Behavioral Testing for Neurosciences

Recruiting at 1 trial location

Overseen By Yoav Kfir, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Must not be taking: Stimulants, Antipsychotics

Disqualifiers: Children, Pregnancy, Anxiety, others

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

Compensation: Varies

Number of Visits: 2

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This proposal aims to study the role that the dorsal prefrontal cortex plays in human social cognition.

Do I have to stop taking my current medications for the trial?

Yes, you will need to stop taking CNS-active medications (drugs that affect the central nervous system) like stimulants and antipsychotics, as they may alter the study results.

What data supports the effectiveness of the treatment Behavioral testing during neuronal recordings?

Behavioral testing has been shown to be reliable and sensitive in assessing neurotoxicity, which suggests it can effectively evaluate changes in brain function. Additionally, intra-operative behavioral tasks during deep brain stimulation surgery have provided valuable insights into brain activity, indicating that similar methods could be useful in understanding neuronal activity during behavioral testing. ^{1 2 3 4 5}

Is behavioral testing for neurosciences generally safe for humans?

Behavioral testing in neurosciences is considered safe as it is used to assess the effects of substances on the nervous system, with a focus on ensuring high-quality data and minimizing risks. These tests are designed to detect any adverse effects on the nervous system, and safety assessments are carefully planned and conducted to ensure participant safety. ^{3 6 7 8 9}

How does this treatment differ from other treatments for this condition?

This treatment is unique because it uses advanced methods to relate behavior to neuronal activity without relying on predefined behavioral events, allowing for more accurate interpretations of brain function. It also integrates high-throughput data collection and advanced imaging techniques, which are not typically used in standard treatments. ^{1 3 10 11 12}

Research Team

Ziv Williams, M.D., Ph.D.

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

This trial is for adults over 18 who can consent to participate. It's not suitable for those under 18, pregnant individuals, people with significant other illnesses, or those on medications that affect the brain like stimulants and antipsychotics. Also excluded are those with claustrophobia or anxiety that could interfere with testing.

Inclusion Criteria

Patients able to give informed consent

I am 18 years old or older.

Exclusion Criteria

Poor tolerance of testing by the patient

Pregnancy

Increased abnormal cortical excitability

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-surgical Assessment

Participants undergo pre-surgical assessment and preparation for DBS electrode placement

1 week

1 visit (in-person)

Neuronal Recording and Task Performance

Neuronal recordings are obtained from the prefrontal cortex as participants perform a brief behavioral task

15 minutes

1 visit (in-person)

DBS Electrode Placement

Standard clinical procedure for DBS electrode placement proceeds as planned

1 day

Follow-up

Participants are monitored for safety and effectiveness after DBS electrode placement

4 weeks

Treatment Details

Interventions

• Behavioral testing during neuronal recordings

Trial Overview The study focuses on how a part of the brain called the dorsal prefrontal cortex is involved in social thinking and behavior. Participants will undergo behavioral tests while their brain activity is recorded.

Participant Groups

Group I: Neurosurgical subjects Experimental Treatment 1 Intervention

Subjects undergoing intracranial neurosurgical procedures

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Brown University

Collaborator

Trials

480

Recruited

724,000+

Findings from Research

A new analytical method for studying single neuronal recordings in monkeys allows researchers to relate neuronal activity to behavior without relying on predefined behavioral events, reducing the risk of drawing false conclusions.

This method assesses the variability of the timing between neuronal activity changes and behavioral events on a trial-by-trial basis, enabling more accurate physiological interpretations of how neuronal activity influences behavior.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new method for relating behavior to neuronal activity in performing monkeys. Montgomery, EB.[2019]

A new, low-cost auditory decision-making task was developed for use during neurosurgery, allowing for real-time behavioral feedback from patients while monitoring their brain activity.

The system was successfully tested with both healthy individuals and Parkinson's disease patients, demonstrating that it can accurately capture behavioral responses and correlate them with neural activity during deep brain stimulation surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modular auditory decision-making behavioral task designed for intraoperative use in humans. Tekriwal, A., Felsen, G., Thompson, JA.[2021]

Recent advancements in behavioral testing methods for assessing neurotoxicity have shown high sensitivity and reliability, as demonstrated by the National Center for Toxicological Research (NCTR) Collaborative Behavioral Teratology Study involving multiple laboratories.

Behavioral assessments are crucial for evaluating overall central nervous system (CNS) function, as they correlate well with neurotoxic compounds that have identifiable neurobiological signatures, providing a broader understanding of neurotoxicity compared to more specific tests.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reliability, sensitivity and validity of behavioral indices of neurotoxicity. Vorhees, CV.[2019]

Deep brain stimulation (DBS) is an effective surgical treatment for patients with Parkinson's disease, essential tremor, and dystonia, showing significant improvements in quality of life and backed by well-powered randomized controlled trials.

