Neuroimaging-Based Biomarkers in Psychiatry: Clinical Opportunities of a Paradigm Shift

Neuroimaging research has substantiated the functional and structural abnormalities underlying psychiatric disorders but has, thus far, failed to have a significant impact on clinical practice. Recently, neuroimaging-based diagnoses and clinical predictions derived from machine learning analysis have shown significant potential for clinical translation. This review introduces the key concepts of this approach, including how the multivariate integration of patterns of brain abnormalities is a crucial component. We survey recent findings that have potential application for diagnosis, in particular early and differential diagnoses in Alzheimer disease and schizophrenia, and the prediction of clinical response to treatment in depression. We discuss the specific clinical opportunities and the challenges for developing biomarkers for psychiatry in the absence of a diagnostic gold standard. We propose that longitudinal outcomes, such as early diagnosis and prediction of treatment response, offer definite opportunities for progress. We propose that efforts should be directed toward clinically challenging predictions in which neuroimaging may have added value, compared with the existing standard assessment. We conclude that diagnostic and prognostic biomarkers will be developed through the joint application of expert psychiatric knowledge in addition to advanced methods of analysis

Research progress in brain morphological characteristics of obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) is a high disabling psychiatric disease with the clinical symptoms of recurrent intrusive thoughts or repetitive behaviors. The etiology and pathogenesis of OCD have not been fully elucidated. Exploring the brain morphological characteristics of OCD is important for understanding the pathological mechanism of OCD. Besides, as potential biomarkers, brain morphological characteristics have a good application prospect in assisting clinical diagnosis and treatment. In recent years, neuromodulation techniques such as repetitive transcranial magnetic stimulation (rTMS) and deep brain stimulation (DBS) have been widely used in the treatment of OCD. Exploring the abnormal brain morphological characteristics of OCD may provide a basis for the selection of neuromodulation targets. Current studies on the brain morphological characteristics of OCD mainly focus on the cortico-striato-thalamo-cortical (CSTC) circuit, which is closely related to the pathological mechanism of OCD. Limited by the differences in inclusion and exclusion criteria, medication and data analysis methods among these studies, there are many inconsistent results on the brain morphological characteristics of OCD, and how to promote the clinical application needs further exploration. This article reviews the research results of brain morphological characteristics of OCD, discusses the clinical application prospect, and points out the future development direction, in order to promote the progress of etiology and clinical treatment of OCD

Comparative Multimodal Meta-analysis of Structural and Functional Brain Abnormalities in Autism Spectrum Disorder and Obsessive-Compulsive Disorder

BACKGROUND: Autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD) share inhibitory control deficits possibly underlying poor control over stereotyped and repetitive and compulsive behaviors, respectively. However, it is unclear whether these symptom profiles are mediated by common or distinct neural profiles. This comparative multimodal meta-analysis assessed shared and disorder-specific neuroanatomy and neurofunction of inhibitory functions. METHODS: A comparative meta-analysis of 62 voxel-based morphometry and 26 functional magnetic resonance imaging (fMRI) studies of inhibitory control was conducted comparing gray matter volume and activation abnormalities between patients with ASD (structural MRI: 911; fMRI: 188) and OCD (structural MRI: 928; fMRI: 247) and control subjects. Multimodal meta-analysis compared groups across voxel-based morphometry and fMRI. RESULTS: Both disorders shared reduced function and structure in the rostral and dorsomedial prefrontal cortex including the anterior cingulate. OCD patients had a disorder-specific increase in structure and function of left basal ganglia (BG) and insula relative to control subjects and ASD patients, who had reduced right BG and insula volumes versus OCD patients. In fMRI, ASD patients showed disorder-specific reduced left dorsolateral-prefrontal activation and reduced posterior cingulate deactivation, whereas OCD patients showed temporoparietal underactivation. CONCLUSIONS: The multimodal comparative meta-analysis shows shared and disorder-specific abnormalities. Whereas the rostrodorsomedial prefrontal cortex was smaller in structure and function in both disorders, this was concomitant with increased structure and function in BG and insula in OCD patients, but a reduction in ASD patients, presumably reflecting a disorder-specific frontostriatoinsular dysregulation in OCD in the form of poor frontal control over overactive BG, and a frontostriatoinsular maldevelopment in ASD with reduced structure and function in this network. Disorder-differential mechanisms appear to drive overlapping phenotypes of inhibitory control abnormalities in patients with ASD and OCD

