Author(s)

Weiming Sun ¹

Affiliation(s)

¹ Department of Rehabilitation Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China

Corresponding Author

Weiming Sun

ABSTRACT

Working memory depends on persistent, delay-period activity in the dorsolateral prefrontal cortex (dlPFC), yet the causal relationship between externally induced electric fields and the neuronal codes that support spatial working memory remains poorly understood in non-human primates. Here, we combine chronic head-post training, oculomotor delayed-response (ODR) behaviour, and two-photon calcium imaging of dlPFC neurons in four rhesus macaques to test whether transcranial direct-current stimulation (tDCS) modulates mnemonic performance and its underlying population dynamics. Anodal tDCS delivered over the left dlPFC during the delay period improved ODR accuracy in a polarity-, intensity-, and duration-dependent manner, with the largest benefit at the longest (5000 ms) memory delays. Cathodal stimulation produced the opposite pattern. At the cellular level, anodal tDCS increased delay-period ΔF/F0, calcium transient frequency, and the duration of mnemonic activity, while sharpening directional tuning. Population decoding of the remembered cue direction was enhanced after anodal stimulation and correlated with the local electric field magnitude predicted by a validated finite-element model. Network analyses further showed that anodal tDCS increased local synchrony, clustering coefficient, and functional connectivity, whereas cathodal tDCS suppressed them. A four-layer elliptical finite-element head model confirmed that the chosen montage delivered mean electric fields of 1.84–7.37 V/m in dlPFC across 0.5–2.0 mA, with a 448% local amplification under a chronic optical window. Together, these results provide a multi-scale mechanistic account of how tDCS modulates prefrontal working memory circuits in primates and establish an experimental platform for cell-type-specific interrogation of non-invasive neuromodulation.

KEYWORDS

tDCS; dlPFC; Oculomotor delayed response; Working memory; Two-photon calcium imaging; Rhesus macaque; Population coding

CITE THIS PAPER

Weiming Sun. Enhancement of visual-spatial working memory and reshaping of delay-period population codes by anodal tDCS over macaque dorsolateral prefrontal cortex. MEDS Basic Medicine (2026). Vol. 4, No. 1, 131-139. DOI: http://dx.doi.org/10.23977/medbm.2026.040117.

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