Neuroimage

Generative adversarial networks (GANs) are one powerful type of deep learning models that have been successfully utilized in numerous fields. They belong to the broader family of generative methods, which learn to generate realistic data with a probabilistic model by learning distributions from real samples. In the clinical context, GANs have shown enhanced capabilities in capturing spatially complex, nonlinear, and potentially subtle disease effects compared to traditional generative methods. This review critically appraises the existing literature on the applications of GANs in imaging studies of various neurological conditions, including Alzheimer's disease, brain tumors, brain aging, and multiple sclerosis. We provide an intuitive explanation of various GAN methods for each application and further discuss the main challenges, open questions, and promising future directions of leveraging GANs in neuroimaging. We aim to bridge the gap between advanced deep learning methods and neurology research by highlighting how GANs can be leveraged to support clinical decision making and contribute to a better understanding of the structural and functional patterns of brain diseases.

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Schizophrenia and states induced by certain psychotomimetic drugs may share some physiological and phenomenological properties, but they differ in fundamental ways: one is a crippling chronic mental disease, while the others are temporary, pharmacologically-induced states presently being explored as treatments for mental illnesses. Building towards a deeper understanding of these different alterations of normal consciousness, here we compare the changes in neural dynamics induced by LSD and ketamine (in healthy volunteers) against those associated with schizophrenia, as observed in resting-state M/EEG recordings. While both conditions exhibit increased neural signal diversity, our findings reveal that this is accompanied by an increased transfer entropy from the front to the back of the brain in schizophrenia, versus an overall reduction under the two drugs. Furthermore, we show that these effects can be reproduced via different alterations of standard Bayesian inference applied on ...

There is mounting evidence that mindfulness meditation is beneficial for the treatment of mood and anxiety disorders, yet little is known regarding the neural mechanisms through which mindfulness modulates emotional responses. Thus, a central objective of this functional magnetic resonance imaging study was to investigate the effects of mindfulness on the neural responses to emotionally laden stimuli. Another major goal of this study was to examine the impact of the extent of mindfulness training on the brain mechanisms supporting the processing of emotional stimuli. Twelve experienced (with over 1000 h of practice) and 10 beginner meditators were scanned as they viewed negative, positive, and neutral pictures in a mindful state and a non-mindful state of awareness. Results indicated that the Mindful condition attenuated emotional intensity perceived from pictures, while brain imaging data suggested that this effect was achieved through distinct neural mechanisms for each group of participants. For experienced meditators compared with beginners, mindfulness induced a deactivation of default mode network areas (medial prefrontal and posterior cingulate cortices) across all valence categories and did not influence responses in brain regions involved in emotional reactivity during emotional processing. On the other hand, for beginners relative to experienced meditators, mindfulness induced a down-regulation of the left amygdala during emotional processing. These findings suggest that the long-term practice of mindfulness leads to emotional stability by promoting acceptance of emotional states and enhanced present-moment awareness, rather than by eliciting control over low-level affective cerebral systems from higher-order cortical brain regions. These results have implications for affect-related psychological disorders.

In this study, we suggest that detrended fluctuation analysis may reveal alternations in long-range temporal correlations associated with epileptic status. We consider two groups of subjects: patients with confirmed focal epilepsy, and healthy controls. Both groups were exposed to intermittent photic stimulation. Analysis based on event-related spectral perturbations revealed that photic driving in epileptic patients is higher in the α band and lower in other bands. This result is related to altered excitability in nonphotosensitive epilepsy. To prove this, we tested two hypotheses. First, we assess long-range temporal correlations using detrended fluctuation analysis, with the objective of evaluating whether this metric differs between epileptic patients and healthy controls through the application of between-subject statistics. Second, we investigate whether detrended fluctuation analysis provides more valuable insights into the aforementioned differences in comparison to traditional spectral analysis of brain signals. More precisely, we test if a machine learning algorithm trained on detrended fluctuation analysis-based features outperforms one trained on the spectral-based features in classifying between epileptic patients and controls. Furthermore, we study whether the features differ between classifiers by implementing feature importance assessment. Our findings demonstrate that the classifier based on detrended fluctuation analysis exhibits higher efficiency, and its features are notably distinct from those of the classifier based on spectral analysis. We postulate that the long-range temporal correlations captured via detrended fluctuation analysis reveal novel aspects of the epileptic brain response to intermittent photic stimulation, and they are more pronounced than the features captured via spectral analysis.

The infant brain is unlike the adult brain, with considerable differences in morphological, neurodynamic, and haemodynamic features. As the majority of current MRI analysis tools were designed for use in adults, a primary objective of the Developing Human Connectome Project (dHCP) is to develop optimised methodological pipelines for the analysis of neonatal structural, resting state, and diffusion MRI data. Here, in an independent neonatal dataset we have extended and optimised the dHCP fMRI preprocessing pipeline for the analysis of stimulusresponse fMRI data. We describe and validate this extended dHCP fMRI preprocessing pipeline to analyse changes in brain activity evoked following an acute noxious stimulus applied to the infant's foot. We compare the results obtained from this extended dHCP pipeline to results obtained from a typical FSL FEAT-based analysis pipeline, evaluating the pipelines' outputs using a wide range of tests. We demonstrate that a substantial increase in spatial specificity and sensitivity to signal can be attained with a bespoke neonatal preprocessing pipeline through optimised motion and distortion correction, ICA-based denoising, and haemodynamic modelling. The improved sensitivity and specificity, made possible with this extended dHCP pipeline, will be paramount in making further progress in our understanding of the development of sensory processing in the infant brain.

