Publications by authors named "Jack Foucher"

29 Publications

  • Page 1 of 1

Movement disorder and sensorimotor abnormalities in schizophrenia and other psychoses - European consensus on assessment and perspectives.

Eur Neuropsychopharmacol 2020 09 23;38:25-39. Epub 2020 Jul 23.

Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. Electronic address:

Over the last three decades, movement disorder as well as sensorimotor and psychomotor functioning in schizophrenia (SZ) and other psychoses has gained greater scientific and clinical relevance as an intrinsic component of the disease process of psychotic illness; this extends to early psychosis prediction, early detection of motor side effects of antipsychotic medication, clinical outcome monitoring, treatment of psychomotor syndromes (e.g. catatonia), and identification of new targets for non-invasive brain stimulation. In 2017, a systematic cooperation between working groups interested in movement disorder and sensorimotor/psychomotor functioning in psychoses was initiated across European universities. As a first step, the members of this group would like to introduce and define the theoretical aspects of the sensorimotor domain in SZ and other psychoses. This consensus paper is based on a synthesis of scientific evidence, good clinical practice and expert opinions that were discussed during recent conferences hosted by national and international psychiatric associations. While reviewing and discussing the recent theoretical and experimental work on neural mechanisms and clinical implications of sensorimotor behavior, we here seek to define the key principles and elements of research on movement disorder and sensorimotor/psychomotor functioning in psychotic illness. Finally, the members of this European group anticipate that this consensus paper will stimulate further multimodal and prospective studies on hypo- and hyperkinetic movement disorders and sensorimotor/psychomotor functioning in SZ and other psychotic disorders.
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http://dx.doi.org/10.1016/j.euroneuro.2020.07.003DOI Listing
September 2020

Wernicke-Kleist-Leonhard phenotypes 
of endogenous psychoses: a review of their validity
.

Dialogues Clin Neurosci 2020 03;22(1):37-49

IKlinik für Psychiatrie and Psychotherapie, Städtisches Klinikum Dresden, Dresden, Germany.

While the ICD-DSM paradigm has been a major advance in clinical psychiatry, its usefulness for biological psychiatry is debated. By defining consensus-based disorders rather than empirically driven phenotypes, consensus classifications were not an implementation of the biomedical paradigm. In the field of endogenous psychoses, the Wernicke-Kleist-Leonhard (WKL) pathway has optimized the descriptions of 35 major phenotypes using common medical heuristics on lifelong diachronic observations. Regarding their construct validity, WKL phenotypes have good reliability and predictive and face validity. WKL phenotypes come with remarkable evidence for differential validity on age of onset, familiality, pregnancy complications, precipitating factors, and treatment response. Most impressive is the replicated separation of high- and low-familiality phenotypes. Created in the purest tradition of the biomedical paradigm, the WKL phenotypes deserve to be contrasted as credible alternatives with other approaches currently under discussion.
.
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http://dx.doi.org/10.31887/DCNS.2020.22.1/jfoucherDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365293PMC
March 2020

A Brain Imaging-Based Diagnostic Biomarker for Periodic Catatonia: Preliminary Evidence Using a Bayesian Approach.

Neuropsychobiology 2020 10;79(4-5):352-365. Epub 2019 Sep 10.

Pôle de Psychiatrie, Santé Mentale et Addictologie, University Hospital Strasbourg, Strasbourg, France.

Periodic catatonia (PC) is a psychomotor phenotype with a progressive-remitting course. While it can fit any disorder diagnosis of the schizoaffective spectrum, its core features consist of a mix of hypo- and hyperkinesias resulting in distortions of expressive movements such as grimacing and parakinesias. The replication of cerebral blood flow (CBF) increases in the left supplementary motor area (L-SMA) and lateral premotor cortex (L-LPM) in acute and remitting PC patients indicates that these increases could be used as diagnostic biomarkers. In this proof-of-concept study, 2 different MRI sequences were repeated on 3 separate days to get reliable measurement values of CBF in 9 PC and 26 non-PC patients during different cognitive tasks. Each patient was compared to 37 controls. In L-SMA [-9; +10; +60] and L-LPM [-46; -12; +43], a test was positive if the t value was >2.02 (α < 0.05; two tailed). The measurements had good analytical performance. Regarding the tests, their sensitivities and specificities were significantly different from the chance level on both measures, except for L-SMA sensitivities. When combining all the tests, among regions and methods, sensitivity was 98% (95% credible interval [CI] 76-100%) and specificity 88% (72-97%). Bayesian inferences of its negative predictive values for PC were >95% regardless of the context, while its positive predictive values reached 94% but only when used in combination with clinical criteria. The case-by-case analysis suggests that non-PC patients with neurological motor deficits are at risk to be false positive.
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http://dx.doi.org/10.1159/000501830DOI Listing
September 2019

A Brain Imaging-Based Diagnostic Biomarker for Periodic Catatonia: Preliminary Evidence Using a Bayesian Approach.

Neuropsychobiology 2020 10;79(4-5):352-365. Epub 2019 Sep 10.

Pôle de Psychiatrie, Santé Mentale et Addictologie, University Hospital Strasbourg, Strasbourg, France.

