Intracranial Stimulation for Memory Enhancement

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Washington University School of Medicine

Disqualifiers: Non-epilepsy, others

No Placebo Group

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial uses small electrical pulses to stimulate a part of the brain called the amygdala. It targets patients with memory problems, such as those from brain injuries or PTSD. The treatment aims to improve memory by enhancing the brain's natural memory circuits, especially when emotions are involved. This method has been explored for various neurological and psychiatric conditions, including memory improvement and PTSD.

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's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Intracranial Stimulation, Deep Brain Stimulation (DBS), Intracranial Electrical Stimulation for memory enhancement?

Research suggests that Deep Brain Stimulation (DBS) can enhance memory for facts and events related to the medial temporal lobe, which is important for memory. Additionally, a study found that hypothalamic DBS improved certain memory functions by engaging the hippocampus, a key brain area for memory. ^{1 2 3 4 5}

Is intracranial stimulation generally safe for humans?

Intracranial stimulation, often called Deep Brain Stimulation (DBS), is generally considered safe, but it can have complications like infection (2-9%), bleeding (1-4%), and seizures (1-3%). These issues are related to the surgery and the equipment used, and while they are not common, they can affect the quality of life. ^{6 7 8 9 10}

How is intracranial stimulation different from other treatments for memory enhancement?

Intracranial stimulation, or deep brain stimulation (DBS), is unique because it involves implanting electrodes directly into the brain to enhance memory, targeting deep brain structures like the hippocampus that are hard to reach with non-invasive methods. This approach is different from other treatments as it offers precise control over brain activity, which is not possible with medications or non-invasive therapies. ^{1 4 11 12 13}

Research Team

Eligibility Criteria

This trial is for English-speaking individuals who can consent to participate, have been diagnosed with epilepsy, and are scheduled for long-term video monitoring of seizures. They must be set to receive intracranial depth electrodes in specific brain regions related to memory.

Inclusion Criteria

Must be able to understand and speak English

Able to provide informed consent

I have been diagnosed with epilepsy.

Exclusion Criteria

I have not been diagnosed with epilepsy.

I am unable to understand and agree to the study's details on my own.

I cannot understand or speak English.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo direct electrical stimulation (DES) of the basolateral complex of the amygdala (BLA) to study memory enhancement

5 years

Multiple visits over the course of the study

Follow-up

Participants are monitored for memory performance and brain activity after treatment

4 weeks

Treatment Details

Interventions

• Intracranial Stimulation (Other)

Trial Overview The study is testing the effects of stimulating the amygdala—a part of the brain—on memory functions. It aims to improve understanding relevant to conditions like traumatic brain injury and post-traumatic stress disorder that affect memory.

Participant Groups

Group I: Brain Stimulation Experimental Treatment 1 Intervention

Neurosurgical epilepsy patients that undergo placement of medial temporal electrode for seizure localizations will be recruited. All participants will view a series of images of emotionally-neutral objects on a computer screen. After each item presentation, they will randomly undergo either active-BLAES or sham-stimulation. Over subsequent days, free recall and recognition memory for these items, relative to new distractor items will be tested. Memory for items presented with and without stimulation will be compared. Brain activity recorded in the medial temporal lobe during item presentations will be used to predict subsequent memory. Such good and bad memory states (biomarkers) will be used to perform closed-loop stimulation when bad memory states are detected in order to enhance subsequent memory.

Intracranial Stimulation is already approved in Canada for the following indications:

Approved in Canada as Deep Brain Stimulation for:

• Parkinson's disease
• Dystonia
• Epilepsy

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

David H. Perlmutter

Washington University School of Medicine

Chief Executive Officer since 2015

MD from Washington University School of Medicine

Paul Scheel

Washington University School of Medicine

Chief Medical Officer since 2022

MD from Washington University School of Medicine

Findings from Research

Deep brain stimulation (DBS) has been shown to effectively treat various neurological and neuropsychiatric disorders, including Parkinson's disease and depression, and may also enhance memory related to the medial temporal lobe, suggesting potential for treating memory disorders like Alzheimer's disease.

The review discusses the mechanisms of how DBS can improve memory and outlines future research directions needed to explore its therapeutic applications for memory-related conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for enhancement of learning and memory. Suthana, N., Fried, I.[2021]

Bilateral hypothalamic deep brain stimulation in a patient with morbid obesity unexpectedly enhanced detailed autobiographical memory recall, suggesting a link between hypothalamic stimulation and memory functions.

The stimulation specifically increased recollection without affecting familiarity-based recognition, indicating that it engages the hippocampus and modulates limbic activity, as confirmed by electroencephalographic source localization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memory enhancement induced by hypothalamic/fornix deep brain stimulation. Hamani, C., McAndrews, MP., Cohn, M., et al.[2022]

Patients considering deep brain stimulation (DBS) for Parkinson's disease often have unrealistic expectations about the outcomes, which can lead to disappointment after surgery.

