Auditory Control Enhancement (ACE) in Schizophrenia

Summary

The purpose of this clinical trial is to investigate neural markers of target engagement to further develop auditory control enhancement (ACE) as a novel, inexpensive, and noninvasive intervention to address treatment-refractory auditory hallucinations. Here, we will address questions about the feasibility and acceptability of ACE, as well as the degree to which ACE results in measurable engagement of biophysical and neurophysiological targets.

Participants will complete:

* Auditory Control Enhancement (ACE): Participants will be assigned by chance (such as a coin flip) into one of two groups to receive a different dosage or level of transcranial direct current stimulation (tDCS) during three sessions of cognitive training. tDCS is used to stimulate the brain for a short period of time. For tDCS one or two thin wet sponges are placed on the head and/or upper arm. The sponges will be connected to electrodes which will deliver a very weak electrical current. The Neuroelectrics Starstim 32 will be used to deliver tDCS.
* Interviews: Before and after ACE, in two separate sessions, participants will be asked questions about a) background; b) functioning in daily life and across different phases of your life and past, present and future medical records.
* Cognitive Tests: During the interview sessions, participants will also perform cognitive tests. Participants will be asked to complete computerized and pen-and-paper tests of attention, concentration, reading, and problem-solving ability.
* EEG scan: Participants will be asked to complete EEG (electroencephalography) studies before and after ACE training. EEG will be measured using the same Neuroelectrics Starstim 32 system used for tDCS. EEG measures the natural activity of the brain using small sensors placed on the scalp. These sensors use conductive gel to provide a connection suitable for recording brain activity. During EEG, participants will watch a silent video while sounds are played over headphones, or sometimes count the sounds. In addition to these auditory tasks, participants will also be asked to perform visual attention tasks, such pressing a button for a letter or image.
* Magnetic Resonance Imaging (MRI) Scan: Participants will also be asked to complete MRI studies before and after ACE training. An MRI is a type of brain scan that takes pictures of the brain that will later be used to create a 3D model of the brain. The MRI does not use radiation, but rather radio waves, a large magnet and a computer to create the images.

Researchers will compare individuals receiving ACE to those receiving sham tDCS during cognitive training to determine effects of ACE.

Conditions

• Auditory Hallucinations

Interventions

DEVICE

Transcranial Direct Current Stimulation (tDCS)

tDCS will be administered using the Starstim system. We will use the freely available Simulation of Non-Invasive Brain Stimulation (SimNIBS) software to optimally target the rVLPFC and left TPJ in each subject. Finite element models will be generated using T1 and T2 scans. We will generate multiple models to maximize on-target stimulation and minimize off-target stimulation, as determined by ratio of the summed current density within and beyond target regions of interest (ROIs). tDCS current in the active stimulation condition will be maintained at 2.0 milliamps (mA) for the first 45 minutes of each one-hour training session. Sham stimulation the same current, only the current will be ramped down to 0 mA after 30 seconds. Our previous research has shown this method to produce indistinguishable skin sensation. During tDCS, patients will be monitored for possible negative side effects.

BEHAVIORAL

Auditory Cognitive Control Training (ACCT)

ACCT incorporates a subset of components from Cognitive Enhancement Therapy found to have early benefits on the cognitive deficits of interest to the proposed studies and can be conducted more time-efficiently to achieve our specific goals. ACCT involves approximately 3 hours of computerized neurocognitive training using cognitive control and processing speed training software developed by Ben-Yishay and colleagues. Deficits in cognitive control are addressed with computer training exercises containing simple stimuli with little inherent emotional or motivational salience. ACCT requires individuals to be vigilant, inhibit irrelevant stimuli, and shift attention between auditory and visual modalities. Computer training exercises facilitate reaction time in a temporal mode using auditory cues (The Attention Reaction Conditioner), spatial focusing with visual cues (the Zero Accuracy Conditioner), and temporal vigilance with auditory and visual cues (Time Estimates).

Sponsors & Collaborators

• National Institute of Mental Health (NIMH)

  collaborator NIH

• Brian A Coffman, PhD

  lead OTHER

Principal Investigators

• Brian A Coffman, PhD · University of Pittsburgh

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

40 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-09-05

Primary Completion

2024-12-18

Completion

2024-12-18

FDA Device

Yes

Countries

• United States

Study Locations