Original ReportMoving Toward Conscious Pain Processing Detection in Chronic Disorders of Consciousness: Anterior Cingulate Cortex Neuromodulation

- γ-Band oscillatory activity (γBO) in the anterior cingulate cortex (ACC) and the centroparietal areas could have a key role in pain processing.
- The modulation of γBO by repetitive transcranial magnetic stimulation (rTMS) of part of the ACC may express the preservation of frontoparietal output related to pain processing in patients with chronic disorders of consciousness.
- We showed modulation of γBO after ACC-rTMS in patients in a minimally conscious state and with unresponsive wakefulness syndrome (UWS).
- This may suggest partial preservation of the frontoparietal network underlying consciousness processes even in some patients with UWS (namely, functional locked-in syndrome).

It has been assumed that patients with chronic disorders of consciousness (DOC) do not feel pain, but it is possible that some of them just cannot report it. Modulation of γ-band oscillatory activity (γBO) in centroparietal areas (considered as a marker of either subjective pain perception processes or pain-related motor behavior preparation) by part of the anterior cingulate cortex (ACC) has been proposed to be suggestive of conscious pain perception and could therefore be used to assess the maintenance of some level of conscious pain perception in patients with DOC. Hence, we used a repetitive transcranial magnetic stimulation (rTMS) approach in an attempt to trigger frontoparietal output. We enrolled 10 healthy participants (HC), 10 patients in a minimally conscious state (MCS), and 10 with unresponsive wakefulness syndrome (UWS), who underwent a 1-Hz rTMS protocol over ACC. Before and after the neurostimulation paradigm, we measured the pain-rating assessment (pVAS), γBO, latency, and the amplitude of cortical nociceptive potentials evoked by transcutaneous electric sinusoidal stimuli (EEP). In all the HC and MCS and in 2 of the UWS subjects, rTMS increased γBO and reduced the EEP amplitude, whereas pVAS scoring improved in the HC. Our findings provide some evidence about conscious pain processing even in patients with severe DOC and show that rTMS over ACC may be a useful approach to better investigate the level of conscious impairment.PerspectivePatients with DOC may not be able to respond to pain stimuli, although they may feel it. The possibility of detecting residual pain perceptions by means of a noninvasive neuromodulation paradigm, studying the correlation between the ACC and centroparietal γBO, may help clinicians to better assess pain in such individuals.