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.

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).

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.

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.

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.

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.

The relationship between cannabis use and taurine: A MRS and metabolomics study.

Taurine is an essential amino acid. It has been shown to be neuroprotective including protecting against the neurotoxic effects of glutamate. The goal of the current study was to examine the relationship between CB use and taurine measured in brain using magnetic resonance spectroscopy (MRS), and peripherally from a urine sample. Two experiments are presented. The first is a reanalysis of published data that examined taurine and glutamate in the dorsal anterior cingulate of a CB user group and non-user group using MRS. The second experiment, in a separate CB user group, used metabolomics analysis to measure taurine levels in urine. Because body composition has been associated with the pharmacokinetics of cannabis and taurine levels, a moderation model was examined with body composition included as the covariate. The MRS study found taurine levels were correlated with glutamate in both groups and taurine was correlated with frequency of CB use in the CB user group. The moderation model demonstrated significant effects of CB use and BMI; the interaction was marginally significant with lower BMI individuals showing a positive relationship between CB use and taurine. A similar finding was observed for the urine analysis. Both CB use and weight, as well as the interaction were significant. In this case, individuals with higher weight showed an association between CB use and taurine levels. This study shows the feasibility and potential importance of examining the relationship between taurine and CB use as it may shed light on a mechanism that underlies the neuroprotective effects of CB.

Association of lifetime major depressive disorder with enhanced attentional sensitivity measured with P3 response in young adult twins.

Major depression is associated with alterations in the auditory P3 event-related potential (ERP). However, the persistence of these abnormalities after recovery from depressive episodes, especially in young adults, is not well known. Furthermore, the potential influence of substance use on this association is poorly understood. Young adult twin pairs (N = 177) from the longitudinal FinnTwin16 study were studied with a psychiatric interview, and P3a and P3b ERPs elicited by task-irrelevant novel sounds and targets, respectively. Dyadic linear mixed-effect models were used to distinguish the effects of lifetime major depressive disorder from familial factors and effects of alcohol problem drinking and tobacco smoking. P3a amplitude was significantly increased and P3b latency decreased, in individuals with a history of lifetime major depression, when controlling the fixed effects of alcohol abuse, tobacco, gender, twins' birth order, and zygosity. These results suggest that past lifetime major depressive disorder may be associated with enhanced attentional sensitivity.

Determinants of utilization of antenatal and delivery care at the community level in rural Bangladesh.

BACKGROUND: Timely utilization of antenatal care and delivery services supports the health of mothers and babies. Few studies exist on the utilization and determinants of timely ANC and use of different types of health facilities at the community level in Bangladesh. This study aims to assess the utilization, timeliness of, and socio-demographic determinants of antenatal and delivery care services in two sub-districts in Bangladesh. METHODS: This cross-sectional study used data collected through a structured questionnaire in the eRegMat cluster-randomized controlled trial, which enrolled pregnant women between October 2018-June 2020. We undertook univariate and multivariate logistic regression analysis to determine the associations of socio-demographic variables with timely first ANC, four timely ANC visits, and facility delivery. We considered the associations in the multivariate logistic regression as statistically significant if the p-value was found to be <0.05. Results are presented as adjusted odds ratios (AOR) with 95% confidence intervals (CI). RESULTS: Data were available on 3293 pregnant women. Attendance at a timely first antenatal care visit was 59%. Uptake of four timely antenatal care visits was 4.2%. About three-fourths of the women delivered in a health facility. Women from all socio-economic groups gradually shifted from using public health facilities to private hospitals as the pregnancy advanced. Timely first antenatal care visit was associated with: women over 30 years of age (AOR: 1.52, 95% CI: 1.05-2.19); nulliparity (AOR: 1.30, 95% CI: 1.04-1.62); husbands with >10 years of education (AOR: 1.40, 95% CI: 1.09-1.81) and being in the highest wealth quintile (AOR: 1.49, 95% CI: 1.18-1.89). Facility deliveries were associated with woman's age; parity; education; the husband's education, and wealth index. None of the available socio-demographic factors were associated with four timely antenatal care visits. CONCLUSIONS: The study observed socio-demographic inequalities associated with increased utilization of timely first antenatal care visit and facility delivery. The pregnant women, irrespective of wealth shifted from public to private facilities for their antenatal care visits and delivery. To increase the health service utilization and promote good health, maternal health care programs should pay particular attention to young, multiparous women, of low socio-economic status, or with poorly educated husbands. CLINICAL TRIAL REGISTRATION: ISRCTN69491836; https://www.isrctn.com/. Registered on December 06, 2018. Retrospectively registered.

