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Dodich and colleagues recently reviewed the evidence supporting clinical use of social cognition assessment in behavioral variant frontotemporal dementia (Dodich et al., 2021). Here, we comment on their methods and present an initiative to address some of the limitations that emerged from their study. In particular, we established the social cognition workgroup within the Neuropsychiatric International Consortium Frontotemporal dementia (scNIC-FTD), aiming to validate social cognition assessment for diagnostic purposes and tracking of change across clinical situations. [ABSTRACT FROM AUTHOR]

Introduction Behavioral variant frontotemporal dementia (bv FTD) is associated with abnormal emotion recognition and moral processing. Methods We assessed emotion detection, discrimination, matching, selection, and categorization as well as judgments of nonmoral, moral impersonal, moral personal low- and high-conflict scenarios. Results bv FTD patients gave more utilitarian responses on low-conflict personal moral dilemmas. There was a significant correlation between a facial emotion processing measure derived through principal component analysis and utilitarian responses on low-conflict personal scenarios in the bv FTD group (controlling for MMSE-score and syntactic abilities). Voxel-based morphometric multiple regression analysis in the bv FTD group revealed a significant association between the proportion of utilitarian responses on personal low-conflict dilemmas and gray matter volume in ventromedial prefrontal areas ( pheight < .0001). In addition, there was a correlation between utilitarian responses on low-conflict personal scenarios in the bv FTD group and resting-state fractional Amplitude of Low Frequency Fluctuations ( fALFF) in the anterior insula ( pheight < .005). Conclusions The results underscore the importance of emotions in moral cognition and suggest a common basis for deficits in both abilities, possibly related to reduced experience of emotional sensations. At the neural level abnormal moral cognition in bv FTD is related to structural integrity of the medial prefrontal cortex and functional characteristics of the anterior insula. The present findings provide a common basis for emotion recognition and moral reasoning and link them with areas in the default mode and salience network. [ABSTRACT FROM AUTHOR]

Background: Very-late-onset schizophrenia-like psychosis (VLOSLP) is associated with significant burden. Its clinical importance is increasing as the global population of older adults rises, yet owing to limited research in this population, the neurobiological underpinnings of VLOSP remain insufficiently clarified. Here we address this knowledge gap using novel morphometry techniques to investigate grey matter volume (GMV) differences between VLOSLP and healthy older adults, and their correlations with neuropsychological scores. Methods: In this cross-sectional study, we investigated whole-brain GMV differences between 35 individuals with VLOSLP (mean age 76.7, 26 female) and 36 healthy controls (mean age 75.7, 27 female) using whole-brain voxel-based morphometry (VBM) and supplementary source-based morphometry (SBM) on high resolution 3D T1-weighted MRI images. Additionally, we investigated relationships between GMV differences and cognitive function assessed with an extensive neuropsychological battery. Results: VBM showed lower GMV in the thalamus, left inferior frontal gyrus and left insula in patients with VLOSLP compared to healthy controls. SBM revealed lower thalamo-temporal GMV in patients with VLOSLP. Processing speed, selective attention, mental flexibility, working memory, verbal memory, semantic fluency and confrontation naming were impaired in patients with VLOSLP. Correlations between thalamic volumes and memory function were significant within the group of individuals with VLOSLP, whereas no significant associations remained in the healthy controls. Conclusions: Lower GMV in the thalamus and fronto-temporal regions may be part of the underlying neurobiology of VLOSLP, with lower thalamic GMV contributing to memory impairment in the disorder. [ABSTRACT FROM AUTHOR]

Progressive deterioration of social cognition and emotion processing are core symptoms of the behavioral variant of frontotemporal dementia (bvFTD). Here we investigate whether bvFTD is also associated with impaired recognition of static (Experiment 1) and dynamic (Experiment 2) bodily expressions. In addition, we compared body expression processing with processing of static (Experiment 3) and dynamic (Experiment 4) facial expressions, as well as with face identity processing (Experiment 5). The results reveal that bvFTD is associated with impaired recognition of static and dynamic bodily and facial expressions, while identity processing was intact. No differential impairments were observed regarding motion (static vs. dynamic) or category (body vs. face). Within the bvFTD group, we observed a significant partial correlation between body and face expression recognition, when controlling for performance on the identity task. Voxel-Based Morphometry (VBM) analysis revealed that body emotion recognition was positively associated with gray matter volume in a region of the inferior frontal gyrus (pars orbitalis/triangularis). The results are in line with a supramodal emotion recognition deficit in bvFTD. [ABSTRACT FROM AUTHOR]

The clinical phenotype of Huntington's disease (HD) consists of motor, cognitive and psychiatric symptoms, of which irritability is an important manifestation. Our aim was to identify the functional and structural brain changes that underlie irritability in premanifest HD (preHD). Twenty preHD carriers and 20 gene-negative controls from HD families took part in the study. Although the 5-year probability of disease onset was only 11%, the preHD group showed striatal atrophy and increased clinical irritability ratings. Functional MRI was performed during a mood induction experiment by means of recollection of emotional (angry, sad, and happy) and neutral autobiographical episodes. While there were no significant group differences in the subjective intensity of the emotional experience, the preHD group showed increased anger-selective activation in a distributed network, including the pulvinar, cingulate cortex, and somatosensory association cortex, compared to gene-negative controls. Pulvinar activation during anger experience correlated negatively with putaminal grey matter volume and positively with irritability rating s in the preHD group. In addition, the preHD group showed a decrease in anger-selective activation in the amygdala, which correlated with putaminal and caudate grey matter volume. In conclusion, compared to gene-negative controls, anger experience in preHD is associated with activity changes in a distributed set of regions known to be involved in emotion regulation. Increased activity is related to behavioral and volumetric measures, providing insight in the pathophysiology of early neuropsychiatric symptoms in preHD. Hum Brain Mapp 36:2681-2690, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Facial expression perception can be influenced by the natural visual context in which the face is perceived. We performed an fMRI experiment presenting participants with fearful or neutral faces against threatening or neutral background scenes. Triangles and scrambled scenes served as control stimuli. The results showed that the valence of the background influences face selective activity in the right anterior parahippocampal place area (PPA) and subgenual anterior cingulate cortex (sgACC) with higher activation for neutral backgrounds compared to threatening backgrounds (controlled for isolated background effects) and that this effect correlated with trait empathy in the sgACC. In addition, the left fusiform gyrus (FG) responds to the affective congruence between face and background scene. The results show that valence of the background modulates face processing and support the hypothesis that empathic processing in sgACC is inhibited when affective information is present in the background. In addition, the findings reveal a pattern of complex scene perception showing a gradient of functional specialization along the posterior–anterior axis: from sensitivity to the affective content of scenes (extrastriate body area: EBA and posterior PPA), over scene emotion–face emotion interaction (left FG) via category–scene interaction (anterior PPA) to scene–category–personality interaction (sgACC). [ABSTRACT FROM AUTHOR]