Die Global-Mean Analyse im funktionellen MRT als klinisches Tool zur Identifikation von sexueller Orientierung

Die global Mean Analyse im funktionellen MRT als neues Tool zur Identifikation von sexueller Orientierung. Besonderes Augenmerk wurde vor allem auf die Hebephilie gelegt. Weiterhin ist es zu einer Differenzierung zwischen Alters- als auch Geschlechtspräferenz gekommen

Aplicación de técnicas de aprendizaje máquina para la caracterización y clasificación de pacientes con trastorno obsesivo compulsivo

El siguiente Trabajo Fin de Grado se basa en el cada vez más habitual empleo de métodos de aprendizaje máquina con el fin de clasificar y caracterizar trastornos psiquiátricos. Concretamente, el sistema diseñado pretende acercarse al diagnóstico de TOC (‘Trastorno Obsesivo Compulsivo’) a través del análisis de imágenes de resonancia magnética (MRI). El sistema diseñado tiene como objetivo plantear un algoritmo capaz de diagnosticar pacientes con TOC y, principalmente, capaz de caracterizar la enfermedad, detectando de manera automática las regiones neuroanatómicas relacionadas con el trastorno. Para ello, se empleará una arquitectura modular creada a partir de dos premisas fundamentales. 1. Análisis por áreas funcionales y/o neuroanatómicas. Cada imagen de resonancia magnética se divide en, aproximadamente, una centena de subconjuntos compuestos por vóxeles asociados a un área funcional o región neuroanatómica del cerebro. Así pues, el objetivo es aplicar un clasificador que facilite la selección de los conjuntos de vóxeles relevantes para la detección de la enfermedad. 2. Caracterización y fusión de áreas funcionales. El sistema utilizará métodos de selección de características sobre las salidas de los clasificadores el objetivo de obtener una selección automática de las áreas relevantes para el diagnóstico de la patología que estamos tratando. Asimismo, el último paso será el estudio de la relación que tienen las áreas entre sí mediante el uso de clasificadores, tanto lineales como no lineales. Una vez desarrollado y aplicado el algoritmo, se aprovecharán los resultados tanto para comparar la clasificación de pacientes con los resultados previos obtenidos mediante métodos tradicionales [1], [2], como para analizar el patrón de áreas neuroanatómicas responsables del trastorno. -------------------------------------------------------This work is based on increasingly common use of machine learning methods in order to classify and characterize psychiatric disorders. Specifically, the designed system tries to be able to diagnose OCD (Obsessive-Compulsive Disorder) though the MRI (Magnetic Resonance Imaging) analysis. The main system's goal is to construct an algorithm able to detect OCD patients and characterize the disease, detecting automatically neuroanatomical regions related to the disorder, supported on a modular arquitecture process with two fundamental principles. 1. Analysis of functional and/or neuroanatomical areas. Each MRI is divided into one hundred subsets composed of voxels associated to a functional area. Thus, the goal is to apply a classifier which facilitates the selection of the relevant voxels sets for the diagnosis of the disease. 2. Characterization and combination of functional areas. The system will use feature selection methods with the outputs of the first classifiers in order to get an automatic selection of the relevant areas for diagnosis of the pathology. The last step will use linear and no liner classifiers to analyze whether the different areas are interrelated. Having the algorithm developed, we will use the results to compare the classifications of patients with previous results got by traditional methods [1], [2], and to analyze the pattern of neuroanatomical areas responsible for the disorder.Ingeniería de Sistemas Audiovisuale

What works best?: Comparing three objective methods for measuring pedophilic sexual orientation

