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BACKGROUND AND HYPOTHESIS: The human visual system streamlines visual processing by suppressing responses to textures that are similar to their surrounding context. Surround suppression is weaker in individuals with schizophrenia (ISZ); this altered use of visuospatial context may relate to the characteristic visual distortions they experience. STUDY DESIGN: To understand atypical surround suppression in psychotic psychopathology, we investigated neurophysiological responses in ISZ, healthy controls (HC), individuals with bipolar disorder (IBP), and first-degree relatives (ISZR/IBPR). Participants performed a contrast judgment task on a circular target with annular surrounds, with concurrent electroencephalography. Orientation-independent (untuned) suppression was estimated from responses to central targets with orthogonal surrounds; the orientation-dependence of suppression was estimated by fitting an exponential function to the increase in suppression as surrounds became more aligned with the center. RESULTS: ISZ exhibited weakened untuned suppression coupled with enhanced orientation-dependence of suppression. The N1 visual evoked potential was associated with the orientation-dependence of suppression, with ISZ and ISZR (but not IBP or IBPR) showing enhanced orientation-dependence of the N1. Collapsed across orientation conditions, the N1 for ISZ lacked asymmetry toward the right hemisphere; this reduction in N1 asymmetry was associated with reduced untuned suppression, real-world perceptual anomalies, and psychotic psychopathology. The overall amplitude of the N1 was reduced in ISZ and IBP. CONCLUSIONS: Key measures of symptomatology for ISZ are associated with reductions in untuned suppression. Increased sensitivity for ISZ to the relative orientation of suppressive surrounds is reflected in the N1 VEP, which is commonly associated with higher-level visual functions such as allocation of spatial attention or scene segmentation.
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Contour integration, the process of joining spatially separated elements into a single unified line, has consistently been found to be impaired in schizophrenia. Recent work suggests that this deficit could be associated with psychotic symptomatology, rather than a specific diagnosis such as schizophrenia. Examining a transdiagnostic sample of participants with psychotic psychopathology, we obtained quantitative indices of contour perception in a psychophysical behavioral task. We found impaired contour discrimination performance among people with psychotic psychopathology (PwPP, n = 62) compared to healthy controls (n = 34) and biological relatives of PwPP (n = 44). Participants with schizophrenia (n = 31) showed impaired task performance compared to participants with bipolar disorder (n = 18). We also measured responses during an analogous task using ultra-high field (7T) functional MRI and found higher responses in the lateral occipital cortex of PwPP compared to controls. Using task-based functional connectivity analyses, we observed abnormal connectivity between visual brain areas during contour perception among PwPP. These connectivity differences only emerged when participants had to distinguish the contour object from background distractors, suggesting that a failure to suppress noise elements relative to contour elements may underlie impaired contour processing in PwPP. Our results are consistent with impaired contour integration in psychotic psychopathology, and especially schizophrenia, that is related to cognitive dysfunction, and may be linked to impaired functional connectivity across visual regions.
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BACKGROUND AND OBJECTIVES: Traumatic brain injury (TBI) is a concern for US service members and veterans (SMV), leading to heterogeneous psychological and cognitive outcomes. We sought to identify neuropsychological profiles of mild TBI (mTBI) and posttraumatic stress disorder (PTSD) among the largest SMV sample to date. METHODS: We analyzed cross-sectional baseline data from SMV with prior combat deployments enrolled in the ongoing Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium prospective longitudinal study. Latent profile analysis identified symptom profiles using 35 indicators, including physical symptoms, depression, quality of life, sleep quality, postconcussive symptoms, and cognitive performance. It is important to note that the profiles were determined independently of mTBI and probable PTSD status. After profile identification, we examined associations between demographic variables, mTBI characteristics, and PTSD symptoms with symptom profile membership. RESULTS: The analytic sample included 1,659 SMV (mean age 41.1 ± 10.0 years; 87% male); among them 29% (n = 480) had a history of non-deployment-related mTBI only, 14% (n = 239) had deployment-related mTBI only, 36% (n = 602) had both non-deployment and deployment-related mTBI, and 30% (n = 497) met criteria for probable PTSD. A 6-profile model had the best fit, with separation on all indicators (p < 0.001). The model revealed distinct neuropsychological profiles, representing a combination of 3 self-reported functioning patterns: high (HS), moderate (MS), and low (LS), and 2 cognitive performance patterns: high (HC) and low (LC). The profiles were (1) HS/HC: n=301, 18.1%; (2) HS/LC: n=294, 17.7%; (3) MS/HC: n=359, 21.6%; (4) MS/LC: n=316, 19.0%; (5) LS/HC: n=228, 13.7%; and (6) LS/LC: n=161, 9.7%. SMV with deployment-related mTBI tended to be grouped into lower functioning profiles and were more likely to meet criteria for probable PTSD. Conversely, SMV with no mTBI exposure or non-deployment-related mTBI were clustered in higher functioning profiles and had a lower likelihood of meeting criteria for probable PTSD. DISCUSSION: Findings suggest varied symptom and functional profiles in SMV, influenced by injury context and probable PTSD comorbidity. Despite diagnostic challenges, comprehensive assessment of functioning and cognition can detect subtle differences related to mTBI and PTSD, revealing distinct neuropsychological profiles. Prioritizing early treatment based on these profiles may improve prognostication and support efficient recovery.
