Special issue: Update on neural oscillations in neuropsychiatric disorders

The present issue highlights recent progress in the analysis of oscillatory activity for the assessment, understanding and remediation of psychiatric and neurologic disorders. Contemporary interest in neural synchrony and oscillations in neuropsychiatric disorders has been motivated by investigations of cellular and network oscillations, modeling of neural networks and advances in signal analysis. Hebb1 proposed that synchronous activation between two neurons strengthened connectivity between them; and that a reverberatory neural circuit could maintain a representation of a stimulus in memory. More recent findings implicate neural synchrony and oscillations in feature binding, attentional selection, arousal, memory operations and consciousness.2-9 Consequently, disturbances of oscillations within and between neural ensembles may contribute to sensory, behavioral and cognitive deficits in neuropsychiatric disorders. Because human EEG and MEG activity are generated by synchronized inhibitory and excitatory post-synaptic potentials within large ensembles of neurons, they are well suited for the detection of neural synchrony and oscillations with millisecond temporal resolution

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 to determine 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

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

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

Is Mitigation Translocation an Effective Strategy for Conserving Common Chuckwallas?

Mitigation translocation remains a popular conservation tool despite ongoing debate regarding its utility for population conservation. To add to the understanding of the effectiveness of mitigation translocation, in 2017 and 2018 we monitored a population of protected common chuckwallas (Sauromalus ater) following translocation away from the area of construction of a new highway near the South Mountains, Phoenix, Arizona, USA. We removed chuckwallas from the construction right-of-way, paint-marked and pit-tagged them, and then released them in a nearby municipal preserve. We deployed very high frequency radio-telemetry transmitters on a sub-sample of 15 translocated adult chuckwallas. We monitored the radio-marked chuckwallas once a day at 1- to 3-day intervals for up to 46 days to document survival, body mass, and post-release movements. The average distance moved following translocation was 359 ± 53 m. Using minimum convex polygons, the average home range size of translocated lizards was 0.9 ± 0.3 ha, which was 18–45 times larger than expected for the species. Following translocations, we surveyed the translocation sites 1 month later and again 1 year later to determine the presence of translocated chuckwallas. Translocated individuals were rarely observed a second time: in 2017, only 11 of 160 translocated chuckwallas were seen again, and in 2018, only 11 of 192 translocated chuckwallas were detected. In the light of low recapture rate, consistent loss of body mass, and large movements of marked lizards, we conclude that survival of translocated chuckwallas was low over a single year. In the future, efficacy of mitigation translocation could be better evaluated by assessing the spatial ecology of both resident and translocated individuals simultaneously using radio-telemetry

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

Semantic Search in Psychosis: Modeling Local Exploitation and Global Exploration

Impairments in category verbal fluency task (VFT) performance have been widely documented in psychosis. These deficits may be due to disturbed “cognitive foraging” in semantic space, in terms of altered salience of cues that influence individuals to search locally within a subcategory of semantically related responses (“clustering”) or globally between subcategories (“switching”). To test this, we conducted a study in which individuals with schizophrenia (n = 21), schizotypal personality traits (n = 25), and healthy controls (n = 40) performed VFT with “animals” as the category. Distributional semantic model Word2Vec computed cosine-based similarities between words according to their statistical usage in a large text corpus. We then applied a validated foraging-based search model to these similarity values to obtain salience indices of frequency-based global search cues and similarity-based local cues. Analyses examined whether diagnosis predicted VFT performance, search strategies, cue salience, and the time taken to switch between vs search within clusters. Compared to control and schizotypal groups, individuals with schizophrenia produced fewer words, switched less, and exhibited higher global cue salience, indicating a selection of more common words when switching to new clusters. Global cue salience negatively associated with vocabulary ability in controls and processing speed in schizophrenia. Lastly, individuals with schizophrenia took a similar amount of time to switch to new clusters compared to control and schizotypal groups but took longer to transition between words within clusters. Findings of altered local exploitation and global exploration through semantic memory provide preliminary evidence of aberrant cognitive foraging in schizophrenia

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

A cohort study to identify and evaluate concussion risk factors across multiple injury settings: findings from the CARE Consortium

BACKGROUND: Concussion, or mild traumatic brain injury, is a major public health concern affecting 42 million individuals globally each year. However, little is known regarding concussion risk factors across all concussion settings as most concussion research has focused on only sport-related or military-related concussive injuries. METHODS: The current study is part of the Concussion, Assessment, Research, and Education (CARE) Consortium, a multi-site investigation on the natural history of concussion. Cadets at three participating service academies completed annual baseline assessments, which included demographics, medical history, and concussion history, along with the Sport Concussion Assessment Tool (SCAT) symptom checklist and Brief Symptom Inventory (BSI-18). Clinical and research staff recorded the date and injury setting at time of concussion. Generalized mixed models estimated concussion risk with service academy as a random effect. Since concussion was a rare event, the odds ratios were assumed to approximate relative risk. RESULTS: Beginning in 2014, 10,604 (n = 2421, 22.83% female) cadets enrolled over 3 years. A total of 738 (6.96%) cadets experienced a concussion, 301 (2.84%) concussed cadets were female. Female sex and previous concussion were the most consistent estimators of concussion risk across all concussion settings. Compared to males, females had 2.02 (95% CI: 1.70-2.40) times the risk of a concussion regardless of injury setting, and greater relative risk when the concussion occurred during sport (Odds Ratio (OR): 1.38 95% CI: 1.07-1.78). Previous concussion was associated with 1.98 (95% CI: 1.65-2.37) times increased risk for any incident concussion, and the magnitude was relatively stable across all concussion settings (OR: 1.73 to 2.01). Freshman status was also associated with increased overall concussion risk, but was driven by increased risk for academy training-related concussions (OR: 8.17 95% CI: 5.87-11.37). Medical history of headaches in the past 3 months, diagnosed ADD/ADHD, and BSI-18 Somatization symptoms increased overall concussion risk. CONCLUSIONS: Various demographic and medical history factors are associated with increased concussion risk. While certain factors (e.g. sex and previous concussion) are consistently associated with increased concussion risk, regardless of concussion injury setting, other factors significantly influence concussion risk within specific injury settings. Further research is required to determine whether these risk factors may aid in concussion risk reduction or prevention

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