Secondary Somatosensory Cortex Research Articles

P 65 Functional adaptations of the sensorimotor cortex in degenerative cervical myelopathy

Objective: Degenerative Cervical Myelopathy (DCM) shows growing prevalence in industrial nations. However, the surgical decision-making is still challenging due to the lack of sufficiently reliable predictors of disease progression and surgical outcome. Neither the interplay of involved pathomechanisms, nor the effect on neural networks within the central nervous system has been investigated sufficiently, yet. Recently, the compensatory potential of reorganization processes within the cerebrospinal motor network has been discussed (Zdunczyk et al., 2018). Somatosensory impairment as an early but often overlooked symptom of DCM, however, was not in the main focus of research so far. Therefore, we investigated how not only the motor, but also the primary and secondary somatosensory cortex (S1 & S2) adapt in DCM. Methods: A cohort of 18 right-handed participants, consisting of 9 DCM patients (age 56 ± 12 years, 7 male, mean JOA score 13.3 ± 2.3) and 9 age- and gender-matched healthy control subjects (age 57 ± 12 years, 7 male) underwent a fMRI (3T) session using a block design. DCM patients were assessed before and 3 months after surgical decompression. The fMRI procedure consisted i.a. of alternating, passive somatosensory stimulation of the subjects' hands and feet by means of a felt stick. Using MATLAB® 2019a and the SPM12 software package, a ROI-wise analysis of BOLD-response was performed at the group level using a three-way ANOVA, including the factors “group” (patients/controls), “limb” (hand/foot) and “side” (left/right). Results : In both, patients and controls, we found a strongly left-lateralized cortical response in S1 and S2 (p≤0.05, FWE-corrected) regarding the somatosensory stimulation of the right (dominant) hand. However, activation in patients was lower than in healthy control subjects (p≤0.001, uncorrected). Regarding the other task conditions, controls showed significant responses within the somatosensory cortex (p≤0.05, FWE-corrected), including a consistent activation within the ipsilateral S2. In contrast, patients showed only weak activation in S1 (p≤0.001, uncorrected) and a much scarcer involvement of ipsilateral areas. Discussion: Our results imply that DCM patients show reduced cortical responsiveness to peripheral stimuli. The cortical somatosensory representation of the right (preferred) hand seems to be more robust to deviations due to DCM than the representations of the other tested limbs. It remains to be investigated whether clinical impairment is correlated with cortical somatosensory responsiveness and if the alterations outlined above are reversible after surgical decompression. References Zdunczyk A, Schwarzer V, Mikhailov M, Bagley B, Rosenstock T, Picht T, Vajkoczy P. The Corticospinal Reserve Capacity: Reorganization of Motor Area and Excitability As a Novel Pathophysiological Concept in Cervical Myelopathy. Neurosurgery. 2018 Oct 1;83(4):810-818. doi: 10.1093/neuros/nyx437. PMID: 29165642.

NT3 treatment alters spinal cord injury-induced changes in the gray matter volume of rhesus monkey cortex

Spinal cord injury (SCI) may cause structural alterations in brain due to pathophysiological processes, but the effects of SCI treatment on brain have rarely been reported. Here, voxel-based morphometry is employed to investigate the effects of SCI and neurotrophin-3 (NT3) coupled chitosan-induced regeneration on brain and spinal cord structures in rhesus monkeys. Possible association between brain and spinal cord structural alterations is explored. The pain sensitivity and stepping ability of animals are collected to evaluate sensorimotor functional alterations. Compared with SCI, the unique effects of NT3 treatment on brain structure appear in extensive regions which involved in motor control and neuropathic pain, such as right visual cortex, superior parietal lobule, left superior frontal gyrus (SFG), middle frontal gyrus, inferior frontal gyrus, insula, secondary somatosensory cortex, anterior cingulate cortex, and bilateral caudate nucleus. Particularly, the structure of insula is significantly correlated with the pain sensitivity. Regenerative treatment also shows a protective effect on spinal cord structure. The associations between brain and spinal cord structural alterations are observed in right primary somatosensory cortex, SFG, and other regions. These results help further elucidate secondary effects on brain of SCI and provide a basis for evaluating the effects of NT3 treatment on brain structure.