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Conmoción Encefálica , Personal Militar , Pruebas Neuropsicológicas , Trastornos por Estrés Postraumático , Humanos , Masculino , Adulto , Femenino , Trastornos por Estrés Postraumático/epidemiología , Trastornos por Estrés Postraumático/psicología , Trastornos por Estrés Postraumático/etiología , Conmoción Encefálica/psicología , Conmoción Encefálica/complicaciones , Conmoción Encefálica/epidemiología , Estudios Transversales , Persona de Mediana Edad , Personal Militar/psicología , Estudios Longitudinales , Veteranos/psicología , Estudios Prospectivos , Despliegue Militar/psicología , Síndrome Posconmocional/psicología , Síndrome Posconmocional/epidemiología , Calidad de VidaRESUMEN
Bi-stable stimuli evoke two distinct perceptual interpretations that alternate and compete for dominance. Bi-stable perception is thought to be driven at least in part by mutual suppression between distinct neural populations that represent each percept. Abnormal visual perception has been observed among people with psychotic psychopathology (PwPP), and there is evidence to suggest that these visual deficits may depend on impaired neural suppression in the visual cortex. However, it is not yet clear whether bi-stable visual perception is abnormal among PwPP. Here, we examined bi-stable perception in a visual structure-from-motion task using a rotating cylinder illusion in a group of 65 PwPP, 44 first-degree biological relatives, and 43 healthy controls. Data from a 'real switch' task, in which physical depth cues signaled real switches in rotation direction were used to exclude individuals who did not show adequate task performance. In addition, we measured concentrations of neurochemicals, including glutamate, glutamine, and γ-amino butyric acid (GABA), involved in excitatory and inhibitory neurotransmission. These neurochemicals were measured non-invasively in the visual cortex using 7 tesla MR spectroscopy. We found that PwPP and their relatives showed faster bi-stable switch rates than healthy controls. Faster switch rates also correlated with significantly higher psychiatric symptom levels, specifically disorganization, across all participants. However, we did not observe any significant relationships across individuals between neurochemical concentrations and SFM switch rates. Our results are consistent with a reduction in suppressive neural processes during structure-from-motion perception in PwPP, and suggest that genetic liability for psychosis is associated with disrupted bi-stable perception.
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Trastornos Psicóticos , Corteza Visual , Percepción Visual , Humanos , Masculino , Femenino , Adulto , Trastornos Psicóticos/fisiopatología , Corteza Visual/fisiopatología , Percepción Visual/fisiología , Adulto Joven , Percepción de Movimiento/fisiología , Espectroscopía de Resonancia Magnética , Persona de Mediana EdadRESUMEN
Formal thought disorder (FTD) is a clinical key factor in schizophrenia, but the neurobiological underpinnings remain unclear. In particular, the relationship between FTD symptom dimensions and patterns of regional brain volume loss in schizophrenia remains to be established in large cohorts. Even less is known about the cellular basis of FTD. Our study addresses these major obstacles by enrolling a large multi-site cohort acquired by the ENIGMA Schizophrenia Working Group (752 schizophrenia patients and 1256 controls), to unravel the neuroanatomy of FTD in schizophrenia and using virtual histology tools on implicated brain regions to investigate the cellular basis. Based on the findings of previous clinical and neuroimaging studies, we decided to separately explore positive, negative and total formal thought disorder. We used virtual histology tools to relate brain structural changes associated with FTD to cellular distributions in cortical regions. We identified distinct neural networks positive and negative FTD. Both networks encompassed fronto-occipito-amygdalar brain regions, but positive and negative FTD demonstrated a dissociation: negative FTD showed a relative sparing of orbitofrontal cortical thickness, while positive FTD also affected lateral temporal cortices. Virtual histology identified distinct transcriptomic fingerprints associated for both symptom dimensions. Negative FTD was linked to neuronal and astrocyte fingerprints, while positive FTD also showed associations with microglial cell types. These results provide an important step towards linking FTD to brain structural changes and their cellular underpinnings, providing an avenue for a better mechanistic understanding of this syndrome.