This study addresses two central and controversial issues in developmental prosopagnosia (DP), configuration- versus feature-based face processing and the influence of affective information from either facial or bodily expressions on face recognition. A sample of 10 DPs and 10 controls were tested with a previously developed face and object recognition and memory battery (Facial Expressive Action Stimulus Test, FEAST), a task measuring the influence of emotional faces and bodies on face identity matching (Face–Body Compound task), and an emotionally expressive face memory task (Emotional Face Memory task, FaMe-E). We show that DPs were impaired in upright, but not inverted, face matching but they performed at the level of controls on part-to-whole matching. Second, DPs showed impaired memory for both neutral and emotional faces and scored within the normal range on the Face–Body Compound task. Third, configural perception but not feature-based processing was significantly associated with memory performance. Taken together the results indicate that DPs have a deficit in configural processing at the perception stage that may underlie the memory impairment. [ABSTRACT FROM AUTHOR]

Abstract: Emotional influences on memory for events have long been documented yet surprisingly little is known about how emotional signals conveyed by contextual cues influence memory for face identity. This study investigated how positively and negatively valenced contextual emotion cues conveyed by body expressions or background scenes influence face memory. The results provide evidence of emotional context influence on face recognition memory and show that faces encoded in emotional (either fearful or happy) contexts (either the body or background scene) are less well recognized than faces encoded in neutral contexts and this effect is larger for body context than for scene context. The findings are compatible with the hypothesis that emotional signals in visual scenes trigger orienting responses which may lead to a less elaborate processing of featural details like the identity of a face, in turn resulting in a decreased facial recognition memory. [Copyright &y& Elsevier]

Most studies investigating emotion recognition in schizophrenia have focused on facial expressions and neglected bodily and vocal expressions. Furthermore, little is known about affective multisensory integration in schizophrenia. In the first experiment, the authors investigated recognition of static, face-blurred, whole-body expressions (instrumental, angry, fearful, and sad) with a two-alternative, forced-choice, simultaneous matching task in a sample of schizophrenia patients, nonschizophrenic psychotic patients, and matched controls. In the second experiment, dynamic, face-blurred, whole-body expressions (fearful and happy) were presented simultaneously with either congruent or incongruent human or animal vocalizations to schizophrenia patients and controls. Participants were instructed to categorize the emotion expressed by the body and to ignore the auditory information. The results of Experiment 1 show an emotion recognition impairment in the schizophrenia group and to a lesser extent in the nonschizophrenic psychosis group, and this for all four expressions. The findings of Experiment 2 show that schizophrenia patients are more influenced by the auditory information than controls, but only when the auditory information consists of human vocalizations. This shows that schizophrenia patients are impaired in recognizing whole-body expressions, and they show abnormal affective multisensory integration of bimodal stimuli originating from the same source. [ABSTRACT FROM AUTHOR]

Patients with striate cortex damage and clinical blindness retain the ability to process certain visual properties of stimuli that they are not aware of seeing. Here we investigated the neural correlates of residual visual perception for dynamic whole-body emotional actions. Angry and neutral emotional whole-body actions were presented in the intact and blind visual hemifield of a cortically blind patient with unilateral destruction of striate cortex. Comparisons of angry vs. neutral actions performed separately in the blind and intact visual hemifield showed in both cases increased activation in primary somatosensory, motor, and premotor cortices. Activations selective for intact hemifield presentation of angry compared with neutral actions were located subcortically in the right lateral geniculate nucleus and cortically in the superior temporal sulcus, prefrontal cortex, precuneus, and intraparietal sulcus. Activations specific for blind hemifield presentation of angry compared with neutral actions were found in the bilateral superior colliculus, pulvinar nucleus of the thalamus, amygdala, and right fusiform gyrus. Direct comparison of emotional modulation in the blind vs. intact visual hemifield revealed selective activity in the right superior colliculus and bilateral pulvinar for angry expressions, thereby showing a selective involvement of these subcortical structures in nonconscious visual emotion perception. [ABSTRACT FROM AUTHOR]

Abstract: Recent studies of monkeys and humans have identified several brain regions that respond to bodies. Researchers have so far mainly addressed the same questions about bodies and bodily expressions that are already familiar from three decades of face and facial expression studies. Our present goal is to review behavioral, electrophysiological and neurofunctional studies on whole body and bodily expression perception against the background of what is known about face perception. We review all currently available evidence in more detail than done so far, but we also argue for a more theoretically motivated comparison of faces and bodies that reflects some broader concerns than only modularity or category specificity of faces or bodies. [Copyright &y& Elsevier]

Abstract: In naturalistic settings emotional events have multiple correlates and are simultaneously perceived by several sensory systems. Recent studies have shown that recognition of facial expressions is biased towards the emotion expressed by a simultaneously presented emotional expression in the voice even if attention is directed to the face only. So far, no study examined whether this phenomenon also applies to whole body expressions, although there is no obvious reason why this crossmodal influence would be specific for faces. Here we investigated whether perception of emotions expressed in whole body movements is influenced by affective information provided by human and by animal vocalizations. Participants were instructed to attend to the action displayed by the body and to categorize the expressed emotion. The results indicate that recognition of body language is biased towards the emotion expressed by the simultaneously presented auditory information, whether it consist of human or of animal sounds. Our results show that a crossmodal influence from auditory to visual emotional information obtains for whole body video images with the facial expression blanked and includes human as well as animal sounds. [Copyright &y& Elsevier]