834 Whole-Brain Visualization of Single-Neuron Activity During the Development of Neuropathic Pain

INTRODUCTION: Chronic neuropathic pain is severely disabling and difficult to treat. The pathophysiological mechanisms behind the transition from an acute to chronic neuropathic pain state are not well defined. METHODS: TRAP2 mice are genetically engineered to express tdTomato under dual control of a c-Fos gene promoter and estrogen receptor activation. Seven adult TRAP2 mice underwent unilateral chronic constrictive injury (CCI) of the sciatic nerve, while another six underwent exposure of the nerve without constriction. The mice were administered 4-OHT (to “TRAP” active neurons) one week, three weeks, or six weeks post-injury and maintained for six days before transcardial perfusion. Tissue clarification and confocal imaging/processing allowed for active neuronal populations in distinct brain regions to then be quantified and compared between groups. RESULTS: Allodynia developed in only the CCI groups, as confirmed by paw withdrawal thresholds. Active neuronal populations in the medial thalamus became significantly increased from baseline in all CCI groups. The anterior insula, secondary somatosensory cortex, and lateral parabrachial nucleus demonstrated significantly increased activity from baseline at one week post-injury, but this activity decreased at three and six weeks post-injury. Neuronal activity in the ventral orbital cortex was significantly increased from baseline only at three weeks post-injury, while activity in the anterior nucleus of the periventricular thalamus increased with time and became significantly elevated from baseline at three and six weeks post-injury. CONCLUSIONS: Our model demonstrates a clear increase in the neuronal activity of pain-related medial thalamic and cortical structures in mice who develop a chronic neuropathic pain state. The TRAP model is an ideal method to study brain plasticity during the transition from an acute pain state to chronic pain condition - enhancing our understanding of the mechanisms responsible for central sensitization to chronic neuropathic pain.

Altered spontaneous cortical activity predicts pain perception in individuals with cerebral palsy.

Cerebral palsy is the most common paediatric neurological disorder and results in extensive impairment to the sensorimotor system. However, these individuals also experience increased pain perception, resulting in decreased quality of life. In the present study, we utilized magnetoencephalographic brain imaging to examine whether alterations in spontaneous neural activity predict the level of pain experienced in a cohort of 38 individuals with spastic diplegic cerebral palsy and 67 neurotypical controls. Participants completed 5 min of an eyes closed resting-state paradigm while undergoing a magnetoencephalography recording. The magnetoencephalographic data were then source imaged, and the power within the delta (2–4 Hz), theta (5–7 Hz), alpha (8–12 Hz), beta (15–29 Hz), low gamma (30–59 Hz) and high gamma (60–90 Hz) frequency bands were computed. The resulting power spectral density maps were analysed vertex-wise to identify differences in spontaneous activity between groups. Our findings indicated that spontaneous cortical activity was altered in the participants with cerebral palsy in the delta, alpha, beta, low gamma and high gamma bands across the occipital, frontal and secondary somatosensory cortical areas (all pFWE < 0.05). Furthermore, we also found that the altered beta band spontaneous activity in the secondary somatosensory cortices predicted heightened pain perception in the individuals with cerebral palsy (P = 0.039). Overall, these results demonstrate that spontaneous cortical activity within individuals with cerebral palsy is altered in comparison to their neurotypical peers and may predict increased pain perception in this patient population. Potentially, changes in spontaneous resting-state activity may be utilized to measure the effectiveness of current treatment approaches that are directed at reducing the pain experienced by individuals with cerebral palsy.

Altered activity of pain processing brain regions in association with hip osteoarthritis

Hip osteoarthritis (OA) is characterized by chronic pain, but there remains a mismatch between symptoms and radiological findings. Recently, brain connectivity has been implicated in the modulation of chronic peripheral pain, however its association with perceived pain in hip OA is not understood. We used resting-state functional magnetic resonance imaging (fMRI) to examine functional connectivity associated with pain in hip OA patients. Thirty participants with hip OA and 10 non-OA controls were recruited. Using the visual analogue scale (VAS), pain scores were obtained before and after performing a painful hip activity. All participants underwent 3.0 T resting-state fMRI, and functional connectivity of brain regions associated with pain was determined and compared between participants, and before and after hip activity. Relative to controls, functional connectivity between the secondary somatosensory cortex and left posterior insula was increased, and functional connectivity between the bilateral posterior insula and motor cortices was significantly decreased in hip OA participants. In response to painful hip activity, functional connectivity increased between the thalamus, periaqueductal grey matter and brainstem. Functional connections between brain regions associated with pain are altered in hip OA patients, and several connections are modulated by performing painful activity. Unique lateralization of left posterior insula and linked brain functional connectivity patterns allows assessment of pain perception in hip OA providing an unbiased method to evaluate pain perception and pain modulation strategies.

