Cognitive Task Analysis for Epilepsy and Brain Cancer

Overseen By Eliana M Klier

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: The University of Texas Health Science Center, Houston

Disqualifiers: Gross structural abnormalities, impaired cognition, others

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

Compensation: Varies

Number of Visits: Unknown

75 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to compare organization of normal brain function as detected using Functional magnetic resonance imaging (fMRI) in normal subjects as opposed to patients with epilepsy or brain tumors, to ascribe precise anatomic labels (including Brodmann Areas) and functional significance to each region involved in cognitive processes as detected by cortical stimulation mapping (CSM) in patients with implanted subdural electrodes (SDE) or depth (sEEG) electrodes, to describe the locations of these regions in Talairach space, for a population of patients without overt structural abnormalities in these regions, to generate a spatial probability map of locations of cortical regions "essential" for these processes, to compare the loci of "crucial" language, visual, motor and cognitive sites as determined by CSM with the loci determined by a battery of tasks using fMRI for each individual and to use these data in patients undergoing intracranial electro-corticographyto determine the loci of essential, involved and uninvolved brain areas, and use sophisticated mathematical analyses of these intracranial recordings to study information flow between these areas.

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 Language-based tasks for epilepsy and brain cancer?

The GE2REC protocol, which involves language and memory tasks, has been shown to map language and memory networks in patients with temporal lobe epilepsy, suggesting it could be useful in clinical practice for assessing cognitive functions. This protocol has been validated in healthy participants and shows potential for guiding neurosurgical planning and understanding brain reorganization in epilepsy patients. ^{1 2 3 4 5}

Is cognitive task analysis safe for humans?

The research does not provide specific safety data for cognitive task analysis in humans, but it does suggest that cognitive tasks are commonly used in clinical trials for brain tumors and other conditions without reported safety concerns. ^{6 7 8 9 10}

How does the Cognitive Task Analysis treatment for epilepsy and brain cancer differ from other treatments?

The Cognitive Task Analysis treatment is unique because it focuses on understanding and mapping cognitive functions like language and memory in patients with epilepsy and brain cancer. This approach helps in identifying how these functions are reorganized in the brain, which can guide personalized treatment plans and improve outcomes, unlike standard treatments that may not consider individual cognitive reorganization. ^{5 9 11 12 13}

Research Team

Nitin Tandon, MD

Principal Investigator

The University of Texas Health Science Center, Houston

Eligibility Criteria

This trial is for English-speaking patients with medically refractory epilepsy or brain tumors near crucial brain regions. They may have electrodes implanted to locate seizure sites and map critical areas, or they might undergo intra-op mapping, a Wada test, or an awake craniotomy.

Inclusion Criteria

Proficiency in English

I have a brain condition and may need or had surgery involving brain function tests.

I have epilepsy that doesn't respond to medication and will have or had surgery to place electrodes in my brain.

Exclusion Criteria

Patients with claustrophobia who cannot undergo an MRI scan without sedation

Cardiac pacemakers, intracranial aneurysm clips, or other potentially mobile implanted metallic devices

I have significant brain abnormalities that could affect critical areas.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neural Recording and Stimulation

Participants undergo neural recordings and stimulation during language tasks using fMRI and cortical stimulation mapping

4-6 weeks

Follow-up

Participants are monitored for safety and effectiveness after neural recordings and stimulation

4 weeks

Treatment Details

Interventions

• Language-based tasks

Trial Overview The study aims to compare normal brain function using fMRI in healthy subjects versus those with epilepsy or brain tumors. It involves language-based tasks and will use data from intracranial recordings to analyze information flow between brain areas.

Participant Groups

Group I: Neural recordings and stimulation during language tasks Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

The University of Texas Health Science Center, Houston

Lead Sponsor

Trials

974

Recruited

361,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Findings from Research

Using a panel of fMRI tasks targeting different aspects of language processing in 26 epilepsy patients improved the accuracy of determining language dominance compared to single-task paradigms.