Periodic catatonia (PC) is a psychomotor phenotype with a progressive-remitting course. While it can fit any disorder diagnosis of the schizoaffective spectrum, its core features consist of a mix of hypo- and hyperkinesias resulting in distortions of expressive movements such as grimacing and parakinesias. The replication of cerebral blood flow (CBF) increases in the left supplementary motor area (L-SMA) and lateral premotor cortex (L-LPM) in acute and remitting PC patients indicates that these increases could be used as diagnostic biomarkers. In this proof-of-concept study, 2 different MRI sequences were repeated on 3 separate days to get reliable measurement values of CBF in 9 PC and 26 non-PC patients during different cognitive tasks. Each patient was compared to 37 controls. In L-SMA [-9; +10; +60] and L-LPM [-46; -12; +43], a test was positive if the t value was >2.02 (α < 0.05; two tailed). The measurements had good analytical performance. Regarding the tests, their sensitivities and specificities were significantly different from the chance level on both measures, except for L-SMA sensitivities. When combining all the tests, among regions and methods, sensitivity was 98% (95% credible interval [CI] 76-100%) and specificity 88% (72-97%). Bayesian inferences of its negative predictive values for PC were >95% regardless of the context, while its positive predictive values reached 94% but only when used in combination with clinical criteria. The case-by-case analysis suggests that non-PC patients with neurological motor deficits are at risk to be false positive.
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http://dx.doi.org/10.1159/000501830DOI Listing
September 2019

Multi-parametric quantitative MRI reveals three different white matter subtypes.

PLoS One 2018 15;13(6):e0196297. Epub 2018 Jun 15.

Laboratoire des Sciences de l'Ingénieur, de l'Informatique et de l'Imagerie (ICube), CNRS UMR 7357, University of Strasbourg, Strasbourg, France.

Introduction: Magnetic resonance imaging (MRI) shows slight spatial variations in brain white matter (WM). We used quantitative multi-parametric MRI to evaluate in what respect these inhomogeneities could correspond to WM subtypes with specific characteristics and spatial distribution.

Materials And Methods: Twenty-six controls (12 women, 38 ±9 Y) took part in a 60-min session on a 3T scanner measuring 7 parameters: R1 and R2, diffusion tensor imaging which allowed to measure Axial and Radial Diffusivity (AD, RD), magnetization transfer imaging which enabled to compute the Macromolecular Proton Fraction (MPF), and a susceptibility-weighted sequence which permitted to quantify R2* and magnetic susceptibility (χm). Spatial independent component analysis was used to identify WM subtypes with specific combination of quantitative parameters values.

Results: Three subtypes could be identified. t-WM (track) mostly mapped on well-formed projection and commissural tracts and came with high AD values (all p < 10(-18)). The two other subtypes were located in subcortical WM and overlapped with association fibers: f-WM (frontal) was mostly anterior in the frontal lobe whereas c-WM (central) was underneath the central cortex. f-WM and c-WM had higher MPF values, indicating a higher myelin content (all p < 1.7 10(-6)). This was compatible with their larger χm and R2, as iron is essentially stored in oligodendrocytes (all p < 0.01). Although R1 essentially showed the same, its higher value in t-WM relative to c-WM might be related to its higher cholesterol concentration.

Conclusions: Thus, f- and c-WMs were less structured, but more myelinated and probably more metabolically active regarding to their iron content than WM related to fasciculi (t-WM). As known WM bundles passed though different WM subtypes, myelination might not be uniform along the axons but rather follow a spatially consistent regional variability. Future studies might examine the reproducibility of this decomposition and how development and pathology differently affect each subtype.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0196297PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6003690PMC
November 2018

A double dissociation between two psychotic phenotypes: Periodic catatonia and cataphasia.

Prog Neuropsychopharmacol Biol Psychiatry 2018 08 17;86:363-369. Epub 2018 Mar 17.

Physiopathologie et Psychopathologie Cognitive de la Schizophrénie - INSERM 1114, FMTS, University of Strasbourg, France; Pôle de Psychiatrie, Santé Mentale et Addictologie, University Hospital Strasbourg, France.

Schizophrenia as a single liability model was confronted to the multiple psychotic phenotypes model proposed by the Wernicke-Kleist-Leonhard school, focusing on two: periodic catatonia (PC) and cataphasia (C). Both are stable and heritable psychotic phenotypes with no crossed liability and are coming with the buildup of specific residual symptoms: impairment of psychomotricity for PC and a specific disorganization of thought and language in C. Regional cerebral blood flow (rCBF) was used as a biomarker. We attempted to refute the single phenotype model by looking at relevant and specific rCBF anomalies for PC and C, that would exceed anomalies in common relative to controls (CTR), i.e. looking for a double dissociation. Twenty subjects with PC, 9 subjects with C and 27 matched controls had two MRI QUIPSS-II arterial spin labeling sequences converted in rCBF. One SPM analysis was performed for each rCBF measurement and the results were given as the conjunction of both analysis. There was a clear double dissociation of rCBF correlates between PC and C, both being meaningful relative to their residual symptomatology. In PC: rCBF was increased in the left motor and premotor areas. In C: rCBF was decreased bilaterally in the temporo-parietal junctions. Conversely, in both (schizophrenia): rCBF was increased in the left striatum which is known to be an anti-psychotics' effect. This evidence refuts the single schizophrenia model and suggests better natural foundations for PC and C phenotypes. This pleads for further research on them and further research on naturally founded psychotic phenotypes.

Clinical Trial: Name of the registry: ClinicalTrials.gov Identification: NCT02868879.
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http://dx.doi.org/10.1016/j.pnpbp.2018.03.008DOI Listing
August 2018

fMRI capture of auditory hallucinations: Validation of the two-steps method.

Hum Brain Mapp 2017 10 28;38(10):4966-4979. Epub 2017 Jun 28.

