Project 1

Multimodal assessment of sensory processing dysfunction in schizophrenia

Project 1 aims to:

• Evaluate the role of oscillatory entrainment deficits in neurocognitive dysfunction in schizophrenia
• Evaluate the relative role of phase-reset vs. amplitude enhancement as basic mechanisms underlying visual processing deficits in schizophrenia
• Evaluate attentional influences on contrast gain impairments in schizophrenia
• Determine the integrity of ultraslow ( < 1 Hz ) synchrony relative to cognitive impairment

Sensory processing deficits are a key component of schizophrenia.  This project analyzes mechanisms underlying sensory processing dysfunction using a multimodal imaging approach incorporating both neurophysiological and MRI-based assessments.  Neurophysiological studies evaluate role of neuronal synchrony and oscillatory hierarchy impairments in etiology of neurocognitive dysfunction.  In particular, it tests the hypothesis that impairments in non-linear stimulus amplification and in oscillatory entrainment may prevent response optimization in patients relative to controls. 

Four experiments have been planned.  The first experiment analyzes the role of oscillatory entrainment in the genesis of previously documented sensory processing deficits and object-attention dysfunction.  For this experiment, hierarchical oscillatory analyses are conducted using mathematical approaches and stimulation paradigms developed from Projects 2 and 3, respectively.  The second experiment analyzes the role of spatial attention in sensory processing dysfunction, also using both standard ERP and oscillatory hierarchy analyses, and also evaluates the role of phase reset vs. exogenous activity in ERP generation in patients and controls.  Experiment 3 evaluates spatial attention effects further using ssVEP approaches.  Deficits in ERP generation are also assessed relative to symptomatic and cognitive measures.  The fourth experiment evaluates the role of structural and functional connectivity impairments in etiology of sensory and attentional deficits using MR measures supported by Core B. DTI measures are used to assess structural connectivity, while resting state fMRI is used to assess functional connectivity.  An underlying hypothesis is that deficits in neurophysiological processes such as non-linear gain and slow oscillatory function that are known to be NMDA receptor-dependent leads to impaired entrainment of higher-frequency oscillations (e.g. delta, theta, gamma), leading to impaired ERP generation and behavior.  Overall, this project tests the hypothesis that deficits in hierarchical processing within regions and structural and functional connectivity between regions lead to deficits in neurocognitive function in schizophrenia.

Investigators: Daniel C. Javitt, MD, PhD (Principal Investigator)