Cognitive Demands and Electrical Stimulation in Memory Function Research

Recruiting at 1 trial location

Overseen By Robert Baudo, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Chicago

Disqualifiers: Non-epilepsy, Under 18, Non-English, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 1.5 hours per session, multiple sessions

66 Participants Needed

Trial Summary

What is the purpose of this trial?

This project tests the role of the human hippocampus in providing online representation of episodic content and providing the top-down signals to brain networks for visuospatial attention and visual processing needed to drive visual sampling for the formation of coherent episodic memories. This hypothesis will be tested in several experiments that measure and manipulate hippocampal activity within eye-tracking tasks designed to isolate the interplay between memory and visual sampling during memory formation. These experiments will be performed in individuals with epilepsy undergoing neurosurgical procedures as part of clinical care, as this provides invasive recordings of neural activity (intracranial electroencephalography, or "iEEG") from the hippocampus and other regions of interest with temporal resolution that matches the rapid pace of eye movements. The temporal resolution of iEEG is key to addressing the hypotheses concerning how the hippocampus drives visual sampling, in addition to responding to it. Direct electrical stimulation through the iEEG electrodes will also be used to test the necessary role of hippocampal processing in driving active visual sampling. By rigorously testing the role of hippocampus in interaction with large-scale networks during the process of memory formation that occurs via active sampling, this project aims to better understand mechanisms relevant to the disruptions of memory formation that occur in neurological and psychiatric disorders.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of this treatment?

Research shows that electrical brain stimulation can improve memory performance, especially when applied during brain states linked to poor memory outcomes. This suggests that targeting specific brain areas with electrical stimulation can help enhance memory function. ^{1 2 3 4 5}

Is electrical brain stimulation generally safe for humans?

Research on electrical brain stimulation, including direct electrical stimulation and transcranial direct current stimulation (tDCS), suggests it is generally safe for humans, though effects can vary. Some studies have shown changes in brain activity and memory performance, but safety guidelines and careful monitoring are important to minimize risks. ^{1 2 5 6 7}

How does the treatment using electrical stimulation and cognitive demands differ from other memory treatments?

This treatment is unique because it combines different cognitive tasks with electrical stimulation to enhance memory, focusing on how specific brain areas respond to stimulation. Unlike traditional methods, it uses adaptive stimulation based on brain activity, potentially offering more personalized and effective memory enhancement. ^{1 2 8 9 10}

Research Team

Joel Voss, PhD

Principal Investigator

University of Chicago

Eligibility Criteria

This study is for adults over 18 with normal or corrected vision who speak English natively. It's designed for individuals with epilepsy undergoing neurosurgical procedures, allowing researchers to record and stimulate brain activity directly.

Inclusion Criteria

I am a native English speaker.

I am 18 years old or older.

My vision is normal or corrected to normal.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants perform eye-tracking memory tasks with iEEG recordings and electrical stimulation in various experimental conditions

1.5 hours per session, multiple sessions

Multiple visits (inpatient)

Follow-up

Participants are monitored for memory task performance and iEEG outcomes

5 minutes post-intervention

Treatment Details

Interventions

• Different cognitive and memory demands during the memory experiment
• Different electrical stimulation parameters during cognitive and memory demands

Trial Overview The trial investigates how the hippocampus influences memory formation and visual processing. Participants will perform eye-tracking tasks while receiving different cognitive challenges and electrical stimulations to their brains.

Participant Groups

Group I: Experiment 6 Experimental Treatment 1 Intervention

The same group of 20 iEEG subjects that are included in Study Experiment Condition 5 will perform the same eye-tracking memory task as described for Study Experiment Condition 2. This experiment condition will be performed on a different day of the inpatient visit than participation in Study Experiment Condition 5.

Group II: Experiment 5 Experimental Treatment 1 Intervention

Subjects with iEEG electrodes implanted will perform the same eye-tracking memory task as described for Study Experiment Condition 1. This is a different group of iEEG subjects selected based on having iEEG electrodes implanted in the hippocampus as well as in at least one location of the Dorsal Attention Network (DAN), which is a region of interest for the experiment condition. 20 subjects undergoing iEEG recordings as part of epilepsy treatment will be assigned to this study experiment condition.