Structural and Functional Hippocampal Correlations in Environmental Enrichment During the Adolescent to Adulthood Transition in Mice.

Environmental enrichment is known to induce neuronal changes; however, the underlying structural and functional factors involved are not fully known and remain an active area of study. To investigate these factors, we assessed enriched environment (EE) and standard environment (SE) control mice over 30 days using structural and functional MRI methods. Naïve adult male mice (n = 30, ≈20 g, C57BL/B6J, postnatal day 60 initial scan) were divided into SE and EE groups and scanned before and after 30 days. Structural analyses included volumetry based on manual segmentation as well as diffusion tensor imaging (DTI). Functional analyses included seed-based analysis (SBA), independent component analysis (ICA), the amplitude of low-frequency fluctuation (ALFF), and fractional ALFF (fALFF). Structural results indicated that environmental enrichment led to an increase in the volumes of cornu ammonis 1 (CA1) and dentate gyrus. Structural results indicated changes in radial diffusivity and mean diffusivity in the visual cortex and secondary somatosensory cortex after EE. Furthermore, SBA and ICA indicated an increase in resting-state functional MRI (rsfMRI) functional connectivity in the hippocampus. Using parallel structural and functional analyses, we have demonstrated coexistent structural and functional changes in the hippocampal subdivision CA1. Future research should map alterations temporally during environmental enrichment to investigate the initiation of these structural and functional changes.

Ipsilateral Stimulus Encoding in Primary and Secondary Somatosensory Cortex of Awake Mice.

Lateralization is a hallmark of somatosensory processing in the mammalian brain. However, in addition to their contralateral representation, unilateral tactile stimuli also modulate neuronal activity in somatosensory cortices of the ipsilateral hemisphere. The cellular organization and functional role of these ipsilateral stimulus responses in awake somatosensory cortices, especially regarding stimulus coding, are unknown. Here, we targeted silicon probe recordings to the vibrissa region of primary (S1) and secondary (S2) somatosensory cortex of awake head-fixed mice of either sex while delivering ipsilateral and contralateral whisker stimuli. Ipsilateral stimuli drove larger and more reliable responses in S2 than in S1, and activated a larger fraction of stimulus-responsive neurons. Ipsilateral stimulus-responsive neurons were rare in layer 4 of S1, but were located in equal proportion across all layers in S2. Linear classifier analyses further revealed that decoding of the ipsilateral stimulus was more accurate in S2 than S1, whereas S1 decoded contralateral stimuli most accurately. These results reveal substantial encoding of ipsilateral stimuli in S1 and especially S2, consistent with the hypothesis that higher cortical areas may integrate tactile inputs across larger portions of space, spanning both sides of the body.SIGNIFICANCE STATEMENT Tactile information obtained by one side of the body is represented in the activity of neurons of the opposite brain hemisphere. However, unilateral tactile stimulation also modulates neuronal activity in the other, or ipsilateral, brain hemisphere. This ipsilateral activity may play an important role in the representation and processing of tactile information, in particular when the sense of touch involves both sides of the body. Our work in the whisker system of awake mice reveals that neocortical ipsilateral activity, in particular that of deep layer excitatory neurons of secondary somatosensory cortex (S2), contains information about the presence and the velocity of unilateral tactile stimuli, which supports a key role for S2 in integrating tactile information across both body sides.

A Randomized, Sham-Controlled Trial of Repetitive Transcranial Magnetic Stimulation Targeting M1 and S2 in Central Poststroke Pain: A Pilot Trial