Univ Lille, CNRS, UMR 9193 - SCALab - Sciences Cognitives et Sciences Affectives, Lille, F-59000, France.

Our purpose was to validate a reliable method to capture brain activity concomitant with hallucinatory events, which constitute frequent and disabling experiences in schizophrenia. Capturing hallucinations using functional magnetic resonance imaging (fMRI) remains very challenging. We previously developed a method based on a two-steps strategy including (1) multivariate data-driven analysis of per-hallucinatory fMRI recording and (2) selection of the components of interest based on a post-fMRI interview. However, two tests still need to be conducted to rule out critical pitfalls of conventional fMRI capture methods before this two-steps strategy can be adopted in hallucination research: replication of these findings on an independent sample and assessment of the reliability of the hallucination-related patterns at the subject level. To do so, we recruited a sample of 45 schizophrenia patients suffering from frequent hallucinations, 20 schizophrenia patients without hallucinations and 20 matched healthy volunteers; all participants underwent four different experiments. The main findings are (1) high accuracy in reporting unexpected sensory stimuli in an MRI setting; (2) good detection concordance between hypothesis-driven and data-driven analysis methods (as used in the two-steps strategy) when controlled unexpected sensory stimuli are presented; (3) good agreement of the two-steps method with the online button-press approach to capture hallucinatory events; (4) high spatial consistency of hallucinatory-related networks detected using the two-steps method on two independent samples. By validating the two-steps method, we advance toward the possible transfer of such technology to new image-based therapies for hallucinations. Hum Brain Mapp 38:4966-4979, 2017. © 2017 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/hbm.23707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6866805PMC
October 2017

Identifying Dynamic Functional Connectivity Changes in Dementia with Lewy Bodies Based on Product Hidden Markov Models.

Front Comput Neurosci 2016 23;10:60. Epub 2016 Jun 23.

Centre National de la Recherche Scientifique, FMTS, University of Strasbourg, ICube-UMR 7357Strasbourg, France; CMRR (Memory Resources and Research Center), University Hospital of Strasbourg, Geriatrics and Neurology ServicesStrasbourg, France.

Exploring time-varying connectivity networks in neurodegenerative disorders is a recent field of research in functional MRI. Dementia with Lewy bodies (DLB) represents 20% of the neurodegenerative forms of dementia. Fluctuations of cognition and vigilance are the key symptoms of DLB. To date, no dynamic functional connectivity (DFC) investigations of this disorder have been performed. In this paper, we refer to the concept of connectivity state as a piecewise stationary configuration of functional connectivity between brain networks. From this concept, we propose a new method for group-level as well as for subject-level studies to compare and characterize connectivity state changes between a set of resting-state networks (RSNs). Dynamic Bayesian networks, statistical and graph theory-based models, enable one to learn dependencies between interacting state-based processes. Product hidden Markov models (PHMM), an instance of dynamic Bayesian networks, are introduced here to capture both statistical and temporal aspects of DFC of a set of RSNs. This analysis was based on sliding-window cross-correlations between seven RSNs extracted from a group independent component analysis performed on 20 healthy elderly subjects and 16 patients with DLB. Statistical models of DFC differed in patients compared to healthy subjects for the occipito-parieto-frontal network, the medial occipital network and the right fronto-parietal network. In addition, pairwise comparisons of DFC of RSNs revealed a decrease of dependency between these two visual networks (occipito-parieto-frontal and medial occipital networks) and the right fronto-parietal control network. The analysis of DFC state changes thus pointed out networks related to the cognitive functions that are known to be impaired in DLB: visual processing as well as attentional and executive functions. Besides this context, product HMM applied to RSNs cross-correlations offers a promising new approach to investigate structural and temporal aspects of brain DFC.
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http://dx.doi.org/10.3389/fncom.2016.00060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4918689PMC
July 2016

Resting-state networks distinguish locked-in from vegetative state patients.

Neuroimage Clin 2016 6;12:16-22. Epub 2016 Jun 6.

ICube, UMR 7357, UdS, CNRS, Fédération de médecine translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France; Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS), France; Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

Purpose: Locked-in syndrome and vegetative state are distinct outcomes from coma. Despite their differences, they are clinically difficult to distinguish at the early stage and current diagnostic tools remain insufficient. Since some brain functions are preserved in locked-in syndrome, we postulated that networks of spontaneously co-activated brain areas might be present in locked-in patients, similar to healthy controls, but not in patients in a vegetative state.

Methods: Five patients with locked-in syndrome, 12 patients in a vegetative state and 19 healthy controls underwent a resting-state fMRI scan. Individual spatial independent component analysis was used to separate spontaneous brain co-activations from noise. These co-activity maps were selected and then classified by two raters as either one of eight resting-state networks commonly shared across subjects or as specific to a subject.

Results: The numbers of spontaneous co-activity maps, total resting-state networks, and resting-state networks underlying high-level cognitive activity were shown to differentiate controls and locked-in patients from patients in a vegetative state. Analyses of each common resting-state network revealed that the default mode network accurately distinguished locked-in from vegetative-state patients. The frontoparietal network also had maximum specificity but more limited sensitivity.

