Neural evidence of switch processes during semantic and phonetic foraging in human memory.

Humans may retrieve words from memory by exploring and exploiting in "semantic space" similar to how nonhuman animals forage for resources in physical space. This has been studied using the verbal fluency test (VFT), in which participants generate words belonging to a semantic or phonetic category in a limited time. People produce bursts of related items during VFT, referred to as "clustering" and "switching." The strategic foraging model posits that cognitive search behavior is guided by a monitoring process which detects relevant declines in performance and then triggers the searcher to seek a new patch or cluster in memory after the current patch has been depleted. An alternative body of research proposes that this behavior can be explained by an undirected rather than strategic search process, such as random walks with or without random jumps to new parts of semantic space. This study contributes to this theoretical debate by testing for neural evidence of strategically timed switches during memory search. Thirty participants performed category and letter VFT during functional MRI. Responses were classified as cluster or switch events based on computational metrics of similarity and participant evaluations. Results showed greater hippocampal and posterior cerebellar activation during switching than clustering, even while controlling for interresponse times and linguistic distance. Furthermore, these regions exhibited ramping activity which increased during within-patch search leading up to switches. Findings support the strategic foraging model, clarifying how neural switch processes may guide memory search in a manner akin to foraging in patchy spatial environments.

Alterations in self-reported sensory gating and interoception in individuals frequently using cannabis.

Background: Cannabis use is associated with altered processing of external (exteroceptive) and internal (interoceptive) sensory stimuli. However, little research exists on whether subjective experiences of these processes are altered in people who frequently use cannabis. Altered exteroception may influence externally oriented attention, whereas interoceptive differences have implications for intoxication, craving, and withdrawal states.Objectives: The goal of the current study was to investigate subjective experiences of exteroceptive sensory gating and interoception in people frequently using cannabis. We hypothesized subjective impairments in sensory gating and elevations in affect-related interoceptive awareness; furthermore, such deviations would relate to cannabis use patterns.Methods: This cross-sectional study of community adults 18-40 years old included 72 individuals (50% female) who used cannabis at least twice a week (not intoxicated during study) and 78 individuals who did not use cannabis (60% female). Participants completed the Sensory Gating Inventory and the Multidimensional Assessment of Interoceptive Awareness-2 surveys. People using cannabis completed surveys on cannabis use patterns. Analyses tested group differences and associations with cannabis use.Results: People using cannabis reported impaired sensory gating (d = 0.37-0.44; all p values < 0.05) and elevations of interoceptive awareness related to detection and affect (d = 0.21-0.61; all p values < 0.05). Problematic cannabis use was associated with increased sensory gating impairments (r = 0.37, p < .05). Interoceptive awareness was unrelated to cannabis use variables.Conclusion: These findings extend literature on subjective experiences of sensory processing in people using cannabis. Findings may inform inclusion of external attentional tendencies and internal bodily awareness in assessments of risk and novel treatment approaches.

Differential Cognitive Performance in Females and Males with Regular Cannabis Use.

OBJECTIVES: Preclinical and clinical studies suggest that males and females may be differentially affected by cannabis use. This study evaluated the interaction of cannabis use and biological sex on cognition, and the association between observed cognitive deficits and features of cannabis use. METHODS: Cognitive measures were assessed in those with regular, ongoing, cannabis use (N = 40; 22 female) and non-using peers (N = 40; 23 female). Intelligence, psychomotor speed, and verbal working memory were measured with the Wechsler Abbreviated Scale of Intelligence, Digit Symbol Test, and Digit Span and Hopkins Verbal Learning Test, respectively. Associations between cognitive measures and cannabis use features (e.g., lifetime cannabis use, age of initiation, time since last use of cannabis, recent high-concentration tetrahydrocannabinoid exposure) were also evaluated. RESULTS: No main effects of group were observed across measures. Significant interactions between group and biological sex were observed on measures of intelligence, psychomotor speed, and verbal learning, with greatest group differences observed between males with and without regular cannabis use. Psychomotor performance was negatively correlated with lifetime cannabis exposure. Female and male cannabis use groups did not differ in features of cannabis use. CONCLUSIONS: Findings suggest that biological sex influences the relationship between cannabis and cognition, with males potentially being more vulnerable to the neurocognitive deficits related to cannabis use.

