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Recent advances in brain imaging technology have furthered our knowledge of the neural basis of auditory and speech processing, often via contributions from invasive brain signal recording and stimulation studies conducted intraoperatively. Herein, an approach for synthesizing vowel sounds straightforwardly from scalp‐recorded electroencephalography (EEG), a noninvasive neurophysiological recording method is demonstrated. Given cortical current signals derived from the EEG acquired while human participants listen to and recall (i.e., imagined) two vowels, /a/ and /i/, sound parameters are estimated by a convolutional neural network (CNN). The speech synthesized from the estimated parameters is sufficiently natural to achieve recognition rates >85% during a subsequent sound discrimination task. Notably, the CNN identifies the involvement of the brain areas mediating the “what” auditory stream, namely the superior, middle temporal, and Heschl's gyri, demonstrating the efficacy of the computational method in extracting auditory‐related information from neuroelectrical activity. Differences in cortical sound representation between listening versus recalling are further revealed, such that the fusiform, calcarine, and anterior cingulate gyri contributes during listening, whereas the inferior occipital gyrus is engaged during recollection. The proposed approach can expand the scope of EEG in decoding auditory perception that requires high spatial and temporal resolution.

One of the major challenges for clinicians who treat patients with Disorders of Consciousness (DoCs) concerns the detection of signs of consciousness that distinguish patients in Vegetative State from those in Minimally Conscious State. Recent studies showed how visual responses to tailored stimuli are one of the first evidence revealing that one patient is changing from one state to another. This study aimed to explore the integrity of the neural structures being part of the visual system in patients with DoCs manifesting a reflexive behavior (visual blink) and in those manifesting a cognitively and cortically mediated behavior (visual pursuit). We collected instrumental data using specialized equipment (EEG following the rules of the International 10-20 system, 3T Magnetic Resonance, and Positron Emission Tomography) in 54 DoC patients. Our results indicated that visual pursuit group showed a better fVEPs response than the visual blink group, because of a greater area under the N2/P2 component of fVEPs (AUC could be seen as an indicator of the residual activity of visual areas). Considering neuroimaging data, the main structural differences between groups were found in the retrochiasmatic areas, specifically in the right optic radiation and visual cortex (V1), areas statistically less impaired in patients able to perform a visual pursuit. FDG-PET analysis confirmed difference between groups at the level of the right calcarine cortex and neighboring right lingual gyrus. In conclusion, although there are methodological and theoretical limitations that should be considered, our study suggests a new perspective to consider for a future diagnostic protocol.

BACKGROUND Head motion during brain structural MRI scans biases brain morphometry measurements but quantitative retrospective methods estimating head motion from structural MRI have not been evaluated. PURPOSE To verify the hypothesis that two metrics retrospectively computed from MR images: 1) average edge strength (AES, reduced with image blurring) and 2) entropy (ENT, increased with blurring and ringing artifacts) could be sensitive to in-scanner head motion during acquisition of T1 -weighted MR images. STUDY TYPE Retrospective. POPULATION/SUBJECTS/PHANTOM/SPECIMEN/ANIMAL MODEL In all, 83 healthy control (HC) and 120 Parkinson's disease (PD) patients. FIELD STRENGTH/SEQUENCE 3D magnetization-prepared rapid gradient-echo (MPRAGE) images at 3T. ASSESSMENT We 1) compared AES and ENT distribution between HC and PD; 2) evaluated the correlation between tremor score (TS) and AES (or ENT) in PD; and 3) investigated cortical regions showing an association between AES (or ENT) and local and network-level covariance measures of cortical thickness (CT), gray to white matter contrast (GWC) and gray matter density maps (GMx). STATISTICAL TESTS 1) Student's t-test. 2) Spearman's rank correlation. 3) General linear model and partial least square analysis. RESULTS AES, but not ENT, differentiated HC and PD (P = 0.02, HC median AES = 39.8, interquartile range = 9.8, PD median AES = 37.6, interquartile range = 8.1). In PD, AES correlated negatively with TS (ρ = -0.21, P = 0.02) and showed a significant relationship (|Z| >3, P

Pain assessment in patients with disorders of consciousness (DoC) is a controversial issue for clinicians, who require tools and standardised procedures for testing nociception in non-communicative patients. The aims of the present study were, first, to analyse the psychometric properties of the Italian version of the Nociception Coma Scale and, second, to evaluate pressure pain thresholds in a group of patients with DoC. The authors conducted a multi-centre study on 40 healthy participants and 60 DoC patients enrolled from six hospitals in Italy. For each group an electronic algometer was used to apply all nociceptive pressure stimuli. Our results show that the Italian version of the NCS retains the good psychometric properties of the original version and is therefore suitable for standardised pain assessment in clinical practice. In our study, pressure pain thresholds measured in a group of patients in vegetative and minimally conscious state were relatively lower than pain threshold values found in a group of healthy participants. Such findings motivate additional investigation on possible pain sensitisation in patients with severe brain injury and multiple co-morbidities, and on application of tailored therapeutic approaches useful for pain management in patients unable verbally to communicate their feelings.

International audience; Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting the corticospinal tract and leading to motor neuron death. According to a recent study, magnetic resonance imaging-visible changes suggestive of neurodegeneration seem absent in the motor cortex of G93A-SOD1 ALS mice. However, it has not yet been ascertained whether the cortical neural activity is intact, or alterations are present, perhaps even from an early stage. Here, cortical neurons from this model were isolated at post-natal day 1 and cultured on multielectrode arrays. Their activity was studied with a comprehensive pool of neurophysiological analyses probing excitability, criticality and network architecture, alongside immunocytochemistry and molecular investigations. Significant hyperexcitability was visible through increased network firing rate and bursting, whereas topological changes in the synchronization patterns were apparently absent. The number of dendritic spines was increased, accompanied by elevated transcriptional levels of the DLG4 gene, NMDA receptor 1 and the early pro-apoptotic APAF1 gene. The extracellular Na+, Ca2+, K+ and Cl- concentrations were elevated, pointing to perturbations in the culture micro-environment. Our findings highlight remarkable early changes in ALS cortical neuron activity and physiology. These changes suggest that the causative factors of hyperexcitability and associated toxicity could become established much earlier than the appearance of disease symptoms, with implications for the discovery of new hypothetical therapeutic targets.

