Faculty Bibliography

Thalamocortical dysrhythmias (TCD) may underlie a variety of neurological and neuropsychiatric symptoms. (1,2) In TCD, pathological theta-range activity from thalamic deafferentation or disfacilitation is hypothesized to trigger thalamocortical (TC) domains to oscillate at low frequency, underlying negative symptoms, surrounded by areas of gamma-band activity, creating an 'edge effect' leading to some positive symptoms. TC connectivity and neuronal properties can distribute and sustain this pathological equilibrium. Spontaneous neuromagnetic activity was recorded from patients (n=5) with refractory OCD and from controls (n=4). Recordings were performed with whole-head MEG (4D Neuroimaging), for 5-10 min (0.1-508Hz) with subjects' eyes closed. Coherence, multitaper-based spectral and independent component analyses (ICA) were performed using Matlab (Mathworks) and in-house software. Power spectra from control recordings demonstrated typical alpha rhythms, while spectra from OCD subjects showed robust activity in the theta range and increased total power. In addition, cross-correlations of spectral amplitude from controls displayed activation of discrete frequencies; patterns from OCD subjects showed high coherence over a wider spectral range. Furthermore, ICA revealed components with theta-range spectral properties and dipolar positions consistent with aberrant resting cortical and basal ganglia oscillations. The conception of TCD may serve as a template for the study and treatment of neurological and psychiatric disorders. 1.Llinas,R et al (1999) PNAS 96:15222-7 2.Llinas,R et al (2001) Thal Rel Sys 1:237-44

Cognitive deficits have come to be viewed as a hallmark feature of schizophrenic illness. Although laboratory based assessment of patients' cognitive deficits has been well investigated, few studies to date have examined the utility of clinical ratings of cognitive symptoms using the Schedule for the Assessment of Negative Symptoms (SANS) attention subscale. In this report, we examined the convergence between clinical ratings of cognitive impairment using the SANS attention subscale and performance on a variety of neurocognitive tests designed to measure attentional impairment, as well as other cognitive constructs such as working memory and executive functioning. A total of 56 acute schizophrenic inpatients were clinically rated with the SANS and completed the Continuous Performance Test, Digit Span Distraction Test, Wisconsin Card Sorting Task, and the Trailmaking Test. A series of correlational and regression analyses were conducted to test the concurrent and discriminant validity of the SANS attention subscale. Performance measures of attention, but not working memory or executive functioning, were significantly correlated with and moderately predicted the severity of SANS rated inattention. Additionally, the attention subscale was discriminated from the other SANS negative symptom subscales in predicting a laboratory measure of attentional functioning. The SANS attention subscale demonstrated both concurrent and discriminant validity. These data indicate that attentional dysfunction in schizophrenia can be meaningfully rated and interpreted using the SANS

Frontal lobe dysfunction is thought to be involved in schizophrenia and age-associated cognitive decline. Frontal lobe volume changes have been investigated in these conditions using MRI, but results have been inconsistent. Few volumetric MRI protocols exist that divide the pre-frontal cortex into its sub-regions. In the present article, we describe a new method, which allows assessment of the superior, middle and inferior frontal gyrus, as well as the orbitofrontal and cingulate regions. The method uses multiple planes to help guide the anatomical decisions and combines this with a geometric approach utilizing readily apparent anatomical landmarks. Using this protocol, the frontal lobe volumes in young healthy subjects were contrasted with those of young schizophrenic patients and elderly healthy subjects (nine male subjects per group). The results showed that the method could be reproduced with high reliability (r(icc)> or =0.88-0.99). Schizophrenic as well as old subjects had specific significant reductions in the superior frontal gyrus and orbitofrontal regions compared with the young group. However, old and schizophrenic subjects did not differ from each another. No volume differences were observed in the other three regions assessed. Whether or not these volume reductions reflect a common pathological process remains to be investigated in future studies

Thalamocortical dysrhythmias (TCD) may underlie a variety of neurological and neuropsychiatric symptoms. In TCD, pathological theta-range (4-8 Hz) activity from thalamic deafferentation or disfacilitation has been hypothesized to trigger thalamocortical (TC) domains to function at low frequency, surrounded by areas of gamma-band activity. This intersection has been viewed as creating an 'edge effect' which underlies some positive symptoms. TC properties could also maintain and distribute TCD. Spontaneous neuromagnetic activity was recorded from patients suffering from refractory obsessive-compulsive disorder (OCD) and/or major depression (MD) and from healthy controls. Recordings were performed with a whole-head magnetoencephalogram (MEG) (4-D Neuroimaging) in a shielded room. Activity was recorded for 5-10 min while subjects rested with eyes closed. Spectral analysis using a multitaper technique and cross-correlations between spectral amplitudes were calculated using Matlab (Mathworks, Inc.) and in-house software on a Linux cluster computer system. Power spectra from control recordings demonstrated typical alpha-rhythms, while spectra from OCD and MD subjects showed robust activity in the theta range and increased total power compared to controls. Coherence patterns from controls displayed activation of discrete frequency ranges, while patterns from OCD and MD subjects showed high coherence over a wide range of frequencies. This may reflect theta-range recursive corticothalamic activation