We present a practical "how-to" guide to help determine whether single-subject fMRI independent components (ICs) characterise structured noise or not. Manual identification of signal and noise after ICA decomposition is required for efficient data denoising: to train supervised algorithms, to check the results of unsupervised ones or to manually clean the data. In this paper we describe the main spatial and temporal features of ICs and provide general guidelines on how to evaluate these. Examples of signal and noise components are provided from a wide range of datasets (3T data, including examples from the UK Biobank and the Human Connectome Project, and 7T data), together with practical guidelines for their identification. Finally, we discuss how the data quality, data type and preprocessing can influence the characteristics of the ICs and present examples of particularly challenging datasets.

How do working memory and perception interact with each other? Recent theories of working memory suggest that they are closely linked, and in fact share certain brain mechanisms. We used a sequential motion imitation task in combination with EEG and ERP techniques for a direct, online examination of memory load's influence on the processing of visual stimuli. Using a paradigm in which subjects tried to reproduce random motion sequences from memory, we found a systematic decrease in ERP amplitude with each additional motion segment that was viewed and memorized for later imitation. High-frequency (>20 Hz) oscillatory activity exhibited a similar position-dependent decrease. When trials were sorted according to the accuracy of subsequent imitation, the amplitude of the ERPs during stimulus presentation correlated with behavioral performance: The larger the amplitude, the more accurate the subsequent imitation. These findings imply that visual processing of sequential stimuli is not uniform. Rather, earlier information elicits stronger neural activity. We discuss possible explanations for this observation, among them competition for attention between memory and perception and encoding of serial order by means of differential activation strengths.

Objective-The objective of the study was to examine whether deep brain stimulation (DBS) of the subthalamic nucleus (STN), the globus pallidus internus (GPi), and/or the ventralis intermedius thalamic nucleus (Vim) was associated with making patients angrier pre to postsurgical intervention. Background-Secondary outcome analysis of the NIH COMPARE Parkinson's Disease DBS trial revealed that participants were angrier and had more mood and cognitive side effects following DBS. Additionally blinded on/off analysis did not change anger scores. The sample size was small but suggested that STN DBS may have been worse than GPi in provoking anger. We endeavored to examine this question utilizing a larger dataset (the UF INFORM database), and also we included a third surgical target (Vim) which has been utilized for a different disease, essential tremor. Methods-Consecutive patients from the University of Florida Movement Disorders Center who were implanted with unilateral DBS for Parkinson's Disease (STN or GPi) or Essential Tremor (Vim) were included. Patients originally implanted at outside institutions were excluded. Pre-and 4-6 month postoperative Visual Analog Mood Scales (VAMS) scores for all three groups were compared; additionally, pre-and 1-3 month scores were compared for STN and GPi patients. A linear regression model was utilized to analyze the relationship between the VAMS anger score and the independent variables of age, years with symptoms, Mini-mental status examination (MMSE) score, handedness, ethnicity, gender, side of surgery, target of surgery, baseline

Objective-The objective of the study was to examine whether deep brain stimulation (DBS) of the subthalamic nucleus (STN), the globus pallidus internus (GPi), and/or the ventralis intermedius thalamic nucleus (Vim) was associated with making patients angrier pre to postsurgical intervention. Background-Secondary outcome analysis of the NIH COMPARE Parkinson's Disease DBS trial revealed that participants were angrier and had more mood and cognitive side effects following DBS. Additionally blinded on/off analysis did not change anger scores. The sample size was small but suggested that STN DBS may have been worse than GPi in provoking anger. We endeavored to examine this question utilizing a larger dataset (the UF INFORM database), and also we included a third surgical target (Vim) which has been utilized for a different disease, essential tremor. Methods-Consecutive patients from the University of Florida Movement Disorders Center who were implanted with unilateral DBS for Parkinson's Disease (STN or GPi) or Essential Tremor (Vim) were included. Patients originally implanted at outside institutions were excluded. Pre-and 4-6 month postoperative Visual Analog Mood Scales (VAMS) scores for all three groups were compared; additionally, pre-and 1-3 month scores were compared for STN and GPi patients. A linear regression model was utilized to analyze the relationship between the VAMS anger score and the independent variables of age, years with symptoms, Mini-mental status examination (MMSE) score, handedness, ethnicity, gender, side of surgery, target of surgery, baseline

Topographic representation of the outside world is a key feature of sensory systems, but so far it has been difficult to define how the activity pattern of the olfactory information is distributed at successive stages in the olfactory system. We studied odor-evoked activation patterns in the main olfactory bulb and the anterior piriform cortex of rats using functional ultrasound (fUS) imaging. fUS imaging is based on the use of ultrafast ultrasound scanners and detects variations in the local blood volume during brain activation. It makes deep brain imaging of ventral structures, such as the piriform cortex, possible. Stimulation with two different odors (hexanal and pentylacetate) induced the activation of odor-specific zones that were spatially segregated in the main olfactory bulb. Interestingly, the same odorants triggered the activation of the entire anterior piriform cortex, in all layers, with no distinguishable odor-specific areas detected in the power Doppler images. These fUS imaging results confirm the spatial distribution of odor-evoked activity in the main olfactory bulb, and furthermore, they reveal the absence of such a distribution in the anterior piriform cortex at the macroscopic scale in vivo.

