Brain Stimulation for Episodic Memory Improvement

(BNI Trial)

Overseen By Mary Blocher

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Northwestern University

Disqualifiers: Children, Pregnant, Prisoners, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

20 Participants Needed

Trial Summary

What is the purpose of this trial?

Brain stimulation is a means to potentially remediate symptoms in a range of neurological and psychiatric diseases, however, precise targeting of stimulation is necessary to ensure efficacy. The proposed project will use recent advances in functional magnetic resonance imaging to delineate distributed brain networks within individuals, and use these network maps to guide selection of intracranial electrodes for stimulation during an episodic memory task. The resulting data will refine the current understanding of the neural systems involved in episodic memory, and provide a proof-of-principle for the use of individual-level network mapping to guide brain stimulation, which could have important implications for brain stimulation therapies for a range of mental health 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. It is best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of this treatment for improving memory?

Research shows that transcranial electrical stimulation (tES) can enhance memory in older individuals, with effects lasting up to 28 days after a single session. Additionally, neurostimulation methods like tES and transcranial magnetic stimulation (TMS) are being explored for memory enhancement in epilepsy patients, suggesting potential benefits for memory improvement. ^{1 2 3 4 5}

Is brain stimulation safe for humans?

Electroconvulsive therapy (ECT), a type of brain stimulation, is generally effective but can cause memory problems and confusion, especially in older adults. Adjusting the electrical charge can help reduce these side effects. ^{6 7 8 9 10}

How does brain stimulation differ from other treatments for memory improvement?

Brain stimulation, such as Transcranial Magnetic Stimulation (TMS) and Transcranial Electrical Stimulation (TES), is unique because it directly targets specific brain areas to enhance memory, unlike other treatments that may not focus on the brain's electrical activity. This approach can modulate brain activity in real-time, potentially improving memory performance by enhancing the brain's natural processes. ^{2 11 12 13 14}

Research Team

Rodrigo M Braga, PhD

Principal Investigator

Northwestern University

Eligibility Criteria

This trial is for adult epilepsy patients at Northwestern Memorial Hospital who are undergoing routine presurgical planning with intracranial EEG, which includes electrode placement in specific brain regions. It's not for minors, pregnant women, prisoners, those unable to consent, or anyone with MRI contraindications like metal implants.

Inclusion Criteria

I am an inpatient at Northwestern Memorial Hospital for epilepsy surgery planning.

Participants' epilepsy monitoring procedures will include placement of recording electrodes at locations of interest to our study, which include the medial temporal lobe, frontal cortex, parietal cortex, and temporal cortex

Exclusion Criteria

Pregnant women

Exclusions for MRI include standard MRI contraindications, including claustrophobia, metal implants or fragments in the body, and actual or potential pregnancy.

I am under 18 years old.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-surgical fMRI Mapping

Participants undergo 1 to 4 sessions of fMRI to map brain networks before surgical implantation of electrodes

1-4 weeks

1-4 visits (in-person)

Post-surgical Monitoring and Experimentation

Participants are monitored post-surgery and participate in experiments involving intracranial electroencephalography and electrical brain stimulation

7 days

Continuous monitoring (in-patient)

Follow-up

Participants are monitored for safety and effectiveness after the experimental procedures

4 weeks

Treatment Details

Interventions

• Brain stimulation

Trial Overview The study tests if using individual brain network maps from advanced imaging can guide precise brain stimulation during memory tasks. This could improve understanding of episodic memory and refine brain stimulation therapies for mental health disorders.

Participant Groups

Group I: Intervention and Control group Experimental Treatment 1 Intervention

Each patient will receive electrical and sham stimulation, meaning that each patient will act as their own control.

