Cortical gray matter progression in idiopathic REM sleep behavior disorder and its relation to cognitive decline

Background: Idiopathic Rapid eye movement sleep behavior disorder (IRBD) is recognized as the prodromal stage of the alpha-Synucleinopathies. Although some studies have addressed the characterization of brain structure in IRBD, little is known about its progression. Objective: The present work aims at further characterizing gray matter progression throughout IRBD relative to normal aging and investigating how these changes are associated with cognitive decline. Methods: Fourteen patients with polysomnography-confirmed IRBD and 18 age-matched healthy controls (HC) underwent neuropsychological, olfactory, motor, and T1-weighted MRI evaluation at baseline and follow-up. We compared the evolution of cortical thickness (CTh), subcortical volumes, smell, motor and cognitive performance in IRBD and HC after a mean of 1.6 years. FreeSurfer was used for CTh and volumetry preprocessing and analyses. The symmetrized percent of change (SPC) of the CTh was correlated with the SPC of motor and neuropsychological performance. Results: IRBD and HC differed significantly in the cortical thinning progression in regions encompassing bilateral superior parietal and precuneus, the right cuneus, the left occipital pole and lateral orbitofrontal gyri (FWE corrected, p < 0.05). The Visual form discrimination test showed worse progression in the IRBD relative to HC, that was associated with gray matter loss in the right superior parietal and the left precuneus. Increasing motor signs in IRBD were related to cortical thinning mainly involving frontal regions, and late-onset IRBD was associated with cortical thinning involving posterior areas (FWE corrected, p < 0.05). Despite finding olfactory identification deficits in IRBD, results did not show decline over the disease course. Conclusion: Progression in IRBD patients is characterized by parieto-occipital and orbitofrontal thinning and visuospatial loss. The cognitive decline in IRBD is associated with degeneration in parietal regions

Sex differences in brain and cognition in de novo Parkinson's disease

Background and objective: Brain atrophy and cognitive impairment in neurodegenerative diseases are influenced by sex. We aimed to investigate sex differences in brain atrophy and cognition in de novo Parkinson's disease (PD) patients. Methods: Clinical, neuropsychological and T1-weighted MRI data from 205 PD patients (127 males:78 females) and 69 healthy controls (40 males:29 females) were obtained from the PPMI dataset. Results: PD males had a greater motor and rapid eye movement sleep behavior disorder symptomatology than PD females. They also showed cortical thinning in postcentral and precentral regions, greater global cortical and subcortical atrophy and smaller volumes in thalamus, caudate, putamen, pallidum, hippocampus, and brainstem, compared with PD females. Healthy controls only showed reduced hippocampal volume in males compared to females. PD males performed worse than PD females in global cognition, immediate verbal recall, and mental processing speed. In both groups males performed worse than females in semantic verbal fluency and delayed verbal recall; as well as females performed worse than males in visuospatial function. Conclusions: Sex effect in brain and cognition is already evident in de novo PD not explained by age per se, being a relevant factor to consider in clinical and translational research in PD

Brain atrophy pattern in de novo Parkinsons disease with probable RBD associated with cognitive impairment

Rapid eye movement sleep behavior disorder (RBD) is associated with high likelihood of prodromal Parkinson's disease (PD) and is common in de novo PD. It is associated with greater cognitive impairment and brain atrophy. However, the relation between structural brain characteristics and cognition remains poorly understood. We aimed to investigate subcortical and cortical atrophy in de novo PD with probable RBD (PD-pRBD) and to relate it with cognitive impairment. We analyzed volumetry, cortical thickness, and cognitive measures from 79 PD-pRBD patients, 126 PD without probable RBD patients (PD-non pRBD), and 69 controls from the Parkinson's Progression Markers Initiative (PPMI). Regression models of cognition were tested using magnetic resonance imaging measures as predictors. We found lower left thalamus volume in PD-pRBD compared with PD-non pRBD. Compared with controls, PD-pRBD group showed atrophy in the bilateral putamen, left hippocampus, left amygdala, and thinning in the right superior temporal gyrus. Specific deep gray matter nuclei volumes were associated with impairment in global cognition, phonemic fluency, processing speed, and visuospatial function in PD-pRBD. In conclusion, cognitive impairment and gray matter atrophy are already present in de novo PD-pRBD. Thalamus, hippocampus, and putamen volumes were mainly associated with these cognitive deficits