Manual segmentation of the hippocampus is the gold standard in volumetric hippocampal magnetic resonance imaging (MRI) analysis; however, this is difficult to achieve reproducibly. This study explores whether application of local registration and calculation of the hippocampal boundary shift integral (HBSI) can reduce random variation compared with manual measures. Hippocampi were outlined on the baseline and registered-repeat MRIs of 32 clinically diagnosed Alzheimer's disease (AD) patients and 47 matched controls (37-86 years) with a wide range of scanning intervals (175-1173 days). The scans were globally registered using 9 degrees of freedom and subsequently locally registered using 6 degrees of freedom and HBSI was then calculated automatically. HBSI significantly reduced the mean rate (P b 0.01) and variation in controls (P b 0.001) and increased group separation between AD cases and controls. When comparing HBSI atrophy rates with manually derived atrophy rates at 90% sensitivity, specificities were 98% and 81%, respectively. From logistic regression models, a 1% increase in HBSI atrophy rates was associated with an 11-fold (CI 3, 36) increase in the odds of a diagnosis of AD. For manually derived atrophy rates, the equivalent odds ratio was 3 (CI 2,4). We conclude that HBSIderived atrophy rates reduce operator time and error, and are at least as effective as the manual equivalent as a diagnostic marker and are a potential marker of progression in longitudinal studies and trials.

Le pharmacien - seul ou en collaboration avec d'autres professionnels de soins - peut permettre de mieux contrôler les facteurs de risque des maladies cardiovasculaires (MCV) tels que l'hypertension, l'hypercholestérolémie ou le tabagisme. C'est la conclusion d'une récente revue systématique parue dans les Archives of Internal Medicine, réalisée par le Dr Valérie Santschi, pharmacienne, PhD et ses collègues de l'Université McGill de Montréal et de l'Institut universitaire de médecine sociale et préventive (IUMSP) du Centre Hospitalier Universitaire Vaudois (CHUV) de Lausanne. Cette revue systématique indique qu'il est pertinent d'intégrer plus systématiquement le pharmacien dans la prévention et la prise en charge des MCV. [Ed.]]]> Cardiovascular Diseases/prevention & control ; Pharmacists fre https://serval.unil.ch/resource/serval:BIB_63E82D690BDA.P001/REF.pdf info:eu-repo/semantics/submittedVersion info:eu-repo/semantics/restrictedAccess Rest...

Human Immunodeficiency Virus (HIV) infection continues to have major adverse public health and clinical consequences despite the effectiveness of combination Antiretroviral Therapy (cART) in reducing HIV viral load and improving immune function. As successfully treated individuals with HIV infection age, their cognition declines faster than reported for normal aging. This phenomenon underlines the importance of improving long-term care, which requires better understanding of the impact of HIV on the brain. In this paper, automated identification of patients and brain regions affected by HIV infection are modeled as a classification problem, whose solution is determined in two steps within our proposed Chained-Regularization framework. The first step focuses on selecting the HIV pattern (i.e., the most informative constellation of brain region measurements for distinguishing HIV infected subjects from healthy controls) by constraining the search for the optimal parameter setting of the classifier via group sparsity (ℓ 2,1norm). The second step improves classification accuracy by constraining the parameterization with respect to the selected measurements and the Euclidean regularization (ℓ 2 -norm). When applied to the cortical and subcortical structural Magnetic Resonance Images (MRI) measurements of 65 controls and 65 HIV infected individuals, this approach is more accurate in distinguishing the two cohorts than more common models. Finally, the brain regions of the identified HIV pattern concur with the HIV literature that uses traditional group analysis models.

Quantifying tissue iron concentration in vivo is instrumental for understanding the role of iron in physiology and in neurological diseases associated with abnormal iron distribution. Herein, we use recently-developed Quantitative Susceptibility Mapping (QSM) methodology to estimate the tissue magnetic susceptibility based on MRI signal phase. To investigate the effect of different regularization choices, we implement and compare ℓ 1 and ℓ 2 norm regularized QSM algorithms. These regularized approaches solve for the underlying magnetic susceptibility distribution, a sensitive measure of the tissue iron concentration, that gives rise to the observed signal phase. Regularized QSM methodology also involves a pre-processing step that removes, by dipole fitting, unwanted background phase effects due to bulk susceptibility variations between air and tissue and requires data acquisition only at a single field strength. For validation, performances of the two QSM methods were measured against published estimates of regional brain iron from postmortem and in vivo data. The in vivo comparison was based on data previously acquired using Field-Dependent Relaxation Rate Increase (FDRI), an estimate of MRI relaxivity enhancement due to increased main magnetic field strength, requiring data acquired at two different field strengths. The QSM analysis was based on susceptibility-weighted images acquired at 1.5T, whereas FDRI analysis used Multi-Shot Echo-Planar Spin Echo images collected at 1.5T and 3.0T. Both datasets were collected in the same healthy young and elderly adults. The in vivo estimates of regional iron concentration comported well with published postmortem measurements; both QSM approaches yielded the same rank ordering of iron concentration by brain structure, with the lowest in white matter and the highest in globus pallidus. Further validation was provided by comparison of the in vivo measurements, ℓ 1 -regularized QSM versus

