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Noninvasive Stimulation of human vmPFC enhances reward learning and alleviates depressive symptoms

Poster No:

Submission Type:

Late-Breaking Abstract Submission

Authors:

Feixue Wang¹, Yiheng Tu¹, Yangyang Yi¹

Institutions:

¹Institute of Psychology, Chinese Academy of Sciences, Beijing, Beijing

First Author:

Feixue Wang
Institute of Psychology, Chinese Academy of Sciences
Beijing, Beijing

Co-Author(s):

Yiheng Tu
Institute of Psychology, Chinese Academy of Sciences
Beijing, Beijing

Yangyang Yi
Institute of Psychology, Chinese Academy of Sciences
Beijing, Beijing

Introduction:

Anhedonia, a hallmark of depression, stems from disrupted reward processing and dysfunction within the frontal-striatal circuit. Here, we report the first non-invasive deep brain stimulation targeting the frontal-striatal circuit, which selectively enhances reward learning and reduces depressive symptoms through three studies.

Methods:

We first modified a classical instrumental learning task and collected fMRI and EEG data from healthy participants during the task. These data were used to identify the spatio-spectral-temporal neural dynamics underlying reward learning which were crucial to design and optimize the TI protocol (study 1). Next, we applied TI with optimal montage and frequency to healthy participants to explore the modulatory effects on reward learning (study 2). Last, we recruited participants with depressive symptoms and conducted a double-blind clinical trial to evaluate the clinical efficacy of neural dynamics-informed TI in alleviating depressive symptoms

Results:

Study 1 identified the spatio-spectral-temporal neural dynamics underlying reward learning using fMRI and computational modeling during an instrumental learning task. We first identified selective activations in the ventromedial prefrontal cortex (vmPFC) and ventral striatum (VS) related to reward outcomes and reward prediction errors (RPEs) and found that reward information originates in the vmPFC, with bidirectional information flow between the vmPFC and VS forming a dynamic loop. Specifically, reward-related increases in vmPFC-to-VS connectivity and decreases in VS-to-vmPFC connectivity suggest a balanced neural mechanism supporting reward learning. EEG recordings further demonstrated that theta/alpha band power in the prefrontal lobe specifically encoded RPEs
Study 2 probed causality of prefrontal theta/alpha oscillations in reward learning through a preregistered, randomized, sham-controlled, and single-blind study. Participants received either 5 Hz or 10 Hz temporal interference (TI) stimulation over the vmPFC while performing the instrumental learning task. Results showed that alpha-band TI significantly enhanced reward learning. In addition, alpha-band TI could alleviate individuals' negative emotions, suggesting its potential for immediate mood enhancement.
Study 3 evaluated the clinical efficacy of alpha-band TI in a double-blind, randomized clinical trial involving depressive individuals. Participants received 20-minute sessions of alpha-band TI, theta-band TI or sham stimulation over three consecutive days. Compared with sham stimulation, individuals who received alpha-band TI demonstrated a significant reduction in depressive symptoms seven days post-intervention, highlighting the therapeutic potential of alpha-band TI for depressive symptom alleviation.

Conclusions:

Taken together, our research reveals distinct frontal-striatal neural dynamics and network structure underlying reward versus punishment learning, and demonstrates the application of non-invasive TI to enhance reward learning and alleviate depressive symptoms. Our findings have significant implications for developing accessible and effective treatments for depression and other disorders of reward processing, offering a non-invasive alternative to deep brain stimulation.

Brain Stimulation:

Non-Invasive Stimulation Methods Other ¹

Disorders of the Nervous System:

Psychiatric (eg. Depression, Anxiety, Schizophrenia) ²

Emotion, Motivation and Social Neuroscience:

Reward and Punishment

Keywords:

Cognition

Emotions

Other - Noninvasive stimulation; Temporal interference stimulation; Depressive symptoms

^1|2Indicates the priority used for review

Abstract Information

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Please indicate below if your study was a "resting state" or "task-activation” study.

Task-activation

Healthy subjects only or patients (note that patient studies may also involve healthy subjects):

Healthy subjects

Was this research conducted in the United States?

Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.

Yes

Were any animal research approved by the relevant IACUC or other animal research panel? NOTE: Any animal studies without IACUC approval will be automatically rejected.

Not applicable

Please indicate which methods were used in your research:

Functional MRI

EEG/ERP

Computational modeling

Other, Please specify - Temporal interference stimulation

For human MRI, what field strength scanner do you use?

3.0T

Which processing packages did you use for your study?

SPM

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