ObjectivesCentral poststroke pain (CPSP), a neuropathic pain condition, is difficult to treat. Repetitive transcranial magnetic stimulation (rTMS) targeted to the primary motor cortex (M1) can alleviate the condition, but not all patients respond. We aimed to assess a promising alternative rTMS target, the secondary somatosensory cortex (S2), for CPSP treatment. Materials and MethodsThis prospective, randomized, double-blind, sham-controlled three-arm crossover trial assessed navigated rTMS (nrTMS) targeted to M1 and S2 (10 sessions, 5050 pulses per session at 10 Hz). Participants were evaluated for pain, depression, anxiety, health-related quality of life, upper limb function, and three plasticity-related gene polymorphisms including Dopamine D2 Receptor (DRD2). We monitored pain intensity and interference before and during stimulations and at one month. A conditioned pain modulation test was performed using the cold pressor test. This assessed the efficacy of the descending inhibitory system, which may transmit TMS effects in pain control. ResultsWe prescreened 73 patients, screened 29, and included 21, of whom 17 completed the trial. NrTMS targeted to S2 resulted in long-term (from baseline to one-month follow-up) pain intensity reduction of ≥30% in 18% (3/17) of participants. All stimulations showed a short-term effect on pain (17–20% pain relief), with no difference between M1, S2, or sham stimulations, indicating a strong placebo effect. Only nrTMS targeted to S2 resulted in a significant long-term pain intensity reduction (15% pain relief). The cold pressor test reduced CPSP pain intensity significantly (p = 0.001), indicating functioning descending inhibitory controls. The homozygous DRD2 T/T genotype is associated with the M1 stimulation response. ConclusionsS2 is a promising nrTMS target in the treatment of CPSP. The DRD2 T/T genotype might be a biomarker for M1 nrTMS response, but this needs confirmation from a larger study.

Functional Brain Changes Due to Chronic Abdominal Pain in Inflammatory Bowel Disease: A Case-Control Magnetic Resonance Imaging Study.

INTRODUCTION:Various chronic pain conditions go along with functional and structural brain changes. This study aimed to investigate functional and structural brain changes by magnetic resonance imaging (MRI) in inflammatory bowel disease (IBD) patients with chronic abdominal pain.METHODS:Sixty-four subjects were included in the final analysis (32 IBD patients with chronic abdominal pain; 32 age-matched and sex-matched controls). All patients suffered from chronic abdominal pain, defined as a score of ≥3/10 on the visual analog scale for at least 3 months in the past 6 months. Besides structural MRI, resting state functional MRI was used to compare functional connectivity of 10 networks between groups.RESULTS:Patients with IBD showed no structural brain alterations but a significantly increased resting state functional connectivity of the secondary somatosensory cortex within the salience network.DISCUSSION:Because the secondary somatosensory cortex saves sensory stimuli and compares novel information with latter experiences, these functions may be maladaptive in IBD patients with abdominal pain.

A preliminary investigation of the effects of patellar displacement on brain activation and perceived pain in young females with patellofemoral pain

ObjectivesTo identify the neural substrates of a clinician-based test and associated pain perception in young female athletes with patellofemoral pain. DesignCross-sectional. MethodsFemales with patellofemoral pain (n = 14; 14.3 ± 3.2 years) completed a patella displacement test during brain functional magnetic resonance imaging. The neuroimaging protocol included 18 s of interspersed rest/test blocks during which an experimenter manually applied intermittent frontal plane stress to the patella during test blocks. Patients rated their pain unpleasantness and pain intensity immediately after testing using a visual analog scale. ResultsDuring the patella displacement test, increased activation was observed in previously identified sensorimotor and neural pain regions, including the primary and secondary somatosensory cortices, primary motor cortex, prefrontal cortex, cerebellum, and other cognitive-related brain regions (z's > 4.4, p's < 0.05). Furthermore, pain unpleasantness during the test was positively correlated with increased activation of the posterior cerebellum (z = 4.51, p = 0.02), which is involved in both motor and pain processing as well as cognitive and affective feedback. ConclusionsThese preliminary findings suggest that the posterior cerebellum may represent a critical modulator in the cognitive appraisal of pain in patellofemoral pain through cortico-cerebellar loops, which may have downstream effects on motor function. However further exploration of task-based functional connectivity between the posterior cerebellum and cortical regions is necessary to support these novel findings and associated interpretations.

Axonal and Dendritic Morphology of Excitatory Neurons in Layer 2/3 Mouse Barrel Cortex Imaged Through Whole-Brain Two-Photon Tomography and Registered to a Digital Brain Atlas.