Cerebellar-cortical dysconnectivity in resting-state associated with sensorimotor tasks in schizophrenia.

Abnormalities of cerebellar function have been implicated in the pathophysiology of schizophrenia. Since the cerebellum has afferent and efferent projections to diverse brain regions, abnormalities in cerebellar lobules could affect functional connectivity with multiple functional systems in the brain. Prior studies, however, have not examined the relationship of individual cerebellar lobules with motor and nonmotor resting-state functional networks. We evaluated these relationships using resting-state fMRI in 30 patients with a schizophrenia-spectrum disorder and 37 healthy comparison participants. For connectivity analyses, the cerebellum was parcellated into 18 lobular and vermal regions, and functional connectivity of each lobule to 10 major functional networks in the cerebrum was evaluated. The relationship between functional connectivity measures and behavioral performance on sensorimotor tasks (i.e., finger-tapping and postural sway) was also examined. We found cerebellar-cortical hyperconnectivity in schizophrenia, which was predominantly associated with Crus I, Crus II, lobule IX, and lobule X. Specifically, abnormal cerebellar connectivity was found to the cerebral ventral attention, motor, and auditory networks. This cerebellar-cortical connectivity in the resting-state was differentially associated with sensorimotor task-based behavioral measures in schizophrenia and healthy comparison participants-that is, dissociation with motor network and association with nonmotor network in schizophrenia. These findings suggest that functional association between individual cerebellar lobules and the ventral attentional, motor, and auditory networks is particularly affected in schizophrenia. They are also consistent with dysconnectivity models of schizophrenia suggesting cerebellar contributions to a broad range of sensorimotor and cognitive operations.

Polarity- and Intensity-Independent Modulation of Timing During Delay Eyeblink Conditioning Using Cerebellar Transcranial Direct Current Stimulation.

Delay eyeblink conditioning (dEBC) is widely used to assess cerebellar-dependent associative motor learning, including precise timing processes. Transcranial direct current stimulation (tDCS), noninvasive brain stimulation used to indirectly excite and inhibit select brain regions, may be a promising tool for understanding how functional integrity of the cerebellum influences dEBC behavior. The aim of this study was to assess whether tDCS-induced inhibition (cathodal) and excitation (anodal) of the cerebellum differentially impact timing of dEBC. A standard 10-block dEBC paradigm was administered to 102 healthy participants. Participants were randomized to stimulation conditions in a double-blind, between-subjects sham-controlled design. Participants received 20-min active (anodal or cathodal) stimulation at 1.5 mA (n = 20 anodal, n = 22 cathodal) or 2 mA (n = 19 anodal, n = 21 cathodal) or sham stimulation (n = 20) concurrently with dEBC training. Stimulation intensity and polarity effects on percent conditioned responses (CRs) and CR peak and onset latency were examined using repeated-measures analyses of variance. Acquisition of CRs increased over time at a similar rate across sham and all active stimulation groups. CR peak and onset latencies were later, i.e., closer to air puff onset, in all active stimulation groups compared to the sham group. Thus, tDCS facilitated cerebellar-dependent timing of dEBC, irrespective of stimulation intensity and polarity. These findings highlight the feasibility of using tDCS to modify cerebellar-dependent functions and provide further support for cerebellar contributions to human eyeblink conditioning and for exploring therapeutic tDCS interventions for cerebellar dysfunction.

Childhood poverty and the organization of structural brain connectome.