Conclusions: This study reinforces previous reports on the preservation of the default mode network in locked-in syndrome in contrast to vegetative state but extends them by suggesting that other networks might be relevant to the diagnosis of locked-in syndrome. The aforementioned analysis of fMRI brain activity at rest might be a step in the development of a diagnostic biomarker to distinguish locked-in syndrome from vegetative state.
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http://dx.doi.org/10.1016/j.nicl.2016.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4913176PMC
November 2017

Melancholia Associated With Severe Cognitive Disorders as the Expression of Late-Onset Postpartum Anti-N-Methyl-d-Aspartic Acid Receptor Limbic Encephalitis.

J Neuropsychiatry Clin Neurosci 2015 ;27(2):e168-9

From the Dept. of Psychiatry, Hôpital Civil, University of Strasbourg, Strasbourg, France (LL, CJ, M-AZ, J-MD, JF); Depts. of Psychiatry (LL, J-MD) and Physiology (JF), Institut National de la Santé et de la Recherche Médicale 1114, Fédération de Médecine Translationnelle de Strasbourg, Hôpitaux Universitaires, Strasbourg, France; Dept. of Clinical Immunology, Nouvel Hôpital Civil, Hopitaux Universitaires de Strasbourg, Strasbourg, France (AG); and ICube, Unité Mixtes de Recherche Centre National de la Recherche Scientifique 7357, Fédération de Médecine Translationnelle de Strasbourg, Laboratoire des Sciences de l'ingénieur, de l'informatique et de l'imagerie, Illkirch, France (JF).

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http://dx.doi.org/10.1176/appi.neuropsych.14040079DOI Listing
January 2016

Right anterior insula: core region of hallucinations in cognitive neurodegenerative diseases.

PLoS One 2014 5;9(12):e114774. Epub 2014 Dec 5.

University of Strasbourg and CNRS, ICube laboratory UMR 7357, FMTS (Fédération de Médecine Translationnelle de Strasbourg), Strasbourg, France.

Objectives: We investigated the neural basis of hallucinations Alzheimer's disease (AD) by applying voxel-based morphometry (VBM) to anatomical and functional data from the AD Neuroimaging Initiative.

Methods: AD patients with hallucinations, based on the Neuropsychiatric Inventory (NPI-Q) (AD-hallu group; n = 39), were compared to AD patients without hallucinations matched for age, sex, educational level, handedness and MMSE (AD-c group; n = 39). Focal brain volume on MRI was analyzed and compared between the two groups according to the VBM method. We also performed voxel-level correlations between brain volume and hallucinations intensity. A similar paradigm was used for the PET analysis. "Core regions" (i.e. regions identified in both MRI and PET analyses, simply done by retaining the clusters obtained from the two analyses that are overlapping) were then determined.

Results: Regions with relative atrophy in association with hallucinations were: anterior part of the right insula, left superior frontal gyrus and lingual gyri. Regions with relative hypometabolism in association with hallucinations were a large right ventral and dorsolateral prefrontal area. "Core region" in association with hallucinations was the right anterior part of the insula. Correlations between intensity of hallucinations and brain volume were found in the right anterior insula, precentral gyrus, superior temporal gyrus, and left precuneus. Correlations between intensity of hallucinations and brain hypometabolism were found in the left midcingulate gyrus. We checked the neuropathological status and we found that the 4 patients autopsied in the AD-hallu group had the mixed pathology AD and Dementia with Lewy bodies (DLB).

Conclusion: Neural basis of hallucinations in cognitive neurodegenerative diseases (AD or AD and DLB) include a right predominant anterior-posterior network, and the anterior insula as the core region. This study is coherent with the top-down/bottom-up hypotheses on hallucinations but also hypotheses of the key involvement of the anterior insula in hallucinations in cognitive neurodegenerative diseases.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0114774PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4257732PMC
April 2016

Manual selection of spontaneous activity maps derived from independent component analysis: criteria and inter-rater reliability study.

J Neurosci Methods 2014 Feb 4;223:30-4. Epub 2013 Dec 4.

ICube, UMR 7357, University of Strasbourg, CNRS, Fédération de médecine translationnelle, Strasbourg, France; HUS, Hôpitaux Universitaires de Strasbourg, Strasbourg, France. Electronic address:

Background: During the last years, many investigations focused on spontaneously active cerebral networks such as the default-mode network. A data-driven technique, the independent component analysis, allows segregating such spontaneous (co-)activity maps (SAM) from noise in functional magnetic resonance imaging (fMRI) time series. The inter-rater reliability of manual selection of not only the default-mode network but all SAMs remained to be assessed.

New Method: The current study was performed on 20 min (400 volumes) fMRI time series of 30 healthy participants. SAMs' selection criteria were first established on past experience and from the literature. The inter-rater reliability of SAMs vs non-SAMs manual selection was then investigated from 250 independent components per participant.

Results: Inter-rater Kappa coefficient was of 0.89 ± 0.01 on whole analysis, and 0.88 ± 0.09 on participant per participant analysis.

Comparison With Existing Methods: Without focusing on specific and predetermined SAMs only, our criteria allow a reliable selection of all SAMs including the idiosyncratic networks.

Conclusions: The proposed SAM's selection criteria are reliable enough to allow scientific exploration of all SAMs at the single subject level.
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http://dx.doi.org/10.1016/j.jneumeth.2013.11.014DOI Listing
February 2014

Manual selection of spontaneous activity maps derived from independent component analysis: criteria and inter-rater reliability study.

J Neurosci Methods 2014 Feb 4;223:30-4. Epub 2013 Dec 4.

