Intracranial Stimulation for Memory Enhancement

Recruiting at 2 trial locations

Overseen By Joan Atencio

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Washington University School of Medicine

Disqualifiers: Non-epilepsy, 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: Unknown

Duration: 5 years

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine how stimulating certain brain areas can boost memory. It focuses on the amygdala, a brain region involved in emotions and memory, to understand its role in storing long-term memories. The study may benefit those with memory issues related to traumatic brain injuries or PTSD. Individuals with epilepsy scheduled for a specific type of brain monitoring might be suitable candidates.

As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to new treatments for memory issues.

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 prior data suggests that intracranial stimulation is safe for memory enhancement?

Research has shown that intracranial stimulation, including deep brain stimulation (DBS), is a common technique in brain science. This method places small wires in the brain to alter its activity. Studies have found that DBS is generally safe and is already approved for treating conditions like epilepsy in some areas. While most people tolerate it well, some have experienced headaches, dizziness, or mood changes, though these side effects are uncommon. The use of intracranial stimulation in treating other conditions supports its safety, but participants should discuss possible risks with their doctors. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Intracranial stimulation for memory enhancement is unique because it directly targets the brain's memory centers with electrical impulses. Unlike standard treatments for memory issues, like medications or cognitive therapies, this approach uses a targeted electrical stimulation method to enhance memory function in real-time. Researchers are excited about this technique because it has the potential to boost memory precisely when it's needed, by detecting and intervening during poor memory states, offering a level of personalization and immediacy not possible with current treatments.

What evidence suggests that intracranial stimulation is effective for memory enhancement?

Research suggests that deep brain stimulation (DBS), which participants in this trial may receive as intracranial stimulation, can improve memory for facts and events by targeting the medial temporal lobe, a crucial area for memory. DBS has shown promise in enhancing memory by adjusting activity in brain areas related to memory. Studies have demonstrated that DBS can help with memory disorders and may also improve memory in people with dementia, anxiety, and addiction. Early findings indicate that DBS might serve as a useful tool for improving memory by altering brain circuit functions. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

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

Able to provide informed consent

I have been diagnosed with epilepsy.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Intracranial Stimulation

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.

How Is the Trial Designed?

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 United States, European Union, Canada for the following indications:

Approved in United States as Deep Brain Stimulation for:

• Parkinson's disease
• Dystonia
• Epilepsy
• Obsessive-compulsive disorder (OCD)

Approved in European Union as Deep Brain Stimulation for:

• Parkinson's disease
• Dystonia
• Epilepsy
• Obsessive-compulsive disorder (OCD)
• Chronic pain

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+

Published Research Related to This Trial

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]

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 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]

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]

Deep brain stimulation (DBS) is an effective neurosurgical treatment for various conditions, including movement disorders, epilepsy, Tourette syndrome, and obsessive-compulsive disorders, highlighting its versatility in managing neurological issues.

DBS has a long history dating back to the 1950s and can target multiple brain areas, such as the sensory thalamus and anterior cingulate cortex, to alleviate pain and other symptoms, demonstrating its broad therapeutic potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation for Chronic Pain. Alamri, A., Pereira, EAC.[2022]

Deep brain stimulation (DBS) is generally safe and effective for treating movement disorders, but this case highlights a rare complication: a cerebral infarction following DBS surgery in a patient with cervical dystonia.

The ischemia may have been caused by high-amplitude microstimulation, potentially leading to small-vessel vasospasm, indicating that while DBS is beneficial, careful monitoring of stimulation parameters is crucial to avoid such complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebral ischemia related to globus pallidus internus stimulation for cervical dystonia. Kang, DW., Kim, HY., Chang, JW.[2011]

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]

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]

The incidence of intracranial bleeding during deep brain stimulation (DBS) surgery is relatively low at 2.5% per patient and 1.4% per implanted lead, indicating that while risks exist, they are infrequent.

Older patients (average 5 years older) are at a higher risk for intracranial bleeding during DBS surgery, and there is a nonsignificant trend suggesting that patients with hypertension may also be at increased risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracranial Bleeding in Deep Brain Stimulation Surgery: A Systematic Review and Meta-Analysis. Tiefenbach, J., Favi Bocca, L., Hogue, O., et al.[2023]

In a study of 200 patients undergoing deep brain stimulation (DBS) procedures over a follow-up period of approximately 43 months, 20% experienced surgical or hardware-related adverse events (AEs), but all resolved without permanent effects.

The most common AEs were surgical site infections (9.95%) and wire tethering (2.49%), indicating that while AEs can occur, major complications requiring further surgery are rare, highlighting the overall safety of DBS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical and Hardware-Related Adverse Events of Deep Brain Stimulation: A Ten-Year Single-Center Experience. Bouwens van der Vlis, TAM., van de Veerdonk, MMGH., Ackermans, L., 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) 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6961776/

The Paradoxical Effect of Deep Brain Stimulation on Memory Deep brain stimulation (DBS) is a promising treatment for many memory-related disorders including dementia, anxiety, and addiction.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6397644/

Deep brain stimulation: current challenges and future directions This study did show a statistically significant interaction between patient age and treatment outcomes, whereby patients older than 65 years showed a trend ...

3. withpower.com withpower.com/trial/phase-memory-disorders-9-2021-043d6

Intracranial 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.

4. sciencedirect.com sciencedirect.com/science/article/pii/S1878747923008772

Deep Brain Stimulation for Disorders of Memory and ... DBS has proven to be an effective means of modulating activity in disrupted motor circuitry, and has shown promise as a modulator of other dysfunctional ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa1107212

Memory Enhancement and Deep-Brain Stimulation ... We tested the hypothesis that deep-brain stimulation of the hippocampus or entorhinal cortex alters memory performance.

6. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf/P960009S219b.pdf

summary of safety and effectiveness data (ssed) Medtronic deep brain stimulation for the treatment of epilepsy is currently approved in. Europe and other geographies. Medtronic markets devices ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6288473/

Reporting Guidelines and Issues to Consider for Using ... We propose in this mini-review a set of guidelines to consider when pursuing intracranial stimulation studies of human declarative memory.

8. mayoclinic.org mayoclinic.org/tests-procedures/deep-brain-stimulation/about/pac-20384562

Deep brain stimulation Deep brain stimulation (DBS) involves implanting electrodes within areas of the brain. The electrodes produce electrical impulses that affect brain activity.

9. health.harvard.edu health.harvard.edu/blog/can-electrical-brain-stimulation-boost-attention-memory-and-more-202303032898

Can electrical brain stimulation boost attention, memory ... Stimulating specific regions of the brain with low levels of electricity might improve focus or memory, mood, or even dementia, according to tDCS advocates.