Hippocampal and striatal responses during motor learning are modulated by prefrontal cortex stimulation

Abstract

While it is widely accepted that motor sequence learning (MSL) is supported by a prefrontal-mediated interaction between hippocampal and striatal networks, it remains unknown whether the functional responses of these networks can be modulated in humans with targeted experimental interventions. The present proofof-concept study employed a comprehensive multimodal neuroimaging approach, including functional magnetic resonance (MR) imaging and MR spectroscopy, to investigate whether individually-tailored theta-burst stimulation of the dorsolateral prefrontal cortex can modulate responses in the hippocampus and striatum during motor learning. Our results indicate that stimulation influenced task-related connectivity patterns within hippocampo-frontal and striatal networks. Stimulation also altered the relationship between the levels of gamma-aminobutyric acid (GABA) in the stimulated prefrontal cortex and learning-related changes in both activity and connectivity in fronto-striato-hippocampal networks. This study provides the first experimental evidence that brain stimulation can alter motor learning-related functional responses in the striatum and hippocampus.

Modulating Visuomotor Sequence Learning by Repetitive Transcranial Magnetic Stimulation: What Do We Know So Far?

“…Hz rTMS (Pascual-Leone et al, 1996) weakened the performance on the SRTT. However, the other two studies found no effects of rTMS (Gann et al, 2021;Wilkinson et al, 2010).…”

“…In some studies, low-frequency rTMS and cTBS over the DLPFC weakened learning (Pascual-Leone et al, 1996;Robertson et al, 2001). However, more recent studies have found no effects (Gann et al, 2021;Wilkinson et al, 2010) or even enhanced learning (Ambrus et al, 2020;Galea et al, 2010). One possible explanation for the behavioral improvement might lie in the competitive relationship between the so-called more-and less-controlled learning processes (Daw et al, 2005).…”

“…On the other hand, three studies chose active control with different control sites (i.e., vertex, occipital and parietal sites). In two studies, members of the control group were simply not exposed to rTMS (Pascual-Leone et al, 1996;Torriero et al, 2004), one study compared cTBS to intermediate TBS (Experiment 2 and 3 in Tunovic et al, 2014) and another study only compared two active stimulation protocols (cTBS and iTBS) to each other (Gann et al, 2021) (see Table 2).…”

“…Examining explicit sequence learning, two of the six studies have found an enhancement for cTBS over the DLPFC (Galea et al, 2010;Experiment 2 in Tunovic et al, 2014). However, one recent study has found no effect of DLPFC stimulation on explicit SRTT (Gann et al, 2021). Two additional studies used probabilistic instead of deterministic sequences.…”

Causal Inferences in Repetitive Transcranial Magnetic Stimulation Research: Challenges and Perspectives

“…Additionally, active protocols with certain frequency patterns are often classified in TMS literature as “inhibitory” or “excitatory”. Thus, sometimes the protocol patterns of rTMS 1 and another active rTMS protocol 2 (rTMS 2 ) differ and might be commonly conceived as being inhibitory and excitatory, respectively; thus, they are used to obtain a difference in T X performance directly (e.g., Gann et al, 2020 ) or to prime cortex excitability before the application of other protocols (e.g., Todd et al, 2009 ). It is important to note that inhibitory and excitatory rTMS properties are extrinsic to the protocol pattern and may vary depending on, e.g., protocol length, current direction, intensity, genome, and the targeted area characteristics, including its tissue excitability history and tissue excitability before protocol application (Polanía et al, 2018 ).…”