The risk of cannabis use disorder is mediated by altered brain connectivity: A chronnectome study.

The brain mechanisms underlying the risk of cannabis use disorder (CUD) are poorly understood. Several studies have reported changes in functional connectivity (FC) in CUD, although none have focused on the study of time-varying patterns of FC. To fill this important gap of knowledge, 39 individuals at risk for CUD and 55 controls, stratified by their score on a self-screening questionnaire for cannabis-related problems (CUDIT-R), underwent resting-state functional magnetic resonance imaging. Dynamic functional connectivity (dFNC) was estimated using independent component analysis, sliding-time window correlations, cluster states and meta-state indices of global dynamics and were compared among groups. At-risk individuals stayed longer in a cluster state with higher within and reduced between network dFNC for the subcortical, sensory-motor, visual, cognitive-control and default-mode networks, relative to controls. More globally, at-risk individuals had a greater number of meta-states and transitions between them and a longer state span and total distance between meta-states in the state space. Our findings suggest that the risk of CUD is associated with an increased dynamic fluidity and dynamic range of FC. This may result in altered stability and engagement of the brain networks, which can ultimately translate into altered cortical and subcortical function conveying CUD risk. Identifying these changes in brain function can pave the way for early pharmacological and neurostimulation treatment of CUD, as much as they could facilitate the stratification of high-risk individuals.

Associations between brain morphology, inflammatory markers and symptoms of fatigue, depression or anxiety in active and remitted Crohn's disease.

BACKGROUND: Fatigue and psychosocial impairments are highly prevalent in IBD, especially during active disease. Disturbed brain-gut-interactions may contribute to these symptoms. This study examined associations between brain structure, faecal calprotectin and symptoms of fatigue, depression and anxiety in persons with Crohn's Disease (CD) in different disease states. METHODS: In this prospective observational study, n=109 participants (n=67 persons with CD, n=42 healthy controls) underwent cranial magnetic resonance imaging, provided stool samples for analysis of faecal calprotectin and completed questionnaires to assess symptoms of fatigue, depression and anxiety. We analysed differences in grey matter volume (GMV) between patients and controls and associations between regional GMV alterations, neuropsychiatric symptoms and faecal calprotectin. RESULTS: Symptoms of fatigue, depression and anxiety were increased in patients with CD compared to controls, with highest scores in active CD. Patients exhibited regionally reduced GMV in cortical and subcortical sensorimotor regions, occipitotemporal and medial frontal areas. Regional GMV differences showed a significant negative association with fatigue, but not with depression or anxiety. Subgroup analyses revealed symptom-GMV-associations for fatigue in remitted, but not in active CD, while fatigue was positively associated with faecal calprotectin in active, but not remitted disease. CONCLUSION: Our findings support disturbed brain-gut-interactions in CD which may be particularly relevant for fatigue during remitted disease. Reduced GMV in the precentral gyrus and other sensorimotor areas could reflect key contributions to fatigue pathophysiology in CD. A sensorimotor model of fatigue in CD could also pave the way for novel treatment approaches.

Functional network interactions in patients with schizophrenia with persistent auditory verbal hallucinations: A multimodal MRI fusion approach using three-way pICA.

Over the last decade, there have been an increasing number of functional magnetic resonance imaging (fMRI) studies examining brain activity in schizophrenia (SZ) patients with persistent auditory verbal hallucinations (AVH) using either task-based or resting-state fMRI (rs-fMRI) paradigms. Such data have been conventionally collected and analyzed as distinct modalities, disregarding putative crossmodal interactions. Recently, it has become possible to incorporate two or more modalities in one comprehensive analysis to uncover hidden patterns of neural dysfunction not sufficiently captured by separate analysis. A novel multivariate fusion approach to multimodal data analysis, i.e., parallel independent component analysis (pICA), has been previously shown to be a powerful tool in this regard. We utilized three-way pICA to study covarying components among fractional amplitude of low-frequency fluctuations (fALFF) for rs-MRI and task-based activation computed from an alertness and a working memory (WM) paradigm of 15 SZ patients with AVH, 16 non-hallucinating SZ patients (nAVH), and 19 healthy controls (HC). The strongest connected triplet (false discovery rate (FDR)-corrected pairwise correlations) comprised a frontostriatal/temporal network (fALFF), a temporal/sensorimotor network (alertness task), and a frontoparietal network (WM task). Frontoparietal and frontostriatal/temporal network strength significantly differed between AVH patients and HC. Phenomenological features such as omnipotence and malevolence of AVH were associated with temporal/sensorimotor and frontoparietal network strength. The transmodal data confirm a complex interplay of neural systems subserving attentional processes and cognitive control interacting with speech and language processing networks. In addition, the data emphasize the importance of sensorimotor regions modulating specific symptom dimensions of AVH.