Many people experience transient difficulties in recognizing faces but only a small number of them cannot recognize their family members when meeting them unexpectedly. Such face blindness is associated with serious problems in everyday life. A better understanding of the neuro-functional basis of impaired face recognition may be achieved by a careful comparison with an equally unique object category and by a adding a more realistic setting involving neutral faces as well facial expressions. We used event-related functional magnetic resonance imaging (fMRI) to investigate the neuro-functional basis of perceiving faces and bodies in three developmental prosopagnosics (DP) and matched healthy controls. Our approach involved materials consisting of neutral faces and bodies as well as faces and bodies expressing fear or happiness. The first main result is that the presence of emotional information has a different effect in the patient vs. the control group in the fusiform face area (FFA). Neutral faces trigger lower activation in the DP group, compared to the control group, while activation for facial expressions is the same in both groups. The second main result is that compared to controls, DPs have increased activation for bodies in the inferior occipital gyrus (IOG) and for neutral faces in the extrastriate body area (EBA), indicating that body and face sensitive processes are less categorically segregated in DP. Taken together our study shows the importance of using naturalistic emotional stimuli for a better understanding of developmental face deficits. [ABSTRACT FROM AUTHOR]

Abstract: Patients with Huntington''s disease (HD) exhibit motor impairments as well as cognitive and emotional deficits. So far impairments in the ability to recognize emotional stimuli have mostly been investigated by using facial expressions and emotional voices. Other important emotional signals are provided by the whole body. To investigate the impact of motor deficits on body recognition and the relation between motor disorders and emotion perception deficits, we tested recognition of emotional body language (instrumental, angry, fearful and sad) in 19 HD patients and their matched controls with a nonverbal whole body expression matching task. Results indicate that HD patients are impaired in recognizing both instrumental and angry whole body postures. Furthermore, the body language perception deficits are correlated with measures of motor deficit. Taken together the results suggest a close relationship between emotion recognition (specifically anger) and motor abilities. [Copyright &y& Elsevier]

Understanding facial emotions is fundamental to interact in social environments and modify behavior accordingly. Neurodegenerative processes can progressively transform affective responses and affect social competence. This exploratory study examined the neurocognitive correlates of face recognition, in individuals with two mild cognitive impairment (MCI) etiologies (prodromal to dementia – MCI, or consequent to Parkinson's disease – PD-MCI). Performance on the identification and memorization of neutral and emotional facial expressions was assessed in 31 individuals with MCI, 26 with PD-MCI, and 30 healthy controls (HC). Individuals with MCI exhibited selective impairment in recognizing faces expressing fear, along with difficulties in remembering both neutral and emotional faces. Conversely, individuals with PD-MCI showed no differences compared with the HC in either emotion recognition or memory. In MCI, no significant association emerged between the memory for facial expressions and cognitive difficulties. In PD-MCI, regression analyses showed significant associations with higher-level cognitive functions in the emotional memory task, suggesting the presence of compensatory mechanisms. In a subset of participants, voxel-based morphometry revealed that the performance on emotional tasks correlated with regional changes in gray matter volume. The performance in the matching of negative expressions was predicted by volumetric changes in brain areas engaged in face and emotional processing, in particular increased volume in thalamic nuclei and atrophy in the right parietal cortex. Future studies should leverage on neuroimaging data to determine whether differences in emotional recognition are mediated by pathology-specific atrophic patterns. [ABSTRACT FROM AUTHOR]

In psychogeriatric units for patients with dementia and behavioral problems, aggression is prevalent. Predictions and timely interventions of aggression are essential to create a safe environment and prevent adverse outcomes. Our study aimed to determine whether aggression severity early during admission to these units could be used as an indicator of adverse outcomes. During one year, all aggressive incidents on a psychogeriatric unit were systematically recorded using the Revised Staff Observation of Aggression Scale (SOAS-R). The study investigated the link between the severity of incidents within the first 48 hours of admission and adverse outcomes. All patients included in the study were admitted to a psychogeriatric unit for dementia and behavioral problems between November 2020 and October 2021. The study population was categorized into groups according to the level of aggression severity during the first 48 hours of admission. The impact of aggression severity on the duration of admission, aggression frequency and severity during admission, medication usage at discharge, discharge destination, and mortality risk were examined. During the initial 2 days of admission, 9 of 88 patients had 1 or more severe aggression incidents. An early manifestation of severe aggression was significantly associated with more incidents during hospitalization, a higher total SOAS-R score, and a sevenfold higher 1-year mortality risk compared with patients who did not or only mildly manifested aggression in the first 48 hours of admission. An early manifestation of aggression not only poses a direct safety risk to all involved but is also an early indicator of patients at risk for more detrimental outcomes, specifically mortality risk. By identifying patients at higher risk for adverse outcomes early, health care providers can provide preventive or timelier interventions, mitigating the risk of adverse outcomes and optimizing care services. [ABSTRACT FROM AUTHOR]

