Adjustment of Regional Cortical Thickness Measures for Global Cortical Thickness Obscures Deficits Across the Schizophrenia Spectrum: A Cautionary Note about Normative Modeling of Brain Imaging Data.

Recent neuroimaging studies and publicly-disseminated analytic tools advocate that regional morphometric analyses covary for global thickness. We empirically demonstrate that this statistical approach severely underestimates regional thickness dysmorphology in psychiatric disorders. Study 1 included 90 healthy controls, 51 clinical high-risk for psychosis, and 78 early illness schizophrenia participants. Study 2 included 56 healthy controls, 83 non-affective psychosis, and 30 affective psychosis participants. We examined global and regional thickness correlations, global thickness group differences, and regional thickness group differences with/without global thickness covariation. Global and regional thickness were strongly correlated across groups. Global thickness was lower in schizophrenia-spectrum groups versus other groups. Regional thickness deficits in schizophrenia-spectrum groups were attenuated/eliminated with global thickness covariation. Depriving regional thickness of its shared variance with global thickness removes disease-related effects. This statistical method results in erroneous conclusions that regional thickness is normal in disorders like schizophrenia or clinical high-risk syndrome.

Brain Age Gap in Early Illness Schizophrenia and the Clinical High-Risk Syndrome: Associations With Experiential Negative Symptoms and Conversion to Psychosis.

BACKGROUND AND HYPOTHESIS: Brain development/aging is not uniform across individuals,spawning efforts to characterize brain age from a biological perspective to model the effects of disease and maladaptive life processes on the brain. The brain age gap represents the discrepancy between estimated brain biological age and chronological age (in this case, based on structural magnetic resonance imaging, MRI). Structural MRI studies report an increased brain age gap (biological age > chronological age) in schizophrenia, with a greater brain age gap related to greater negative symptom severity. Less is known regarding the nature of this gap early in schizophrenia (ESZ), if this gap represents a psychosis conversion biomarker in clinical high-risk (CHR-P) individuals, and how altered brain development and/or agingmap onto specific symptom facets. STUDY DESIGN: Using structural MRI, we compared the brain age gap among CHR-P (n = 51), ESZ (n = 78), and unaffected comparison participants (UCP; n = 90), and examined associations with CHR-P psychosis conversion (CHR-P converters n = 10; CHR-P non-converters; n = 23) and positive and negative symptoms. STUDY RESULTS: ESZ showed a greater brain age gap relative to UCP and CHR-P (Ps < .010). CHR-P individuals who converted to psychosis showed a greater brain age gap (P = .043) relative to CHR-P non-converters. A larger brain age gap in ESZ was associated with increased experiential (P = .008), but not expressive negative symptom severity. CONCLUSIONS: Consistent with schizophrenia pathophysiological models positing abnormal brain maturation, results suggest abnormal brain development is present early in psychosis. An increased brain age gap may be especially relevant to motivational and functional deficits in schizophrenia.

Pons-to-Cerebellum Hypoconnectivity Along the Psychosis Spectrum and Associations With Sensory Prediction and Hallucinations in Schizophrenia.

BACKGROUND: Sensory prediction allows the brain to anticipate and parse incoming self-generated sensory information from externally generated signals. Sensory prediction breakdowns may contribute to perceptual and agency abnormalities in psychosis (hallucinations, delusions). The pons, a central node in a cortico-ponto-cerebellar-thalamo-cortical circuit, is thought to support sensory prediction. Examination of pons connectivity in schizophrenia and its role in sensory prediction abnormalities is lacking. METHODS: We examined these relationships using resting-state functional magnetic resonance imaging and the electroencephalography-based auditory N1 event-related potential in 143 participants with psychotic spectrum disorders (PSPs) (with schizophrenia, schizoaffective disorder, or bipolar disorder); 63 first-degree relatives of individuals with psychosis; 45 people at clinical high risk for psychosis; and 124 unaffected comparison participants. This unique sample allowed examination across the psychosis spectrum and illness trajectory. Seeding from the pons, we extracted average connectivity values from thalamic and cerebellar clusters showing differences between PSPs and unaffected comparison participants. We predicted N1 amplitude attenuation during a vocalization task from pons connectivity and group membership. We correlated participant-level connectivity in PSPs and people at clinical high risk for psychosis with hallucination and delusion severity. RESULTS: Compared to unaffected comparison participants, PSPs showed pons hypoconnectivity to 2 cerebellar clusters, and first-degree relatives of individuals with psychosis showed hypoconnectivity to 1 of these clusters. Pons-to-cerebellum connectivity was positively correlated with N1 attenuation; only PSPs with heightened pons-to-postcentral gyrus connectivity showed this pattern, suggesting a possible compensatory mechanism. Pons-to-cerebellum hypoconnectivity was correlated with greater hallucination severity specifically among PSPs with schizophrenia. CONCLUSIONS: Deficient pons-to-cerebellum connectivity linked sensory prediction network breakdowns with perceptual abnormalities in schizophrenia. Findings highlight shared features and clinical heterogeneity across the psychosis spectrum.

