optimize the displacement sensitivity used in the DENSE acquisition. The DENSE sequence acquired with a T2 magnetization preparation showed the most consistent results when compared to the Phase Contrast. In conclusion, this project managed to study and quantify CSF behavior in the brain, which allows for the optimization of future sequences that desire a more detailed study of this fluid’s in specific brain regions.

The study of the mapping class group Mod(S) is a classical topic that is experiencing a renaissance. It lies at the juncture of geometry, topology, and group theory. This book explains as many important theorems, examples, and techniques as possible, quickly and directly, while at the same time giving full details and keeping the text nearly self-contained. The book is suitable for graduate students. It begins by explaining the main group-theoretical properties of Mod(S), from finite generation by Dehn twists and low-dimensional homology to the Dehn–Nielsen–Baer–theorem. Along the way, central objects and tools are introduced, such as the Birman exact sequence, the complex of curves, the braid group, the symplectic representation, and the Torelli group. The book then introduces Teichmüller space and its geometry, and uses the action of Mod(S) on it to prove the Nielsen-Thurston classification of surface homeomorphisms. Topics include the topology of the moduli space of Riemann surfaces, the connection with surface bundles, pseudo-Anosov theory, and Thurston's approach to the classification.

Intracranial electroencephalography (iEEG) is used to localize the focus of seizures and determine vital adjacent cortex before epilepsy surgery. The two most commonly used electrode types are subdural and depth electrodes. Foramen ovale electrodes are less often used. Combinations of electrode types are possible. The choice depends on the presumed focus site. Careful planning is needed before implantation, taking into account the results of noninvasive studies. While subdural recordings allow better mapping of functional cortex, depth electrodes can reach deep structures. There are no guidelines on how to read ictal intracranial EEG recordings, but a focal onset (<5 contacts) and a high-frequency onset herald a good prognosis. High-frequency oscillations have been described as a potential biomarker of the seizure onset zone. Intracranial recordings provide a focal but magnified view of the brain, which is also exemplified by the use of microelectrodes, which allow the recording of single-unit or multi-unit activity.

AbstractWe report herein the case of a 41-year-old man operated on for a small inferior parietal lobule ganglioglioma with a sleep-awake-sleep protocol and language mapping to avoid major speech disorders. Postoperatively, however, writing disturbance was characterized by persistent graphemic errors that lasted for about 8 months. The topic is discussed in light of recent literature, exploring the possible relationship between writing difficulties and disconnections produced by a combination of resecting supramarginal gyrus components and interrupting arcuate fasciculus fibers. Awake mapping of eloquent structures is typically done using direct brain stimulation to maximize the extent of the resection while minimizing permanent neurological deficits. However, most intraoperative language tests focus on language skills such as oral and reading skills. Therefore, the detection of dysgraphia requires a high degree of attention from the surgical team and direct examination intra-and perioperatively. To this end, employing an intraoperative writing test during awake surgery may be considered. Advances in this field may aid in increasing the accuracy during parenchymal dissections, influencing the extent of the resection, improving the patient’s functional prognosis and long-term quality of life.

Abstract I decided to become a psychiatrist in the early 1970s, motivated by a strong desire to do research on major mental illnesses such as schizophrenia, depression, and dementia, each of which was fascinating in a different way. Cardiology (another specialty that I liked), appealing in its precision, was too easy by comparison. As a medical student I found mental illnesses to be the most interesting and challenging diseases that I had encountered. What could explain how some people experienced the loss of autonomy over their minds that characterized schizophrenia, leading to the intrusion of alien voices or the theft of their emotional vitality? What caused people to fall into a deep depression, depriving them of all confidence and self-esteem, just when things seemed to be going very well for them? Why did some older people, previously bright and alert, begin to lose their mental capacities, and ultimately their whole personalities, ending in a wordless fetal-like helplessness? Not only were these questions fascinating, but the diseases were very common. Getting a handle on any one of them would help millions of people.

Abstract: The convergence of artificial intelligence (AI) and neuroengineering is redefining the future of human cognition, paving the way for brain uploading, memory transfer, and digital consciousness. This chapter explores the scientific and philosophical dimensions of AI-driven neural interfaces, high-resolution brain mapping, and whole-brain emulation (WBE), examining how AI enhances our ability to decode, replicate, and potentially transfer human thought. From synthetic neurons and neuroprosthetics to AI-assisted memory replication, advancements in brain-computer interfaces (BCIs) and computational neuroscience are bringing us closer to preserving and enhancing consciousness beyond biological limitations. However, the emergence of AI-merged cognition introduces complex ethical dilemmas, including identity continuity, artificial sentience, and digital immortality. By addressing the opportunities and risks of AI-driven neuroengineering, this chapter outlines the path toward a future where human intelligence coexists with machine-enhanced cognition, reshaping medicine, ethics, and the very nature of consciousness itself. Keywords: AI-enhanced neuroengineering, brain uploading, memory transfer, digital consciousness, artificial intelligence, whole-brain emulation, neural interfaces, brain-computer interfaces (BCIs), cognitive augmentation, neuroprosthetics, synthetic neurons, computational neuroscience, neuroplasticity, AI-driven cognition, mind uploading, artificial sentience, digital immortality, neuroscience, ethics of AI, post-human intelligence.

This chapter focuses on neurosurgical oncology. The first set of studies explores various preoperative parameters that impact survival in patients with glioblastoma multiforme, identifies a cancer stem cell in human brain tumors, and demonstrates the importance of language mapping for glioma resection and its impact on functional outcomes. The second set of studies provides an analysis of the recurrence and progression of meningioma. The third set of studies evaluates the efficacy of surgery, whole-brain radiotherapy, and stereotactic radiosurgery in the treatment of patients with brain metastases. The last study, included for its historical value, is Dr. Simpson's paper in which he proposed a grading system for the recurrence rates of meningiomas but also the relationship between these rates and extent of resection of meningioma.

