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Frontotemporal dementia (FTD) is a heterogeneous group of neurodegenerative brain disorders, primarily affecting the frontal and/or temporal lobes. Three main subtypes are recognised, each with distinct clinical and cognitive profiles: behavioural-variant FTD (bvFTD), semantic dementia (SD), and progressive nonfluent aphasia (PNFA). Subtype-specific cerebellar grey matter atrophy has been associated with cognitive dysfunction in FTD; however, the extent and severity of structural abnormalities in the cerebro-cerebellar circuits in these disorders has not been investigated. This study aimed to identify patterns of cerebellar white matter changes and their relations to cognitive deficits in the main FTD subtypes. Results revealed bilateral cerebellar white matter changes in all FTD subtypes compared with controls, with greater cerebellar white matter changes in bvFTD than SD and PNFA. Both afferent and efferent cerebellar pathways were associated with cognition. The profiles of the involvement of cerebellar pathways in cognition varied across FTD syndromes. In bvFTD, the output pathway of the cerebellum was only associated with measures of episodic memory. The input pathway was associated with measures of attention, working memory, visuospatial, episodic memory, executive function, and emotion. In SD, both the output and input pathways were associated with measures of working memory, language, and emotion. Finally, in PNFA, both the output and input pathway of the cerebellum were associated with attention, language, and executive function. Additionally, the input pathway was associated with working memory, visuospatial, and emotion. This study is the first to identify patterns of cerebellar white matter changes across FTD syndromes, which in turn relate to cognitive deficits. These findings extend our understanding of the cerebro-cerebellar networks and provide new insight into the role of cerebellar white matter in cognition.

Background Frontotemporal dementia (FTD) is associated with complex changes in eating behavior and metabolism, which potentially affect disease pathogenesis and survival. It is currently not known if body composition changes and changes in fat deposition also exist in FTD, the relationship of these changes in eating behavior and appetite, and whether these changes are centrally mediated. Methods Body composition was measured in 28 people with behavioral‐variant frontotemporal dementia (bvFTD), 16 with Alzheimer’s disease (AD), and 19 healthy controls, using dual energy x‐ray absorptiometry. Changes in body composition were correlated to brain grey matter atrophy using voxel‐based morphometry on high‐resolution magnetic resonance imaging. Results Behavioral‐variant FTD was characterized by changes in body composition, with increased total fat mass, visceral adipose tissue area (VAT area), and android: gynoid ratio compared to control and AD participants (all P values

ObjectiveTo test the hypothesis that white matter hyperintensities (WMH) in behavioral-variant frontotemporal dementia (bvFTD) and Alzheimer disease (AD) are associated with disease variables such as disease severity, cortical atrophy, and cognition, we conducted a cross-sectional brain MRI study with volumetric and voxel-wise analyses.MethodsA total of 129 patients (64 bvFTD, 65 AD) and 66 controls underwent high-resolution brain MRI and clinical and neuropsychological examination. Genetic screening was conducted in 124 cases (54 bvFTD, 44 AD, 26 controls) and postmortem pathology was available in 18 cases (13 bvFTD, 5 AD). WMH were extracted using an automated segmentation algorithm and analyses of total volumes and spatial distribution were conducted. Group differences in total WMH volume and associations with vascular risk and disease severity were examined. Syndrome-specific voxel-wise associations between WMH, cortical atrophy, and performance across different cognitive domains were assessed.ResultsTotal WMH volumes were larger in patients with bvFTD than patients with AD and controls. In bvFTD, WMH volumes were associated with disease severity but not vascular risk. Patients with bvFTD and patients with AD showed distinct spatial patterns of WMH that mirrored characteristic patterns of cortical atrophy. Regional WMH load correlated with worse cognitive performance in discrete cognitive domains. WMH-related cognitive impairments were shared between syndromes, with additional associations found in bvFTD.ConclusionIncreased WMH are common in patients with bvFTD and patients with AD. Our findings suggest that WMH are partly independent of vascular pathology and associated with the neurodegenerative process. WMH occur in processes independent of and related to cortical atrophy. Furthermore, increased WMH in different regions contributes to cognitive deficits.