Cortical and subcortical brain morphometry abnormalities in youth at clinical high-risk for psychosis and individuals with early illness schizophrenia.

Neuroimaging studies have documented morphometric brain abnormalities in schizophrenia, but less is known about them in individuals at clinical high-risk for psychosis (CHR-P), including how they compare with those observed in early schizophrenia (ESZ). Accordingly, we implemented multivariate profile analysis of regional morphometric profiles in CHR-P (n = 89), ESZ (n = 93) and healthy controls (HC; n = 122). ESZ profiles differed from HC and CHR-P profiles, including 1) cortical thickness: significant level reduction and regional non-parallelism reflecting widespread thinning, except for entorhinal and pericalcarine cortex, 2) basal ganglia volume: significant level increase and regional non-parallelism reflecting larger caudate and pallidum, and 3) ventricular volume: significant level increase with parallel regional profiles. CHR-P and ESZ cerebellar profiles showed significant non-parallelism with HC profiles. Regional profiles did not significantly differ between groups for cortical surface area or subcortical volume. Compared to CHR-P followed for ≥18 months without psychosis conversion (n = 31), CHR-P converters (n = 17) showed significant non-parallel ventricular volume expansion reflecting specific enlargement of lateral and inferolateral regions. Antipsychotic dosage in ESZ was significantly correlated with frontal cortical thinning. Results suggest that morphometric abnormalities in ESZ are not present in CHR-P, except for ventricular enlargement, which was evident in CHR-P who developed psychosis.

Mismatch Negativity and Theta Oscillations Evoked by Auditory Deviance in Early Schizophrenia.

BACKGROUND: Amplitude reduction of mismatch negativity (MMN), an event-related potential component indexing NMDA receptor-dependent auditory echoic memory and predictive coding, is widely replicated in schizophrenia. Time-frequency analyses of single-trial electroencephalography epochs suggest that theta oscillation abnormalities underlie MMN deficits in schizophrenia. However, this has received less attention in early schizophrenia (ESZ). METHODS: Patients with ESZ (n = 89), within 5 years of illness onset, and healthy control subjects (n = 105) completed an electroencephalography MMN paradigm (duration-deviant, pitch-deviant, duration + pitch double-deviant). Repeated measures analyses of variance assessed group differences in MMN, theta intertrial phase coherence (ITC), and theta total power from frontocentral electrodes, after normal age adjustment. Group differences were retested after covarying MMN and theta measures. RESULTS: Relative to healthy control subjects, patients with ESZ showed auditory deviance deficits. Patients with ESZ had MMN deficits for duration-deviants (p = .041), pitch-deviants (ps = .007), and double-deviants (ps < .047). Patients with ESZ had reduced theta ITC for standards (ps < .040) and duration-deviants (ps < .030). Furthermore, patients with ESZ had reduced theta power across deviants at central electrodes (p = .013). MMN group deficits were not fully accounted for by theta ITC and power, and neither were theta ITC group deficits fully accounted for by MMN. Group differences in theta total power were no longer significant after covarying for MMN. CONCLUSIONS: Patients with ESZ showed reduced MMN and theta total power for all deviant types. Theta ITC showed a relatively specific reduction for duration-deviants. Although MMN and theta ITC were correlated in ESZ, covarying for one did not fully account for deficits in the other, raising the possibility of their sensitivity to dissociable pathophysiological processes.