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Blast-related mild traumatic brain injury (BR mTBI) is a critical research area in recent combat veterans due to increased prevalence of survived blasts. Post-BR mTBI outcomes are highly heterogeneous and defining neurological differences may help in discrimination and prediction of cognitive outcomes. This study investigates whether white matter integrity, measured with diffusion tensor imaging (DTI), could influence how remote BR mTBI history is associated with executive control. The sample included 151 Veterans from the Minneapolis Veterans Affairs Medical Center who were administered a clinical/TBI assessment, neuropsychological battery, and DTI scan as part of a larger battery. From previous research, six white matter tracts were identified as having a putative relationship with blast severity: the cingulum, hippocampal cingulum, corticospinal tract, inferior fronto-occipital fasciculus, superior longitudinal fasciculus and uncinate. Fractional anisotropy (FA) of the a priori selected white matter tracts and report of BR mTBI were used as predictors of Trail-Making Test B (TMT-B) performance in a multiple linear regression model. Statistical analysis revealed that FA of the hippocampal cingulum moderated the association between report of at least one BR mTBI and poorer TMT-B performance (p < 0.008), such that lower FA value was associated with worse TMT-B outcomes in individuals with BR mTBI. No significant moderation existed for other selected tracts, and the effect was not observed with predictors aside from history of BR mTBI. Investigation at the individual-tract level may lead to a deeper understanding of neurological differences between blast-related and non-blast related injuries.
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Background: Intrusive traumatic re-experiencing domain (ITRED) was recently introduced as a novel perspective on posttraumatic psychopathology, proposing to focus research of posttraumatic stress disorder (PTSD) on the unique symptoms of intrusive and involuntary re-experiencing of the trauma, namely, intrusive memories, nightmares, and flashbacks. The aim of the present study was to explore ITRED from a neural network connectivity perspective. Methods: Data were collected from 9 sites taking part in the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) PTSD Consortium (n= 584) and included itemized PTSD symptom scores and resting-state functional connectivity (rsFC) data. We assessed the utility of rsFC in classifying PTSD, ITRED-only (no PTSD diagnosis), and trauma-exposed (TE)-only (no PTSD or ITRED) groups using a machine learning approach, examining well-known networks implicated in PTSD. A random forest classification model was built on a training set using cross-validation, and the averaged cross-validation model performance for classification was evaluated using the area under the curve. The model was tested using a fully independent portion of the data (test dataset), and the test area under the curve was evaluated. Results: rsFC signatures differentiated TE-only participants from PTSD and ITRED-only participants at about 60% accuracy. Conversely, rsFC signatures did not differentiate PTSD from ITRED-only individuals (45% accuracy). Common features differentiating TE-only participants from PTSD and ITRED-only participants mainly involved default mode network-related pathways. Some unique features, such as connectivity within the frontoparietal network, differentiated TE-only participants from one group (PTSD or ITRED-only) but to a lesser extent from the other group. Conclusions: Neural network connectivity supports ITRED as a novel neurobiologically based approach to classifying posttrauma psychopathology.
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BACKGROUND AND HYPOTHESIS: Cognitive control deficits are prominent in individuals with psychotic psychopathology. Studies providing evidence for deficits in proactive control generally examine average performance and not variation across trials for individuals-potentially obscuring detection of essential contributors to cognitive control. Here, we leverage intertrial variability through drift-diffusion models (DDMs) aiming to identify key contributors to cognitive control deficits in psychosis. STUDY DESIGN: People with psychosis (PwP; Nâ =â 122), their first-degree biological relatives (Nâ =â 78), and controls (Nâ =â 50) each completed 120 trials of the dot pattern expectancy (DPX) cognitive control task. We fit full hierarchical DDMs to response and reaction time (RT) data for individual trials and then used classification models to compare the DDM parameters with conventional measures of proactive and reactive control. STUDY RESULTS: PwP demonstrated slower drift rates on proactive control trials suggesting less efficient use of cue information. Both PwP and relatives showed protracted nondecision times to infrequent trial sequences suggesting slowed perceptual processing. Classification analyses indicated that DDM parameters differentiated between the groups better than conventional measures and identified drift rates during proactive control, nondecision time during reactive control, and cue bias as most important. DDM parameters were associated with real-world functioning and schizotypal traits. CONCLUSIONS: Modeling of trial-level data revealed that slow evidence accumulation and longer preparatory periods are the strongest contributors to cognitive control deficits in psychotic psychopathology. This pattern of atypical responding during the DPX is consistent with shallow basins in attractor dynamic models that reflect difficulties in maintaining state representations, possibly mediated by excess neural excitation or poor connectivity.
