Mesial-Temporal Epileptic Ripples Correlate With Verbal Memory Impairment

Abstract

Rationale: High frequency oscillations (HFO; ripples = 80-200, fast ripples 200-500 Hz) are promising epileptic biomarkers in patients with epilepsy. However, especially in temporal epilepsies differentiation of epileptic and physiological HFO activity still remains a challenge. Physiological sleep-spindle-ripple formations are known to play a role in slow-wave-sleep memory consolidation. This study aimed to find out if higher rates of mesial-temporal spindle-ripples correlate with good memory performance in epilepsy patients and if surgical removal of spindle-ripple-generating brain tissue correlates with a decline in memory performance. In contrast, we hypothesized that higher rates of overall ripples or ripples associated with interictal epileptic spikes correlate with poor memory performance.

Methods: Patients with epilepsy implanted with electrodes in mesial-temporal structures, neuropsychological memory testing and subsequent epilepsy surgery were included. Ripples and epileptic spikes were automatically detected in intracranial EEG and sleep-spindles in scalp EEG. The coupling of ripples to spindles was automatically analyzed. Mesial-temporal spindle-ripple rates in the speech-dominant-hemisphere (left in all patients) were correlated with verbal memory test results, whereas ripple rates in the non-speech-dominant hemisphere were correlated with non-verbal memory test performance, using Spearman correlation).

Results: Intracranial EEG and memory test results from 25 patients could be included. All ripple rates were significantly higher in seizure onset zone channels (p < 0.001). Patients with pre-surgical verbal memory impairment had significantly higher overall ripple rates in left mesial-temporal channels than patients with intact verbal memory (Mann-Whitney-U-Test: p = 0.039). Spearman correlations showed highly significant negative correlations of the pre-surgical verbal memory performance with left mesial-temporal spike associated ripples (r_s = -0.458; p = 0.007) and overall ripples (r_s = -0.475; p = 0.006). All three ripple types in right-sided mesial-temporal channels did not correlate with pre-surgical nonverbal memory. No correlation for the difference between post- and pre-surgical memory and pre-surgical spindle-ripple rates was seen in patients with left-sided temporal or mesial-temporal surgery.

Discussion: This study fails to establish a clear link between memory performance and spindle ripples. This highly suggests that spindle-ripples are only a small portion of physiological ripples contributing to memory performance. More importantly, this study indicates that spindle-ripples do not necessarily compromise the predictive value of ripples in patients with temporal epilepsy. The majority of ripples were clearly linked to areas with poor memory function.

Keywords: epilepsy; high frequency oscillations (HFO); memory; ripples; sleep spindles; temporal lobe epilepsy.

Figure 1

(A) Example for hippocampal ripples in intracranial EEG channels co-occurring with a frontal sleep spindle in scalp EEG. (B) Example for hippocampal ripples co-occurring with interictal epileptic spikes in the same intracranial EEG channels.

Figure 2

Rates of three ripple types per min in channels outside the seizure onset zone (NSOZ) compared to ripples in channels inside the seizure onset zone (SOZ). Significantly higher overall ripple, IES ripple, and Spindle ripple rates were found in SOZ channels (^*p < 0.001, respectively).

Figure 3

(A) Rates of left-sided mesial-temporal ripples in patients with healthy vs. impaired pre-surgical verbal memory. Patients with impaired verbal memory had significantly higher overall ripple rates than patients with healthy memory. (All Ripples: *p = 0.039; IES Ripples: p = 0.078; Spindle ripples: p = 0.379). α = 0.05. (B) Rates of all right-sided mesial-temporal overall Ripples and IES Ripples in patients with healthy vs. impaired pre-surgical non-verbal memory. No significant differences were seen for all three ripple types (All Ripples: p = 0.606; IES Ripples: p = 0.541; Spindle Ripples: p = 0.423); α = 0.05.

Figure 4

(A) Scatterplot of the overall left mesial-temporal ripple rate and pre-surgical verbal memory results. A significant negative correlation between ripple rates and memory performance was seen (r_s = −0.475; p = 0.006). (B) Scatterplot of the left mesial-temporal IES ripple rate and pre-surgical verbal memory results. A significant negative Spearman correlation was seen (r_s = −0.458; p = 0.007). (C) Scatterplot of the left sided spindle ripple rate and pre-surgical verbal memory results. No significant Spearman correlation was seen (r_s = −0.194; p = 0.149).