Socioeconomic disadvantage is associated with atypical development in specific brain regions, yet the relation between poverty and whole brain network organization (i.e., the connectome, a set of brain regions connected with neuronal pathways) has not been characterized. Developmental studies indicate that the connectome undergoes rapid change during childhood and is consequently likely to be highly sensitive to both salutary and detrimental influences. We investigated associations between the socioeconomic disparities measured by the income-to-needs ratio (INR) in childhood and structural brain network organization with 144 healthy children between 6 and 11 years of age (mean age = 8 years). INR of girls was positively and logarithmically associated with the extent to which brain networks were efficiently organized, suggesting that girls in more impoverished environments had less efficient brain network organization. Lower INR was associated with network inefficiency in multiple cortical regions including prefrontal cortex, cingulate, and insula, and in subcortical regions including the hippocampus and amygdala. These findings suggest that childhood poverty may result in wide-spread disruptions of the brain connectome among girls, particularly at the lowest INR levels, and are differentially expressed in females and males.

Aberrant structural-functional coupling in adult cannabis users.

Cellular studies indicate that endocannabinoid type-1 retrograde signaling plays a major role in synaptic plasticity. Disruption of these processes by delta-9-tetrahydrocannabinol (THC) could produce alterations either in structural and functional brain connectivity or in their association in cannabis (CB) users. Graph theoretic structural and functional networks were generated with diffusion tensor imaging and resting-state functional imaging in 37 current CB users and 31 healthy non-users. The primary outcome measures were coupling between structural and functional connectivity, global network characteristics, association between the coupling and network properties, and measures of rich-club organization. Structural-functional (SC-FC) coupling was globally preserved showing a positive association in current CB users. However, the users had disrupted associations between SC-FC coupling and network topological characteristics, most perturbed for shorter connections implying region-specific disruption by CB use. Rich-club analysis revealed impaired SC-FC coupling in the hippocampus and caudate of users. This study provides evidence of the abnormal SC-FC association in CB users. The effect was predominant in shorter connections of the brain network, suggesting that the impact of CB use or predispositional factors may be most apparent in local interconnections. Notably, the hippocampus and caudate specifically showed aberrant structural and functional coupling. These structures have high CB1 receptor density and may also be associated with changes in learning and habit formation that occur with chronic cannabis use.

Reduced electroencephalogram responses to standard and target auditory stimuli in bipolar disorder and the impact of psychotic features: Analysis of event-related potentials, spectral power, and inter-trial coherence.

BACKGROUND: Bipolar disorder (BD) is associated with reductions in the P3b event-related potential (ERP) response to target auditory stimuli, which suggests deficits in context updating. Previous studies have typically examined these responses in the temporal domain, which may not capture alterations in specific frequencies of phase-locked or induced electrophysiological activity. Therefore, the present study examined early and late ERPs in temporal and frequency domains in a bipolar sample with and without current psychotic features. METHODS: The electroencephalogram (EEG) was recorded during an auditory oddball task. Seventy-five BD patients and 98 healthy controls (HCs) discriminated between standard and target tones. N1 ERPs to standards and P3b ERPs to targets were analyzed in the temporal domain. Event-related spectral perturbation (ERSP) and inter-trial coherence (ITC) were analyzed in the frequency domain. RESULTS: The early N1 response to standard tones was not significantly different between the total HC and BD samples irrespective of psychotic features. However, N1 amplitude was reduced in BD patients with psychotic features (BDP) compared to HCs and BD patients without psychotic features. P3b was reduced in BD patients versus HCs, with the BDP sample having the most reduced amplitude. In the time-frequency analysis, delta and theta ERSP and ITC were reduced across the time window for both standard and target stimuli in BD patients compared to HCs, but did not differ in the psychotic features analysis. CONCLUSIONS: The results provide neural evidence that BD is associated with disrupted sensory, attentional, and cognitive processing of auditory stimuli, which may be worsened with the presence of psychotic features.

Auditory feature perception and auditory hallucinatory experiences in schizophrenia spectrum disorder.