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Schizophrenia is a prototypical network disorder with widespread brain-morphological alterations, yet it remains unclear whether these distributed alterations robustly reflect the underlying network layout. We tested whether large-scale structural alterations in schizophrenia relate to normative structural and functional connectome architecture, and systematically evaluated robustness and generalizability of these network-level alterations. Leveraging anatomical MRI scans from 2439 adults with schizophrenia and 2867 healthy controls from 26 ENIGMA sites and normative data from the Human Connectome Project (n = 207), we evaluated structural alterations of schizophrenia against two network susceptibility models: (i) hub vulnerability, which examines associations between regional network centrality and magnitude of disease-related alterations; (ii) epicenter mapping, which identifies regions whose typical connectivity profile most closely resembles the disease-related morphological alterations. To assess generalizability and specificity, we contextualized the influence of site, disease stages, and individual clinical factors and compared network associations of schizophrenia with that found in affective disorders. Our findings show schizophrenia-related cortical thinning is spatially associated with functional and structural hubs, suggesting that highly interconnected regions are more vulnerable to morphological alterations. Predominantly temporo-paralimbic and frontal regions emerged as epicenters with connectivity profiles linked to schizophrenia's alteration patterns. Findings were robust across sites, disease stages, and related to individual symptoms. Moreover, transdiagnostic comparisons revealed overlapping epicenters in schizophrenia and bipolar, but not major depressive disorder, suggestive of a pathophysiological continuity within the schizophrenia-bipolar-spectrum. In sum, cortical alterations over the course of schizophrenia robustly follow brain network architecture, emphasizing marked hub susceptibility and temporo-frontal epicenters at both the level of the group and the individual. Subtle variations of epicenters across disease stages suggest interacting pathological processes, while associations with patient-specific symptoms support additional inter-individual variability of hub vulnerability and epicenters in schizophrenia. Our work outlines potential pathways to better understand macroscale structural alterations, and inter- individual variability in schizophrenia.
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BACKGROUND: Schizophrenia is associated with hypoactivation of reward sensitive brain areas during reward anticipation. However, it is unclear whether these neural functions are similarly impaired in other disorders with psychotic symptomatology or individuals with genetic liability for psychosis. If abnormalities in reward sensitive brain areas are shared across individuals with psychotic psychopathology and people with heightened genetic liability for psychosis, there may be a common neural basis for symptoms of diminished pleasure and motivation. METHODS: We compared performance and neural activity in 123 people with a history of psychosis (PwP), 81 of their first-degree biological relatives, and 49 controls during a modified Monetary Incentive Delay task during fMRI. RESULTS: PwP exhibited hypoactivation of the striatum and anterior insula (AI) during cueing of potential future rewards with each diagnostic group showing hypoactivations during reward anticipation compared to controls. Despite normative task performance, relatives demonstrated caudate activation intermediate between controls and PwP, nucleus accumbens activation more similar to PwP than controls, but putamen activation on par with controls. Across diagnostic groups of PwP there was less functional connectivity between bilateral caudate and several regions of the salience network (medial frontal gyrus, anterior cingulate, AI) during reward anticipation. CONCLUSIONS: Findings implicate less activation and connectivity in reward processing brain regions across a spectrum of disorders involving psychotic psychopathology. Specifically, aberrations in striatal and insular activity during reward anticipation seen in schizophrenia are partially shared with other forms of psychotic psychopathology and associated with genetic liability for psychosis.
