Pain is a complex phenomenon involving perceptual, motor, and autonomic responses, but how the brain translates noxious stimuli into these different dimensions of pain is unclear. Here, we assessed ...perceptual, motor, and autonomic responses to brief noxious heat stimuli and recorded brain activity using electroencephalography (EEG) in humans. Multilevel mediation analysis reveals that each pain dimension is subserved by a distinct pattern of EEG responses and, conversely, that each EEG response differentially contributes to the different dimensions of pain. In particular, the translation of noxious stimuli into autonomic and motor responses involved the earliest N1 wave, whereas pain perception was mediated by later N2 and P2 waves. Gamma oscillations mediated motor responses rather than pain perception. These findings represent progress towards a mechanistic understanding of the brain processes translating noxious stimuli into pain and suggest that perceptual, motor, and autonomic dimensions of pain are partially independent rather than serial processes.
Chronic pain is a major health care problem. A better mechanistic understanding and new treatment approaches are urgently needed. In the brain, pain has been associated with neural oscillations at ...alpha and gamma frequencies, which can be targeted using transcranial alternating current stimulation (tACS). Thus, we investigated the potential of tACS to modulate pain and pain-related autonomic activity in an experimental model of chronic pain in 29 healthy participants. In 6 recording sessions, participants completed a tonic heat pain paradigm and simultaneously received tACS over prefrontal or somatosensory cortices at alpha or gamma frequencies or sham tACS. Concurrently, pain ratings and autonomic responses were collected. Using the present setup, tACS did not modulate pain or autonomic responses. Bayesian statistics confirmed a lack of tACS effects in most conditions. The only exception was alpha tACS over somatosensory cortex where evidence was inconclusive. Taken together, we did not find significant tACS effects on tonic experimental pain in healthy humans. Based on our present and previous findings, further studies might apply refined stimulation protocols targeting somatosensory alpha oscillations.
The study protocol was pre-registered at ClinicalTrials.gov (NCT03805854).
Modulating brain oscillations is a promising approach for the treatment of pain. We therefore applied transcranial alternating current stimulation (tACS) to modulate experimental pain in healthy participants. However, tACS did not modulate pain, autonomic responses, or EEG oscillations. These findings help to shape future tACS studies for the treatment of pain.
•Systematic review of potential transdiagnostic EEG-based biomarkers of fatigue.•Increased theta and decreased alpha power in patients with fatigue.•Potential transdiagnostic biomarker and future ...treatment target in fatigue.
Fatigue is a highly prevalent and disabling symptom of many disorders and syndromes, resulting from different pathomechanisms. However, whether and how different mechanisms converge and result in similar symptomatology is only partially understood, and transdiagnostic biomarkers that could further the diagnosis and treatment of fatigue are lacking. We, therefore, performed a transdiagnostic systematic review (PROSPERO: CRD42022330113) of quantitative resting-state electroencephalography (EEG) and magnetoencephalography (MEG) studies in adult patients suffering from pathological fatigue in different disorders. Studies investigating fatigue in healthy participants were excluded. The risk of bias was assessed using a modified Newcastle-Ottawa Scale. Semi-quantitative data synthesis was conducted using modified albatross plots. After searching MEDLINE, Web of Science Core Collection, and EMBASE, 26 studies were included. Cross-sectional studies revealed increased brain activity at theta frequencies and decreased activity at alpha frequencies as potential diagnostic biomarkers. However, the risk of bias was high in many studies and domains. Together, this transdiagnostic systematic review synthesizes evidence on how resting-state M/EEG might serve as a diagnostic biomarker of pathological fatigue. Beyond, this review might help to guide future M/EEG studies on the development of fatigue biomarkers.
Reliable and objective biomarkers promise to improve the assessment and treatment of chronic pain. Resting-state electroencephalography (EEG) is broadly available, easy to use, and cost efficient ...and, therefore, appealing as a potential biomarker of chronic pain. However, results of EEG studies are heterogeneous. Therefore, we conducted a systematic review (PROSPERO CRD42021272622) of quantitative resting-state EEG and magnetoencephalography (MEG) studies in adult patients with different types of chronic pain. We excluded populations with severe psychiatric or neurologic comorbidity. Risk of bias was assessed using a modified Newcastle-Ottawa Scale. Semiquantitative data synthesis was conducted using modified albatross plots. We included 76 studies after searching MEDLINE, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, and EMBASE. For cross-sectional studies that can serve to develop diagnostic biomarkers, we found higher theta and beta power in patients with chronic pain than in healthy participants. For longitudinal studies, which can yield monitoring and/or predictive biomarkers, we found no clear associations of pain relief with M/EEG measures. Similarly, descriptive studies that can yield diagnostic or monitoring biomarkers showed no clear correlations of pain intensity with M/EEG measures. Risk of bias was high in many studies and domains. Together, this systematic review synthesizes evidence on how resting-state M/EEG might serve as a diagnostic biomarker of chronic pain. Beyond, this review might help to guide future M/EEG studies on the development of pain biomarkers.
Biomarker discovery in neurological and psychiatric disorders critically depends on reproducible and transparent methods applied to large-scale datasets. Electroencephalography (EEG) is a promising ...tool for identifying biomarkers. However, recording, preprocessing, and analysis of EEG data is time-consuming and researcher-dependent. Therefore, we developed DISCOVER-EEG, an open and fully automated pipeline that enables easy and fast preprocessing, analysis, and visualization of resting state EEG data. Data in the Brain Imaging Data Structure (BIDS) standard are automatically preprocessed, and physiologically meaningful features of brain function (including oscillatory power, connectivity, and network characteristics) are extracted and visualized using two open-source and widely used Matlab toolboxes (EEGLAB and FieldTrip). We tested the pipeline in two large, openly available datasets containing EEG recordings of healthy participants and patients with a psychiatric condition. Additionally, we performed an exploratory analysis that could inspire the development of biomarkers for healthy aging. Thus, the DISCOVER-EEG pipeline facilitates the aggregation, reuse, and analysis of large EEG datasets, promoting open and reproducible research on brain function.
