Variability and effect sizes of intracranial current source density estimations during pain: Systematic review, experimental findings, and future perspectives.

Pain arises from the integration of sensory and cognitive processes in the brain, resulting in specific patterns of neural oscillations that can be characterized by measuring electrical brain activity. Current source density (CSD) estimation from low-resolution brain electromagnetic tomography (LORETA) and its standardized (sLORETA) and exact (eLORETA) variants, is a common approach to identify the spatiotemporal dynamics of the brain sources in physiological and pathological pain-related conditions. However, there is no consensus on the magnitude and variability of clinically or experimentally relevant effects for CSD estimations. Here, we systematically examined reports of sample size calculations and effect size estimations in all studies that included the keywords pain, and LORETA, sLORETA, or eLORETA in Scopus and PubMed. We also assessed the reliability of LORETA CSD estimations during non-painful and painful conditions to estimate hypothetical sample sizes for future experiments using CSD estimations. We found that none of the studies included in the systematic review reported sample size calculations, and less than 20% reported measures of central tendency and dispersion, which are necessary to estimate effect sizes. Based on these data and our experimental results, we determined that sample sizes commonly used in pain studies using CSD estimations are suitable to detect medium and large effect sizes in crossover designs and only large effects in parallel designs. These results provide a comprehensive summary of the effect sizes observed using LORETA in pain research, and this information can be used by clinicians and researchers to improve settings and designs of future pain studies.

Characterization of Source-Localized EEG Activity During Sustained Deep-Tissue Pain.

Musculoskeletal pain is a clinical condition that is characterized by ongoing pain and discomfort in the deep tissues such as muscle, bones, ligaments, nerves, and tendons. In the last decades, it was subject to extensive research due to its high prevalence. Still, a quantitative description of the electrical brain activity during musculoskeletal pain is lacking. This study aimed to characterize intracranial current source density (CSD) estimations during sustained deep-tissue experimental pain. Twenty-three healthy volunteers received three types of tonic stimuli for three minutes each: computer-controlled cuff pressure (1) below pain threshold (sustained deep-tissue no-pain, SDTnP), (2) above pain threshold (sustained deep-tissue pain, SDTP) and (3) vibrotactile stimulation (VT). The CSD in response to these stimuli was calculated in seven regions of interest (ROIs) likely involved in pain processing: contralateral anterior cingulate cortex, contralateral primary somatosensory cortex, bilateral anterior insula, contralateral dorsolateral prefrontal cortex, posterior parietal cortex and contralateral premotor cortex. Results showed that participants exhibited an overall increase in spectral power during SDTP in all seven ROIs compared to both SDTnP and VT, likely reflecting the differences in the salience of these stimuli. Moreover, we observed a difference is CSD due to the type of stimulus, likely reflecting somatosensory discrimination of stimulus intensity. These results describe the different contributions of neural oscillations within these brain regions in the processing of sustained deep-tissue pain.

Accuracy of the Upper Limb Prediction Algorithm PREP2 Applied 2 Weeks Poststroke: A Prospective Longitudinal Study.

BACKGROUND: The Predict Recovery Potential algorithm (PREP2) was developed to predict upper limb (UL) function early after stroke. However, assessment in the acute phase is not always possible. OBJECTIVE: To assess the prognostic accuracy of the PREP2 when applied in a subacute neurorehabilitation setting. METHODS: This prospective longitudinal study included patients ≥18 years old with UL impairment following stroke. Patients were assessed in accordance with the PREP2 approach. However, 2 main components, the shoulder abduction finger extension (SAFE) score and motor-evoked potentials (MEPs) were obtained 2 weeks poststroke. UL function at 3 months was predicted in 1 of 4 categories and compared with the actual outcome at 3 months as assessed by the Action Research Arm Test. The prediction accuracy of the PREP2 was quantified using the correct classification rate (CCR). RESULTS: Ninety-one patients were included. Overall CCR of the PREP2 was 60% (95% CI 50%-71%). Within the 4 categories, CCR ranged from the lowest value at 33% (95% CI 4%-85%) for the category Limited to the highest value at 78% (95% CI 43%-95%) for the category Poor. In the present study, the overall CCR was significantly lower (P < .001) than the 75% reported by the PREP2 developers. CONCLUSIONS: The low overall CCR makes PREP2 obtained 2 weeks poststroke unsuited for clinical implementation. However, PREP2 may be used to predict either excellent UL function in already well-recovered patients or poor UL function in patients with persistent severe UL paresis.