Communication between cortical areas contributes importantly to sensory perception and cognition. On the millisecond time scale, information is signaled from one brain area to another by action potentials propagating across long-range axonal arborizations. Here, we develop and test methodology for imaging and annotating the brain-wide axonal arborizations of individual excitatory layer 2/3 neurons in mouse barrel cortex through single-cell electroporation and two-photon serial section tomography followed by registration to a digital brain atlas. Each neuron had an extensive local axon within the barrel cortex. In addition, individual neurons innervated subsets of secondary somatosensory cortex; primary somatosensory cortex for upper limb, trunk, and lower limb; primary and secondary motor cortex; visual and auditory cortical regions; dorsolateral striatum; and various fiber bundles. In the future, it will be important to assess if the diversity of axonal projections across individual layer 2/3 mouse barrel cortex neurons is accompanied by functional differences in their activity patterns.

Asymmetrical organization of oral structures in the primary and secondary somatosensory cortices in rats: An optical imaging study.

In rodents, the representation of the body surface in the primary somatosensory cortex (S1) forms a mirror image along the ventral border of the S1 in the secondary somatosensory cortex (S2). Sensory information from the oral region is processed in the S1 and the border region between the S2 and insular oral region (IOR). We examined the relationship between somatosensory representations in the S1 and S2/IOR using optical imaging with a voltage-sensitive dye in urethane-anesthetized rats. In reference to the rhinal fissure and middle cerebral artery, we made a somatosensory map by applying electrical or air puff stimulation. The initial neural excitation in the S1 to facial structures, including the eyebrow, cornea, pinna, whisker pad, nasal tip, and nasal mucosa, spread toward the ventral area, putatively the S2. The initial cortical responses in the S1 to oral structures, including the lower lip, tongue, and teeth, were spatially separated from those in the S2/IOR. The representation of the tongue center, tongue tip, mandibular molar pulp, mandibular incisor pulp, and mandibular incisor periodontal ligament were almost linearly arranged from caudal to rostral in both S1 and S2/IOR. The lower lip was represented in the dorsal area from the representation of teeth and tongue in both S1 and S2/IOR. The representations of maxillary teeth were caudal and dorsal to the representations of mandibular teeth in the S1 and S2/IOR, respectively. These results suggest that the representation of oral structures in the S1 formed a non-mirror image, not a mirror image, in the S2/IOR.

Nociceptive Intra-epidermal Electric Stimulation Evokes Steady-State Responses in the Secondary Somatosensory Cortex

Recent studies have established the presence of nociceptive steady-state evoked potentials (SSEPs), generated in response to thermal or intra-epidermal electric stimuli. This study explores cortical sources and generation mechanisms of nociceptive SSEPs in response to intra-epidermal electric stimuli. Our method was to stimulate healthy volunteers (n = 22, all men) with 100 intra-epidermal pulse sequences. Each sequence had a duration of 8.5 s, and consisted of pulses with a pulse rate between 20 and 200 Hz, which was frequency modulated with a multisine waveform of 3, 7 and 13 Hz (n = 10, 1 excluded) or 3 and 7 Hz (n = 12, 1 excluded). As a result, evoked potentials in response to stimulation onset and contralateral SSEPs at 3 and 7 Hz were observed. The SSEPs at 3 and 7 Hz had an average time delay of 137 ms and 143 ms respectively. The evoked potential in response to stimulation onset had a contralateral minimum (N1) at 115 ms and a central maximum (P2) at 300 ms. Sources for the multisine SSEP at 3 and 7 Hz were found through beamforming near the primary and secondary somatosensory cortex. Sources for the N1 were found near the primary and secondary somatosensory cortex. Sources for the N2-P2 were found near the supplementary motor area. Harmonic and intermodulation frequencies in the SSEP power spectrum remained below a detectable level and no evidence for nonlinearity of nociceptive processing, i.e. processing of peripheral firing rate into cortical evoked potentials, was found.

Dynamic causal modeling of sensorimotor networks elicited by saltatory pneumotactile velocity in the glabrous hand.