Schizophrenia spectrum disorder (SZ) is associated with deficits in auditory perception as well as auditory verbal hallucinations (AVH). However, the relationship between auditory feature perception and auditory verbal hallucinations (AVH), one of the most commonly occurring symptoms in psychosis, has not been well characterized. This study evaluated perception of a broad range of auditory features in SZ and determined whether current AVHs relate to auditory feature perception. Auditory perception, including frequency, intensity, duration, pulse-train and temporal order discrimination, as well as an embedded tone task, was assessed in both AVH (n = 20) and non-AVH (n = 24) SZ individuals and in healthy controls (n = 29) with the Test of Basic Auditory Capabilities (TBAC). The Hamilton Program for Schizophrenia Voices Questionnaire (HPSVQ) was used to assess the experience of auditory hallucinations in patients with SZ. Findings suggest that compared to controls, the SZ group had greater deficits on an array of auditory features, with non-AVH SZ individuals showing the most severe degree of abnormality. IQ and measures of cognitive processing were positively associated with performance on the TBAC for all SZ individuals, but not with the HPSVQ scores. These findings indicate that persons with SZ demonstrate impaired auditory perception for a broad range of features. It does not appear that impaired auditory perception is associated with recent auditory verbal hallucinations, but instead associated with the degree of intellectual impairment in SZ.

Prenatal Maternal Cortisol Has Sex-Specific Associations with Child Brain Network Properties.

Elevated maternal cortisol concentrations have the potential to alter fetal development in a sex-specific manner. Female brains are known to show adaptive behavioral and anatomical flexibility in response to early-life exposure to cortisol, but it is not known how these sex-specific effects manifest at the whole-brain structural networks. A prospective longitudinal study of 49 mother child dyads was conducted with serial assessments of maternal cortisol levels from 15 to 37 gestational weeks. We modeled the structural network of typically developing children (aged 6-9 years) and examined its global connectome properties, rich-club organization, and modular architecture. Network segregation was susceptible only for girls to variations in exposure to maternal cortisol during pregnancy. Girls generated more connections than boys to maintain topologically capable and efficient neural circuits, and this increase in neural cost was associated with higher levels of internalizing problems. Maternal cortisol concentrations at 31 gestational weeks gestation were most strongly associated with altered neural connectivity in girls, suggesting a sensitive period for the maternal cortisol-offspring brain associations. Our data suggest that girls exhibit an adaptive response by increasing the neural network connectivity necessary for maintaining homeostasis and efficient brain function across the lifespan.

Children's intellectual ability is associated with structural network integrity.

Recent structural and functional neuroimaging studies of adults suggest that efficient patterns of brain connectivity are fundamental to human intelligence. Specifically, whole brain networks with an efficient small-world organization, along with specific brain regions (i.e., Parieto-Frontal Integration Theory, P-FIT) appear related to intellectual ability. However, these relationships have not been studied in children using structural network measures. This cross-sectional study examined the relation between non-verbal intellectual ability and structural network organization in 99 typically developing healthy preadolescent children. We showed a strong positive association between the network's global efficiency and intelligence, in which a subtest for visuo-spatial motor processing (Block Design, BD) was prominent in both global brain structure and local regions included within P-FIT as well as temporal regions involved with pattern and form processing. BD was also associated with rich club organization, which encompassed frontal, occipital, temporal, hippocampal, and neostriatal regions. This suggests that children's visual construction ability is significantly related to how efficiently children's brains are globally and locally integrated. Our findings indicate that visual construction and reasoning may make general demands on globally integrated processing by the brain.

Longer gestation is associated with more efficient brain networks in preadolescent children.

Neurodevelopmental benefits of increased gestation have not been fully characterized in terms of network organization. Since brain function can be understood as an integrated network of neural information from distributed brain regions, investigation of the effects of gestational length on network properties is a critical goal of human developmental neuroscience. Using diffusion tensor imaging and fiber tractography, we investigated the effects of gestational length on the small-world attributes and rich club organization of 147 preadolescent children, whose gestational length ranged from 29 to 42 weeks. Higher network efficiency was positively associated with longer gestation. The longer gestation was correlated with increased local efficiency in the posterior medial cortex, including the precuneus, cuneus, and superior parietal regions. Rich club organization was also observed indicating the existence of highly interconnected structural hubs formed in preadolescent children. Connectivity among rich club members and from rich club regions was positively associated with the length of gestation, indicating the higher level of topological benefits of structural connectivity from longer gestation in the predominant regions of brain networks. The findings provide evidence that longer gestation is associated with improved topological organization of the preadolescent brain, characterized by the increased communication capacity of the brain network and enhanced directional strength of brain connectivity with central hub regions.