Auditory "oddball" event-related potentials (aoERPs), resting state functional magnetic resonance imaging (rsfMRI) connectivity, and electroencephalographic (rsEEG) rhythms were tested as longitudinal functional biomarkers of prodromal Alzheimer's disease (AD). Data were collected at baseline and four follow-ups at 6, 12, 18, and 24 months in amnesic mild cognitive impairment (aMCI) patients classified in two groups: "positive" (i.e., "prodromal AD" n=81) or "negative" (n=63) based on a diagnostic marker of AD derived from cerebrospinal samples (Aβ 42 /P-tau ratio). A linear mixed model design was used to test functional biomarkers for Group, Time, and Group×Time effects adjusted by nuisance covariates (only data until conversion to dementia was used). Functional biomarkers that showed significant Group effects ("positive" versus "negative", p

The visual fixation represents a doubtful behavioral sign to discriminate Vegetative from Minimally Conscious State (MCS). To disentangle its meaning, we fitted univariate and multivariable logistic regression models matching different neurophysiological and neuroimaging data of 54 patients with Disorders of Consciousness to select the best model predicting which visual performance (visual blink or pursuit) was shown by patients and the best predictors set. The best models found highlighted the importance of the structural MRI and the visual evoked potentials data in predicting visual pursuit. Then, a qualitative pilot test was made on four patients showing visual fixation revealing that the obtained models correctly predict whether the patients' visual performance could support/correlate to a cognitively mediated behavior. The present pilot models could help clinicians to evaluate if the visual fixation response can support the MCS diagnosis.

Objective Understanding residual brain function in disorders of consciousness poses extraordinary challenges, and imaging examinations are needed to complement clinical assessment. The default-mode network (DMN) is known to be dysfunctional, although correlation with level of consciousness remains controversial. We investigated DMN activity with resting-state functional magnetic resonance imaging (rs-fMRI), alongside its structural and metabolic integrity, aiming to elucidate the corresponding associations with clinical assessment. Methods We enrolled 119 consecutive patients: 72 in a vegetative state/unresponsive wakefulness state (VS/UWS), 36 in a minimally conscious state (MCS), and 11 with severe disability. All underwent structural MRI and rs-fMRI, and a subset also underwent 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET). Data were analyzed with manual and automatic approaches, in relation to diagnosis and clinical score. Results Excluding the quartile with largest head movement, DMN activity was decreased in VS/UWS compared to MCS, and correlated with clinical score. Independent-component and seed-based analyses provided similar results, although the latter and their combination were most informative. Structural MRI and FDG-PET were less sensitive to head movement and had better diagnostic accuracy than rs-fMRI only when all cases were included. rs-fMRI indicated relatively preserved DMN activity in a small subset of VS/UWS patients, 2 of whom evolved to MCS. The integrity of the left hemisphere appears to be predictive of a better clinical status. Interpretation rs-fMRI of the DMN is sensitive to clinical severity. The effect is consistent across data analysis approaches, but heavily dependent on head movement. rs-fMRI could be informative in detecting residual DMN activity for those patients who remain relatively still during scanning and whose diagnosis is uncertain. Ann Neurol 2016;79:841-853.

Understanding how to reduce the influence of physiological noise in resting state fMRI data is important for the interpretation of functional brain connectivity. Limited data is currently available to assess the performance of physiological noise correction techniques, in particular when evaluating longitudinal changes in the default mode network (DMN) of healthy elderly participants. In this 3T harmonized multisite fMRI study, we investigated how different retrospective physiological noise correction (rPNC) methods influence the within-site test-retest reliability and the across-site reproducibility consistency of DMN-derived measurements across 13 MRI sites. Elderly participants were scanned twice at least a week apart (five participants per site). The rPNC methods were: none (NPC), Tissue-based regression, PESTICA and FSL-FIX. The DMN at the single subject level was robustly identified using ICA methods in all rPNC conditions. The methods significantly affected the mean z-scores and, albeit less markedly, the cluster-size in the DMN; in particular, FSL-FIX tended to increase the DMN z-scores compared to others. Within-site test-retest reliability was consistent across sites, with no differences across rPNC methods. The absolute percent errors were in the range of 5-11% for DMN z-scores and cluster-size reliability. DMN pattern overlap was in the range 60-65%. In particular, no rPNC method showed a significant reliability improvement relative to NPC. However, FSL-FIX and Tissue-based physiological correction methods showed both similar and significant improvements of reproducibility consistency across the consortium (ICC = 0.67) for the DMN z-scores relative to NPC. Overall these findings support the use of rPNC methods like tissue-based or FSL-FIX to characterize multisite longitudinal changes of intrinsic functional connectivity. Hum Brain Mapp 37:2114-2132, 2016. © 2016 Wiley Periodicals, Inc.

The differential diagnosis between vegetative state and minimally conscious state is still complex and the development of an evaluation systems is one of the challenging tasks for researchers and professionals. The Coma Recovery Scale-revised is considered the gold standard for clinical/behavioral assessment and for the differential diagnosis of patients with disorder of consciousness. However, the scale presents some limitations in that (i) scores may partially overlap between different diagnoses and (ii) there is an underlying assumption that if a patient is able to show higher-level behaviors, he/she is also able to show lower-level responses. In the present study, a procedure to calculate a modified Coma Recovery Scale-revised score is presented that attempts to avoid these problems. To exemplify this new scoring approach, 60 patients with disorder of consciousness were studied and the results showed the usefulness of the Modified Score.

Humans can innately track a moving target by anticipating its future position from a brief history of observations. While ballistic trajectories can be readily extrapolated, many natural and artificial systems are governed by more general nonlinear dynamics and, therefore, can produce highly irregular motion. Yet, relatively little is known regarding the behavioral and physiological underpinnings of prediction and tracking in the presence of chaos. Here, we investigated in lab settings whether participants could manually follow the orbit of a paradigmatic chaotic system, the Rössler equations, on the (x,y) plane under different settings of a control parameter, which determined the prominence of transients in the target position. Tracking accuracy was negatively related to the level of unpredictability and folding. Nevertheless, while participants initially reacted to the transients, they gradually learned to anticipate it. This was accompanied by a decrease in muscular co-contraction, alongside enhanced activity in the theta and beta EEG bands for the highest levels of chaoticity. Furthermore, greater phase synchronization of breathing was observed. Taken together, these findings point to the possible ability of the nervous system to implicitly learn topological regularities even in the context of highly irregular motion, reflecting in multiple observables at the physiological level.