Oxytocin effects on amygdala reactivity to angry faces in males and females with antisocial personality disorder.

The amygdala is a key region in current neurocircuitry models of reactive aggression as it is crucially involved in detecting social threat and provocation. An increased amygdala reactivity to angry faces has been reported in aggression-prone individuals and the neuropeptide oxytocin (OT) could dampen anger-related amygdala reactivity in a number of mental disorders. One example is the antisocial personality disorder (ASPD) which has so far only been studied in limited numbers. To address the question whether OT can normalize amygdala hyperreactivity to emotional faces, we conducted a functional magnetic resonance imaging experiment with 20 men and 18 women with ASPD and 20 male and 20 female healthy control (HC) participants in a double-blind, randomized, placebo (PLC)-controlled within-subject design. Participants were exposed to an emotion classification task (fearful, angry, and happy faces) after receiving an intranasal dose (24 IU) of synthetic OT or PLC. We found OT to attenuate right amygdala hyperactivity to angry faces in participants with ASPD to such an extent that the intensity of amygdala activity in the ASPD group in the OT condition decreased to the level of amygdala activity in the PLC condition in the HC group. There was also a trend that OT effects were generally larger in women than in men. These findings suggest that OT differentially modulates the amygdala following social threatening or provoking cues in dependence of psychopathology (ASPD vs. HC) and sex (male vs. female). Particularly female ASPD patients could benefit from OT in the treatment of reactive aggression.

Cognitive domain-independent aberrant frontoparietal network strength in individuals with excessive smartphone use.

Excessive smartphone use (ESU) may fulfill criteria for addictive behavior. In contrast to other related behavioral addictions, particularly Internet Gaming Disorder, little is known about the neural correlates underlying ESU. In this study, we used functional magnetic resonance imaging (fMRI) to acquire task data from three distinct behavioral paradigms, i.e. cue-reactivity, inhibition, and working memory, in individuals with psychometrically defined ESU (n = 19) compared to controls (n-ESU; n = 20). The Smartphone Addiction Inventory (SPAI) was used to quantify ESU-severity according to a novel five-factor model (SPAI-I). A multivariate data fusion approach, i.e. joint Independent Component Analysis (jICA) was employed to analyze fMRI-data derived from three separate experimental conditions, but analyzed jointly to detect converging and domain-independent neural signatures that differ between persons with vs. those without ESU. Across the three functional tasks, jICA identified a predominantly frontoparietal system that showed lower network strength in individuals with ESU compared to n-ESU (p < 0.05 FDR-corrected). Furthermore, significant associations between frontoparietal network strength and SPAI-I's dimensions "time spent" and "craving" were found. The data suggest a frontoparietal cognitive control network as cognitive domain-independent neural signature of excessive and potentially addictive smartphone use.

Functional correlates of neurological soft signs in heavy cannabis users.

