TMS Therapy Holds Promise for Autism

Complex analysis of brain activity guides novel therapeutics for autism.

Updated June 17, 2025 | Reviewed by Margaret Foley

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition affecting 1 in 36 children, with boys being diagnosed five times more often than girls. As with attention deficit/hyperactivity disorder (ADHD), girls are frequently underdiagnosed or present differently, which can delay recognition. Autism manifests with challenges in social communication and interaction, alongside restricted and repetitive behaviors, interests, or activities, as outlined in the DSM-5 . Symptoms often emerge early in life, ranging from mild to severe, though milder cases may go unnoticed as individuals “mask” symptoms to blend in socially, delaying diagnosis and treatment.

Neural Rigidity in Autism

Autism affects the integration of diverse neural information and is characterized by rigidity in global brain dynamics. Prior research (e.g., Watanabe et al., 2019) finds that people with autism have difficulty shifting brain states, with related brain networks showing less connectivity due to "functional segregation." This overlaps with ADHD, with the frontoparietal network (FPN) and left prefrontal cortex implicated in neural rigidity and corresponding mental inflexibility.

Historically, autism treatment has been somewhat effective but limited by current therapeutics, including medications, behavioral therapy, and other approaches. Autism frequently occurs with other conditions beyond ADHD, including anxiety disorders, depression , and obsessive-compulsive disorder (OCD). Often, these comorbidities become the focus of adjunctive treatment, with difficulty identifying and directly targeting autism itself.

Brain Stimulation to Increase Neural Flexibility

In a recent Nature Neuroscience publication (Watanabe & Yamasue, 2025), researchers tested a targeted noninvasive brain stimulation approach using transcranial magnetic stimulation (TMS). They timed excitatory stimulation over the right parietal lobule using real-time EEG recordings to increase neural flexibility by providing stimulation precisely when low connectivity would interfere—a technique called "brain state-driven neural stimulation" (BDNS).

The right parietal lobule processes sensory and spatial information and integrates sensory inputs. When damaged, it can lead to neglect—unawareness of surroundings or even one's own body. TMS works by using strong magnetic fields to cause neurons to fire, stimulating the brain's surface, and is approved for treating major depression and OCD, with additional potential applications under development. In this context, TMS essentially normalizes right parietal lobule function to alleviate autism's characteristic rigidity, though the details are much more nuanced, as the work below illustrates.

Researchers conducted six related studies with 50 ASD participants matched with 50 typically developing (TD) controls, though 10 ASD participants dropped out midway. They analyzed brain states via EEG to gauge neural rigidity in real time and to identify key points where neural rigidity interfered with brain state switching, using three tests:

The experiments revealed four brain states related to switching in ASD and TD controls—two major and two minor states—replicating prior work. Brain states correlated with performance on the three tests, with ASD participants showing higher energy barriers for transition and transition frequency relating to symptom burden, as well as directly measured neural rigidity. The researchers confirmed EEG studies accurately reflected resting state MRI activity and developed methods to track transitions during TMS protocols, an important proof-of-concept for clinical use, as it is much easier to administer TMS with EEG than in an MRI scanner.

Improving Brain State Switching

Their BDNS protocol made brain state transitioning easier for ASD participants. Stimulation of the frontoparietal network via the right parietal lobule increased flexible transition between major states via minor states ("indirect transition"). Only when the brain was in major state 1 did BDNS produce these changes during this experiment.

After showing single BDNS session efficacy, they conducted a more clinically significant trial with weekly sessions for 12 weeks, for a total of 12 sessions. By comparison, TMS for depression typically involves 36 sessions 1 , and for OCD, 29 sessions, suggesting that ASD protocols could require more treatment sessions for future clinical applications.

This 12-session protocol reduced neural rigidity as shown by EEG findings and improved all three test measures. Neural rigidity and cognitive flexibility improved earliest (by week 1), perceptual overstability by week 7, and nonverbal information processing by week 9.