Rich-club connectivity and structural connectome organization in youth at clinical high-risk for psychosis and individuals with early illness schizophrenia.

Brain dysconnectivity has been posited as a biological marker of schizophrenia. Emerging schizophrenia connectome research has focused on rich-club organization, a tendency for brain hubs to be highly-interconnected but disproportionately vulnerable to dysconnectivity. However, less is known about rich-club organization in individuals at clinical high-risk for psychosis (CHR-P) and how it compares with abnormalities early in schizophrenia (ESZ). Combining diffusion tensor imaging (DTI) and magnetic resonance imaging (MRI), we examined rich-club and global network organization in CHR-P (n = 41) and ESZ (n = 70) relative to healthy controls (HC; n = 74) after accounting for normal aging. To characterize rich-club regions, we examined rich-club MRI morphometry (thickness, surface area). We also examined connectome metric associations with symptom severity, antipsychotic dosage, and in CHR-P specifically, transition to a full-blown psychotic disorder. ESZ had fewer connections among rich-club regions (ps < .024) relative to HC and CHR-P, with this reduction specific to the rich-club even after accounting for other connections in ESZ relative to HC (ps < .048). There was also cortical thinning of rich-club regions in ESZ (ps < .013). In contrast, there was no strong evidence of global network organization differences among the three groups. Although connectome abnormalities were not present in CHR-P overall, CHR-P converters to psychosis (n = 9) had fewer connections among rich-club regions (ps < .037) and greater modularity (ps < .037) compared to CHR-P non-converters (n = 19). Lastly, symptom severity and antipsychotic dosage were not significantly associated with connectome metrics (ps < .012). Findings suggest that rich-club and connectome organization abnormalities are present early in schizophrenia and in CHR-P individuals who subsequently transition to psychosis.

Advanced brain age correlates with greater rumination and less mindfulness in schizophrenia.

BACKGROUND: Individual variation in brain aging trajectories is linked with several physical and mental health outcomes. Greater stress levels, worry, and rumination correspond with advanced brain age, while other individual characteristics, like mindfulness, may be protective of brain health. Multiple lines of evidence point to advanced brain aging in schizophrenia (i.e., neural age estimate > chronological age). Whether psychological dimensions such as mindfulness, rumination, and perceived stress contribute to brain aging in schizophrenia is unknown. METHODS: We estimated brain age from high-resolution anatomical scans in 54 healthy controls (HC) and 52 individuals with schizophrenia (SZ) and computed the brain predicted age difference (BrainAGE-diff), i.e., the delta between estimated brain age and chronological age. Emotional well-being summary scores were empirically derived to reflect individual differences in trait mindfulness, rumination, and perceived stress. Core analyses evaluated relationships between BrainAGE-diff and emotional well-being, testing for slopes differences across groups. RESULTS: HC showed higher emotional well-being (greater mindfulness and less rumination/stress), relative to SZ. We observed a significant group difference in the relationship between BrainAge-diff and emotional well-being, explained by BrainAGE-diff negatively correlating with emotional well-being scores in SZ, and not in HC. That is, SZ with younger appearing brains (predicted age < chronological age) had emotional summary scores that were more like HC, a relationship that endured after accounting for several demographic and clinical variables. CONCLUSIONS: These data reveal clinically relevant aspects of brain age heterogeneity among SZ and point to case-control differences in the relationship between advanced brain aging and emotional well-being.

Impact of Alcohol Use, Traumatic Stress, and Cigarette Smoking on Cognitive Functioning in Veterans With Co-occurring Alcohol Use Disorder and Posttraumatic Stress Disorder.

