Hippocampal ripples predict motor learning during brief rest breaks in humans

Abstract

Critical aspects of motor learning and memory happen offline, during both wake and sleep. When healthy young people learn a motor sequence task, most of their performance improvement happens not while typing, but offline, during interleaved rest breaks. In contrast, the performance of patients with dense amnesia due to hippocampal damage actually gets worse over the rest breaks and improves while typing. These findings indicate that an intact hippocampus is necessary for offline motor learning during wake, but do not specify its mechanism. Here, we studied epilepsy patients (n = 17) undergoing direct intracranial electroencephalographic monitoring of the hippocampus as they learned the same motor sequence task. Like healthy young people, they show greater speed gains across rest breaks than while typing. They also show higher hippocampal ripple rates during these rest breaks that predict offline gains in speed. This suggests that motor learning during brief rest breaks during wake is mediated by hippocampal ripples. These results expand our understanding of the role of hippocampal ripples beyond declarative memory to include enhancing motor procedural memory.

Fig. 1. Micro-online and -offline gains across MST trials.

A Left: Participants (n = 17) rested four fingers on a key pad with keys labeled 1, 2, 3, 4. They were instructed to repeatedly type a five-digit sequence (e.g., 4-1-3-2-4) as quickly and accurately as possible. During the 30 s typing trials, the screen was green, and the sequence was displayed on top. After 30 s, the screen turned red and participants rested for 30 s. Training consisted of 12 typing trials and 11 rest breaks. Middle: Plot of mean online (blue solid line) and offline (dashed red line) gains over the 30 s of each typing and rest period across participants (x-axis), with the standard error (blue shading) of the typing speed. Right: Violin plots showing distribution of the sum of total gains, micro-online gains and micro-offline gains across 11 trials across participants. The black dots represent participants’ means, and horizontal lines represent group means. B Boxplots of micro-online and -offline gains by trial. Each circle is the gain for each of the 17 participants in a given trial. Boxes extend to the median and 25^th and 75^th percentiles of gains. Whisker lines extend to the maximum/minimum non-outlier values (less than 1.5 of the interquartile range from the upper or lower quartile). Horizontal lines represent trial medians. The rightmost boxplot pair represents the mean of micro-online and -offline gains across trials for each participant. Significant results from paired and one-sample two-tailed t tests are indicated with corrected p-values.

Fig. 2. Oscillatory and spectral characteristics of detected ripples.

A Wide-band filtered signal, 70–150 Hz filtered signal, and time- frequency spectrograms for a single ripple and averaged ripples across all 17 participants (highlighted in red) during online (typing) and offline (rest) periods. Ripple peaks were aligned before averaging. Time-frequency spectrograms are normalized to the mean across the entire MST run at each frequency. The white line indicates where 60 Hz signal was removed using a notch filter. Each plot is centered on maximum power in the 70–150 Hz filtered signal at the time of a detected ripple. B Online and offline ripple characteristics. Each dot represents the mean value of each of the 17 participants’ ripples’ peak frequency, peak amplitude, duration, and number of oscillatory cycles. Boxes extend to the median and the 25^th and 75^th percentiles. Whisker lines extend to the maximum/minimum non-outlier values (less than 1.5 of the interquartile range from the upper or lower quartile). Horizontal lines represent medians.

Fig. 3. Hippocampal ripple rates during online and offline periods and their relations to micro-online and -offline gains.

A Boxplots of hippocampal ripples during online and offline periods for each trial. Each circle is an individual data point for each participant (n = 17). Boxes extend to the median and 25^th and 75^th percentiles of ripple rate across participants. Whisker lines extend to the maximum/minimum non-outlier values (less than 1.5 of the interquartile range from the upper or lower quartile). Horizontal lines represent medians. Mean online and offline ripple rates across trials per participant (far right). Significant results from the paired two-tailed t-test is indicated with the p-value. B Scatter plots of mean ripple rate and mean gains across trials. Each participant (n = 17) is a circle. The gray shading represents the standard error of the regression line. C Scatter plots of ripple rates and gains per trial for each participant (n = 17) for online and offline periods. The shading represents the standard error of the regression line.