Mounting evidence suggests an association between cerebellar atrophy and cognitive impairment in the main frontotemporal dementia syndromes. In contrast, whether cerebellar atrophy is present in the motor syndromes associated with frontotemporal lobar degeneration (corticobasal syndrome and progressive supranuclear palsy) and the extent of its contribution to their cognitive profile remain poorly understood. The current study aimed to comprehensively chart profiles of cognitive impairment in relation to cerebellar atrophy in 49 dementia patients (corticobasal syndrome = 33; progressive supranuclear palsy = 16) compared to 33 age-, sex- and education-matched healthy controls. Relative to controls, corticobasal syndrome and progressive supranuclear palsy patients demonstrated characteristic cognitive impairment, spanning the majority of cognitive domains including attention and processing speed, language, working memory, and executive function with relative preservation of verbal and nonverbal memory. Voxel-based morphometry analysis revealed largely overlapping patterns of cerebellar atrophy in corticobasal syndrome and progressive supranuclear palsy relative to controls, primarily involving bilateral Crus II extending into adjacent lobules VIIb and VIIIa. After controlling for overall cerebral atrophy and disease duration, exploratory voxel-wise general linear model analysis revealed distinct cerebellar subregions differentially implicated across cognitive domains in each patient group. In corticobasal syndrome, reduction in grey matter intensity in the left Crus I was significantly correlated with executive dysfunction. In progressive supranuclear palsy, integrity of the vermis and adjacent right lobules I–IV was significantly associated with language performance. These results are consistent with the well-established role of Crus I in executive functions and provide further supporting evidence for vermal involvement in cognitive processing. The current study presents the first detailed exploration of the role of cerebellar atrophy in cognitive deficits in corticobasal syndrome and progressive supranuclear palsy, offering insights into the cerebellum’s contribution to cognitive processing even in neurodegenerative syndromes characterized by motor impairment., Voxel-based morphometry analysis revealed that cerebellar atrophy in the left Crus I was correlated with executive dysfunction in corticobasal syndrome, whereas the vermis and adjacent right lobules I–IV were associated with language performance in progressive supranuclear palsy, demonstrating cerebellar contributions to cognition even in neurodegenerative syndromes characterized by motor impairment., Graphical Abstract Graphical Abstract

Introduction Timely diagnosis of behavioral variant frontotemporal dementia (bvFTD) remains challenging because it depends on clinical expertise and potentially ambiguous diagnostic guidelines. Recent recommendations highlight the role of multimodal neuroimaging and machine learning methods as complementary tools to address this problem. Methods We developed an automatic, cross-center, multimodal computational approach for robust classification of patients with bvFTD and healthy controls. We analyzed structural magnetic resonance imaging and resting-state functional connectivity from 44 patients with bvFTD and 60 healthy controls (across three imaging centers with different acquisition protocols) using a fully automated processing pipeline, including site normalization, native space feature extraction, and a random forest classifier. Results Our method successfully combined multimodal imaging information with high accuracy (91%), sensitivity (83.7%), and specificity (96.6%). Discussion This multimodal approach enhanced the system's performance and provided a clinically informative method for neuroimaging analysis. This underscores the relevance of combining multimodal imaging and machine learning as a gold standard for dementia diagnosis., Highlights • A multimodal computational approach was implemented to identify patients with bvFTD. • We combined features from structural MRI data and fMRI-based functional connectivity. • Our approach was validated over 103 subjects from three different centers. • Our multimodal approach yielded high classification accuracy (91%) across centers. • Multimodal computational approaches may be useful complements for dementia diagnosis.

Eye movement desensitization and reprocessing (EMDR) is a relatively new psychotherapy that has gradually gained popularity for the treatment of post-traumatic stress disorder. In the present work, the standardised EMDR protocol is introduced, along with current hypotheses of its mechanism of action, as well as a critical review of the available literature on its clinical effectiveness in adult post-traumatic stress disorder. A systematic review of the published literature was performed using PubMed and PsycINFO databases with the keywords «eye movement desensitization and reprocessing» and «post-traumatic stress disorder» and its abbreviations «EMDR» and «PTSD». Fifteen randomised controlled trials of good methodological quality were selected. These studies compared EMDR with unspecific interventions, waiting lists, or specific therapies. Overall, the results of these studies suggest that EMDR is a useful, evidence-based tool for the treatment of post-traumatic stress disorder, in line with recent recommendations from different international health organisations.

Objective:To identify distinct behavioral phenotypes of behavioral-variant frontotemporal dementia (bvFTD) and to elucidate differences in functional, neuroimaging, and progression to residential care placement.Methods:Eighty-eight patients with bvFTD were included in a cluster analysis applying levels of disinhibition and apathy (Cambridge Behavioural Inventory-Revised) to identify phenotypic subgroups. Between-group (Kruskal-Wallis, Mann-Whitney U) functional differences (Disability Assessment for Dementia) and time to residential care placement (survival analyses) were examined. Cortical thickness differences (whole-brain MRI) were analyzed in patients with bvFTD vs healthy controls (n = 30) and between phenotypic subgroups.Results:Four phenotypic subgroups were identified: primary severe apathy (n = 26), severe apathy and disinhibition (n = 26), mild apathy and disinhibition (n = 27), and primary severe disinhibition (n = 9). Patients with severely apathetic phenotypes were more functionally impaired and had more extensive brain atrophy than those with mild apathy or severe disinhibition alone. Further imaging analyses indicated that the right middle temporal region is critical for the development of disinhibition, an association that remains with disease progression and in the context of severe apathy. Finally, no difference in time to residential care admission was found between phenotypes.Conclusions:This study reveals that different clinical behavioral phenotypes of bvFTD have differing profiles of functional decline and distinct patterns of associated cortical changes. These findings emphasize the importance of apathy in functional impairment, highlight the role of the right temporal region in disinhibition, and suggest that disability may be a sensitive outcome measure for treatments targeting reduction of apathy. These phenotypes could also support understanding of prognosis and clinical management.