Previous imaging studies with positron emission tomography (PET) have reliably demonstrated an age-associated decline in the dopamine system. Most of these studies have focused on the densities of dopamine receptor subtypes D2/3R (D2R family) in the striatum using antagonist radiotracers that are largely nonselective for D2R vs. D3R subtypes. Therefore, less is known about any possible age effects in D3-rich extrastriatal areas such as the substantia nigra/ventral tegmental area (SN/VTA) and hypothalamus. This study sought to investigate whether the receptor availability measured with [(11)C](+)PHNO, a D3R-preferring agonist radiotracer, also declines with age. Forty-two healthy control subjects (9 females, 33 males; age range 19-55years) were scanned with [(11)C](+)PHNO using a High Resolution Research Tomograph (HRRT). Parametric images were computed using the simplified reference tissue model (SRTM2) with cerebellum as the reference region. Binding potentials (BPND) were calculat...

The development of chemical exchange saturation transfer (CEST) and magnetization transfer (MT) contrast in MRI have enabled the enhanced detection of metabolites and biomarkers in vivo. In brain MRI, the separation between CEST and MT contrast has been particularly difficult due to overlaps in the frequency responses of the contrast mechanisms. We demonstrate here that MT and CEST contrast can be separated in the brain by the so-called uniform-MT (uMT) technique, thus opening the door to addressing long-standing ambiguities in this field. These methods could be useful for keeping track of important endogenous metabolites and for providing an improved understanding of neurological and neurodegenerative disorders. Examples are shown from white and gray matter regions in healthy volunteers and patients with multiple sclerosis, which demonstrated that the MT effects in the brain were asymmetric and that the uMT method could make them uniform.

A epilepsia afeta cerca de 50 milhões de pessoas em todo o mundo, onde, a cada ano, 5 milhões de pessoas são diagnosticadas com epilepsia globalmente. A grande maioria das epilepsias focais em adultos se origina no lobo temporal. Os medicamentos anticrises podem controlar as crises epilépticas, mas para aqueles que respondem mal ao tratamento médico, as intervenções cirúrgicas podem ser benéficas. A Epilepsia do Lobo Temporal Mesial (ELTM) atinge as estruturas como o hipocampo, polo temporal e tálamo. A anisotropia fracionária (FA), a difusividade axial (AD), a difusividade radial (RD) e a difusividade média (MD) são as métricas que refletem o movimento das moléculas de água ao pós-processar o Imagem Difusor Tensão (DTI), que permite obter o nível estimado e integridade da substância branca e também reconstruir e renderizar fibras (tractografia). Por meio do nosso protocolo e rotina de processamento de imagens, este trabalho foi capaz de avaliar diferenças de conectividade estrutural entre paciente que responderam bem ou não ao procedimento cirúrgico. Os resultados indicam que as métricas FA, RD e MD no ROI ’hipocampo e polo temporal’ ipsilateral ao foco epileptogênico, RD para o ROI ’hipocampo e polo temporal’ contralateral foco epileptogênico e o FA para o ROI ’hipocampo e tálamo’ contralateral ao foco epileptogênico, são biomarcadores que podem correlacionar o nível da conectividade ao controle de crises pós cirúrgico.

While there is a profusion of functional investigations involving the superior temporal sulcus (STS), our knowledge of the anatomy of this sulcus is still limited by a large variability across individuals. Several “plis de passage” (PPs), annectant gyri buried inside the fold, can separate the STS into distinct segments and could explain part of the observed variability. However, an accurate characterization is lacking to properly extract and fully understand the nature of PPs. The aim of the present study is twofold: i. to characterize the STS PPs by directly identifying them within individual STS, using the geometry of the surrounding surface and considering both deep and superficial PPs. ii. to test the hypothesis that PPs constitute local increases of the short-range structural connectivity. Performed on 90 subjects from the Human Connectome Project database, our study revealed that PPs constitute surface landmarks that can be identified from the geometry of the STS walls and th...

The aim of the present study was to explore brain activities associated with creativity and expertise in literary writing. Using functional magnetic resonance imaging (fMRI), we applied a real-life neuroscientific setting that consisted of different writing phases (brainstorming and creative writing; reading and copying as control conditions) to well-selected expert writers and to an inexperienced control group. During creative writing, experts showed cerebral activation in a predominantly left-hemispheric fronto-parieto-temporal network. When compared to inexperienced writers, experts showed increased left caudate nucleus and left dorsolateral and superior medial prefrontal cortex activation. In contrast, less experienced participants recruited increasingly bilateral visual areas. During creative writing activation in the right cuneus showed positive association with the creativity index in expert writers. High experience in creative writing seems to be associated with a network of...