INTRODUCTION: Alcohol use disorder (AUD) and PTSD have high rates of co-occurrence in U.S. Military Veterans resulting in incrementally worse functional outcomes relative to having either one of these disorders alone. Cognitive dysfunction can impede one's ability to benefit from standard behavioral AUD and PTSD treatments. Cigarette smoking is also highly prevalent among U.S. Military Veterans, and cognitive dysfunction is associated with chronic cigarette use among individuals with AUD and PTSD independently. However, much less is known about to what extent cigarette smoking further impairs cognitive functioning in individuals with both co-occurring AUD and PTSD. MATERIALS AND METHODS: U.S. Veterans with co-occurring AUD and PTSD (n = 162) completed a comprehensive cognitive assessment covering various domains: working memory, processing speed, mental switching, cognitive inhibition, auditory-verbal learning, auditory-verbal memory, and verbal fluency. To examine the impact of alcohol use, traumatic stress, and cigarette smoking on cognitive function, we conducted a three-way interaction examining the moderated effects of smoking status on the association between alcohol use and PTSD symptoms on a composite domain of global cognition. RESULTS: Smoking status in Veterans with co-occurring AUD and PTSD moderated the relationship between alcohol use and global cognition (P = .042), such that higher levels of alcohol use in the past week were related to worse global cognitive function among Veterans cigarette smokers (P = .015) but not among nonsmokers (P = .833). On follow-up analyses of individual cognitive domains, greater alcohol use in the past week was associated with lower cognitive inhibition in smokers but not nonsmokers, with traumatic stress symptoms moderating this effect (P = .039). Additionally, smoking status moderated the relationship between alcohol use and auditory-verbal learning, such that there was a differential relationship between alcohol use and auditory-verbal learning between smokers and nonsmokers. CONCLUSIONS: Overall, results provide evidence for the compounding impact of alcohol use, traumatic stress, and cigarette smoking on cognitive functioning. Impaired cognitive performance on a global level as well as on individual domains of cognitive inhibition and auditory-verbal learning were evident. Cognitive dysfunction may impede a Veteran's ability to benefit from therapeutic treatment, and these cognitive domains may represent potential targets for cognitive training efforts. Further, study results support smoking cessation initiatives and smoke-free policies enacted at Veterans Affairs healthcare facilities and medical centers.

Examining associations between social anhedonia and convergent thinking using the Remote Associates Test.

Introduction: Social anhedonia (SocAnh) predicts increased risk of schizophrenia-spectrum disorders, with evidence that these disorders are associated with increased creativity. However, it is still largely unknown whether SocAnh is associated with one central aspect of creative thinking, convergent thinking.Methods: In two studies, college students with either extreme levels of SocAnh (n = 44 and n = 70) or controls with an average level of SocAnh (n = 111 and n = 100) completed a convergent thinking task, the Remote Associates Test, and also completed measures of current affect. In the second study, participants also completed a divergent thinking task.Results: In both studies, the SocAnh group had better performance than controls on the convergent thinking task. Further, this group difference remained after removing shared variance with current affect. In Study 2, groups did not differ on divergent thinking.Conclusions: Overall, consistent with research linking schizophrenia-spectrum disorders and creativity, the current research suggests that SocAnh is associated with increases in some aspects of creativity.

Consider the pons: bridging the gap on sensory prediction abnormalities in schizophrenia.

A shared mechanism across species heralds the arrival of self-generated sensations, helping the brain to anticipate, and therefore distinguish, self-generated from externally generated sensations. In mammals, this sensory prediction mechanism is supported by communication within a cortico-ponto-cerebellar-thalamo-cortical loop. Schizophrenia is associated with impaired sensory prediction as well as abnormal structural and functional connections between nodes in this circuit. Despite the pons' principal role in relaying and processing sensory information passed from the cortex to cerebellum, few studies have examined pons connectivity in schizophrenia. Here, we first briefly describe how the pons contributes to sensory prediction. We then summarize schizophrenia-related abnormalities in the cortico-ponto-cerebellar-thalamo-cortical loop, emphasizing the dearth of research on the pons relative to thalamic and cerebellar connections. We conclude with recommendations for advancing our understanding of how the pons relates to sensory prediction failures in schizophrenia.

Alcohol use in emerging adults associated with lower rich-club connectivity and greater connectome network disorganization.

