Gamma Band Oscillations Reflect Sensory and Affective Dimensions of Pain

Pain is a multidimensional process, which can be modulated by emotions; however, the mechanisms underlying this modulation are unknown. We used pictures with different emotional valence (negative, positive, and neutral) as primes and applied electrical painful stimuli as targets to healthy participants. We assessed pain intensity and unpleasantness ratings and recorded electroencephalograms (EEGs). We found that pain unpleasantness and not pain intensity ratings were modulated by emotion, with increased ratings for negative and decreased ratings for positive pictures. We also found two consecutive gamma band oscillations (GBOs) related to pain processing from time frequency analyses of the EEG signals. The early GBO had a cortical distribution contralateral to the painful stimulus and its amplitude was positively correlated with intensity and unpleasantness ratings, but not with prime valence. The late GBO had a centroparietal distribution and its amplitude was larger for negative compared to neutral and positive pictures. The emotional modulation effect (negative vs. positive) of the late GBO amplitude was positively correlated with pain unpleasantness. The early GBO might reflect the overall pain perception, possibly involving the thalamocortical circuit, while the late GBO might be related to the affective dimension of pain and top-down-related processes.

Conditioned Excitation And Inhibition of Short Latency Gamma Band Oscillations In Early Visual Cortex During Fear Learning In Humans

Over the course of evolution the human brain has been shaped to prioritize cues that signal potential danger. Thereby, the brain does not only favor specie-specific prepared stimulus sets such as snakes or spiders, but can learn associations between new cues and aversive outcomes. One important mechanism to achieve this is associated with learning induced plasticity changes in sensory cortex that optimizes the representation of motivationally relevant sensory stimuli. Animal studies have shown that the modulation of gamma band oscillations predicts cholinergic driven plasticity changes in sensory cortices shifting neurons’ responses to fear relevant features as acquired by Pavlovian fear conditioning. Here, we report conditioned excitatory and inhibitory gamma band modulations in humans during fear conditioning of orthogonally oriented sinus gratings representing fear relevant and irrelevant conditioned cues, respectively. Thereby, pairing of a sinus grating with an aversive loud noise not only increased short latency (during the first 180 ms) evoked visual gamma band responses, but was also accompanied by strong gamma power reductions for the fear irrelevant control grating. The current findings will be discussed in the light of recent neurobiological models of cholinergic driven plasticity changes in sensory cortices and classic learning models such as the Rescorla-Wagner framework.

Glycine attenuates impairments of stimulus-evoked gamma oscillation in the ketamine model of schizophrenia

Although a substantial number of studies suggests some clinical benefit concerning negative symptoms in schizophrenia through the modulation of NMDA-receptor function, none of these approaches achieved clinical approval. Given the large body of evidence concerning glutamatergic dysfunction in a subgroup of patients, biomarkers to identify those with a relevant clinical benefit through glutamatergic modulation are urgently needed. A similar reduction of the early auditory evoked gamma-band response (aeGBR) as found in schizophrenia patients can be observed in healthy subjects in the ketamine-model, which addresses the putative excitation / inhibition (E/I) imbalance of the diseases. Moreover, this change in gamma-band oscillations can be related to the emergence of negative symptoms. Accordingly, this study investigated whether glycine-related increases of the aeGBR accompany an improvement concerning negative symptoms in the ketamine-model. The impact of subanesthetic ketamine doses and the pretreatment with glycine was examined in twenty-four healthy male participants while performing a cognitively demanding aeGBR paradigm with 64-channel electroencephalography. Negative Symptoms were assessed through the Positive and Negative Syndrome Scale (PANSS). Ketamine alone caused a reduction of the aeGBR amplitude associated with more pronounced negative symptoms compared to placebo. Pretreatment with glycine attenuated both, the ketamine-induced alterations of the aeGBR amplitude and the increased PANSS negative scores in glycine-responders, classified based on relative aeGBR increase. Thus, we propose that the aeGBR represents a possible biomarker for negative symptoms in schizophrenia related to insufficient glutamatergic neurotransmission. This would allow to identify patients with negative symptoms, who might benefit from glutamatergic treatment.