Sex differences in brain atrophy and cognitive impairment in Parkinson's disease patients with and without probable rapid eye movement sleep behavior disorder

Background: The presence of rapid eye movement sleep behavior disorder (RBD) contributes to increase cognitive impairment and brain atrophy in Parkinson's disease (PD), but the impact of sex is unclear. We aimed to investigate sex differences in cognition and brain atrophy in PD patients with and without probable RBD (pRBD). Methods: Magnetic resonance imaging and cognition data were obtained for 274 participants from the Parkinson's Progression Marker Initiative database: 79 PD with pRBD (PD-pRBD; male/female, 54/25), 126 PD without pRBD (PD-non pRBD; male/female, 73/53), and 69 healthy controls (male/female, 40/29). FreeSurfer was used to obtain volumetric and cortical thickness data. Results: Males showed greater global cortical and subcortical gray matter atrophy than females in the PD-pRBD group. Significant group-by-sex interactions were found in the pallidum. Structures showing a within-group sex effect in the deep gray matter differed, with significant volume reductions for males in one structure in in PD-non pRBD (brainstem), and three in PD-pRBD (caudate, pallidum and brainstem). Significant group-by-sex interactions were found in Montreal Cognitive Assessment (MoCA) and Symbol Digits Modalities Test (SDMT). Males performed worse than females in MoCA, phonemic fluency and SDMT in the PD-pRBD group. Conclusion: Male sex is related to increased cognitive impairment and subcortical atrophy in de novo PD-pRBD. Accordingly, we suggest that sex differences are relevant and should be considered in future clinical and translational research

Hierarchical cluster analysis of multimodal imaging data identifies brain atrophy and cognitive patterns in Parkinson's disease

Background: Parkinson's disease (PD) is a heterogeneous condition. Cluster analysis based on cortical thickness has been used to define distinct patterns of brain atrophy in PD. However, the potential of other neuroimaging modalities, such as white matter (WM) fractional anisotropy (FA), which has also been demonstrated to be altered in PD, has not been investigated. Objective: We aim to characterize PD subtypes using a multimodal clustering approach based on cortical and subcortical gray matter (GM) volumes and FA measures. Methods: We included T1-weighted and diffusion-weighted MRI data from 62 PD patients and 33 healthy controls. We extracted mean GM volumes from 48 cortical and 17 subcortical regions using FSL-VBM, and the mean FA from 20 WM tracts using Tract-Based Spatial Statistics (TBSS). Hierarchical cluster analysis was performed with the PD sample using Ward's linkage method. Whole-brain voxel-wise intergroup comparisons of VBM and TBSS data were also performed using FSL. Neuropsychological and demographic statistical analyses were conducted using IBM SPSS Statistics 25.0. Results: We identified three PD subtypes, with prominent differences in GM patterns and little WM involvement. One group (n = 15) with widespread cortical and subcortical GM volume and WM FA reductions and pronounced cognitive deficits; a second group (n = 21) with only cortical atrophy limited to frontal and temporal regions and more specific neuropsychological impairment, and a third group (n = 26) without detectable atrophy or cognition impairment. Conclusion: Multimodal MRI data allows classifying PD patients into groups according to GM and WM patterns, which in turn are associated with the cognitive profile

Impaired Structural Connectivity In Parkinson's Disease Patients With Mild Cognitive Impairment: A Study Based On Probabilistic Tractography

Background: Probabilistic tractography, in combination with graph theory, has been used to reconstruct the structural whole-brain connectome. Threshold-free network-based statistics (TFNBS) is a useful technique to study structural connectivity in neurodegenerative disorders; however, there are no previous studies using TFNBS in Parkinson's disease (PD) with and without mild cognitive impairment (MCI). Methods: Sixty-two PD patients, 27 of whom classified as PD-MCI, and 51 healthy controls (HC) underwent diffusion-weighted 3T MRI. Probabilistic tractography, using FSL, was used to compute the number of streamlines (NOS) between regions. NOS matrices were used to find group differences with TFNBS, and to calculate global and local measures of network integrity using graph theory. A binominal logistic regression was then used to assess the discrimination between PD with and without MCI using non-overlapping significant tracts. Tract-based spatial statistics (TBSS) were also performed with FSL to study changes in fractional anisotropy (FA) and mean diffusivity (MD). Results: PD-MCI showed 37 white matter (WM) connections with reduced connectivity strength compared to HC, mainly involving temporo-occipital regions. These were able to differentiate PD-MCI from PD without MCI with an area under the curve of 83-85%. PD without MCI showed disrupted connectivity in 18 connections involving fronto-temporal regions. No significant differences were found in graph measures. Only PD-MCI showed reduced FA compared with HC. Discussion: TFNBS based on whole-brain probabilistic tractography can detect structural connectivity alterations in PD with and without MCI. Reduced structural connectivity in fronto-striatal and posterior corticocortical connections is associated with PD-MCI