BACKGROUND: Emerging adulthood is a critical neurodevelopmental stage, with alcohol use during this period consistently associated with brain abnormalities and damage in anatomical structure and white matter integrity. However, it is less clear how alcohol use is associated with the brain's structural organization (i.e., white matter connections between anatomical regions). Recent connectome research has focused on rich-club regions, a collection of highly-interconnected hubs that are critical in brain communication and global network organization and disproportionately vulnerable to insults. METHODS: For the first time, we examined alcohol use associations with structural rich-club and connectome organization in emerging adults (N = 66). RESULTS: Greater lifetime drinks and current monthly drinks were significantly associated with lower rich-club organization (rs =-0.38, ps < 0.003) and lower rich-club connectivity (rs <-0.34, ps < 0.007). Additionally, rich-club connectivity was significantly more negatively correlated with alcohol use than connectivity among non-rich-club regions (ps < 0.035). Examining overall structural organization, greater lifetime drinks and current monthly drinks were significantly associated with lower network density (i.e., lower network resilience; rs <-0.36, ps = 0.004). Additionally, greater lifetime drinks and current monthly drinks were significantly associated with higher network segregation (i.e., network's tendency to divide into subnetworks; rs >0.33, ps<0.008). Alcohol use was not significantly associated with network integration (i.e., network's efficiency in combining information across the brain; ps > 0.064). CONCLUSIONS: Results provide novel evidence that alcohol use is associated with decreased rich-club connectivity and structural network disorganization. Given that both are critical in global brain communication, these results highlight the importance of examining alcohol use and brain relationships in emerging adulthood.

Relations between lab indices of emotion dysregulation and negative affect reactivity in daily life in two independent studies.

BACKGROUND: We investigated the extent to which physiological/biological measures of emotion dysregulation collected in the lab, resting respiratory sinus arrhythmia (RSA) in Study 1 and amygdala activation in response to negative stimuli in Study 2, combined with daily measures of interpersonal stressors predicted negative emotional states in outpatients better than the stressors alone. METHODS: Participants were adult outpatients with emotional distress disorders (N=30 individuals in Study 1, and N=26 women in Study 2). After completing a laboratory session that collected physiological/biological measures of emotion dysregulation, participants then completed 1-3 weeks of ambulatory assessment during which they reported on interpersonal stressors and negative affective states several times per day. RESULTS: Laboratory measures of emotion dysregulation were largely unrelated to either momentary or mean levels of daily-life hostility, sadness, and fear in both studies. However, resting RSA significantly moderated the association between day-level interpersonal stressors and momentary fear such that low resting RSA strengthened this association. Similarly, amygdala activation tended to moderate this relationship in the predicted direction. LIMITATIONS: Both samples were relatively small and focused on only a limited set of diagnoses associated with emotion dysregulation. Only two possible physiological/biological markers of emotion dysregulation were examined. CONCLUSIONS: The current studies support the collection of physiological/biological data on emotion dysregulation when indexing daily-life emotion dysregulation as the degree of emotional reactivity to stressors in daily life among outpatients with emotional distress disorders.

Associations between long-term psychosis risk, probabilistic category learning, and attenuated psychotic symptoms with cortical surface morphometry.

Neuroimaging studies have consistently found structural cortical abnormalities in individuals with schizophrenia, especially in structural hubs. However, it is unclear what abnormalities predate psychosis onset and whether abnormalities are related to behavioral performance and symptoms associated with psychosis risk. Using surface-based morphometry, we examined cortical volume, gyrification, and thickness in a psychosis risk group at long-term risk for developing a psychotic disorder (n = 18; i.e., extreme positive schizotypy plus interview-rated attenuated psychotic symptoms [APS]) and control group (n = 19). Overall, the psychosis risk group exhibited cortical abnormalities in multiple structural hub regions, with abnormalities associated with poorer probabilistic category learning, a behavioral measure strongly associated with psychosis risk. For instance, the psychosis risk group had hypogyria in a right posterior midcingulate cortical hub and left superior parietal cortical hub, as well as decreased volume in a right pericalcarine hub. Morphometric measures in all of these regions were also associated with poorer probabilistic category learning. In addition to decreased right pericalcarine volume, the psychosis risk group exhibited a number of other structural abnormalities in visual network structural hub regions, consistent with previous evidence of visual perception deficits in psychosis risk. Further, severity of APS hallucinations, delusional ideation, and suspiciousness/persecutory ideas were associated with gyrification abnormalities, with all domains associated with hypogyria of the right lateral orbitofrontal cortex. Thus, current results suggest that structural abnormalities, especially in structural hubs, are present in psychosis risk and are associated both with poor learning on a psychosis risk-related task and with APS severity.

Cerebellar stimulation in schizophrenia: A systematic review of the evidence and an overview of the methods.

