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.

Impaired Sleep Mediates the Relationship Between Interpersonal Trauma and Subtypes of Delusional Ideation.

BACKGROUND AND HYPOTHESIS: Trauma is a robust risk factor for delusional ideation. However, the specificity and processes underlying this relationship are unclear. Qualitatively, interpersonal traumas (i.e., trauma caused by another person) appear to have a specific relationship with delusional ideation, particularly paranoia, given the commonality of social threat. However, this has not been empirically tested and the processes by which interpersonal trauma contributes to delusional ideation remain poorly understood. Given the role of impaired sleep in both trauma and delusional ideation, it may be a critical mediator between these variables. We hypothesized that interpersonal trauma, but not non-interpersonal trauma, would be positively related to subtypes of delusional ideation, especially paranoia, and that impaired sleep would mediate these relationships. STUDY DESIGN: In a large, transdiagnostic community sample (N = 478), an exploratory factor analysis of the Peter's Delusion Inventory identified three subtypes of delusional ideation, namely magical thinking, grandiosity, and paranoia. Three path models, one for each subtype of delusional ideation, tested whether interpersonal trauma and non-interpersonal trauma were related to subtypes of delusional ideation, and impaired sleep as a mediating variable of interpersonal trauma. STUDY RESULTS: Paranoia and grandiosity were positively related to interpersonal trauma and unrelated to non-interpersonal trauma. Furthermore, these relationships were significantly mediated by impaired sleep, which appeared strongest for paranoia. In contrast, magical thinking was unrelated to traumatic experiences. CONCLUSIONS: These findings support a specific relationship between interpersonal trauma and paranoia as well as grandiosity, with impaired sleep appearing as an important process by which interpersonal trauma contributes to both.

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.

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.

Emotion regulation and delusion-proneness relate to empathetic tendencies in a transdiagnostic sample.

Empathetic tendencies (i.e., perspective taking and empathic concern) are a key factor in interpersonal relationships, which may be impacted by emotion regulation (i.e., reappraisal and suppression) and mental health symptoms, such as psychotic-like experiences. However, it is unclear if certain psychotic-like experiences, such as delusion-proneness, are still associated with reduced empathetic tendencies after accounting for emotion regulation style and dimensions of psychopathology that are often comorbid. In the current study, linear models tested these associations in a transdiagnostic community sample (N = 128), using the Interpersonal Reactivity Index (IRI), Emotion Regulation Questionnaire, and the Peter's Delusion Inventory. Results indicated that perspective taking was positively associated with reappraisal and negatively associated with delusion-proneness, after controlling for age, sex, race, intelligence, and symptoms of anxiety and depression. A significant change in R 2 supported the addition of delusion-proneness in this model. Specificity analyses demonstrated perspective taking was also negatively associated with suppression, but this relationship did not remain after accounting for the effects of reappraisal and delusion-proneness. Additional specificity analyses found no association between empathic concern and reappraisal or delusion-proneness but replicated previous findings that empathic concern was negatively associated with suppression. Taken together, delusion-proneness accounts for unique variance in perspective taking, which can inform future experimental research and may have important implications for psychosocial interventions.

Cerebellar Structure and Function in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by early-onset repetitive behaviors, restricted interests, sensory and motor difficulties, and impaired social interactions. Converging evidence from neuroimaging, lesion and postmortem studies, and rodent models suggests cerebellar involvement in ASD and points to promising targets for therapeutic interventions for the disorder. This review elucidates understanding of cerebellar mechanisms in ASD by integrating and contextualizing recent structural and functional cerebellar research.

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.

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.

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.

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.

Prism Adaptation Deficits in Schizophrenia.