ICube, UMR 7357, University of Strasbourg, CNRS, Fédération de médecine translationnelle, Strasbourg, France; HUS, Hôpitaux Universitaires de Strasbourg, Strasbourg, France. Electronic address:

Background: During the last years, many investigations focused on spontaneously active cerebral networks such as the default-mode network. A data-driven technique, the independent component analysis, allows segregating such spontaneous (co-)activity maps (SAM) from noise in functional magnetic resonance imaging (fMRI) time series. The inter-rater reliability of manual selection of not only the default-mode network but all SAMs remained to be assessed.

New Method: The current study was performed on 20 min (400 volumes) fMRI time series of 30 healthy participants. SAMs' selection criteria were first established on past experience and from the literature. The inter-rater reliability of SAMs vs non-SAMs manual selection was then investigated from 250 independent components per participant.

Results: Inter-rater Kappa coefficient was of 0.89 ± 0.01 on whole analysis, and 0.88 ± 0.09 on participant per participant analysis.

Comparison With Existing Methods: Without focusing on specific and predetermined SAMs only, our criteria allow a reliable selection of all SAMs including the idiosyncratic networks.

Conclusions: The proposed SAM's selection criteria are reliable enough to allow scientific exploration of all SAMs at the single subject level.
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http://dx.doi.org/10.1016/j.jneumeth.2013.11.014DOI Listing
February 2014

Electroconvulsive therapy for psychosis in a patient with epilepsy related to hypothalamic hamartoma.

Epileptic Disord 2013 Sep;15(3):347-51

Neurology Department, University Hospital of Strasbourg and Medical School of Strasbourg, Institut des Neurosciences Cellulaires et Intégratives CNRS UPR 3212, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.

Psychosis is more common in people with temporal lobe epilepsy than it is in the general population. Treatment can be difficult in these patients because of the complex interactions between antipsychotic and antiepileptic drugs. Some antipsychotic drugs also decrease the seizure threshold. We report the case of a 49-year-old man with a hypothalamic hamartoma, with a history of both gelastic and temporal lobe seizures. The patient was rendered seizure-free after three neurosurgical procedures but developed a drug-resistant paranoid psychosis. He was treated with electroconvulsive therapy (ECT). After two weeks with six stimulations that resulted in seizures, the psychiatric phenomena disappeared completely. There was no relapse of either the psychiatric symptoms or the seizures during the 42 months of follow-up. This case report suggests that ECT might be safe for psychosis in patients with a history of seizures that have previously been successfully treated with neurosurgery, although caution should be exercised in drawing general conclusions from a single case report.
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http://dx.doi.org/10.1684/epd.2013.0589DOI Listing
September 2013

White matter atrophy and cognitive dysfunctions in neuromyelitis optica.

PLoS One 2012 3;7(4):e33878. Epub 2012 Apr 3.

Neuropsychology Service, Department of Neurology, University Hospital of Strasbourg, Strasbourg, France.

Neuromyelitis optica (NMO) is an inflammatory disease of central nervous system characterized by optic neuritis and longitudinally extensive acute transverse myelitis. NMO patients have cognitive dysfunctions but other clinical symptoms of brain origin are rare. In the present study, we aimed to investigate cognitive functions and brain volume in NMO. The study population consisted of 28 patients with NMO and 28 healthy control subjects matched for age, sex and educational level. We applied a French translation of the Brief Repeatable Battery (BRB-N) to the NMO patients. Using SIENAx for global brain volume (Grey Matter, GM; White Matter, WM; and whole brain) and VBM for focal brain volume (GM and WM), NMO patients and controls were compared. Voxel-level correlations between diminished brain concentration and cognitive performance for each tests were performed. Focal and global brain volume of NMO patients with and without cognitive impairment were also compared. Fifteen NMO patients (54%) had cognitive impairment with memory, executive function, attention and speed of information processing deficits. Global and focal brain atrophy of WM but not Grey Matter (GM) was found in the NMO patients group. The focal WM atrophy included the optic chiasm, pons, cerebellum, the corpus callosum and parts of the frontal, temporal and parietal lobes, including superior longitudinal fascicle. Visual memory, verbal memory, speed of information processing, short-term memory and executive functions were correlated to focal WM volumes. The comparison of patients with, to patients without cognitive impairment showed a clear decrease of global and focal WM, including brainstem, corticospinal tracts, corpus callosum but also superior and inferior longitudinal fascicles. Cognitive impairment in NMO patients is correlated to the decreased of global and focal WM volume of the brain. Further studies are needed to better understand the precise origin of cognitive impairment in NMO patients, particularly in the WM.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0033878PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3317931PMC
August 2012

Design and evaluation of a robotic system for transcranial magnetic stimulation.

IEEE Trans Biomed Eng 2012 Mar 15;59(3):805-15. Epub 2011 Dec 15.

Laboratoire des Sciences de l’Image, de l’Informatique et de la Télédétection, CNRS, University of Strasbourg, Strasbourg, France.

Transcranial magnetic stimulation is a noninvasive brain stimulation technique. It is based on current induction in the brain with a stimulation coil emitting a strong varying magnetic field. Its development is currently limited by the lack of accuracy and repeatability of manual coil positioning. A dedicated robotic system is proposed in this paper. Contrary to previous approaches in the field, a custom design is introduced to maximize the safety of the subject. Furthermore, the control of the force applied by the coil on the subject's head is implemented. The architecture is original and its experimental evaluation demonstrates its interest: the compensation of the head motion is combined with the force control to ensure accuracy and safety during the stimulation.
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http://dx.doi.org/10.1109/TBME.2011.2179938DOI Listing
March 2012

fMRI working memory hypo-activations in schizophrenia come with a coupling deficit between arousal and cognition.

