The effect of chronic cannabinoids on broadband EEG neural oscillations in humans.

Animal and cellular work has shown that central cannabinoid-1 receptors modulate neural oscillations in the gamma range (40 Hz), which may be important for normal perceptual and cognitive processes. In order to assess the effect of cannabinoids on broadband-frequency neural oscillations in humans, the current study examined the effect of chronic cannabis use on auditory steady-state responses (ASSRs) utilizing electroencephalography (EEG). Passive ASSRs were assessed using varying rates of binaural stimulation (auditory click-trains; 10-50 Hz in increments of 5 Hz; 80 dB SPL) in carefully screened cannabis users and controls. Chronic cannabis users (n=22; 12 h abstinence before study; positive 11-nor-9-carboxy-delta-9-tetrahydrocannabinol urine levels) and cannabis naïve controls (n=24) were evaluated. Time X frequency analyses on EEG data were performed using Fourier-based mean trial power (MTP) and phase-locking (inter-trial coherence; ITC). Transient ERPs to stimulus onset (auditory N100 components) were also evaluated. As predicted, a decrease in spectral power (MTP) at 40 Hz was observed in the cannabis group (p<0.018). No effects on phase-locking (ITC) or the N100 were observed. Further, within the cannabis group, lower 40 Hz power correlated with an earlier age of onset of cannabis use (p<0.04). These data suggest that chronic exposure to exogenous cannabinoids can alter the ability to generate neural oscillations, particularly in the gamma range. This is consistent with preclinical animal and cellular data, which may have implications for understanding the short- and long-term psychopharmacological effects of cannabis.

Sensory gating impairments in heavy cannabis users are associated with altered neural oscillations.

Central cannabinoid receptors mediate neural oscillations and are localized to networks implicated in auditory P50 sensory gating, including the hippocampus and neocortex. The current study examined whether neural oscillations evoked by the paired clicks (S1, S2) are associated with abnormal P50 gating reported in cannabis users. Seventeen heavy cannabis users and 16 cannabis naïve controls participated. Analyses included P50 amplitudes, and time-frequency analyses (event-related spectral perturbations, ERSPs; intertrial coherence, ITC). Consistent with prior studies, cannabis users exhibited reduced P50 gating. The ERSP analysis yielded attenuated high frequency activity in the beta range (13-29 Hz) post-S1 and in the gamma range (30-50 Hz) post-S2 in the cannabis group, compared with the control group. Greater levels of cannabis use were positively associated with high P50 ratios and negatively with post-S2 ERSP gamma power. Findings suggest that heavy cannabis use is associated with aberrant beta and gamma activity in the dual-click procedure, which corroborates recent work demonstrating disruption of beta/gamma by cannabinoid receptor (CB1) agonists in a rat analogue of this task and highlights the translational potential of the dual-click procedure [corrected]

Treatment of gallbladder disease during operations Iraqi Freedom and Enduring Freedom.

BACKGROUND: We examined the outcome after treatment for gallbladder disease in deployed military service members and the impact of instituting a clinical pathway to expedite return to duty (RTD). METHODS: A retrospective chart review of 97 medically evacuated patients with gallbladder disease was carried out. These patients were evacuated from the field to Landstuhl Regional Medical Center (LRMC), Germany, between March 2003 and November 2004. In October 2003, a clinical pathway was established to facilitate returning these deployed patients back to their combat units. These service members were compared with 90 local patients who underwent the same surgery during the study period. RESULTS: Twenty-nine patients were treated before the implementation of the clinical pathway. Of those, five had complications, five were converted to open, and 52% returned to their deployed units. After the clinical pathway was established, there were no complications (p = 0.023), two were converted to open (p = 0.002), and 84% returned to duty (p = 0.002). The Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) service members had delayed presentations for definitive treatment. When compared with the local patient group, OIF/OEF surgical cases were more often male (78 vs. 32%, p < 0.001), younger (average 31 vs. 35 years, p < 0.001), and associated with longer operative times (89 vs. 52 min, p < 0.001), and had higher conversion rate to open (7.2 vs. 2.2%, p = 0.17) and higher major complication rate (5.1 vs. 0%, p = 0.06). Time to operation and final pathologic diagnosis were significantly different between the two groups. CONCLUSIONS: Gallbladder surgery can be performed in a delayed manner in the deployed service member, although with a significantly higher morbidity as compared with the local population. We suggest that changes in the immediate treatment and transportation of these service members should occur at the theater level. The use of a clinical pathway facilitates the rapid RTD of soldiers diagnosed with gallbladder disease.