Biomarkers represent a critical research area in neurodegeneration disease as they can contribute to studying potential disease-modifying agents, fostering timely therapeutic interventions, and alleviating associated financial costs. Functional connectivity (FC) analysis represents a promising approach to identify early biomarkers in specific diseases. Yet, virtually no study has tested whether potential FC biomarkers prove to be reliable and reproducible across different centers. As such, their implementation remains uncertain due to multiple sources of variability across studies: the numerous international centers capable conducting FC research vary in their scanning equipment and their samples’ socio-cultural background, and, more troublingly still, no gold-standard method exists to analyze FC. In this unprecedented study, we aim to address both issues by performing the first multicenter FC research in the behavioral-variant frontotemporal dementia (bvFTD), and by assessing multiple FC approaches to propose a gold-standard method for analysis. We enrolled 52 bvFTD patients and 60 controls from three international clinics (with different fMRI recording parameters), and three additional neurological patient groups. To evaluate FC, we focused on seed analysis, inter-regional connectivity, and several graph-theory approaches. Only graph-theory analysis, based on weighted-matrices, yielded consistent differences between bvFTD and controls across centers. Also, graph metrics robustly discriminated bvFTD from the other neurological conditions. The consistency of our findings across heterogeneous contexts highlights graph-theory as a potential gold-standard approach for brain network analysis in bvFTD. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Background Clinical differentiation between Alzheimer's disease (AD) and behavioural-variant frontotemporal dementia (bvFTD) is challenging due to overlapping clinical features at presentation. Whilst diagnostic criteria for both disorders incorporate evidence of frontal and temporal cortical atrophy, understanding of the progression of atrophy in these disorders is limited. This study aimed to elucidate common and disease-specific progressive changes in cortical and subcortical brain structures in AD and bvFTD. Methods Forty-one AD, 37 bvFTD and 33 healthy controls underwent baseline MRI and of these longitudinal follow-up was obtained for 20 AD and 20 bvFTD (1 to 4 years). A total of 87 AD and 70 bvFTD consecutive scans were included in the study. The trajectories of progression in cortical and subcortical structures were identified with FreeSurfer and linear mixed effect modelling. Results The results uncovered cortical and subcortical disease-specific trajectories of neurodegeneration in AD and bvFTD. Specifically, direct comparisons between patient groups revealed that over time AD showed greater cortical atrophy in the inferior parietal and posterior cingulate cortex than bvFTD. Conversely, bvFTD patients showed greater atrophy in the striatum than AD over time. Conclusions These results indicate that atrophy in the posterior cingulate and the striatum diverges with disease progression in these dementia syndromes and may represent a potential diagnostic biomarker for tracking rates of progression of AD and bvFTD. These findings may help inform future drug trials by identifying appropriate outcome measures to quantify drug efficacy and their ability to modulate disease progression over time.

Background A key finding underlying the continuum of psychosis concept is the presence of psychotic-like experiences (PLEs) in healthy subjects. However, it remains uncertain to what extent these experiences are related to the genetic risk for schizophrenia and how far they actually resemble attenuated forms of psychotic symptoms. Methods Forty-nine adults with no history of mental illness in first-degree relatives and 59 siblings of patients with schizophrenia were rated on the psychosis section of the Computerized Diagnostic Interview Schedule IV (C DIS-IV) and the Rust Inventory of Schizotypal Cognitions (RISC). Those who rated positive on the CDIS-IV were re-interviewed using the lifetime version of the Present State Examination 9th edition (PSE-9) and the Structured interview for Schizotypy (SIS). Results Seventeen (34.69%) of the non-relatives and 22 (37.29%) of the relatives responded positively to one or more of the psychosis questions on the DIS. This difference was not significant. RISC scores were also similar between the groups. At follow-up interview with the PSE-9, 13/40 PLEs (32.50%) in the non-relatives were classified as possible or probable psychotic symptoms compared to 11/46 (23.91%) in the relatives. Using liberal symptom thresholds, 5 of those who attended the follow-up interview (2 non-relatives and 3 relatives) met SIS criteria for schizotypal personality disorder. Conclusions Rates of PLEs, however considered, do not differ substantially between relatives and non-relatives of patients with schizophrenia. Only a minority of PLEs picked up by screening interviews resemble attenuated forms of psychotic symptoms.

Background: Brain structural and functional changes in bipolar disorder (BD) are well-established findings, but it is uncertain whether these changes are already present in first episode mania (FEM).Methods: We compared 31 FEM subjects, with 31 healthy individuals matched for age, sex, and premorbid IQ. Whole-brain voxel-wise morphometry, functional magnetic resonance imaging during the n-back task, and a functional connectivity analysis were performed.Results: There were no volumetric differences between the 2 groups. During the 2-back task, FEM patients did not perform differently from controls and activated similar regions, but they showed less deactivation in the ventromedial prefrontal cortex (vmPFC), the anterior hub of the default mode network (DMN). They showed preserved functional connectivity between the vmPFC and other regions of the DMN, but increased connectivity with the superior frontal gyrus.Conclusions: The absence of volumetric changes in FEM patients suggests that these changes could be related to progression of the illness. On the other hand, the failure of deactivation of the anterior hub of the DMN is present from the onset of the illness and may represent a core pathophysiological feature of BD.

