In the field of neuropharmacology, the search for the next medical breakthrough often feels like a high-stakes gamble. For decades, the pharmaceutical industry has struggled with a central nervous system (CNS) drug success rate of roughly 5%. At East Tennessee State University’s Gatton College of Pharmacy, Dr. Siva Digavalli is working to improve those odds by introducing a sophisticated and increasingly powerful tool into the drug development pipeline: electroencephalography (EEG)–based neural synchrony.
Traditional drug discovery has long relied on behavioral data from preclinical models, observing how a subject responds to a given compound. While these approaches can be informative, they are inherently subjective and often fail to accurately reflect the clinical features of human disease. To address these limitations, Dr. Digavalli’s lab is advancing the field by focusing on gamma oscillations, synchronized, high-frequency brain waves that play a critical role in attention, sensory processing, and cognitive function. These core mental processes are profoundly disrupted in neuropsychiatric disorders.
By studying gamma wave synchrony, Dr. Digavalli provides an objective, real-time view of how a drug interacts with brain circuitry. Tracking these oscillations allows researchers to directly confirm target engagement, demonstrating that a compound is not only reaching the intended brain region but also modulating a key circuit-level physiological activity. This type of evidence is foundational for sustaining confidence, investment, and momentum in high-risk neuropsychiatric drug development.
This specialized focus on the brain’s electrical rhythms offers a level of precision that behavioral observation alone cannot provide. EEG-based biomarkers create a clear, data-driven path for linking genetic risk factors to clinical outcomes through measurable cellular- and circuit-level changes in brain function and drug response.
A major frontier for this research is schizophrenia, a disorder in which aberrant or reduced gamma-band activity, particularly at 40 Hz, has been consistently linked to negative symptoms and cognitive impairments that are difficult to model accurately in animals. EEG biomarkers provide a clearer alternative. Dr. Digavalli’s work with 40 Hz auditory steady-state responses (ASSR) offers a functional measure of how well neural networks entrain to rhythmic sensory stimuli, providing a direct window into the brain’s internal communication. Importantly, this response is conserved across species, strengthening its translational value.
Cortical oscillatory dynamics represent a “novel and promising translational biomarker with important applications in CNS drug development,” according to Dr. Digavalli’s research. By examining how these oscillatory patterns differ across brain regions and disease states, his lab can identify specific network-level dysfunctions associated with schizophrenia. In affected individuals, the ability to sustain high-frequency oscillations is often significantly impaired. Emerging evidence suggests that pharmacological strategies aimed at restoring or stabilizing these rhythms may help alleviate cognitive deficits and improve patient outcomes.
Dr. Digavalli’s commitment to this new model of discovery is shaped by more than 18 years of experience as a Principal Scientist in leading biopharmaceutical companies. During that time, he witnessed firsthand how promising CNS programs could stall in the absence of objective measures of target engagement.
“You get assigned to a project, you’re working on it, and suddenly business decisions change, owing to the perceived risk,” he said. By developing reliable, reproducible biomarkers such as gamma oscillations, researchers can generate the concrete evidence needed to sustain critical scientific investments.
His scientific journey has been global, beginning with pharmacy training in India and culminating in a PhD from LSU Health Sciences Center. He later completed a postdoctoral fellowship at Harvard Medical School, where he deepened his expertise in studying brain function within the intact physiological system. Now back in academia, Dr. Digavalli believes universities provide the stability necessary for long-term, high-impact discovery in EEG modeling.
“I think generally speaking, R&D is a little more stable in academia,” he said.
Through his focus on gamma oscillations and EEG-based biomarkers, Dr. Digavalli is working to ensure that the next generation of neuropsychiatric discoveries rests on strong empirical foundations. As his lab continues to expand its translational research efforts, he is currently seeking a motivated PhD student to join the team. For aspiring scientists, this represents a rare opportunity to work at the cutting edge of neuropsychiatric research, moving beyond surface-level observation and into the fundamental rhythms of the brain.
By prioritizing the brain’s internal electrical dynamics, Dr. Digavalli and his team are not simply searching for new drugs; they are redefining how therapeutic success is measured and validated. This shift holds the promise of transforming historically low success rates into a more reliable pathway toward meaningful breakthroughs in neuropsychiatric medicine.
Jargon Buster:
- R&D (Research and Development): The investigative process where scientists discover and test new ideas to create or improve medical treatments.
- Gamma Oscillations: Fast-paced electrical rhythms in the brain that act as a “heartbeat” for critical thinking, memory, and focus.
- EEG (Electroencephalography): A non-invasive way to record the brain’s electrical activity using small sensors placed on the scalp.
- Biomarker: A measurable biological “clue,” such as a specific brain wave pattern, that indicates if a disease is present or if a medicine is working.