In dieser Arbeit habe ich drei objektive Verfahren zur Messung pädophiler Orientierungen bei Männern verglichen: Das Viewing Time Verfahren (VT), die Phallometrie bzw. Penisplethysmographie (PPG) und die funktionelle Magnetresonanztomographie (fMRT). Dazu habe ich eine Teilstichprobe des nationalen Forschungsverbundes „NeMUP“ genutzt. Insgesamt habe ich 38 teleiophile Männer (Orientierung auf das erwachsene Körperschema) mit 34 pädo- oder hebephilen Männern (Orientierung auf ein vor- bzw. intrapuberales Körperschema) verglichen. Bis auf drei Probanden haben alle ihre sexuelle Orientierung offen eingeräumt. Die Einteilung der Probanden in die Gruppe der teleiophilen bzw. der pädohebephilen Gruppe geschah überwiegend anhand eines halbstrukturierten, klinischen Interviews. Für jedes objektive Messverfahren wurde ein Index zur Vorhersage der sexuellen Orientierung errechnet. Die Indizes der einzelnen Verfahren waren alle miteinander korreliert (r = .39 bis .58). Die mittlere Klassifikationsgenauigkeit der Verfahren unterschied sich nicht erheblich (87 bis 100 %). Die Kombination mehrere Verfahren führte zu einer Steigerung der Validitätswerte. Auf Grundlage dieser Ergebnisse empfehle ich die Nutzung objektiver Messverfahren unter anderem im therapeutischen Kontext. Wichtig ist die Integration und Interpretation der Befunde unter Zuhilfenahme der Angaben des Patienten. Die Auswertung der Messdaten sollte von Experten vorgenommen werden und nicht zu einer überschätzten Bedeutung indirekter Verfahren führen. Diese erlauben die Messung sexueller Orientierungen, nicht aber von straffälligem Verhalten. Unter anderem daher halte ich eine Anwendung als Screeningverfahren für ungeeignet.In my thesis I compared three objective methods for measuring pedophilic orientation in men: the viewing time method (VT), penisplethysmography (PPG) and functional magnetic resonance imaging (fMRI). I used a subsample of the national research network "NeMUP". Overall 38 teleiophilic (sexual preference for a postpubescent body schema) and 34 pedophilic respectively hebephilic (sexual preference for a pre- respectively intrapubescent body schema) men were included in this study. Only three participants denied their sexual orientation for children. Participants were assigned to the teleiophilic respectively pedohebephilic group based on a semi-structured clinical interviews. For each objective method, an index for predicting sexual orientation was calculated. The indices of the three methods were all correlated with each other (r = .39 to .58). The average classification accuracy of the methods did not differ substantially (87 to 100%). Combining several methods increased validity. Based on these results, I recommend the use of objective measurements for example in sex offender therapy. The carefully integration and interpretation of the objective methods is of great importance and should include the self-report of the patient. The evaluation of the methods should be done by experts and not lead to an overestimation of the meaningfulness of objective measures. Objective methods measure sexual orientation and not delinquent behavior. Among other reasons I therefore deem these methods inappropriate with respect to screening whole populations (like for example prospective kindergarten teacher)

Psicopatologia obsessivo-compulsiva na distonia focal primária : aspectos neuropsiquiátricos de uma doença do movimento