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Trastornos Psicóticos , Esquizofrenia , Adulto , Humanos , Recompensa , Encéfalo/diagnóstico por imagen , Trastornos Psicóticos/diagnóstico por imagen , Motivación , Esquizofrenia/diagnóstico por imagen , Imagen por Resonancia Magnética , Anticipación Psicológica/fisiologíaRESUMEN
BACKGROUND: Neural oscillations support perception, attention, and higher-order decision making. Aberrations in the strength or consistency of these oscillations in response to stimuli may underlie impaired visual perception and attention in schizophrenia. Here, we examined the phase and power of alpha oscillations (8-12 Hz) as well as aspects of beta and theta frequency oscillations during a demanding visual sustained attention task. METHODS: Patients with schizophrenia (n = 74) and healthy control participants (n = 68) completed the degraded stimulus continuous performance task during electroencephalography. We used time-frequency analysis to evaluate the consistency (intertrial phase coherence) of the alpha cycle shortly after stimulus presentation (50-250 ms). For oscillation strength, we examined event-related desynchronization in a later window associated with decision making (360-700 ms). RESULTS: Alpha intertrial phase coherence was reduced in schizophrenia, and similar reductions were observed in theta (4-7 Hz) and beta (13-20 Hz), suggesting a lack of responsiveness in slower oscillations to visual stimuli. Alpha and beta event-related desynchronization were also reduced in schizophrenia and associated with worse task performance, increased symptoms, and poorer cognition, suggesting that limited responsiveness of oscillations is related to impairments in the disorder. Individuals with lower intertrial phase coherence had slower resting-state alpha rhythms consistent with dysfunctional oscillations persisting across default and task-related brain states. CONCLUSIONS: In schizophrenia, abnormalities in the phase consistency and strength of slower oscillations during visual perception are related to symptoms and cognitive functioning. Altered visual perception and impaired attention in the disorder may be the consequence of aberrant slower oscillations that fail to dynamically reset and modulate in response to stimuli.
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Esquizofrenia , Humanos , Electroencefalografía , Encéfalo , Percepción Visual/fisiología , Ritmo alfa/fisiologíaRESUMEN
Posttraumatic stress disorder (PTSD) is associated with lower cortical thickness (CT) in prefrontal, cingulate, and insular cortices in diverse trauma-affected samples. However, some studies have failed to detect differences between PTSD patients and healthy controls or reported that PTSD is associated with greater CT. Using data-driven dimensionality reduction, we sought to conduct a well-powered study to identify vulnerable networks without regard to neuroanatomic boundaries. Moreover, this approach enabled us to avoid the excessive burden of multiple comparison correction that plagues vertex-wise methods. We derived structural covariance networks (SCNs) by applying non-negative matrix factorization (NMF) to CT data from 961 PTSD patients and 1124 trauma-exposed controls without PTSD. We used regression analyses to investigate associations between CT within SCNs and PTSD diagnosis (with and without accounting for the potential confounding effect of trauma type) and symptom severity in the full sample. We performed additional regression analyses in subsets of the data to examine associations between SCNs and comorbid depression, childhood trauma severity, and alcohol abuse. NMF identified 20 unbiased SCNs, which aligned closely with functionally defined brain networks. PTSD diagnosis was most strongly associated with diminished CT in SCNs that encompassed the bilateral superior frontal cortex, motor cortex, insular cortex, orbitofrontal cortex, medial occipital cortex, anterior cingulate cortex, and posterior cingulate cortex. CT in these networks was significantly negatively correlated with PTSD symptom severity. Collectively, these findings suggest that PTSD diagnosis is associated with widespread reductions in CT, particularly within prefrontal regulatory regions and broader emotion and sensory processing cortical regions.