Cerebellar Activation Deficits in Schizophrenia During an Eyeblink Conditioning Task.

The cognitive dysmetria theory of psychotic disorders posits that cerebellar circuit abnormalities give rise to difficulties coordinating motor and cognitive functions. However, brain activation during cerebellar-mediated tasks is understudied in schizophrenia. Accordingly, this study examined whether individuals with schizophrenia have diminished neural activation compared to controls in key regions of the delay eyeblink conditioning (dEBC) cerebellar circuit (eg, lobule VI) and cerebellar regions associated with cognition (eg, Crus I). Participants with schizophrenia-spectrum disorders (n = 31) and healthy controls (n = 43) underwent dEBC during functional magnetic resonance imaging (fMRI). Images were normalized using the Spatially Unbiased Infratentorial Template (SUIT) of the cerebellum and brainstem. Activation contrasts of interest were "early" and "late" stages of paired tone and air puff trials minus unpaired trials. Preliminary whole brain analyses were conducted, followed by cerebellar-specific SUIT and region of interest (ROI) analyses of lobule VI and Crus I. Correlation analyses were conducted between cerebellar activation, neuropsychological test scores, and psychotic symptom scores. In controls, the largest clusters of cerebellar activation peaked in lobule VI during early dEBC and Crus I during late dEBC. The schizophrenia group showed robust cortical activation to unpaired trials but no significant conditioning-related cerebellar activation. Crus I ROI activation during late dEBC was greater in the control than schizophrenia group. Greater Crus I activation correlated with higher working memory scores in the full sample and lower positive psychotic symptom severity in schizophrenia. Findings indicate functional cerebellar abnormalities in schizophrenia which relate to psychotic symptoms, lending direct support to the cognitive dysmetria framework.

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.

Decision Making and Impulsivity in Young Adult Cannabis Users.

Aims: Chronic cannabis users show impairments on laboratory measures of decision making which reflect risk factors for initiation and continued use of cannabis. However, the differential sensitivity of these tasks to cannabis use has not been established. Moreover, studies to date have often lacked assessment of psychiatric histories and use of other illicit substances, both of which may influence decision making outcomes. The current study aimed to address these limitations by (1) including multiple types of decision making tasks, (2) implementing the Probabilistic Reversal Learning Task, a measure of decision making under uncertainty, for the first time in cannabis users, (3) including young adult cannabis users with no other psychiatric disorders, and (4) conducting urinalysis to exclude users of other illicit drugs. Methods: Thirty-three current cannabis users without comorbid psychiatric disorders and 35 cannabis non-users completed behavioral measures of decision-making (Iowa Gambling Task), reward discounting (Delay Discounting Task), choice-outcome learning (the Probabilistic Reversal Learning Task) and a questionnaire assessment of impulsivity (Barratt Impulsiveness Scale). Results: Relative to non-users, cannabis users demonstrated greater preference for immediate vs. delayed rewards on the Delay Discounting Task, made fewer advantageous decisions on the Iowa Gambling Task, and endorsed greater impulsivity on the Barratt Impulsiveness Scale scales. Cannabis users and non-users showed comparable performance on the Probabilistic Reversal Learning Task. Frequency of past-month cannabis use and total years of use did not predict decision making or impulsivity. Conclusions: Young adult cannabis users demonstrated higher discounting rates and impairments in learning cost-benefit contingencies, while reversal learning was unaffected. Self-reported impulsivity was elevated as well. None of these measures correlated with current or lifetime estimates of cannabis use, arguing against a dose-relationship. Interventions that target improvement in affected components of decision making may be helpful in reducing cannabis use and relapse.

Altered cerebellar-cortical resting-state functional connectivity in cannabis users.