Group III: Experiment 4 Experimental Treatment 2 Interventions

The same 20 subjects with iEEG electrodes implanted who perform Study Experiment Condition 1 will perform the same eye-tracking memory task described for Study Experiment Condition 2. For these subjects, high-frequency electrical stimulation will be delivered through the iEEG electrodes on a subset of study trials, with half of stimulated trials receiving stimulation of the hippocampus and the other half receiving stimulation of the amygdala. This memory task will take about 1.5 hours to complete and will be performed on a different day of their inpatient visit than the procedures for Study Experiment Condition 1.

Group IV: Experiment 3 Experimental Treatment 2 Interventions

The same 20 subjects with iEEG electrodes implanted who perform Study Experiment Condition 2 will perform the same eye-tracking memory task described for Study Experiment Condition 1. For these subjects, high-frequency electrical stimulation will be delivered through the iEEG electrodes on a subset of study trials, with half of stimulated trials receiving stimulation of the hippocampus and the other half receiving stimulation of the amygdala. This memory task will take about 1.5 hours to complete and will be performed on a different day of their inpatient visit than the procedures for Study Experiment Condition 2.

Group V: Experiment 2 Experimental Treatment 1 Intervention

Subjects with iEEG electrodes implanted will perform an eye-tracking memory task in which they view arrays of everyday objects arranged as a grid and later undergo memory testing for these object image arrays. Half of the object-image arrays are studied actively (subjects view objects in any order they wish) and half are studied passively (viewing patterns are predetermined and subjects must follow along). For the memory test, subjects attempt to pick studied objects from among novel (foil) objects and replace them at studied locations using the computer mouse. Eye movements will be remotely (noninvasively) tracked using a camera during the study phases. This memory task will take about 1.5 hours to complete. 20 subjects undergoing iEEG recordings as part of epilepsy treatment will be assigned to this study experiment condition.

Group VI: Experiment 1 Experimental Treatment 1 Intervention

Subjects with iEEG electrodes implanted will perform an eye-tracking memory task in which they view pictures of naturalistic scenes and later undergo memory testing for these scene pictures. For the memory test, studied scenes will be repeated and presented along with novel (foil) scenes. Subjects will attempt to discriminate studied from novel scenes using button press responses. Eye movements will be remotely (noninvasively) tracked using a camera during both study and test. This memory task will take about 1.5 hours to complete. 20 subjects undergoing iEEG recordings as part of epilepsy treatment will be assigned to this study experiment condition.

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Findings from Research

In a study involving 22 patients, direct electrical stimulation of specific brain regions (hippocampus, parahippocampal region, neocortex, prefrontal cortex, and lateral temporal cortex) was shown to modulate high γ activity during verbal memory tasks, particularly affecting memory performance.

The modulation of high γ activity correlated with memory outcomes: stimulation in some areas decreased memory performance, while stimulation in the lateral temporal cortex enhanced memory, suggesting that high γ activity could serve as a biomarker for optimizing brain stimulation therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electrical Stimulation Modulates High γ Activity and Human Memory Performance. Kucewicz, MT., Berry, BM., Kremen, V., et al.[2019]

The review emphasizes the need for standardized guidelines in intracranial stimulation studies of human memory to improve consistency and comparability across research, which currently suffers from methodological inconsistencies.

It outlines important technical and safety considerations for researchers, including electrode placement and behavioral task design, to enhance the reliability of findings in future studies on memory modulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reporting Guidelines and Issues to Consider for Using Intracranial Brain Stimulation in Studies of Human Declarative Memory. Suthana, N., Aghajan, ZM., Mankin, EA., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Direct electrical brain stimulation of human memory: lessons learnt and future perspectives. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Electrical Stimulation Modulates High γ Activity and Human Memory Performance. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Direct Brain Stimulation Modulates Encoding States and Memory Performance in Humans. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Human Memory: Brain-State-Dependent Effects of Stimulation. [2019]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Reporting Guidelines and Issues to Consider for Using Intracranial Brain Stimulation in Studies of Human Declarative Memory. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Using the Cambridge Neuropsychological Test Automated Battery (CANTAB) to assess the cognitive impact of electroconvulsive therapy on visual and visuospatial memory. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Impact of oscillatory tDCS targeting left prefrontal cortex on source memory retrieval. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Unleashing potential: transcranial direct current stimulation over the right posterior parietal cortex improves change detection in low-performing individuals. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Direct Electrical Stimulation of the Human Brain Has Inverse Effects on the Theta and Gamma Neural Activities. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

A network approach for modulating memory processes via direct and indirect brain stimulation: Toward a causal approach for the neural basis of memory. [2018]