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Trastornos por Estrés Postraumático , Humanos , Trastornos por Estrés Postraumático/psicología , Imagen por Resonancia Magnética , Encéfalo , Emociones , Corteza PrefrontalRESUMEN
The chronic mental health consequences of mild traumatic brain injury (TBI) are a leading cause of disability. This is surprising given the expectation of significant recovery after mild TBI, which suggests that other injury-related factors may contribute to long-term adverse outcomes. The objective of this study was to determine how number of prior injuries, gender, and environment/context of injury may contribute to depressive symptoms after mild TBI among deployed United States service members and veterans (SMVs). Data from the Long-term Impact of Military-Relevant Brain Injury Consortium Prospective Longitudinal Study was used to assess TBI injury characteristics and depression scores previously measured on the Patient Health Questionnaire-9 (PHQ-9) among a sample of 1456 deployed SMVs. Clinical diagnosis of mild TBI was defined via a multi-step process centered on a structured face-to-face interview. Logistical and linear regressions stratified by gender and environment of injury were used to model depressive symptoms controlling for sociodemographic and combat deployment covariates. Relative to controls with no history of mild TBI (n = 280), the odds ratios (OR) for moderate/severe depression (PHQ-9 ≥ 10) were higher for SMVs with one mild TBI (n = 358) OR: 1.62 (95% confidence interval [CI] 1.09-2.40, p = 0.016) and two or more mild TBIs (n = 818) OR: 1.84 (95% CI 1.31-2.59, p < 0.001). Risk differences across groups were assessed in stratified linear models, which found that depression symptoms were elevated in those with a history of multiple mild TBIs compared with those who had a single mild TBI (p < 0.001). Combat deployment-related injuries were also associated with higher depression scores than injuries occurring in non-combat or civilian settings (p < 0.001). Increased rates of depression after mild TBI persisted in the absence of post-traumatic stress disorder. Both men and women SMVs separately exhibited significantly increased depressive symptom scores if they had had combat-related mild TBI. These results suggest that contextual information, gender, and prior injury history may influence long-term mental health outcomes among SMVs with mild TBI exposure.
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Conmoción Encefálica , Lesiones Traumáticas del Encéfalo , Personal Militar , Traumatismo Múltiple , Trastornos por Estrés Postraumático , Veteranos , Masculino , Humanos , Femenino , Estados Unidos/epidemiología , Conmoción Encefálica/complicaciones , Depresión/epidemiología , Depresión/etiología , Depresión/psicología , Estudios Longitudinales , Estudios Prospectivos , Personal Militar/psicología , Lesiones Traumáticas del Encéfalo/complicaciones , Veteranos/psicología , Trastornos por Estrés Postraumático/etiologíaRESUMEN
Background: Psychotic-like experiences (PLEs) are considered the subclinical portion of the psychosis continuum. Research suggests that there are resting-state functional connectivity (rsFC) substrates of PLEs, yet it is unclear if the same substrates underlie more severe psychosis. Here, to our knowledge, we report the first study to build a cross-validated rsFC model of PLEs in a large community sample and directly test its ability to explain psychosis in an independent sample of patients with psychosis and their relatives. Methods: Resting-state FC of 855 healthy young adults from the WU-Minn Human Connectome Project (HCP) was used to predict PLEs with elastic net. An rsFC composite score based on the resulting model was correlated with psychotic traits and symptoms in 118 patients with psychosis, 71 nonpsychotic first-degree relatives, and 45 healthy control subjects from the psychosis HCP. Results: In the HCP, the cross-validated model explained 3.3% of variance in PLEs. Predictive connections spread primarily across the default, frontoparietal, cingulo-opercular, and dorsal attention networks. The model partially generalized to a younger, but not older, subsample in the psychosis HCP, explaining two measures of positive/disorganized psychotic traits (the Structured Interview for Schizotypy: ß = 0.25, pone-tailed = .027; the Schizotypy Personality Questionnaire positive factor: ß = 0.14, pone-tailed = .041). However, it did not differentiate patients from relatives and control subjects or explain psychotic symptoms in patients. Conclusions: Some rsFC substrates of PLEs are shared across the psychosis continuum. However, explanatory power was modest, and generalization was partial. It is equally important to understand shared versus distinct rsFC variances across the psychosis continuum.