RESUMO: pela contracção involuntária de grupos musculares de extensão variável, originando movimentos involuntários e posturas anómalas, por vezes dolorosas. O tratamento convencional consiste em injecções localizadas de toxina botulínica, podendo, em casos refractários, estar indicado o tratamento por estimulação cerebral profunda. A neurobiologia da distonia focal primária permanece incompletamente compreendida. Os estudos de neuro-imagem estrutural e funcional revelam alterações subtis da anatomia e funcionamento do estriado e das vias cortico-basais, com destaque para o aumento do volume, da actividade metabólica e da neuroplasticidade do putamen e de áreas corticais motoras, pré-motoras e sensitivas. O conjunto destas alterações aponta para uma disrupção da regulação inibitória de programas motores automáticos sustentados pelo estriado e pelas vias ortico-subcorticais. Nos últimos anos tem crescido o interesse pelas manifestações psiquiátricas e cognitivas da distonia (estas últimas muito pouco estudadas). Tem despertado particular interesse a possível associação entre distonia focal primária e perturbação obsessivo-compulsiva (POC), cuja neurobiologia parece notavelmente sobreponível à da distonia primária. Com efeito, os estudos de neuro-imagem estrutural e funcional na POC revelam consistentemente aumento do volume e actividade do estriado e do córtex órbito-frontal, apontando mais uma vez para uma disfunção do controlo inibitório, no estriado, de programas comportamentais e cognitivos automáticos. Objectivos: 1. Explorar a prevalência e intensidade de psicopatologia em geral, e de psicopatologia obsessivo-compulsiva em particular, numa amostra de indivíduos com distonia focal primária; 2. Explorar a ocorrência, natureza e intensidade de alterações do funcionamento cognitivo numa amostra de indivíduos com distonia focal primária; 3. Investigar a associação entre a gravidade da distonia focal, a intensidade da psicopatologia, e a intensidade das alterações cognitivas. Metodologia: Estudo de tipo transversal, caso-controlo, observacional e descritivo, com objectivos puramente exploratórios. Casos: 45 indivíduos com distonia focal primária (15 casos de blefaroespasmo, 15 de cãibra do escrivão, 15 de distonia cervical espasmódica), recrutados através da Associação Portuguesa de Distonia. Critérios de inclusão: idade = 18; distonia focal primária pura (excluindo casos de distonia psicogénica possível ou provável de acordo com os critérios de Fahn e Williams); Metabolismo do cobre e Ressonância Magnética Nuclear sem alterações. Controlos doentes: 46 casos consecutivos recrutados a partir da consulta externa do Hospital Egas Moniz: 15 doentes com espasmo hemifacial, 14 com espondilartropatia cervical, 17 com síndrome do canal cárpico. Controlos saudáveis: 30 voluntários. Critérios de exclusão para todos os grupos: Mini-Mental State Examination patológico, tratamento actual com anti-colinérgicos, antipsicóticos, inibidores selectivos da recaptação da serotonina, antidepressivos tri- ou tetracíclicos. Avaliação: Avaliação neurológica: história e exame médico e neurológico completos. Cotação da gravidade da distonia com a Unified Dystonia Rating Scale. Avaliação psicopatológica: Symptom Check-List-90-Revised; entrevista psiquiátrica de 60 minutos incluindo a Mini-International Neuropsychiatric Interview (MINI), versão 4.4 (validada em Português), complementada com os módulos da MINI Plus versão 5.0.0 para depressão ao longo da vida e dependência/ abuso do álcool e outras substâncias ao longo da vida; Yale-Brown Obsessive-Compulsive Symptom Checklist e a Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Avaliação neuropsicológica: Wisconsin Card Sorting Test (WCST; flexibilidade cognitiva); Teste de Stroop (inibição de resposta); Block Assembly Test (capacidade visuo-construtiva); Teste de Retenção Visual de Benton (memória de trabalho visuo-espacial). Análise estatística:os dados foram analisados com a aplicação informática SPSS for Windows, versão 13. Para a comparação de proporções utilizaram-se o teste do Chi-quadrado e o teste de Fisher. Para a comparação de variáveis quantitativas entre dois grupos utilizou-se o teste t de Student ou o teste U de Mann-Whitney (teste de Wilcoxon no caso de amostras emparelhadas). Para comparações de médias entre três grupos recorreu-se à Análise de Variância a um factor (variáveis de intervalo e de rácio), ou ao teste de Kruskal-Wallis (variáveis ordinais). Para o estudo da associação entre variáveis foram utilizados os coeficientes de correlação de Pearson ou de Spearman, a análise de correlações canónicas, a análise de trajectórias e a regressão logística. Adoptou-se um Alpha de 0.05. Resultados: Os doentes com distonia focal primária apresentaram uma pontuação média na Y- -BOCS significativamente superior à dos dois grupos de controlo. Em 24.4% dos doentes com distonia a pontuação na Y-BOCS foi superior a 16. Estes doentes eram predominantemente mulheres, tinham uma maior duração média da doença e referiam predominantemente sintomas obsessivo-compulsivos (SOC) de contaminação e lavagem. Os dois grupos com doença crónica apresentaram pontuações médias superiores às dos indivíduos saudáveis nas escalas de ansiedade, somatização e psicopatologia geral. Os doentes com distonia tratados com toxina botulínica apresentaram pontuações inferiores às dos doentes não tratados nas escalas de ansiedade generalizada, fobia, somatização e depressão, mas não na Y-BOCS. Sessenta por cento dos doentes com distonia apresentavam pelo menos um diagnóstico psiquiátrico