To help manage these expectations, a simple mnemonic device has been introduced to educate patients and their families about potential outcomes, aiming to improve satisfaction and understanding of the DBS procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A mnemonic for Parkinson disease patients considering DBS: a tool to improve perceived outcome of surgery. Okun, MS., Foote, KD.[2019]

Direct brain stimulation using implanted electrodes can target deep brain structures like the hippocampus, which are crucial for memory, but results can vary widely, with some studies showing improvements and others showing impairments.

In this study, stimulating specific interconnected brain regions during a memory task selectively impaired spatial memory retrieval, indicating that effective modulation of cognitive function may depend on targeting the right network nodes and timing of stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Network-based brain stimulation selectively impairs spatial retrieval. Kim, K., Schedlbauer, A., Rollo, M., et al.[2021]

Deep brain stimulation (DBS) has been explored as a treatment for dementia, with three studies focusing on its effects, including one on fornix DBS for Alzheimer's disease and two on nucleus basalis of Meynert for Alzheimer's and Parkinson's disease dementia.

Current evidence for the effectiveness of DBS in treating dementia is still preliminary and limited, indicating a need for further research to understand its potential clinical benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for the treatment of Alzheimer disease and dementias. Laxton, AW., Lozano, AM.[2022]

A systematic review of 96 studies found that the most common complications from Deep Brain Stimulation (DBS) procedures include infections (5.12% of patients) and lead migration (1.60%), highlighting the importance of monitoring for these issues post-surgery.

Patients with conditions like dystonia and off-label indications such as Tourette's syndrome are at a higher risk for hardware-related complications, suggesting that these patients should receive thorough pre-surgical counseling and close follow-up care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review of hardware-related complications of Deep Brain Stimulation: Do new indications pose an increased risk? Jitkritsadakul, O., Bhidayasiri, R., Kalia, SK., et al.[2022]

Deep brain stimulation (DBS) for Parkinson's disease is generally safe, with a low mortality rate of 0.2% and permanent morbidity at 0.6%, but complications such as intracerebral hemorrhage (ICH) and seizures can occur in a small percentage of cases.

The study found that the type of lead used in DBS can influence complications, with Medtronic's leads associated with higher rates of perielectrode brain edema compared to Boston Scientific's, highlighting the need for further research on hardware design to improve safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications of deep brain stimulation in Parkinson's disease: a single-center experience of 517 consecutive cases. Servello, D., Galbiati, TF., Iess, G., et al.[2023]

Deep Brain Stimulation (DBS) for Parkinson's disease can lead to rare complications, such as an intracranial abscess, as demonstrated in a case involving a 59-year-old male who developed significant inflammation and required multiple surgeries after the procedure.

Despite the complications, the patient's Parkinson's symptoms improved after the abscess was surgically drained, suggesting that the abscess may have inadvertently provided some therapeutic benefit similar to a subthalomotomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracerebral abscess: a rare complication of Deep Brain Stimulation. Brandão, E., Rosas, MJ., Abreu, P., et al.[2013]

Deep brain stimulation (DBS) is an effective treatment for movement disorders, particularly Parkinson's disease, showing improvements in tremor, dyskinesia, and quality of life by 25% to 50% based on various rating scales.

While DBS has proven efficacy for neurological conditions, it has not shown significant benefits for psychiatric disorders, as evidenced by early termination of trials for depression due to lack of efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation in Neurological and Psychiatric Disorders. Coenen, VA., Amtage, F., Volkmann, J., et al.[2018]

References

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

Deep brain stimulation for enhancement of learning and memory. [2021]

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

Memory enhancement induced by hypothalamic/fornix deep brain stimulation. [2022]

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

A mnemonic for Parkinson disease patients considering DBS: a tool to improve perceived outcome of surgery. [2019]

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

Network-based brain stimulation selectively impairs spatial retrieval. [2021]

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

Deep brain stimulation for the treatment of Alzheimer disease and dementias. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Cerebral ischemia related to globus pallidus internus stimulation for cervical dystonia. [2011]

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

Systematic review of hardware-related complications of Deep Brain Stimulation: Do new indications pose an increased risk? [2022]

8. Austria pubmed.ncbi.nlm.nih.gov

Complications of deep brain stimulation in Parkinson's disease: a single-center experience of 517 consecutive cases. [2023]

9. Spain pubmed.ncbi.nlm.nih.gov

Intracerebral abscess: a rare complication of Deep Brain Stimulation. [2013]

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

Surgical and Hardware-Related Adverse Events of Deep Brain Stimulation: A Ten-Year Single-Center Experience. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Intracranial Bleeding in Deep Brain Stimulation Surgery: A Systematic Review and Meta-Analysis. [2023]

12. Germany pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation in Neurological and Psychiatric Disorders. [2018]

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

Deep Brain Stimulation for Chronic Pain. [2022]