BACKGROUND: Cannabis use has been associated with abnormalities in cerebellar mediated motor and non-motor (i.e. cognition and personality) phenomena. Since the cerebellum is a region with high cannabinoid type 1 receptor density, these impairments may reflect alterations of signaling between the cerebellum and other brain regions. AIMS: We hypothesized that cerebellar-cortical resting-state functional connectivity (rsFC) would be altered in cannabis users, relative to their non-using peers. It was also hypothesized that differences in rsFC would be associated with cannabis use features, such as age of initiation and lifetime use. METHODS: Cerebellar-cortical and subcortical rsFCs were computed between 28 cerebellar lobules, defined by a spatially unbiased atlas template of the cerebellum, and individual voxels in the cerebral regions, in 41 regular cannabis users (20 female) and healthy non-using peers (N = 31; 18 female). We also investigated associations between rsFC and cannabis use features (e.g. lifetime cannabis use and age of initiation). RESULTS: Cannabis users demonstrated hyperconnectivity between the anterior cerebellar regions (i.e. lobule I-IV) with the posterior cingulate cortex, and hypoconnectivity between the rest of the cerebellum (i.e. Crus I and II, lobule VIIb, VIIIa, VIIIb, IX, and X) and the cortex. No associations were observed between features of cannabis use and rsFC. CONCLUSIONS: Cannabis use was associated with altered patterns of rsFC from the cerebellum to the cerebral cortex which may have a downstream impact on behavior and cognition.

Bifactor Structure of the Schizotypal Personality Questionnaire Across the Schizotypy Spectrum.

Despite widespread use in schizophrenia-spectrum research, uncertainty remains around an empirically supported and theoretically meaningful factor structure of the Schizotypal Personality Questionnaire (SPQ). Current identified structures are limited by reliance on exclusively nonclinical samples. The current study compared factor structures of the SPQ in a sample of 335 nonpsychiatric individuals, 292 schizotypy-spectrum individuals (schizophrenia, schizoaffective disorder, or schizotypal personality disorder), and the combined group (N = 627). Unidimensional, correlated, and hierarchical models were assessed in addition to a bifactor model, wherein subscales load simultaneously onto a general factor and a specific factor. The best-fitting model across samples was a two-specific factor bifactor model, consistent with the nine symptom dimensions of schizotypy as primarily a direct manifestation of a unitary construct. Such findings, for the first time demonstrated in a clinical sample, have broad implications for transdiagnostic approaches, including reifying schizotypy as a construct underlying diverse manifestations of phenomenology across a wide range of severity.

Does Chronic Cannabis Use Impact Risky Decision-Making: An Examination of fMRI Activation and Effective Connectivity?

With the increase in use of cannabis and its shifting legal status in the United States, cannabis use has become an important research focus. While studies of other drug populations have shown marked increases in risky decision-making, the literature on cannabis users is not as clear. The current study examined the performance of 17 cannabis users and 14 non-users on the Balloon Analog Risk Task (BART) using behavioral, fMRI and effective connectivity methods. Significant attenuation was found in a functional pathway projecting from the dorsal anterior cingulate cortex (dACC) to the nucleus accumbens (NAc) in cannabis users compared to non-using controls as well as decreases in risk-taking behaviors. These findings suggest that cannabis users may process and evaluate risks and rewards differently than non-users.

Investigating cerebellar neural function in schizophrenia using delay eyeblink conditioning: A pilot fMRI study.

There is accruing evidence of cerebellar abnormalities in individuals with schizophrenia as measured by performance on a variety of tasks believed to be dependent on cerebellar integrity, including delay eyeblink conditioning. There is also evidence of cerebellar dysfunction on a neural level in schizophrenia from both task-based and resting state neuroimaging studies, however few studies have examined cerebellar neural function while the cerebellum is directly recruited in individuals with schizophrenia. In the current pilot study, we examined neural activity during an explicitly cerebellar task in individuals with schizophrenia or schizoaffective disorder and non-psychiatric controls. Participants underwent delay eyeblink conditioning during fMRI. Results indicated eyeblink conditioning impairment in patients as evidenced by a group by time interaction for conditioned responses. A significant cluster of cerebellar activation was present in controls but not patients during the first half of conditioning; there were no significant differences in activation between groups. An ROI analysis focused on the cerebellum in patients revealed two significant clusters that were inversely associated with negative symptom severity. These results are broadly consistent with the theory of cognitive dysmetria, wherein cerebellar abnormalities are theorized to contribute to motor as well as cognitive and affective disturbances in schizophrenia.