The study found excellent agreement between fMRI results and the intracarotid amobarbital test (IAT) in 21 out of 25 patients, demonstrating that a multi-task approach enhances interrater reliability and reduces nondiagnostic findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

fMRI language task panel improves determination of language dominance. Gaillard, WD., Balsamo, L., Xu, B., et al.[2023]

A study involving 487 epilepsy cases highlighted that common methods for assessing cognitive deficits often face issues like poor test selection and sampling problems, which can affect the results.

Even when using advanced multivariate techniques to analyze seizure history variables, the relationships with cognitive functioning remained limited, indicating that many factors influencing cognitive abilities in epilepsy are still not well understood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interictal cognitive aspects of epilepsy. Dodrill, CB.[2007]

Cognitive impairment in frontal lobe epilepsy (FLE) is linked to reduced activation in attentional and executive brain systems, as well as insufficient deactivation of the default mode network, indicating a disorganized response during cognitive tasks.

While there are similarities in cognitive impairment patterns between frontal lobe epilepsy (FLE) and temporal lobe epilepsy (TLE), specific differences exist, such as more pronounced default mode dysfunction in FLE and greater issues with language processing in TLE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Disorganization of language and working memory systems in frontal versus temporal lobe epilepsy. Caciagli, L., Paquola, C., He, X., et al.[2023]

In a study of 136 patients with severe intractable epilepsy, cognitive decline was found to be significant across various functions, with the frequency of generalized tonic-clonic seizures being the strongest predictor of this decline.

Good seizure control, even after long periods of intractability, was associated with better cognitive outcomes, suggesting that managing seizures can positively impact cognitive health over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive decline in severe intractable epilepsy. Thompson, PJ., Duncan, JS.[2022]

The GE2REC protocol effectively maps language and memory networks in patients with left temporal lobe epilepsy (LTLE), demonstrating significant reorganization in brain activity compared to healthy controls, based on a study involving 18 LTLE patients.

This protocol is beneficial for clinical practice as it is quick to perform, assesses cognitive functions at an individual level, and provides insights into the interaction between language and memory, which can aid in neurosurgical planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mapping of Language-and-Memory Networks in Patients With Temporal Lobe Epilepsy by Using the GE2REC Protocol. Banjac, S., Roger, E., Cousin, E., et al.[2022]

In a study involving four women with breast cancer and 18 healthy controls, no significant cognitive or language performance differences were found between the groups during the early stages of tamoxifen treatment, although women with breast cancer generally performed worse than controls.

Some women with breast cancer did show cognitive and language declines during the initial treatment with tamoxifen, indicating that monitoring these changes is important and may lead to the need for future language interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tamoxifen Effects on Cognition and Language in Women with Breast Cancer. Sharma, S., Wright, HH.[2023]

In a large study of 581 breast cancer patients and 364 age-matched controls, patients reported significantly greater cognitive difficulties after chemotherapy, with 45.2% experiencing a clinically significant decline in cognitive function compared to only 10.4% of controls.

The study found that increased baseline anxiety and depression were linked to lower cognitive function scores, while treatment type (chemotherapy regimen, hormone, or radiation therapy) did not significantly affect cognitive outcomes post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive Complaints in Survivors of Breast Cancer After Chemotherapy Compared With Age-Matched Controls: An Analysis From a Nationwide, Multicenter, Prospective Longitudinal Study. Janelsins, MC., Heckler, CE., Peppone, LJ., et al.[2022]

Adjuvant chemotherapy for breast cancer may lead to cognitive deficits that can significantly affect patients' quality of life, with ongoing studies aiming to better quantify these effects and identify susceptible subgroups.

There is a growing interest in understanding the cognitive impact of estrogen deprivation from aromatase inhibitors and exploring supportive measures to mitigate cognitive effects associated with chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of adjuvant therapy for breast cancer on cognitive function: current evidence and directions for research. Rugo, HS., Ahles, T.[2019]

In a study of 68 brain tumor patients, 58.8% showed cognitive impairment on at least one neuropsychological test, highlighting the prevalence of cognitive challenges in this population.