DBS not only helps patients but also allows researchers to study brain activity in real-time during surgery, providing insights into neuronal behavior and cognitive functions, which can enhance the precision of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intra-operative behavioral tasks in awake humans undergoing deep brain stimulation surgery. Gale, JT., Martinez-Rubio, C., Sheth, SA., et al.[2021]

Recent advancements in neurology emphasize the importance of quantitative tests alongside traditional qualitative assessments to measure various neurological functions, such as strength, coordination, and mental state.

The report highlights the need for validated quantitative tests in clinical trials, suggesting that these tests can provide objective evaluations of sensory and motor functions, which are crucial for assessing treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative methods in assessment of neurologic function. Potvin, AR., Tourtellotte, WW., Syndulko, K., et al.[2017]

The MotorMonitor v. 4.01 system was validated for accuracy and precision in measuring motor activity in rats, showing reliable results for most parameters except fine movements and x/y ambulations.

Biologic validation demonstrated that the system could effectively detect changes in motor activity in response to pharmacological agents, with diazepam reducing activity and D-amphetamine increasing it, confirming the system's specificity and sensitivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Validation of a motor activity system by a robotically controlled vehicle and using standard reference compounds. Patterson, JP., Markgraf, CG., Cirino, M., et al.[2019]

The paper highlights the challenges in interpreting behavioral effects in neurotoxic hazard assessments, emphasizing the need for clear identification of effects and their relationship to chemical exposure.

It suggests improvements to current testing strategies, including better study designs and specific testing requirements for different chemical classes, to enhance the validity and interpretability of behavioral data in neurotoxicity evaluations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complexity of neurotoxicological assessment. Sette, WF.[2019]

A workshop involving various sectors of the neuroscience community emphasized the importance of high-quality experimental design and methodology in behavioral testing to reliably assess neurotoxicity and safety of chemicals.

Consensus was reached on key factors affecting data quality in behavioral assessments, including test method selection, control of confounding variables, and appropriate statistical analyses, which are crucial for effective safety evaluations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Behavioral test methods workshop. Slikker, W., Acuff, K., Boyes, WK., et al.[2018]

Regulatory guidelines recommend specialized safety pharmacology assessments in animals to evaluate drug effects on the central nervous system (CNS) before human trials, but the effectiveness of these tests in detecting subtle neurotoxic effects is under scrutiny.

A survey of experts revealed that while certain endpoints in neurofunctional assessments (like convulsions and stereotypic behaviors) are deemed highly impactful, many others are considered less relevant, suggesting a need for a revised approach to improve the translational value of these assessments and potentially reduce animal use without compromising safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurofunctional test batteries in safety pharmacology - Current and emerging considerations for the drug development process. Jackson, SJ., Authier, S., Brohmann, H., et al.[2020]

The new mouse behavioral learning platform allows for voluntary head fixation and automated data collection, making it easier to integrate complex behavioral tasks with physiological measurements.

This platform has been experimentally validated through training mice in visual discrimination and auditory detection tasks, and it can be coupled with advanced imaging techniques like two-photon microscopy to study cortical networks at a single-cell level.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An automated platform for high-throughput mouse behavior and physiology with voluntary head-fixation. Aoki, R., Tsubota, T., Goya, Y., et al.[2018]

Optical recording of cortical activity in awake monkeys can successfully capture visual information from the primary visual cortex (V1) even when the monkeys are engaged in body movements, indicating the method's robustness in studying cognitive functions.

The study demonstrated that orientation maps from V1 could be consistently obtained despite the monkey's active behavior, suggesting that optical recording can be effectively applied to various behavioral tasks in cognitive research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intrinsic signal recording from a monkey whose behavior was maintained by a schedule of reinforcement. Wakita, M.[2019]

By implementing specific measures to manage temporal errors, researchers can achieve high temporal accuracy (1 ms) in psychophysical tasks, which is crucial for aligning behavioral and neural events.

This advancement addresses the concerns about using high-level programming environments for behavioral neuroscience, potentially speeding up the development and sharing of experimental paradigms across different labs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Achieving behavioral control with millisecond resolution in a high-level programming environment. Asaad, WF., Eskandar, EN.[2021]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

A new method for relating behavior to neuronal activity in performing monkeys. [2019]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Modular auditory decision-making behavioral task designed for intraoperative use in humans. [2021]

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

Reliability, sensitivity and validity of behavioral indices of neurotoxicity. [2019]

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

Intra-operative behavioral tasks in awake humans undergoing deep brain stimulation surgery. [2021]

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

Quantitative methods in assessment of neurologic function. [2017]

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

Validation of a motor activity system by a robotically controlled vehicle and using standard reference compounds. [2019]

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

Complexity of neurotoxicological assessment. [2019]

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

Behavioral test methods workshop. [2018]

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

Neurofunctional test batteries in safety pharmacology - Current and emerging considerations for the drug development process. [2020]

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

An automated platform for high-throughput mouse behavior and physiology with voluntary head-fixation. [2018]

11. Ireland pubmed.ncbi.nlm.nih.gov

Intrinsic signal recording from a monkey whose behavior was maintained by a schedule of reinforcement. [2019]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Achieving behavioral control with millisecond resolution in a high-level programming environment. [2021]