Gamma-Band Oscillations Preferential for Nociception can be Recorded in the Human Insula

Abstract

Transient nociceptive stimuli elicit robust phase-locked local field potentials (LFPs) in the human insula. However, these responses are not preferential for nociception, as they are also elicited by transient non-nociceptive vibrotactile, auditory, and visual stimuli. Here, we investigated whether another feature of insular activity, namely gamma-band oscillations (GBOs), is preferentially observed in response to nociceptive stimuli. Although nociception-evoked GBOs have never been explored in the insula, previous scalp electroencephalography and magnetoencephalography studies suggest that nociceptive stimuli elicit GBOs in other areas such as the primary somatosensory and prefrontal cortices, and that this activity could be closely related to pain perception. Furthermore, tracing studies showed that the insula is a primary target of spinothalamic input. Using depth electrodes implanted in 9 patients investigated for epilepsy, we acquired insular responses to brief thermonociceptive stimuli and similarly arousing non-nociceptive vibrotactile, auditory, and visual stimuli (59 insular sites). As compared with non-nociceptive stimuli, nociceptive stimuli elicited a markedly stronger enhancement of GBOs (150-300 ms poststimulus) at all insular sites, suggesting that this feature of insular activity is preferential for thermonociception. Although this activity was also present in temporal and frontal regions, its magnitude was significantly greater in the insula as compared with these other regions.

Distinct patterns of brain activity mediate perceptual and motor and autonomic responses to noxious stimuli

“…Lastly, our results showed that gamma responses, which likely originate from primary somatosensory 11 , 12 and insular 30 cortex, were significantly involved in translating noxious stimuli into motor responses. At first glance, this observation seems to be at variance with previous evidence showing that gamma responses to noxious stimuli are often 10 – 12 , but not always 10 , 13 , closely related to pain perception.…”

The search for pain biomarkers in the human brain

“…Nevertheless, some studies have suggested that lesions of the insula impair the ability to perceive pain and that direct cortical stimulation of the insula or epileptic activity in the insula can generate pain, although only in rare cases ( Isnard et al , 2011 ; Mazzola et al , 2012 ). Furthermore, intracerebral recordings of local field potentials in the human insula have shown that painful heat stimuli elicit gamma-band oscillations that are not observed in response to similarly salient tactile, auditory or visual stimuli ( Liberati et al , 2018 ) ( Fig. 1 ).…”

“…Similarly, although the insula has been proposed to be strongly involved in pain perception, equally salient nociceptive and non-nociceptive stimuli trigger similar local field potentials (LFPs) recorded directly within the insula ( Liberati et al , 2016 ). Nevertheless, other less prominent features of the sampled activity might be more selective for pain or nociception, as reflected by the selective increase of gamma-band oscillations (GBOs) when painful heat stimuli are presented ( Liberati et al , 2018 ). BOLD = blood-oxygen level-dependent; ER% = event-related change in oscillation amplitude; ERP = event-related potential.…”

Designing Brains for Pain: Human to Mollusc

“…Similar pathways have been demonstrated by neuroimaging studies in humans ( Brooks and Tracey, 2005 ; Omori et al, 2013 ). Human neurophysiological studies have also revealed nociceptive responses within SI, SII, insular and cingulate cortices ( Frot et al, 2001 , 2013 , 2014; Liberati et al, 2017 ). Lesions and electrical stimulation in these cortical regions as well as strokes involving the spinothalamic tract in the internal capsule have together confirmed a role of this cortical network in human pain awareness ( Ballantine et al, 1967 ; Berthier et al, 1988 ; Kim, 1992 ; Cereda et al, 2002 ; Torta et al, 2013 ; Boccard et al, 2014 , 2017 ; Hirayama et al, 2014 ; Russo and Sheth, 2015 ; Agarwal et al, 2016 ; Denis et al, 2016 ; Wang et al, 2017 ).…”