actual ou pregresso. O risco de apresentar um diagnóstico psiquiátrico actual era menor nos doentes tratados com toxina botulínica, aumentando com a gravidade da doença. A prevalência de POC foi 8,3% e a de depressão major 37,7%. No WCST e na Prova de Benton, os doentes com distonia focal primária demonstraram um desempenho inferior ao de ambos os grupos de controlo, cometendo sobretudo erros perseverativos. Os doentes com distonia e pontuação na Y-BOCS > 16 cometeram mais erros e respostas perseverativas no WCST do que os restantes doentes com distonia. As análises de correlações e de trajectórias revelaram que nos doentes com distonia a gravidade da distonia foi, juntamente com a idade e a escolaridade, o factor que mais interagiu com o desempenho cognitivo. Discussão: o nosso estudo é o primeiro a descrever, nos mesmos doentes com distonia focal primária, SOC significativos e alterações cognitivas. Os nossos resultados confirmam a hipótese de uma associação clínica específica entre distonia focal primária e psicopatologia obsessivo-compulsiva. Confirmam igualmente que a distonia focal primária está associada a um maior risco de desenvolver morbilidade psiquiátrica ansiosa e depressiva. O tratamento com toxina botulínica reduz este risco, mas não influencia os SOC. Entre os doentes com distonia, os que têm SOC significativos poderão diconstituir um grupo particular com maior duração da doença (mas não uma maior gravidade), predomínio do sexo feminino e predomínio de SOC de contaminação e limpeza. Em termos cognitivos, os indivíduos com distonia focal primária apresentam défices significativos de flexibilidade cognitiva (particularmente acentuados nos doentes com SOC significativos) e de memória de trabalho visuo-espacial. Estes últimos devem-se essencialmente a um défice executivo e não a uma incapacidade visuo-construtiva ou visuo-perceptiva. A disfunção cognitiva não é explicável pela psicopatologia depressiva nem pela incapacidade motora, já que os controlos com doença periférica crónica tiveram um desempenho superior ao dos doentes com distonia. No seu conjunto os nossos resultados sugerem que os SOC que ocorrem na distonia focal primária constituem uma das manifestações clínicas da neurobiologia desta doença do movimento. O predomínio de sintomas relacionados com higiene e o perfil disexecutivo de alterações cognitivas–perseveração e dificuldades executivas de memória de trabalho visuo-espacial – apontam para a via cortico-basal dorso-lateral e para as áreas corticais que lhe estão associadas como estando implicadas na tripla associação entre sintomas motores, obsessivo-compulsivos e cognitivos. Conclusões: A distonia focal primária é um síndrome neuropsiquiátrico complexo com importantes manifestações não motoras, nomeadamente compromisso cognitivo do tipo disexecutivo e sintomas obsessivo-compulsivos. Clinicamente estas manifestações representam necessidades de tratamento que vão muito para além da simples incapacidade motora, devendo ser activamente exploradas e tratadas.-------------- ABSTRACT: Introduction: primary focal dystonia is an idiopathic movement disorder that manifests as involuntary, sustained contraction of muscular groups, leading to abnormal and often painful postures of the affected body part. Treatment is symptomatic, usually with local intramuscular injections of botulinum toxin. The neurobiology of primary focal dystonia remains unclear. Structural and functional neuroimaging studies have revealed subtle changes in striatal and cortical-basal pathway anatomy and function. The most consistent findings involve increased volume and metabolic activity of the putamen and of motor, pre-motor and somato-sensitive cortical areas. As a whole, these changes have been interpreted as reflecting a failure of striatal inhibitory control over automatic motor programs sustained by cortical-basal pathways. The last years have witnessed an increasing interest for the possible non-motor – mainly psychiatric and cognitive – manifestations of primary focal dystonia. The possible association of primary focal dystonia with obsessive-compulsive disorder (OCD) has raised particular interest. The neurobiology of the two disorders has indeed remarkable similarities: structural and functional neuroimaging studies in OCD have revealed increased volume and metabolic activity of the striatum and orbital-frontal cortex, again pointing to a disruption of inhibitory control of automatic cognitive and behavioural programs by the striatum. Objectives: 1. To explore the prevalence and severity of psychopathology – with a special emphasis on obsessive-compulsive symptoms (OCS) – in a sample of patients with primary focal dystonia;2. To explore the nature and severity of possible cognitive dysfunction in a sample of patients with primary focal dystonia; 3. To explore the possible association between dystonia severity, psychiatric symptom severity, and cognitive performance, in a sample of patients with primary focal dystonia. Methods: cross-sectional, case-control, descriptive study. Cases: forty-five consecutive, primary pure focal dystonia patients recruited from the Portuguese Dystonia Association case register (fifteen patients with blepharospasm, 15 with cervical dystonia and 15 with writer’s cramp). Inclusion criteria were: age = 18; primary pure focal, late-onset dystonia (excluding possible or probable psychogenic dystonia according to the Fahn & Williams criteria); normal copper metabolism and Magnetic Resonance Imaging. Diseased controls: forty-six consecutive subjects from