The next set of experiments examined the different time frames for change, finding they related to coupling among brain areas, affecting FPN and visual network (VN) connectivity, which was weaker in the ASD group. This allowed refinement of the stimulation protocol for faster responses for visual processing. They examined couplings in the FPN-NV-SN and found correlations with nonverbal information processing improvements when precisely stimulating while the default mode network (DMN 2 ) and SN were active, and the FPN inactive. The DMN has been shown to be altered in ASD, with hyperconnectivity within the network, less connectivity with other networks, differences in gray and white matter structure, a different developmental path over time (Padmanabhan et al., 2017), and, as noted, functional segregation.

Implications for Autism Treatment

This pioneering approach using TMS timed to EEG measurements can be implemented in clinical settings with additional development and advances our understanding of ASD pathophysiology. By identifying specific resting brain network states that differ between people with autism and those without, including key brain "hubs" mediating cognitive, perceptual, and social rigidity, we better understand how core ASD symptoms operate.

While this research doesn't explain why these networks operate differently in ASD or the underlying problem leading to these observations, the findings identify putative causal patterns sustaining ASD symptoms related to inflexible brain state switching and associated performance measures. The BDNS protocol is an important proof of concept, showing measurable changes after only 12 sessions. Whether this translates into robust, clinically significant functional improvements and quality of life benefits remains to be seen in future trials measuring real-world clinical and functional outcomes, likely requiring more stimulation sessions, potentially delivered over a shorter time frame, often referred to as "accelerated" TMS, to maximize neuroplastic change. While part of longer-term work within this research group, this is a small study which primarily focuses on cortical brain areas, rather than deep brain areas—which are also relevant for developing novel treatment approaches.

This work demonstrates sophisticated, potentially personalizable TMS targeting using EEG and brain state analysis, which could identify ASD subtypes based on specific dysconnectivity patterns to develop individualized protocols and perform precision "network surgery," which may also work synergistically with behavioral and psychotherapeutic efforts 3 . Simultaneously, identifying generalizable, easily implemented protocols would improve treatment accessibility.

Current TMS protocols are relatively static, treating specific brain regions with set protocols for depression and OCD as FDA-cleared treatments, and other conditions off-label. Neuronavigation can enable more precise treatment if needed. Research in PTSD identifies individual-specific brain areas likely to yield robust responses when treated with TMS (Siddiqi et al., 2024). As interventional psychiatry evolves, treatments will become both more sophisticated and easier to implement clinically, offering hope for many refractory conditions where psychotherapy , medication , and lifestyle modifications have limited effectiveness.

Accelerated TMS for Major Depression
Default Mode Network as Core of Consciousness
TMS-Assisted Psychotherapy (TAP): Toward a Paradigm Shift

Padmanabhan, A., Lynch, C. J., Schaer, M., & Menon, V. (2017). The default mode network in autism. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 2 (6), 476–486. https://doi.org/10.1016/j.bpsc.2017.04.004

Siddiqi SH, Philip NS, Palm ST, Carreon DM, Arulpragasam AR, Barredo J, Bouchard H, Ferguson MA, Grafman JH, Morey RA, Fox MD. A potential target for noninvasive neuromodulation of PTSD symptoms derived from focal brain lesions in veterans. Nat Neurosci. 2024 Nov;27(11):2231-2239. doi: 10.1038/s41593-024-01772-7. Epub 2024 Sep 24. PMID: 39317797.

Watanabe, T., Lawson, R. P., Walldén, Y. S. E., & Rees, G. (2019). A neuroanatomical substrate linking perceptual stability to cognitive rigidity in autism. Journal of Neuroscience, 39(33), 6540–6554. https://doi.org/10.1523/JNEUROSCI.2831-18.2019

Watanabe, T., Yamasue, H. Noninvasive reduction of neural rigidity alters autistic behaviors in humans. Nat Neurosci 28, 1348–1360 (2025). https://doi.org/10.1038/s41593-025-01961-y

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Grant Hilary Brenner, M.D., a psychiatrist and psychoanalyst, helps adults with mood and anxiety conditions, and works on many levels to help unleash their full capacities and live and love well.

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This article is part of the Bringwise Psychology Journal — daily insights on human behavior, mental health, and personal growth.