Disturbances of visual motion perception in bipolar disorder.

OBJECTIVES: While cognitive deficits have been well documented in patients with bipolar disorder, visual perception has been less well characterized. Such deficits appear in schizophrenia, which shares genetic risk factors with bipolar disorder, and may contribute to disturbances in visual cognition and learning. METHODS: The present study investigated visual perception in bipolar disorder using psychophysical tests of contrast sensitivity, dot motion discrimination, and form discrimination. The relationship of these measures to mood state, medication status, and cognitive function was investigated. Sixty-one patients with type I bipolar disorder and 67 comparison subjects were tested. RESULTS: Results indicated a deficit in dot motion trajectory discrimination in both euthymic and ill individuals with bipolar disorder, as well as a global deficit in moving grating contrast sensitivity. Ill individuals with bipolar disorder were impaired in psychomotor processing, but this finding was not related to visual processing performance. CONCLUSIONS: These findings could be due to disturbances in specific visual pathways involved in the processing of motion properties, or to a more general deficit which impairs processing of temporally modulated stimuli.

Alcohol consumption's effects on working memory: Examining familial confounding.

OBJECTIVE: The purpose of our study was to provide a more rigorous test of the causal hypothesis that chronic alcohol use impairs working memory performance. METHOD: We measured linear associations between a latent factor representing alcohol consumption and accuracy across four working memory tasks before and after accounting for familial confounding using a cotwin control design. Specifically, this study examined accuracy through a latent working memory score, the National Institutes of Health (NIH) Toolbox List Sorting, NIH Toolbox Picture Sequence, Penn Word Memory, and 2-back tasks. The study included data from 158 dizygotic and 278 monozygotic twins (Mage = 29 ± 3 years). RESULTS: In our initial sample-wide analysis, we did not detect any statistically significant associations between alcohol use and working memory accuracy. However, our cotwin control analyses showed that twins with greater levels of alcohol use exhibited worse scores on the latent working memory composite measure (B = -.25, CI [-.43, -.08], p < .01), Picture Sequence (B = -.31, CI [-.55, -.08], p < .01), and List Sorting (B = -.28, CI [-.51, -.06 ], p = .01) tasks than did their cotwins. CONCLUSIONS: These results are consistent with a potentially causal relationship between alcohol use and working memory performance that can be detected only after accounting for confounding familial factors. This highlights the importance of understanding the mechanisms that may underlie negative associations between alcohol use and cognitive performance, as well as the potential factors that influence both alcohol behaviors and cognition. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The auditory steady-state response (ASSR): a translational biomarker for schizophrenia.

Electrophysiological methods have demonstrated disturbances of neural synchrony and oscillations in schizophrenia which affect a broad range of sensory and cognitive processes. These disturbances may account for a loss of neural integration and effective connectivity in the disorder. The mechanisms responsible for alterations in synchrony are not well delineated, but may reflect disturbed interactions within GABAergic and glutamatergic circuits, particularly in the gamma range. Auditory steady-state responses (ASSRs) provide a non-invasive technique used to assess neural synchrony in schizophrenia and in animal models at specific response frequencies. ASSRs are electrophysiological responses entrained to the frequency and phase of a periodic auditory stimulus generated by auditory pathway and auditory cortex activity. Patients with schizophrenia show reduced ASSR power and phase locking to gamma range stimulation. We review alterations of ASSRs in schizophrenia, schizotypal personality disorder, and first-degree relatives of patients with schizophrenia. In vitro and in vivo approaches have been used to test cellular mechanisms for this pattern of findings. This translational, cross-species approach provides support for the role of N-methyl-D-aspartate and GABAergic dysregulation in the genesis of perturbed ASSRs in schizophrenia and persons at risk.

Race and self-reported paranoia: Increased item endorsement on subscales of the SPQ.