The hippocampus is one of the earliest brain regions affected in Alzheimer's disease (AD) and tests of hippocampal function have the potential to detect AD in its earliest stages. Given that the hippocampus is critically involved in allocentric spatial memory, this study applied a short test of spatial memory, the 4 Mountains Test (4MT), to determine whether test performance can differentiate mild cognitive impairment (MCI) patients with and without CSF biomarker evidence of underlying AD and whether the test can distinguish patients with MCI and mild AD dementia when applied in different cultural settings. Healthy controls (HC), patients with MCI, and mild AD dementia were recruited from study sites in UK and Italy. Study numbers were: HC (UK 20, Italy 10), MCI (UK 21, Italy 14), and AD (UK 11, Italy 9). Nineteen UK MCI patients were grouped into CSF biomarker-positive (MCI+, n = 10) and biomarker-negative (MCI–, n = 9) subgroups. Behavioral data were correlated with hippocampal volume and cortical thickness of the precuneus and posterior cingulate gyrus. Spatial memory was impaired in both UK and Italy MCI and AD patients. Test performance additionally differentiated between MCI+ and MCI– subgroups (P = 0.001). A 4MT score of ≤8/15 was associated with 100% sensitivity and 90% specificity for detection of early AD (MCI+ and mild AD dementia) in the UK population, and with 100% sensitivity and 50% specificity for detection of MCI and AD in the Italy sample. 4MT performance correlated with hippocampal volume in the UK population and cortical thickness of the precuneus in both study populations. In conclusion, performance on a hippocampus-sensitive test of spatial memory differentiates MCI due to AD with high diagnostic sensitivity and specificity. The observation that similar diagnostic sensitivity was obtained in two separate study populations, allied to the scalability and usability of the test in community memory clinics, supports future application of the 4MT in the diagnosis of pre-dementia due to AD. © 2015 Wiley Periodicals, Inc.

The pool size ratio measured by quantitative magnetization transfer MRI is hypothesized to closely reflect myelin density, but their relationship has so far been confirmed mostly in ex vivo conditions. We investigate the correspondence between this parameter measured in vivo at 7.0 T, with Black Gold II staining for myelin fibres, and with myelin basic protein and beta-tubulin immunofluorescence in a hybrid longitudinal study of C57BL/6 and SJL/J mice treated with cuprizone, a neurotoxicant causing relatively selective myelin loss followed by spontaneous remyelination upon treatment suspension. Our results confirm that pool size ratio measurements correlate with myelin content, with the correlation coefficient depending on strain and staining method, and demonstrate the in vivo applicability of this MRI technique to experimental mouse models of multiple sclerosis.

Objective: The study compared the metric characteristics (discriminant capacity and factorial structure) of two different methods for scoring the items of the Coma Recovery Scale-Revised and it analysed scale scores collected using the standard assessment procedure and a new proposed method. Design: Cross sectional design/methodological study. Setting: Inpatient, neurological unit. Participants: A total of 153 patients with disorders of consciousness were consecutively enrolled between 2011 and 2013. Intervention: All patients were assessed with the Coma Recovery Scale-Revised using standard (rater 1) and inverted (rater 2) procedures. Main outcome measures: Coma Recovery Scale-Revised score, number of cognitive and reflex behaviours and diagnosis. Results: Regarding patient assessment, rater 1 using standard and rater 2 using inverted procedures obtained the same best scores for each subscale of the Coma Recovery Scale-Revised for all patients, so no clinical (and statistical) difference was found between the two procedures. In 11 patients (7.7%), rater 2 noted that some Coma Recovery Scale-Revised codified behavioural responses were not found during assessment, although higher response categories were present. A total of 51 (36%) patients presented the same Coma Recovery Scale-Revised scores of 7 or 8 using a standard score, whereas no overlap was found using the modified score. Unidimensionality was confirmed for both score systems. Conclusion: The Coma Recovery Scale Modified Score showed a higher discriminant capacity than the standard score and a monofactorial structure was also supported. The inverted assessment procedure could be a useful evaluation method for the assessment of patients with disorder of consciousness diagnosis.

WOS:000390259700002; International audience; Free water elimination (FWE) in brain diffusion MRI has been shown to improve tissue specificity in human white matter characterization both in health and in disease. Relative to the classical diffusion tensor imaging (DTI) model, FWE is also expected to increase sensitivity to microstructural changes in longitudinal studies. However, it is not clear if these two models differ in their test-retest reproducibility. This study compares a bi-tensor model for FWE with DTI by extending a previous longitudinal-reproducibility 3T multisite study (10 sites, 7 different scanner models) of 50 healthy elderly participants (55-80 years old) scanned in two sessions at least 1 week apart. We computed the reproducibility of commonly used DTI metrics (FA: fractional anisotropy, MD: mean diffusivity, RD: radial diffusivity, and AXD: axial diffusivity), derived either using a DTI model or a FWE model. The DTI metrics were evaluated over 48 white-matter regions of the JHU-ICBM-DTI-81 white-matter labels atlas, and reproducibility errors were assessed. We found that relative to the DTI model, FWE significantly reduced reproducibility errors in most areas tested. In particular, for the FA and MD metrics, there was an average reduction of approximately 1% in the reproducibility error. The reproducibility scores did not significantly differ across sites. This study shows that FWE improves sensitivity and is thus promising for clinical applications, with the potential to identify more subtle changes. The increased reproducibility allows for smaller sample size or shorter trials in studies evaluating biomarkers of disease progression or treatment effects. Hum Brain Mapp 38:12-26, 2017. (c) 2016 Wiley Periodicals, Inc.

Differential diagnosis between Vegetative State and Minimally Conscious State is a challenging task that requires specific assessment scales, involvement of expert neuropsychologists or physicians and use of tailored stimuli for eliciting behavioural responses. Although misdiagnosis rate as high as 40 % has been reported, no clear guidelines are available in literature on the optimal setting for assessment. The present study aims to analyse score differences in behavioural assessments of persons with disorders of consciousness (DOC) with or without family members and to determine whether the presence of caregivers could improve clinical accuracy in diagnostic evaluation. The research was conducted on 92 adults with DOC among 153 consecutive patients enrolled in the Coma Research Centre of the Neurological Institute C. Besta of Milan between January 2011 and May 2013. The results indicate that in almost half of the sample the scoring, thus the performance, observed with caregivers was better than without them. Furthermore, in 16 % of the sample, when assessment was performed with caregivers there was a change in diagnosis, from Vegetative to Minimally Conscious State or from that to Severe Disability. Finally, statistical differences were found in relation to diagnosis between mean scores in the “visual function” Coma Recovery Scale revised’s subscale obtained by raters plus caregiver and rates only assessment. This study demonstrates how the presence of caregivers can positively affect behavioural assessments of persons with DOC, thus contributing to the definition of the optimal setting for behavioural evaluation of patients, to decrease misdiagnosis rates.

