Neurological disorders strike millions of people worldwide. A number of these varied disorders are associated with the important attribute of thalamocortical dysrhythmia, which is produced by abnormal oscillatory activity in the major neural circuit that links the brain’s thalamus and cortex. In certain of the main neuropsychiatric disorders, Llinas describes the neurophysiologic state of thalamocortical dysrhytmia as:
- Hyperpolarization through disfacilitation and/or overinhibition of thalamic relay and/or reticular cells by the disease source. In psychotic disorders, such a source anomaly may be found in the paralimbic cortical domain or in the paralimbic striatum, the cortical anomaly providing corticothalamic disfacilitation, the striatal one pallidothalamic overinhibition. The possibility of the alternative triggering of a neuropsychiatric disorder by a chronic dysfunction of the cognitive network (comprising conceptual, emotional, mnestic and attentional functions) is discussed below.
- This hyperpolarized state is the source of calcium T-channel deinactivation causing the production of low threshold calcium spike (LTS) bursts by thalamic and/or reticular neurons.
- Neurons in such a state impose a slow rhythmicity to the thalamocortical loops they are part of, being locked in the theta low frequency domain by their ionic properties. Recurrent divergent corticothalamic and reticulothalamic projections back to the thalamus provide the necessary coherent diffusion of these frequencies to various related cortical areas. Our MEG recordings indeed demonstrate increased theta power. Its existence has also been revealed by EEG studies and may be directly correlated with cortical and thalamic hypometabolism in PET studies.
- The final step in the description of this syndrome is the proposed existence of an activation of high frequency (beta and gamma) cortical domains due to an asymmetrical corticocortical GABAergic collateral inhibition. The proposed mechanism, an “edge effect” as observed in the retina due to lateral inhibition, would result from the asymmetrical inhibition between a low frequency cortical area and neighboring high frequency domains, providing a ring of reduced inhibition onto, and thus activation of, the cortex surrounding this low frequency area. Our coherence studies support the proposition of such an “edge effect” as evidenced by an increased multifrequency coherence between theta and beta domains, an event seen with much less prominence in the normal brain. This activation of high frequency areas might express itself through abnormal EEG spiking activity, as demonstrated in psychotic patients.”
In pain, Sherman describes the process as “a pathophysiological chain reaction at the origin of neurogenic pain. It consists of:
- a reduction of excitatory inputs onto thalamic cells, which results in cell membrane hyperpolarization;
- the production of low-threshold calcium spike bursts by deinactivation of calcium T-channels, discharging at low (theta) frequency;
- a progressive increase of the number of thalamocortical modules discharging at theta frequency; and
- a cortical high frequency activation through asymmetric corticocortical inhibition. These events have been documented by thalamic and cortical recordings in patients suffering from peripheral and central neurogenic pain. “