Recent clinical and neurobehavioral evidence suggests cerebellar dysfunction in schizophrenia (SZ). We used the prism adaptation motor task (PAT) to probe specific cerebellar circuits in the disorder. PAT requires cerebellum-dependent motor adaptation, perceptual remapping, and strategic control. A failure to engage in early corrective processes may indicate impairment within either the cerebellum or regions contributing to strategic components, such as the parietal lobe, while an inability to develop and retain a visuomotor shift with time strongly suggests cerebellar impairment. Thirty-one individuals with SZ and 31 individuals without a history of psychological disorders completed PAT. Subjects reached to a target before, during, and following prism exposure, while their movements were recorded using motion-sensing technology. The SZ group performed worse on conditions consisting of adaptation, post-adaptation, aftereffects, and reorientation, thereby demonstrating a failure to adapt to the same degree as healthy controls. SZ performance remained impaired even with visual feedback and did not differ from controls at baseline, suggesting the observed deficit is specific to adaptation. Results indicate that sensorimotor adaptation is impaired in SZ and implicate disturbances in cerebellar circuits.

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.

Relationship of Metacognition and Insight to Neural Synchronization and Cognitive Function in Early Phase Psychosis.

Metacognition is the process of thinking about one's own mental states. It involves a range of faculties that allow an individual to integrate information and form understanding of self and others, and use this understanding to respond to life challenges. Clinical insight is the awareness of one's mental illness, its consequences, and the need for treatment. Persons with psychotic disorders show impaired metacognition and insight, but the neurobiological bases for these impairments are not well characterized. We hypothesized that metacognition and insight may depend on capacity of neural circuits to synchronize at gamma frequencies, as well as the integrity of underlying cognitive processes. In order to test these hypotheses, 17 adults with early phase psychosis were evaluated. Metacognition was assessed with the Metacognition Assessment Scale-Abbreviated, and insight was assessed with the Scale of Unawareness of Illness-Abbreviated. The auditory steady state response (ASSR) to gamma range stimulation (40 Hz) was used as an index of neural synchronization. Cognitive function was assessed using the Brief Assessment of Cognition in Schizophrenia. Increases in ASSR power were associated with poorer metacognition and insight. Higher cognitive performance was associated with higher levels of metacognitive function and insight. These findings suggest that altered neural synchronization and constituent cognitive processes affect both metacognition and insight in early phase psychosis and may offer targets for both pharmacological and psychotherapeutic interventions.

Relationship of auditory electrophysiological responses to magnetic resonance spectroscopy metabolites in Early Phase Psychosis.

Both auditory evoked responses and metabolites measured by magnetic resonance spectroscopy (MRS) are altered in schizophrenia and other psychotic disorders, but the relationship between electrophysiological and metabolic changes are not well characterized. We examined the relation of MRS metabolites to cognitive and electrophysiological measures in individuals during the early phase of psychosis (EPP) and in healthy control subjects. The mismatch negativity (MMN) of the auditory event-related potential to duration deviant tones and the auditory steady response (ASSR) to 40 Hz stimulation were assessed. MRS was used to quantify glutamate+glutamine (Glx), N-Acetylasparate (NAA), creatine (Cre), myo-inositol (Ins) and choline (Cho) at a voxel placed medially in the frontal cortex. MMN amplitude and ASSR power did not differ between groups. The MRS metabolites Glx, Cre and Cho were elevated in the psychosis group. Partial least squares analysis in the patient group indicated that elevated levels of MRS metabolites were associated with reduced MMN amplitude and increased 40 Hz ASSR power. There were no correlations between the neurobiological measures and clinical measures. These data suggest that elevated neurometabolites early in psychosis are accompanied by altered auditory neurotransmission, possibly indicative of a neuroinflammatory or excitotoxic disturbance which disrupts a wide range of metabolic processes in the cortex.

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.

Postural Sway Abnormalities in Schizotypal Personality Disorder.

