Cognitive deficits in neuropsychiatric disorders are profoundly disabling and effective treatments are lacking. Understanding the pathophysiology of cognitive deficits can guide investigations of neuropathology, genetic mechanisms and the development of targeted interventions. The primary goal of our research program is to elucidate the mechanisms underlying cognitive deficits so that these deficits can be more effectively prevented and treated. We primarily focus on individuals with schizophrenia and autism spectrum disorder (ASD).
The Manoach Lab is presently conducting investigations of the contribution of abnormal sleep to cognitive deficits. Although schizophrenia and ASD are defined by waking phenomena, abnormal sleep is a common feature. In particular, schizophrenia is characterized by reduced sleep spindle activity. Sleep spindles correlate with IQ and are thought to promote long-term potentiation and enhance memory consolidation. Reduced spindle activity in schizophrenia may impair sleep-dependent memory consolidation, contribute to symptoms and be a useful novel treatment biomarker. Studies showing that spindles can be pharmacologically enhanced in schizophrenia and that increasing spindles improves memory in healthy individuals suggest that treating spindle deficits in schizophrenia may improve cognition. Spindle activity is highly heritable and recent genetic studies have identified schizophrenia and ASD risk genes that may contribute to spindle deficits and illuminate their mechanisms. The ultimate goal of this research program is to forge empirical links in causal chains from risk genes to proteins and cellular functions, through to endophenotypes, cognitive impairments, symptoms and diagnosis, with the hope of advancing the mechanistic understanding and treatment of schizophrenia and ASD. To achieve this goal, we collaborate with a multidisciplinary team of researchers including engineers and basic scientists studying animal models and human geneticists.
Our tools include behavioral studies, functional MRI (fMRI), diffusion tensor imaging (DTI), electroencephalography (EEG) and magnetoencephalography (MEG). We use these tools in complementary ways to achieve a high degree of spatial and temporal precision.