Pavlovian fear conditioning has been thoroughly studied in the visual, auditory and somatosensory domain, but evidence is scarce with regard to the chemosensory modality. Under the assumption that Pavlovian conditioning relies on the supra-modal mechanism of salience attribution, the present study was set out to attest the existence of chemosensory aversive conditioning in humans as a specific instance of salience attribution. fMRI was performed in 29 healthy subjects during a differential aversive conditioning paradigm. Two odors (rose, vanillin) served as conditioned stimuli (CS), one of which (CS+) was intermittently coupled with intranasally administered CO 2 . On the neural level, a robust differential response to the CS+ emerged in frontal, temporal, occipito-parietal and subcortical brain regions, including the amygdala. These changes were paralleled by the development of a CS+-specific connectivity profile of the anterior midcingulate cortex (aMCC), which is a key structure for processing salience information in order to guide adaptive response selection. Increased coupling could be found between key nodes of the salience network (anterior insula, neo-cerebellum) and sensorimotor areas, representing putative input and output structures of the aMCC for exerting adaptive motor control. In contrast, behavioral and skin conductance responses did not show significant effects of conditioning, which has been attributed

A saccade involves both a step in eye position and an obligatory shift in spatial attention. The traditional division of saccades into two types, the "reflexive" saccade made in response to an exogenous stimulus change in the visual periphery and the "voluntary" saccade based on an endogenous judgement to move gaze, is supported by lines of evidence which include the longer onset latency of the latter and the differential effects of lesions in humans and primates on each. It has been supposed that differences between the two types of saccade derive from differences in how the spatial attention shifts involved in each are processed. However, while functional imaging studies have affirmed the close link between saccades and attentional shifts by showing they activate overlapping cortical networks, attempts to contrast exogenous with endogenous ("covert") attentional shifts directly have not revealed separate patterns of cortical activation. We took the "overt" approach, contrasting whole reflexive and voluntary saccades using event-related fMRI. This demonstrated that, relative to reflexive saccades, voluntary saccades produced greater activation within the frontal eye fields and the saccade-related area of the intraparietal sulci. The reverse contrast showed reflexive saccades to be associated with relative activation of the angular gyrus of the inferior parietal lobule, strongest in the right hemisphere. The frequent involvement of the right inferior parietal lobule in lesions causing hemispatial neglect has long implicated this parietal region in an important, though as yet uncertain, role in the awareness and exploration of space. This is the first study to demonstrate preferential activation of an area in its posterior part, the right angular gyrus, during production of exogenously triggered rather than endogenously generated saccades, a finding which we propose is consistent with an important role for the angular gyrus in exogenous saccadic orienting.

PURPOSE: To study in detail the MR anatomy of the spinal cord and the ce rvicomed ullary junction that could serve as a reference for clinical MR studies. METHODS: Specimens of fresh human spinal cord and forma lin-fixed cervicom edullary transition zones were imaged with a 9 .4-T vertical bore magnet. Using a multisection spin-warp pul se sequence the param eters were se lected to produce essentially proton density images. RESULTS: The images obtai ned depict the microanatomical organization of the spinal cord and cervicom edullary junction. In the spinal cord , the central gray has the expected higher signal intensity compared with the white matter, which is, apart from its darker general appearance, characterized by the presence of a dense rad iall y structured neurogl ial framework of high signal intensity . A natomica ll y m ore compl ex regio ns such as the dorsal root entry zone, the adjacent posterior horn complex , and the crossi ng fibers of the cervicomedullary junction are seen as wel l as parts of th e microvascular system . CONCLUSION: Although cellular details are still beyond the limits of this investigati on , the images at 9.4 T show the spinal cord and cervicomedullary junction with detail comparable to low-power microscopic images of fixed sections, especially with respect to distinguishing gray and white matter, nuclei , tracts , and angioarchitecture .

