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Kim JH, Chien JH, Liu CC, Lenz FA. Painful cutaneous laser stimuli induce event-related gamma-band activity in the lateral thalamus of humans. J Neurophysiol 113: 1564 -1573, 2015. First published December 10, 2014 doi:10.1152/jn.00778.2014.-Although the thalamus is an important module in "pain networks," there are few studies of the effect of experimental pain upon thalamic oscillations. We have now examined the hypothesis that, during a series of painful cutaneous laser stimuli, thalamic signals will show stimulus-related gamma-band spectral activity, which is modulated by attention to vs. distraction from the painful stimulus. When the series of laser stimuli was presented, attention was focused by counting the laser stimuli (count laser task), while distraction was produced by counting backward (count back plus laser task). We have studied the effect of a cutaneous laser on thalamic local field potentials and EEG activity during awake procedures (deep brain stimulation implants) for the treatment of essential tremor. At different delays after the stimulus, three low gamma-(30 -50 Hz) and two high gamma-band (70 -90 Hz) activations were observed during the two tasks. Greater high-gamma activation was found during the count laser task for the earlier window, while greater high-gamma activation was found during the count back plus laser task for the later window. Thalamic signals were coherent with EEG signals in the beta band, which indicated significant synchrony. Thalamic cross-frequency coupling analysis indicated that the phase of the lower frequency activity (theta to beta) modulated the amplitude of the higher frequency activity (low and high gamma) more strongly during the count laser task than during the count back plus laser task. This modulation might result in multiplexed signals each encoding a different aspect of pain. attention; thalamus; gamma band oscillations; EEG; human; pain A BROAD RANGE OF EVIDENCE demonstrates the involvement of both the thalamus and the cortex in nociceptive processing (Apkarian et al. 2005;

Animal Models are used extensively in basic epilepsy research. In many studies, there is a need to accurately score and quantify all epileptic spike and wave discharges (SWDs) as captured by electroencephalographic (EEG) recordings. Manual scoring of long term EEG recordings is a time-consuming and tedious task that requires inordinate amount of time of laboratory personnel and an experienced electroencephalographer. In this paper, we adapt a SWD detection algorithm, originally proposed by the authors for absence (petit mal) seizure detection in humans, to detect SWDs appearing in EEG recordings of Fischer 334 rats. The algorithm is robust with respect to the threshold parameters. Results are compared to manual scoring and the effect of different threshold parameters is discussed.

OBJECTIVE Chronic pain results in an enormous societal and financial burden. Opioids are the mainstay of treatment, but opioid abuse has led to an epidemic in the United States. Nonpharmacological treatment strategies like deep brain stimulation could be applied to refractory chronic pain if safe and effective brain targets are identified. The anterior insula is a putative mediator of pain-related affective-motivational and cognitive-evaluative cerebral processing. However, the effect of anterior insula stimulation on pain perception is still unknown. Here, the authors provide behavioral and neurophysiological evidence for stimulating the anterior insula as a means of potential therapeutic intervention for patients with chronic pain. METHODS Six patients with epilepsy in whom intracerebral electrodes had been implanted for seizure localization were recruited to the study. The direct anterior insula stimulations were performed in the inpatient epilepsy monitoring unit while subjects were fully awake, comfortable, and without sedating medications. The effects of anterior insula stimulation were assessed with quantitative sensory testing for heat pain threshold, nociceptive-specific cutaneous laser-evoked potentials, and intracranial electroencephalogram (EEG) recordings. Control stimulation of noninsular brain regions was performed to test stimulation specificity. Sham stimulations, in which no current was delivered, were also performed to control for potential placebo effects. The safety of these stimulations was evaluated by bedside physicians, real-time intracranial EEG monitoring, and electrocardiogram recordings. RESULTS Following anterior insula stimulations, the heat pain threshold of each patient significantly increased from baseline (p < 0.001) and correlated with stimulation intensity (regression analysis: β = 0.5712, standard error 0.070, p < 0.001). Significant changes in ongoing intracranial EEG frequency band powers (p < 0.001), reduction in laser pain intensity, and attenuated laser-evoked potentials were also observed following stimulations. Furthermore, the observed behavioral and neurophysiological effects persisted beyond the stimulations. Subjects were not aware of the stimulations, and there were no cardiovascular or untoward effects. CONCLUSIONS Additional, nonpharmacological therapies are imperative for the future management of chronic pain conditions and to mitigate the ongoing opioid crisis. This study suggests that direct stimulation of the anterior insula can safely alter cerebral pain processing in humans. Further investigation of the anterior insula as a potential target for therapeutic neuromodulation is underway.