Accumulating evidence suggests that neural oscillations at different frequencies and their synchrony between brain regions play a crucial role in the processing of nociceptive input and the emergence ...of pain. Most findings are limited by their correlative nature, however, which impedes causal inferences.
To move from correlative towards causal evidence, methods that allow to experimentally manipulate oscillatory brain activity are needed.
Transcranial alternating current stimulation (tACS) is a noninvasive brain stimulation technique designed to modulate neural oscillations in a frequency specific manner and as such a suitable method to investigate the contribution of oscillatory brain activity to pain. Despite its appeal, tACS has been barely applied in the field of pain research. In the present review, we address this issue and discuss how tACS can be used to gather mechanistic evidence for the relationship between pain and neural oscillations in humans.
Transcranial alternating current stimulation holds great potential for the investigation of the neural mechanisms underlying pain and the development of new treatment approaches for chronic pain if necessary methodological precautions are taken.
Several million subclavian-vein catheters are placed in patients each year in the United States to enable care givers to administer chemotherapy, total parenteral nutrition, or long-term antibiotics ...or to manage perioperative fluids. Subclavian venipuncture requires the position of a deep vein to be identified with only surface landmarks. The precise location of the vein is not known, and it is usually impossible to detect a vascular occlusion or anomaly.
Subclavian venipuncture is often a successful and uncomplicated procedure. Reported complication rates range from 0.3 to 12 percent, according to the experience of the physician and the definition of complications.
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Chronic pain is a common and severely disabling disease whose treatment is often unsatisfactory. Insights into the brain mechanisms of chronic pain promise to advance the understanding of the ...underlying pathophysiology and might help to develop disease markers and novel treatments. Here, we systematically exploited the potential of electroencephalography to determine abnormalities of brain function during the resting state in chronic pain. To this end, we performed state-of-the-art analyses of oscillatory brain activity, brain connectivity, and brain networks in 101 patients of either sex suffering from chronic pain. The results show that global and local measures of brain activity did not differ between chronic pain patients and a healthy control group. However, we observed significantly increased connectivity at theta (4-8 Hz) and gamma (>60 Hz) frequencies in frontal brain areas as well as global network reorganization at gamma frequencies in chronic pain patients. Furthermore, a machine learning algorithm could differentiate between patients and healthy controls with an above-chance accuracy of 57%, mostly based on frontal connectivity. These results suggest that increased theta and gamma synchrony in frontal brain areas are involved in the pathophysiology of chronic pain. Although substantial challenges concerning the reproducibility of the findings and the accuracy, specificity, and validity of potential electroencephalography-based disease markers remain to be overcome, our study indicates that abnormal frontal synchrony at theta and gamma frequencies might be promising targets for noninvasive brain stimulation and/or neurofeedback approaches.
The perception of pain is shaped by somatosensory information about threat. However, pain is also influenced by an individual's expectations. Such expectations can result in clinically relevant ...modulations and abnormalities of pain. In the brain, sensory information, expectations (predictions), and discrepancies thereof (prediction errors) are signaled by an extended network of brain areas which generate evoked potentials and oscillatory responses at different latencies and frequencies. However, a comprehensive picture of how evoked and oscillatory brain responses signal sensory information, predictions, and prediction errors in the processing of pain is lacking so far. Here, we therefore applied brief painful stimuli to 48 healthy human participants and independently modulated sensory information (stimulus intensity) and expectations of pain intensity while measuring brain activity using electroencephalography (EEG). Pain ratings confirmed that pain intensity was shaped by both sensory information and expectations. In contrast, Bayesian analyses revealed that stimulus-induced EEG responses at different latencies (the N1, N2, and P2 components) and frequencies (alpha, beta, and gamma oscillations) were shaped by sensory information but not by expectations. Expectations, however, shaped alpha and beta oscillations before the painful stimuli. These findings indicate that commonly analyzed EEG responses to painful stimuli are more involved in signaling sensory information than in signaling expectations or mismatches of sensory information and expectations. Moreover, they indicate that the effects of expectations on pain are served by brain mechanisms which differ from those conveying effects of sensory information on pain.
Pain is a complex phenomenon that is served by neural oscillations and connectivity involving different brain areas and frequencies. Here, we aimed to systematically and comprehensively assess the ...pattern of neural oscillations and connectivity characterizing the state of tonic experimental pain in humans. To this end, we applied 10‐min heat pain stimuli consecutively to the right and left hand of 39 healthy participants and recorded electroencephalography. We systematically analyzed global and local measures of oscillatory brain activity, connectivity, and graph theory‐based network measures during tonic pain and compared them to a nonpainful control condition. Local measures showed suppressions of oscillatory activity at alpha frequencies together with stronger connectivity at alpha and beta frequencies in sensorimotor areas during tonic pain. Furthermore, sensorimotor areas contralateral to stimulation showed significantly increased connectivity to a common area in the medial prefrontal cortex at alpha frequencies. Together, these observations indicate that the state of tonic experimental pain is associated with a sensorimotor‐prefrontal network connected at alpha frequencies. These findings represent a step further toward understanding the brain mechanisms underlying long‐lasting pain states in health and disease.
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