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Thomas Nickl-Jockschat

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8 papers

1 author row

YNICL Journal 2025 Journal Article

Association between white matter microstructural changes and aggressiveness. A case-control diffusion tensor imaging study

Stephanie Seidenbecher
Jörn Kaufmann
Maria Schöne
Henrik Dobrowolny
Kolja Schiltz
Thomas Frodl
Johann Steiner
Bernhard Bogerts

Research has focused on identifying neurobiological risk factors associated with aggressive behavior in order to improve prevention and treatment efforts. This study aimed to characterize microstructural differences in white matter (WM) integrity in individuals prone to aggression. We hypothesized that altered cerebral WM microstructure may underlie normal individual variability in aggression and tested this using a case-control design in healthy individuals. Diffusion tensor imaging (DTI) was used to examine WM changes in martial artists (n = 29) and age-matched controls (n = 31). We performed tract-based spatial statistics (TBSS) to identify differences in axial diffusivity (AD), fractional anisotropy (FA) and mean diffusivity (MD) between the two groups at the whole-brain level. Martial artists were significantly more aggressive than controls, with increased MD in parietal and occipital areas and increased AD in widespread fiber tracts in the frontal, parietal and temporal areas. Positive associations between AD/MD and (physical) appetitive aggression were identified in several clusters, including the corpus callosum, the superior longitudinal fasciculus and the corona radiata. Our study found evidence for WM microstructural changes associated with aggressiveness in a community case-control sample. Longitudinal studies with larger cohorts, taking into account the dimensional nature of aggressiveness, are needed to better understand the underlying neurobiology.

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YNIMG Journal 2021 Journal Article

Differential resting-state patterns across networks are spatially associated with Comt and Trmt2a gene expression patterns in a mouse model of 22q11.2 deletion

Natalia Gass
Zeru Peterson
Jonathan Reinwald
Alexander Sartorius
Wolfgang Weber-Fahr
Markus Sack
Junfang Chen
Han Cao

Copy number variations (CNV) involving multiple genes are ideal models to study polygenic neuropsychiatric disorders. Since 22q11.2 deletion is regarded as the most important single genetic risk factor for developing schizophrenia, characterizing the effects of this CNV on neural networks offers a unique avenue towards delineating polygenic interactions conferring risk for the disorder. We used a Df(h22q11)/+ mouse model of human 22q11.2 deletion to dissect gene expression patterns that would spatially overlap with differential resting-state functional connectivity (FC) patterns in this model (N = 12 Df(h22q11)/+ mice, N = 10 littermate controls). To confirm the translational relevance of our findings, we analyzed tissue samples from schizophrenia patients and healthy controls using machine learning to explore whether identified genes were co-expressed in humans. Additionally, we employed the STRING protein-protein interaction database to identify potential interactions between genes spatially associated with hypo- or hyper-FC. We found significant associations between differential resting-state connectivity and spatial gene expression patterns for both hypo- and hyper-FC. Two genes, Comt and Trmt2a, were consistently over-expressed across all networks. An analysis of human datasets pointed to a disrupted co-expression of these two genes in the brain in schizophrenia patients, but not in healthy controls. Our findings suggest that COMT and TRMT2A form a core genetic component implicated in differential resting-state connectivity patterns in the 22q11.2 deletion. A disruption of their co-expression in schizophrenia patients points out a prospective cause for the aberrance of brain networks communication in 22q11.2 deletion syndrome on a molecular level.

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YNICL Journal 2021 Journal Article

Neurobiological substrates of the positive formal thought disorder in schizophrenia revealed by seed connectome-based predictive modeling

Ji Chen
Tobias Wensing
Felix Hoffstaedter
Edna C. Cieslik
Veronika I. Müller
Kaustubh R. Patil
André Aleman
Birgit Derntl

