High-Frequency (600Hz) SEP Oscillations – Generators and Pathophysiological Aspects

Human median nerve somatosensory evoked potentials (SEP) contain a low-amplitude (<500 nV) high-frequency (˜600Hz) burst of repetitive wavelets (HFOs) which are superimposed onto the primary cortical response 'N20'. The following studies in human subjects are aimed to further clarify the cortical and subcortical structures involved in the generation of the HFOs and the (patho)physiological meaning of this somatosensory oscillatory activity. 1) 128-channel SEP recordings were obtained to right median nerve stimulation and ulnar nerve stimulation. Different source evaluation strategies provided converging evidence for a cortical HFO origin, with two different almost orthogonally oriented generators being active in parallel. The cortical HFO source constellation points to a „precortical“ source in terminals of thalamocortical fibers and a second intracortical HFO origin. Additionally, generation of the HFOs was localized in subcortical, near thalamic and subthalamic source sites. 2) We tested the hypothesis that HFOs might be more sensitive to temporal dispersion caused by demyelinating lesions in multiple sclerosis (MS) than the N20. HFOs in median nerve SEPs in 50 patients with definite MS and in 30 healthy controls were recorded. Three patterns of SEP alterations were found: (i) abolished HFOs with either normal (11% of stimulated limbs), or delayed N20 (16%); (ii) an attenuation of N20 amplitude with preserved HFOs (13%); and (iii) a mixture of both patterns (21%). The first pattern -normal N20 with abolished HFOs- indicates that the HFOs are a sensitive marker of slight demyelination. The second pattern is suggestive of a mainly axonal lesion type, while the third pattern points to a combined axonal/demyelinating process or a conduction block. Analysis of HFOs allows identification of slight demyelinating processes in MS patients in whom the N20 SEP component remains unaffected. 3) The behavior of HFOs in a cohort of schizophrenic patients in comparison to an age- and sex-matched group of controls was tested. HFOs in the group of patients showed a delayed latency. In the low frequency part of the SEPs an increase in amplitude was found. These results are interpreted as a lack of somatosensory inhibition in the somatosensory pathway, either on a thalamic or a cortical level. HFOs are an interesting tool to explore functionality and pathophysiology of the lemniscal system, especially of dysfunctions in thalamocortical impulse propagation.