Deficits in social cognition may be present in frontotemporal dementia (FTD) and Alzheimer's disease (AD). Here, we conduct a qualitative synthesis and meta-analysis of facial expression recognition studies in which we compare the deficits between both disorders. Furthermore, we investigate the specificity of the deficit regarding phenotypic variant, domain-specificity, emotion category, task modality, and geographical region. The results reveal that both FTD and AD are associated with facial expression recognition deficits, that this deficit is more pronounced in FTD compared to AD and that this applies for the behavioral as well as for language FTD-variants, with no difference between the latter two. In both disorders, overall emotion recognition was most frequently impaired, followed by recognition of anger in FTD and by fear in AD. Verbal categorization was the most frequently used task, although matching or intensity rating tasks may be more specific. Studies from Oceania revealed larger deficits. On the other hand, non-emotional control tasks were more impacted by AD than by FTD. The present findings sharpen the social cognitive phenotype of FTD and AD, and support the use of social cognition assessment in late-life neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether mild motor signs (MMS) in old age correlate with synaptic density in the brain. Background: Normal aging is associated with a decline in movement quality and quantity, commonly termed "mild parkinsonian signs" or more recently MMS. Whether MMS stem from global brain aging or pathology within motor circuits remains unresolved. The synaptic vesicle glycoprotein 2A positron emission tomography (PET) ligand 11C‐UCB‐J allows the investigation of brain‐motor associations at the synaptic level in vivo. Method: Fifty‐eight healthy older adults (≥50 years) were included from two monocentric control cohorts. Brain magnetic resonance imaging and 11C‐UCB‐J PET data were available in 54 participants. 11C‐UCB‐J PET binding was quantified by standardized uptake value ratio (SUVR) values in grey matter (GM) volumes of interest (VOIs): caudate, putamen, globus pallidus, substantia nigra, thalamus, cerebellum, and the frontal, parietal, temporal, and occipital cortex. Multiple linear regression analyses were performed with Movement Disorder Society‐Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) part III score measuring MMS as the dependent variable and mean SUVR values in each VOI as the independent variable with age, Fazekas score (white matter lesion [WML] load), VOI and cohort as covariates. Results: Participants (68 ± 7.5 years; 52% female) had an average MDS‐UPDRS part III score of 3.3 ± 2.8. The MDS‐UPDRS part III score was inversely associated with synaptic density, independently of WML load or GM volume, in the caudate, substantia nigra, thalamus, cerebellum, and parietal, occipital, temporal cortex. Cohen's f2 showed moderate effect sizes for subcortical (range, 0.30–0.35), cortical (0.28–0.35) and cerebellar VOIs (0.31). Conclusion: MMS in healthy aging are associated with lower synaptic density throughout the brain. © 2023 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Psychological construction models of emotion state that emotions are variable concepts constructed by fundamental psychological processes, whereas according to basic emotion theory, emotions cannot be divided into more fundamental units and each basic emotion is represented by a unique and innate neural circuitry. In a previous study, we found evidence for the psychological construction account by showing that several brain regions were commonly activated when perceiving different emotions (i.e. a general emotion network). Moreover, this set of brain regions included areas associated with core affect, conceptualization and executive control, as predicted by psychological construction models. Here we investigate directed functional brain connectivity in the same dataset to address two questions: 1) is there a common pathway within the general emotion network for the perception of different emotions and 2) if so, does this common pathway contain information to distinguish between different emotions? We used generalized psychophysiological interactions and information flow indices to examine the connectivity within the general emotion network. The results revealed a general emotion pathway that connects neural nodes involved in core affect, conceptualization, language and executive control. Perception of different emotions could not be accurately classified based on the connectivity patterns from the nodes of the general emotion pathway. Successful classification was achieved when connections outside the general emotion pathway were included. We propose that the general emotion pathway functions as a common pathway within the general emotion network and is involved in shared basic psychological processes across emotions. However, additional connections within the general emotion network are required to classify different emotions, consistent with a constructionist account. [ABSTRACT FROM AUTHOR]

Several brain regions are involved in the processing of emotional stimuli, however, the contribution of specific regions to emotion perception is still under debate. To investigate this issue, we combined behavioral testing, structural and resting state imaging in patients diagnosed with behavioral variant frontotemporal dementia (bvFTD) and age matched controls, with task-based functional imaging in young, healthy volunteers. As expected, bvFTD patients were impaired in emotion detection as well as emotion categorization tasks, testing dynamic emotional body expressions as stimuli. Interestingly, their performance in the two tasks correlated with gray matter volume in two distinct brain regions, the left anterior temporal lobe for emotion detection and the left inferior frontal gyrus (IFG) for emotion categorization. Confirming this observation, multivoxel pattern analysis in healthy volunteers demonstrated that both ROIs contained information for emotion detection, but that emotion categorization was only possible from the pattern in the IFG. Furthermore, functional connectivity analysis showed reduced connectivity between the two regions in bvFTD patients. Our results illustrate that the mentalizing network and the action observation network perform distinct tasks during emotion processing. In bvFTD, communication between the networks is reduced, indicating one possible cause underlying the behavioral symptoms. Hum Brain Mapp 37:4472-4486, 2016. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background: It has been argued that symptom onset in neurodegeneration reflects the overload of compensatory mechanisms. The present study aimed to investigate whether neural functional compensation can be observed in the manifest neurodegenerative disease stage, by focusing on a core deficit in frontotemporal dementia, i.e. social cognition, and by combining psychophysical assessment, structural MRI and functional MRI with multidimensional neural markers that allow quantification of neural computations. Methods: Nineteen patients with clinically manifest behavioral variant frontotemporal dementia (bvFTD) and 20 controls performed facial expression recognition tasks in the MRI-scanner and offline. Group differences in grey matter volume, neural response amplitude and neural patterns were assessed via a combination of voxel-wise whole-brain, searchlight, and ROI-analyses and these measures were correlated with psychophysical measures of emotion, valence and arousal ratings. Results: Significant group effects were observed only outside task-relevant regions, converging in the caudate nucleus. This area showed a diagnostic neural pattern as well as hyperactivation and stronger neural representation of facial expressions in the bvFTD sample. Furthermore, response amplitude was associated with behavioral arousal ratings. Conclusions: The combined findings reveal converging support for compensatory processes in clinically manifest neurodegeneration, complementing accounts that clinical onset synchronizes with the breakdown of compensatory processes. Furthermore, active compensation may proceed along nodes in intrinsically connected networks, rather than along the more task-specific networks. The findings underscore the potential of distributed multidimensional functional neural characteristics that may provide a novel class of biomarkers with both diagnostic and therapeutic implications, including biomarkers for clinical trials. [ABSTRACT FROM AUTHOR]

Affective experience colours everyday perception and cognition, yet its fundamental and neurobiological basis is poorly understood. The current debate essentially centers around the communalities and specificities across individuals, events, and emotional categories like anger, sadness, and happiness. Using fMRI during the experience of these emotions, we critically compare the two dominant conflicting theories on human affect. Basic emotion theory posits emotions as discrete universal entities generated by dedicated emotion category-specific neural circuits, while psychological construction theory claims emotional events as unique, idiosyncratic, and constructed by psychological primitives like core affect and conceptualization, which underlie each emotional event and operate in a predictive framework. Based on the findings of 8 a priori-defined model-specific prediction tests on the neural response amplitudes and patterns, we conclude that the neurobiological basis of affect is primarily characterized by idiosyncratic mechanisms and a common neural basis shared across emotion categories, consistent with psychological construction theory. The findings provide further insight into the organizational principles of the neural basis of affect and brain function in general. Future studies in clinical populations with affective symptoms may reveal the corresponding underlying neural changes from a psychological construction perspective. Analysis of fMRI recordings from an autobiographical memory recall tasks suggests that neural activation during emotional experiences can be better predicted by psychological construction theory, rather than classic basic emotions theory. [ABSTRACT FROM AUTHOR]