To track neural correlates of naming performance with disease progression, we estimated key areas affected in nonfluent/agrammatic (nfvPPA) and logopenic (lvPPA) primary progressive aphasia variants over time and changes in naming correlates over time. Twenty-nine non-semantic PPA participants (17 nfvPPA and 12 lvPPA) were selected based upon current diagnostic criteria and PiB-PET status and conducted a confrontation-naming task and a structural MRI. Linear mixed-effect models implemented in FreeSurfer were used for tracking cortical thickness and epicenters of atrophy over time. Using averaged cortical thickness of epicenters and naming performance as variables of interest, two sets of multivariate analyses were conducted to compare atrophy progression and naming correlates across groups. While all PPA participants demonstrated naming deterioration and progressive cortical thinning in the left temporal lobe and the left inferior frontal gyrus, the lvPPA cohort showed greater naming deterioration and thinning in the left posterior inferior parietal cortex over time than it did the nfvPPA cohort. The multivariate analyses confirmed a widespread cortical thinning in lvPPA over time, but a more rapid thinning in the right superior frontal gyrus of nfvPPA participants. Impaired naming correlated with common cortical regions in both groups. These regions included the left anterior superior temporal gyrus and the posterior middle temporal gyrus, which was primarily affected in lvPPA. Non-semantic PPA variants initially present with separate epicenters of atrophy and different spatial-temporal patterns of neurodegeneration over time, but the common involvement in key cortical regions of the left temporal lobe accounts for naming deterioration in both groups.

Background Structural pathology in the hippocampus is well-documented in schizophrenia, but brain functional changes have not been consistently found. We used spatial navigation in a virtual reality environment, a task that is known to produce robust hippocampal activation in healthy subjects, to examine task-related activations and de-activations in the disorder. Methods Twenty-seven DSM IV schizophrenia patients and 32 healthy controls underwent fMRI while they navigated to a goal through a virtual reality town. Activations and de-activations were examined at the whole brain level and also using a region-of-interest (ROI) in the hippocampus. Results Spatial navigation was associated with activation in the posterior hippocampus and parahippocampal gyrus plus widespread neocortical areas. The patients showed reduced activation compared to the controls in the left dorsolateral prefrontal cortex (DLPFC) and the left occipital/temporal cortex. No differences in hippocampal activation were seen either at the whole-brain level or in the ROI analysis. The patients showed failure of de-activation affecting some but not all subregions of the default mode network. Conclusions Schizophrenia is associated with task-related hypoactivation in the DLPFC during spatial navigation, but not with functional changes in the hippocampus. The failure of de-activation also found adds to evidence for default mode network dysfunction in the disorder.

Schizophrenia is considered a disorder of abnormal brain connectivity. Although whole brain maps of averaged bivariate voxel correlations have been successfully applied to study connectivity abnormalities in schizophrenia these maps do not adequately explore the multivariate nature of brain connectivity. Here we adapt a novel method for high-dimensional regression (supervised principal component regression) to estimate brain maps of multivariate non redundant connectivity (NRC) from resting functional Magnetic Resonance Imaging (fMRI) data of 116 patients with schizophrenia and 122 matched controls. Disorder related differences in NRC involved caudate hyper-connectivity and hypo-connectivity of several cortical areas such as the dorsal cingulate, the cuneus and the right postcentral cortex. These abnormalities were coupled with abnormalities in the amplitude of signal fluctuations and, to a minor extent, with differences in the dimensionality of connectivity patterns as quantified by the number of supervised principal components. Second level seed correlation analyses linked the observed abnormalities to an additional set of brain regions relevant to schizophrenia such as the thalamus and the temporal cortex. The non redundant connectivity maps proposed here are a new tool that will complement the information provided by other already available voxel based whole brain connectivity measures.

The typical presentation of semantic dementia is associated with marked, left predominant anterior temporal lobe atrophy and with changes in language. About 30% of individuals, however, present with predominant right anterior temporal lobe atrophy, usually accompanied by behavioural changes and prosopagnosia. Here, we aimed to establish whether these initially distinct clinical presentations evolve into a similar syndrome at the neural and behavioural level. Thirty-one patients who presented with predominant anterior temporal lobe atrophy were included. Based on imaging, patients were categorized as either predominant left (n = 22) or right (n = 9) semantic dementia. Thirty-three Alzheimer's disease patients and 25 healthy controls were included for comparison. Participants completed the Addenbrooke's Cognitive Examination, a Face and Emotion Processing Battery and the Cambridge Behavioural Inventory, and underwent magnetic resonance imaging annually. Longitudinal neuroimaging analyses showed greater right temporal pole atrophy in left semantic dementia than Alzheimer's disease, whereas right semantic dementia showed greater orbitofrontal and left temporal lobe atrophy than Alzheimer's disease. Importantly, direct comparisons between semantic dementia groups revealed that over time, left semantic dementia showed progressive thinning in the right temporal pole, whereas right semantic dementia showed thinning in the orbitofrontal cortex and anterior cingulate. Behaviourally, longitudinal analyses revealed that general cognition declined in all patients. In contrast, patients with left and right semantic dementia showed greater emotion recognition decline than Alzheimer's disease. In addition, left semantic dementia showed greater motivation loss than Alzheimer's disease. Correlational analyses revealed that emotion recognition was associated with right temporal pole, right medial orbitofrontal and right fusiform integrity, while changes in motivation were associated with right temporal pole cortical thinning. While left and right semantic dementia show distinct profiles at presentation, both phenotypes develop deficits in emotion recognition and behaviour. These findings highlight the pervasive socio-emotional deficits in frontotemporal dementia, even in patients with an initial language presentation. These changes reflect right anterior temporal and orbitofrontal cortex degeneration, underscoring the role of these regions in social cognition and behaviour.

