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Updated: Apr 13, 2026
Optogenetic Entrainment of Hippocampal Theta Oscillations in Behaving Mice
Published on: June 29, 2018
Frequency-dependent modulation of human reward circuitry: A comparative study of theta, gamma, and high-frequency
Yongxi Zhang1, Zhenxiang Zang2, Rui Liu2
1Beijing Key Laboratory of Intelligent Drug Research and Development for Mental Disorders, National Clinical Research Center for Mental Disorders, National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing 100088, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 100069, China.
Background:
Temporal interference (TI) stimulation offers a noninvasive neuromodulation technique for targeting deep brain structures while sparing overlying cortical tissue. While early applications have validated TI's capacity to engage subcortical targets such as the hippocampus and striatum, the frequency-dependent mechanisms governing its efficacy remain poorly understood. This is particularly critical for the nucleus accumbens (NAc), a key hub in reward circuitry where invasive deep brain stimulation (DBS) typically operates at high frequencies (∼130 Hz).
Methods:
In this study, we investigated whether TI stimulation induces frequency-specific modulation of NAc activity and its functional coupling with the prefrontal cortex. Using a within-subject, counterbalanced design, we applied individualized NAc-targeted TI stimulation at three distinct envelope frequencies (5 Hz, 40 Hz, and 130 Hz) in 24 healthy adults. Resting-state fMRI was acquired pre- and post-stimulation.
Results:
Results revealed a distinct dissociation between local and circuit-level effects: TI stimulation induced no statistically significant changes in local spontaneous activity within the NAc across any frequency condition. In contrast, 130 Hz stimulation selectively reduced functional connectivity between the NAc and the medial prefrontal cortex (mPFC), whereas 5 Hz and 40 Hz conditions produced no such effect. Notably, despite the absence of significant group-level local modulation, the magnitude of individual NAc activity reduction under 130 Hz stimulation was significantly correlated with the extent of NAc-mPFC decoupling (r = -0.53). Exploratory analyses further revealed increased activity in the adjacent dorsal striatum (right putamen), consistent with a conduction-block model at the target core.
Conclusions:
These findings suggest that high-frequency TI mimics the network-disrupting effects of high-frequency DBS, offering evidence that TI can noninvasively modulate deep reward circuits in a parameter-specific manner for potential clinical application.