Sensorimotor dysfunction has been previously reported in persons with cannabis dependence. Such individuals can exhibit increased levels of neurological soft signs (NSS), particularly involving motor coordination, sensorimotor integration and complex motor task performance. Abnormal NSS levels can also be detected in non-dependent individuals with heavy cannabis use (HCU), yet very little is known about the functional correlates underlying such deficits. Here, we used resting-state functional magnetic resonance imaging (MRI) to investigate associations between NSS and intrinsic neural activity (INA) in HCU (n = 21) and controls (n = 26). Compared with controls, individuals with HCU showed significantly higher NSS across all investigated subdomains. Three of these subdomains, that is, motor coordination, sensorimotor integration and complex motor task behaviour, were associated with specific use-dependent variables, particularly age of onset of cannabis use and current cannabis use. Between-group comparisons of INA revealed lower regional homogeneity (ReHo) in left precentral gyrus, left inferior occipital gyrus, right triangular pat of the inferior frontal gyrus and right precentral gyrus in HCU compared with controls. In addition, HCU showed also higher ReHo in right cerebellum and left postcentral gyrus compared with controls. Complex motor task behaviour in HCU was significantly related to INA in postcentral, inferior frontal and occipital cortices. Our findings indicate abnormal ReHo in HCU in regions associated with sensorimotor, executive control and visuomotor-integration processes. Importantly, we show associations between ReHo, cannabis-use behaviour and execution of complex motor tasks. Given convergent findings in manifest psychotic disorders, this study suggests an HCU endophenotype that may present with a cumulative risk for psychosis.

Structure/function interrelationships and illness insight in patients with schizophrenia: a multimodal MRI data fusion study.

Illness insight in schizophrenia (SZ) has an important impact on treatment outcome, integration into society and can vary over the course of the disorder. To deal with and treat reduced or absent illness insight, we need to better understand its functional and structural correlates. Previous studies showed regionally abnormal brain volume in brain areas related to cognitive control and self-reference. However, little is known about associations between illness insight and structural and functional network strength in patients with SZ. This study employed a cross-sectional design to examine structural and functional differences between patients with SZ (n = 74) and healthy controls (n = 47) using structural and resting-state functional magnetic resonance imaging (MRI). Voxel-based morphometry was performed on structural data, and the amplitude of low frequency fluctuations (ALFF) was calculated for functional data. To investigate abnormal structure/function interrelationships and their association with illness insight, we used parallel independent component analysis (pICA). Significant group (SZ vs. HC) differences were detected in distinct structural and functional networks, predominantly comprising frontoparietal, temporal and cerebellar regions. Significant associations were found between illness insight and two distinct structural networks comprising frontoparietal (pre- and postcentral gyrus, inferior parietal lobule, thalamus, and precuneus) and posterior cortical regions (cuneus, precuneus, lingual, posterior cingulate, and middle occipital gyrus). Finally, we found a significant relationship between illness insight and functional network comprising temporal regions (superior temporal gyrus). This study suggests that aberrant structural and functional integrity of neural systems subserving cognitive control, memory and self-reference are tightly coupled to illness insight in SZ.

Structural Correlates of Lifetime Voice-Hearing in Patients with Borderline Personality Disorder: A Pilot Study.

INTRODUCTION: Auditory verbal hallucinations (AVH) are transdiagnostic phenomena that can occur in several mental disorders, including borderline personality disorder (BPD). Despite the transdiagnostic relevance of these symptoms, very little is known about neural signatures of AVH in BPD. METHODS: We used structural magnetic resonance imaging to investigate multiple markers of brain morphology in BPD patients presenting with a lifetime history of AVH (AVH, n = 6) versus BPD patients without AVH (nAVH, n = 10) and healthy controls (HC, n = 12). The Computational Anatomy Toolbox (CAT12) was used for surface-based morphometric analyses that considered cortical thickness (CTh), gyrification (CG), and complexity of cortical folding (CCF). Factorial models were used to explore differences between AVH patients and HC, as well as between the patient groups. RESULTS: Compared to HC, AVH patients showed distinct abnormalities in key regions of the language network, i.e., aberrant CTh and CG in right superior temporal gyrus and abnormal CCF in left inferior frontal gyrus. Further abnormalities were found in right prefrontal cortex (CTh) and left orbitofrontal cortex (CCF). Compared to nAVH patients, individuals with AVH showed abnormal CTh in right prefrontal cortex, along with CCF differences in right transverse temporal, superior parietal, and parahippocampal gyri. CG differences between the patient groups were found in left orbitofrontal cortex. CONCLUSION: The data suggest a transdiagnostic neural signature of voice-hearing that converges on key regions involved in speech generation and perception, memory and executive control. It is possible that cortical features of distinct evolutionary and genetic origin, i.e., CTh and CG/CCF, differently contribute to AVH vulnerability in BPD.