our hospital case register (15 patients with hemi-facial spasm; 14 with cervical spondilarthropathy and cervical spinal root compression; 17 with carpal tunnel syndrome). Healthy controls were 30 volunteers.Exclusion criteria for all groups: Mini-Mental State Examination score below the validated cut-off for the Portuguese population (11 years); use of anti-cholinergics, neuroleptics, selective serotonin reuptake inhibitors, triciclic or tetraciclic antidepressants. Assessment: neurological assessment: complete medical and neurological history and physical examination; dystonia severity scoring with the Unified Dystonia Rating Scale. Psychiatric assessment:Symptom Check-List-90-Revised; 60 minute-long psychiatric interview, including Mini-International Neuropsychiatric Interview (MINI), version 4.4 (validated Portuguese version), extended with the sections for life-time major depressive disorder and life-time alcohol and substance abuse disorder from MINI-Plus version 5.0.0; Yale-Brown Obsessive-Compulsive Symptom Checklist and Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Cognitive assessment: Wisconsin Card Sorting Test (WCST; cognitive set-shifting ability); Stroop Test (response inhibition); Block Assembly Test(visual-constructive ability); Benton’s Visual Retention Test (visual-spatial working memory). Statistic analysis: Data were analyzed with SPSS for Windows version 13. Proportions were compared using Chi-Square test, or Fisher’s exact test when appropriate. Student’s t-test or Mann-Whitney’s U test (or Wilcoxon’s teste in the case of matched samples) were used for two-group comparisons. P-values were corrected for multiple comparisons. One-way ANOVA with Bonferroni post-hoc analysis (interval data), or the Kruskal-Wallis Test (ordinal data), were used for three-group comparisons. Associations were analysed with Pearson’s or Spearman’s correlation coefficients, canonical correlations, path analysis and logistic regression analysis. Alpha was set at 0.05. Results: Dystonia patients had higher Yale-Brown Obsessive-Compulsive Symptom scores than both control groups. 24.4% of primary dystonia patients had a Y-BOCS score > 16. These patients were predominantly women; they had longer disease duration, and showed a predominance of hygiene-related OCS. The two groups with chronic disease had higher anxiety, somatization and global psychopathology scores than healthy subjects. Primary dystonia patients undergoing treatment with botulinum toxin had lower anxiety, phobia, somatization and depression scores than their untreated counterparts, but similar Y-BOCS scores. Sixty percent of primary dystonia patients had at least one lifetime psychiatric diagnosis. The odds of having a currently active psychiatric diagnosis were lower in botulinum toxin treated patients, and increased with dystonia severity. The prevalence of OCD was 6.7%, and the lifetime prevalence of major depression was 37.7%. Primary dystonia patients had a lower performance than the two control groups in both the WCST and Benton’s Visual Retention Test, mainly due to an excess of perseveration errors. Primary dystonia patients with Y-BOCS score > 16 had much higher perseveration error and perseveration response scores than dystonia patients with Y-BOCS = 16. Correlation and path analysis showed that, in the primary dystonia group, dystonia severity, along with age and education, was the main factor influencing cognitive performance. Discussion: our study is the first description ever of concomitant significant OCS and cognitive impairment in primary dystonia patients. Our results confirm that primary dystonia is specifically associated with obsessive-compulsive psychopathology. They also confirm that primary focal dystonia patients are at a higher risk of developing anxious and depressive psychiatric morbidity. Treatment with botulinum toxin decreases this risk, but does not influence OCS. Primary focal dystonia patients with significant OCS may constitute a particular subgroup. They are predominantly women, with higher disease duration (but not severity) and a predominance of hygiene related OCS.In terms of cognitive performance, primary focal dystonia patients have significant deficits involving set-shifting ability and visual-spatial working memory. The latter result from an essentially executive deficit, rather than from a primary visual-constructive apraxia or perceptual deficit. Furthermore, cognitive flexibility difficulties were more prominent in the subset of primary dystonia patients with significant OCS. The cognitive dysfunction found in dystonia patients is not attributable to depressive psychopathology or motor disability, as their performance was significantly lower than that of similarly impaired diseased controls. Our results suggest that OCS in primary focal dystonia are a direct, primary manifestation of the motor disorder’s neurobiology. The predominance of hygiene-related symptoms and the disexecutive pattern of cognitive impairment – set-shifting and visual-spatial working memory deficits – suggest that the dorsal-lateral cortical-basal pathway may play a decisive role in the triple association of motor dysfunction, OCS and cognitive impairment. Conclusions: primary focal dystonia is a complex neuropsychiatric syndrome with significant non- -motor manifestations, namely cognitive executive deficits and obsessive-compulsive symptoms.Clinically, our results show that PFD patients may have needs for care that extend far beyond a merely motor disability and must be actively searched for and treated