Mnemonic enhanced memory has been observed for negative events. Here, we investigate its association with spatiotemporal attention, consolidation, and age. An ingenious method to study visual attention for emotional stimuli is eye tracking. Twenty young adults and twenty-one older adults encoded stimuli depicting neutral faces, angry faces, and houses while eye movements were recorded. The encoding phase was followed by an immediate and delayed (48 h) recognition assessment. Linear mixed model analyses of recognition performance with group, emotion, and their interaction as fixed effects revealed increased performance for angry compared to neutral faces in the young adults group only. Furthermore, young adults showed enhanced memory for angry faces compared to older adults. This effect was associated with a shorter fixation duration for angry faces compared to neutral faces in the older adults group. Furthermore, the results revealed that total fixation duration was a strong predictor for face memory performance. [ABSTRACT FROM AUTHOR]

It is part of basic emotions like fear or anger that they prepare the brain to act adaptively. Hence scenes representing emotional events are normally associated with characteristic adaptive behavior. Normally, face and body representation areas in the brain are modulated by these emotions when presented in the face or body. Here, we provide neuroimaging evidence (using functional magnetic resonance imaging) that the extrastriate body area (EBA) is highly responsive when subjects observe isolated faces presented in emotional scenes. This response of EBA to threatening scenes in which no body is present gives rise to speculation about its function. We discuss the possibility that the brain reacts proactively to the emotional meaning of the scene. [ABSTRACT FROM AUTHOR]

Most face processing studies in humans show stronger activation in the right compared to the left hemisphere. Evidence is largely based on studies with static stimuli focusing on the fusiform face area (FFA). Hence, the pattern of lateralization for dynamic faces is less clear. Furthermore, it is unclear whether this property is common to human and non-human primates due to predisposing processing strategies in the right hemisphere or that alternatively left sided specialization for language in humans could be the driving force behind this phenomenon. We aimed to address both issues by studying lateralization for dynamic facial expressions in monkeys and humans. Therefore, we conducted an event-related fMRI experiment in three macaques and twenty right handed humans. We presented human and monkey dynamic facial expressions (chewing and fear) as well as scrambled versions to both species. We studied lateralization in independently defined face-responsive and face-selective regions by calculating a weighted lateralization index (LIwm) using a bootstrapping method. In order to examine if lateralization in humans is related to language, we performed a separate fMRI experiment in ten human volunteers including a ‘speech’ expression (one syllable non-word) and its scrambled version. Both within face-responsive and selective regions, we found consistent lateralization for dynamic faces (chewing and fear) versus scrambled versions in the right human posterior superior temporal sulcus (pSTS), but not in FFA nor in ventral temporal cortex. Conversely, in monkeys no consistent pattern of lateralization for dynamic facial expressions was observed. Finally, LIwms based on the contrast between different types of dynamic facial expressions (relative to scrambled versions) revealed left-sided lateralization in human pSTS for speech-related expressions compared to chewing and emotional expressions. To conclude, we found consistent laterality effects in human posterior STS but not in visual cortex of monkeys. Based on our results, it is tempting to speculate that lateralization for dynamic face processing in humans may be driven by left-hemispheric language specialization which may not have been present yet in the common ancestor of human and macaque monkeys. [ABSTRACT FROM AUTHOR]

The endocannabinoid system (ECS) is an important modulatory and potentially neuroprotective homeostatic system in the brain. In Alzheimer's disease (AD), the role of type 1 cannabinoid receptor (CB1R) is unclear, with contradictory findings in post-mortem studies showing upregulation, downregulation or unchanged CB1R status. We have investigated CB1R availability in vivo in patients with AD, in relation to amyloid deposition, cognitive functioning and apolipoprotein E (ApoE) genotype. Eleven AD patients and 7 healthy volunteers (HV) underwent combined [18F]MK-9470 PET and [11C]PIB PET scans to assess CB1R availability and amyloid deposition, respectively, and T1 volumetric MRI for partial volume correction. We found no difference in CB1R availability between AD and HV, VOI-based fractional uptake values (FUR) were 0.043±0.01 for AD and 0.045±0.01 for controls (p=0.9). CB1R availability did not correlate with neuropsychological test scores and was not modulated by ApoE genotype. As expected, global [11C]PIB SUVR (standardized uptake value ratio) was increased in AD (SUVR 1.9±0.3) compared to HV (1.2±0.1) with p<0.001, but no correlation was found between amyloid β (Aβ) deposition and CB1R availability. In conclusion, we found no in vivo evidence for a difference in CB1R availability in AD compared to age-matched controls. Taken together with recently reported in vivo CB1R changes in Parkinson's and Huntington's disease, these data suggest that the CB1R is differentially involved in neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

Abstract: Emotional facial expressions play an important role in social communication across primates. Despite major progress made in our understanding of categorical information processing such as for objects and faces, little is known, however, about how the primate brain evolved to process emotional cues. In this study, we used functional magnetic resonance imaging (fMRI) to compare the processing of emotional facial expressions between monkeys and humans. We used a 2×2×2 factorial design with species (human and monkey), expression (fear and chewing) and configuration (intact versus scrambled) as factors. At the whole brain level, neural responses to conspecific emotional expressions were anatomically confined to the superior temporal sulcus (STS) in humans. Within the human STS, we found functional subdivisions with a face-selective right posterior STS area that also responded to emotional expressions of other species and a more anterior area in the right middle STS that responded specifically to human emotions. Hence, we argue that the latter region does not show a mere emotion-dependent modulation of activity but is primarily driven by human emotional facial expressions. Conversely, in monkeys, emotional responses appeared in earlier visual cortex and outside face-selective regions in inferior temporal cortex that responded also to multiple visual categories. Within monkey IT, we also found areas that were more responsive to conspecific than to non-conspecific emotional expressions but these responses were not as specific as in human middle STS. Overall, our results indicate that human STS may have developed unique properties to deal with social cues such as emotional expressions. [Copyright &y& Elsevier]

