Employing Transcranial Magnetic Stimulation in a Resource Limited Environment to Establish Brain-Behavior Relationships
April 20th, 2022
Transcranial Magnetic Stimulation (TMS) and low-frequency TMS (lfTMS) have been demonstrated to be major contributors to brain literature. Here we highlight the methods for investigating the cortical correlates of self-deception using TMS.
Vital discoveries in neuroscience can be made in resource limited environments. Here, we detail how to employ transcranial magnetic stimulation using valid and reliable methods. Single pulse and low frequency TMS provides causal, not correlational brain behavior relationships.
This allows one to make much stronger conclusions about brain behavior relationships. TMS is used routinely to treat depression. By training minorities and other resource limited students in TMS, we are expanding the pool of trained professionals.
TMS is used in almost every clinical and scientific application. However, it has been able to answer questions on consciousness and self-awareness that have baffled great thinkers for centuries. Anyone starting out with TMS should work on motor systems because you can actually see the effects of TMS immediately with a hand or leg movement.
The other possibility is working on the visual system and asking participants to report the phosphenes that they see. Both systems give feedback immediately to the learning student. Begin by marking swim caps along the nasion or inion line and the midpoint taken using a magic marker.
Measure pre-auricular points and take those midpoints, as well. From here, plot 10/20 coordinates. Using the right hemisphere pre-auricular line, go 33%down in the ventral direction and begin searching for the optimal location for the Abductor Pollicis Brevis or APB using the TMS coil.
Discharge the TMS machine using the coil trigger, the foot switch, and disengaging the safety. Orient the TMS coil at 45 degrees for all searches in TMS deliveries, then start the stimulation output at 20%total machine output by using the dial on the front of the machine. Raise in 2%increments using the dial until a movement is noted.
Here, as the stimulation is increased in terms of intensity, move the location also. There is a careful interplay between coil movement and stimulation intensity. Mark the coil tip site on the cap to allow an accurate placement and trace the entire anterior portion of the coil onto the swim cap using a magic marker.
Once the optimal location is found, that is the site that provided the maximum APB response, determined the MT.For the visual inspection method, start at 20%of machine intensity and workup. The dial should be raised and lowered in response to increased or decreased finger movements. Use approximately 20 pulses to find what stimulation level results in 5 out of 10 APB responses.
Once 5 out of 10 responses have been obtained, record the individual's MT by noting what the machine is displaying as the intensity. For the MEP method, place disposable electrodes on the APB and the tendon of the thumb and a ground. Define a positive MEP response as an MEP with greater than or equal to 50 microvolts peak-to-peak amplitude.
Similar to visual inspection, stimulate until 5 out of 10 positive MEPs are observed. The MEPs should be greater than 50 microvolts. If 50%of the MEPs are above, it can be said that MT has been identified.
Set the TMS machine to the appropriate stimulation level. 90%of the motor threshold is an ideal balance between effective, active TMS and safety. Randomly select the order of all sites.
Place the coil over the active site and start a presentation software. Stimulation should proceed automatically and in sync with stimuli. Collect all behavioral data using the presentation software.
Give two practice trials and introduce the analog scale to the participants. All participants easily adjust to the equipment. The instructions are given orally and the participants are told to rate how well they know the word.
If the word is familiar to them, it should be given a high rating. If they sort of know the word, they are to give a medium rating. If the word is not that familiar to them, they will assign a low rating.
A total of 144 words should be used. Participants have unlimited time to respond. Following the response on the analog scale, the next word is presented.
Self-deception can be modulated using TMS. Participants were given social pressure to know words in one condition and no social pressure in another condition. The social pressure was a series of verbal prompts that indicated that every person knew these words and they were easy or that the words were difficult and most people did not know them.
Means and the standard errors are presented here. Because social cognition is a medial prefrontal cortex, or MPFC function, it was assumed that TMS delivered in an inhibitory manner would decrease overclaiming. This was found to be the case.
Measuring out the 10/20 system and correctly gauging motor threshold is important for safety and reliable results. Instead of the 10/20 system, narrow navigation can be used. TMS was a first major technique that determined causal relationships between brain and behavior.
Additionally, it is now a major therapeutic technique using the treatment of depression.
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Overview
This study explores the use of Transcranial Magnetic Stimulation (TMS) and low-frequency TMS (lfTMS) to investigate self-deception mechanisms in the brain. The research focuses on employing TMS to establish causal relationships between brain activity and behavior, particularly in understanding consciousness and self-awareness.
Key Study Components
Area of Science
- Neuroscience
- Transcranial Magnetic Stimulation
- Behavioral Neuroscience
Background
- TMS is commonly used as a therapeutic tool for depression.
- This method provides insights into brain behavior relationships.
- The study aims to train minorities in TMS for broader accessibility.
- Self-deception links to social cognition processes in the medial prefrontal cortex.
