Extended remediation of sleep deprived-induced working memory deficits using fMRI-guided transcranial magnetic stimulation

Abstract

Study objectives: We attempted to prevent the development of working memory (WM) impairments caused by sleep deprivation using fMRI-guided repetitive transcranial magnetic stimulation (rTMS). Novel aspects of our fMRI-guided rTMS paradigm included the use of sophisticated covariance methods to identify functional networks in imaging data, and the use of fMRI-targeted rTMS concurrent with task performance to modulate plasticity effects over a longer term.

Design: Between-groups mixed model.

Setting: TMS, MRI, and sleep laboratory study.

Participants: 27 subjects (13 receiving Active rTMS, and 14 Sham) completed the sleep deprivation protocol, with another 21 (10 Active, 11 Sham) non-sleep deprived subjects run in a second experiment.

Interventions: Our previous covariance analysis had identified a network, including occipital cortex, which demonstrated individual differences in resilience to the deleterious effects of sleep deprivation on WM performance. Five Hz rTMS was applied to left lateral occipital cortex while subjects performed a WM task during 4 sessions over the course of 2 days of total sleep deprivation.

Measurements and results: At the end of the sleep deprivation period, Sham sleep deprived subjects exhibited degraded performance in the WM task. In contrast, those receiving Active rTMS did not show the slowing and lapsing typical in sleep deprivation, and instead performed similarly to non- sleep deprived subjects. Importantly, the Active sleep deprivation group showed rTMS-induced facilitation of WM performance a full 18 hours after the last rTMS session.

Conclusions: Over the course of sleep deprivation, these results indicate that rTMS applied concurrently with WM task performance affected neural circuitry involved in WM to prevent its full impact.

Keywords: TMS; fMRI; neuroplasticity; sleep deprivation; working memory.

Figures

Figure 1

Schematic diagram of the DMS paradigm. Two trials are shown, the first with a set size of one and requiring a “yes” response, and the second with a set size of 6 and requiring a “no” response. The trial phases and their durations are listed at the right (ITI = inter-trial interval).

Figure 2

Schematic diagram of the study procedure over the course of two days.

Figure 3

Baseline and Day 3 RTs for Active-sd and Sham-sd groups. The Sham-sd group shows a significant increase in RT (*P

Figure 4

Mean number of lapses in active and sham groups in the DMS task performed in non-MRI testing sessions on Day 3, at the end of the sleep deprivation period. There were no lapses in either group in pre-sleep deprivation baseline performance.

Figure 5

(A) The expression of the first spatial fMRI pattern for each subject in the Active-sd group is plotted on the left while the expression of each Sham-sd subject is plotted on the right. (B) Same for subject expression of the second spatial pattern.

Figure 6

The activated regions in the first spatial fMRI pattern. These regions were similarly activated for both the Active-sd and the Sham-sd groups in the Day 3 – Baseline contrast.

Figure 7

Coronal (A), sagittal (C), and transverse (E) sections of a template MRI showing the region (in green) activated in the Active-sd group. The blue circle represents the area targeted by rTMS. B, D, F show the electric field strength distribution computed from three-sphere model (shown as inset in F) and superimposed on the coronal, sagittal, and transverse sections, respectively. L, left.

Figure 8

Difference in mRT (Day 3 – Baseline, non-MRI testing sessions) for non-sleep deprived (on the left) and sleep deprived (on the right) active and sham groups (gray and black, respectively) for set sizes 1 and 6. Positive values indicate relatively slower RTs on Day 3, while negative values indicate speeded responses. Active-sd subjects showed speeded responses similar to non-sleep deprived subjects, while Sham-sd subjects displayed RT slowing typical in sleep deprivation at both set sizes. Bars show mean error.