Neurochemical Correlates of Cue Reactivity in Individuals with Excessive Smartphone Use.

BACKGROUND: Excessive smartphone use (ESU), that is, a pattern of smartphone use that shows specific features of addictive behavior, has increasingly attracted societal and scientific interest in the past years. On the neurobiological level, ESU has recently been related to structural and functional variation in reward and salience processing networks, as shown by, for example, aberrant patterns of neural activity elicited by specific smartphone cues. OBJECTIVES: Expanding on these findings, using cross-modal correlations of magnetic resonance imaging (MRI)-based measures with nuclear imaging-derived estimates, we aimed at identifying neurochemical pathways that are related to ESU. METHODS: Cross-modal correlations between functional MRI data derived from a cue-reactivity task administered in persons with and without ESU and specific PET/SPECT receptor probability maps. RESULTS: The endogenous mu-opioid receptor (MOR) system was found to be significantly (FDR-corrected) correlated with fMRI data, and z-transformed correlation coefficients showed an association (albeit nonsignificant after FDR-correction) between MOR and the Smartphone Addiction Inventory "withdrawal" dimension. CONCLUSIONS: We could identify the MOR system as a neurochemical pathway associated with ESU. The MOR system is closely linked to the reward system, which has been recognized as a key player in addictive disorders. Together with its potential link to withdrawal, the MOR system hints toward a biologically highly relevant marker, which should be taken into consideration in the ongoing scientific discussion on technology-related addictive behaviors.

Practical challenges of continuous real-time functional magnetic resonance imaging neurofeedback with multiband accelerated echo-planar imaging and short repetition times.

Continuous real-time functional magnetic resonance imaging (fMRI) neurofeedback is gaining increasing scientific attention in clinical neuroscience and may benefit from the short repetition times of modern multiband echoplanar imaging sequences. However, minimizing feedback delay can result in technical challenges. Here, we report a technical problem we experienced during continuous fMRI neurofeedback with multiband echoplanar imaging and short repetition times. We identify the possible origins of this problem, describe our current interim solution and provide openly available workflows and code to other researchers in case they wish to use a similar approach.

Effects of Mindfulness-Based Interventions on Gray Matter Volume in Patients with Opioid Dependence.

INTRODUCTION: Recently, several mindfulness-based programs showed promising clinical effects in the treatment of psychiatric disorders including substance use disorders. However, very little is known about the effects of mindfulness-based interventions (MBIs) on brain structure in such patients. METHODS: This study aimed to detect changes in gray matter volume (GMV) in opioid-dependent patients receiving MBI during their first month of treatment. Thirty patients were assigned to either 3 weeks of MBI (n = 16) or treatment as usual (TAU, n = 14) and were investigated using structural magnetic resonance imaging before and after treatment. Longitudinal pipeline of the Computational Anatomy Toolbox for SPM (CAT12) was used to detect significant treatment-related changes over time. The identified GMV changes following treatment were related to clinically relevant measures such as impulsivity, distress tolerance, and mindfulness. RESULTS: After treatment, increased mindfulness scores were found in individuals receiving MBI compared to TAU. In the MBI group, there were also significant differences with respect to distress tolerance and impulsivity. Effects on mindfulness, distress tolerance, and impulsivity were also found in the TAU group. Longitudinal within-group analysis revealed increased left anterior insula GMV in individuals receiving MBI. Anterior insula volume increase was associated with decreased impulsivity levels. In the TAU group, significant GMV changes were found in the right lingual gyrus and right entorhinal cortex. DISCUSSION/CONCLUSION: MBI can yield significant clinical effects during early abstinence from opioid dependence. MBI is particularly associated with increased insula GMV, supporting an important role of this region in the context of MBI-induced neural changes.

Aberrant intrinsic neural network strength in individuals with "smartphone addiction": An MRI data fusion study.

