Differential effects of two early life stress paradigms on cerebellar-dependent delay eyeblink conditioning

Early life stress paradigms have become prominent in the animal literature to model atypical development. Currently, two models have prevailed within the literature: (1) limited bedding or nesting and (2) maternal separation or deprivation. Both models have produced aberrations spanning behavior and neural circuitry. Surprisingly, these two models have yet to be directly compared. The current study utilized delay eyeblink conditioning, an associative learning task with a well-defined cerebellar circuit, to compare the behavioral effects of standard limited bedding (postnatal day 2–9, n = 15) and maternal separation (60 min per day during postnatal day 2–14, n = 13) early life stress paradigms. Animals in all groups exhibited robust learning curves. Surprisingly, facilitated conditioning was observed in the maternal separation group. Rats that underwent limited bedding did not differ from the control or maternal separation groups on any conditioning measures. This study contributes to a clearer understanding of early life stress paradigms and the claims made about their mechanisms, which if better clarified can be properly leveraged to increase translational value

Correction to: Psychometric evaluation of the Pinocchio Illusion Questionnaire

The authors would like to correct the following. Erratum for: Psychometric evaluation of the Pinocchio Illusion Questionnaire. Purcell JR, Chen J, Moussa-Tooks AB, Hetrick WP. Atten Percept Psychophys. 2020 Jul;82(5):2728-2737. doi: 10.3758/s13414-020-02011-4. PMID: 32185641 Free PMC article

Psychometric evaluation of the Pinocchio Illusion Questionnaire

Perceived nose elongation resulting from vibratory stimulation to the bicep brachii tendon in the absence of visual input while the finger is touching the nose, known as the Pinocchio Illusion (PI), is used to investigate how afferent signals can contribute to aberrant top-down perception of body representation. The Pinocchio Illusion Questionnaire (PIQ) was developed to empirically quantify PI perception, allowing for external validation of the PI with psychologically relevant phenomenon. The current study (n=60) examined the PIQ’s test-retest reliability, internal consistency, factor structure, and correlations with self-reported interoceptive awareness and schizotypal traits. The PIQ demonstrated strong test-retest reliability and internal validity; however, a Principal Component Analysis did not yield a latent variable structure that distinguished PI-specific perceptual aberrations from unrelated or contradictory perceptual experiences. Additionally, decreased reports of PI-specific perceptual aberrations during two elicitations of the PI on the PIQ’s open-ended free-response section (percent of sample endorsement=5% [first elicitation]; 8.3% [second elicitation]) compared to its 11-item section (endorsement of PI-specific items ranging 30–53.33% [first]; 31.67–46.67% [second]) suggest that these responses may be heavily influenced by demand characteristics rather than accurately capturing PI perception. Therefore, further psychometric development of the PIQ and standardization of procedures to elicit the illusion are recommended

The Sensory Gating Inventory-Brief

The Sensory Gating Inventory (SGI) is a 36-item measure used to assess an individual’s subjective ability to modulate, filter, over-include, discriminate, attend to, and tolerate sensory stimuli. Due to its theoretical and empirical link with sensory processing deficits, this measure has been used extensively in studies of psychosis and other psychopathology. The current work fills a need within the field for a briefer measure of sensory gating aberrations that maintains the original measure’s utility. For this purpose, large samples (total n = 1552) were recruited from 2 independent sites for item reduction/selection and brief measure validation, respectively. These samples reflected subgroups of individuals with a psychosis-spectrum disorder, at high risk for a psychosis-spectrum disorder, nonpsychiatric controls, and nonpsychosis psychiatric controls. Factor analyses and item-response models were used to create the SGI-Brief (SGI-B; 10 Likert-rated items), a unidimensional self-report measure that retains the original SGI’s transdiagnostic (ie, present across disorders) utility and content breadth. Findings show that the SGI-B has excellent psychometric properties (alpha = 0.92) and demonstrates external validity through strong associations with measures of psychotic symptomatology, theoretically linked measures of personality (eg, perceptual dysregulation), and modest associations with laboratory-based sensory processing tasks in the auditory and visual domains on par with the original version. Accordingly, the SGI-B will be a valuable tool for dimensional and transdiagnostic examination of sensory gating abnormalities within clinical science research, while reducing administrator and participant burden

Impaired Effective Connectivity During a Cerebellar-Mediated Sensorimotor Synchronization Task in Schizophrenia

Prominent conceptual models characterize schizophrenia as a dysconnectivity syndrome, with recent research focusing on the contributions of the cerebellum in this framework. The present study examined the role of the cerebellum and its effective connectivity to the cerebrum during sensorimotor synchronization in schizophrenia. Specifically, the role of the cerebellum in temporally coordinating cerebral motor activity was examined through path analysis. Thirty-one individuals diagnosed with schizophrenia and 40 healthy controls completed a finger-tapping fMRI task including tone-paced synchronization and self-paced continuation tapping at a 500 ms intertap interval (ITI). Behavioral data revealed shorter and more variable ITIs during self-paced continuation, greater clock (vs motor) variance, and greater force of tapping in the schizophrenia group. In a whole-brain analysis, groups showed robust activation of the cerebellum during self-paced continuation but not during tone-paced synchronization. However, effective connectivity analysis revealed decreased connectivity in individuals with schizophrenia between the cerebellum and primary motor cortex but increased connectivity between cerebellum and thalamus during self-paced continuation compared with healthy controls. These findings in schizophrenia indicate diminished temporal coordination of cerebral motor activity by cerebellum during the continuation tapping portion of sensorimotor synchronization. Taken together with the behavioral finding of greater temporal variability in schizophrenia, these effective connectivity results are consistent with structural and temporal models of dysconnectivity in the disorder

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

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

Long-Term Aberrations To Cerebellar Endocannabinoids Induced By Early-Life Stress

Emerging evidence points to the role of the endocannabinoid system in long-term stress-induced neural remodeling with studies on stress-induced endocannabinoid dysregulation focusing on cerebral changes that are temporally proximal to stressors. Little is known about temporally distal and sex-specific effects, especially in cerebellum, which is vulnerable to early developmental stress and is dense with cannabinoid receptors. Following limited bedding at postnatal days 2-9, adult (postnatal day 70) cerebellar and hippocampal endocannabinoids, related lipids, and mRNA were assessed, and behavioral performance evaluated. Regional and sex-specific effects were present at baseline and following early-life stress. Limited bedding impaired peripherally-measured basal corticosterone in adult males only. In the CNS, early-life stress (1) decreased 2-arachidonoyl glycerol and arachidonic acid in the cerebellar interpositus nucleus in males only; (2) decreased 2-arachidonoyl glycerol in females only in cerebellar Crus I; and (3) increased dorsal hippocampus prostaglandins in males only. Cerebellar interpositus transcriptomics revealed substantial sex effects, with minimal stress effects. Stress did impair novel object recognition in both sexes and social preference in females. Accordingly, the cerebellar endocannabinoid system exhibits robust sex-specific differences, malleable through early-life stress, suggesting the role of endocannabinoids and stress to sexual differentiation of the brain and cerebellar-related dysfunctions

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