Sex differences in brain atrophy in dementia with Lewy bodies

Publisher Copyright: © 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.INTRODUCTION: Sex influences neurodegeneration, but it has been poorly investigated in dementia with Lewy bodies (DLB). We investigated sex differences in brain atrophy in DLB using magnetic resonance imaging (MRI). METHODS: We included 436 patients from the European-DLB consortium and the Mayo Clinic. Sex differences and sex-by-age interactions were assessed through visual atrophy rating scales (n = 327; 73 ± 8 years, 62% males) and automated estimations of regional gray matter volume and cortical thickness (n = 165; 69 ± 9 years, 72% males). RESULTS: We found a higher likelihood of frontal atrophy and smaller volumes in six cortical regions in males and thinner olfactory cortices in females. There were significant sex-by-age interactions in volume (six regions) and cortical thickness (seven regions) across the entire cortex. DISCUSSION: We demonstrate that males have more widespread cortical atrophy at younger ages, but differences tend to disappear with increasing age, with males and females converging around the age of 75. Highlights: Male DLB patients had higher odds for frontal atrophy on radiological visual rating scales. Male DLB patients displayed a widespread pattern of cortical gray matter alterations on automated methods. Sex differences in gray matter measures in DLB tended to disappear with increasing age.Peer reviewe

Subtypes in Parkinson's disease and Dementia with Lewy bodies: MRI and neuropsychological profiles