Frontotemporal dementia (FTD) is a neurodegenerative brain disorder primarily affecting the frontal and/or temporal lobes. Three main subtypes have been recognized: behavioural-variant FTD (bvFTD), semantic dementia (SD), and progressive nonfluent aphasia (PNFA), each of which has a distinct clinical and cognitive profile. Although the role of the cerebellum in cognition is increasingly accepted, knowledge of cerebellar changes across neuroimaging modalities and their contribution to behavioural and cognitive changes in FTD syndromes is currently scant. We conducted an anatomical/activation likelihood estimation (ALE) meta-analysis in 53 neuroimaging studies (structural MRI: 42; positron emission tomography: 6; functional MRI: 4; single-photon emission computed tomography: 1) to identify the patterns of cerebellar changes and their relations to profiles of behavioural and cognitive deficits in FTD syndromes. Overall, widespread bilateral cerebellar changes were found in FTD and notably the patterns were subtype specific. In bvFTD, ALE peaks were identified in the bilateral Crus, left lobule VI, right lobules VIIb and VIIIb. In SD, focal cerebellar changes were located in the left Crus I and lobule VI. A separate ALE meta-analysis on PNFA studies was not performed due to the limited number of studies available. In addition, the ALE analysis indicated that bilateral Crus I and Crus II were associated with behavioural disruption and cognitive dysfunction. This ALE meta-analysis provides the quantification of the location and extent of cerebellar changes across the main FTD syndromes, which in turn provides evidence of cerebellar contributions to behavioural and cognitive changes in FTD. These results bring new insights into the mechanisms mediating FTD symptomatology.

Objective Increasing evidence suggests that cerebellar damage impacts on cognitive functions. Frontotemporal dementias (FTDs) are neurodegenerative brain conditions, primarily affecting the frontal and/or temporal lobe. Three main phenotypes are recognized, each with a distinct clinical and cognitive profile: behavioral-variant FTD (bvFTD), semantic dementia (SD), and progressive nonfluent aphasia (PNFA). The severity of cerebellar changes and their relation to cognition in FTD, however, remain unclear. This study aimed to establish cerebellar gray matter changes on magnetic resonance imaging (MRI) and their relation to profiles of cognitive deficits in FTD subtypes. Methods Ninety-six FTD patients (45 bvFTD, 28 SD, and 23 PNFA), meeting current clinical diagnostic criteria, and 35 age-, sex-, and education-matched controls underwent brain MRI and cognitive assessment. Cerebral and cerebellar gray matter integrity were investigated using voxel-based morphometry. Results Compared with controls, widespread bilateral cerebellar changes were observed in all FTD subtypes, with the greatest atrophy present in bvFTD. Significant associations were found between cerebellar integrity and cognitive performance in attention and working memory in bvFTD, visuospatial function in SD, and language-motor function in PNFA. Bilateral atrophy of crus and lobule VI were most commonly associated with cognitive deficits, irrespective of FTD phenotype. Interpretation This study is the first to identify distinct patterns of cerebellar atrophy across FTD syndromes, which in turn relate to discrete cognitive dysfunctions, after accounting for the effect of cerebral atrophy. These findings extend our understanding of the cerebellum and point to its involvement across an array of processes beyond the domain of motor function. Ann Neurol 2018;83:98-109.

Amann BL, Canales-Rodriguez EJ, Madre M, Radua J, Monte G,Alonso-Lana S, Landin-Romero R, Moreno-Alcazar A,Bonnin CM, Sarro S, Ortiz-Gil J, Gomar JJ, Moro N,Fernandez-Corcuera P, Goikolea JM, Blanch J, Salvador R, Vieta E,McKenna PJ, Pomarol-Clotet E. Brain structural changes inschizoaffective disorder compared to schizophrenia and bipolar disorder.Objective: Brain structural changes in schizoaffective disorder, and howfar they resemble those seen in schizophrenia and bipolar disorder, haveonly been studied to a limited extent.Method: Forty-five patients meeting DSM-IV and RDC criteria forschizoaffective disorder, groups of patients with 45 matchedschizophrenia and bipolar disorder, and 45 matched healthy controlswere examined using voxel-based morphometry (VBM).Results: Analyses comparing each patient group with the healthycontrol subjects found that the patients with schizoaffective disorderand the patients with schizophrenia showed widespread andoverlapping areas of significant volume reduction, but the patients withbipolar disorder did not. A subsequent analysis compared the combinedgroup of patients with the controls followed by extraction of clusters. Inregions where the patients differed significantly from the controls, nosignificant differences in mean volume between patients withschizoaffective disorder and patients with schizophrenia in any of fiveregions of volume reduction were found, but mean volumes in thepatients with bipolar disorder were significantly smaller in three of five.Conclusion: The findings provide evidence that, in terms of structuralgray matter brain abnormality, schizoaffective disorder resemblesschizophrenia more than bipolar disorder.