Conditioned pain modulation affects the withdrawal reflex pattern to nociceptive stimulation in humans.

Human studies have repeatedly shown that conditioning pain modulation (CPM) exerts an overall descending inhibitory effect over spinal nociceptive activity. Previous studies have reported a reduction of the nociceptive withdrawal reflex (NWR) under CPM. Still, how descending control influences the muscle activation patterns involved in this protective behavior remains unknown. This study aimed to characterize the effects of CPM on the withdrawal pattern assessed by a muscle synergy analysis of several muscles involved in the lower limb NWR. To trigger descending inhibition, CPM paradigm was applied using the cold-pressor test (CPT) as conditioning stimulus. Sixteen healthy volunteers participated. The NWR was evoked by electrical stimulation on the arch of the foot before, during and after the CPT. Electromyographic (EMG) activity of two proximal (rectus femoris and biceps femoris) and two distal (tibialis anterior and soleus) muscles was recorded. A muscle synergy analysis was performed on the decomposition of the EMG signals, based on a non-negative matrix factorization algorithm. Results showed that two synergies (Module I and II) were sufficient to describe the NWR pattern. Under CPM, Module I activation amplitude was significantly reduced in a narrow time-window interval (118-156 ms) mainly affecting distal muscles, whereas Module II activation amplitude was significantly reduced in a wider time-window interval (150-250 ms), predominantly affecting proximal muscles. These findings suggest that proximal muscles are largely under supraspinal control. The descending inhibitory drive exerted onto the spinal cord may adjust the withdrawal pattern by differential recruitment of the muscles involved in the protective behavior.

Cognitive Processing for Step Precision Increases Beta and Gamma Band Modulation During Overground Walking.

The aim of this study was to investigate whether cognitive processing for defining step precision during walking could induce changes in electrocortical activity. Ten healthy adults (21-36 years) were asked to walk overground in three different conditions: (1) normal walking in a straight path (NW); (2) walking in a pre-defined pathway forcing variation in step width and length by stepping on green marks on the floor (only one color: W1C), and (3) walking in the same pre-defined W1C pathway while evaluating different combinations among the colors green, yellow and red, in which only one color was the footfall target (evaluating two colors: W2C). Walking speed, stride duration and scalp electroencephalography (EEG) were recorded from all conditions. Event-related spectral perturbation was calculated for channels Fz, Cz, C3, C4, Pz and Oz in each condition, which were all time-normalized in relation to the gait cycle. The results showed that walking speed was reduced and stride duration was increased for W2C when compared to both NW and W1C (p < 0.01). Moreover, Event-related spectral perturbation analysis revealed significant changes (p < 0.05) during mid-stance in the frontal lobe and motor/sensorimotor regions, a phase in the gait cycle in which participants define the correct foot placement for the next step. These results suggest that greater cognitive demands during precision stepping influences electrocortical dynamics especially towards step transitions. Therefore, increased electrocortical activity in cognitive, motor and sensorimotor areas may be relevant to produce patterned and safe locomotion through challenging paths.

Psychophysical and Electrophysiological Evidence for Enhanced Pain Facilitation and Unaltered Pain Inhibition in Acute Low Back Pain Patients.

The aim of this case-control study was to examine differences in neural correlates of pain facilitatory and inhibitory mechanisms between acute low back pain (LBP) patients and healthy individuals. Pressure pain tolerance, electrical pain detection thresholds, pain ratings to repetitive suprathreshold electrical stimulation (SES) and conditioned pain modulation (CPM) were assessed in 18 patients with acute LBP and 18 healthy control participants. Furthermore, event-related potentials (ERPs) in response to repetitive SES were obtained from high-density electroencephalography. Results showed that the LBP group presented lower pressure pain tolerance and higher pain ratings to SES compared with the control group. Both groups displayed effective CPM, with no differences in CPM magnitude between groups. Both groups presented similar reductions in ERP amplitudes during CPM, but ERP responses to repetitive SES were significantly larger in the LBP group. In conclusion, acute LBP patients presented enhanced pain facilitatory mechanisms, whereas no significant changes in pain inhibitory mechanisms were observed. These results provide new insight into the central mechanisms underlying acute LBP. PERSPECTIVE: This article present evidence that acute LBP patients show enhanced pain facilitation and unaltered pain inhibition compared with pain-free volunteers. These results provide new insight into the central mechanisms underlying acute LBP.