[eng] INTRODUCTION: Parkinson’s disease (PD) and Dementia with Lewy bodies (DLB) appear as neurodegenerative disorders with a wide range of symptomatology that differs among patients, among which are different levels of cognitive impairment. For instance, mild cognitive impairment (MCI) in PD contributes to a specific clinical profile with a higher risk of developing dementia. Looking at PD and DLB together provides evidence of the existence of different subtypes within both diseases. In recent years, complex imaging techniques, such as magnetic resonance imaging (MRI), have been used to study pathologies of the brain. MRI measures can be used to better characterize the brain basis of PD and DLB symptomatology, such as MCI. The reconstruction of the whole-brain connectome is a complex approach that can help to describe the heterogeneous symptomatology in neurodegenerative disorders. In addition, MRI in combination with new data-driven methods, such as cluster analysis, has been used to group patients according to their similarities, which allows subtypes to be identified. Until now, most studies in PD have described subtypes based on clinical and neuropsychological data, and just a few have used MRI measures to identify subtypes with different brain patterns. As DLB research is still in a relatively early stage, no cluster analyses have been yet performed based on MRI data. OBJECTIVES AND HYPOTHESES: Given this context, the current Doctoral Thesis focuses on the heterogeneity that characterizes PD and DLB. The main objectives were to identify subtypes based on structural MRI measures in PD and DLB, as well as to characterize the structural brain connectivity of PD associated with MCI. We hypothesized that there would be PD subtypes with different patterns of grey and white matter alterations that would be associated with particular clinical and cognitive profiles. We also hypothesized that there would be DLB subtypes characterized by different grey matter (GM) patterns, and that these patterns would explain specific symptomatology of the disease and would be differentially associated to concomitant brain changes seen in cerebrovascular and Alzheimer’s diseases. Finally, we expected that PD-MCI would present a characteristic pattern of impaired structural connectivity. In order to examine and clarify these issues, the current Doctoral Thesis is presented as a compendium of three studies. METHODS: In Study 1, to identify subtypes in PD, we performed a hierarchical cluster analysis based on multimodal imaging using the Ward’s linkage method. We performed the analysis in a sample of 62 PD patients. GM volumes of cortical and subcortical brain regions as well as fractional anisotropy (FA) white matter (WM) measures were combined. Once the subtypes were identified, voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) analyses were carried out in order to compare the pattern of GM and WM of the PD subtypes to the 33 healthy control group. Demographical, clinical and neuropsychological data were used to characterize the subtypes. In Study 2, the sample consisted of 27 PD-MCI and 35 PD without MCI, as well as 51 healthy controls. In this study we applied threshold-free network-based statistics (TFNBS), a novel technique based on whole-brain probabilistic tractography data useful to study structural connectivity. We complemented the analysis with TBSS and graph theory analyses (global and local measures). Study 3 included 165 DLB subjects from the Mayo Clinic and 3 centres from the European DLB consortium (E-DLB). We performed a cluster analysis based on GM volumes using a random forest method, and characterized the subtypes based on GM volumes, clinical, demographical data as well as tau, β-amyloid and cerebrovascular biomarkers. Additionally, we characterized cognitive trajectories of the subtypes in a 3-year follow- up. RESULTS: In Study 1, we identified 3 PD subtypes which mainly differed in GM patterns, while WM involvement appeared to be more limited. PD1 (24%) was characterized by temporo-parieto-occipital GM atrophy and subcortical atrophy, as well as FA reductions mainly affecting fronto-occipital WM tracts. This subtype was the oldest and had the worse neuropsychological profile. The second subtype, PD2 (34%), was characterized by GM atrophy limited to frontal and temporal cortical regions, and a third subtype, PD3 (42%), with non-detectable GM atrophy or WM impairment, and preserved cognitive profile. In Study 2, we found that PD patients had fewer streamlines (NOS) compared with healthy controls. Structural connectivity impairments were present in PD with and without MCI. However, the pattern and degree of connectivity impairment were different. PD-MCI showed a higher number of abnormal connections, primarily involving those between deep GM structures and cortical regions and posterior cortico-cortical connections, mainly in the temporal and occipital regions. PD without MCI showed fewer altered connections, and unlike PD-MCI, they were mainly located in the bilateral prefrontal cortex. What is more, the logistic regression and ROC curve analysis showed that the decreased NOS in the impaired connections characteristic of PD-MCI, were able to discriminate between both PD groups with high accuracy. The TBSS analysis revealed that only PD-MCI had reduced FA values compared to controls. The graph theory analysis showed PD groups differed in local graph measures. In Study 3, three DLB subtypes with the same disease evolution were identified based on their GM volumes. The cortical predominant subtype (30%) was characterized by widespread reduced cortical GM, older age, worse cognition at baseline and faster cognitive decline over 3 years. The second