Purpose of Study
- To assess the effects of TMS on social cognition and self-deception.
- To improve accessibility to TMS training in diverse populations.
- To explore the immediate effects of TMS on motor and visual systems.
Methods Used
- TMS was used to target specific brain regions related to motor and visual responses.
- Participants underwent procedures following the 10/20 electrode placement system.
- Motor threshold (MT) was determined through pulse intensity adjustments.
- Behavioral data were collected using an analog scale rating system during word retrieval tasks.
Main Results
- TMS effectively modulated participants' responses to social pressure regarding word knowledge.
- Behavioral data indicated changes in self-deception under varying social conditions.
- Inhibitory TMS influenced overclaiming responses linked to the medial prefrontal cortex.
- Identifying MT is crucial for safe and effective TMS application.
Conclusions
- The study demonstrates TMS's role in elucidating self-deceptive processes.
- Applying TMS in this manner allows researchers to investigate complex cognitive functions.
- The findings have implications for understanding social cognition and brain behavior relationships.
Frequently Asked Questions
Executive Industry Relevance
Establishing causal brain-behavior relationships in resource-limited settings expands access to mechanistic neuroscience tools, supporting early-stage target validation and hypothesis testing. This approach enables predictive de-risking of neuropsychiatric targets by linking neural modulation to measurable behavioral outputs, such as self-deception and social cognition. It provides a scalable, low-cost pathway for training diverse research teams in neuromodulation techniques relevant to CNS drug discovery.
Strategic Applications in Biopharma R&D
Early Discovery & Target Validation
- Scientific Value: Enables interrogation of therapeutic hypotheses by establishing causal links between prefrontal cortex modulation and changes in self-deceptive responding.
- Operational Value: Supports biological de-risking of neuropsychiatric targets using non-invasive stimulation with immediate behavioral readouts.
- Predictive Value: Provides quantitative behavioral data (e.g., analog scale ratings) to assess target engagement and mechanism of action in social cognition pathways.
Screening & Assay Development
- Scientific Value: Generates reliable, reproducible motor-evoked potential (MEP) and behavioral outputs suitable for assay standardization in neuromodulation screening.
- Operational Value: Uses defined thresholds (e.g., 5 out of 10 positive MEPs) to establish consistent stimulation parameters across sessions and users.
- Assay Readiness: Enables preparation of validated biological systems (motor cortex) for downstream evaluation of neuromodulatory compounds.
Translational & Preclinical Research
- Translational Continuity: Links discovery-phase TMS findings to preclinical models by targeting conserved neural circuits involved in social cognition and self-awareness.
- Mechanistic De-risking: Clarifies prefrontal cortex contributions to behavioral phenotypes, reducing ambiguity in target mechanism prior to lead identification.
- Predictive Confidence: Supports go/no-go decisions by demonstrating how target modulation translates to measurable changes in complex cognitive behaviors.
Pipeline & Workflow Integration
The method fits within the discovery continuum from target hypothesis testing through lead identification, particularly for CNS targets modulating social cognition and self-awareness networks.
- Discovery Biology: Supports hypothesis testing by enabling causal interrogation of medial prefrontal cortex function in self-deception pathways.
- Screening: Delivers assay-ready, quantitative outputs (MEP amplitude, behavioral ratings) that allow comparison of stimulation conditions and compound effects.
- Analytics: Provides measurable dependent variables (motor threshold, MEP response rates, analog scale scores) for statistical comparison across experimental groups.
- Translational Research: Connects early target validation to preclinical continuity by focusing on evolutionarily conserved circuits involved in social behavior.
- Enterprise Reuse: Establishes a portable, low-resource neuromodulation platform applicable across multiple CNS discovery programs.
Operational & Enterprise Impact
- Scientific Value: Predictive confidence in target mechanism through causal brain-behavior mapping and reduction of correlational ambiguity.
- Operational Value: Standardized procedures for coil placement, threshold determination, and stimulation delivery ensure reproducibility across sites and users.
- Strategic Value: Informs capital-efficient go/no-go decisions by validating target engagement in early discovery using accessible neuromodulation tools.
- Portfolio Impact: Enables risk-adjusted prioritization of CNS targets based on demonstrated modulation of disease-relevant behavioral phenotypes.
Implementation Considerations
- Requires expertise in neurophysiology, TMS safety protocols, and 10/20 electrode placement system for accurate targeting.
- Depends on TMS stimulator, coil, disposable electrodes for MEP recording, and analog scale or presentation software for behavioral data collection.
- Necessitates cross-team standardization of motor threshold testing procedures and stimulation intensity reporting to ensure data comparability.
- Adaptation across model systems requires validation of equivalent cortical targets and behavioral readouts (e.g., motor or visual evoked responses).
- Practical limitations include dependence on individual anatomical variability and the need for careful coil-intensity interplay to avoid false negatives in threshold determination.
