Auditory attention in first episode psychosis

点击翻译按钮获取中文摘要

Selective attention, the ability to focus on one percept among others, is one of the first executive functions affected by psychosis. Basic neuroscience work has begun to elucidate the underlying mechanisms of how selective attention, arising in prefrontal cortex, modulates sensory cortex activity via connections with posterior parietal cortex. In terms of physiology, alpha waves (~10 Hz) and gamma waves (~40 Hz) appear to play a central role in the effects of attention, by which sensory activity to to-be-attended events is increased, while sensory activity to to-be-ignored events is decreased. In human cognitive neuroscience research, studies that examine functional connectivity between different areas of the brain on the basis of specific oscillations (rather than at the scalp) are relatively few. The proposed studies will expand our knowledge of how attention increases sensory activity in the human brain, and how these processes go awry in newly emerging psychosis. In human psychopathology research, several emerging threads have changed the way psychosis is understood. First, evidence indicates progressive cognitive and cortical gray matter decline during the early disease course, even prior to the emergence of psychosis. Second, increasing evidence suggests that psychosis not only affects the highest levels of cognition, but that sensory processes are affected as well. What is not known is to what degree these sensory deficits are due to progressive pathology of cortical sensory areas or to progressive pathology of executive control centers in prefrontal cortex and posterior parietal cortex, such that modulation of sensory activity by executive centers is impaired via reduced functional connectivity. Both schizophrenia and affective psychosis are thought to be late neurodevelopmental disorders with progressive worsening. We hypothesize that higher-order operations that require long range communication and synchronization between multiple distal cortical areas and highly complex integrated processing will be affected first. Hence, we suggest selective attention-based modulation of sensory activity will be impaired quite early in disease course. Our primary goal is to examine how attention affects sensory activity in the auditory system as subjects attend or ignore one tone, two tones, or four tones, thereby increasing the attentional demand for each task. We will use combined EEG & MEG reconstructed into individual brain morphology from structural MRI which will allow for highly precise measurement of neural activity within the brain as participants perform the tasks. Subjects will be tested at first psychotic episode and 6 months later to follow any progressive pathology, and at 12 months to assign definitive diagnoses. A secondary goal is to determine if deficits in the ability to modulate sensory activity by attention, as indicated in our preliminary data, may serve as biomarkers for emerging psychosis. If so, our next step would be to examine attentional modulation of sensory signals in high-risk possibly prodromal help seekers. Thus our strategy is to validate potential pre- psychosis biomarkers right at the emergence of psychosis in known cases, which may then be used to detect the relatively few high-risk help seekers that are actually prodromal for psychosis.