Long-term Potentiation Disruption Underlying Cognitive Impairment in ECT

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.

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.

Eligibility Criteria:
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).