Psychiatry Res 2011 Oct 24;194(1):21-9. Epub 2011 Aug 24.

Université de Strasbourg, Strasbourg, France.

Cognition has become a target for therapeutic intervention and favoring arousal could be a way to help patients. Working memory is an arousal dependent cognitive function. This study used functional MRI (fMRI) as a surrogate marker of working memory to evaluate the sensitivity of patients' hypoactive regions to arousal in a subpopulation of rehabilitated patients. Are hypoactive regions sensitive to arousal? Does the deficit result from arousal deficit or improper coupling with cognitive activity? Eighteen patients and matched controls were recruited. Participants performed a working memory task during combined electroencephalographic (EEG) and fMRI measurements. Cortical regions sensitive to arousal were defined as those which were inversely correlated with low EEG frequencies. Overlap between the arousal-sensitive and hypoactive regions was assessed by mutual information. Arousal-cognitive coupling was evaluated by the correlation between the arousal effect and the task effect. In the patient group, most hypoactive voxels were sensitive to arousal and corresponded to the prefronto-parietal network. But patients had no arousal deficit. Although arousal seems to improve cognitive activity in most of the patients' cortical areas, this coupling appears to be specifically disturbed in their hypoactive regions. In conclusion, although increasing arousal may help cognition, it may do so in an unspecific way.
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http://dx.doi.org/10.1016/j.pscychresns.2011.06.004DOI Listing
October 2011

Correcting for the echo-time effect after measuring the cerebral blood flow by arterial spin labeling.

J Magn Reson Imaging 2011 Oct 18;34(4):785-90. Epub 2011 Jul 18.

UdS, Université de Strasbourg, Strasbourg, France; INSERM U666-Physiopathologie et Psychopathologie Cognitive de la Schizophrénie, Strasbourg, France.

Purpose: To take into account the echo time (TE) influence on arterial spin labeling (ASL) signal when converting it in regional cerebral blood flow (rCBF). Gray matter ASL signal decrease with increasing TE as a consequence of the difference in the apparent transverse relaxation rates between labeled water in capillaries and nonlabeled water in the tissue (δR 2*). We aimed to measure ASL/rCBF changes in different parts of the brain and correct them.

Materials And Methods: Fifteen participants underwent ASL measurements at TEs of 9.7-30 ms. Decreases in ASL values were localized by statistical parametric mapping. The corrections assessed were a subject-per-subject adjustment, an average δR 2* value adjustment, and a two-compartment model adjustment.

Results: rCBF decreases associated with increasing TEs were found for gray matter and were corrected using an average δR 2* value of 20 s(-1) . Conversely, for white matter, rCBF values increased with increasing TEs (δR 2* = -23 s(-1)).

Conclusion: Our correction was as good as using a two-compartment model. However, it must be done separately for the gray and white matter rCBF values because the capillary R 2* values are, respectively, larger and smaller than those of surrounding tissues.
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http://dx.doi.org/10.1002/jmri.22678DOI Listing
October 2011

Gray matter volume decreases in elderly patients with schizophrenia: a voxel-based morphometry study.

Schizophr Bull 2012 Jun 4;38(4):796-802. Epub 2011 Jan 4.

INSERM U666--Physiopathologie et psychopathologie cognitive de la Schizophrénie, Strasbourg, France.

Background: Aged patients (>50 years old) with residual schizophrenic symptoms differ from young patients. They represent a subpopulation with a more unfavorable Kraepelinian course and have an increased risk (up to 30%) for dementia of unknown origin. However, our current understanding of age-related brain changes in schizophrenia is derived from studies that included less than 17% of patients who were older than 50 years of age. This study investigated the anatomical distribution of gray matter (GM) brain deficits in aged patients with ongoing schizophrenia.

Methods: Voxel-based morphometry was applied to 3D-T1 magnetic resonance images obtained from 27 aged patients with schizophrenia (mean age of 60 years) and 40 age-matched normal controls.

Results: Older patients with schizophrenia showed a bilateral reduction of GM volume in the thalamus, the prefrontal cortex, and in a large posterior region centered on the occipito-temporo-parietal junction. Only the latter region showed accelerated GM volume loss with increasing age. None of these results could be accounted for by institutionalization, antipsychotic medication, or cognitive scores.

Conclusions: This study replicated most common findings in patients with schizophrenia with regard to thalamic and frontal GM deficits. However, it uncovered an unexpected large region of GM atrophy in the posterior tertiary cortices. The latter observation may be specific to this aged and chronically symptomatic subpopulation, as atrophy in this region is rarely reported in younger patients and is accelerated with age.
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http://dx.doi.org/10.1093/schbul/sbq150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3406517PMC
June 2012

A multi-level parcellation approach for brain functional connectivity analysis.

Annu Int Conf IEEE Eng Med Biol Soc 2009 ;2009:3497-500

LSIIT/MIV (UMR 7005), CNRS, Université de Strasbourg.

Most brain functional connectivity methods in fMRI require a brain parcellation into functionally homogeneous regions. In this work we propose a novel parcellation approach based on a spatial hierarchical clustering, that provides clusters within a multi-level framework. The method has the advantage of producing several brain parcellations rather than a single one from a fixed size-homogeneity criterion. Results obtained on real data demonstrate the relevance of the approach. Finally, a connectivity study shows the benefit of a prior multi-level parcellation of the brain.
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http://dx.doi.org/10.1109/IEMBS.2009.5334578DOI Listing
April 2010

The right parahippocampal gyrus contributes to the formation and maintenance of bound information in working memory.