The effective connectivity of neuronal networks during passive saltatory pneumotactile velocity stimulation to the glabrous hand with different velocities is still unknown. The present study investigated the effectivity connectivity elicited by saltatory pneumotactile velocity arrays placed on the glabrous hand at three velocities (5, 25, and 65 cm/second). Dynamic causal modeling (DCM) was used on functional MRI data sampled from 20 neurotypical adults. Five brain regions, including the left primary somatosensory (SI) and motor (M1) cortices, bilateral secondary somatosensory (SII) cortices, and right cerebellar lobule VI, were used to build model space. Three velocities (5, 25, and 65 cm/second) of saltatory pneumotactile stimuli were processed in both serial and parallel modes within the sensorimotor networks. The medium velocity of 25 cm/second modulated forward interhemispheric connection from the contralateral SII to the ipsilateral SII. Pneumotactile stimulation at the medium velocity of 25 cm/second also influenced contralateral M1 through contralateral SI. Finally, the right cerebellar lobule VI was involved in the sensorimotor networks. Our DCM results suggest the coexistence of both serial and parallel processing for saltatory pneumotactile velocity stimulation. Significant contralateral M1 modulation promotes the prospect that the passive saltatory pneumotactile velocity arrays can be used to design sensorimotor rehabilitation protocols to activate M1. The effective connectivity from the right cerebellar lobule VI to other cortical regions demonstrates the cerebellum's role in the sensorimotor networks through feedforward and feedback neuronal pathways.

Dissection of brain-wide resting-state and functional somatosensory circuits by fMRI with optogenetic silencing

To further advance functional MRI (fMRI)-based brain science, it is critical to dissect fMRI activity at the circuit level. To achieve this goal, we combined brain-wide fMRI with neuronal silencing in well-defined regions. Since focal inactivation suppresses excitatory output to downstream pathways, intact input and suppressed output circuits can be separated. Highly specific cerebral blood volume-weighted fMRI was performed with optogenetic stimulation of local GABAergic neurons in mouse somatosensory regions. Brain-wide spontaneous somatosensory networks were found mostly in ipsilateral cortical and subcortical areas, which differed from the bilateral homotopic connections commonly observed in resting-state fMRI data. The evoked fMRI responses to somatosensory stimulation in regions of the somatosensory network were successfully dissected, allowing the relative contributions of spinothalamic (ST), thalamocortical (TC), corticothalamic (CT), corticocortical (CC) inputs, and local intracortical circuits to be determined. The ventral posterior thalamic nucleus receives ST inputs, while the posterior medial thalamic nucleus receives CT inputs from the primary somatosensory cortex (S1) with TC inputs. The secondary somatosensory cortex (S2) receives mostly direct CC inputs from S1 and a few TC inputs from the ventral posterolateral nucleus. The TC and CC input layers in cortical regions were identified by laminar-specific fMRI responses with a full width at half maximum of <150 µm. Long-range synaptic inputs in cortical areas were amplified approximately twofold by local intracortical circuits, which is consistent with electrophysiological recordings. Overall, whole-brain fMRI with optogenetic inactivation revealed brain-wide, population-based, long-range circuits, which could complement data typically collected in conventional microscopic functional circuit studies.

The role of right supra-marginal gyrus and secondary somatosensory cortex in age-related differences in human emotional egocentricity

Emotional egocentric bias (EEB) occurs when, due to a partial failure in self-other distinction, empathy for another's emotion is influenced by our own emotional state. Recent studies have revealed a higher EEB in children, adolescents and older adults compared to young adults, but the neural correlates of this finding are largely unknown. We asked female participants (N = 95) from three different age groups (adolescents, young and older adults) to perform a well-validated EEB task in an MRI scanner. We assessed task-based changes in activity and effective connectivity as well as morphometric changes in regions of interest to pinpoint functional and structural age-related differences. Results revealed higher EEB in older compared to young adults and adolescents. Connectivity between right supramarginal gyrus (rSMG) and somatosensory cortices acted as a partial mediator between age and EEB. The findings suggest that an intact connectivity of rSMG, rather than its regional activity, with sensory-perceptual brain areas is crucial for overcoming egocentric biases of empathic judgments.

Intrinsic network activity reflects the fluctuating experience of tonic pain.

Although we know sensation is continuous, research on long-lasting and continuously changing stimuli is scarce and the dynamic nature of ongoing cortical processing is largely neglected. In a longitudinal study, 38 participants across four sessions were asked to continuously rate the intensity of an applied tonic heat pain for 20min. Using group-independent component analysis and dual regression, we extracted the subjects' time courses of intrinsic network activity. The relationship between the dynamic fluctuation of network activity with the varying time courses of three pain processing entities was computed: pain intensity, the direction of pain intensity changes, and temperature. We were able to dissociate the spatio-temporal patterns of objective (temperature) and subjective (pain intensity/changes of pain intensity) aspects of pain processing in the human brain. We found two somatosensory networks with distinct functions: one network that encodes the small fluctuations in temperature and consists mainly of bilateral primary somatosensory cortex (SI), and a second right-lateralized network that encodes the intensity of the subjective experience of pain consisting of SI, secondary somatosensory cortex, the posterior cingulate cortex, and the thalamus. We revealed the somatosensory dynamics that build up toward a current subjective percept of pain. The timing suggests a cascade of subsequent processing steps toward the current pain percept.

