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Principal Investigator: Alfredo Luis Sklar
Organization: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
Fiscal Year: 2024
Award: $188,136
Funding agency: National Institute of Mental Health
Abstract
Psychosis is a debilitating chronic illness associated with marked impairments of functional capacity in individuals
and a significant economic burden for society. Despite various treatment options to address the positive
symptoms of the illness, relatively few have been successfully developed to target cognitive symptoms that
account for significant deficits in social and occupational functioning. Recent work suggests that deficits in
bottom-up visual perceptual processes contribute to these more established cognitive impairments and their
associated functional decline. Furthermore, distortions in visual perception have a significant clinical impact,
particularly during early stages of the illness, despite being underappreciated in traditional clinical settings.
Unfortunately, our limited understanding of the relationship between perceptual and cognitive systems in
psychosis hinders our ability to isolate targets for therapeutic interventions. The proposed study will examine
disruptions in bottom-up perceptual responses emerging from local cortical processes in addition to their
modulation by coordinated activity across a distributed attentional network and ascertain the impact of each on
clinical outcomes in first-episode psychosis. Response amplification in visual contrast perception, a well-
documented disruption in chronic psychosis with implications for treatment of the disorder, remains understudied
at disease onset. Moreover, the top-down modulation of this fundamental perceptual mechanism remains
unexplored in psychotic illness despite significant literature detailing the facilitation of contrast perception via
attention in healthy populations. I hypothesize that this modulation, mediated by long-range cortical
communication across a distributed visual attention network, will exhibit marked disruption and be more closely
associated with cognitive and functional deficits in early psychosis compared to disruptions in local perceptual
responses. I will use simultaneously recorded M/EEG data to localize regions of visual cortex exhibiting altered
stimulus contrast processing. This approach will also be used to isolate sources of impaired connectivity across
regions of the dorsal attention network underlying the modulation of contrast perception by attention in healthy
adults. Finally, symptoms and functional impairments will be assessed using validated clinical instruments to
quantify the clinical impact of these visual processing deficits in first-episode patients. Identifying the various
levels of information processing at which dysfunctions arise in psychosis is key to elucidating the mechanisms
underlying its least well treated yet most devastating symptoms. Results from this study will inform interventional
approaches targeting specific disruptions in visual processing associated with negative clinical outcomes.
Examining disruptions at an early illness stage will help disambiguate the effects of primary disease processes
from confounds such as age and medication usage and inform longitudinal trajectories of these disease
impairments to identify vulnerable developmental timepoints and maximize the benefits of our interventions.
Terms: <21+ years old><Activities of Daily Living><Activities of everyday life><Address><Adult><Adult Human><Age><Attention><Biologic Models><Biological Models><Brain><Brain Nervous System><Chronic><Chronic Disease><Chronic Illness><Chronic Schizophrenia><Clinical><Clinical assessments><Cognitive><Cognitive Disturbance><Cognitive Impairment><Cognitive Manifestations><Cognitive Symptoms><Cognitive decline><Cognitive deficits><Cognitive function abnormal><Communication><Communities><Conflict><Conflict (Psychology)><Cues><Data><Detection><Development><Diminished Vision><Disease><Disorder><Disturbance in cognition><Dorsal><Drugs><Dysfunction><EEG><Economic Burden><Electroencephalogram><Electroencephalography><Encephalon><Evoked Potentials><Exhibits><Frequencies><Functional disorder><Functional impairment><Future><Goals><Human><Impaired cognition><Impairment><Individual><Intervention><Intervention Strategies><Left><Link><Literature><Low Vision><MEG imaging><Magnetoencephalography><Mediating><Medication><Model System><Modern Man><Morbidity><Morbidity - disease rate><Neurobehavioral Manifestations><Neurobehavioral Signs and Symptoms><Occupational><Onset of illness><Outcome><Partial Sight><Patients><Perception><Performance><Pharmaceutical Preparations><Phase><Physiopathology><Population><Prevalence><Primates><Primates Mammals><Process><Psychoses><Psychotic Disorders><Reduced Vision><Research><Scalp><Scalp structure><Schizophrenia><Schizophrenic Disorders><Sensory><Sight><Societies><Source><Stimulus><Subnormal Vision><Symptom Burden><Symptoms><System><Therapeutic Intervention><Variant><Variation><Vision><Visual><Visual Cortex><Visual Perception><Visual System><Visual attention><Visual impairment><Work><adulthood><ages><attention modulation><attentional modulation><chronic disorder><cognitive defects><cognitive dysfunction><cognitive loss><cognitive system><critical period><daily living function><daily living functionality><decline in function><decline in functional status><dementia praecox><develop therapy><developmental><disease onset><disorder onset><drug/agent><early psychosis><effective intervention><experience><first episode psychosis><first episode schizophrenia><functional ability><functional capacity><functional decline><functional status decline><improved><information processing><instrument><intervention development><intervention therapy><interventional strategy><magnetoencephalogram><magnetoencephalographic imaging><neural><neural correlate><neurobehavioral symptom><non-invasive brain stimulation><noninvasive brain stimulation><pathophysiology><psychotic><psychotic illness><response><schizophrenic><selective attention><social><stimulus processing><targeted drug therapy><targeted drug treatments><targeted therapeutic><targeted therapeutic agents><targeted therapy><targeted treatment><therapy development><treatment development><vision impairment><visual cortical><visual function><visual process><visual processing><visually impaired>