subtype, the fronto-occipital subtype (46%), had lower GM volumes in frontal and occipital regions. Finally, the subcortical predominant subtype (24%) was characterized by the greatest GM volumes, and relatively low GM volumes in the basal ganglia, as they were the only brain regions where the 3 subtypes had equivalent GM volumes. The subcortical predominant subtype was also characterized by the highest frequency of cognitive fluctuations. CONCLUSIONS: Our overall findings support the existence of different PD and DLB subtypes that can be identified by means of cluster analyses based on MRI data, which are in turn associated with specific cognitive profiles, and that cognitive impairment in PD is also associated to a specific pattern of structural connectivity impairment. These results contribute to clarifying the basis of heterogeneity in DLB and PD and give further information about which characteristics could be considered biomarkers of worse prognosis, with the final aim of approaching a more personalized medicine.[cat] INTRODUCCIÓ: La malaltia de Parkinson i la Demència amb cossos de Lewy són malalties neurodegeneratives que es presenten amb una àmplia varietat de símptomes, els quals difereixen entre pacients. El deteriorament cognitiu lleu, per exemple, és un possible símptoma de la malaltia de Parkinson que contribueix en un perfil clínic concret amb un elevat risc de desenvolupar demència. Tot plegat aporta evidència de l’existència de diferents subtipus (grups) dins d’ambdues malalties. En els últims anys, s’han utilitzat tècniques d’imatge complexes, com la imatge per ressonància magnètica (IRM), per estudiar les malalties que afecten al cervell. Les diferents mesures obtingudes de la IRM, es poden utilitzar per caracteritzar les bases de la simptomatologia de la malaltia de Parkinson i de la Demència amb cossos de Lewy, com per exemple el deteriorament cognitiu lleu. La reconstrucció del connectoma de tot el cervell és una aproximació complexa que pot ajudar a descriure la simptomatologia heterogènia de les malalties neurodegeneratives, a més, la IRM en combinació amb noves tècniques guiades per les dades, com els anàlisis de clúster, s’han utilitzat per agrupar els pacient d’acord a les seves similituds, el que permet trobar subtipus de pacients. Fins ara, la majoria dels estudis en la malaltia de Parkinson han trobat subtipus basant les anàlisis en dades clíniques i neuropsicològiques, i només escassos treballs s’han basat en dades derivades d’IRM. En la Demència amb cossos de Lewy, degut a que la recerca es troba en fases més primerenques que no pas la recerca en la malaltia Parkinson, encara no s’ha realitzat cap anàlisis de clúster basat en dades d’IRM. OBJECTIUS I HIPÒTESIS: Donat aquest context, la Tesi Doctoral que aquí es presenta es centra en l’heterogeneïtat que caracteritza la malaltia de Parkinson i a la Demència amb cossos de Lewy. Els objectius principals han estat identificar subtipus basats en dades d’IRM en Parkinson i Demència amb cossos de Lewy, així com caracteritzar la connectivitat cerebral a nivell estructural del deteriorament cognitiu lleu en la malaltia de Parkinson. Hem hipotetitzat que hi haurien subtipus en la malaltia de Parkinson que presentarien diferents patrons d’alteració de la substància grisa i la substància blanca que s’associarien amb un perfil clínic i cognitiu específic. En aquesta línia també hem hipotetitzat que hi haurien subtipus dins de la Demència amb cossos de Lewy que es caracteritzarien per diferents patrons d’alteració de la substància grisa, i que aquests patrons, podran explicar diferències en la simptomatologia de la malaltia i es trobaran diferencialment associats a marcadors biològics d’altres processos degeneratius associats a l’envelliment, com els canvis que es troben en processos cerebrovasculars i en la malaltia d’Alzheimer. Finalment, esperaríem que el deteriorament cognitiu lleu en la malaltia de Parkinson presentés un patró característic de connectivitat estructural alterada. Amb la intenció de donar resposta a aquestes qüestions, l’actual Tesi Doctoral es presenta com un compendi de 3 estudis. MÈTODES: En l’estudi 1, per tal d’identificar subtipus en la malaltia de Parkinson, es va dur a terme un anàlisis de clúster jeràrquic aglomeratiu, utilitzant dades multimodals d’IRM. L’anàlisi es va dur a terme en una mostra de 62 pacients i es van combinar volums de substància grisa de regions corticals i subcorticals amb mesures d’anisotropia fraccional de la substància blanca. Un cop identificats els subtipus, es va dur a terme una morfometria basada en vòxels (voxel-based morphometry (VBM), en anglès) i una estadística espacial basada en tractes (Tract-based spatial statistics (TBSS), en anglès) per tal de comparar els patrons de substància grisa i blanca amb un grup de 33 controls sans. A més, vam utilitzar dades demogràfiques, clíniques i neuropsicològiques per caracteritzar els subtipus. A l’estudi 2, la mostra consistia en 27 pacients amb malaltia de Parkinson i deteriorament cognitiu lleu i 35 pacients sense deteriorament cognitiu, així com de 51 controls sans. En aquest estudi vam aplicar una tècnica nova que en anglès rep el nom de threshold-free network-based statistics (TFNBS), aquesta tècnica resulta útil per estudiar la connectivitat estructural i la vam utilitzar amb dades de tractografia probabilística de tot el cervell. A més, vam complementar l’anàlisi amb TBSS i mesures globals i locals de graf. A l’estudi 3, vam incloure 165 pacients amb Demència amb cossos de Lewy que procedien de la Clínica Mayo i de 3 centres que formen part del consorci europeu de Demència amb cossos de Lewy, abreviat com a E-DLB. Vam realitzar un anàlisi de clúster basat en random forest en el que hi