Understanding why transcranial magnetic stimulation produces different effects from one person to another remains one of the biggest challenges in interventional psychiatry. Recent TMS working memory research offers new insight into this question by combining single pulse TMS with functional near-infrared spectroscopy (fNIRS), an imaging technology that measures changes in brain blood flow while participants complete cognitive tasks. This emerging approach highlights the growing role of advances in interventional psychiatry in identifying objective markers of how the brain responds to stimulation.
Although TMS has become an established treatment for conditions including major depressive disorder, researchers continue to investigate why some individuals experience significant clinical improvement while others show only modest benefit. Better methods for measuring target engagement and individual brain responses could help refine treatment strategies and improve outcomes.
Why Measuring Brain Activity During TMS Matters
Traditional TMS studies often focus on behavioral outcomes alone, such as changes in symptoms or cognitive performance. While these measures remain important, they do not fully explain what is happening inside the brain during stimulation.
The new study addressed this limitation by pairing online single pulse TMS with whole head fNIRS while healthy adults performed working memory tasks. Researchers targeted the left dorsolateral prefrontal cortex, a region involved in executive function and commonly stimulated during depression treatment. Participants completed both lower demand and higher demand memory tasks with and without TMS, allowing investigators to compare brain activation patterns under different conditions.
How TMS Working Memory Research Used Simultaneous Brain Imaging
The investigators enrolled 20 healthy adults and recorded brain activity using concurrent TMS and fNIRS. Participants also completed separate sessions during which single TMS pulses were delivered while resting, allowing researchers to compare brain responses both during active cognition and at rest.
Unlike MRI based approaches, fNIRS offers a relatively portable and practical method for measuring hemodynamic responses during TMS. Because the technologies do not interfere with one another, researchers were able to observe changes in cortical activity throughout stimulation with fewer logistical challenges than simultaneous MRI studies.
This design allowed the team to examine not only whether TMS changed cognitive performance, but also whether distinct patterns of brain activation were associated with those changes.
Individual Brain Responses Tell A More Complete Story
One of the study’s most interesting observations was that the overall group showed little change in working memory accuracy or reaction time after TMS. At first glance, this might suggest that stimulation had minimal impact.
However, a deeper analysis revealed substantial differences between individuals. Some participants performed better during stimulation, some performed worse, and others showed little measurable change. These behavioral differences corresponded with distinct patterns of hemodynamic activity across several brain regions, including the dorsolateral prefrontal cortex, precuneus, superior frontal cortex, superior medial gyrus, angular gyrus, and superior parietal lobule.
Rather than producing a single uniform response, TMS appeared to interact differently with existing brain networks in different individuals.
Brain Networks May Predict Future Response
The researchers also examined brain activity recorded during resting single pulse TMS sessions without any cognitive task.
Interestingly, resting hemodynamic responses were associated with later performance during the working memory task. Participants whose cognitive performance improved during online TMS demonstrated different activation patterns than those whose performance declined, even though these measurements were collected during separate sessions.
This finding raises the possibility that baseline physiological responses to TMS could eventually help predict how an individual may respond during more complex cognitive or therapeutic stimulation protocols. The authors emphasize that additional research is needed before these observations can be translated into clinical decision making.
What Makes This Study Different
Many previous investigations have relied on functional MRI to study TMS related brain activity. While highly informative, MRI based methods can be expensive, technically demanding, and less practical for widespread clinical implementation.
By demonstrating the feasibility of combining online TMS with whole head fNIRS, this work introduces a potentially more accessible framework for studying target engagement. The approach also highlights that evaluating individual response patterns may provide more useful information than relying solely on average group results.
Rather than treating variability as statistical noise, the investigators viewed it as an opportunity to better understand the biological mechanisms that influence responsiveness to brain stimulation.
What These Findings Could Mean For Interventional Psychiatry
Although this research was conducted in healthy volunteers and remains a preprint that has not yet undergone peer review, it contributes to a growing effort to personalize neuromodulation therapies.
If future studies confirm these findings in patients with depression and other neuropsychiatric disorders, clinicians may eventually be able to use physiological biomarkers to better identify optimal stimulation targets, predict treatment response, and monitor target engagement throughout therapy.
As precision medicine continues to expand within psychiatry, combining TMS with practical brain imaging technologies such as fNIRS may help move the field closer to individualized neuromodulation strategies that are guided by each patient’s unique brain activity rather than a one size fits all approach.
Citations
- Edwards S, Smith Q, Farrand J, et al. The Effect of Single Pulse TMS on Working Memory Performance: An Online TMS And fNIRS Study. medRxiv. 2026. https://www.medrxiv.org/content/10.64898/2026.07.22.26358678v1
- Sack AT, Paneva J, Küthe T, et al. Target Engagement and Brain State Dependence of Transcranial Magnetic Stimulation: Implications for Clinical Practice. Biological Psychiatry. 2024;95(6):536-544.https://doi.org/10.1016/j.biopsych.2023.09.011
Explore more at https://www.interventionalpsychiatry.org/