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BACKGROUND: Military services provide a unique opportunity for studying resilience, a dynamic process of successful adaptation (ie, doing well in terms of functioning and symptoms) in response to significant adversity. Despite the tremendous interest in positive adaptation among military service members, little is known about the processes underlying their resilience. Understanding the neurobiological, cognitive, and social mechanisms underlying adaptive functioning following military stressor exposure is essential for enhancing the resilience of military service members. OBJECTIVE: The primary objective of the Advancing Research on Mechanisms of Resilience (ARMOR) longitudinal study is to characterize the trajectories of positive adaptation among young military recruits in response to basic combat training (BCT), a well-defined, uniform, and 10-week period of intense stress (aim 1), and identify promotive and protective processes contributing to individual variations in resilience (aim 2). The secondary objective is to investigate the pathways by which neurobehavioral markers of self-regulation assessed using electroencephalography and magnetic resonance imaging contribute to adaptive trajectories (aim 3). METHODS: ARMOR is an ongoing, prospective longitudinal cohort study of young military recruits who recently joined the National Guard but have not yet shipped out for BCT. Participants (N=1201) are assessed at 5 time points over the initial >2 years of military service beginning before BCT (baseline) and followed up at 2 weeks and 6, 12, and 18 months after BCT. Participants complete web-based questionnaires assessing vulnerability and protective factors, mental health, and socioemotional functioning at each time point and a battery of neurocognitive tests at time 0. A subset of participants also complete structured diagnostic interviews and additional self-report measures and perform neurobehavioral tasks before and after BCT during electroencephalography sessions and before BCT only during magnetic resonance imaging sessions. RESULTS: This UG3/UH3 project was initially funded in August 2017, with the UG3 pilot work completed at the end of 2018. The UH3 phase of the project was funded in March 2019. Study enrollment for the UH3 phase began on April 14, 2019, and ended on October 16, 2021. A total of 1201 participants are enrolled in the study. Follow-up data collection for the UH3 phase is ongoing and projected to continue through February 2024. We will disseminate the findings through conferences, webinars, open access publications, and communications with participants and stakeholders. CONCLUSIONS: The ARMOR study provides a rich data set to identify the predictors and mechanisms of resilient and nonresilient outcomes in the context of military stressors, which are intended to empirically inform the development of prevention and intervention strategies to enhance the resilience of military trainees and potentially other young people facing significant life challenges. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/51235.
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Objective: Long-term changes to EEG spectra after mild traumatic brain injury (mTBI, i.e., concussion) have been reported; however, the role of injury characteristics in long-term EEG changes is unclear. It is also unclear how any chronic EEG changes may underlie either subjective or objective cognitive difficulties, which might help explain the variability in recovery after mTBI. Methods: This study included resting-state high-density electroencephalography (EEG) and mTBI injury data from 340 service members and veterans collected on average 11 years after injury as well as measures of objective and subjective cognitive functioning. The average absolute power within standard bands was computed across 11 spatial regions of the scalp. To determine how variation in brain function was accounted for by injury characteristics and aspects of cognition, we used regression analyses to investigate how EEG power was predicted by mTBI history characteristics [number, number with post-traumatic amnesia and witnessed loss of consciousness (PTA + LOC), context of injury (combat or non-combat), potentially concussive blast exposures], subjective complaints (TBIQOL General Cognitive and Executive Function Concerns), and cognitive performance (NIH Toolbox Fluid Intelligence and premorbid IQ). Results: Post-traumatic amnesia (PTA) and loss of consciousness (LOC), poorer cognitive performance, and combat experience were associated with reduced power in beta frequencies. Executive function complaints, lower premorbid IQ, poorer cognitive performance, and higher psychological distress symptoms were associated with greater power of delta frequencies. Multiple regression confirmed the relationship between PTA + LOC, poor cognitive performance, cognitive complaints, and reduced power in beta frequencies and revealed that repetitive mTBI was associated with a higher power in alpha and beta frequencies. By contrast, neither dichotomous classification of the presence and absence of mTBI history nor blast exposures showed a relationship with EEG power variables. Conclusion: Long-term alterations in resting EEG spectra measures of brain function do not appear to reflect any lasting effect of a history of mTBI or blast exposures. However, power in higher frequencies reflects both injury characteristics and subjective and objective cognitive difficulties, while power in lower frequencies is related to cognitive functions and psychological distress associated with poor long-term outcomes after mTBI.
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Adolescent onset is common in bipolar disorders (BDs) and is associated with a worse illness course in adulthood. A model of BDs suggests that a dysregulated behavioral approach system (BAS), a neural system that mobilizes reward-seeking behavior, is at the root of BDs. Normative adolescence is often accompanied by dynamic changes to neural structures underlying the BAS and related cognitive processes. It is possible that adolescent-onset BDs is associated with abnormal BAS neurodevelopment. Consistently, the present study is the first to compare specific BAS-relevant anticipatory and consummatory reward processes as indexed by event-related potentials (ERPs) in adolescents with BDs and typically developing peers. Using a sample of 43 adolescents with BDs and 56 without psychopathology, we analyzed N1 and P3 responses to anticipatory cues and feedback-related negativity (FRN) and P3 responses to feedback stimuli during a monetary incentive delay (MID) task. Hierarchical linear models examined relationships between ERP amplitudes and diagnostic group, MID condition, sex, and age. During anticipation phase, adolescent boys with BDs exhibited significantly larger N1 amplitudes in loss than even or gain trials. During feedback phase, compared to their healthy peers, adolescents with BDs had smaller FRN amplitudes across all conditions. Additional effects involving age, sex and trial type were observed. The findings indicate subtle, non-ubiquitous BAS-relevant neural abnormalities involving early attentional processes during reward anticipation and reward learning following feedback in adolescents with BDs. Adolescents with BDs did not show overall hypersensitive neural responses to monetary reward anticipation or feedback observed in adults with BDs.
