Mapping brain-behavior space relationships along the psychosis spectrum.
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ABSTRACT:
SUBMITTER: Ji JL
PROVIDER: S-EPMC8315806 | biostudies-literature | 2021 Jul
REPOSITORIES: biostudies-literature
Publications
Mapping brain-behavior space relationships along the psychosis spectrum.
Ji Jie Lisa JL Helmer Markus M Fonteneau Clara C Burt Joshua B JB Tamayo Zailyn Z Demšar Jure J Adkinson Brendan D BD Savić Aleksandar A Preller Katrin H KH Moujaes Flora F Vollenweider Franz X FX Martin William J WJ Repovš Grega G Cho Youngsun T YT Pittenger Christopher C Murray John D JD Anticevic Alan A
eLife 20210720
Difficulties in advancing effective patient-specific therapies for psychiatric disorders highlight a need to develop a stable neurobiologically grounded mapping between neural and symptom variation. This gap is particularly acute for psychosis-spectrum disorders (PSD). Here, in a sample of 436 PSD patients spanning several diagnoses, we derived and replicated a dimensionality-reduced symptom space across hallmark psychopathology symptoms and cognitive deficits. In turn, these symptom axes mapped ...[more]
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Project description:BACKGROUND:Cognitive and structural brain abnormalities range from mild to severe in psychosis. The relationships of specific cognitive functions to specific brain structures across the psychosis spectrum is less certain. METHODS:Participants (n = 678) with bipolar, schizoaffective, or schizophrenia psychoses and healthy control subjects were recruited via the Bipolar-Schizophrenia Network for Intermediate Phenotypes. The Schizo-Bipolar Scale was used to create a psychosis continuum (from purely affective to purely nonaffective). Canonical correlation between 14 cognitive measures and structural brain measures (gray matter volume, cortical thickness, cortical surface area, and local gyrification indices) for 68 neocortical regions yielded constructs that defined shared cognition-brain structure relationships. Canonical discriminant analysis was used to integrate these constructs and efficiently summarize cognition-brain structure relationships across the psychosis continuum. RESULTS:General cognition was associated with larger gray matter volumes and thicker cortices but smaller cortical surface area in frontoparietal regions. Working memory was associated with larger volume and surface area in frontotemporal regions. Faster response speed was associated with thicker frontal cortices. Constructs that captured general cognitive ability and working memory and their relationship to cortical volumes primarily defined an ordered psychosis spectrum (purely affective, least abnormal through purely nonaffective, and most abnormal). A construct that captured general cognitive ability and its relationship to cortical surface area differentiated purely affective cases from other groups. CONCLUSIONS:General cognition and working memory with cortical volume deviations characterized more nonaffective psychoses. Alternatively, affective psychosis cases with general cognitive deficits had deviations in cortical surface area, perhaps accounting for heterogeneous findings across previous studies.
| S-EPMC6167203 | biostudies-literature
Project description:BackgroundIndividuals with subclinical psychotic symptoms provide a unique window on the pathophysiology of psychotic experiences as these individuals are free of confounders such as hospitalization, negative and cognitive symptoms and medication use. Brain network disturbances of white matter connections are thought to play a central role in the pathophysiology of psychosis. Based on the structural network disconnection hypothesis in schizophrenia, we expect less and weaker connections, and altered brain network organization in individuals with clinical and those with subclinical psychotic symptoms.MethodsWe used diffusion tensor imaging to study 35 patients with a psychotic disorder, 35 subjects with subclinical psychotic symptoms, and 36 healthy controls. The structural brain network was analyzed on 3 levels: connection density, white matter microstructure (fractional anisotropy, mean diffusivity, and magnetic transfer ratio), and network organization. Network organization was studied with minimum spanning tree analysis, a method to reconstruct a backbone of structural highways in the brain.ResultsDecreased fractional anisotropy and increased mean diffusivity was found in both groups with psychotic symptoms, while their network topology showed decreased overlap with a healthy reference network. Decreased centrality was found in several brain regions, including parietal hubs and language areas, in both groups with psychotic symptoms. Deviation of network characteristics was more apparent in clinical subjects than in subclinical subjects.DiscussionWeaker connections and decreased centrality of parietal hubs characterize the structural brain network in subjects with psychotic symptoms. These differences are more notable in clinical than in subclinical subjects with psychotic experiences.