Late-life depression (LLD) is associated with a risk of developing Alzheimer's disease (AD). However, the role of AD-pathophysiology in LLD, and its association with clinical symptoms and cognitive function are elusive. In this study, one hundred subjects underwent amyloid positron emission tomography (PET) imaging with [18F]-flutemetamol and structural MRI: 48 severely depressed elderly subjects (age 74.1 ± 7.5 years, 33 female) and 52 age-/gender-matched healthy controls (72.4 ± 6.4 years, 37 female). The Geriatric Depression Scale (GDS) and Rey Auditory Verbal Learning Test (RAVLT) were used to assess the severity of depressive symptoms and episodic memory function respectively. Amyloid deposition was quantified using the standardized uptake value ratio. Whole-brain voxel-wise comparisons of amyloid deposition and gray matter volume (GMV) between LLD and controls were performed. Multivariate analysis of covariance was conducted to investigate the association of regional differences in amyloid deposition and GMV with clinical factors, including GDS and RAVLT. As a result, there were no significant group differences in amyloid deposition. In contrast, LLD showed significant lower GMV in the left temporal and parietal region. GMV reduction in the left temporal region was associated with episodic memory dysfunction, but not with depression severity. Regional GMV reduction was not associated with amyloid deposition. LLD is associated with lower GMV in regions that overlap with AD-pathophysiology, and which are associated with episodic memory function. The lack of corresponding associations with amyloid suggests that lower GMV driven by non-amyloid pathology may play a central role in the neurobiology of LLD presenting as a psychiatric disorder. Trial registration: European Union Drug Regulating Authorities Clinical Trials identifier: EudraCT 2009-018064-95. [ABSTRACT FROM AUTHOR]

Repetition suppression (RS) reflects a neural attenuation during repeated stimulation. We used fMRI and the subsequent memory paradigm to test the predictive coding hypothesis for RS during visual memory processing by investigating the interaction between RS and differences due to memory in category-selective cortex (FFA, pSTS, PPA, and RSC). Fifty-six participants encoded face and house stimuli twice, followed by an immediate and delayed (48 h) recognition memory assessment. Linear Mixed Model analyses with repetition, subsequent recognition performance, and their interaction as fixed effects revealed that absolute RS during encoding interacts with probability of future remembrance in face-selective cortex. This effect was not observed for relative RS, i.e. when controlled for adapter-response. The findings also reveal an association between adapter response and RS, both for short and long term (48h) intervals, after controlling for the mathematical dependence between both measures. These combined findings are challenging for predictive coding models of visual memory and are more compatible with adapter-related and familiarity accounts. In order to examine underlying mechanisms of repetition suppression, Stam et al conducted an fMRI study in which participants were presented with face and house stimuli followed by an immediate and 48 h-delayed memory task. Their data demonstrated that adapter-related and familiarity account modelling are more likely to be more accurate for visual memory than previous predictive coding models. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorders rank in the top ten causes of ill health in all but four countries worldwide and are the leading cause of years lived with disability in Europe (WHO). Recent research suggests that neurodegenerative pathology may contribute to the development of late-life depression (LLD) in a sub-group of patients and represent a target for prevention and early diagnosis. In parallel, electroconvulsive therapy (ECT), which is the most effective treatment for severe LLD, has been associated with significant brain structural changes. In both LLD and ECT hippocampal volume change plays a central role; however, the neurobiological mechanism underlying it and its relevance for clinical outcomes remain unresolved. Methods: This is a monocentric, clinical cohort study with a cross-sectional arm evaluating PET-MR imaging and behavioural measures in 64 patients with LLD compared to 64 healthy controls, and a longitudinal arm evaluating the same imaging and behavioural measures after 10 ECT sessions in 20 patients receiving ECT as part of their normal clinical management. Triple tracer PET-MRI data will be used to measure: hippocampal volume (high resolution MRI), synaptic density using [11C]UCB-J, which targets the Synaptic Vesicle Glycoprotein 2A receptor, tau pathology using [18F]MK-6240, and cerebral amyloid using [18F]-Flutemetamol, which targets beta-amyloid neuritic plaques in the brain. Additional MRI measures and ultrasound will assess cerebral vascular structure and brain connectivity. Formal clinical and neuropsychological assessments will be conducted alongside experience sampling and physiological monitoring to assess mood, stress, cognition and psychomotor function. Discussion: The main aim of the study is to identify the origin and consequences of hippocampal volume differences in LLD by investigating how biomarkers of pathological ageing contribute to medial temporal lobe pathology. Studying how synaptic density, tau, amyloid and vascular pathology relate to neuropsychological, psychomotor function, stress and ECT, will increase our pathophysiological understanding of the in vivo molecular, structural and functional alterations occurring in depression and what effect this has on clinical outcome. It may also lead to improvements in the differential diagnosis of depression and dementia yielding earlier, more optimal, cost-effective clinical management. Finally, it will improve our understanding of the neurobiological mechanism of ECT. Trial registration: ClinicalTrials.gov Identifier: NCT03849417, 21/2/2019. [ABSTRACT FROM AUTHOR]

The human amygdala is considered a key region for successful emotion recognition. We recently reported that temporal lobe surgery (TLS), including resection of the amygdala, does not affect emotion recognition performance (Journal of Neuroscience, 2018, 38, 9263). In the present study, we investigate the neural basis of this preserved function at the network level. We use generalized psychophysiological interaction and graph theory indices to investigate network level characteristics of the emotion recognition network in TLS patients and healthy controls. Based on conflicting emotion processing theories, we anticipated two possible outcomes: a substantial increase of the non‐amygdalar connections of the emotion recognition network to compensate functionally for the loss of the amygdala, in line with basic emotion theory versus only minor changes in network level properties as predicted by psychological construction theory. We defined the emotion recognition network in the total sample and investigated group differences on five network level indices (i.e. characteristic path length, global efficiency, clustering coefficient, local efficiency and small‐worldness). The results did not reveal a significant increase in the left or right temporal lobectomy group (compared to the control group) in any of the graph measures, indicating that preserved behavioural emotion recognition in TLS is not associated with a massive connectivity increase between non‐amygdalar nodes at network level. We conclude that the emotion recognition network is robust and functionally able to compensate for structural damage without substantial global reorganization, in line with a psychological construction theory. [ABSTRACT FROM AUTHOR]

The human amygdala is considered a key region for successful emotion recognition. We recently reported that temporal lobe surgery (TLS), including resection of the amygdala, does not affect emotion recognition performance (Journal of Neuroscience, 2018, 38, 9263). In the present study, we investigate the neural basis of this preserved function at the network level. We use generalized psychophysiological interaction and graph theory indices to investigate network level characteristics of the emotion recognition network in TLS patients and healthy controls. Based on conflicting emotion processing theories, we anticipated two possible outcomes: a substantial increase of the non‐amygdalar connections of the emotion recognition network to compensate functionally for the loss of the amygdala, in line with basic emotion theory versus only minor changes in network level properties as predicted by psychological construction theory. We defined the emotion recognition network in the total sample and investigated group differences on five network level indices (i.e. characteristic path length, global efficiency, clustering coefficient, local efficiency and small‐worldness). The results did not reveal a significant increase in the left or right temporal lobectomy group (compared to the control group) in any of the graph measures, indicating that preserved behavioural emotion recognition in TLS is not associated with a massive connectivity increase between non‐amygdalar nodes at network level. We conclude that the emotion recognition network is robust and functionally able to compensate for structural damage without substantial global reorganization, in line with a psychological construction theory. [ABSTRACT FROM AUTHOR]