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Cognitive control deficits are consistently identified in individuals with schizophrenia and other psychotic psychopathologies. In this analysis, we delineated proactive and reactive control deficits in psychotic psychopathology via hierarchical Drift Diffusion Modeling (hDDM). People with psychosis (PwP; N=123), their first-degree relatives (N=79), and controls (N=51) completed the Dot Pattern Expectancy task, which allows differentiation between proactive and reactive control. PwP demonstrated slower drift rates on proactive control trials suggesting less efficient use of cue information for proactive control. They also showed longer non-decision times than controls on infrequent stimuli sequences suggesting slower perceptual processing. An explainable machine learning analysis indicated that the hDDM parameters were able to differentiate between the groups better than conventional measures. Through DDM, we found that cognitive control deficits in psychosis are characterized by slower motor/perceptual time and slower evidence-integration primarily in proactive control.
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Introduction: Psychosis is in part defined by disturbances in perception. Recent investigations have implicated the speed of alpha oscillations observed in brain electrical activity as reflective of a sampling rate of the visual environment and perception. Although both slowed alpha oscillations and aberrant percept formation are evident in disorders of psychotic psychopathology such as schizophrenia it is unclear whether slow alpha accounts for abnormal visual perception in these disorders. Methods: To examine the role of the speed of alpha oscillations in perception in psychotic psychopathology we gathered resting-state magneto-encephalography data from probands with psychotic psychopathology (i.e., schizophrenia, schizoaffective disorder, and bipolar disorder with a history of psychosis), their biological siblings, and healthy controls. We appraised visual perceptual function without the confound of cognitive ability and effort through the use of a simple binocular rivalry task. Results: We found a slowed pace of alpha oscillations in psychotic psychopathology that was associated with longer percept durations during binocular rivalry, consistent with the assertion that occipital alpha oscillations govern the rate of accumulation of visual information used to generate percepts. Alpha speed varied widely across individuals with psychotic psychopathology and was highly stable across several months indicating that it is likely a trait characteristic of neural function that is relevant to visual perception. Finally, a lower speed of alpha oscillation was associated with a lower IQ and greater disorder symptomatology implying that the effects of the endogenous neural oscillation on visual perception may have wider consequences for everyday functioning. Discussion: Slowed alpha oscillations in individuals with psychotic psychopathology appear to reflect altered neural functions related to percept formation.
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Objective: Over half of US military veterans with posttraumatic stress disorder (PTSD) use alcohol heavily, potentially to cope with their symptoms. This study investigated the neural underpinnings of PTSD symptoms and heavy drinking in veterans. We focused on brain responses to salient outcomes within predictive coding theory. This framework suggests the brain generates prediction errors (PEs) when outcomes deviate from expectations. Alcohol use might provide negative reinforcement by reducing the salience of negatively-valenced PEs and dampening experiences like loss. Methods: We analyzed electroencephalography (EEG) responses to unpredictable gain/loss feedback in veterans of Operations Enduring and Iraqi Freedom. We used time-frequency principal components analysis of event-related potentials to isolate neural responses indicative of PEs, identifying mediofrontal theta linked to losses (feedback-related negativity, FRN) and central delta associated with gains (reward positivity, RewP). Results: Intrusive reexperiencing symptoms of PTSD were associated with intensified mediofrontal theta signaling during losses, suggesting heightened negative PE sensitivity. Conversely, increased hazardous alcohol use was associated with reduced theta responses, implying a dampening of these negative PEs. The separate delta-RewP component showed associations with alcohol use but not PTSD symptoms. Conclusions: Findings suggest a common neural component of PTSD and hazardous alcohol use involving altered PE processing. We suggest that reexperiencing enhances the intensity of salient negative PEs, while chronic alcohol use may reduce their intensity, thereby providing negative reinforcement by muting emotional disruption from reexperienced trauma. Modifying the mediofrontal theta response could address the intertwined nature of PTSD symptoms and alcohol use, providing new avenues for treatment.