Background: Cerebellar structural and functional abnormalities underlie widespread deficits in clinical, cognitive, and motor functioning that are observed in schizophrenia. Consequently, the cerebellum is a promising target for novel schizophrenia treatments. Here we conducted an updated systematic review examining the literature on cerebellar stimulation efficacy and tolerability for mitigating symptoms of schizophrenia. We discuss the purported mechanisms of cerebellar stimulation, current methods for implementing stimulation, and future directions of cerebellar stimulation for intervention development with this population. Methods: Two independent authors identified 20 published studies (7 randomized controlled trials, 7 open-label studies, 1 pilot study, 4 case reports, 1 preclinical study) that describe the effects of cerebellar circuitry modulation in patients with schizophrenia or animal models of psychosis. Published studies up to October 11, 2022 were identified from a search within PubMed, Scopus, and PsycInfo. Results: Most studies stimulating the cerebellum used transcranial magnetic stimulation or transcranial direct-current stimulation, specifically targeting the cerebellar vermis/midline. Accounting for levels of methodological rigor across studies, these studies detected post-cerebellar modulation in schizophrenia as indicated by the alleviation of certain clinical symptoms (mainly negative and depressive symptoms), as well as increased frontal-cerebellar connectivity and augmentation of canonical neuro-oscillations known to be abnormal in schizophrenia. In contrast to a prior review, we did not find consistent evidence for cognitive improvements following cerebellar modulation stimulation. Modern cerebellar stimulation methods appear tolerable for individuals with schizophrenia, with only mild and temporary side effects. Conclusion: Cerebellar stimulation is a promising intervention for individuals with schizophrenia that may be more relevant to some symptom domains than others. Initial results highlight the need for continued research using more methodologically rigorous designs, such as additional longitudinal and randomized controlled trials. Systematic review registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42022346667].

Functional connectivity between the ventral anterior cingulate and amygdala during implicit emotional conflict regulation and daily-life emotion dysregulation.

Emotional conflict adaptation involving ventral anterior cingulate cortex (ACC) suppression of the amygdala is thought to be important in emotion regulation, with evidence of impaired implicit emotion regulation in emotional distress disorders. However, it is unclear how this impairment is associated with daily-life emotion dysregulation in emotional distress disorders. In the current study, female participants with an emotional distress disorder (N = 27) were scanned with MRI while completing an implicit emotion conflict regulation task that involved identifying the facial expression of an image while ignoring an overlaid congruent or incongruent affect label. Participants then completed two weeks of ambulatory assessment of daily-life emotion dysregulation. Consistent with previous research on comorbid emotional distress disorders (Etkin and Schatzberg, 2011), there was no behavioral effect of emotional conflict adaptation (p = .701) but a significant effect of congruent adaptation (p = .006), suggesting impairment is specific to implicit emotional conflict regulation. Additionally, there was no neural evidence of emotional conflict adaptation in the ventral ACC and amygdala (ps > .766). Further, in our primary psychophysiological interactions analyses, we examined ventral ACC-amygdala functional connectivity. As hypothesized, increased ventral ACC-amygdala functional connectivity for emotional conflict adaptation was associated with increased daily-life affective instability (p = .022), but not mean daily-life negative affect (p = .372). Overall, results provide behavioral and neural evidence of impaired implicit emotional conflict adaptation in individuals with emotional distress disorders and suggests that this impairment is related to daily-life affective instability in these disorders.

Prospective Study Examining the Effects of Extreme Drinking on Brain Structure in Emerging Adults.

BACKGROUND: Emerging adulthood is a critical neurodevelopment period in which extreme drinking has a potentially pronounced neurotoxic effect. Therefore, extreme drinking, even a single episode, could be particularly harmful to the developing brain's structure. Relatedly, heavy alcohol use in emerging adults has been associated with structural brain damage, especially in the corpus callosum. However, it is unclear whether and how much a single extreme drinking episode would affect brain morphometry. METHODS: For the first time in the literature, the current study prospectively examined the impact of an extreme drinking episode (i.e., twenty-first birthday celebration) on the brain morphometry of emerging adults immediately following their birthday celebration (n = 50) and approximately 5 weeks post-birthday celebration (n = 29). RESULTS: We found evidence that a single extreme drinking episode was associated with structural changes immediately post-birthday celebration. Specifically, higher twenty-first birthday estimated blood-alcohol concentration was associated with decreased volume of the posterior and central corpus callosum immediately post-birthday celebration. This extreme drinking episode was not associated with further structural changes, or recovery, 5 weeks post-twenty-first birthday celebration. CONCLUSIONS: Overall, results suggest that a single episode of heavy drinking in emerging adulthood may be associated with immediate structural changes of the corpus callosum. Thus, emerging adulthood, which is characterized by high rates of extreme drinking, could be a critical period for targeted prevention and intervention.