Brain Cogn 2010 Mar 17;72(2):255-63. Epub 2009 Oct 17.

Physiopathologie Clinique et Expérimentale de la Schizophrénie, INSERM U666, Strasbourg, France.

Working memory is devoted to the temporary storage and on-line manipulation of information. Recently, an integrative system termed the episodic buffer has been proposed to integrate and hold information being entered or retrieved from episodic memory. Although the brain system supporting such an integrative buffer is still in debate, the medial temporal lobe appears to be a promising candidate for the maintenance of bound information. In the current work, binding was assessed by comparing two conditions in which participants had to retain three letters and three spatial locations presented either bound or separate. At the behavioral level, lower performance was found for bound information than for separate information. When contrasting the two conditions, activation in the right parahippocampal gyrus was greater for the encoding and maintenance of bound information. No activation was observed in the medial temporal lobe during the retrieval of bound information. Together, our results suggest that the parahippocampal gyrus may underlie the integrative and maintenance functions of the episodic buffer.
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http://dx.doi.org/10.1016/j.bandc.2009.09.009DOI Listing
March 2010

Abnormal medial temporal activity for bound information during working memory maintenance in patients with schizophrenia.

Hippocampus 2010 Aug;20(8):936-48

Physiopathologie Clinique et Expérimentale de la Schizophrénie, INSERM U666, Strasbourg, France.

Alterations of binding in long-term memory in schizophrenia are well established and occur as a result of aberrant activity in the medial temporal lobe (MTL). In working memory (WM), such a deficit is less clear and the pathophysiological bases remain unstudied. Seventeen patients with schizophrenia and 17 matched healthy controls performed a WM binding task while undergoing functional magnetic resonance imaging. Binding was assessed by contrasting two conditions comprising an equal amount of verbal and spatial information (i.e., three letters and three spatial locations), but differing in the absence or presence of a link between them. In healthy controls, MTL activation was observed for encoding and maintenance of bound information but not for its retrieval. Between-group comparisons revealed that patients with schizophrenia showed MTL hypoactivation during the maintenance phase only. In addition, BOLD signals correlated with behavioral performance in controls but not in patients with schizophrenia. Our results confirm the major role that the MTL plays in the pathophysiology of schizophrenia. Short-term and long-term relational memory deficits in schizophrenia may share common cognitive and functional pathological bases. Our results provide additional information about the episodic buffer that represents an integrative interface between WM and long-term memory.
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http://dx.doi.org/10.1002/hipo.20689DOI Listing
August 2010

Extended visual simultaneity thresholds in patients with schizophrenia.

Schizophr Bull 2009 Jul 21;35(4):816-25. Epub 2008 Mar 21.

INSERM U666, Centre Hospitalier Régional de Strasbourg, Pôle de Psychiatrie, BP 406, 67091 Strasbourg Cedex, France.

Clinical observations suggest that the experience of time phenomenology is disturbed in schizophrenia, possibly originating disorders in dynamic cognitive functions such as language or motor planning. We examined the subjective evaluation of temporal structure using an experimental approach involving judgments of simultaneity of simple, visually presented stimuli. We included a priming procedure, ie, a subthreshold presentation of simultaneous or asynchronous stimuli. This allowed us to evaluate the effects of subthreshold synchrony and to check for bias effects, ie, changes in the criteria used by the subjects to rate the stimuli. Primes were adapted to the responses of the subjects. Bias effects were thus expected to yield a change in the efficiency of the prime and to induce a change in the amplitude of the priming effect. Nineteen outpatients with schizophrenia and their individually matched controls participated in the study. In all tests, patients required longer delays between stimuli to detect that they were asynchronous. In other words, they judged stimuli to be synchronous even when their onset was separated by delays of 100 milliseconds and even more in some cases. These results contrasted with preserved effects of subthreshold synchrony. Our findings argue against the hypothesis that the patients' responses were influenced by biases. We conclude that the subjective evaluation of simultaneity/asynchrony is impaired in schizophrenia, thus leading to impairment in the phenomenology of event-structure coding. The method used in the present study provides a novel approach to the assessment of those disturbances related to time in patients with schizophrenia.
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http://dx.doi.org/10.1093/schbul/sbn016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2696372PMC
July 2009

Assessment of single and bound features in a working memory task in schizophrenia.

Schizophr Res 2008 Mar 21;100(1-3):153-60. Epub 2008 Feb 21.

INSERM U. 666, Physiopathologie clinique et expérimentale de la schizophrénie, Département de Psychiatrie, Hôpital Civil, 67091 Strasbourg Cedex, France.

If disturbance of binding in long term memory is well established in schizophrenia, data concerning working memory maintenance are less clear. Feature binding in working memory was investigated in 19 patients with schizophrenia and 19 healthy controls. Binding was assessed by comparing two conditions in which participants had to retain four letters and four spatial locations. These features were presented either bound or separate. Results showed that both groups had better performances for bound than separate features, despite the fact that patients performed significantly worse than controls. When maintenance for isolated features was assessed, patients were severely disturbed for spatial locations but not for letters. Such a result suggests that reduced working memory performance in patients with schizophrenia for bound features is probably a consequence of a spatial deficit rather than a specific deficit of the binding process. Thus, not all form of binding are disturbed in schizophrenia.
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http://dx.doi.org/10.1016/j.schres.2007.11.004DOI Listing
March 2008

Psychosis related to neurological conditions: pro and cons of the dis- / mis-connectivity models of schizophrenia.

