Schizophrenia Clinical Trial
Official title:
Target Engagement of the Early Auditory Processing Network by Transcranial Direct Current Stimulation (tDCS): A Pilot Study
Individuals with schizophrenia have difficulties in functioning in the community. No one
really knows what factors determine how well patients manage in the real world. The purpose
of this pilot study is to try a new approach to improving a potential determinant of good
community functioning, namely how we process sounds. Specifically, we propose to examine the
benefit of transcranial direct current stimulation (tDCS), a new tool that is being developed
as a safe and non-invasive neurostimulation method, for improving processing of sounds.
Transcranial direct current stimulation involves placing a wet sponge electrode on the head
and one on the arm. Electrical current from a device powered by a 9-volt battery will flow
from one electrode to the other. A small portion of the current will pass through the skull
and stimulate the brain. This procedure is non-invasive and painless and it results in
increase or decrease of spontaneous neuronal firing in the brain. Neurons are brain cells
that send electrochemical messages to each other. Its safety and beneficial effect on mental
functions has been demonstrated in healthy individuals and several clinical populations.
The purpose of this study is to determine if transcranial direct current stimulation can
effect how we process sounds.
Neurocognitive and social cognitive deficits are increasingly recognized as core features of
schizophrenia. The severity of these deficits closely correlate to functional impairment and
patient outcomes in this population. Current pharmacological treatments do not address these
illness domains and psychosocial interventions that do are not consistently available.
Underlying these higher level cognitive domains are basic sensory processing deficits in the
auditory and visual realm that contribute to higher order dysfunction. Evidence of these
sensory defects are not readily apparent on clinical exam and are best appreciated using
functional imaging and electrophysiological measures. Interventions that remediate these
sensory deficits may lead to functional improvement as sensory level improvements may cascade
up to higher cognitive domains.
Deficits in auditory processing are evidenced using EEG based event related potentials (ERP).
A robust measure of early auditory processing deficits in schizophrenia is the use of an
auditory oddball paradigm to elicit Mismatch Negativity (MMN). The MMN ERP is generated when
a rare deviant signal is detected in the context of a series of standards. The amplitude of
the MMN in schizophrenia patients is decreased compared to healthy controls which reflects a
deficit in detecting novel stimuli. This decreased auditory MMN has been shown to be closely
correlated with deficits in auditory emotion recognition tasks in subjects with schizophrenia
and patient functional outcomes.
This deficit in early auditory processing is thought to be secondary to regions of cortical
hypoactivity. Transcranial direct current stimulation (tDCS) is a non-invasive
neuromodulation technique that targets cortical regions with direct current and can either
increase or decrease cortical excitability depending on the polarity of the tDCS electrode.
The MMN network is composed of several generators that serve to process the auditory signal,
establish an auditory memory trace, and signal the appearance of the deviant signal. The
initial aim of this proposed study will be to determine if tDCS stimulation over the auditory
cortex can modulate early auditory processing as measured by the MMN response. Our second aim
will be to determine the effect of tDCS stimulation over the auditory cortex on performance
measures of auditory processing as assessed by a tone matching task.
Aims and Hypotheses
Aim 1 Determine whether the early auditory processing network can be engaged and modulated by
tDCS of the superior temporal lobe, where the earliest generators of the network maybe
located, as assessed by changes in the auditory mismatch negativity ERP.
Hypothesis 1 Active tDCS stimulation of the superior temporal lobe will modulate the early
auditory processing network resulting in an effect measurable by amplitude changes in the
mismatch negativity ERP compared to control sham stimulation.
Aim 2 Determine the effect of tDCS at the temporal generators on the early auditory
processing network as assessed by the tone matching task performance measure
Hypothesis 2 Active tDCS stimulation of the temporal generators will modulate the early
auditory processing network resulting in a performance change on the tone-matching task
compared to sham control stimulation.
Study Protocol
The study will be a within subject, cross over design counterbalanced for order of both
stimulation condition and post-stimulation measurement. All patients will receive anodal,
cathodal and sham stimulation targeted bilaterally to the superior temporal region
(unipolarity, dual-site stimulation). We do not have a directional prediction for the active
stimulations (anode and cathode) in terms of increasing or decreasing the amplitude of the
MMN ERP, but we do expect active stimulation to change the MMN ERP amplitude. Patients with
schizophrenia will be randomly assigned to one of six block stimulation sequences
counterbalanced for order of stimulation condition. The goal will be to have complete and
usable data from 12 subjects, and thus up to 30 subjects will be enrolled to account for
screen failures and drop-outs. At the first visit, subjects will be screened, assessed, and
consented if they meet selection criteria. They will then be randomized to one of the
counterbalanced stimulation sequences and receive their first stimulation session followed by
EEG assessment and tone matching task. Subjects will return in one week for visit 2 and the
following week for visit 3. At visits 2 and 3, subjects will receive a tDCS session followed
by EEG and tone matching task assessment. All visits will be separated by at least 1 week to
washout the effect from the previous stimulation. Each patient will return for a total of 3
stimulation visits.
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