Formal thought disorder (FTD) is a core symptom cluster of schizophrenia, but its neurobiological substrates remain poorly understood. Here we collected resting-state fMRI data from 276 subjects at seven sites and employed machine-learning to investigate the neurobiological correlates of FTD along positive and negative symptom dimensions in schizophrenia. Three a priori, meta-analytically defined FTD-related brain regions were used as seeds to generate whole-brain resting-state functional connectivity (rsFC) maps, which were then compared between schizophrenia patients and controls. A repeated cross-validation procedure was realized within the patient group to identify clusters whose rsFC patterns to the seeds were repeatedly observed as significantly associated with specific FTD dimensions. These repeatedly identified clusters (i.e., robust clusters) were functionally characterized and the rsFC patterns were used for predictive modeling to investigate predictive capacities for individual FTD dimensional-scores. Compared with controls, differential rsFC was found in patients in fronto-temporo-thalamic regions. Our cross-validation procedure revealed significant clusters only when assessing the seed-to-whole-brain rsFC patterns associated with positive-FTD. RsFC patterns of three fronto-temporal clusters, associated with higher-order cognitive processes (e.g., executive functions), specifically predicted individual positive-FTD scores (p = 0.005), but not other positive symptoms, and the PANSS general psychopathology subscale (p > 0.05). The prediction of positive-FTD was moreover generalized to an independent dataset (p = 0.013). Our study has identified neurobiological correlates of positive FTD in schizophrenia in a network associated with higher-order cognitive functions, suggesting a dysexecutive contribution to FTD in schizophrenia. We regard our findings as robust, as they allow a prediction of individual-level symptom severity.

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YNICL Journal 2021 Journal Article

The functional neural architecture of dysfunctional reward processing in autism

Hildegard Janouschek
Henry W. Chase
Rachel J. Sharkey
Zeru J. Peterson
Julia A. Camilleri
Ted Abel
Simon B. Eickhoff
Thomas Nickl-Jockschat

Functional imaging studies have found differential neural activation patterns during reward-paradigms in patients with autism spectrum disorder (ASD) compared to neurotypical controls. However, publications report conflicting results on the directionality and location of these aberrant activations. We here quantitatively summarized relevant fMRI papers in the field using the anatomical likelihood estimation (ALE) algorithm. Patients with ASD consistently showed hypoactivations in the striatum across studies, mainly in the right putamen and accumbens. These regions are functionally involved in the processing of rewards and are enrolled in extensive neural networks involving limbic, cortical, thalamic and mesencephalic regions. The striatal hypo-activations found in our ALE meta-analysis, which pooled over contrasts derived from the included studies on reward-processing in ASD, highlight the role of the striatum as a key neural correlate of impaired reward processing in autism. These changes were present for studies using social and non-social stimuli alike. The involvement of these regions in extensive networks associated with the processing of both positive and negative emotion alike might hint at broader impairments of emotion processing in the disorder.

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YNICL Journal 2020 Journal Article

Electroconvulsive therapy modulates grey matter increase in a hub of an affect processing network

Julia A. Camilleri
Felix Hoffstaedter
Maxim Zavorotny
Rebecca Zöllner
Robert Christian Wolf
Philipp Thomann
Ronny Redlich
Nils Opel

A growing number of recent studies has suggested that the neuroplastic effects of electroconvulsive therapy (ECT) might be prominent enough to be detected through changes of regional gray matter volumes (GMV) during the course of the treatment. Given that ECT patients are difficult to recruit for imaging studies, most publications, however, report only on small samples. Addressing this challenge, we here report results of a structural imaging study on ECT patients that pooled patients from five German sites. Whole-brain voxel-based morphometry (VBM) analysis was performed to detect structural differences in 85 patients with unipolar depression before and after ECT, when compared to 86 healthy controls. Both task-independent and task-dependent physiological whole-brain functional connectivity patterns of these regions were modeled using additional data from healthy subjects. All emerging regions were additionally functionally characterized using the BrainMap database. Our VBM analysis detected a significant increase of GMV in the right hippocampus/amygdala region in patients after ECT compared to healthy controls. In healthy subjects this region was found to be enrolled in a network associated with emotional processing and memory. A region in the left fusiform gyrus was additionally found to have higher GMV in controls when compared with patients at baseline. This region showed minor changes after ECT. Our data points to a GMV increase in patients post ECT in regions that seem to constitute a hub of an emotion processing network. This appears as a plausible antidepressant mechanism and could explain the efficacy of ECT not only in the treatment of unipolar depression, but also of affective symptoms across heterogeneous disorders.

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YNIMG Journal 2017 Journal Article

Searching for behavior relating to grey matter volume in a-priori defined right dorsal premotor regions: Lessons learned

Sarah Genon
Tobias Wensing
Andrew Reid
Felix Hoffstaedter
Svenja Caspers
Christian Grefkes
Thomas Nickl-Jockschat
Simon B. Eickhoff

