Anterior thalamic stimulation improves working memory precision judgments

Abstract

Background: The anterior nucleus of thalamus (ANT) has been suggested as an extended hippocampal system. The circuit of ANT and hippocampus has been widely demonstrated to be associated with memory function. Both lesions to each region and disrupting inter-regional information flow can induce working memory impairment. However, the role of this circuit in working memory precision remains unknown. Objective: To test the role of the hippocampal-anterior thalamic pathway in working memory precision, we delivered intracranially electrical stimulation to the ANT. We hypothesize that ANT stimulation can improve working memory precision. Methods: Presurgical epilepsy patients with depth electrodes in ANT and hippocampus were recruited to perform a color-recall working memory task. Participants were instructed to point out the color they were supposed to recall by clicking a point on the color wheel, while the intracranial EEG data were synchronously recorded. For randomly selected half trials, a bipolar electrical stimulation was delivered to the ANT electrodes. Results: We found that compared to non-stimulation trials, working memory precision judgements were significantly improved for stimulation trials. ANT electrical stimulation significantly increased spectral power of gamma (30e100 Hz) oscillations and decreased interictal epileptiform discharges (IED) in the hippocampus. Moreover, the increased gamma power during the pre-stimulus and retrieval period predicted the improvement of working memory precision judgements. Conclusion: ANT electrical stimulation can improve working memory precision judgements and modulate hippocampal gamma activity, providing direct evidence on the role of the human hippocampalanterior thalamic axis in working memory precision.

Bifurcating Neurons In The Anterior Thalamic Nuclei

“…The ATN have reciprocal connections with at least three distinct memory structures, namely the medial prefrontal cortex (mPFC), retrosplenial cortex (RSC) and subicular regions of the hippocampal formation (HF) (Bubb et al, 2017;Mathiasen et al, 2017). The importance of the ATN for memory is supported by extensive clinical and experimental evidence (Aggleton, 2008;Aggleton et al, 2016;Barnett et al, 2021;Carlesimo et al, 2011;Dalrymple-Alford et al, 2015;Harding et al, 2000;Kim et al, 2009;Kopelman, 2015;Liu et al, 2021;Maillard et al, 2021;Sweeney-Reed et al, 2021;Wolff et al, 2015). This evidence is consistent with the perspective that the ATN are a critical hub that actively coordinates information processing among telencephalic memory structures (Wolff and Vann, 2019).…”

“…Electrophysiological recordings in drugresistant epilepsy patients suggest that the ATN integrate information from diverse cortical sources during encoding to guide successful recall (Sweeney-Reed et al, 2021). More recent studies have shown that working memory in both humans and rats can be improved by stimulation of the ATN (Barnett et al, 2021;Liu et al, 2021).…”

“…Extensive clinical and experimental evidence supports the conclusion that the anterior thalamic nuclei (ATN) make a significant contribution to memory function (Aggleton, 2008; Aggleton et al, 2016; Barnett et al, 2021; Carlesimo et al, 2011; Dalrymple-Alford et al, 2015; Harding et al, 2000; Kim et al, 2009; Kopelman, 2015; Liu et al, 2021; Maillard et al, 2021; Sweeney-Reed et al, 2021; Wolff et al, 2015). This influence is consistent with the ATN’s strong reciprocal connections with three distinct memory structures, namely the medial prefrontal cortex (mPFC), retrosplenial cortex (RSC) and the hippocampal formation (HF) (Aggleton et al, 2016; Bubb et al, 2017; Mathiasen et al, 2017; Nelson, 2021; Shibata, 1993a, 1993b; van Groen et al, 1999; van Groen and Wyss, 1990; van Groen and Wyss, 1995).…”

Anterior thalamic nuclei neurons sustain memory

“…Our study provides compelling evidence for an active role of the ATN in a distributed memory network. Previously, electrical stimulation has been used, but this manipulation is less specific and resulted in mixed effects in rats (Hamani et al, 2010(Hamani et al, , 2011, although there is recent evidence that electrical stimulation of the ATN improves working memory in drugresistant epilepsy patients (Liu et al, 2021). Here, we showed that optogenetic activation of ATN glutamatergic projection neurons using exogenously-triggered regular TBS immediately improved spatial working memory in rats with MTT lesions that otherwise showed profound and persistent deficits.…”

“…This recovery might reflect information conveyed by the mammillothalamic tract (MTT), which constitutes axons from the MB that project to the ATN. More direct evidence comes from intracranial electrophysiological recordings made in epilepsy patients, which suggests that the ATN integrates information from diverse cortical sources during encoding to guide successful recall and that 50 Hz stimulation of the ATN improves working memory (Liu et al, 2021;Sweeney-Reed et al, 2021). In rats, however, there is mixed evidence for the impact of electrical stimulation of the ATN on memory.…”