Eye-blink conditioning deficits indicate temporal processing abnormalities in schizophrenia.

Theoretical models suggest that symptoms of schizophrenia may be due to a dysfunctional modulatory system associated with the cerebellum. Although it has long been known that the cerebellum plays a critical role in associative learning and motor timing, recent evidence suggests that it also plays a role in nonmotor psychological processes. Indeed, cerebellar anomalies in schizophrenia have been linked to cognitive dysfunction and poor long-term outcome. To test the hypothesis that schizophrenia is associated with cerebellar dysfunction, cerebellar-dependent, delay eye-blink conditioning was examined in 62 individuals with schizophrenia and 62 age-matched non-psychiatric comparison subjects. The conditioned stimulus was a 400 ms tone, which co-terminated with a 50 ms unconditioned stimulus air puff. A subset of participants (25 with schizophrenia and 29 controls) also completed the Wechsler Abbreviated Scale of Intelligence. Participants with schizophrenia exhibited lower rates of eye-blink conditioning, including earlier (less adaptively timed) conditioned response latencies. Cognitive functioning was correlated with the rate of conditioned responsing in the non-psychiatric comparison subjects but not among those with schizophrenia, and the magnitude of these correlations significantly differed between groups. These findings are consistent with models of schizophrenia in which disruptions within the cortico-cerebellar-thalamic-cortical (CCTC) brain circuit are postulated to underlie the cognitive fragmentation that characterizes the disorder.

Eyeblink conditioning anomalies in bipolar disorder suggest cerebellar dysfunction.

OBJECTIVES: Accumulating research implicates the cerebellum in non-motor psychological processes and psychiatric diseases, including bipolar disorder (BD). Despite recent evidence that cerebellar lesions have been documented to trigger bipolar-like symptoms, few studies have directly examined the functional integrity of the cerebellum in those afflicted with BD. METHODS: Using a single-cue delay eyeblink conditioning procedure, the functional integrity of the cerebellum was examined in 28 individuals with BD (9 manic, 8 mixed, and 11 euthymic) and 28 age-matched healthy controls. RESULTS: Analysis of the bipolar group as a whole indicated a conditioned response acquisition and timing deficit compared to controls. However, when the bipolar group was categorized according to mood state (mixed, manic, euthymic), individuals tested during mixed episodes were strikingly impaired, performing significantly worse than all other groups on both the acquisition and timing of conditioned responses. CONCLUSIONS: These findings extend prior research implicating cerebellar functional abnormalities in BD and suggest that cerebellar dysfunction may be associated with mood state and course of illness.

Assessment of forebrain-dependent trace eyeblink conditioning in chronic cannabis users.

While CB1 knockout mice exhibit striking impairments on a cerebellar-dependent task called delay eyeblink conditioning (dEBC), these animals demonstrate intact forebrain-dependent trace EBC (tEBC). Although heavy human cannabis users also show impaired delay EBC, their performance on tEBC is currently unknown. Therefore, 13 heavy cannabis users and 13 cannabis naive controls completed a tEBC procedure. The cannabis group exhibited similar rates of conditioned responding compared to controls in the acquisition and extinction phase. Consistent with reports of overt attentional abnormalities, the cannabis group exhibited decreased N100 ERP amplitudes to the tone CS that were unrelated to mean levels of conditioning across blocks during the acquisition phase. The lack of a significant effect of heavy cannabis use on tEBC reported here, combined with the previous report of impaired dEBC in such users, mirrors the findings observed in CB1 knockout mice, and suggests that the cannabinoid system differentially mediates forebrain- and cerebellar-dependent learning processes in both humans and animals.

P50 and acoustic startle gating are not related in healthy participants.

Although P50 event-related potential (ERP) suppression and acoustic startle prepulse inhibition are conceptualized as measures of sensory and sensorimotor gating, respectively, the relationship between these measures is unclear. In the present study, P50 and prepulse inhibition trials were interleaved in a single testing session to determine their relationship. Thirty-one healthy participants were presented with startle- and P50-eliciting stimuli across six trial blocks. Lead stimuli (i.e., the prepulse to the acoustic startle and the first click in the dual click ERP paradigm) resulted in significant gating, or amplitude attenuation, of responses to the startle probe and second paired click. There were no meaningful correlations between the P50 and prepulse inhibition variables, indicating that P50 suppression and acoustic startle prepulse inhibition measure distinct neural mechanisms. The implications of these findings for operationally defining the psychological construct of gating with these psychophysiological measures are discussed.