Cognitions and emotions can be influenced by bodily physiology. Here, we investigated whether the processing of brief fear stimuli is selectively gated by their timing in relation to individual heartbeats. Emotional and neutral faces were presented to human volunteers at cardiac systole, when ejection of blood from the heart causes arterial baroreceptors to signal centrally the strength and timing of each heartbeat, and at diastole, the period between heartbeats when baroreceptors are quiescent. Participants performed behavioral and neuroimaging tasks to determine whether these interoceptive signals influence the detection of emotional stimuli at the threshold of conscious awareness and alter judgments of emotionality of fearful and neutral faces. Our results show that fearful faces were detected more easily and were rated as more intense at systole than at diastole. Correspondingly, amygdala responses were greater to fearful faces presented at systole relative to diastole. These novel findings highlight a major channel by which short-term interoceptive fluctuations enhance perceptual and evaluative processes specifically related to the processing of fear and threat and counter the view that baroreceptor afferent signaling is always inhibitory to sensory perception.

We investigated changes in functional network architecture in amnestic mild cognitive impairment using graph-based analysis of task-free functional magnetic resonance imaging and fine cortical parcellation. Widespread disconnection was observed primarily in cortical hubs known to manifest early Alzheimer's disease pathology, namely precuneus, parietal lobules, supramarginal and angular gyri, and cuneus, with additional involvement of subcortical regions, sensorimotor cortex and insula. The connectivity changes determined using graph-based analysis significantly exceed those detected using independent component analysis both in amplitude and topographical extent, and are largely decoupled from the presence of overt atrophy. This superior ability of graph-based analysis to detect disease-related disconnection highlights its potential use in the determination of biomarkers of early dementia. Graph-based analysis source code is provided as supplementary material.

The hippocampus is one of the first regions to exhibit neurodegeneration in Alzheimer’s disease (AD) and knowledge of its role in allocentric spatial memory may therefore aid early diagnosis of AD. The 4 Mountains Test (4MT) is a short and easily administered test of spatial memory based on the cognitive map theory of hippocampal function as derived from rodent single cell and behavioral studies. The 4MT has been shown in previous cross-sectional studies to be sensitive and specific for mild cognitive impairment due to AD. This report describes the initial results of a longitudinal study testing the hypothesis that allocentric spatial memory is predictive of conversion from mild cognitive impairment to dementia. Fifteen patients with mild cognitive impairment underwent baseline testing on the 4MT in addition to CSF amyloid/tau biomarker studies, volumetric MRI and neuropsychological assessment including the Rey Auditory Verbal Learning Test (RAVLT) and Trail Making Test “B” (TMT-B). At 24 months, 9/15 patients had converted to AD dementia. The 4MT predicted conversion to AD with 93% accuracy (Cohen’s d = 2.52). The predictive accuracies of the comparator measures were as follows: CSF tau/β-amyloid1-42 ratio 92% (d = 1.81), RAVLT 64% (d = 0.41), TMT-B 78% (d = 1.56), and hippocampal volume 77% (d = 0.65). CSF tau levels were strongly negative correlated with 4MT scores (r = -0.71). This proof-of-concept study provides initial support for the hypothesis that allocentric spatial memory testing is a predictive cognitive marker of hippocampal neurodegeneration in pre-dementia AD. The 4MT is a brief, noninvasive, straightforward spatial memory test and is therefore ideally suited for use in routine clinical diagnostic practice. This is of particular importance given the current unmet need for simple accurate diagnostic tests for early AD and the ongoing development of potential disease-modifying therapeutic agents which may be more efficacious when given earlier in the disease course. By applying a test based on studies of hippocampal function in rodents to patient populations this work represents the first step in the development of translatable biomarkers of hippocampal involvement in early AD for use in both animal models and human subjects.

Although several brain regions show significant specialization, higher functions such as cross-modal information integration, abstract reasoning and conscious awareness are viewed as emerging from interactions across distributed functional networks. Analytical approaches capable of capturing the properties of such networks can therefore enhance our ability to make inferences from functional MRI, electroencephalography and magnetoencephalography data. Graph theory is a branch of mathematics that focuses on the formal modelling of networks and offers a wide range of theoretical tools to quantify specific features of network architecture (topology) that can provide information complementing the anatomical localization of areas responding to given stimuli or tasks (topography). Explicit modelling of the architecture of axonal connections and interactions among areas can furthermore reveal peculiar topological properties that are conserved across diverse biological networks, and highly sensitive to disease states. The field is evolving rapidly, partly fuelled by computational developments that enable the study of connectivity at fine anatomical detail and the simultaneous interactions among multiple regions. Recent publications in this area have shown that graph-based modelling can enhance our ability to draw causal inferences from functional MRI experiments, and support the early detection of disconnection and the modelling of pathology spread in neurodegenerative disease, particularly Alzheimer's disease. Furthermore, neurophysiological studies have shown that network topology has a profound link to epileptogenesis and that connectivity indices derived from graph models aid in modelling the onset and spread of seizures. Graph-based analyses may therefore significantly help understand the bases of a range of neurological conditions. This review is designed to provide an overview of graph-based analyses of brain connectivity and their relevance to disease aimed principally at general neuroscientists and clinicians.

