Key Takeaways
- The study, published in Nature Neuroscience by Pagani et al. (2026), identified two brain-connectivity subtypes of autism using cross-species fMRI (https://doi.org/10.1038/s41593-026-02287-z).
- The “hypoconnectivity” subtype is linked to synaptic pathways; the “hyperconnectivity” subtype is linked to immune-related pathways.
- The subtypes were identified in approximately 25% of the 940 autistic individuals studied, most participants did not fit either pattern.
- Autism remains a behaviorally defined diagnosis. No brain imaging test is used to diagnose autism in clinical practice today.
- Clinical care should continue to prioritize individualized, whole-child assessment across disciplines.
A new Nature Neuroscience study by Pagani et al. (2026) is drawing attention because it addresses one of the central questions in autism care: why do individuals with the same diagnosis often present so differently?
Clinicians see this variability every day. One child with autism may have significant language delays and intellectual disability. Another may be verbally fluent but struggle with social communication, flexibility, anxiety, or sensory regulation. The study does not erase that complexity. Instead, it offers evidence that, for some individuals, autism-related differences in brain connectivity may cluster into biologically meaningful subtypes.
The findings are scientifically important, but they should be interpreted carefully. They do not change how autism is diagnosed today, and they do not suggest that brain imaging should guide treatment decisions in current clinical practice.
What the Pagani Study Found: Two Autism Connectivity Subtypes
A team led by the Istituto Italiano di Tecnologia (IIT) in Rovereto, Italy, and the Child Mind Institute in New York compared brain connectivity patterns from autism-related mouse models with brain imaging data from nearly 2,000 people, including 940 individuals with autism. Their goal was to see whether patterns found in the animal models also appeared in people with autism.
The study identified two broad patterns of altered brain connectivity in autism: hypoconnectivity and hyperconnectivity. One group showed primarily reduced connectivity between brain regions, or hypoconnectivity. This pattern was associated with synaptic pathways, including processes involved in synaptic signaling and plasticity. A second group showed primarily increased connectivity, or hyperconnectivity. This pattern was linked most clearly to immune-related pathways, and in the rodent analyses, to transcription-related pathways as well.
The researchers then looked for similar patterns in the human brain imaging data. They found two broad patterns: one involving lower-than-typical connectivity between some brain regions, and another involving higher-than-typical connectivity. These patterns were associated with different behavioral profiles, but they were found in only about 25% of the 940 individuals with autism in the study. For that reason, the results should not be interpreted as showing that autism has two simple types.
What the Researchers Did Not Find
The study does not show that autism can now be divided into two clinical categories. It does not mean that every autistic person fits neatly into a “hypoconnected” or “hyperconnected” group. It also does not establish a biomarker that can diagnose autism, predict prognosis, or guide treatment selection.
That distinction matters. Autism remains a behaviorally defined diagnosis. Current diagnostic practice relies on developmental history, caregiver report, clinical observation, and standardized diagnostic criteria—not biological tests. The CDC notes that there is no medical test, such as a blood test, used to diagnose autism; clinicians look at development and behavior.
Why the Findings Matter
The study matters because it strengthens a long-standing clinical reality: autism is not a single developmental pathway with one underlying cause. It is a highly heterogeneous condition that likely reflects many different combinations of genetic, neurodevelopmental, environmental, and biological influences.
For research, biologically informed subtyping could eventually help the field ask better questions: Which children are being studied? Which outcomes matter for which profiles? Who benefits from which supports, under what conditions, and why?
For clinical care today, the message is more practical. A diagnosis alone is not enough to guide intervention. High-quality care still depends on understanding the whole child: communication, cognition, adaptive skills, sensory and motor needs, social development, emotional regulation, co-occurring conditions, family priorities, and the environments in which the child needs to function.
Clinical Implications by Discipline
For Pediatricians
The study reinforces the importance of developmental surveillance, early screening, and timely referral when concerns arise. It does not change screening recommendations, but it supports a humble, individualized approach when discussing autism with families.
For Psychologists and Developmental Specialists
The findings underscore the need for comprehensive assessment. Cognitive, adaptive, language, behavioral, social communication, and mental health profiles all matter.
For Speech-Language Pathologists
It highlights the wide variability in communication profiles, from foundational communication to pragmatic language, flexibility, and self-advocacy.
For Occupational Therapists
It reinforces the importance of individualized supports for sensory, motor, adaptive, and regulation needs in real-life contexts.
For Psychiatrists
It highlights the need to consider developmental complexity and co-occurring conditions such as anxiety, ADHD, sleep problems, irritability, and mood symptoms.
The Practical Takeaway
The most clinically relevant message is not that autism now has two subtypes. It is that autism’s diversity is real, meaningful, and likely biologically complex.
For now, clinicians should not change diagnostic practice or rush toward brain-based treatment matching. The best response is to continue doing what strong interdisciplinary teams already do: assess the whole child, understand the family’s priorities, coordinate across disciplines, and individualize supports around meaningful goals.
This research aligns closely with how Kyo approaches ABA. Because Kyo therapists work alongside families in the home and community, they observe the routines, challenges, strengths, and opportunities that aren’t visible in a clinic setting. Those real-world insights shape highly individualized treatment plans that reflect how each child actually lives and learns, helping build meaningful skills that generalize to everyday life. See how Kyo’s in-home model supports meaningful skill development.
As autism research becomes more biologically precise, clinical care should remain individualized, practical, and connected to real life.
Reference
Pagani, M., et al. (2026). Autism subtypes identified using cross-species functional connectivity analyses. Nature Neuroscience. https://doi.org/10.1038/s41593-026-02287-z