Background Many studies having shown significant improvements in non-social and social cognitive performance in smoking FEP patients compared to non-smoking FEP patients. The findings are controversial. This study analyzed the effects of tobacco use on non-social and social cognitive function in a large group of FEP patients and a matched healthy control group. Methods A sample of 335 patients with FEP and 253 healthy controls was divided into four subgroups: control tobacco users (CTU), control non-tobacco users (CNTU), patient tobacco users (PTU) and patient non-tobacco users (PNTU). Demographic variables, tobacco use variables (presence or absence, frequency and duration of tobacco use), neurocognitive (non-social) performance and social cognition were assessed. Results Comparison of 4 subgroups in non-social cognitive function revealed significant differences after controlling for covariables in executive functions (F = 13.45; p ≤0.001) and working memory domains (F = 4.30; p = 0.005). CTU and CNTU subgroups scored higher in all the domains compared to the PTU and the PNTU subgroups respectively. Social cognitive function was also significantly different within the four subgroups, with control subgroups showing better social cognition than patient subgroups. Significant differences in the executive functions domain were observed when comparing PTU and CTU groups (F = 19.60; p ≤0.001). No significant differences were revealed in the comparison between the patient groups. Conclusions This large study suggests that tobacco use in FEP patients is not related to better non-social or social cognitive performance.

Background/Aims: Although some patients with primary progressive aphasia (PPA) exhibit novel or improved skills after the onset of dementia, these changes have yet to be quantified. Therefore, this study systematically explored and identified the emergence of positive behaviours after dementia onset. Methods: This study included 48 carers of patients with PPA: 12 nonfluent/agrammatic PPA (nfvPPA), 22 semantic variant PPA (svPPA), and 14 logopenic variant PPA (lvPPA). The presence and frequency of positive behaviour changes after dementia onset were established using the Hypersensory and Social/Emotional Scale (HSS). Results: Scores on Sensitivity to Details, Visuospatial Activities, and Music Activities differed significantly among the groups. More specifically, svPPA was associated with increased visuospatial activity, but only in the mild stage of the disease; nfvPPA was associated with increased visuospatial activity and decreased music activity, while lvPPA exhibited the reverse profile. Conclusions: The results demonstrate that subsets of PPA patients show novel or increased positive behaviours following dementia onset, and differences among subtypes may be helpful for improving diagnostic accuracy. Additionally, harnessing these skills may improve the quality of life of both patients and carers.

Altres ajuts: Plan Nacional 2013-2016 with a Miguel Servet Research Contract (MS14/00041). We acknowledge also the generous support by the Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain. Up to 60% of patients with bipolar disorder (BD) have a history of traumatic events, which is associated with greater episode severity, higher risk of comorbidity and higher relapse rates. Trauma-focused treatment strategies for BD are thus necessary but studies are currently scarce. The aim of this study is to examine whether Eye Movement Desensitization and Reprocessing (EMDR) therapy focusing on adherence, insight, de-idealisation of manic symptoms, prodromal symptoms and mood stabilization can reduce episode severity and relapse rates and increase cognitive performance and functioning in patients with BD. This is a single-blind, randomized controlled, multicentre trial in which 82 patients with BD and a history of traumatic events will be recruited and randomly allocated to one of two treatment arms: EMDR therapy or supportive therapy. Patients in both groups will receive 20 psychotherapeutic sessions, 60 min each, during 6 months. The primary outcome is a reduction of affective episodes after 12 and 24 months in favour of the EMDR group. As secondary outcome we postulate a greater reduction in affective symptoms in the EMDR group (as measured by the Bipolar Depression Rating Scale, the Young Mania Rating Scale and the Clinical Global Impression Scale modified for BD), and a better performance in cognitive state, social cognition and functioning (as measured by the Screen for Cognitive Impairment in Psychiatry, The Mayer-Salovey-Caruso Emotional Intelligence Test and the Functioning Assessment Short Test, respectively). Traumatic events will be evaluated by The Holmes-Rahe Life Stress Inventory, the Clinician-administered PTSD Scale and the Impact of Event Scale. The results of this study will provide evidence whether a specific EMDR protocol for patients with BD is effective in reducing affective episodes, affective symptoms and functional, cognitive and trauma symptoms. The trial is registered at ClinicalTrials.gov, identifier: . Registered on 3 December 2015. The online version of this article (doi:10.1186/s13063-017-1910-y) contains supplementary material, which is available to authorized users.