In patients with temporal lobe epilepsy (TLE), assessment of language lateralization is important as anterior temporal lobectomy may lead to language impairments. Despite the widespread use of fMRI, evidence of its usefulness in predicting postsurgical language performance is scant. We investigated whether preoperative functional lateralization is related to the preoperative language performance, peri-ictal aphasia, and can predict language outcome one year post-surgery. We studied a total of 72 TLE patients (42 left, 30 right), by using three fMRI tasks: Naming, Verb Generation and Fluency. Functional lateralization indices were analyzed with neuropsychological scores and presence of peri-ictal aphasia. The key findings are:1)Both left and right TLE patients show decreased left lateralization compared to controls.2)Lateralization correlates with language performance before surgery. In left TLE, decreased left lateralization correlates with better fluency performance. In right TLE, increased left lateralization during the Naming task correlates with better naming.3)Left lateralization correlates with peri-ictal aphasia in left TLE patients.4)Lateralization correlates with language performance after surgery. In a subgroup of left TLE who underwent surgery (17 left), decreased left lateralization is predictive of better naming performance at 6 and 12 months after surgery. The present study highlights the clinical relevance of fMRI language lateralization in TLE, especially to predict language outcome one year post-surgery. We also underline the importance of using fMRI tasks eliciting frontal and anterior temporal activations, when studying left and right TLE patients., Highlights • We used preoperative fMRI to predict language performance in 72 TLE patients. • Language lateralization is clinically important for left and right TLE patients. • Lateralization correlates with language performance before surgery. • Left lateralization correlates with peri-ictal aphasia in left TLE. • Left lateralization predicts language performance 1 year after surgery in left TLE.

The majority of existing functional MRI studies on olfactory perception have addressed the relationship between stimulus features and the intensity of activity in separate regions considered in isolation. However, anatomical studies as well as neurophysiological recordings in rats and insects suggest that odor features may also be represented in a sparse manner through the simultaneous activity of multiple cortical areas interacting as a network. Here, we aimed to map the interdependence of neural activity among regions of the human brain, representing functional connectivity, during passive smelling. Seventeen healthy participants were scanned while performing a blocked-design task alternating exposure to two unpleasant odorants and breathing fresh air. High efferent connectivity was detected for the piriform cortex and the amygdala bilaterally. By contrast, the medial orbitofrontal cortex was characterized by high afferent connectivity, notably in the absence of an overall change in the intensity of hemodynamic activity during olfactory stimulation. Our results suggest that, even in the context of an elementary task, information on olfactory stimuli is scattered by the amygdala and piriform cortex onto an anatomically sparse representation and then gathered and integrated in the medial orbitofrontal cortex.

Asperger syndrome (AS) is an Autism Spectrum Disorder (ASD) characterised by qualitative impairment in the development of emotional and social skills with relative preservation of general intellectual abilities, including verbal language. People with AS may nevertheless show atypical language, including rate and frequency of speech production. We previously observed that abnormalities in grey matter homogeneity (measured with texture analysis of structural MR images) in AS individuals when compared with controls are also correlated with the volume of caudate nucleus. Here, we tested a prediction that these distributed abnormalities in grey matter compromise the functional integrity of brain networks supporting verbal communication skills. We therefore measured the functional connectivity between caudate nucleus and cortex during a functional neuroimaging study of language generation (verbal fluency), applying psycho-physiological interaction (PPI) methods to test specifically for differences attributable to grey matter heterogeneity in AS participants. Furthermore, we used dynamic causal modelling (DCM) to characterise the causal directionality of these differences in interregional connectivity during word production. Our results revealed a diagnosis-dependent influence of grey matter heterogeneity on the functional connectivity of the caudate nuclei with right insula/inferior frontal gyrus and anterior cingulate, respectively with the left superior frontal gyrus and right precuneus. Moreover, causal modelling of interactions between inferior frontal gyri, caudate and precuneus, revealed a reliance on bottom-up (stimulus-driven) connections in AS participants that contrasted with a dominance of top-down (cognitive control) connections from prefrontal cortex observed in control participants. These results provide detailed support for previously hypothesised central disconnectivity in ASD and specify discrete brain network targets for diagnosis and therapy in ASD., Highlights • We used MRI techniques to assess the connectivity in language networks in AS. • Grey-matter heterogeneity of MR images correlated with volume of caudate in AS. • Hence, caudate nuclei were used as seed ROIs in connectivity analyses: PPI, DCM. • Grey-matter heterogeneity differently tuned caudate connectivity in AS, controls. • DCM of language circuitry featured bottom-up models in AS and top-down in controls.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by selective motor neuron degeneration in the motor cortex, brainstem and spinal cord. It is generally accepted that ALS is caused by death of motor neurons, however the exact temporal cascade of degenerative processes is not yet completely known. To identify the early pathological changes in spinal cord of G93A-SOD1 AIS mice we performed a comprehensive longitudinal analysis employing diffusion-tensor magnetic resonance imaging alongside histology and electron microscopy, in parallel with peripheral nerve histology. We showed the gradient of degeneration appearance in spinal cord white and gray matter, starting earliest in the ventral white matter, due to a cascade of pathological events including axon dysfunction and mitochondrial changes. Notably, we found that even the main sensory regions are affected by the neurodegenerative process at symptomatic disease phase. Overall our results attest the applicability of DTI in determining disease progression in ALS mice. These findings suggest that DTI could be potentially adapted in humans to aid the assessment of ALS progression and eventually the evaluation of treatment efficacy. (C) 2017 Elsevier Inc. All rights reserved.

Neurodegenerative diseases comprise a broad swath of different neurologic diseases characterized by loss of neurons in the central nervous system. The most common neurodegenerative disease is Alzheimer disease, a dementing disease. Dementia is commonly understood as loss of function in at least two cognitive domains that is severe enough to affect daily activities in the social or occupational spheres. Elderly adults represent a significant and rapidly expanding proportion of the population. Some estimates state that by 2030 there will be 72 million individuals over the age of 65 years in the United States, constituting 19% of the population. The World Health Organization estimated in 2010 that there were 36.5 million people worldwide living with dementia, with the global cost for care being $604 billion per year. A new case of dementia is diagnosed approximately every 4 seconds. As the prevalence of many neurologic diseases increases with age, it can be difficult to differentiate between the effects of aging and those of prodromal age-related disease. Advances in neuroimaging have afforded significant insight into progressive neurodegenerative disorders and their mimics. Besides the improvements in structural imaging that have come about through thinner slices, 3-dimensional volumes, and higher spatial resolution, molecular and cellular imaging have made a big impact on how we look at the brain and its function. MR spectroscopy, diffusion tensor imaging, perfusion imaging, functional MRI, and PET scans have further increased our understanding of the pathophysiology of neurodegenerative disorders. Distinguishing between preventable diseases, potentially reversible diseases, and progressive, irreversible diseases is important in planning for a patient’s future medical, social, and economic spheres. Imaging of Neurodegenerative Disorders is a comprehensive, updated reference covering the latest techniques used in neuroimaging as well as the basic structural imaging that facilitates diagnosis of various neurodegenerative disorders. Because there never has been a dedicated textbook on the imaging of neurodegenerative diseases, the aim of this book is to cover each disease as it is currently understood and to show what it might look like using various imaging techniques. Imaging helps enormously in affirming suspicions, differentiating entities that have a clinical overlap, and charting the progression of neurodegenerative diseases. The book is organized into 16 parts with 41 chapters written by 83 contributors who have brought fresh insights and expertise that encompass many disease entities. They attempt to fill the gap of knowledge that exists in the imaging and understanding of neurodegenerative diseases. Chapters are arranged by specific diseases and cover their clinical features, pathologic characteristics, and imaging. Along with a brief discussion of each disease are the images themselves—superb in quality and quite illustrative—in addition to what tests to order, what to look for, what one expects to see for each disorder, and what new clinical and research modalities are available. This book is useful for radiologists, neuroradiologists, neurologists, neurosurgeons, and other internal or family medical physicians, as well as anyone seeking to understand neurodegenerative disorders through the lens of imaging techniques that are becoming increasingly sophisticated.