| S-EPMC4838099 | biostudies-literature
Project description:ImportanceStructural brain abnormalities are prominent in psychotic disorders, including schizophrenia. However, it is unclear when aberrations emerge in the disease process and if such deficits are present in association with less severe psychosis spectrum (PS) symptoms in youth.ObjectiveTo investigate the presence of structural brain abnormalities in youth with PS symptoms.Design, setting, and participantsThe Philadelphia Neurodevelopmental Cohort is a prospectively accrued, community-based sample of 9498 youth who received a structured psychiatric evaluation. A subsample of 1601 individuals underwent neuroimaging, including structural magnetic resonance imaging, at an academic and children's hospital health care network between November 1, 2009, and November 30, 2011.Main outcomes and measuresMeasures of brain volume derived from T1-weighted structural neuroimaging at 3 T. Analyses were conducted at global, regional, and voxelwise levels. Regional volumes were estimated with an advanced multiatlas regional segmentation procedure, and voxelwise volumetric analyses were conducted as well. Nonlinear developmental patterns were examined using penalized splines within a general additive model. Psychosis spectrum (PS) symptom severity was summarized using factor analysis and evaluated dimensionally.ResultsFollowing exclusions due to comorbidity and image quality assurance, the final sample included 791 participants aged youth 8 to 22 years. Fifty percent (n = 393) were female. After structured interviews, 391 participants were identified as having PS features (PS group) and 400 participants were identified as typically developing comparison individuals without significant psychopathology (TD group). Compared with the TD group, the PS group had diminished whole-brain gray matter volume (P = 1.8 × 10-10) and expanded white matter volume (P = 2.8 × 10-11). Voxelwise analyses revealed significantly lower gray matter volume in the medial temporal lobe (maximum z score = 5.2 and cluster size of 1225 for the right and maximum z score = 4.5 and cluster size of 310 for the left) as well as in frontal, temporal, and parietal cortex. Volumetric reduction in the medial temporal lobe was correlated with PS symptom severity.Conclusions and relevanceStructural brain abnormalities that have been commonly reported in adults with psychosis are present early in life in youth with PS symptoms and are not due to medication effects. Future longitudinal studies could use the presence of such abnormalities in conjunction with clinical presentation, cognitive profile, and genomics to predict risk and aid in stratification to guide early interventions.
| S-EPMC5048443 | biostudies-literature
Project description:Psychosis is associated with abnormal structural changes in the brain including decreased regional brain volumes and abnormal brain morphology. However, the underlying causes of these structural abnormalities are less understood. The immune system, including microglial activation, has been implicated in the pathophysiology of psychosis. Although previous studies have suggested a connection between peripheral proinflammatory cytokines and structural brain abnormalities in schizophrenia, no in-vivo studies have investigated whether microglial activation is also linked to brain structure alterations previously observed in schizophrenia and its putative prodrome. In this study, we investigated the link between mitochondrial 18 kDa translocator protein (TSPO) and structural brain characteristics (i.e. regional brain volume, cortical thickness, and hippocampal shape) in key brain regions such as dorsolateral prefrontal cortex and hippocampus of a large group of participants (N = 90) including individuals at clinical high risk (CHR) for psychosis, first-episode psychosis (mostly antipsychotic-naïve) patients, and healthy volunteers. The participants underwent structural brain MRI scan and [18F]FEPPA positron emission tomography (PET) targeting TSPO. A significant [18F]FEPPA binding-by-group interaction was observed in morphological measures across the left hippocampus. In first-episode psychosis, we observed associations between [18F]FEPPA VT (total volume of distribution) and outward and inward morphological alterations, respectively, in the dorsal and ventro-medial portions of the left hippocampus. These associations were not significant in CHR or healthy volunteers. There was no association between [18F]FEPPA VT and other structural brain characteristics. Our findings suggest a link between TSPO expression and alterations in hippocampal morphology in first-episode psychosis.