There is a need for accurate quantitative non-invasive biomarkers to monitor myelin pathology in vivo and distinguish myelin changes from other pathological features including inflammation and axonal loss. Conventional MRI metrics such as T 2 , magnetization transfer ratio and radial diffusivity have proven sensitivity but not specificity. In highly coherent white matter bundles, compartment-specific white matter tract integrity (WMTI) metrics can be directly derived from the diffusion and kurtosis tensors: axonal water fraction, intra-axonal diffusivity, and extra-axonal radial and axial diffusivities. We evaluate the potential of WMTI to quantify demyelination by monitoring the effects of both acute (6 weeks) and chronic (12 weeks) cuprizone intoxication and subsequent recovery in the mouse corpus callosum, and compare its performance with that of conventional metrics (T 2 , magnetization transfer, and DTI parameters). The changes observed in vivo correlated with those obtained from quantitative electron microscopy image analysis. A 6week intoxication produced a significant decrease in axonal water fraction (p < 0.001), with only mild changes in extra-axonal radial diffusivity, consistent with patchy demyelination, while a 12week intoxication caused a more marked decrease in extra-axonal radial diffusivity (p = 0.0135), consistent with more severe demyelination and clearance of the extra-axonal space. Results thus revealed increased specificity of the axonal water fraction and extra-axonal radial diffusivity parameters to different degrees and patterns of demyelination. The specificities of these parameters were corroborated by their respective correlations with microstructural features: the axonal water fraction correlated significantly with the electron microscopy derived total axonal water fraction (ρ = 0.66; p = 0.0014) but not with the g-ratio, while the extra-axonal radial diffusivity correlated with the g-ratio (ρ = 0.48; p = 0.0342) but not with the electron microscopy derived axonal water fraction. These parameters represent promising candidates as clinically feasible biomarkers of demyelination and remyelination in the white matter.

Human behavioral response timing is highly variable from trial to trial. While it is generally understood that behavioral variability must be due to trial-by-trial variations in brain function, it is still largely unknown which physiological mechanisms govern the timing of neural activity as it travels through networks of neuronal populations, and how variations in the timing of neural activity relate to variations in the timing of behavior. In our study, we submitted recordings from the cortical surface to novel analytic techniques to chart the trajectory of neuronal population activity across the human cortex in single trials, and found joint modulation of the timing of this activity and of consequent behavior by neuronal oscillations in the alpha band (8-12 Hz). Specifically, we established that the onset of population activity tends to occur during the trough of oscillatory activity, and that deviations from this preferred relationship are related to changes in the timing of population activity and the speed of the resulting behavioral response. These results indicate that neuronal activity incurs variable delays as it propagates across neuronal populations, and that the duration of each delay is a function of the instantaneous phase of oscillatory activity. We conclude that the results presented in this paper are supportive of a general model for variability in the effective speed of information transmission in the human brain and for variability in the timing of human behavior.

This study shows that electrocorticographic (ECoG) signals recorded from the surface of the brain provide detailed information about shifting of visual attention and its directional orientation in humans. ECoG allows for the identification of the cortical areas and time periods that hold the most information about covert attentional shifts. Our results suggest a transient distributed frontoparietal mechanism for orienting of attention that is represented by different physiological processes. This neural mechanism encodes not only whether or not a subject shifts their attention to a location, but also the locus of attention. This work contributes to our understanding of the electrophysiological representation of attention in humans. It may also eventually lead to braincomputer interfaces (BCIs) that optimize user interaction with their surroundings or that allow people to communicate choices simply by shifting attention to them.

Brain atlas construction has attracted significant attention lately in the neuroimaging community due to its application to the characterization of neuroanatomical shape abnormalities associated with various neurodegenerative diseases or neuropsychiatric disorders. Existing shape atlas construc-

Brain atlas construction has attracted significant attention lately in the neuroimaging community due to its application to the characterization of neuroanatomical shape abnormalities associated with various neurodegenerative diseases or neuropsychiatric disorders. Existing shape atlas construc-

Social connectedness theory posits that the brain processes social rejection as a threat to survival. Recent electrophysiological evidence suggests that midfrontal theta (4-8Hz) oscillations in the EEG provide a window on the processing of social rejection. Here we examined midfrontal theta dynamics (power and inter-trial phase synchrony) during the processing of social evaluative feedback. We employed the Social Judgment paradigm in which 56 undergraduate women (mean age=19.67 years) were asked to communicate their expectancies about being liked vs. disliked by unknown peers. Expectancies were followed by feedback indicating social acceptance vs. rejection. Results revealed a significant increase in EEG theta power to unexpected social rejection feedback. This EEG theta response could be source-localized to brain regions typically reported during activation of the saliency network (i.e., dorsal anterior cingulate cortex, insula, inferior frontal gyrus, frontal pole, and the supplem...

2 Title Negative emotional stimulation decreases respiratory sensory gating in healthy humans. Abstract We tested the hypothesis that negative emotions decrease the respiratory-related evoked potentials (RREP) sensory gating (RSG). RREP were elicited by paired inspiratory occlusions. RSG was calculated as the difference in the averaged RREP peak N1 amplitude between the second (S2) and the first occlusion (S1). RSG was compared between unpleasant and neutral emotional conditions elicited by viewing affective pictures from the IAPS system in thirteen healthy adults. Results are expressed as median [min;max]. Compared to neutral pictures, viewing unpleasant pictures decreased the RREP We concluded that a negative emotional stimulation could attract subject&#39;s attention to the detriment of the respiratory sensory inputs and produced an overall decrease in the RSG. This latter finding might participate in an over-perception of repeatedly presented respiratory stimuli.

Damage to the corticospinal tract is widely studied following unilateral subcortical stroke, whereas less is known about changes to other sensorimotor pathways. This may be due to the fact that many studies investigated morphological changes in the brain, where the majority of descending and ascending brain pathways are overlapping, and did not investigate the brainstem where they separate. Moreover, these pathways continue passing through separate regions in the spinal cord. Here, using a high-resolution structural MRI of both the brainstem and the cervical spinal cord, we were able to identify a number of microstructurally altered pathways, in addition to the corticospinal tract, post stroke. Moreover, decreases in ipsi-lesional corticospinal tract integrity and increases in contra-lesional medial reticulospinal tract integrity were correlated with motor impairment severity in individuals with stroke.