The Prediction of Acute Postoperative Pain Based on Neural Oscillations Measured before the Surgery

Even with an improved understanding of pain mechanisms and advances in perioperative pain management, inadequately controlled postoperative pain remains. Predicting acute postoperative pain based on presurgery physiological measures could provide valuable insights into individualized, effective analgesic strategies, thus helping improve the analgesic efficacy. Considering the strong correlation between pain perception and neural oscillations, we hypothesize that acute postoperative pain could be predicted by neural oscillations measured shortly before the surgery. Here, we explored the relationship between neural oscillations 2 hours before the thoracoscopic surgery and the subjective intensity of acute postoperative pain. The spectral power density of resting-state beta and gamma band oscillations at the frontocentral region was significantly different between patients with different levels of acute postoperative pain (i.e., low pain vs. moderate/high pain). A positive correlation was also observed between the spectral power density of resting-state beta and gamma band oscillations and subjective reports of postoperative pain. Then, we predicted the level of acute postoperative pain based on features of neural oscillations using machine learning techniques, which achieved a prediction accuracy of 92.54% and a correlation coefficient between the real pain intensities and the predicted pain intensities of 0.84. Altogether, the prediction of acute postoperative pain based on neural oscillations measured before the surgery is feasible and could meet the clinical needs in the future for better control of postoperative pain and other unwanted negative effects. The study was registered on the Clinical Trial Registry (https://clinicaltrials.gov/ct2/show/NCT03761576?term=NCT03761576&draw=2&rank=1) with the registration number NCT03761576.

A Role for Somatostatin-Positive Interneurons in Neuro-Oscillatory and Information Processing Deficits in Schizophrenia

Alterations in neocortical GABAergic interneurons (INs) have been affiliated with neuropsychiatric diseases, including schizophrenia (SZ). Significant progress has been made linking the function of a specific subtype of GABAergic cells, parvalbumin (PV) positive INs, to altered gamma-band oscillations, which, in turn, underlie perceptual and feedforward information processing in cortical circuits. Here, we review a smaller but growing volume of literature focusing on a separate subtype of neocortical GABAergic INs, somatostatin (SST) positive INs. Despite sharing similar neurodevelopmental origins, SSTs exhibit distinct morphology and physiology from PVs. Like PVs, SSTs are altered in postmortem brain samples from multiple neocortical regions in SZ, although basic and translational research into consequences of SST dysfunction has been relatively sparse. We highlight a growing body of work in rodents, which now indicates that SSTs may also underlie specific aspects of cortical circuit function, namely low-frequency oscillations, disinhibition, and mediation of cortico-cortical feedback. SSTs may thereby support the coordination of local cortical information processing with more global spatial, temporal, and behavioral context, including predictive coding and working memory. These functions are notably deficient in some cases of SZ, as well as other neuropsychiatric disorders, emphasizing the importance of focusing on SSTs in future translational studies. Finally, we highlight the challenges that remain, including subtypes within the SST class.

Insular responses to transient painful and non-painful thermal and mechanical spinothalamic stimuli recorded using intracerebral EEG

Brief thermo-nociceptive stimuli elicit low-frequency phase-locked local field potentials (LFPs) and high-frequency gamma-band oscillations (GBOs) in the human insula. Although neither of these responses constitute a direct correlate of pain perception, previous findings suggest that insular GBOs may be strongly related to the activation of the spinothalamic system and/or to the processing of thermal information. To disentangle these different features of the stimulation, we compared the insular responses to brief painful thermonociceptive stimuli, non-painful cool stimuli, mechano-nociceptive stimuli, and innocuous vibrotactile stimuli, recorded using intracerebral electroencephalograpic activity in 7 epileptic patients (9 depth electrodes, 58 insular contacts). All four types of stimuli elicited consistent low-frequency phase-locked LFPs throughout the insula, possibly reflecting supramodal activity. The latencies of thermo-nociceptive and cool low-frequency phase-locked LFPs were shorter in the posterior insula compared to the anterior insula, suggesting a similar processing of thermal input initiating in the posterior insula, regardless of whether the input produces pain and regardless of thermal modality. In contrast, only thermo-nociceptive stimuli elicited an enhancement of insular GBOs, suggesting that these activities are not simply related to the activation of the spinothalamic system or to the conveyance of thermal information.

Early gamma-oscillations as correlate of localized nociceptive processing in primary sensorimotor cortex

Gamma-band oscillations show hand-foot somatotopy compatible with generation in primary sensorimotor cortex and are present following nociceptive but not tactile stimulation of the hand and foot in humans.