The behavioural variant of frontotemporal dementia (bvFTD) is a frequent cause of early-onset dementia. The diagnosis of bvFTD remains challenging because of the limited accuracy of neuroimaging in the early disease stages and the absence of molecular biomarkers, and therefore relies predominantly on clinical assessment. BvFTD shows significant symptomatic overlap with non-degenerative primary psychiatric disorders including major depressive disorder, bipolar disorder, schizophrenia, obsessive-compulsive disorder, autism spectrum disorders and even personality disorders. To date, ∼50% of patients with bvFTD receive a prior psychiatric diagnosis, and average diagnostic delay is up to 5-6 years from symptom onset. It is also not uncommon for patients with primary psychiatric disorders to be wrongly diagnosed with bvFTD. The Neuropsychiatric International Consortium for Frontotemporal Dementia was recently established to determine the current best clinical practice and set up an international collaboration to share a common dataset for future research. The goal of the present paper was to review the existing literature on the diagnosis of bvFTD and its differential diagnosis with primary psychiatric disorders to provide consensus recommendations on the clinical assessment. A systematic literature search with a narrative review was performed to determine all bvFTD-related diagnostic evidence for the following topics: bvFTD history taking, psychiatric assessment, clinical scales, physical and neurological examination, bedside cognitive tests, neuropsychological assessment, social cognition, structural neuroimaging, functional neuroimaging, CSF and genetic testing. For each topic, responsible team members proposed a set of minimal requirements, optimal clinical recommendations, and tools requiring further research or those that should be developed. Recommendations were listed if they reached a ≥ 85% expert consensus based on an online survey among all consortium participants. New recommendations include performing at least one formal social cognition test in the standard neuropsychological battery for bvFTD. We emphasize the importance of 3D-T1 brain MRI with a standardized review protocol including validated visual atrophy rating scales, and to consider volumetric analyses if available. We clarify the role of 18F-fluorodeoxyglucose PET for the exclusion of bvFTD when normal, whereas non-specific regional metabolism abnormalities should not be over-interpreted in the case of a psychiatric differential diagnosis. We highlight the potential role of serum or CSF neurofilament light chain to differentiate bvFTD from primary psychiatric disorders. Finally, based on the increasing literature and clinical experience, the consortium determined that screening for C9orf72 mutation should be performed in all possible/probable bvFTD cases or suspected cases with strong psychiatric features. [ABSTRACT FROM AUTHOR]

• Emotion-attention interactions impact many aspects of daily life. • These interactions involve interplays between affective and executive brain systems. • Individual differences (age, sex, personality) can modulate emotion and attention. • Maladaptive emotion-attention interactions are common in affective disorders. • Training and interventions can optimize emotion-attention interactions. Due to their ability to capture attention, emotional stimuli tend to benefit from enhanced perceptual processing, which can be helpful when such stimuli are task-relevant but hindering when they are task-irrelevant. Altered emotion-attention interactions have been associated with symptoms of affective disturbances, and emerging research focuses on improving emotion-attention interactions to prevent or treat affective disorders. In line with the Human Affectome Project's emphasis on linguistic components, we also analyzed the language used to describe attention-related aspects of emotion, and highlighted terms related to domains such as conscious awareness, motivational effects of attention, social attention, and emotion regulation. These terms were discussed within a broader review of available evidence regarding the neural correlates of (1) Emotion-Attention Interactions in Perception , (2) Emotion-Attention Interactions in Learning and Memory , (3) Individual Differences in Emotion-Attention Interactions , and (4) Training and Interventions to Optimize Emotion-Attention Interactions. This comprehensive approach enabled an integrative overview of the current knowledge regarding the mechanisms of emotion-attention interactions at multiple levels of analysis, and identification of emerging directions for future investigations. [ABSTRACT FROM AUTHOR]

Background: Gray matter volume decrease, white matter vascular pathology and amyloid accumulation are age-related brain changes that have been related to the pathogenesis of late life depression (LLD). Furthermore, lower hippocampal volume and more white matter hyperintensities (WMH) may contribute to poor response to electroconvulsive therapy (ECT) in severely depressed older adults. We hypothesized that the accumulation of age-related brain changes negatively affects outcome following ECT in LLD.Methods: 34 elderly patients with severe LLD were treated twice weekly with ECT until remission. All had both 3T structural magnetic resonance imaging (MRI) and β-amyloid positron emission tomography (PET) imaging using 18F-flutemetamol at baseline. MADRS and MMSE were obtained weekly which included 1 week prior to ECT (T0), after the sixth ECT (T1), and one week (T2) after the last ECT as well as at four weeks (T3) and 6 months (T4) after the last ECT. We conducted a multiple logistic regression analysis and a survival analysis with neuroimaging measures as predictors, and response, remission and relapse as outcome variable.Results: We did not find any association between baseline hippocampal volume, white matter hyperintensity volume and total amyloid load and response or remission at 1 and 4 weeks post ECT, nor with relapse at week 4.Limitations: The present exploratory study was conducted at a single center academic hospital, the sample size was small, the focus was on hippocampal volume and the predictive effect of structural and molecular changes associated with aging were used.Conclusions: Our study shows no evidence of relationship between response to ECT and age-related structural or molecular brain changes, implying that ECT can be applied effectively in depressed patients irrespective of accumulating age-related brain changes. [ABSTRACT FROM AUTHOR]

Humans with amygdalar lesions show proportional reductions of the emotional response to facial expressions in the fusiform face area as well as deficits in emotion recognition from facial expressions. While processing of bodily expressions shares many similarities with facial expressions, there is no substantial evidence that lesions of the amygdala result in similar behavioral and neural sequelae. We combined behavioral assessment with functional neuroimaging in a group of male and female humans with unilateral anterior temporal lobe (ATL) resections, including the amygdala (right: n = 10, left: t i = 10) and 12 matched controls. The objective was to assess whether the amygdala is crucial for the recognition of body expressions and for modulatory effects on distant areas during perception of body expressions. The behavioral results revealed normal performance in both patient groups on emotion categorization of body expressions. The neuroimaging results showed that ATL patients displayed no enhanced activations in right fusiform body area and left extrastriate body area and that left ATL patients additionally displayed no enhanced activations in right posterior superior temporal sulcus and right extrastriate body area, respectively. Multivoxel pattern analysis revealed altered categorization capacity between emotional and neutral stimuli in right posterior superior temporal sulcus in right ATL patients. In addition, we also found emotional enhancement in frontal, parietal, occipital, and cingulate regions in controls. Together, our data show that the amygdala and ATLs are not necessary for recognition of dynamic body expressions, but suggest that amygdala lesions affect body emotion processing in distant brain areas. [ABSTRACT FROM AUTHOR]