Recently, we showed that the functional heterogeneity of the right dorsal premotor (PMd) cortex could be better understood by dividing it into five subregions that showed different behavioral associations according to task-based activations studies. The present study investigated whether the revealed behavioral profile could be corroborated and complemented by a structural brain behavior correlation approach in two healthy adults cohorts. Grey matter volume within the five volumes of interest (VOI-GM) was computed using voxel-based morphometry. Associations between the inter-individual differences in VOI-GM and performance across a range of neuropsychological tests were assessed in the two cohorts with and without correction for demographical variables. Additional analyses were performed in random smaller subsamples drawn from each of the two cohorts. In both cohorts, correlation coefficients were low; only few were significant and a considerable number of correlations were counterintuitive in their directions (i. e. , higher performance related to lower grey matter volume). Furthermore, correlation patterns were inconsistent between the two cohorts. Subsampling revealed that correlation patterns could vary widely across small samples and that negative correlations were as likely as positive correlations. Thus, the structural brain-behavior approach did not corroborate the functional profiles of the PMd subregions inferred from activation studies, suggesting that local recruitment by fMRI studies does not necessarily imply covariance of local structure with behavioral performance in healthy adults. We discuss the limitations of such studies and related recommendations for future studies.

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YNICL Journal 2016 Journal Article

White matter microstructural changes in adolescent anorexia nervosa including an exploratory longitudinal study

Katja Vogel
Inge Timmers
Vinod Kumar
Thomas Nickl-Jockschat
Matteo Bastiani
Alard Roebroek
Beate Herpertz-Dahlmann
Kerstin Konrad

BACKGROUND: Anorexia nervosa (AN) often begins in adolescence, however, the understanding of the underlying pathophysiology at this developmentally important age is scarce, impeding early interventions. We used diffusion tensor imaging (DTI) to investigate microstructural white matter (WM) brain changes including an experimental longitudinal follow-up. METHODS: We acquired whole brain diffusion-weighted brain scans of 22 adolescent female hospitalized patients with AN at admission and nine patients longitudinally at discharge after weight rehabilitation. Patients (10-18 years) were compared to 21 typically developing controls (TD). Tract-based spatial statistics (TBSS) were applied to compare fractional anisotropy (FA) across groups and time points. Associations between average FA values of the global WM skeleton and weight as well as illness duration parameters were analyzed by multiple linear regression. RESULTS: We observed increased FA in bilateral frontal, parietal and temporal areas in AN patients at admission compared to TD. Higher FA of the global WM skeleton at admission was associated with faster weight loss prior to admission. Exploratory longitudinal analysis showed this FA increase to be partially normalized after weight rehabilitation. CONCLUSIONS: Our findings reveal a markedly different pattern of WM microstructural changes in adolescent AN compared to most previous results in adult AN. This could signify a different susceptibility and reaction to semi-starvation in the still developing brain of adolescents or a time-dependent pathomechanism differing with extend of chronicity. Higher FA at admission in adolescents with AN could point to WM fibers being packed together more closely.

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YNIMG Journal 2012 Journal Article

The impact of a Dysbindin schizophrenia susceptibility variant on fiber tract integrity in healthy individuals: A TBSS-based diffusion tensor imaging study

Thomas Nickl-Jockschat
Tony Stöcker
Valentin Markov
Axel Krug
Ruihuang Huang
Frank Schneider
Ute Habel
Klaus Zerres

Schizophrenia is a severe neuropsychiatric disorder with high heritability, though its exact etiopathogenesis is yet unknown. An increasing number of studies point to the importance of white matter anomalies in the pathophysiology of schizophrenia. While several studies have identified the impact of schizophrenia susceptibility gene variants on gray matter anatomy in both schizophrenia patients and healthy risk variant carriers, studies dealing with the impact of these gene variants on white matter integrity are still scarce. We here present a study on the effects of a Dysbindin schizophrenia susceptibility gene variant on fiber tract integrity in healthy young subjects. 101 subjects genotyped for Dysbindin-gene variant rs1018381, though without personal or first degree relative history of psychiatric disorders underwent diffusion tensor imaging (DTI), 83 of them were included in the final analysis. We used Tract-Based Spatial Statistics (TBSS) analysis to delineate the major fiber tracts. Carriers of the minor allele T of the rs1018381 in the Dysbindin gene showed two clusters of reduced fractional anisotropy (FA) values in the perihippocampal region of the right temporal lobe compared to homozygote carriers of the major allele C. Clusters of increased FA values in T-allele carriers were found in the left prefrontal white matter, the right fornix, the right midbrain area, the left callosal body, the left cerebellum and in proximity of the right superior medial gyrus. Dysbindin has been implicated in neurite outgrowth and morphology. Impairments in anatomic connectivity as found associated with the minor Dysbindin allele in our study may result in increased risk for schizophrenia due to altered fiber tracts.

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