Brain rhythms of pain

Pain is an integrative phenomenon that results from dynamic interactions between sensory and contextual (i.e., cognitive, emotional, and motivational) processes. In the brain the experience of pain is associated with neuronal oscillations and synchrony at different frequencies. However, an overarching framework for the significance of oscillations for pain remains lacking. Recent concepts relate oscillations at different frequencies to the routing of information flow in the brain and the signaling of predictions and prediction errors. The application of these concepts to pain promises insights into how flexible routing of information flow coordinates diverse processes that merge into the experience of pain. Such insights might have implications for the understanding and treatment of chronic pain

Gamma oscillations in human primary somatosensory cortex reflect pain perception

Pain is a highly subjective sensation of inherent behavioral importance and is therefore expected to receive enhanced processing in relevant brain regions. We show that painful stimuli induce high-frequency oscillations in the electrical activity of the human primary somatosensory cortex. Amplitudes of these pain-induced gamma oscillations were more closely related to the subjective perception of pain than to the objective stimulus attributes. They correlated with participants' ratings of pain and were stronger for laser stimuli that caused pain, compared with the same stimuli when no pain was perceived. These findings indicate that gamma oscillations may represent an important mechanism for processing behaviorally relevant sensory information

PYRO-NN: Python Reconstruction Operators in Neural Networks

Purpose: Recently, several attempts were conducted to transfer deep learning to medical image reconstruction. An increasingly number of publications follow the concept of embedding the CT reconstruction as a known operator into a neural network. However, most of the approaches presented lack an efficient CT reconstruction framework fully integrated into deep learning environments. As a result, many approaches are forced to use workarounds for mathematically unambiguously solvable problems. Methods: PYRO-NN is a generalized framework to embed known operators into the prevalent deep learning framework Tensorflow. The current status includes state-of-the-art parallel-, fan- and cone-beam projectors and back-projectors accelerated with CUDA provided as Tensorflow layers. On top, the framework provides a high level Python API to conduct FBP and iterative reconstruction experiments with data from real CT systems. Results: The framework provides all necessary algorithms and tools to design end-to-end neural network pipelines with integrated CT reconstruction algorithms. The high level Python API allows a simple use of the layers as known from Tensorflow. To demonstrate the capabilities of the layers, the framework comes with three baseline experiments showing a cone-beam short scan FDK reconstruction, a CT reconstruction filter learning setup, and a TV regularized iterative reconstruction. All algorithms and tools are referenced to a scientific publication and are compared to existing non deep learning reconstruction frameworks. The framework is available as open-source software at \url{https://github.com/csyben/PYRO-NN}. Conclusions: PYRO-NN comes with the prevalent deep learning framework Tensorflow and allows to setup end-to-end trainable neural networks in the medical image reconstruction context. We believe that the framework will be a step towards reproducible researchComment: V1: Submitted to Medical Physics, 11 pages, 7 figure

Brain oscillations differentially encode noxious stimulus intensity and pain intensity

Noxious stimuli induce physiological processes which commonly translate into pain. However, under certain conditions, pain intensity can substantially dissociate from stimulus intensity, e.g. during longer-lasting pain in chronic pain syndromes. How stimulus intensity and pain intensity are differentially represented in the human brain is, however, not yet fully understood. We therefore used electroencephalography (EEG) to investigate the cerebral representation of noxious stimulus intensity and pain intensity during 10 min of painful heat stimulation in 39 healthy human participants. Time courses of objective stimulus intensity and subjective pain ratings indicated a dissociation of both measures. EEG data showed that stimulus intensity was encoded by decreases of neuronal oscillations at alpha and beta frequencies in sensorimotor areas. In contrast, pain intensity was encoded by gamma oscillations in the medial prefrontal cortex. Contrasting right versus left hand stimulation revealed that the encoding of stimulus intensity in contralateral sensorimotor areas depended on the stimulation side. In contrast, a conjunction analysis of right and left hand stimulation revealed that the encoding of pain in the medial prefrontal cortex was independent of the side of stimulation. Thus, the translation of noxious stimulus intensity into pain is associated with a change from a spatially specific representation of stimulus intensity by alpha and beta oscillations in sensorimotor areas to a spatially independent representation of pain by gamma oscillations in brain areas related to cognitive and affective-motivational processes. These findings extend the understanding of the brain mechanisms of nociception and pain and their dissociations during longer-lasting pain as a key symptom of chronic pain syndromes