Functional imaging studies have implicated the hippocampus and parahippocampal gyrus in cue-guided spatial navigation, but also many other regions. Furthermore, little is known about de-activations that take place during performance of navigation tasks, something that is of interest given that the hippocampus is a component of the default mode network, which de-activates during attention-demanding tasks. In this study 22 healthy subjects underwent whole-brain functional Magnetic Resonance Imaging (fMRI) while they navigated toward a previously learned goal in a virtual reality environment. At a threshold of p0.05 corrected, the subjects showed a pattern of widespread cortical activations, including the parahippocampal and retrosplenial cortex and also parts of the frontal, temporal and occipital cortex. Hippocampal activation, however, was restricted to the posterior portion of the structure bilaterally. De-activations were seen in the medial frontal cortex and other regions of the default mode network, but not in the posterior cingulate cortex/precuneus. The findings support the involvement of the hippocampus in cue-guided navigation, but suggest that its posterior regions are particularly important. Cue-guided spatial navigation is associated with de-activation in some but not all parts of the default mode network.

Eye Movement Desensitization and Reprocessing (EMDR) is considered highly efficacious for the treatment of Post-traumatic Stress Disorder and has proved to be a valid treatment approach with a wide range of applications. However, EMDR’s mechanisms of action is not yet fully understood. This is an active area of clinical and neurophysiological research, and several different hypotheses have been proposed. This paper discusses a conjecture which focuses on the similarity between the delta waves recorded by electroencephalography during Slow Wave Sleep (SWS) and those registered upon typical EMDR bilateral stimulation (eye movements or alternate tapping) during recurrent distressing memories of an emotionally traumatic event. SWS appears to have a key role in memory consolidation and in the reorganization of distant functional networks, as well as Eye Movements seem to reduce traumatic episodic memory and favor the reconsolidation of new associated information. The SWS hypothesis may put forward an explanation of how EMDR works, and is discussed also in light of other theories and neurobiological findings.

Progressive and relatively circumscribed loss of semantic knowledge, referred to as semantic dementia (SD) which falls under the broader umbrella of frontotemporal dementia, was officially identified as a clinical syndrome less than 50 years ago. Here, we review recent neuroimaging, pathological, and genetic research in SD. From a neuroimaging perspective, SD is characterised by hallmark asymmetrical atrophy of the anterior temporal pole and anterior fusiform gyrus, which is usually left lateralised. Functional magnetic resonance imaging (fMRI) studies have revealed widespread changes in connectivity, implicating the anterior temporal regions in semantic deficits in SD. Task-related fMRI have also demonstrated the relative preservation of frontal and parietal regions alongside preserved memory performance. In addition, recent longitudinal studies have demonstrated that, with disease progression, atrophy encroaches into the contralateral temporal pole and medial prefrontal cortices, which reflects emerging changes in behaviour and social cognition. Notably, unlike other frontotemporal dementia subtypes, recent research has demonstrated strong clinicopathological concordance in SD, with TDP43 type C as the most common pathological subtype. Moreover, an underlying genetic cause appears to be relatively rare in SD, with the majority of cases having a sporadic form of the disease. The relatively clear diagnosis, clinical course, and pathological homogeneity of SD make this syndrome a promising target for novel disease-modifying interventions. The development of neuroimaging markers of disease progression at the individual level is an important area of research for future studies to address, in order to assist with this endeavour.

Compromised autobiographical memory (ABM) retrieval is well established in dementia, attributable to degeneration of a core memory brain network. It remains unclear, however, how the progressive spread of atrophy with advancing disease severity impacts ABM retrieval across life epochs. To this end, we conducted a longitudinal study of recent and remote ABM in Alzheimer's disease (AD, n =11), and a frontotemporal lobar degeneration group (FTD, n =13) comprising 7 behavioral variant FTD and 6 semantic dementia patients, in comparison with 23 healthy older Controls. Patients were re-assessed approximately one year following their initial visit and underwent repeat testing and brain imaging. Linear mixed modeling neuroimaging analyses explored disease-specific cortical changes driving ABM alterations over time. AD patients showed comparable ABM profiles across assessment periods however, follow-up performance correlated strongly with lateral temporal lobe integrity. In contrast, recent ABMs were disproportionately disrupted at follow-up relative to baseline in the FTD group, attributable to cortical thinning in posterior brain regions, including the right posterior cingulate cortex. Our findings offer new insights regarding the potential time-specific role of discrete cortical regions in ABM retrieval and the differential fate of formerly evocative memories with advancing disease severity in dementia syndromes.