Steady state auditory evoked potential (SSAEPs) in the electroencephalogram (EEG) and magnetoencephalogram (MEG) have been reported to be reduced in schizophrenia, most consistently to frequencies in the gamma range (40 Hz and greater). The current study evaluated the specificity of this deficit over a broad range of stimulus frequencies and harmonics, the relationship between phase locking and signal power, and whether induced 40 Hz activity was also affected. SSAEPs to amplitude modulated tones from 5 to 50 Hz were obtained from subjects with schizophrenia (SZ) and healthy control subjects in 5 Hz steps. Time-frequency spectral analysis was used to differentiate EEG activity synchronized in phase across trials using Phase Locking Factor (PLF) and Mean Power (MP) change from baseline activity. In the SSAEP frequency response condition, patients with SZ showed broad band reductions in both PLF and MP. In addition, the control subjects showed a more pronounced increase in PLF with increases in power compared to SZ subjects. A noise pulse embedded in 40 Hz stimuli resulted in a transient reduction of PLF and MP at 40 Hz in control subjects, while SZ showed diminished overall PLF. Finally, induced gamma (around 40 Hz) response to unmodulated tone stimuli was also reduced in SZ, indicating that disturbances in this oscillatory activity are not confined to SSAEPs. In summary, SZ subjects show impaired oscillatory responses in the gamma range across a wide variety of experimental conditions. Reduction of PLF along with reduced MP may reflect abnormalities in the auditory cortical circuits, such as a reduction in pyramidal cell volume, spine density and alterations in GABAergic neurons.

Functional magnetic resonance imaging was used to examine developmental change in hemispheric biases for globally and locally directed analysis of hierarchical forms. In a previous reaction time (RT) study, which presented hierarchical stimuli to the visual hemifields, children 7 to 14 years of age demonstrated an emerging pattern of hemispheric differences. Initially children analyzed local elements more slowly, without a strongly lateralized advantage for local or global level processing. With age, children's development was marked by a left hemisphere advantage for local level processing that resembled an adult's and a trend toward a right hemisphere advantage for global. In the current study, 20 children 12 to 14 years old were imaged during attend-global and attend-local conditions to determine whether the developmental change in cognitive measures corresponded to a change in distribution of functional activation. Children formed two groups based on their RT performance, immature-bilateral (IB) or mature-lateralized (ML). The volume of task-related activation within lateral temporo-occipital regions of interest was compared for global and local conditions between the two groups. The IB children showed greater activation overall for local level processing, comparable activation across the two hemispheres for the global condition, and a trend of right greater than left hemisphere activation for local. In contrast, the ML children displayed right greater than left hemisphere activation during global analysis and the opposite during local processing. Importantly these patterns of functional activation mirror the profiles of RT performance. Together they demonstrate a shift from undifferentiated, bilateral processing toward hemispheric lateralization.

Functional magnetic resonance imaging was used to examine developmental change in hemispheric biases for globally and locally directed analysis of hierarchical forms. In a previous reaction time (RT) study, which presented hierarchical stimuli to the visual hemifields, children 7 to 14 years of age demonstrated an emerging pattern of hemispheric differences. Initially children analyzed local elements more slowly, without a strongly lateralized advantage for local or global level processing. With age, children's development was marked by a left hemisphere advantage for local level processing that resembled an adult's and a trend toward a right hemisphere advantage for global. In the current study, 20 children 12 to 14 years old were imaged during attend-global and attend-local conditions to determine whether the developmental change in cognitive measures corresponded to a change in distribution of functional activation. Children formed two groups based on their RT performance, immature-bilateral (IB) or mature-lateralized (ML). The volume of task-related activation within lateral temporo-occipital regions of interest was compared for global and local conditions between the two groups. The IB children showed greater activation overall for local level processing, comparable activation across the two hemispheres for the global condition, and a trend of right greater than left hemisphere activation for local. In contrast, the ML children displayed right greater than left hemisphere activation during global analysis and the opposite during local processing. Importantly these patterns of functional activation mirror the profiles of RT performance. Together they demonstrate a shift from undifferentiated, bilateral processing toward hemispheric lateralization.

This research tests the hypothesis that comprehension of human events will engage an extended semantic representation system, independent of the input modality (sentence vs. picture). To investigate this, we examined brain activation and connectivity in 19 subjects who read sentences and viewed pictures depicting everyday events, in a combined fMRI and DTI study. Conjunction of activity in understanding sentences and pictures revealed a common fronto-temporo-parietal network that included the middle and inferior frontal gyri, the parahippocampal-retrosplenial complex, the anterior and middle temporal gyri, the inferior parietal lobe in particular the temporo-parietal cortex. DTI tractography seeded from this temporo-parietal cortex hub revealed a multi-component network reaching into the temporal pole, the ventral frontal pole and premotor cortex. A significant correlation was found between the relative pathway density issued from the temporo-parietal cortex and the imageability of ...