Brain stimulation is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Transcranial Magnetic Stimulation (TMS) for:

• Treatment-resistant depression (TRD)

Approved in United States as Deep Brain Stimulation (DBS) for:

• Treatment-resistant depression (TRD)
• Obsessive-compulsive disorder (OCD)

Approved in United States as Electroconvulsive Therapy (ECT) for:

• Severe depression
• Bipolar disorder
• Schizophrenia

Approved in European Union as Transcranial Magnetic Stimulation (TMS) for:

• Treatment-resistant depression (TRD)

Approved in European Union as Deep Brain Stimulation (DBS) for:

• Treatment-resistant depression (TRD)
• Obsessive-compulsive disorder (OCD)

Approved in European Union as Electroconvulsive Therapy (ECT) for:

• Severe depression
• Bipolar disorder
• Schizophrenia

Approved in Canada as Transcranial Magnetic Stimulation (TMS) for:

• Treatment-resistant depression (TRD)

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

Findings from Research

In a randomized, double-blind study comparing unilateral-nondominant (UND) and bilateral (BL) electroconvulsive therapy (ECT), both methods showed significant clinical improvement shortly after treatment and 6 months later, with no differences in efficacy between the two groups.

While memory function worsened immediately after ECT for both groups, it returned to baseline levels after 6 months, indicating that memory side effects may be temporary and not significantly different between UND and BL ECT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of unilateral-nondominant vs. bilateral ECT on memory and depression: a preliminary report. Janicak, PG., Sharma, RP., Israni, TH., et al.[2009]

Transcranial direct current stimulation (tDCS) shows a small enhancement in memory for neuropsychological patients, while other methods like transcranial magnetic stimulation (TMS) generally do not improve memory.

Intracranial stimulation techniques, particularly chronic stimulation of the fornix and task-responsive stimulation of the lateral temporal lobe, provide the most evidence for significant memory enhancement, suggesting a promising future for neurostimulation in treating memory deficits associated with epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurostimulation for Memory Enhancement in Epilepsy. Meisenhelter, S., Jobst, BC.[2019]

In a study of 74 patients with major depressive disorder undergoing electroconvulsive therapy (ECT), it was found that measuring time to reorientation early in treatment can predict the risk of retrograde amnesia, highlighting the importance of monitoring cognitive status before treatment.

Older patients and those with lower baseline cognitive abilities are at a higher risk for cognitive side effects from ECT, suggesting that treatment techniques that minimize these effects should be prioritized for these individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predicting Retrograde Autobiographical Memory Changes Following Electroconvulsive Therapy: Relationships between Individual, Treatment, and Early Clinical Factors. Martin, DM., Gálvez, V., Loo, CK.[2018]

Transcutaneous electrical stimulation targeting the greater occipital nerve (ON-tES) has been shown to enhance memory in older adults (ages 55-70) after just one session, with effects lasting up to 28 days.

The mechanism of action is believed to involve activation of the locus coeruleus-noradrenaline (LC-NA) pathway, indicated by changes in α-amylase levels, and the treatment was found to be safe with no significant side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Greater Occipital Nerve Stimulation Boosts Associative Memory in Older Individuals: A Randomized Trial. Luckey, AM., McLeod, SL., Robertson, IH., et al.[2021]

Magnetic seizure therapy (MST) shows promise as an effective treatment for major depressive disorder (MDD), with a notable remission rate of 33.3% in patients receiving high-frequency MST (100 Hz).

MST appears to have minimal impact on cognitive function, with most cognitive measures remaining stable, suggesting it may be a safer alternative to electroconvulsive therapy (ECT) for patients concerned about memory loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic seizure therapy (MST) for major depressive disorder. Daskalakis, ZJ., Dimitrova, J., McClintock, SM., et al.[2021]

In a study of 20 depressed patients (10 receiving ECT and 10 receiving antidepressants), immediate working memory was slightly impaired after the first ECT session, but this effect was not statistically significant.

One month after treatment, both groups showed significant improvements in working memory, with ECT patients demonstrating different cognitive outcomes compared to those on medication, suggesting that ECT's impact on memory is temporary and may correlate with overall recovery from depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Working memory disturbances in patients with major depression after ECT treatment]. Datka, W., Siwek, M., Dudek, D., et al.[2013]

Electroconvulsive therapy (ECT) can lead to immediate memory-related side effects, such as transient amnesia, as demonstrated in a case study of a 39-year-old woman with recurrent major depressive disorder.

The case highlights the need for careful monitoring and management of memory effects following ECT, especially after a symptom-free period, to better understand the treatment's impact on cognitive function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delayed amnesia and disorientation after electroconvulsive treatment. Grinshpoon, A., Mester, R., Spivak, B., et al.[2018]

Electroconvulsive therapy (ECT) is increasingly prescribed for older adults, who are particularly at risk for cognitive side effects such as confusion and memory deficits after treatment.

