Spontaneous magnetoencephalographic activity was recorded in awake, healthy human controls and in patients suffering from neurogenic pain, tinnitus, Parkinson's disease, or depression. Compared with controls, patients showed increased low-frequency rhythmicity, in conjunction with a widespread and marked increase of coherence among high-and low-frequency oscillations. These data indicate the presence of a thalamocortical dysrhythmia, which we propose is responsible for all the above mentioned conditions. This coherent activity, the result of a resonant interaction between thalamus and cortex, is due to the generation of lowthreshold calcium spike bursts by thalamic cells. The presence of these bursts is directly related to thalamic cell hyperpolarization, brought about by either excess inhibition or disfacilitation. The emergence of positive clinical symptoms is viewed as resulting from ectopic ␥-band activation, which we refer to as the ''edge effect.'' This effect is observable as increased coherence between low-and high-frequency oscillations, probably resulting from inhibitory asymmetry between high-and low-frequency thalamocortical modules at the cortical level.edge effect ͉ activity ͉ ␥ activity ͉ humans
To improve anatomical definition and stereotactic precision of thalamic targets in neurosurgical treatments of chronic functional disorders, a new atlas of the human thalamus has been developed. This atlas is based on multiarchitectonic parcellation in sections parallel or perpendicular to the standard intercommissural reference plane. The calcium-binding proteins parvalbumin (PV), calbindin D-28K (CB), and calretinin (CR) were used as neurochemical markers to further characterize thalamic nuclei and delimit subterritories of functional significance for stereotactic explorations. Their overall distribution reveals a subcompartmentalization of thalamic nuclei into several groups. Predominant PV immunostaining characterizes primary somatosensory, visual and auditory nuclei, the ventral lateral posterior nucleus, reticular nucleus (R), and to a lesser degree also, lateral part of the centre median nucleus, and anterior, lateral, and inferior divisions of the pulvinar complex. In contrast, CB immunoreactivity is prevalent in medial thalamic nuclei (intralaminar and midline), the posterior complex, ventral posterior inferior nucleus, the ventral lateral anterior nucleus, ventral anterior, and ventral medial nuclei. The complementary distributions of PV and CB appear to correlate with distinct lemniscal and spinothalamic somatosensory pathways and to cerebellar and pallidal motor territories, respectively. Calretinin, while overlapping with CB in medial thalamic territories, is also expressed in R and limbic associated anterior group nuclei that contain little or no CB. Preliminary analysis indicates that interindividual nuclear variations cannot easily be taken into account by standardization procedures. Nevertheless, some corrections in antero-posterior coordinates in relation to different intercommissural distances are proposed.
To study the mechanisms of chronic neurogenic pain, we compared the power spectra of the resting EEG of patients (n = 15, 38-75 years, median 64 years, 6 women) and healthy controls (n = 15, 41-71 years, median 60 years, 8 women). On an average, the patient group exhibited higher spectral power over the frequency range of 2-25 Hz, and the dominant peak was shifted towards lower frequencies. Maximal differences appeared in the 7-9 Hz band in all electrodes. Frontal electrodes contributed most to this difference in the 13-15 Hz band. Bicoherence analysis suggests an enhanced coupling between theta (4-9 Hz) and beta (12-25 Hz) frequencies in patients. The subgroup of six patients free from centrally acting medication showed higher spectral power in the 2-18 Hz frequency range. On an individual basis, the combination of peak height and peak frequency discriminated between patient and control groups: discriminant analysis classified 87% of all subjects correctly. After a therapeutic lesion in the thalamus (central lateral thalamotomy, CLT) we carried out follow-up for a subgroup of seven patients. Median pain relief was 70 and 95% after 3 and 12 months, respectively. The average EEG power of all seven patients gradually decreased in the theta band and approached normal values only after 12 months. The excess theta EEG power in patients and its decrease after thalamic surgery suggests that both EEG and neurogenic pain are determined by tightly coupled thalamocortical loops. The small therapeutic CLT lesion is thought to initiate a progressive normalization in the affected thalamocortical system, which is reflected in both decrease of EEG power and pain relief.
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