Understanding events requires interplaying cognitive processes arising in neural networks whose organisation and connectivity remain subjects of controversy in humans. In the present study, by combining diffusion tensor imaging and functional interaction analysis, we aim to provide new insights on the organisation of the structural and functional pathways connecting the multiple nodes of the identified semantic system -shared by vision and language . We investigated a group of 19 healthy human subjects during experimental tasks of reading sentences or seeing pictures. The structural connectivity was realised by deterministic tractography using an algorithm to extract white matter fibers terminating in the selected regions of interest (ROIs) and the functional connectivity by independent component analysis to measure correlated activities among these ROIs. The major connections link ventral neural stuctures including the parietal and temporal cortices through inferior and middle longitudinal fasciculi, the retrosplenial and parahippocampal cortices through the cingulate bundle, and the temporal and prefrontal structures through the uncinate fasciculus. The imageability score provided when the subject was reading a sentence was significantly correlated with the factor of anisotropy of the left parietotemporal connections of the middle longitudinal fasciculus. A large part of this ventrally localised structural connectivity corresponds to functional interactions between the main parietal, temporal and frontal nodes. More precisely, the strong coactivation both in the anterior temporal pole and in the region of the temporo-parietal cortex suggests dual and cooperating roles for these areas within the semantic system. These findings are discussed in terms of two semantics-related sub-systems responsible for conceptual representation.

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Greater physical activity and cardiorespiratory fitness are associated with reduced age-related cognitive decline and lower risk for dementia. However, significant gaps remain in the understanding of how physical activity and fitness protect the brain from adverse effects of brain aging. The primary goal of the current study was to empirically evaluate the independent relationships between physical activity and fitness with functional brain health among healthy older adults, as measured by the functional connectivity of cognitively and clinically relevant resting state networks. To build context for fitness and physical activity associations in older adults, we first demonstrate that young adults have greater within-network functional connectivity across a broad range of cortical association networks. Based on these results and previous research, we predicted that individual differences in fitness and physical activity would be most strongly associated with functional integrity of the networks most sensitive to aging. Consistent with this prediction, and extending on previous research, we showed that cardiorespiratory fitness has a positive relationship with functional connectivity of several cortical networks associated with age-related decline, and effects were strongest in the Default Mode Network (DMN). Furthermore, our results suggest that the positive association of fitness with brain function can occur independent of habitual physical activity. Overall, our findings provide further support that cardiorespiratory fitness is an important factor in moderating the adverse effects of aging on cognitively and clinically relevant functional brain networks.

White matter structure declines with advancing age and has been associated with a decline in memory and executive processes in older adulthood. Yet, recent research suggests that higher physical activity and fitness levels may be associated with less white matter degeneration in late life, although the tract-specificity of this relationship is not well understood. In addition, these prior studies infrequently associate measures of white matter microstructure to cognitive outcomes, so the behavioral importance of higher levels of white matter microstructural organization with greater fitness levels remains a matter of speculation. Here we tested whether cardiorespiratory fitness (VO 2max ) levels were associated with white matter microstructure and whether this relationship constituted an indirect pathway between cardiorespiratory fitness and spatial working memory in two large, cognitively and neurologically healthy older adult samples. Diffusion tensor imaging was used to determine white matter microstructure in two separate groups: Experiment 1, N = 113 (mean age = 66.61) and Experiment 2, N = 154 (mean age = 65.66). Using a voxel-based regression approach, we found that higher VO 2max was associated with higher fractional anisotropy (FA), a measure of white matter microstructure, in a diverse network of white matter tracts, including the anterior corona radiata, anterior internal capsule, fornix, cingulum, and corpus callosum (P FDR-corrected b .05). This effect was consistent across both samples even after controlling for age, gender, and education. Further, a statistical mediation analysis revealed that white matter microstructure within these regions, among others, constituted a significant indirect path between VO 2max and spatial working memory performance. These results suggest that greater aerobic fitness levels are associated with higher levels of white matter microstructural organization, which may, in turn, preserve spatial memory performance in older adulthood.

Rhythm in terms of the modulation of syllable durations represents an information-bearing feature of verbal utterances contributing both to the meaning of a sentence (linguistic prosody) as well as a speaker's emotional expression (affective prosody). In order to delineate the neural structures subserving rhythmic shaping of speech production, functional magnetic resonance imaging (fMRI) was performed during (a) monotonous syllable repetitions and (b) production of syllable triplets with lengthening either of the initial or final unit. The latter pattern of syllable durations can be considered the prototypical rhythmic structure contributing both to linguistic and affective prosody. A cognitive subtraction approach (rhythmic versus monotonous iterations) revealed activation of right-sided perisylvian areas (superior temporal gyrus, Broca analogon and adjacent premotor cortex) as well as contralateral subcortical structures (putamen and thalamus). Presumably, these responses reflect a righthemisphere rehearsal mechanism of rhythmic patterns and lefthemisphere monitoring of verbal output.