BACKGROUND AND OBJECTIVES: Excessive smartphone use, also referred to as "smartphone addiction" (SPA), has increasingly attracted neuroscientific interest due to its similarities with other behavioral addictions, particularly internet gaming disorder. Little is known about the neural mechanisms underlying smartphone addiction. We explored interrelationships between brain structure and function to specify neurobiological correlates of SPA on a neural system level. METHODS: Gray matter volume (GMV) and intrinsic neural activity (INA) were investigated in individuals with SPA (n = 20) and controls (n = 24), using multimodal magnetic resonance imaging and multivariate data fusion techniques, that is, parallel independent component analysis. RESULTS: The joint analysis of both data modalities explored shared information between GMV and INA. In particular, two amplitudes of low frequency fluctuations-based independent neural systems significantly differed between individuals with SPA and controls. A medial/dorsolateral prefrontal system exhibited lower functional network strength in individuals with SPA versus controls, whereas the opposite pattern was detected in a parietal cortical/cerebellar system. Neural network strength was significantly related to duration of smartphone use and sleep difficulties. DISCUSSION AND CONCLUSIONS: We show modality-specific associations of the brain's resting-state activity with distinct and shared SPA symptom dimensions. In particular, the data suggest contributions of aberrant prefrontal and parietal neural network strength as a possible signature of deficient executive control in SPA. SCIENTIFIC SIGNIFICANCE: This study suggests distinct neural mechanisms underlying specific biological and behavioral dimensions of excessive smartphone use.

Structural alterations of amygdala and hypothalamus contribute to catatonia.

At present, current diagnostic criteria and systems neglect affective symptom expression in catatonia. This potentially serious omission could explain why putative contributions of limbic system structures, such as amygdala, hippocampus or hypothalamus, to catatonia in schizophrenia spectrum disorders (SSD) have been scarcely investigated so far. To determine whether topographical alterations of the amygdala, hippocampus and hypothalamus contribute to catatonia in SSD patients, we conducted structural magnetic resonance imaging (MRI) of SSD patients with (SSD-Cat, n = 30) and without (SSD-nonCat, n = 28) catatonia as defined by a Northoff Catatonia Rating Scale (NCRS) total score of ≥3 and =0, respectively, in comparison with healthy controls (n = 20). FreeSurfer v7.2 was used for automated segmentation of the amygdala and its 9 nuclei, hippocampus and its 21 subfields and hypothalamus and its associated 5 subunits. SSD-Cat had significantly smaller anterior inferior hypothalamus, cortical nucleus of amygdala, and hippocampal fimbria volumes when compared to SSD-nonCat. SSD-Cat had significantly smaller amygdala, hippocampus and hypothalamus whole and subunit volumes when compared to healthy controls. In SSD-Cat according to DSM-IV-TR (n = 44), we identified positive correlations between Brief Psychiatric Rating Scale (BPRS) item #2 (reflecting anxiety) and respective amygdala nuclei as well as negative correlation between NCRS behavioral score and hippocampus subiculum head. The lower volumes of respective limbic structures involved in affect regulation may point towards central affective pathomechanisms in catatonia.

Cortical surface variation in individuals with excessive smartphone use.

Excessive smartphone use has been repeatedly related to adverse effects on mental health and psychological well-being in young adults. The continued investigation of the neurobiological mechanism underlying excessive smartphone use-sometimes also referred to as "smartphone addiction"(SPA)-is considered a top priority in system neuroscience research. Despite progress in the past years, cortical morphology associated with SPA is still poorly understood. Here, we used structural magnetic resonance imaging (MRI) at 3 T to investigate two cortical surface markers of distinct neurodevelopmental origin such as the complexity of cortical folding (CCF) and cortical thickness (CTh) in individuals with excessive smartphone use (n = 19) compared to individuals not fulfilling SPA criteria (n-SPA; n = 22). SPA was assessed using the Smartphone Addiction Inventory (SPAI). CCF and CTh were investigated using the Computational Anatomy Toolbox (CAT12). SPA individuals showed lower CCF in the right superior frontal gyrus as well as in the right caudal (cACC) and rostral anterior cingulate cortex (rACC) compared to n-SPA individuals (TFCE, uncorrected at p < 0.001). Following a dimensional approach, across the entire sample, CCF of the right cACC was significantly associated with SPAI total score, as well as with distinct SPAI subdimensions, particularly time spent with the device, compulsivity, and sleep interference in all participants (n = 41; p < 0.05, FDR-corrected). Collectively, these findings suggest that SPA is associated with aberrant structural maturation of regions important for cognitive control and emotional regulation.

