Scientists Unveil Distinct Neural Pattern Associated with Depression

Rewards significantly shape human and animal behaviors, a concept explored extensively in neuroscience but with limited understanding of the underlying neural processes. A new study has pinpointed beta frequency neural activity in the anterior cingulate cortex as crucial in reward recognition and decision-making, a discovery that extends to understanding and potentially treating anhedonia in depression. This research, backed by the NIH BRAIN Initiative, introduces a potential biomarker for anhedonia and explores altering brain activity as a treatment strategy.

As parents, teachers, and pet owners can attest, rewards play a significant role in shaping behaviors in both humans and animals. Rewards, whether in the form of edible treats, gifts, words of appreciation, praise, fame, or monetary benefits, serve as positive reinforcement for associated behaviors. This correlation between rewards and future choices has been a well-established paradigm in neuroscience research for over a century. However, the neural processes underlying this phenomenon—specifically how the brain encodes, remembers, and translates reward cues into desired future behaviors—remain largely unknown.

A recent study led by Dr. Sameer Sheth, professor and vice chair of research in the Department of Neurosurgery at Baylor College of Medicine, director of the Gordon and Mary Cain Pediatric Neurology Research Foundation Laboratories and investigator at the Jan and Dan Duncan Neurological Research Institute (Duncan NRI) at Texas Children’s Hospital, identified beta frequency neural activity in the anterior cingulate cortex (ACC) of the brain’s frontal lobe as the key neural signature underlying processes associated with recognizing rewards and determining subsequent choices and, thus, shaping future behaviors.

Furthermore, the study, published in Nature Communications, reports this neural signature is altered in patients with depression, opening an exciting possibility of using these neural signals as a new biomarker and a potential innovative avenue for therapy.

Human beings derive pleasure through various physical or mental activities, sensory experiences, and interactions with family and friends. However, individuals with depression often experience feelings of hopelessness, sadness, or despair for prolonged periods due to disengagement and anhedonia – a medical term meaning loss of the ability to feel joy or contentment in activities and things that they once found pleasurable, all of which has a profound negative impact on their quality of life.

Anhedonia is also associated with other psychiatric and neurological disorders such as schizophrenia and bipolar disorder, substance abuse disorder, anxiety, and Parkinson’s disease. Traditional antidepressants and standard treatments often fail to adequately address this symptom in individuals with severe treatment-resistant depression and other conditions. A better understanding of anhedonia can guide the development of targeted and more effective treatments for depression and related conditions.

To identify the underlying neural basis for anhedonia, Sheth and team recorded and analyzed neural activity from four brain regions of 15 patients with medication-resistant epilepsy who were undergoing invasive monitoring to localize the zone from where their seizures originated.

As their brain activity was being monitored, these patients performed a perceptual discrimination task called the probabilistic reward task (PRT), a well-validated behavioral task that objectively measures anhedonia by observing subtle changes in behavior related to reward.

“We found that the unequal assignment of reward between two correct responses in this task produced a response bias toward the more frequently rewarded stimulus,” said lead author Dr. Jiayang Xiao, who conducted this study as a graduate student in the Sheth lab. “We found that based on feedback, most individuals modified their subsequent responses to make choices that were likely to get rewarded, irrespective of the accuracy of their answers.”

Moreover, they found a specific signal – neural oscillations in the beta frequency range – originating from the anterior cingulate cortex (ACC) in the frontal lobe of the brain, showed a consistently strong and positive correlation with the reward bias behavior and tracked closely with the receipt of rewards and their value. Further, they found that this specific brain region was engaged in evaluating both reward stimuli and outcomes, potentially acting as a critical node with a common mechanism for reward assessment.