Psychosis risk is associated with decreased white matter integrity in limbic network corticostriatal tracts.

It is thought that altered connectivity between the striatum and the cortex could contribute to psychosis. However, whether psychosis risk is associated with altered white matter connectivity between the striatum and any cortical region is still unclear. Further, no previous study has directly examined whether psychosis risk is associated with altered striatal connectivity with specific cortical networks. The current study examined the integrity of corticostriatal white matter tracts in psychosis risk (n=18) and in non-psychosis risk comparison participants (n=19). We used probabilistic tractography to identify white matter tracts connecting each of four different striatal subregions with their most functionally connected cortical network: limbic, default mode, frontoparietal, and motor networks. We then compared groups on fractional anisotropy in these four tracts. Psychosis risk was associated with decreased fractional anisotropy in white matter tracts connecting the limbic striatum with the limbic cortical network, especially in an anterior right external capsule segment and in tracts specifically connected to the right prefrontal cortex. In contrast, psychosis risk was not associated with decreased white matter integrity in other corticostriatal tracts. Hence, the current research suggests that psychosis risk is especially associated with decreased corticostriatal white matter integrity involved in processing emotional and personally relevant information.

Alcohol use in young adults associated with cortical gyrification.

BACKGROUND: Young adulthood has the highest rates of alcohol use and high-risk drinking behavior. This period is also a critical neurodevelopmental stage, with neural insults having a profound neurotoxic effect on the brain. Cortical gyrification is thought, in part, to reflect early brain maturation (e.g., hypogyrification in fetal alcohol syndrome). There is also evidence that cortical gyrification is sensitive to later-life events (e.g., fluctuations in malnutrition in young adults). However, no study has examined how alcohol use in young adulthood is associated with cortical gyrification. METHODS: We examined the associations between cortical gyrification with lifetime alcohol use and past year hangover symptoms in young adults (N = 78). RESULTS: Lifetime alcohol use was associated with hypogyria in multiple cortical regions (rs ≤ -.27, ps ≤ .0159; right orbitofrontal, right temporal pole, and left lateral occipital). Further, past year hangover symptoms were associated with hypogyria (rs ≤ -.27, ps ≤ .0034), overlapping with lifetime alcohol use (right orbitofrontal and left lateral occipital). Hangover symptoms were also uniquely associated with hypogyria of other cortical regions (rs ≤ -.30, ps ≤ .0002; right parahippocampal gyrus, left inferior temporal/parahippocampal gyrus and right anterior insula). CONCLUSIONS: Thus, results suggest that young adulthood is a critical period for targeted prevention and intervention, especially for individuals exhibiting heavy alcohol consumption and high-risk drinking behavior.

Daily-life affective instability in emotional distress disorders is associated with function and structure of posterior parietal cortex.

Affective instability (i.e., large and frequent shifts in negative emotions) is a key emotion dysregulation symptom in emotional distress disorders and can be reliably and validly assessed using ambulatory assessment. However, no study has examined whether affective instability is associated with brain function and structure. Using multimodal neuroimaging and ambulatory assessment, we examined associations between functional activation and cortical structure with ambulatory-assessed affective instability in emotional distress disorders (n = 27). Increased daily life-affective instability was associated with decreased neural activation on an emotion regulation task in a left inferior parietal region consistently associated with emotion regulation. Daily-life affective instability was also associated with hypogyria in this same left inferior parietal region, with hypogyria extending into additional posterior parietal regions. This study found evidence that daily-life affective instability was associated with both functionstructure of the posterior parietal cortex, a key attentional control region involved in emotion regulation.