BackgroundThe pathological basis of tardive dyskinesia is unknown. Although its clinical features implicate the basal ganglia, imaging studies have not found clear evidence that it is associated with volume changes in these or other brain structures.AimsTo determine, using voxel-based structural imaging, whether there are regions of grey matter volume change in people with schizophrenia who also have tardive dyskinesia compared with those without tardive dyskinesia.MethodA total of 81 people with chronic schizophrenia, 32 with tardive dyskinesia and 49 without, were examined using magnetic resonance imaging (MRI) and whole-brain, optimised voxel-based morphometry. A comparison group of 61 healthy controls was also examined.ResultsCompared with those without tardive dyskinesia, patients with tardive dyskinesia showed a pattern of volume reductions in predominantly subcortical regions, including the basal ganglia and the thalamus. Within the basal ganglia, volume reductions were seen in the caudate nucleus, to a lesser extent in the putamen, and only marginally in the globus pallidus. The patients with tardive dyskinesia, but not those without, showed significant volume reductions in the basal ganglia compared with the healthy controls but both groups had smaller volumes than controls in other affected areas.ConclusionsThe pathological process or processes that underlie the development of tardive dyskinesia are not just neurochemical in nature, but affect brain structure.

Background: The profile of grey matter abnormalities and related white-matter pathology in schizoaffective disorder has only been studied to a limited extent. The aim of this study was to identify grey- and white-matter abnormalities in patients with schizoaffective disorder using complementary structural imaging techniques. Methods: Forty-five patients meeting Diagnostic and Statistical Manual of Mental Disorders–Fourth Edition criteria and Research Diagnostic Criteria for schizoaffective disorder and 45 matched healthy controls underwent structural-T1 and diffusion magnetic resonance imaging to enable surface-based brain morphometry and diffusion tensor imaging analyses. Analyses were conducted to determine group differences in cortical volume, cortical thickness and surface area, as well as in fractional anisotropy and mean diffusivity. Results: At a threshold of p = 0.05 corrected, all measures revealed significant differences between patients and controls at the group level. Spatial overlap of abnormalities was observed across the various structural neuroimaging measures. In grey matter, patients with schizoaffective disorder showed abnormalities in the frontal and temporal lobes, striatum, fusiform, cuneus, precuneus, lingual and limbic regions. White-matter abnormalities were identified in tracts connecting these areas, including the corpus callosum, superior and inferior longitudinal fasciculi, anterior thalamic radiation, uncinate fasciculus and cingulum bundle. Conclusion: The spatial overlap of abnormalities across the different imaging techniques suggests widespread and consistent brain pathology in schizoaffective disorder. The abnormalities were mainly detected in areas that have commonly been reported to be abnormal in schizophrenia, and to some extent in bipolar disorder, which may explain the clinical and aetiological overlap in these disorders.

Ng et al.1 reported that Neuropsychiatric Inventory (NPI) scores predict hypometabolism in the posterior cingulate cortex (PCC) in preclinical Alzheimer disease (AD) with PCC hypermetabolism at baseline preceding hypometabolism 2 years later. Early and progressive hypometabolism/atrophy of the PCC in AD is a well-established finding,2,3 but early hypermetabolism is more difficult to reconcile with current network-based models of neurodegeneration. Whether it is suitable to classify groups according to average metabolic changes in the same regions that emerge in subsequent analyses (e.g., orbitofrontal, PCC) is unclear.

Abnormal eating behaviour and metabolic parameters including insulin resistance dyslipidaemia and body mass index are increasingly recognized as important components of neurodegenerative disease and may contribute to survival. It has previously been established that behavioural variant frontotemporal dementia is associated with abnormal eating behaviour characterized by increased sweet preference. In this study it was hypothesized that behavioural variant frontotemporal dementia might also be associated with altered energy expenditure. A cohort of 19 patients with behavioural variant frontotemporal dementia 13 with Alzheimer{\textquoteright}s disease and 16 (age and sex matched) healthy control subjects were studied using Actiheart devices (CamNtech) to assess resting and stressed heart rate. Actiheart devices were fitted for 7 days to measure sleeping heart rate activity levels and resting active and total energy expenditure. Using high resolution structural magnetic resonance imaging the neural correlates of increased resting heart rate were investigated including cortical thickness and region of interest analyses. In behavioural variant frontotemporal dementia resting (P = 0.001) stressed (P = 0.037) and sleeping heart rate (P = 0.038) were increased compared to control subjects and resting heart rate (P = 0.020) compared to Alzheimer disease patients. Behavioural variant frontotemporal dementia was associated with decreased activity levels compared to controls (P = 0.002) and increased resting energy expenditure (P = 0.045) and total energy expenditure (P = 0.035). Increased resting heart rate correlated with behavioural (Cambridge Behavioural Inventory) and cognitive measures (Addenbrooke{\textquoteright}s Cognitive Examination). Increased resting heart rate in behavioural variant frontotemporal dementia correlated with atrophy involving the mesial temporal cortex insula and amygdala regions previously suggested to be involved exclusively in social and emotion processing in frontotemporal dementia. These neural correlates overlap the network involved in eating behaviour in frontotemporal dementia suggesting a complex interaction between eating behaviour autonomic function and energy homeostasis. As such the present study suggests that increased heart rate and autonomic changes are prevalent in behavioural variant frontotemporal dementia and are associated with changes in energy expenditure. An understanding of these changes and neural correlates may have potential relevance to disease progression and prognosis.AbbreviationsALSamyotrophic lateral sclerosisBMIbody mass indexbvFTDbehavioural variant frontotemporal dementiaFTDfrontotemporal dementiaRMSSDroot mean squared of successive differences