Cortical morphology and illness insight in patients with schizophrenia.

Insight into illness in schizophrenia (SZ) patients has a major impact on treatment adherence and outcome. Previous studies have linked distinct deviations of brain structure to illness insight, specifically in frontoparietal and subcortical regions. Some of these abnormalities are thought to reflect aberrant cortical development. In this study, we used cross-sectional data to examine associations between illness insight and two cortical surface markers that are known to follow distinct neurodevelopmental trajectories, i.e. cortical gyrification (CG) and thickness (CT). CG and CT was investigated in SZ patients (n = 82) and healthy controls (HC, n = 48) using 3 T structural magnetic resonance imaging. Illness insight in SZ patients was measured using the OSSTI scale, an instrument that provides information on two distinct dimensions of illness insight, i.e. treatment adherence (OSSTI-A) and identification of disease-related symptoms (OSSTI-I). CT and CG were computed using the Computational Anatomy Toolbox (CAT12). Whole-brain and regions-of-interest (ROI)-based analyses were performed. SZ patients showed higher CG in anterior cingulate, superior frontal and temporal gyrus and reduced CG in insular and superior frontal cortex when compared to HC. SZ patients showed decreased CT in pre- and paracentral, occipital, cingulate, frontoparietal and temporal regions. Illness insight in SZ patients was significantly associated with both CG and CT in the left inferior parietal lobule (OSSTI-A) and the right precentral gyrus (CG/OSSTI-A, CT/OSSTI-I). The data support a multi-parametric neuronal model with both pre- and postnatal brain developmental factors having an impact on illness insight in patients with SZ.

Multimodal MRI data fusion reveals distinct structural, functional and neurochemical correlates of heavy cannabis use.

Heavy cannabis use (HCU) is frequently associated with a plethora of cognitive, psychopathological and sensorimotor phenomena. Although HCU is frequent, specific patterns of abnormal brain structure and function underlying HCU in individuals presenting without cannabis-use disorder or other current and life-time major mental disorders are unclear at present. This multimodal magnetic resonance imaging (MRI) study examined resting-state functional MRI (rs-fMRI) and structural MRI (sMRI) data from 24 persons with HCU and 16 controls. Parallel independent component analysis (p-ICA) was used to examine covarying components among grey matter volume (GMV) maps computed from sMRI and intrinsic neural activity (INA), as derived from amplitude of low-frequency fluctuations (ALFF) maps computed from rs-fMRI data. Further, we used JuSpace toolbox for cross-modal correlations between MRI-based modalities with nuclear imaging derived estimates, to examine specific neurotransmitter system changes underlying HCU. We identified two transmodal components, which significantly differed between the HCU and controls (GMV: p = 0.01, ALFF p = 0.03, respectively). The GMV component comprised predominantly cerebello-temporo-thalamic regions, whereas the INA component included fronto-parietal regions. Across HCU, loading parameters of both components were significantly associated with distinct HCU behavior. Finally, significant associations between GMV and the serotonergic system as well as between INA and the serotonergic, dopaminergic and µ-opioid receptor system were detected. This study provides novel multimodal neuromechanistic insights into HCU suggesting co-altered structure/function-interactions in neural systems subserving cognitive and sensorimotor functions.

Structural alterations in brainstem, basal ganglia and thalamus associated with parkinsonism in schizophrenia spectrum disorders.