To enhance the safety and effectiveness of ECT, strategies like unilateral electrode placement and careful adjustment of electrical charge based on individual seizure thresholds are recommended, although challenges remain as these thresholds can increase over the course of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alfentanil anesthetic augmentation lengthens seizure duration in electroconvulsive therapy with older people. D'Cunha, C., Plakiotis, C., O'Connor, DW.[2017]

In a study of 140 patients undergoing bilateral brief-pulse electroconvulsive therapy (ECT), subjective memory complaints increased after the first and third sessions, indicating memory disturbances as a notable side effect of ECT.

Patients with manic episodes reported less severe memory disturbances compared to those with depressive episodes, suggesting that the impact of ECT on memory may vary based on the patient's psychiatric diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early effects of modern electroconvulsive therapy on subjective memory in patients with mania or depression. Bag, S., Canbek, O., Atagun, IM., et al.[2018]

In a study of 154 patients receiving electroconvulsive therapy (ECT) for major depression, reducing the electrical stimulus dose from high to moderate significantly decreased the risk of subjective memory worsening from 44% to 25%.

Despite the lower dosage leading to fewer memory issues, the effectiveness of ECT in alleviating depressive symptoms remained unchanged, indicating that it is possible to minimize cognitive side effects without sacrificing treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Less memory complaints with reduced stimulus dose during electroconvulsive therapy for depression. Kronsell, A., Nordenskjöld, A., Tiger, M.[2020]

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]

In a study involving 42 healthy adults, both anodal transcranial direct current stimulation (tDCS) and theta transcranial alternating current stimulation (tACS) negatively impacted word recall compared to sham stimulation, indicating potential risks of using these methods for memory enhancement.

Participants experienced significantly more memory errors during tACS than during sham stimulation, suggesting that certain types of transcranial electrical stimulation may hinder rather than help memory processes in the left temporal lobe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Theta tACS impairs episodic memory more than tDCS. Murray, NWG., Graham, PL., Sowman, PF., et al.[2023]

Using a closed-loop electrical stimulation system on the lateral temporal cortex can significantly improve memory encoding and recall in humans, addressing previous inconsistencies seen with open-loop stimulation methods.

This targeted approach suggests that stimulating the lateral temporal cortex may be an effective therapeutic strategy for enhancing memory and treating memory dysfunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Closed-loop stimulation of temporal cortex rescues functional networks and improves memory. Ezzyat, Y., Wanda, PA., Levy, DF., et al.[2018]

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

Effects of unilateral-nondominant vs. bilateral ECT on memory and depression: a preliminary report. [2009]

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

Neurostimulation for Memory Enhancement in Epilepsy. [2019]

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

Predicting Retrograde Autobiographical Memory Changes Following Electroconvulsive Therapy: Relationships between Individual, Treatment, and Early Clinical Factors. [2018]

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

Greater Occipital Nerve Stimulation Boosts Associative Memory in Older Individuals: A Randomized Trial. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Magnetic seizure therapy (MST) for major depressive disorder. [2021]

6. Poland pubmed.ncbi.nlm.nih.gov

[Working memory disturbances in patients with major depression after ECT treatment]. [2013]

7. Canada pubmed.ncbi.nlm.nih.gov

Delayed amnesia and disorientation after electroconvulsive treatment. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Alfentanil anesthetic augmentation lengthens seizure duration in electroconvulsive therapy with older people. [2017]

9. India pubmed.ncbi.nlm.nih.gov

Early effects of modern electroconvulsive therapy on subjective memory in patients with mania or depression. [2018]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Less memory complaints with reduced stimulus dose during electroconvulsive therapy for depression. [2020]

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

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

12. England pubmed.ncbi.nlm.nih.gov

Theta tACS impairs episodic memory more than tDCS. [2023]

13. England pubmed.ncbi.nlm.nih.gov

Closed-loop stimulation of temporal cortex rescues functional networks and improves memory. [2018]

14. Switzerland pubmed.ncbi.nlm.nih.gov

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