Kevin Spencer - US grants

DESCRIPTION (provided by applicant): We propose to use event-related brain potentials (ERPs) and transcranial magnetic stimulation (TMS) to examine the mechanisms associated with a particular abnormality of spatial attention in schizophrenia: increased facilitatory and decreased inhibitory priming at short prime-target intervals. We propose that abnormal spatial priming in schizophrenia is related to a dysfunction of an early inhibitory mechanism in prefrontal cortex. To test this hypothesis we will study the performance of schizophrenic and matched healthy individuals in a standard spatial priming task, using ERPs and TMS respectively to examine the stages of processing and brain areas involved. We predict that: 1) Relative to controls, schizophrenic participants will display abnormal spatial priming effects on overt responses (reaction time and accuracy) at the short prime-target interval. 2) Spatial priming effects on the P1 ERP component will be reduced in schizophrenia patients relative to controls at the short prime-target interval, consistent with impaired early inhibitory control. 3) In a subset of the healthy participants, prefrontal as opposed to parietal TMS will produce similar abnormal priming effects on overt responses as found for the patients, consistent with dysfunction of an early prefrontal mechanism. We hope that these results will advance our understanding of the neurocognitive bases of schizophrenia and ultimately contribute to the treatment of this disorder.

[unreadable] DESCRIPTION (provided by applicant): This proposal describes a B/START project that will use measures of neural synchrony in the electroencephalogram (EEG) to examine the functional integrity of neural circuitry in schizophrenia. Schizophrenia has been conceptualized as a failure of cognitive integration, and abnormalities in neural circuitry have been proposed as a basis for this disorder. We hypothesize that abnormalities in gamma-band EEG oscillations reflect impairments in the synchronization of neural circuits in schizophrenia, and are directly related to core cognitive impairments. (Please note that the PI is a newly independent investigator in schizophrenia research, having finished his postdoctoral training in this field 2 years ago, and thus is at an ideal stage in his career for a B/START grant.) Previously we reported two major abnormalities in the gamma-band oscillations elicited by visual Gestalt patterns in schizophrenics: 1) the stimulus-evoked oscillation (SEO) was absent, and 2) the response-locked oscillation (RLO) occurred in a lower frequency band for patients than controls. In schizophrenics, the RLO was positively correlated with visual hallucinations, thought disorder, and disorganization. We hypothesize that the absence of the SEO in schizophrenics is due to a lack of top-down attentional enhancement of synchrony at this stage of early visual processing, which would be consistent with the attentional deficits that characterize schizophrenia. Given that the RLO appears to be generated in visual cortex but is coupled to reaction time, and is related to core perceptual and cognitive dysfunctions in schizophrenia, we hypothesize that the RLO reflects a synchrony-based neural mechanism that is closely involved in the generation of conscious perceptions, and is sensitive to primary neural circuit abnormalities in schizophrenia. Thus, a better understanding of the functional significance of the SEO and RLO may lead to new insights into the neural substrates of cognitive dysfunction of schizophrenia. To test these hypotheses, we will examine neural synchrony in chronic schizophrenia patients and matched healthy controls while they perform visual perception tasks which presumably involve feature integration via neuronal synchronization. Our specific aims are to: 1) Test whether the absence of the SEO in schizophrenics is stimulus-independent, and 2) reflects a lack of attentional enhancement of synchrony. 3) Test that the RLO reflects a feature-binding mechanism involved in conscious object perception. 4) Confirm our previous findings of schizophrenic abnormalities and symptom correlations in the RLO. To treat and ultimately prevent neuropsychiatric disorders, we must understand how the mind and brain are interrelated. This project seeks to further this goal by studying how brainwave synchronization is related to perception and thinking in people who are healthy, and in people who have schizophrenia. [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): This project will use measures of neural synchrony in the scalp-recorded electroencephalogram (EEG) to examine the functional integrity of neural circuitry in schizophrenia. Schizophrenia has been conceptualized as a failure of cognitive integration, and abnormalities in neural circuitry (particularly inhibitory interneurons) have been proposed as a basis for this disorder. A growing number of studies have reported that individuals with schizophrenia demonstrate abnormal synchronization in the "gamma" band of the EEG (30-100 Hz). Gamma oscillations may mediate perceptual and cognitive processes, and are known to rely upon inhibitory interneurons. Therefore, we propose that abnormalities in gamma-band EEG oscillations in schizophrenia patients reflect dysfunctional synchronization of neural circuitry. In our studies of chronic schizophrenia patients (SZ) and healthy control subjects (HC) we have identified several abnormalities in gamma oscillations related to sensory and perceptual processing. 1) In studies using auditory steady-state responses (ASSRs) to probe the integrity of neural circuitry in auditory cortex, SZ show reductions in the ASSRs evoked by gamma frequency stimulation, but not by stimulation at lower frequencies. 2) The early visual stimulus-evoked oscillation (SEO) appears to be reduced in SZ irrespective of stimuli or task demands. In contrast, the auditory SEO evoked by complex sounds but not simple tones is reduced in SZ, and thus this deficit may be related to stimulus features. 3) In studies utilizing Gestalt stimuli to examine visual feature-binding mechanisms, a response-locked oscillation (RLO) potentially related to feature-binding was reduced in frequency from the gamma to the beta frequency range in SZ. RLO phase locking was positively correlated with thought disorder, conceptual disorganization, and visual hallucination symptoms in SZ. These data and others demonstrate that schizophrenia is associated with abnormalities in a variety of sensory- and perception-related gamma oscillations. To elucidate the dysfunctional neural dynamics that are manifested by gamma oscillations in schizophrenia, we propose the following studies in chronic SZ and matched HC. Oscillatory brain activity will be measured using wavelet-based time-frequency methods. Our specific aims are to: 1) determine the factors underlying the ASSR gamma driving deficit;2) determine the effects of stimulus features and attentional demands on the deficits of the auditory and visual SEOs;3) reveal the oscillatory dynamics underlying the ASSR and SEO deficits in SZ. PUBLIC HEALTH RELEVANCE To treat and ultimately prevent neuropsychiatric disorders, we must understand how the mind and brain are interrelated. This project seeks to further this goal by studying how brainwave synchronization is related to perception and thinking in people who are healthy, and in people who have schizophrenia.