A brief battery of four specific cognitive tests (Figure Copy, Coding, List Recognition, and Story Recall) effectively identified 90% of the impaired patients, suggesting these tasks are crucial for assessing cognitive changes in clinical trials for brain tumor therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing neuropsychological tasks to optimize brief cognitive batteries for brain tumor clinical trials. Lageman, SK., Cerhan, JH., Locke, DE., et al.[2022]

Approximately 31% of cancer patients undergoing chemotherapy reported significant cognitive decline, indicating that cognitive impairment is a common issue during treatment.

Risk factors for cognitive decline included increased fatigue and undergoing two or more cycles of chemotherapy, suggesting that monitoring cognitive function early in treatment could be beneficial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy-associated cognitive impairments in Korean cancer patients: Risk factors and functional outcome. Kim, HJ., Barsevick, AM., Chan, A., et al.[2019]

In a study of 45 patients with epilepsy and a left hemisphere seizure focus, researchers found that language processing regions can reorganize, with some patients showing increased activation in the left temporal area while others recruited right hemisphere regions.

The study identified four sub-groups of patients based on their brain activation patterns, suggesting that inter-hemispheric reorganization is constrained and that some patients exhibit limited intra-hemispheric reorganization, which could have implications for understanding language processing in both healthy and disordered brains.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Limitations to plasticity of language network reorganization in localization related epilepsy. Mbwana, J., Berl, MM., Ritzl, EK., et al.[2022]

A study of 23 patients with drug-resistant epilepsy found that interictal discharges (IEDs) significantly contribute to word-finding difficulties, particularly through impairments in long-term lexicosemantic memory and phonological working memory.

Medial temporal lobe IEDs were especially impactful, suggesting that targeting these discharges with new treatments like pharmacological interventions or neurostimulation could help improve memory and language issues in epilepsy patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interictal epileptiform discharges contribute to word-finding difficulty in epilepsy through multiple cognitive mechanisms. Silva, AB., Leonard, MK., Oganian, Y., et al.[2023]

In a study of 10 glioma patients compared to 60 healthy controls, patients generally performed well on most multimodal processing tasks but struggled specifically with productive picture-naming, receptive verbal judgment, and visual/graphic tasks.

The difficulties experienced by glioma patients did not correlate with the location of their tumors or tumor type, suggesting that individual variability plays a significant role in how gliomas affect cognitive functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Strengths and weaknesses of multimodal processing in a group of adults with gliomas. Plaza, M., Capelle, L., Maigret, G., et al.[2013]

References

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

fMRI language task panel improves determination of language dominance. [2023]

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

Interictal cognitive aspects of epilepsy. [2007]

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

Disorganization of language and working memory systems in frontal versus temporal lobe epilepsy. [2023]

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

Cognitive decline in severe intractable epilepsy. [2022]

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

Mapping of Language-and-Memory Networks in Patients With Temporal Lobe Epilepsy by Using the GE2REC Protocol. [2022]

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

Tamoxifen Effects on Cognition and Language in Women with Breast Cancer. [2023]

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

Cognitive Complaints in Survivors of Breast Cancer After Chemotherapy Compared With Age-Matched Controls: An Analysis From a Nationwide, Multicenter, Prospective Longitudinal Study. [2022]

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

The impact of adjuvant therapy for breast cancer on cognitive function: current evidence and directions for research. [2019]

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

Comparing neuropsychological tasks to optimize brief cognitive batteries for brain tumor clinical trials. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Chemotherapy-associated cognitive impairments in Korean cancer patients: Risk factors and functional outcome. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Limitations to plasticity of language network reorganization in localization related epilepsy. [2022]

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

Interictal epileptiform discharges contribute to word-finding difficulty in epilepsy through multiple cognitive mechanisms. [2023]

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

Strengths and weaknesses of multimodal processing in a group of adults with gliomas. [2013]