Transsylvian selective amygdalohippocampectomy resulted in postoperative verbal memory decline in patients with mesial temporal lobe epilepsy of the language-dominant side. Mapping whole-brain connectivity changes have been studied recently of different surgical resection approaches for temporal lobe epilepsy. The subtemporal resection is the least disruptive to long-range connectivity, which may explain its better cognitive outcome. Finally, the authors introduced subtemporal multiple hippocampal transections technique in a case of hippocampal sclerosis negative left mesial temporal lobe epilepsy, and postoperative neuropsychological examinations revealed improvement of cognitive function immediately after the operation contrasting transsylvian multiple hippocampal transections in which verbal memory remains dropped. The authors introduced another new operation to left mesial temporal lobe epilepsy patient with hippocampal sclerosis by multiple hippocampal transections plus disconnection between CA1 and subiculum at the hippocampal head. Operative result is satisfactory in terms of neuropsychological and operative outcome.

Abstract The first papers on functional magnetic resonance imaging (FMRI) were published just fifteen years ago, and in the relative short time since, FMRI has assumed a major role in mapping human brain functions. A search of the term “FMRI” in the medline database reveals that more than 5000 peer reviewed original articles have been produced world-wide, a number which has increased exponentially, since last year alone more than one FMRI article a day was published. Almost nine out of ten publications cover either technical aspects of FMRI or the neurophysiological research concerned with the function of the human brain in normal subjects. The latter field is undergoing an explosive growth due to several distinctly advantageous characteristics of FMRI. These include total noninvasiveness, relatively high spatial and temporal resolution, and the ease of imaging the underlying anatomy. In addition, state-of-the-art whole brain FMRI can now be performed on almost all recently installed clinical MR scanners, and online analysis tools allow the visualization of neuronal activity at the level of the single subject (or patient) in real time. The non-invasive character means that subjects can be studied repeatedly, without harm, allowing for longitudinal studies. These benefits have thus led to a considerable growth of neurophysiological data of the human brain — normal and pathological. The development of applications of FMRI for diagnostic and therapeutic purposes in patients with neurological, neurosurgical, or psychiatric diseases forms about ten per cent of the total number of publications since the beginning of the FMRI era, and this field is growing almost as fast as that of ‘neurophysiological FMRI’. This (at first view) limited share of clinical FMRI is actually a tremendous achievement, considering the fact that clinical FMRI is much more difficult to perform than non-clinical FMRI. The reasons for this are multiple and pertain to all aspects of functional imaging. First, at the design stage of a FMRI experiment, compared to the paradigms or stimuli employed in the neurophysiological study of volunteers, those that will be used to elucidate neuronal activity in patients will have to be adapted to their pathology. Second, at the stage of acquiring the functional scans, acquisition time will often be much more limited than in young healthy volunteers. Third, the post-processing of the FMRI data will often have to be altered or improved due to the presence of ‘unexpected’ signals from the brain abnormalities.

In our contribution to this special issue focusing on Advances in Alzheimer’s Disease (AD) research since the centennial, we will briefly review some of our own studies applying magnetic resonance imaging (MRI) measures of function and connectivity for characterization of genetic contributions to the neuropathology of AD and as candidate biomarkers. We review how functional MRI during both memory encoding and at rest is able to define APOE4 genotype-dependent physiological changes decades before potential development of AD and demonstrate changes distinct from those with healthy aging. More generally, imaging provides a powerful quantitative measure of phenotype for understanding associations arising from whole genome studies in AD. Structural connectivity measures derived from diffusion tensor MRI (DTI) methods offer additional markers of neuropathology arising from the secondary changes in axonal caliber and myelination that accompany decreased neuronal activity and neurodegeneration. We illustrate applications of DTI for more finely mapping neurodegenerative changes with AD in the thalamus in vivo and for defining neuropathological changes in the white matter itself. The latter efforts have highlighted how sensitivity to the neuropathology can be enhanced by using more specific DTI measures and interpreting them relative to knowledge of local white matter anatomy in the healthy brain. Together, our studies and related work are helping to establish the exciting potential of a new range of MRI methods as neuropathological measures and as biomarkers of disease progression.

Chapter 9 begins by arguing that all perceptual attributives are iconic. The notions of iconic representation and iconic information registration are explained. The iconic structure of perceptual representational content is a specific instance of the noun-phrase-like determiner-governed form of perceptual content discussed in earlier chapters. Evidence for relations between iconic relations among visual receptors, visual field maps in the brain, non-representational information registration, and perceptual content, on one hand, and aspects of the environment, on the other, are discussed in connection with perceptual iconic spatial representation. Temporal, qualitative, and other aspects of perceptual iconic representation are outlined. Ways of thinking about iconicity that do not center on exercises of capacities are criticized. The chapter explores relations between iconic representation in perception and iconic representation in thought. It develops aspects of part–whole representation in perception and in realist pictures. Iconic perceptual representation is compositional, as a consequence of its basic noun-phrase-like attributional structure. The fact that vision depends on mapping an array of surfaces deepens understanding of the iconicity of visual representation. Despite the stupendous complexity of perceptual representation, it is tractable for a psychological system because of its iconic nature.

High-density diffuse optical tomography uses a dense array of overlapping measurements that provides functional brain images validated against fMRI. We doubled this optode density, improving resolution and expanding the field of view to whole-head coverage.