Abstracts

Cognitive effects of vagus nerve stimulation (VNS) in epilepsy patients are still under discussion. According to the Cyberonics Patient Registry (03/2003, 12-months follow-up, N=2221) many patients report subjective improvements of alertness ([gt]50%) and memory ([gt]30%). Clinical studies using a psychometric approach confirmed absence of adverse cognitive effects but failed to reveal cognition enhancement (Dodrill & Morrison 2001; Hoppe et al. 2001). Experimental studies revealed positive (Clark et al. 1999) but also negative (Helmstaedter et al. 2000) VNS memory effects. In a new experimental approach, we tried to more effectively mask the experimental conditions to the patient and to avoid some methodological shortcomings of former studies.
A computer-based task battery on memory (word/figure list learning) and alertness (response selection) was administered to a total of 53 adult VNS patients with epilepsy. Clinical VNS conditions were left unchanged. The stimulation computer was individually synchronized to the VNS pulse generator (by a clock) allowing separated analysis for ON and OFF phases as well as adaptation of the individual test procedure to specific stimulation conditions. Memory: Patients were randomly assigned to a group VR/FP in which VNS was delivered during the retention phase in the verbal memory test (VR) but during presentation in the figural learning test (FP) or to group VP/FR (vice versa). This test was optimized for patients under standard cycle (300/30). Alertness: Response selection times were separately analyzed for ON and OFF phases as well as for the left and right hand. This test was optimized for patients under rapid cycle (30/7). In addition, the general cognitive level was estimated (cancellation task, vocabulary). Multivariate ANOVAs were performed.
Memory: The group mean patterns of correct items (free recall) and hits (recognition) was compatible to the hypothesis that VNS during retention is advantageous as compared to VNS during presentation (verbal: VR/FP[gt]VP/FR, figural: VR/FP[lt]VP/FR). However, this interaction was not significant. Furthermore, no differences were obtained in more integrative measures of recognition performance (accuracy = area under ROC-curve). Alertness: Including age as covariate revealed a general significant negative VNS effect on response selection times. More specific positive and negative, partly lateralized VNS effects were revealed depending on specific stimulation cycle and output current conditions.
In general, these findings support the hypothesis of cognitive effects due to peripheral neurostimulation. VNS may affect response selection times, but memory effects could not be confirmed. Effects on stimulus identification and response latency may be explained by VNS effects on the thalamus. However, clinical reports of substantial cognitive benefits cannot be explained by the available experimental data as yet. Unspecific co-effects of mood improvement under VNS on subjective cognitive performance have to be considered.
[Supported by: Cyberonics Inc.]