Scientists Uncover a Specific Neural Signature of Depression

Rewards have a huge bearing on human and animal behavior, very well-studied in neuroscience, with little understanding of neural processes involved. A new study identified beta frequency neural activity in the anterior cingulate cortex as key to reward recognition and in making decisions. The finding may reach anunderstanding and possible therapy of anhedonia in depression. This NIH BRAIN Initiative–funded study describes a putative anhedonia biomarker and manipulation of brain activity as a potential therapeutic approach.

A study explains that beta frequency activity in the anterior cingulate cortex area of the brain holds the key to how rewards work in governing behavior and therefore probably links to new treatments for anhedonia in depression. Any parent, teacher, or pet owner can tell you that rewards are powerful tools for shaping behaviors in both humans and animals. It is a positive reinforcement for associated behaviors by the form of rewards, whether edible, gifts, words of appreciation, praise, fame, or monetary. Relating these rewards to the options available in the future has been a very old paradigm in neuroscience research, going as far back as over a century ago. That is, the neural processes underlying—the way in which the brain encodes, remembers, and translates the reward cues into the desired future behaviors—remain substantially unknown.

Now, in a study, Dr. Sameer Sheth, who is a 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 at Texas Children’s Hospital, identified beta frequency neural activity in the anterior cingulate cortex in the frontal lobe of the brain as the key neural signature underlying reward recognition processes and determination of choice based on those rewards, and thus ultimately shaping future behaviors.

A changed neural signature of anhedonia in individuals with depression was reported in a study in Nature Communications. The exciting possibility opened up by these neural signals is their use as a new biomarker and as a possible innovative avenue for therapy.

Anhedonia is considered one of the central symptoms of depression and other psychiatric conditions. Humans derive pleasure through various physical or mental activities, sensory experiences, and social contacts with family and friends. On the other hand, the majority of individuals with depression get hopeless, gloomy, or despairing due to a disengagement and anhedonia – medical terms that connote loss of ability to experience pleasure or enjoyment in activities and things that a person previously liked – all of which very negatively impacts the quality of life.

Anhedonia is related to major psychiatric and neurological disorders, including schizophrenia, bipolar disorder, substance abuse disorder, anxiety, and even Parkinson’s disease. Traditional antidepressants and regular treatments often are not able to alleviate this symptom among people who have severe, treatment-resistant depression or other conditions. Further research in anhedonia will greatly help the development of more efficient treatments against depression and related disorders.

Control over reward bias by beta activity in frontal lobe
To know the underlying neural basis of anhedonia, Sheth and his coworkers recorded and analyzed the neural activity from four different regions of the brain of 15 patients who had medication-resistant epilepsy. These people were undergoing invasive monitoring to localize the zone from which their seizures originate.

While brain activity was recorded, these patients performed a perceptual discrimination task known as the probabilistic reward task, which is one rigorously validated behavioral task that could provide an objective measure of anhedonia through subtle behavioral changes related to reward.

“We found that the unequal assignment of reward for two correct responses in this task created a response bias toward the more frequently rewarded stimulus,” said the lead author, Dr. Jiayang Xiao, who performed this work as a graduate student in the Sheth Lab. “What we found was that most people changed their subsequent responses, making choices to probably get rewarded, regardless of whether answers were correct or not, in response to feedback.”

They found another type of signal as well: neural oscillations in the beta frequency range that showed a strong positive correlation to a behavior in biasing reward, finally being located in the anterior cingulate cortex region at the frontal lobe of the brain, closely following delivery and value in rewards. Moreover, they showed that the particular brain area being scrutinized was involved in reward stimuli and outcome evaluation and thus might offer a decisive node in which reward is assessed by some shared mechanism.

“Our study has addressed a long-standing fundamental question in neuroscience – which specific brain region and signal regulates the classic reward bias response, a famous example of which is the Pavlovian conditioning where dogs learned to associate the sound of a ringing bell to food,” said Dr. Benjamin Hayden, co-senior author and professor of neurosurgery at Baylor.

Reward bias response altered in treatment-resistant depression patients
Next, Sheth and his colleagues tried the PRT in four subjects with very severe, treatment-resistant depression. In such a group of subjects, they revealed alteration in reward processing within the ACC. Behaviorally, the subjects did not demonstrate typical responses—that is, preference for more frequently rewarded choices. These observations were taken to indicate a lack of reward-oriented anticipation; their choices were less driven by reward feedback. Connected with this change in reward bias behavior, beta activity in the ACC region was diminished and delayed in these subjects.

“In this paper, we identified beta activity in the ACC as a putative biomarker of anhedonia,” said Sheth, also McNair Scholar and Cullen Foundation Endowed Chair at Baylor. It could therefore have a range of potential benefits to improve diagnosis and monitoring of symptoms in patients with severe depression and other psychiatric conditions associated with anhedonia. Furthermore, our results offer the exciting prospect that modulation of the activity of the ACC-beta may be an effective treatment for anhedonia, a hypothesis we plan to test in future clinical trials.

Improvements in neurotechnologies associated with this research have moved ahead at unprecedentedly rapid rates, in part due to funding at the National Institutes of Health Brain Research Through Advancing Innovative Neurotechnologies Initiative, known as the BRAIN Initiative.

“This study is a great example of how BRAIN-funded research is already translating into the clinic today,” said Dr. John Ngai, director of the NIH BRAIN Initiative. “The innovations described in this study in data collection and providing individualized deep brain stimulation may enable an entirely new generation of precision treatments.”

The results of this study therefore extend beyond understanding the neural substrates of reward processing to potentially revolutionizing the treatment of depression and related psychiatric disorders. One hallmark of depression is anhedonia, a deeply impacting symptom in daily life, because it reduces one’s ability to experience pleasure from activities that they used to enjoy and remarkably decreased the quality of life. This symptom is often poorly responsive to traditional treatments in patients with severe treatment-resistant depression.

These findings implicate beta-frequency neural activity within the anterior cingulate cortex as a key anhedonia biomarker. In patients with depression, this neural signature is changed and associated with the flattening of responses to stimuli rewarding behavioral tasks. The result gives insight into how depression affects reward processing and offers up the potential target for innovative therapeutic interventions.

Such manipulation of the ACC beta activity thus holds within itself the promise of being utilized in alleviating anhedonic symptoms in the future. It opens the way for hope in personalized treatment that will be capable of restoring the ability of a person to feel and foresee rewards, regaining mental health. This then allowed the researchers to take advantage of neurotechnological advances enabled by funding initiatives like the BRAIN Initiative and translate basic discoveries into clinical applications that might transform strategies for the treatment of depression and related disorders.

Source: https://scitechdaily.com/

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