Prefrontal gamma oscillations encode tonic pain in humans

Under physiological conditions, momentary pain serves vital protective functions. Ongoing pain in chronic pain states, on the other hand, is a pathological condition that causes widespread suffering and whose treatment remains unsatisfactory. The brain mechanisms of ongoing pain are largely unknown. In this study, we applied tonic painful heat stimuli of varying degree to healthy human subjects, obtained continuous pain ratings, and recorded electroencephalograms to relate ongoing pain to brain activity. Our results reveal that the subjective perception of tonic pain is selectively encoded by gamma oscillations in the medial prefrontal cortex. We further observed that the encoding of subjective pain intensity experienced by the participants differs fundamentally from that of objective stimulus intensity and from that of brief pain stimuli. These observations point to a role for gamma oscillations in the medial prefrontal cortex in ongoing, tonic pain and thereby extend current concepts of the brain mechanisms of pain to the clinically relevant state of ongoing pain. Furthermore, our approach might help to identify a brain marker of ongoing pain, which may prove useful for the diagnosis and therapy of chronic pain

Dissociable Neural Mechanisms Underlying the Modulation of Pain and Anxiety? An fMRI Pilot Study

The down-regulation of pain through beliefs is commonly discussed as a form of emotion regulation. In line with this interpretation, the analgesic effect has been shown to co-occur with reduced anxiety and increased activity in the ventrolateral prefrontal cortex (VLPFC), which is a key region of emotion regulation. This link between pain and anxiety modulation raises the question whether the two effects are rooted in the same neural mechanism. In this pilot fMRI study, we compared the neural basis of the analgesic and anxiolytic effect of two types of threat modulation: a “behavioral control” paradigm, which involves the ability to terminate a noxious stimulus, and a “safety signaling” paradigm, which involves visual cues that signal the threat (or absence of threat) that a subsequent noxious stimulus might be of unusually high intensity. Analgesia was paralleled by VLPFC activity during behavioral control. Safety signaling engaged elements of the descending pain control system, including the rostral anterior cingulate cortex that showed increased functional connectivity with the periaqueductal gray and VLPFC. Anxiety reduction, in contrast, scaled with dorsolateral prefrontal cortex activation during behavioral control but had no distinct neural signature during safety signaling. Our pilot data therefore suggest that analgesic and anxiolytic effects are instantiated in distinguishable neural mechanisms and differ between distinct stress- and pain-modulatory approaches, supporting the recent notion of multiple pathways subserving top-down modulation of the pain experience. Additional studies in larger cohorts are needed to follow up on these preliminary findings

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

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

Neural oscillations and connectivity characterizing the state of tonic experimental pain in humans

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

No Evidence for Disease History as a Risk Factor for Narcolepsy after A(H1N1)pdm09 Vaccination

OBJECTIVES: To investigate disease history before A(H1N1)pdm09 vaccination as a risk factor for narcolepsy.METHODS: Case-control study in Sweden. Cases included persons referred for a Multiple Sleep Latency Test between 2009 and 2010, identified through diagnostic sleep centres and confirmed through independent review of medical charts. Controls, selected from the total population register, were matched to cases on age, gender, MSLT-referral date and county of residence. Disease history (prescriptions and diagnoses) and vaccination history was collected through telephone interviews and population-based healthcare registers. Conditional logistic regression was used to investigate disease history before A(H1N1)pdm09 vaccination as a risk-factor for narcolepsy.RESULTS: In total, 72 narcolepsy cases and 251 controls were included (range 3-69 years mean19-years). Risk of narcolepsy was increased in individuals with a disease history of nervous system disorders (OR range = 3.6-8.8) and mental and behavioural disorders (OR = 3.8, 95% CI 1.6-8.8) before referral. In a second analysis of vaccinated individuals only, nearly all initial associations were no longer statistically significant and effect sizes were smaller (OR range = 1.3-2.6). A significant effect for antibiotics (OR = 0.4, 95% CI 0.2-0.8) and a marginally significant effect for nervous system disorders was observed. In a third case-only analysis, comparing cases referred before vaccination to those referred after; prescriptions for nervous system disorders (OR = 26.0 95% CI 4.0-170.2) and ADHD (OR = 35.3 95% CI 3.4-369.9) were statistically significant during the vaccination period, suggesting initial associations were due to confounding by indication.CONCLUSION: The findings of this study do not support disease history before A(H1N1)pdm09 vaccination as a risk factor for narcolepsy