This R21 application aims to develop new auditory working memory (WM) paradigms, which would be of particular value in studies of cognitive function in patients having schizophrenia (SZ). When used with event-related potential (ERP) and event-related oscillation (ERO) EEG measures, it will provide new insights into the contribution of perceptual, attentional, and cognitive control processes to WM deficits. Although there is considerable agreement that WM is a core cognitive deficit in SZ, few studies have used auditory tests and little is known about the cognitive and neurophysiological processes involved in these deficits. Existing neuropsychological tests for assessing WM often confound several cognitive processes and provide no insight as to whether a deficit is related to memory, attention or cognitive control. The auditory WM tests, which use Ignore/Suppress tasks in conjunction with ERPs and EROs, will yield critical information on the role of perceptual bottom-up and top-down attention or inhibitory control processes in WM. EEG will be recorded during the encoding, maintenance, and retrieval of information in WM, which is ideal for evaluating the extent to which behavioral deficits are related to disturbance in sensory/attention processing, maintenance of information, or memory retrieval. Two different tests are used to assess the impact of selective attention and inhibitory control on auditory WM: (1) Ignore test, in which the subject selectively attends to letters presented to one ear and ignores those in the other ear; (2) Suppress test, in which the subject selectively suppresses items in WM (i.e., letters that were presented to one ear). The critical cue is provided either before (Ignore) or after (Suppress) the encoding series, allowing one to dissociate the associated attentional/cognitive control processes and their relation to sustained ERP activity and event-related mid-frontal theta. There are three types of recognition probes, valid (attended ear), lure (irrelevant ear), or control (not presented on trial). The critical comparison is between control and lure, the latter incurring greater intrusion costs (increased RTs) in the Suppress task due to proactive interference. These tests are also ideal for evaluating the extent to which behavioral and early ERP deficits, such as N1, are influenced by selective attention and are lateralized to the right or left hemisphere. Specifically we aim: (1) to measure ERPs and EROs of 40 healthy controls during these auditory Ignore/Suppress tests; (2) determine and refine specific ERP and ERO measures that relate to perceptual, attentional and cognitive control processes; (3) to evaluate the psychometric properties of behavioral and ERP/ERO measures in these tests (i.e., test-retest reliability and internal consistency); (4) to test a sample of 20 SZ patients so as determine feasibility of applying these tests in patients and provide preliminary data evaluating the role of bottom-up and top-down processes underlying auditory WM deficits in SZ. These tests will also be of value in clinical trials for developing and evaluating new treatments for improving cognitive function in patients having SZ.

Public Health Relevance

This research aims to develop new tests for assessing attention and cognitive control in auditory working memory (WM), which when used with event-related potentials and EEG oscillations will give new insights into the cognitive processes and neurophysiological mechanisms underlying WM deficits. It will also contribute toward the development of cost-effective cognitive or pharmacological treatments and for identifying patients who may benefit most from different forms of treatments for neuropsychiatric disorders such as schizophrenia.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21MH106905-01A1
Application #
9034412
Study Section
Special Emphasis Panel (ZRG1-BBBP-J (03))
Program Officer
Morris, Sarah E
Project Start
2016-02-11
Project End
2017-12-31
Budget Start
2016-02-11
Budget End
2016-12-31
Support Year
1
Fiscal Year
2016
Total Cost
$243,000
Indirect Cost
$93,000
Name
New York State Psychiatric Institute
Department
Type
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032
Tenke, Craig E; Kayser, Jürgen; Alvarenga, Jorge E et al. (2018) Temporal stability of posterior EEG alpha over twelve years. Clin Neurophysiol 129:1410-1417