There is a dearth of research examining how individual-level and systemic racism may lead to elevated diagnostic and symptom rates of paranoia in Black Americans. The present study employed item response theory methods to investigate item- and subscale-level functioning in the Schizotypal Personality Questionnaire (SPQ) in 388 Black and 450 White participants across the schizophrenia-spectrum (i.e., non-psychiatric controls, individuals with schizophrenia, schizoaffective disorder, or schizotypal personality disorder). It was predicted that (1) Black participants would score significantly higher than Whites on the Suspiciousness and Paranoid Ideation subscale of the SPQ, while controlling for total SPQ severity and relevant demographics and (2) Black participants would endorse these subscale items at a lower latent severity level (i.e., total SPQ score) compared to Whites. Generalized linear modeling showed that Black participants endorsed higher scores on subscales sampling paranoia (e.g., Suspiciousness and Paranoid Ideation), while White participants endorsed higher rates within disorganized/positive symptomatology subscales (e.g., Odd or Eccentric Behavior). IRT analyses showed that Black individuals also endorse items within the Suspiciousness and Paranoid Ideation subscale at lower latent severity levels, leading to inflated subscale scores when compared to their White counterparts. Results indicate prominent race effects on self-reported paranoia as assessed by the SPQ. This study provides foundational data to parse what could be normative endorsements of paranoia versus indicators of clinical risk in Black Americans. Implications and recommendations for paranoia research and assessment are discussed.

Temporal and Spectral Properties of the Auditory Mismatch Negativity and P3a Responses in Schizophrenia.

The mismatch negativity (MMN) event-related potential (ERP) indexes relatively automatic detection of changes in sensory stimuli and is typically attenuated in individuals with schizophrenia. However, contributions of different frequencies of electroencephalographic (EEG) activity to the MMN and the later P3a attentional orienting response in schizophrenia are poorly understood and were the focus of the present study. Participants with a schizophrenia-spectrum disorder (n = 85) and non-psychiatric control participants (n = 74) completed a passive auditory oddball task containing 10% 50 ms "deviant" tones and 90% 100 ms "standard" tones. EEG data were analyzed using spatial principal component analysis (PCA) applied to wavelet-based time-frequency analysis and MMN and P3a ERPs. The schizophrenia group compared to the control group had smaller MMN amplitudes and lower deviant-minus-standard theta but not alpha event-related spectral perturbation (ERSP) after accounting for participant age and sex. Larger MMN and P3a amplitudes but not latencies were correlated with greater theta and alpha time-frequency activity. Multiple linear regression analyses revealed that control participants showed robust relationships between larger MMN amplitudes and greater deviant-minus-standard theta inter-trial coherence (ITC) and between larger P3a amplitudes and greater deviant-minus-standard theta ERSP, whereas these dynamic neural processes were less tightly coupled in participants with a schizophrenia-spectrum disorder. Study results help clarify frequency-based contributions of time-domain (ie, ERP) responses and indicate a potential disturbance in the neural dynamics of detecting change in sensory stimuli in schizophrenia. Overall, findings add to the growing body of evidence that psychotic illness is associated with widespread neural dysfunction in the theta frequency band.

Sex differences in neuroendocrine, sympathetic nervous system, and affect responses to acute stress in cannabis users.

RATIONALE: Cannabis is the most widely used illicit substance in the USA and is often reportedly used for stress reduction. Indeed, cannabinoids modulate signaling of the hypothalamic-pituitary-adrenal axis and sympathetic nervous system. However, the role of biological sex in this interaction between cannabis use and stress is poorly understood, despite sex differences in neurobiological stress responsivity, endocannabinoid signaling, and clinical correlates of cannabis use. OBJECTIVE: The study aims to examine the role of biological sex in multisystem stress responsivity in cannabis users. METHODS: Frequent cannabis users (> 3 times/week, n = 48, 52% male) and non-users (n = 41, 49% male) participated in an acute psychosocial stress paradigm. Saliva was collected at eight timepoints and analyzed for hypothalamic-pituitary-adrenal (cortisol) and sympathetic (alpha-amylase) indices of stress responsivity, and basal estradiol. Subjective ratings of negative affect, including distress, were collected at three timepoints. RESULTS: Cannabis users showed blunted pre-to-post-stress cortisol reactivity. Female cannabis users demonstrated greater blunted cortisol reactivity than their male counterparts. Sex moderated the effect of cannabis use on alpha-amylase responsivity over time, wherein female cannabis users showed flattened alpha-amylase responses across the stressor compared to male cannabis users and both non-user groups. Qualitatively, female cannabis users demonstrated the greatest pre-to-post-stress change in subjective distress. Differences in stress responding were not explained by estradiol or distress intolerance. CONCLUSIONS: Biological sex impacts multisystem stress responding in cannabis users. Paradoxically, female cannabis users showed the least physiological, but greatest subjective, responses to the stressor. Further research into sex differences in the effects of cannabis use is warranted to better understand mechanisms and clinical implications.