WOS:000366646700041; International audience; To date, limited data are available regarding the inter-site consistency of test-retest reproducibility of functional connectivity measurements, in particular with regard to integrity of the Default Mode Network (DMN) in elderly participants. We implemented a harmonized resting-state fMRI protocol on 13 clinical scanners at 3.0 T using vendor-provided sequences. Each site scanned a group of 5 healthy elderly participants twice, at least a week apart. We evaluated inter-site differences and test-retest reproducibility of both temporal signal-to-noise ratio (tSNR) and functional connectivity measurements derived from: i) seed-based analysis (SBA) with seed in the posterior cingulate cortex (PCC), ii) group independent component analysis (ICA) separately for each site (site ICA), and iii) consortium ICA, with group ICA across the whole consortium. Despite protocol harmonization, significant and quantitatively important inter-site differences remained in the tSNR of resting-state fMRI data; these were plausibly driven by hardware and pulse sequence differences across scanners which could not be harmonized. Nevertheless, the tSNR test-retest reproducibility in the consortium was high (ICC = 0.81). The DMN was consistently extracted across all sites and analysis methods. While significant inter-site differences in connectivity scores were found, there were no differences in the associated test-retest error. Overall, ICA measurements were more reliable than PCC-SBA, with site ICA showing higher reproducibility than consortium ICA. Across the DMN nodes, the PCC yielded the most reliable measurements (approximate to 4% test-retest error, ICC = 0.85), the medial frontal cortex the least reliable (approximate to 12%, ICC = 0.82) and the lateral parietal cortices were in between (site ICA). Altogether these findings support usage of harmonized multisite studies of resting-state functional connectivity to characterize longitudinal effects in studies that assess disease progression and treatment response. (C) 2015 Elsevier Inc. All rights reserved.

Brain imaging studies contribute to the neurobiological understanding of Autism Spectrum Conditions (ASC). Herein, we tested the prediction that distributed neurodevelopmental abnormalities in brain development impact on the homogeneity of brain tissue measured using texture analysis (TA; a morphological method for surface pattern characterization). TA was applied to structural magnetic resonance brain scans of 54 adult participants (24 with Asperger syndrome (AS) and 30 controls). Measures of mean gray-level intensity, entropy and uniformity were extracted from gray matter images at fine, medium and coarse textures. Comparisons between AS and controls identified higher entropy and lower uniformity across textures in the AS group. Data reduction of texture parameters revealed three orthogonal principal components. These were used as regressors-of-interest in a voxel-based morphometry analysis that explored the relationship between surface texture variations and regional gray matter volume. Across the AS but not control group, measures of entropy and uniformity were related to the volume of the caudate nuclei, whereas mean gray-level was related to the size of the cerebellar vermis. Similar to neuropathological studies, our study provides evidence for distributed abnormalities in the structural integrity of gray matter in adults with ASC, in particular within corticostriatal and corticocerebellar networks. Additionally, this in-vivo technique may be more sensitive to fine microstructural organization than other more traditional magnetic resonance approaches and serves as a future testable biomarker in AS and other neurodevelopmental disorders.

Can conscious awareness be ascertained from physiological responses alone? We evaluate a novel learning-based procedure permitting detection of conscious awareness without reliance on language comprehension or behavioural responses. The method exploits a situation whereby only consciously detected violations of an expectation alter skin conductance responses (SCRs). Thirty participants listened to sequences of piano notes that, without their being told, predicted a pleasant fanfare or an aversive noise according to an abstract rule. Stimuli were presented without distraction (attended), or while distracted by a visual task to remove awareness of the rule (unattended). A test phase included occasional violations of the rule. Only participants attending the sounds reported awareness of violations and only they showed significantly greater SCR for noise occurring in violation, vs. accordance, with the rule. Our results establish theoretically significant dissociations between conscious and unconscious processing and furnish new opportunities for clinical assessment of residual consciousness in patient populations.

Lexical–gustatory synaesthesia is a rare phenomenon in which the individual experiences flavour sensations when they read, hear, or imagine words. In this study, we provide insight into the neural basis of this form of synaesthesia using functional neuroimaging. Words known to evoke pleasant, neutral, and unpleasant synaesthetic tastes and synaesthetically tasteless words were presented to two lexical–gustatory synaesthetes, during fMRI scanning. Ten non-synaesthetic participants were also scanned on the same list of words. The synaesthetic brain displayed a different pattern of activity to words when compared to the non-synaesthetes, with insula activation related to viewing words that elicited tastes that have an associated emotional valence (i.e., pleasant or unpleasant tastes). The subjective intensity of the synaesthesia was correlated with activity in the medial parietal lobes (precuneus/retrosplenial cortex), which are implicated in polymodal imagery and self-directed thought. This region has also previously been activated in studies of lexical–colour synaesthesia, suggesting its role may not be limited to the type of synaesthesia explored here.