Dialogues Clin Neurosci 2006 ;8(1):17-27

Clinique Psychiatrique - INSERM U666, Hôpitaux Universitaires, BP 406 - 67091 Strasbourg, France.

Schizophrenia is still a condition with obscure causes and psychopathology. This paper aims to discuss the "disconnectivity" hypothesis in relation to some neurological conditions which are known to alter brain connectivity, as well as mimicking some aspects of the disorder. After a short historical introduction to the concept, we will examine the evidence for connectivity problems in schizophrenia, separating the anatomical level from the functional level. Then, we will discuss three different issues concerning connectivity: i) local reduction in connectivity without neuronal loss (within the gray matter); ii) reduction in or alteration of long-range connectivity (within the white matter); and iii) abnormal targets for connections. For each of these aspects, we will look at the conditions able to reproduce anomalies capable of increasing susceptibility to schizophrenia. We conclude that psychosis is more likely to occur: i) when long-range connectivity is concerned; ii) when lesions result in lengthening and scattering of conduction times; and iii) when there are high dopamine levels, shedding light on or adding weight to the idea of an interaction between dopamine and connectivity.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181754PMC
June 2006

Hidden Markov event sequence models: toward unsupervised functional MRI brain mapping.

Acad Radiol 2005 Jan;12(1):25-36

Université Louis Pasteur, Strasbourg, France.

Rationale And Objectives: Most methods used in functional MRI (fMRI) brain mapping require restrictive assumptions about the shape and timing of the fMRI signal in activated voxels. Consequently, fMRI data may be partially and misleadingly characterized, leading to suboptimal or invalid inference. To limit these assumptions and to capture the broad range of possible activation patterns, a novel statistical fMRI brain mapping method is proposed. It relies on hidden semi-Markov event sequence models (HSMESMs), a special class of hidden Markov models (HMMs) dedicated to the modeling and analysis of event-based random processes.

Materials And Methods: Activation detection is formulated in terms of time coupling between (1) the observed sequence of hemodynamic response onset (HRO) events detected in the voxel's fMRI signal and (2) the "hidden" sequence of task-induced neural activation onset (NAO) events underlying the HROs. Both event sequences are modeled within a single HSMESM. The resulting brain activation model is trained to automatically detect neural activity embedded in the input fMRI data set under analysis. The data sets considered in this article are threefold: synthetic epoch-related, real epoch-related (auditory lexical processing task), and real event-related (oddball detection task) fMRI data sets.

Results: Synthetic data: Activation detection results demonstrate the superiority of the HSMESM mapping method with respect to a standard implementation of the statistical parametric mapping (SPM) approach. They are also very close, sometimes equivalent, to those obtained with an "ideal" implementation of SPM in which the activation patterns synthesized are reused for analysis. The HSMESM method appears clearly insensitive to timing variations of the hemodynamic response and exhibits low sensitivity to fluctuations of its shape (unsustained activation during task). Real epoch-related data: HSMESM activation detection results compete with those obtained with SPM, without requiring any prior definition of the expected activation patterns thanks to the unsupervised character of the HSMESM mapping approach. Along with activation maps, the method offers a wide range of additional fMRI analysis functionalities, including activation lag mapping, activation mode visualization, and hemodynamic response function analysis. Real event-related data: Activation detection results confirm and validate the overall strategy that consists in focusing the analysis on the transients, time-localized events that are the HROs.

Conclusion: All the experiments performed on synthetic and real fMRI data demonstrate the relevance of HSMESMs in fMRI brain mapping. In particular, the statistical character of these models, along with their learning and generalizing abilities are of particular interest when dealing with strong variabilities of the active fMRI signal across time, space, experiments, and subjects.
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http://dx.doi.org/10.1016/j.acra.2004.09.012DOI Listing
January 2005

The BOLD response and the gamma oscillations respond differently than evoked potentials: an interleaved EEG-fMRI study.

BMC Neurosci 2003 Sep 19;4:22. Epub 2003 Sep 19.

Clinique Psychiatrique-INSERM U405, Hôpitaux Universitaires-BP 406-67091 Strasbourg Cedex-France.

Background: The integration of EEG and fMRI is attractive because of their complementary precision regarding time and space. But the relationship between the indirect hemodynamic fMRI signal and the more direct EEG signal is uncertain. Event-related EEG responses can be analyzed in two different ways, reflecting two different kinds of brain activity: evoked, i.e. phase-locked to the stimulus, such as evoked potentials, or induced, i.e. non phase-locked to the stimulus such as event-related oscillations. In order to determine which kind of EEG activity was more closely related with fMRI, EEG and fMRI signals were acquired together, while subjects were presented with two kinds of rare events intermingled with frequent distractors. Target events had to be signaled by pressing a button and Novel events had to be ignored.

Results: Both Targets and Novels triggered a P300, of larger amplitude in the Novel condition. On the opposite, the fMRI BOLD response was stronger in the Target condition. EEG event-related oscillations in the gamma band (32-38 Hz) reacted in a way similar to the BOLD response.

Conclusions: The reasons for such opposite differential reactivity between oscillations / fMRI on the one hand, and evoked potentials on the other, are discussed in the paper. Those results provide further arguments for a closer relationship between fast oscillations and the BOLD signal, than between evoked potentials and the BOLD signal.
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http://dx.doi.org/10.1186/1471-2202-4-22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC222904PMC
September 2003