Insular and Striatal Correlates of Uncertain Risky Reward Pursuit in Schizophrenia.

BACKGROUND AND HYPOTHESIS: Risk-taking in specific contexts can be beneficial, leading to rewarding outcomes. Schizophrenia is associated with disadvantageous decision-making, as subjects pursue uncertain risky rewards less than controls. However, it is unclear whether this behavior is associated with more risk sensitivity or less reward incentivization. Matching on demographics and intelligence quotient (IQ), we determined whether risk-taking was more associated with brain activation in regions affiliated with risk evaluation or reward processing. STUDY DESIGN: Subjects (30 schizophrenia/schizoaffective disorder, 30 controls) completed a modified, fMRI Balloon Analogue Risk Task. Brain activation was modeled during decisions to pursue risky rewards and parametrically modeled according to risk level. STUDY RESULTS: The schizophrenia group exhibited less risky-reward pursuit despite previous adverse outcomes (Average Explosions; F(1,59) = 4.06, P = .048) but the comparable point at which risk-taking was volitionally discontinued (Adjusted Pumps; F(1,59) = 2.65, P = .11). Less activation was found in schizophrenia via whole brain and region of interest (ROI) analyses in the right (F(1,59) = 14.91, P < 0.001) and left (F(1,59) = 16.34, P < 0.001) nucleus accumbens (NAcc) during decisions to pursue rewards relative to riskiness. Risk-taking correlated with IQ in schizophrenia, but not controls. Path analyses of average ROI activation revealed less statistically determined influence of anterior insula upon dorsal anterior cingulate bilaterally (left: χ2 = 12.73, P < .001; right: χ2 = 9.54, P = .002) during risky reward pursuit in schizophrenia. CONCLUSIONS: NAcc activation in schizophrenia varied less according to the relative riskiness of uncertain rewards compared to controls, suggesting aberrations in reward processing. The lack of activation differences in other regions suggests similar risk evaluation. Less insular influence on the anterior cingulate may relate to attenuated salience attribution or inability for risk-related brain region collaboration to sufficiently perceive situational risk.

Evidence of familial confounding of the association between cannabis use and cerebellar-cortical functional connectivity using a twin study.

Cerebellar-cortical resting-state functional connectivity (rsFC) has been reported to be altered in cannabis users. However, this association may be due to genetic and environmental confounding rather than a causal relationship between cannabis use and changes in rsFC. In this co-twin control study, linear mixed models were used to assess relationships between the number of lifetime cannabis uses (NLCU) and age of cannabis onset (ACO) with cerebellar-cortical rsFC. The rsFC with seven functional networks was evaluated in 147 monozygotic and 82 dizygotic twin pairs. Importantly, the use of genetically informed models in this twin sample facilitated examining whether shared genetic or environmental effects underlie crude associations between cannabis measures and connectivity. Individual-level phenotypic analyses (i.e., accounting for twin-pair non-independence) showed that individuals in the full sample with earlier ACO and higher NLCU had lower cerebellar rsFC within the VA, DA, and FP networks. Yet, there were no significant differences in cerebellar-cortical rsFC between monozygotic twins who were discordant for cannabis measures. These findings suggest shared genetic or environmental confounds contribute to associations between cannabis use and altered cerebellar-cortical rsFC, rather than unique causal impacts of cannabis use on cerebellar-cortical rsFC.