Highlights ► We recorded NIRS from the visual cortex during pattern-reversal stimulation. ► Transient blood pressure changes were induced by arm-raising. ► Blood pressure changes significantly altered deep and shallow NIRS recordings. ► The effect appears to originate from both intra- and extra-cranial regions. ► Blood pressure must be considered as a potential confound in NIRS studies., Brain near-infrared spectroscopy (NIRS) is an emerging neurophysiological tool that combines straightforward activity localization with cost–economy, portability and patient compatibility. NIRS is proving its empirical utility across specific cognitive and emotional paradigms. However, a potential limitation is that it is not only sensitive to haemodynamic changes taking place in the cortex, and task-related cardiovascular responses expressed in the perfusion of extracranial layers may be confounding. Existing literature reports correlations between brain NIRS and systemic blood pressure, yet it falls short of establishing whether in normal participants the blood pressure changes encountered in experimental settings can have confounding effects. Here, we tested this hypothesis by performing two experimental manipulations while recording from superficial occipital cortex, encompassing striate and extrastriate regions. Visual stimulation with reversing chequerboards evoked cortical haemodynamic responses. Simultaneously and independently, transient systemic blood pressure changes were generated through rapid arm-raising. Shallow-penetration NIRS recordings, probing only extra-cerebral tissues, highlighted close haemodynamic coupling with blood pressure. A different coupling pattern was observed in deep-penetration recordings directed at haemodynamic signals from visual cortex. In absence of blood-pressure changes, NIRS signals tracked differences in visual stimulus duration. However when blood pressure was actively manipulated, this effect was absent and replaced by a very large pressure-related response. Our observations demonstrate that blood pressure fluctuations can exert confounding effects on brain NIRS, through expression in extracranial tissues and within the brain itself. We highlight the necessity for continuous blood pressure monitoring alongside brain NIRS, and for further research on methods to correct for physiological confounds.

Electrophysiological studies indicate that Unverricht-Lundborg's disease (ULD), the most common form of progressive myoclonus epilepsy in Europe, is characterized by the involvement of multiple cortical regions in degenerative changes that lead to enhanced excitation and deficient inhibition. We searched for the haemodynamic correlates of these effects using functional MRI (fMRI) of self-paced index extensions, a well-accepted task highlighting significant differences. EEG and fMRI were simultaneously acquired in 11 ULD patients and 16 controls, performing the index extensions individually (event-related task) as well as repetitively (block task). ERD/ERS analysis was performed for the EEG data in the alpha and beta bands. fMRI time-series were analyzed using the traditional general linear model, as well as with an assumption-free approach, and by means of cross-region correlations representing functional connectivity. In line with the existing literature, ULD patients had enhanced desynchronization in the alpha band and reduced post-movement synchronization in the beta band. By contrast, fMRI did not reveal any difference between the two groups; there were no activation intensity, latency or extent effects, no significant engagement of additional regions, and no changes to functional connectivity. We conclude that, so long as the patients are executing a task which does not induce obvious action myoclonus, the hypothesized abnormalities in pyramidal neuron and interneuron dynamics are relatively subtle, embodied in processes which are not metabolically-demanding and take place at a time-scale invisible to fMRI.

BACKGROUND AND PURPOSE: The neostriatum is known to be affected in HD. In this work, our aim was to determine whether microstructural and volumetric alterations occur in the neostriatum of presymptomatic HD gene carriers and in patients with early-stage HD. MATERIALS AND METHODS: We studied a group of 15 presymptomatic gene carriers who were far from the estimated symptom onset (16% probability of developing the disease within 5 years), a group of 9 patients with early symptomatic HD, and 2 groups of age-matched controls. Volumetric MR imaging and DWIs were acquired, and statistical analyses were performed on the volumes of the caudate nucleus and putamen and on the corresponding MD measurements. RESULTS: Neostriatal volumes were significantly smaller in both presymptomatic HD gene carriers and symptomatic patients with respect to controls. However, whereas the diffusivity in the caudate nucleus was increased in the symptomatic patients, it was decreased in the presymptomatic gene carriers. CONCLUSIONS: Altered diffusivity and reduced volume of the caudate nucleus in presymptomatic HD gene carriers indicate that the neostriatum is affected well before the onset of symptoms. The observed initial decrease and subsequent increase of MD might be related to the combined effect of increased oligodendroglial population, putatively a developmental abnormality, and incipient neurodegeneration.

Functional neuroimaging and electroencephalography reveal emotional effects in the early visual cortex. Here, we used functional near-infrared spectroscopy to examine haemodynamic responses evoked by neutral, positive and negative emotional pictures, matched for brightness, contrast, hue, saturation, spatial frequency and entropy. Emotion content modulated amplitude and latency of oxy, deoxy and total haemoglobin response peaks, and induced peripheral autonomic reactions. The processing of positive and negative pictures enhanced haemodynamic response amplitude, and this effect was paralleled by blood pressure changes. The processing of positive pictures was reflected in reduced haemodynamic response peak latency. Together these data suggest that the early visual cortex holds amplitude-dependent representation of stimulus salience and latency-dependent information regarding stimulus valence, providing new insight into affective interaction with sensory processing.

Combining human functional neuroimaging with other forms of psychophysiological measurement, including autonomic monitoring, provides an empirical basis for understanding brain–body interactions. This approach can be applied to characterize unwanted physiological noise, examine the neural control and representation of bodily processes relevant to health and morbidity, and index covert expression of affective and cognitive processes to enhance the interpretation of task-evoked regional brain activity. In recent years, human neuroimaging has been dominated by functional magnetic resonance imaging (fMRI) studies. The spatiotemporal information of fMRI regarding central neural activity is valuably complemented by parallel physiological monitoring, yet such studies still remain in the minority. This review article highlights fMRI studies that employed cardiac, vascular, respiratory, electrodermal, gastrointestinal and pupillary psychophysiological indices to address specific questions regarding interaction between brain and bodily state in the context of experience, cognition, emotion and behaviour. Physiological monitoring within the fMRI environment presents specific technical issues, most importantly related to safety. Mechanical and electrical hazards may present dangers to scanned subjects, operator and/or equipment. Furthermore, physiological monitoring may interfere with the quality of neuroimaging data, or itself be compromised by artefacts induced by the operation of the scanner. We review the sources of these potential problems and the current approaches and advice to enable the combination of fMRI and physiological monitoring in a safe and effective manner.

BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) offers a unique window on the connectivity changes, extending beyond the basal ganglia, which accompany the cognitive symptoms of Parkinson disease (PD). The primary purpose of this study was to assess the microstructural damage to cerebral white matter occurring in idiopathic PD. MATERIALS AND METHODS: Our sample included patients with PD without dementia (n = 10; Hoehn and Yahr stages I and II; Unified Parkinson Disease Rating Scale, 20.5 ± 8.3; and Mini-Mental State Examination, 28.3 ± 1.5) and age-matched healthy control subjects (n = 10). DTI was performed on a 1.5T scanner, and mean diffusivity (MD) and fractional anisotropy (FA) maps were obtained. Regions of interest (ROIs) were drawn on the major fiber bundles as well as on gray matter nuclei. RESULTS: In patients, the MD was increased at borderline significance in the substantia nigra but was unaltered in the thalamus, globus pallidus, putamen, and in the head of the caudate nucleus. The FA and MD were unaltered in the corticospinal tract in the midbrain and at the level of the internal capsule, and in the splenium of the corpus callosum. By contrast, the MD was increased and the FA was decreased in the genu of the corpus callosum and in the superior longitudinal fasciculus; in the cingulum, only the MD was altered. The observed changes were not significantly lateralized. CONCLUSIONS: Widespread microstructural damage to frontal and parietal white matter occurs already in the early stages of PD.

This comprehensive, pedagogically-oriented review is aimed at a heterogeneous audience representative of the allied disciplines involved in research and patient care. After a foreword on epidemiology, genetics, and risk factors, the amyloid cascade model is introduced and the main neuropathological hallmarks are discussed. The progression of memory, language, visual processing, executive, attentional, and praxis deficits, and of behavioral symptoms is presented. After a summary on neuropsychological assessment, emerging biomarkers from cerebrospinal fluid assays, magnetic resonance imaging, nuclear medicine, and electrophysiology are discussed. Existing treatments are briefly reviewed, followed by an introduction to emerging disease-modifying therapies such as secretase modulators, inhibitors of Abeta aggregation, immunotherapy, inhibitors of tau protein phosphorylation, and delivery of nerve growth factor.

BACKGROUND AND PURPOSE: In recent years, the discovery that mutations in the glial fibrillary acidic protein gene (GFAP) were responsible for Alexander disease (AD) brought recognition of adult cases. The purpose of this study was to demonstrate that MR imaging allows identification of cases of AD with adult onset (AOAD), which are remarkably different from infantile cases. MATERIALS AND METHODS: In this retrospective study, brain and spinal cord MR imaging studies of 11 patients with AOAD (7 men, 4 women; age range, 26–64 years; mean age, 43.6 years), all but 1 genetically confirmed, were reviewed. Diffusion and spectroscopic investigations were available in 6 patients each. RESULTS: Atrophy and changes in signal intensity in the medulla oblongata and upper cervical spinal cord were present in 11 of 11 cases and were the diagnostic features of AOAD. Minimal to moderate supratentorial periventricular abnormalities were seen in 8 patients but were absent in the 3 oldest patients. In these patients, postcontrast enhancement was also absent. Mean diffusivity was not altered except in abnormal white matter (WM). Increase in myo-inositol (mIns) was also restricted to abnormal periventricular WM. CONCLUSIONS: Awareness of the MR pattern described allows an effective selection of the patients who need genetic investigations for the GFAP gene. This MR pattern even led to identification of asymptomatic cases and should be regarded as highly characteristic of AOAD.

Background The predictive value of the El-Ganzouri risk index (EGRI) for difficult intubation has been evaluated using Macintosh laryngoscopy as reference standard. The Glidescope ® videolaryngoscope provides improved visualization of the glottis. We studied the predictive value of the EGRI using videolaryngoscopy as reference standard. Methods Data from two subsequent groups of patients, intubated with Macintosh laryngoscopy (ML, n = 994) and videolaryngoscopy (VL, n = 843), were retrospectively analysed. The EGRI was taken as index test. The two types of laryngoscopy were adopted as reference for the presence of Cormack and Lehane grading III–IV. For both groups, sensitivity, specificity, and positive and negative post-test probabilities (PTP) were calculated for thresholds on the EGRI scale. Receiver operating characteristic curves and corresponding areas (AUC) were obtained. Results Sensitivity and specificity were 69.7% and 66.3% at the cut-off value of 2 in the ML group, and 93.3% and 76.6% at the cut-off value of 3 in the VL group. Corresponding positive and negative PTP were 12.81% and 3.15% in the ML group, and 6.73% and 0.16% in the VL group. At the threshold of 4, positive and negative PTP were 31.34% and 4.85% in the ML group. At the threshold of 7, positive and negative PTP were 85.71% and 1.08% in the VL group. The AUC was 0.74 in the ML group and 0.91 in the VL group. Conclusions The predictive value of the EGRI may have been underestimated due to limited accuracy of Macintosh laryngoscopy. Using videolaryngoscopy, the EGRI might be reconsidered as a decisional tool.

Although most meningiomas are slow-growing tumours associated with favourable prognosis, they often present local recurrence after surgical treatment; by contrast, extracranial metastatic meningiomas are rare, occurring in less than 1% of the cases. Risk factors for distal spread remain largely unknown. We report three cases with lung or bone metastases from intracranial recurrent meningiomas. Loss of heterozygosity (LOH) analysis on 1p, 9p, 10q, 14q, and 22q was conducted in available primary, recurrent and metastatic lesions, showing the same LOH pattern in the distal metastases and in the intracranial meningioma. LOH at 1p, 14q and 9p, known to be associated with increased aggressiveness, were found. The results highlight the potential clinical relevance of integrating histopathological studies with molecular genetic analysis in the follow-up of patients with different types of meningiomas.

In vivo magnetic resonance spectroscopy (MRS), functional magnetic resonance imaging (fMRI), and diffusion-tensor imaging (DTI) have recently opened new possibilities for noninvasively assessing the metabolic, functional, and connectivity correlates of aging in research and clinical settings. The purpose of this article is to provide a conceptual review intended for a multidisciplinary audience, covering physical principles and main findings related to normal aging and senile cognitive impairment. This article is divided into 3 sections, dedicated to MRS, to fMRI, and to DTI. The spectroscopy section surveys physiological function of the observable metabolites, concentration changes in normal aging and their interpretation, and correlation with cognitive performance. The functional MRI section surveys the hemispheric asymmetry reduction model from compensation and de-differentiation viewpoints, memory encoding, retrieval and consolidation, inhibitory control, perception and action, resting-state networks, and functional deactivations. The DTI section surveys age-related changes, correlation with behavioral scores, and transition to cognitive impairment.