Cognitive difficulties are among the most disabling aspects of schizophrenia, and they are often particularly severe in adolescent-onset schizophrenia. Yet standard neuroimaging analyses usually focus either on regional activation — which areas are more or less active — or on functional connectivity — which areas fluctuate together. In this study, in collaboration with Konasale Prasad and other collaborators in Pittsburgh, PA, we take a complementary approach: they ask whether cognition is related to the “energy” of whole-brain functional states.
Here, energy does not mean metabolic energy. It comes from statistical physics and maximum entropy modeling. In this framework, a brain state is a pattern of activity across multiple regions, and its energy reflects how likely or unlikely that pattern is to occur. Low-energy states are more easily accessible; high-energy states are less probable and may require stronger coordination or control to reach.
Using 7T task-fMRI data from individuals with adolescent-onset schizophrenia and healthy participants, the authors modeled brain activity patterns with pairwise maximum entropy models. This approach integrates both regional activity and pairwise interactions between regions into a single energy-based description of functional brain states. Rather than treating brain regions separately, it captures how distributed patterns of activity are organized across the brain.
The main finding is that the energy of functional brain states correlates with cognition. In other words, cognitive performance is not only related to whether a particular region is activated, or whether two regions are connected, but also to the accessibility of broader activity patterns in the brain’s functional landscape. This suggests that cognitive impairment may reflect a change in the organization of the brain’s dynamical repertoire: some useful states may become harder to reach, less stable, or less efficiently recruited.
This perspective is especially relevant for adolescent-onset schizophrenia, a rare and under-studied form of the disorder associated with marked cognitive deficits and poor functional outcomes. By reducing high-dimensional fMRI activity into interpretable energy landscapes, the study provides a way to link complex neural dynamics with clinical and cognitive measures.
A useful way to summarize the contribution is: cognition may depend not only on which brain regions are active, but on how easily the brain can enter the right functional states. In schizophrenia, part of the problem may be that the landscape of possible brain states is altered — making some cognitive configurations harder to access or maintain.
This work highlights the value of statistical-physics-inspired tools for psychiatry. By describing brain activity in terms of functional states, probabilities, and energy landscapes, it moves beyond static markers of dysfunction and toward a dynamical view of cognitive impairment. Such approaches may ultimately help identify which aspects of brain-state organization are most relevant for symptoms, cognition, and treatment response.
To know more:
- Theis, N., Bahuguna, J., Rubin, J. E., Banerjee, S. S., Muldoon, B., & Prasad, K. M. (2025). Energy of functional brain states correlates with cognition in adolescent-onset schizophrenia and healthy persons. Human Brain Mapping, 46, e70129. doi:10.1002/hbm.70129.