Elsevier

NeuroImage

Volume 138, September 2016, Pages 100-108
NeuroImage

Pre-stimulus thalamic theta power predicts human memory formation

https://doi.org/10.1016/j.neuroimage.2016.05.042Get rights and content

Highlights

  • Pre-stimulus theta power in dorsomedial thalamic nucleus predicts memory formation.

  • Pre-stimulus thalamic theta predicts post-stimulus neural correlates of memory.

  • Pre-stimulus brain states conducive to memory encoding include subcortical regions.

Abstract

Pre-stimulus theta (4–8 Hz) power in the hippocampus and neocortex predicts whether a memory for a subsequent event will be formed. Anatomical studies reveal thalamus-hippocampal connectivity, and lesion, neuroimaging, and electrophysiological studies show that memory processing involves the dorsomedial (DMTN) and anterior thalamic nuclei (ATN). The small size and deep location of these nuclei have limited real-time study of their activity, however, and it is unknown whether pre-stimulus theta power predictive of successful memory formation is also found in these subcortical structures. We recorded human electrophysiological data from the DMTN and ATN of 7 patients receiving deep brain stimulation for refractory epilepsy. We found that greater pre-stimulus theta power in the right DMTN was associated with successful memory encoding, predicting both behavioral outcome and post-stimulus correlates of successful memory formation. In particular, significant correlations were observed between right DMTN theta power and both frontal theta and right ATN gamma (32–50 Hz) phase alignment, and frontal-ATN theta-gamma cross-frequency coupling. We draw the following primary conclusions. Our results provide direct electrophysiological evidence in humans of a role for the DMTN as well as the ATN in memory formation. Furthermore, prediction of subsequent memory performance by pre-stimulus thalamic oscillations provides evidence that post-stimulus differences in thalamic activity that index successful and unsuccessful encoding reflect brain processes specifically underpinning memory formation. Finally, the findings broaden the understanding of brain states that facilitate memory encoding to include subcortical as well as cortical structures.

Introduction

Memory formation arises from interactions between environmental events and a continually varying brain state (Fox et al., 2007). Pre-stimulus activity, reflecting the brain state preceding memory formation, has recently been shown to predict whether a memory will be formed (e.g., Cohen et al., 2015, Guderian et al., 2009, Otten et al., 2006, Otten et al., 2010, Park and Rugg, 2011). Studies have focused on the medial temporal lobe (MTL) (Fell et al., 2011, Guderian et al., 2009) and frontal cortex (Otten et al., 2006) due to the well-known roles of these regions in memory formation. For instance, hippocampal and rhinal cortical theta (4–8 Hz) oscillations predict encoding success (Fell et al., 2011). However, whether pre-stimulus activity in subcortical structures or pre-stimulus subcortical–cortical interactions play a role in determining encoding success remains unknown. Recent evidence highlights important roles for the anterior and dorsomedial thalamic nuclei (ATN and DMTN respectively) in memory processing (Aggleton, 2012, Staudigl et al., 2012, Sweeney-Reed et al., 2014, Sweeney-Reed et al., 2015). Based on these findings and established thalamo-hippocampal connectional anatomy (Aggleton, 2012, Aggleton et al., 2010, Vertes et al., 2001), we hypothesized that pre-stimulus thalamic theta power preceding presentation would predict successful memory performance.

To test this hypothesis, we examined electrophysiological activity recorded directly from the DMTN and ATN during memory encoding in human participants who had received electrodes implanted for deep brain stimulation therapy for refractory epilepsy. Our primary objective was to investigate whether pre-stimulus theta oscillations in thalamic nuclei predict successful memory formation. To assess whether thalamic theta activity before an event has a direct relationship to event memory, we also examined whether individual differences in memory performance were predicted by pre-stimulus theta power. Additionally, we assessed the correlation between pre-stimulus thalamic theta power and recently identified post-stimulus neural correlates of successful memory formation. Pre- and post-stimulus cortical activity predicting successful memory formation are partially correlated (Otten et al., 2006), and we hypothesized that thalamic pre-stimulus theta power would also predict some of the post-stimulus electrophysiological measures of successful encoding. These included post-stimulus frontal-ATN theta-gamma cross-frequency coupling (CFC) and theta phase synchrony, as well as ATN theta phase alignment, all predictive of successful memory formation (Sweeney-Reed et al., 2014, Sweeney-Reed et al., 2015). We discuss our findings in the context of the hypothesis that the DMTN and ATN are differentially involved in memory systems supporting encoding resulting in enhanced familiarity (perirhinal-medial dorsal thalamic system) or in enhanced recollection (hippocampal-anterior thalamic: ‘extended hippocampus system’) (Aggleton and Brown, 1999). We also consider the findings from the perspective of anatomical connectivity between the DMTN and the amygdala and in the context of a role in oculomotor control.

Section snippets

Materials and methods

We analyzed intracranial electroencephalogram (EEG) recorded directly from 8 bilateral contacts (4 on each electrode probe) in the ATN and DMTN in 7 human volunteers receiving electrodes implanted for stimulation treatment of pharmacoresistant focal epilepsy (Fig. 1), as well as from a single frontal scalp EEG contact (Table 1). The frontal electrode location (Fz, AFz, or Fpz) differed slightly across participants, because differing bandage placements dictated the electrode location. We note

Results

We begin with the behavioral analysis, in which the memory performance during the experimental paradigm was assessed, before providing the results of the electrophysiological data analysis. The EEG analysis is presented in three stages. First, the difference in pre-stimulus power preceding successful and unsuccessful memory formation is evaluated, then assessment is made of prediction of behavioral and of post-stimulus neurophysiological correlates of successful memory formation by DMTN

Discussion

We observed that pre-stimulus theta power in the RDMTN predicts encoding success. Enhanced theta power predicted both better performance on a later test of recognition memory as well as frontal and RATN post-stimulus neural correlates of successful memory formation. Post-stimulus RATN theta synchrony correlates with successful memory encoding and is a core component of an ‘extended hippocampal system’ proposed to support episodic memory formation (Aggleton and Brown, 1999, Sweeney-Reed et al.,

Conclusions

We present direct electrophysiological evidence in humans for a key role of the DMTN in memory processing, These findings are consistent with reports of the involvement of the DMTN in encoding in both animal lesion and human fMRI studies (Aggleton and Brown, 1999, Mitchell and Gaffan, 2008, Pergola et al., 2013). Notably, intrinsic pre-stimulus DMTN theta activity predicted both subsequent memory and its post-stimulus neural correlates in the ATN. Our finding of pre-stimulus thalamic effects on

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