Motor abnormalities are among the most robust findings in schizophrenia, and increasing evidence suggests they are a core feature of the disorder. Postural sway during balance tasks is a highly sensitive probe of sensorimotor systems including the cerebellum, basal ganglia, and motor cortices. Postural sway deficits are present in schizophrenia as well as groups at high risk for psychosis, suggesting altered postural control may be sensitive to the pathophysiological processes associated with risk and expression of schizophrenia spectrum disorders. This study examined postural sway performance in schizotypal personality disorder (SPD). Individuals with SPD have attenuated psychotic symptoms and share genetic risk with schizophrenia but are usually free from antipsychotic medication and other illness confounds, making SPD useful for assessing candidate biomarkers. We measured postural sway using force plates in 27 individuals with SPD, 27 carefully matched controls, and 27 matched patients with schizophrenia. It was predicted that postural sway in the SPD group would fall intermediate to schizophrenia and controls. In all conditions (eyes open and closed, with feet together or apart), the SPD group swayed significantly more than the controls, as measured by path length and sway area. Moreover, the magnitude of the sway deficit was comparable in the SPD and schizophrenia groups. These findings suggest that postural sway measures may represent a sensorimotor biomarker of schizophrenia spectrum disorders.

Disturbances of postural sway components in cannabis users.

INTRODUCTION: A prominent effect of acute cannabis use is impaired motor coordination and driving performance. However, few studies have evaluated balance in chronic cannabis users, even though density of the CB1 receptor, which mediates the psychoactive effects of cannabis, is extremely high in brain regions critically involved in this fundamental behavior. The present study measured postural sway in regular cannabis users and used rambling and trembling analysis to quantify the integrity of central and peripheral nervous system contributions to the sway signal. METHODS: Postural sway was measured in 42 regular cannabis users (CB group) and 36 non-cannabis users (N-CB group) by asking participants to stand as still as possible on a force platform in the presence and absence of motor and sensory challenges. Center of pressure (COP) path length was measured, and the COP signal was decomposed into rambling and trembling components. Exploratory correlational analyses were conducted between sway variables, cannabis use history, and neurocognitive function. RESULTS: The CB group had significantly increased path length and increased trembling in the anterior-posterior (AP) direction. Exploratory correlational analyses suggested that AP rambling was significantly inversely associated with visuo-motor processing speed. DISCUSSION: Regular cannabis use is associated with increased postural sway, and this appears to be predominantly due to the trembling component, which is believed to reflect the peripheral nervous system's contribution to the sway signal.

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.

Acute Phencyclidine Alters Neural Oscillations Evoked by Tones in the Auditory Cortex of Rats.

BACKGROUND/AIMS: The onset response to a single tone as measured by electroencephalography (EEG) is diminished in power and synchrony in schizophrenia. Because neural synchrony, particularly at gamma frequencies (30-80 Hz), is hypothesized to be supported by the N-methyl-D-aspartate receptor (NMDAr) system, we tested whether phencyclidine (PCP), an NMDAr antagonist, produced similar deficits to tone stimuli in rats. METHODS: Experiment 1 tested the effect of a PCP dose (1.0, 2.5, and 4.5 mg/kg) on response to single tones on intracranial EEG recorded over the auditory cortex in rats. Experiment 2 evaluated the effect of PCP after acute administration of saline or PCP (5 mg/kg), after continuous subchronic administration of saline or PCP (5 mg/kg/day), and after a week of drug cessation. In both experiments, a time-frequency analysis quantified mean power (MP) and phase locking factor (PLF) between 1 and 80 Hz. Event-related potentials (ERPs) were also measured to tones, and EEG spectral power in the absence of auditory stimuli. RESULTS: Acute PCP increased PLF and MP between 10 and 30 Hz, while decreasing MP and PLF between approximately 50 and 70 Hz. Acute PCP produced a dose-dependent broad-band increase in EEG power that extended into gamma range frequencies. There were no consistent effects of subchronic administration on gamma range activity. Acute PCP increased ERP amplitudes for the P16 and N70 components. CONCLUSIONS: Findings suggest that acute PCP-induced NMDAr hypofunction has differential effects on neural power and synchrony which vary with dose, time course of administration and EEG frequency. EEG synchrony and power appear to be sensitive translational biomarkers for disrupted NMDAr function, which may contribute to the pathophysiology of schizophrenia and other neuropsychiatric disorders.