The relative roles of brainstem, thalamus and striatum in parkinsonism in schizophrenia spectrum disorder (SSD) patients are largely unknown. To determine whether topographical alterations of the brainstem, thalamus and striatum contribute to parkinsonism in SSD patients, we conducted structural magnetic resonance imaging (MRI) of SSD patients with (SSD-P, n = 35) and without (SSD-nonP, n = 64) parkinsonism, as defined by a Simpson and Angus Scale (SAS) total score of ≥ 4 and < 4, respectively, in comparison with healthy controls (n = 20). FreeSurfer v6.0 was used for segmentation of four brainstem regions (medulla oblongata, pons, superior cerebellar peduncle and midbrain), caudate nucleus, putamen and thalamus. Patients with parkinsonism had significantly smaller medulla oblongata (p = 0.01, false discovery rate (FDR)-corrected) and putamen (p = 0.02, FDR-corrected) volumes when compared to patients without parkinsonism. Across the entire patient sample (n = 99), significant negative correlations were identified between (a) medulla oblongata volumes and both SAS total (p = 0.034) and glabella-salivation (p = 0.007) scores, and (b) thalamic volumes and both SAS total (p = 0.033) and glabella-salivation (p = 0.007) scores. These results indicate that brainstem and thalamic structures as well as basal ganglia-based motor circuits play a crucial role in the pathogenesis of parkinsonism in SSD.

Structural correlates of sensorimotor dysfunction in heavy cannabis users.

Sensorimotor dysfunction has been previously reported in persons with cannabis dependence. Such individuals can exhibit increased levels of neurological soft signs (NSS), particularly involving motor coordination and sensorimotor integration. Whether such abnormalities may also apply to non-dependent individuals with heavy cannabis use (HCU) is unknown, as much as the neural correlates underlying such deficits. In this study, we investigated associations between NSS and gray matter volume (GMV) in males with HCU and male controls. Twenty-four persons with HCU and 17 controls were examined using standardized assessment of NSS and structural magnetic resonance imaging (MRI) at 3 T. GMV was calculated using voxel-based morphometry algorithms provided by the Computational Anatomy Toolbox (CAT12). Individuals with HCU showed higher NSS total scores compared to controls. In particular, significant NSS-subdomain effects were found for "motor coordination" (MoCo), "complex motor tasks" (CoMT), and "hard signs" (HS) expression in HCU (p < 0.05, Bonferroni-corrected). Compared to controls, persons with HCU showed significant NSS/GMV interactions in putamen and inferior frontal cortex (MoCo), right cerebellum (CoMT) and middle and superior frontal cortices, and bilateral precentral cortex and thalamus (HS). In between-group analyses, individuals with HCU showed lower GMV in the right anterior orbital and precentral gyrus, as well as higher GMV in the right superior frontal gyrus and left supplementary motor cortex compared to controls. The data support the notion of abnormal sensorimotor performance associated with HCU. The data also provide a neuromechanistic understanding of such deficits, particularly with respect to aberrant cortical-thalamic-cerebellar-cortical circuit.

A neurodevelopmental signature of parkinsonism in schizophrenia.

While sensorimotor abnormalities in schizophrenia (SZ) are of increasing scientific interest, little is known about structural changes and their developmental origins that may underlie parkinsonism. This multimodal magnetic resonance imaging (MRI) study examined healthy controls (HC, n = 20) and SZ patients with (SZ-P, n = 38) and without (SZ-nonP, n = 35) parkinsonism, as defined by Simpson-Angus Scale total scores of ≥4 or ≤1, respectively. Using the Computational Anatomy Toolbox (CAT12), voxel- and surface-based morphometry were applied to investigate cortical and subcortical gray matter volume (GMV) and three cortical surface markers of distinct neurodevelopmental origin: cortical thickness (CTh), complexity of cortical folding (CCF) and sulcus depth. In a subgroup of patients (29 SZ-nonP, 25 SZ-P), resting-state fMRI data were also analyzed using a regions-of-interest approach based on fractional amplitude of low frequency fluctuations (fALFF). SZ-P patients showed increased CCF in the left supplementary motor cortex (SMC) and decreased left postcentral sulcus (PCS) depth compared to SZ-nonP patients (p < 0.05, FWE-corrected at cluster level). In SMC, CCF was associated negatively with activity, which also differed significantly between the patient groups and between patients and HC. In regression models, severity of parkinsonism was associated negatively with left middle frontal CCF and left anterior cingulate CTh. These data provide novel insights into altered trajectories of cortical development in SZ patients with parkinsonism. These cortical surface changes involve the sensorimotor system, suggesting abnormal neurodevelopmental processes tightly coupled with cortical activity and subcortical morphology that convey increased risk for sensorimotor abnormalities in SZ.