| S-EPMC6289857 | biostudies-literature
Project description:BackgroundSensorimotor communication is frequently observed in complex joint actions and social interactions. However, it remains challenging to explore the cognitive foundations behind sensorimotor communication.MethodsThe present study extends previous research by introducing a single-person baseline condition and formulates two distinct categories of asymmetric joint action tasks: distance tasks and orientation tasks. This research investigates the action performance of 65 participants under various experimental conditions utilizing a 2 (cooperative intention: Coop, No-coop) × 2 (task characteristic: distance, orientation) × 4 (target: T1, T2, T3, T4) repeated-measures experimental design to investigate the cognitive mechanisms underlying sensorimotor communication between individuals.ResultsThe results showed that (1) target key dwell time, motion time, total motion time, and maximum motion height in the Coop condition are more than in the No-coop condition. (2) In the distance task without cooperative intention, the dwell time of T4 is smaller than T1, T2, T3, and its variability of T1, T2, T3, and T4 were no different. In the distance task with cooperative intention, the dwell time and its variability of T1, T2, T3, and T4 displayed an increasing trend. (3) In the orientation task without cooperative intention, the dwell time of T1 is smaller than T2, T3, T4, and variability of the target keys T1, T2, T3, and T4 had no difference. In the orientation task with cooperative intention, the dwell time and variability of the target keys T1, T2, T3, and T4 had increasing trends.ConclusionsThose findings underscore the importance of cooperative intention for sensorimotor communication. In the distance task with cooperative intention, message senders establish a mapping relationship characterized by "near-small, far-large" between the task distance and the individual's action characteristics through sensorimotor experience. In the orientation task with cooperative intention, message senders combined sensorimotor experience and verbal metaphors to establish a mapping relationship between task orientation and action characteristics, following the sequence of "left-up, right-up, left-down, right-down" to transmit the message to others.
| S-EPMC10789189 | biostudies-literature
Project description:Mapping the structural and functional connectivity of the brain is a major focus of systems neuroscience research and will help to identify causally important changes in neural circuitry responsible for behavioral dysfunction. Several methods for examining brain activity in humans have been extended to rodent and monkey models in which molecular and genetic manipulations exist for linking to human disease. In this review, which is part of a special issue focused on bridging brain connectivity information across species and spatiotemporal scales, we address mapping brain activity and neural connectivity in rodents using optogenetics in conjunction with either functional magnetic resonance imaging or optical intrinsic signal imaging. We chose to focus on these techniques because they are capable of reporting spontaneous or evoked hemodynamic activity most closely linked to human neuroimaging studies. We discuss the capabilities and limitations of blood-based imaging methods, usage of optogenetic techniques to map neural systems in rodent models, and other powerful mapping techniques for examining neural connectivity over different spatial and temporal scales. We also discuss implementing strategies for mapping brain connectivity in humans with both basic and clinical applications, and conclude with how cross-species mapping studies can be utilized to influence preclinical imaging studies and clinical practices alike.
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Project description:Purpose Understanding the brain basis of language and cognitive outcomes is a major goal of aphasia research. Prior studies have not often considered the many ways that brain features can relate to behavioral outcomes or the mechanisms underlying these relationships. The purpose of this review article is to provide a new framework for understanding the ways that brain features may relate to language and cognitive outcomes from stroke. Method Brain-behavior relationships that may be important for aphasia outcomes are organized into a taxonomy, including features of the lesion and features of brain tissue spared by the lesion. Features of spared brain tissue are categorized into those that change after stroke and those that do not. Features that change are further subdivided, and multiple mechanisms of brain change after stroke are discussed. Results Features of the stroke, including size, location, and white matter damage, relate to many behavioral outcomes and likely account for most of the variance in outcomes. Features of the spared brain tissue that are unchanged by stroke, such as prior ischemic disease in the white matter, contribute to outcomes. Many different neurobiological and behavioral mechanisms may drive changes in the brain after stroke in association with behavioral recovery. Changes primarily driven by neurobiology are likely to occur in brain regions with a systematic relationship to the stroke distribution. Changes primarily driven by behavior are likely to occur in brain networks related to the behavior driving the change. Conclusions Organizing the various hypothesized brain-behavior relationships according to this framework and considering the mechanisms that drive these relationships may help investigators develop specific experimental designs and more complete statistical models to explain language and cognitive abilities after stroke. Eight main recommendations for future research are provided. Presentation Video https://doi.org/10.23641/asha.10257578.
