Thalamocortical dysrhythmia (TCD) has been proposed by Rodolfo Llinas as a common pathophysiological mechanism for neurogenic pain, tinnitus, Parkinson's disease, epilepsy and depression. This is based on spontaneous magnetoencephalographic activity in awake patients suffering from these clinical entities. TCD is characterized by increased low-frequency theta rhythmicity, in conjunction with a widespread and marked increase of coherence among gamma and theta oscillations. This coherent thalamocortical theta activity is due to the generation of low-threshold calcium spike bursts by thalamic cells, as confirmed by intraoperative thalamic recordings in patients with pain, Parkinson’s disease,  tinnitus, epilepsy and major depression . Thalamocortical dysrhythmia is based on the concept that the thalamus and cortex are interconnected and act in a coherent way. In the sleeping state the thalamus oscillates at theta frequencies 4-7 Hz (and 1-3 Hz during slow wave sleep), in the resting awake state the thalamus oscillates around 10 Hz, driving the cortex to oscillate at the same rate. When sensory stimuli are presented the thalamocortical rhythm becomes activated and increases its oscillation rate to approximately 40 Hz or gamma band activity. However in a deafferented state the oscillation rate in the thalamocortical columns slows down in the awake state to 4-7 Hz, decreasing lateral inhibition, with a resultant halo of gamma band activity, known as the edge effect. It is hypothesized that this spontaneous and constant gamma band hyperactivity generates the positive symptoms of the clinical entities involved.

Tinnitus based on the concept of thalamocortical dysrhythmia auditory cortex stimulation with transcranial magnetic stimulation and implanted electrodes overlying the auditory cortex have been performed, in an attempt to suppress the pathological theta-gamma dysrhythmia. This dysrhythmia can be visualized using magnetoencephalographie, EEG, and fMRI, as the BOLD signal correlates with gamma band activity.

Pain: a similar approach has been developed for deafferentation pain also using transcranial magnetic stimulation and implanted electrodes overlying the somatosensory cortex.

Obsessive compulsive spectrum disorder is a family of disorders with phenomenological similarities with OCD, either obsessive or compulsive behaviour. The different pathologies also demonstrate similar evolutions in the illness pattern, comorbidities and family history patterns. But also biological abnormalities and treatment responses are similar to OCD. Cluster analysis has created 3 subgroups: 1. reward deficiency syndrome, including trichotillomania, Tourette's disorder, pathological gambling, and hypersexual disorder, 2. impulsivity cluster, including compulsive shopping, kleptomania, eating disorders, self-injury, and intermittent explosive disorder, and 3. somatic cluster, including body dysmorphic disorder and hypochondriasis. Since many of these conditions also demonstrate mood changes, it has been hypothesized that the OCD spectrum disorder family may belong to the larger family of affective spectrum disorder. If many disorders are potentially linked by common pathophysiological mechanisms as proposed by thalamocortical dysrhythmia and OCSD then similar methods of neuromodulation could be beneficial for these clusters of disorders. It is BRAI²N’s aim to explore the therapeutic neuromodulation approaches that might be commonly beneficial for each cluster of disorders, developing treatments where few other treatments are helpful.

Morality and religion: using functional imaging research on morality and self-perception BRAI²N also starts research on the mechanisms of morality and religion, in collaboration with the Moral Brain group (www.themoralbrain.be). A theoretical concept on the possible applications of neuromodulation for morality dysfunction has been proposed (PDF). A first study is also initiated to develop a validated picture set to study the neurobiology of religion scientificly, first by describing the ‘religion network(s)’, and subsequently by modulating the hubs to extract the causal relationships of the functional correlations.