Preprint · Jul 6, 2026
Modulating Motor Learning and Memory Consolidation in Older Adults via Hippocampal Temporal Interference Stimulation
By Taylor J, King BR, Pan X et al.
Aging is associated with declines in motor function, including reduced capacity to retain new motor skills. Previous research employing motor sequence learning tasks has demonstrated that healthy older adults exhibit comparable learning during active task practice as younger adults, suggesting that “online” learning is relatively preserved with healthy aging (Fogel et al., 2014a; Gudberg et al., 2015; King et al., 2013; Spencer et al., 2007). However, “offline” learning (i.e., performance changes across periods of no active task engagement) is impaired in older adults (Brown et al., 2009; Mylonas et al., 2024; Nemeth & Janacsek, 2010; Roig et al., 2014; Spencer et al., 2007; Van Roy et al., 2024; Wilson et al., 2012). These deficits were first observed on the timescale of hours to days following an initial learning session (Brown et al., 2009; Nemeth & Janacsek, 2010; Roig et al., 2014; Spencer et al., 2007; Van Roy et al., 2024; Wilson et al., 2012) (i.e., “macro-offline”). However, recent research has extended this finding to a faster timescale of seconds to minutes that takes place during the short rest intervals between practice blocks (i.e., “micro-offline”) (Mylonas et al., 2024). Importantly, converging evidence from neuroimaging and clinical research has demonstrated that the hippocampus is critically involved in offline motor sequence learning processes on both timescales (Albouy, King, et al., 2013; Albouy, Sterpenich, et al., 2013; E. Buch et al., 2021; Chen et al., 2024; Gann et al., 2023; Jacobacci, Armony, Yeffal, Lerner, Amaro, Jovicich, Doyone, et al., 2020; King et al., 2022; Mylonas et al., 2024; Schapiro et al., 2019; Sjøgård et al., 2025). Thus, the aging hippocampus represents a promising and novel target for interventions aimed at mitigating age-related declines in offline motor learning. The goal of this study is to assess the potential of a novel experimental intervention (transcranial electrical Temporal Interference Stimulation (TIS)) to enhance motor learning and memory processes in healthy older adults (i.e., ≥ 55 years). TIS is a noninvasive brain stimulation technique capable of selectively targeting deep brain structures, such as the hippocampus, while minimizing stimulation of overlying cortical regions by delivering two high-frequency electrical currents with slightly different frequencies (e.g., 2.000 kHz and 2.005 kHz) through separate pairs of scalp electrodes (Grossman et al., 2017). Where these electric fields intersect, they generate a low-frequency amplitude-modulated envelope equal to the delta frequency between the two currents (e.g., 5 Hz), allowing stimulation to be focused within deep neural tissue. Recent human studies have demonstrated that TIS can enhance hippocampus-dependent episodic and spatial memory (Beanato et al., 2024; Violante et al., 2023) and facilitate motor sequence learning through striatal stimulation (Wessel et al., 2023). In the present study, TIS will be applied to the right hippocampus of older adults during motor sequence learning (MSL). Since older adults tend to demonstrate deficits in offline learning (Fogel et al., 2014; Mylonas et al., 2024), stimulation will be applied during the micro-offline epoch (offline-TIS), i.e. during the short rest periods interspersed with task practice that are known to host the fast consolidation process (Bönstrup et al., 2019; Buch et al., 2021; Chen et al., 2024; Gann et al., 2023). As the hippocampus is also described to play an important role in the slow consolidation process (Albouy et a., 2008; 2013), performance will be assessed at a 24-hour retest to examine the effect of stimulation on memory retention. In addition, because the hippocampus is thought to encode abstract spatiotemporal representations of motor sequences (Albouy et al., 2015) that facilitate the application of learned skills to novel contexts (Robertson, 2018), a transfer test using a novel sequence will be administered to explore whether transfer differs between the active and control stimulation conditions.