Background: Epilepsy surgery often causes changes in cognition and cerebral glucose metabolism. Our aim was to explore relationships between pre- and postoperative cerebral metabolism as measured with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and neuropsychological test scores in patients with left mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS), who were rendered seizure-free after epilepsy surgery.Results: Thirteen patients were included. All had neuropsychological testing and an interictal FDG-PET scan of the brain pre- and postoperative. Correlations between changes in neuropsychological test scores and metabolism were examined using statistical parametric mapping (SPM). There were no significant changes in the neuropsychological test scores pre- and postoperatively at the group level. Decreased metabolism was observed in the left mesial temporal regions and occipital lobe. Increased metabolism was observed in the bi-frontal and right parietal lobes, temporal lobes, occipital lobes, thalamus, cerebellum, and vermis. In these regions, we did not find a correlation between changes in metabolism and neuropsychological test scores. A significant negative correlation, however, was found between metabolic changes in the precuneus and Boston Naming Test (BNT) scores.Conclusions: There are significant metabolic decreases in the left mesial temporal regions and increases in the bi-frontal lobes; right parietal, temporal, and occipital lobes; right thalamus; cerebellum; and vermis in patients with left MTLE-HS who were rendered seizure-free after epilepsy surgery. We could not confirm that these changes translate into significant cognitive changes. A significant negative correlation was found between changes in confrontation naming and changes in metabolism in the precuneus. We speculate that the precuneus may play a compensatory role in patients with postoperative naming difficulties after left TLE surgery. Understanding of these neural mechanisms may aid in designing cognitive rehabilitation strategies. [ABSTRACT FROM AUTHOR]

Objective: Hippocampal volume is commonly decreased in late-life depression. According to the depression-as-late-life-neuropsychiatric-disorder model, lower hippocampal volume in late-life depression is associated with neurodegenerative changes. The purpose of this prospective study was to examine whether lower hippocampal volume in late-life depression is associated with Alzheimer's disease pathology.Method: Of 108 subjects who participated, complete, good-quality data sets were available for 100: 48 currently depressed older adults and 52 age- and gender-matched healthy comparison subjects who underwent structural MRI, [18F]flutemetamol amyloid positron emission tomography imaging, apolipoprotein E genotyping, and neuropsychological assessment. Hippocampal volumes were defined manually and normalized for total intracranial volume. Amyloid binding was quantified using the standardized uptake value ratio in one cortical composite volume of interest. The authors investigated group differences in hippocampal volume (both including and excluding amyloid-positive participants), group differences in amyloid uptake and in the proportion of positive amyloid scans, and the association between hippocampal volume and cortical amyloid uptake.Results: A significant difference was observed in mean normalized total hippocampal volume between patients and comparison subjects, but there were no group differences in cortical amyloid uptake or proportion of amyloid-positive subjects. The difference in hippocampal volume remained significant after the amyloid-positive subjects were excluded. There was no association between hippocampal volume and amyloid uptake in either patients or comparison subjects.Conclusions: Lower hippocampal volume was not related to amyloid pathology in this sample of patients with late-life depression. These data counter the common belief that changes in hippocampal volume in late-life depression are due to prodromal Alzheimer's disease. [ABSTRACT FROM AUTHOR]

• HV discriminated depression from AD in half of cases in a psychiatry setting. • MRI can be used to identify patients who would benefit from amyloid assessment. • Combining amyloid PET with HV improves the differential diagnosis of AD and LLD. Amyloid positron emission tomography (PET) and hippocampal volume derived from magnetic resonance imaging may be useful clinical biomarkers for differentiating between geriatric depression and Alzheimer's disease (AD). Here we investigated the incremental value of using hippocampal volume and 18F-flutemetmol amyloid PET measures in tandem and sequentially to improve discrimination in unclassified participants. Two approaches were compared in 41 participants with geriatric depression and 27 participants with probable AD: (1) amyloid and hippocampal volume combined in one model and (2) classification based on hippocampal volume first and then subsequent stratification using standardized uptake value ratio (SUVR)-determined amyloid positivity. Hippocampal volume and amyloid SUVR were significant diagnostic predictors of depression (sensitivity: 95%, specificity: 89%). 51% of participants were correctly classified according to clinical diagnosis based on hippocampal volume alone, increasing to 87% when adding amyloid data (sensitivity: 94%, specificity: 78%). Our results suggest that hippocampal volume may be a useful gatekeeper for identifying depressed individuals at risk for AD who would benefit from additional amyloid biomarkers when available. [ABSTRACT FROM AUTHOR]

The article presents a study which examined how the cognitive defects experienced by some breast cancer survivors are related to chemotherapy-induced structural changes in cerebral white matter (WM). It also provides neuropsychological, fractional anisotropy (FA) and magnetic resonance (MR) image assessment of the subjects. It suggests that WM integrity is lower in chemotherapy-treated breast cancer patients when compared with healthy controls or with nonchemotherapy-treated patients.

Summary: A patient with bilateral damage to primary visual (striated) cortex has provided the opportunity to assess just what visual capacities are possible in the absence of geniculo-striate pathways. Patient TN suffered two strokes in succession, lesioning each visual cortex in turn and causing clinical blindness over his whole visual field. Functional and anatomical brain imaging assessments showed that TN completely lacks any functional visual cortex. We report here that, among other retained abilities, he can successfully navigate down the extent of a long corridor in which various barriers were placed. A video recording shows him skillfully avoiding and turning around the blockages. This demonstrates that extra-striate pathways in humans can sustain sophisticated visuo-spatial skills in the absence of perceptual awareness, akin to what has been previously reported in monkeys. It remains to be determined which of the several extra-striate pathways account for TN''s intact navigation skills. [Copyright &y& Elsevier]