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Project description:ObjectiveAdults with established diagnoses of serious mental illness (bipolar disorder and schizophrenia) exhibit structural brain abnormalities, yet less is known about how such abnormalities manifest earlier in development.MethodCross-sectional data publicly available from the Philadelphia Neurodevelopmental Cohort (PNC) were analyzed. Structural magnetic resonance neuroimaging data were collected on a subset of the PNC (N = 989; 9-22 years old). Cortical thickness, surface area (SA), and subcortical volumes were calculated. Study participants were assessed for psychiatric symptomatology using a structured interview and the following groups were created: typically developing (n = 376), psychosis spectrum (PS; n = 113), bipolar spectrum (BP; n = 117), and BP + PS (n = 109). Group and developmental differences in structural magnetic resonance neuroimaging measures were examined. In addition, the extent to which any structural aberration was related to neurocognition, global functioning, and clinical symptomatology was examined.ResultsCompared with other groups, PS youth exhibited significantly decreased SA in the orbitofrontal, cingulate, precentral, and postcentral regions. PS youth also exhibited deceased thalamic volume compared with all other groups. The strongest effects for precentral and posterior cingulate SA decreases were seen during early adolescence (13-15 years old) in PS youth. The strongest effects for decreases in thalamic volume and orbitofrontal and postcentral SA were observed in mid-adolescence (16-18 years) in PS youth. Across groups, better overall functioning was associated with increased lateral orbitofrontal SA. Increased postcentral SA was associated with better executive cognition and less severe negative symptoms in the entire sample.ConclusionIn a community-based sample, decreased cortical SA and thalamic volume were present early in adolescent development in youth with PS symptoms, but not in youth with BP symptoms or with BP and PS symptoms. These findings point to potential biological distinctions between PS and BP conditions, which could suggest additional biomarkers relevant to early identification.
| S-EPMC7110691 | biostudies-literature
Project description:Young chronological age is one of the strongest predictors for antisocial behaviour in the general population and for violent offending in individuals with psychotic disorders. An individual's age can be predicted with high accuracy using neuroimaging and machine-learning. The deviation between predicted and chronological age, i.e., brain age gap (BAG) has been suggested to reflect brain health, likely relating partly to neurodevelopmental and aging-related processes and specific disease mechanisms. Higher BAG has been demonstrated in patients with psychotic disorders. However, little is known about the brain-age in violent offenders with psychosis and the possible associations with psychopathy traits. We estimated brain-age in 782 male individuals using T1-weighted MRI scans. Three machine learning models (random forest, extreme gradient boosting with and without hyper parameter tuning) were first trained and tested on healthy controls (HC, n = 586). The obtained BAGs were compared between HC and age matched violent offenders with psychosis (PSY-V, n = 38), violent offenders without psychosis (NPV, n = 20) and non-violent psychosis patients (PSY-NV, n = 138). We ran additional comparisons between BAG of PSY-V and PSY-NV and associations with Positive and Negative Syndrome Scale (PANSS) total score as a measure of psychosis symptoms. Psychopathy traits in the violence groups were assessed with Psychopathy Checklist-revised (PCL-R) and investigated for associations with BAG. We found significantly higher BAG in PSY-V compared with HC (4.9 years, Cohen'sd = 0.87) and in PSY-NV compared with HC (2.7 years, d = 0.41). Total PCL-R scores were negatively associated with BAG in the violence groups (d = 1.17, p < 0.05). Additionally, there was a positive association between psychosis symptoms and BAG in the psychosis groups (d = 1.12, p < 0.05). While the significant BAG differences related to psychosis and not violence suggest larger BAG for psychosis, the negative associations between BAG and psychopathy suggest a complex interplay with psychopathy traits. This proof-of-concept application of brain age prediction in severe mental disorders with a history of violence and psychopathy traits should be tested and replicated in larger samples.
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Project description:Working memory (WM) function has traditionally been investigated in terms of two dimensions: within-individual effects of WM load, and between-individual differences in task performance. In human neuroimaging studies, the N-back task has frequently been used to study both. A reliable finding is that activation in frontoparietal regions exhibits an inverted-U pattern, such that activity tends to decrease at high load levels. Yet it is not known whether such U-shaped patterns are a key individual differences factor that can predict load-related changes in task performance. The current study investigated this question by manipulating load levels across a much wider range than explored previously (N = 1-6), and providing a more comprehensive examination of brain-behavior relationships. In a sample of healthy young adults (n = 57), the analysis focused on a distinct region of left lateral prefrontal cortex (LPFC) identified in prior work to show a unique relationship with task performance and WM function. In this region it was the linear slope of load-related activity, rather than the U-shaped pattern, that was positively associated with individual differences in target accuracy. Comprehensive supplemental analyses revealed the brain-wide selectivity of this pattern. Target accuracy was also independently predicted by the global resting-state connectivity of this LPFC region. These effects were robust, as demonstrated by cross-validation analyses and out-of-sample prediction, and also critically, were primarily driven by the high-load conditions. Together, the results highlight the utility of high-load conditions for investigating individual differences in WM function.
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