Long-term Potentiation Disruption Underlying Cognitive Impairment in ECT (LTP-DUCIECT)

Cognitive problems, like memory loss, are common after brain injuries like trauma or stroke. These problems make daily life harder, and the investigators don't yet know the best ways to help the brain recover. Scientists think that a process in the brain called long-term potentiation (LTP) is important for memory and learning. When LTP isn't working properly, it may cause problems with thinking and memory. But studying LTP in people is hard because it happens deep inside the brain.

Our research uses a treatment called electroconvulsive therapy (ECT) to better understand LTP. ECT is a treatment for severe depression that works by causing a controlled seizure in the brain. While ECT often helps depression, it can temporarily cause memory and thinking problems, which usually improve over time. This makes ECT a good way to study how thinking and memory recover.

The investigators will use a tool called electroencephalography (EEG) to measure brain activity during different stages of ECT treatment. EEG is a safe and non-invasive way to track changes in LTP. Specifically, the investigators will measure how the brain responds to visual signals using something called visual evoked potentials (VEPs). These signals can show how LTP is affected by ECT.

The study's main goal is to track changes in LTP using VEPs during and after ECT. By studying these changes, the investigators hope to learn how ECT affects the brain and how it recovers. This could help improve treatments for brain injuries and other conditions that cause memory and thinking problems.

Study Overview

• Status: Withdrawn
• Conditions: Major Depressive Disorder; Bipolar Disorder II
• Intervention / Treatment: Procedure: Electroconvulsive Therapy

Detailed Description

This study aims to investigate changes in long-term potentiation (LTP)-like phenomena using visual evoked potentials (VEPs) in patients undergoing electroconvulsive therapy (ECT) for treatment-resistant depression. LTP is a fundamental neurophysiological process involved in synaptic plasticity and memory formation, and its disruption has been proposed as a potential mechanism underlying the cognitive side effects of ECT.

Study Design:

The study employs a paired pre- and post-intervention design. VEPs will be recorded using electroencephalography (EEG) at two time points:

Pre-ECT: Prior to the initiation of the ECT treatment series. Post-ECT: Immediately following the completion of the ECT series. The VEP paradigm consists of repetitive visual stimulation presented on a computer monitor. The primary outcome is the amplitude of the N1 component of the VEP, a negative deflection occurring approximately 100 milliseconds after stimulus onset, which is sensitive to changes in LTP-like synaptic plasticity.

Methodology:

Participants will undergo EEG sessions using a high-density EEG system with either a 64-lead cap. Visual stimuli will be presented in a controlled environment to elicit VEPs, and the data will be analyzed to assess changes in the N1 component amplitude between the pre- and post-ECT recordings.

Analysis:

A paired t-test will be used to compare N1 amplitudes before and after the ECT series to evaluate the hypothesis that ECT disrupts LTP-like phenomena, as reflected by changes in VEPs.

This study provides a novel application of VEPs to investigate the neurophysiological effects of ECT and aims to enhance our understanding of synaptic plasticity in the context of therapeutic brain stimulation. Findings from this research could inform future strategies to mitigate the side effects of ECT while preserving its clinical efficacy.

• Study Type: Interventional
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • Domenici Hall

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Study Population

Participants will be recruited from the inpatient and outpatient electroconvulsive therapy (ECT) services at the University of New Mexico (UNM) Hospital. This population consists of individuals referred for ECT treatment as part of their clinical care, ensuring a real-world sample of patients receiving this therapy. Recruitment will focus on patients meeting clinical indications for ECT within this healthcare setting.

Description

Inclusion criteria:

• diagnosis of major depressive disorder (MDD; with or without psychotic features) or bipolar 2 most recent episode depressed;
• clinical indications for ECT with right unilateral electrode placement including treatment resistance or a need for a rapid and definitive response,
• age range adults 18-85 years, and
• English-speaking (many of the neuropsychological tests are only available in English). Antidepressant medications will be continued as clinically indicated. To maintain feasibility and retention, as needed medications will be permitted for anxiety and insomnia.

Exclusion criteria:

• Defined neurological or neurodegenerative disorder (e.g., traumatic brain injury, epilepsy, Alzheimer's disease);
• other psychiatric conditions (e.g., schizophrenia, bipolar I disorder);
• current drug or alcohol use disorder (except for nicotine);
• prisoners; and
• pregnancy (pre- menopausal participants will receive pregnancy test, which is clinically indicated for ECT and not part of study protocol).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Participants undergoing ECT; Participants undergoing ECT for depressive episode

Procedure: Electroconvulsive Therapy; Electroconvulsive therapy (ECT) is a medical treatment that uses controlled electrical stimulation to induce a brief, generalized seizure in the brain. This intervention is performed under general anesthesia with muscle relaxants to ensure patient comfort and safety. ECT is typically used to treat severe depression, bipolar disorder, and other mental health conditions when other treatments, such as medication and psychotherapy, have not been effective.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Evoked Potential	The primary outcome of this study is to measure changes in long-term potentiation (LTP)-like phenomena using visual evoked potentials (VEPs), a non-invasive marker of brain activity recorded through electroencephalography (EEG). VEPs are brain responses to visual stimuli, and the N1 component, a negative peak occurring approximately 100 milliseconds after the stimulus, serves as a reliable index of LTP-like phenomena in humans. In this study, participants will undergo a visual stimulation paradigm designed to elicit and measure changes in the amplitude of the N1 component. This approach allows us to assess changes in synaptic plasticity (a key feature of LTP) before, during, and after a series of electroconvulsive therapy (ECT) treatments. These measurements will be correlated with cognitive performance and memory changes to explore the relationship between ECT-induced cognitive effects and LTP disruption.	From enrollment to eight weeks after enrollment

Collaborators and Investigators

• Sponsor: University of New Mexico
• Collaborators: National Institute of General Medical Sciences (NIGMS)

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: December 10, 2024
• First Submitted That Met QC Criteria: December 10, 2024
• First Posted (Actual): December 13, 2024

Study Record Updates

• Last Update Posted (Actual): January 21, 2026
• Last Update Submitted That Met QC Criteria: January 16, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: major depressive disorder; cognitive impairment; electroconvulsive therapy; bipolar disorder, type II; brain recovery; long-term potentiation
• Additional Relevant MeSH Terms: Bipolar and Related Disorders; Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Mood Disorders; Depressive Disorder; Cognitive Dysfunction; Bipolar Disorder; Depressive Disorder, Major; Behavioral Disciplines and Activities; Convulsive Therapy; Psychiatric Somatic Therapies; Electroshock; Psychological Techniques; Electroconvulsive Therapy
• Other Study ID Numbers: 23-286; 5P20GM109089-10 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The decision to share individual participant data (IPD) is currently undecided. While the study aims to contribute to scientific knowledge and improve understanding of electroconvulsive therapy (ECT)-associated cognitive impairment, logistical and regulatory considerations regarding data de-identification, storage, and sharing policies are still under review. The research team is evaluating whether sharing IPD, such as de-identified EEG data and cognitive performance results, would align with institutional guidelines and participant consent. Updates on the IPD sharing decision will be provided upon final determination.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No