vam introduir volums de substància grisa de regions corticals i subcorticals de tot el cervell. En conseqüència, els subtipus els vam caracteritzar en base als volums de substància grisa, però també en base a dades clíniques, demogràfiques i de biomarcadors de tau, β-amiloide i malaltia cerebrovascular. A més, vam caracteritzar les trajectòries cognitives dels subtipus amb un seguiment de 3 anys. RESULTATS: A l’estudi 1, vam definir 3 subtipus en la malaltia de Parkinson que principalment diferien en substància grisa, mentre que la implicació de la substància blanca era molt baixa. El primer subtipus (PD1, 24%) es caracteritzava per presentar atròfia de la substància grisa a nivell de còrtex temporal, parietal i occipital així com en regions subcorticals. A més, presentava reduccions de l’anisotropia fraccional principalment en tractes fronto-occipitals de substància blanca. Aquest subtipus, el PD1, incloïa als pacients de més edat amb el pitjor perfil neuropsicològic. El segon subtipus (PD2, 34%) es caracteritzava per atròfia de la substància grisa en regions frontals i temporals. El tercer subtipus (PD3, 42%), no presentava alteracions detectables ni a nivell de substància grisa ni de blanca, i presentava un perfil cognitiu preservat. En l’estudi 2, vam trobar que els pacients amb malaltia de Parkinson presentaven menor número de fibres en nombroses connexions cerebrals en comparació amb controls sans. Es van trobar alteracions en la connectivitat estructural tant en pacients amb deteriorament cognitiu lleu com sense deteriorament cognitiu, tot i així, el patró i grau de les alteracions en connectivitat estructural eren diferents entre grups de pacients. Els pacients amb deteriorament cognitiu lleu presentaven major número de connexions alterades, les quals principalment involucraven connexions corticals en regions temporals i occipitals així com connexions entre l’escorça cerebral i els nuclis grisos de la base. Els pacients amb malaltia de Parkinson però sense deteriorament cognitiu, presentaven menys connexions alterades que, a diferència dels pacients amb deteriorament cognitiu lleu, es localitzaven principalment en regions bilaterals del còrtex prefrontal. A més, la regressió logística i la corba ROC van mostrar que el número reduït de fibres en les connexions alterades que caracteritzaven el grup de pacients amb deteriorament cognitiu lleu, permetien la discriminació entre els dos grups de pacients amb una precisió elevada. L’anàlisi de TBSS va mostrar que només el pacients amb deteriorament cognitiu lleu presentaven reduccions en l’anisotropia fraccional en comparació al grup de controls sans, i l’anàlisi de graf va mostrar que els 2 grups de pacients diferien en mesures locals. En l’estudi 3, es van identificar 3 subtipus dins de la Demència amb cossos de Lewy en base als volums de substància grisa. El subtipus amb predominança cortical (30%) es caracteritzava per una reducció generalitzada dels volums corticals de substància grisa, incloïa els pacients de més edat, pitjor cognició global i deteriorament cognitiu més ràpid en el transcurs de 3 anys. El segon subtipus, el fronto-occipital (46%), presentava menors volums de substància grisa en regions frontals i occipitals. Finalment, el subtipus amb predominança subcortical (24%), es caracteritzava per majors volums de substància grisa en regions corticals i volums relativament baixos en estructures subcorticals, donat que eren les úniques estructures en les que no hi havia diferències entre els 3 subtipus. Aquest últim subtipus amb predominança subcortical, també es caracteritzava per una major freqüència de pacients amb fluctuacions cognitives. CONCLUSIONS: En conjunt, les troballes presentades en aquesta Tesi Doctoral donen suport a l’existència de diferents subtipus, tant en la malaltia de Parkinson com en la Demència amb cossos de Lewy, que poden ser identificats mitjançant anàlisis de clúster basats en dades d’IMR. A més, aquests subtipus reflecteixen perfils cognitius específics. El deteriorament cognitiu en la malaltia de Parkinson també es troba associat a un patró concret d’alteracions en connectivitat estructural. Així, aquests resultats contribueixen a aclarir les bases de l’heterogeneïtat descrita en la malaltia de Parkinson i en la Demència amb cossos de Lewy, i aporten informació rellevant sobre quines característiques podrien ser considerades com biomarcadors de pitjor pronòstic, amb l’objectiu final d’apropar-nos a una medicina més personalitzada

Automatic quantification of juvenile zebrafish aggression.

BACKGROUND: Although aggression is a common symptom of psychiatric disorders the drugs available to treat it are non-specific and can have unwanted side effects. The zebrafish is an ideal model for aggression research. Zebrafish are small, amenable to genetic and pharmacological manipulation, and agonistic behaviour can be measured reliably. NEW METHOD: In this study we have established a novel setup to automatically quantify aggression and locomotion in one-month old juvenile zebrafish, a stage at which fish exhibit adult-like behaviour but are small so that one camera can film several animals. RESULTS: We have validated our novel software by comparison to manual quantification of behaviour, characterised the aggression of one-month old fish, and demonstrated that we can detect alterations to aggression caused by mutation or drug application. COMPARISON WITH OTHER METHODS: The ability to record up to 12 juvenile fish allows us to speed up and standardise data acquisition compared to studies of single fish. CONCLUSIONS: This setup appears to be suitable to screen for drugs that decrease zebrafish aggression as a first step toward developing novel treatments for this behaviour