Tonic, Burst, and Burst-Cycle Spinal Cord Stimulation Lead to Differential Brain Activation Patterns as Detected by Functional Magnetic Resonance Imaging

ObjectiveThe objective of this preclinical study was to examine the responses of the brain to noxious stimulation in the presence and absence of different modes of spinal cord stimulation (SCS) using blood-oxygen-level-dependent functional magnetic resonance imaging (BOLD-fMRI). Materials and MethodsSprague-Dawley rats were randomized to groups based on the mode of SCS delivered which included tonic stimulation (n = 27), burst stimulation (n = 30), and burst-cycle stimulation (n = 29). The control (sham) group (n = 28) received no SCS. The SCS electrode was inserted between T10 and T12 spinal levels prior to fMRI session. The experimental protocol for fMRI acquisition consisted of an initial noxious stimulation phase, a treatment phase wherein the SCS was turned on concurrently with noxious stimulation, and a residual effect phase wherein the noxious stimulation alone was turned on. The responses were statistically analyzed through paired t-test and the results were presented as z-scores for the quantitative analysis of the fMRI data. ResultsThe treatment with different SCS modes attenuated the BOLD brain responses to noxious hindlimb stimulation. The tonic, burst, and burst-cycle SCS treatment attenuated BOLD responses in the caudate putamen (CPu), insula (In), and secondary somatosensory cortex (S2). There was little to no corresponding change in sham control in these three regions. The burst and burst-cycle SCS demonstrated greater attenuation of BOLD signals in CPu, In, and S2 compared to tonic stimulation. ConclusionThe high-resolution fMRI study using a rat model demonstrated the potential of different SCS modes to act on several pain-matrix-related regions of the brain in response to noxious stimulation. The burst and burst-cycle SCS exhibited greater brain activity reduction in response to noxious hindlimb stimulation in the caudate putamen, insula, and secondary somatosensory cortex compared to tonic stimulation.

Cerebral processing of sharp mechanical pain measured with arterial spin labeling.

IntroductionArterial spin labeling (ASL) is a functional neuroimaging technique that has been frequently used to investigate acute pain states. A major advantage of ASL as opposed to blood‐oxygen‐level‐dependent functional neuroimaging is its applicability for low‐frequency designs. As such, ASL represents an interesting option for studies in which repeating an experimental event would reduce its ecological validity. Whereas most ASL pain studies so far have used thermal stimuli, to our knowledge, no ASL study so far has investigated pain responses to sharp mechanical pain.MethodsAs a proof of concept, we investigated whether ASL has the sensitivity to detect brain activation within core areas of the nociceptive network in healthy controls following a single stimulation block based on 96 s of mechanical painful stimulation using a blunt blade.ResultsWe found significant increases in perfusion across many regions of the nociceptive network such as primary and secondary somatosensory cortices, premotor cortex, posterior insula, inferior parietal cortex, parietal operculum, temporal gyrus, temporo‐occipital lobe, putamen, and the cerebellum. Contrary to our hypothesis, we did not find any significant increase within ACC, thalamus, or PFC. Moreover, we were able to detect a significant positive correlation between pain intensity ratings and pain‐induced perfusion increase in the posterior insula.ConclusionWe demonstrate that ASL is suited to investigate acute pain in a single event paradigm, although to detect activation within some regions of the nociceptive network, the sensitivity of our paradigm seemed to be limited. Regarding the posterior insula, our paradigm was sensitive enough to detect a correlation between pain intensity ratings and pain‐induced perfusion increase. Previous experimental pain studies have proposed that intensity coding in this region may be restricted to thermal stimulation. Our result demonstrates that the posterior insula encodes intensity information for mechanical stimuli as well.

The Biology of BDSM: A Systematic Review

BDSM is an abbreviation used to reference the concepts of bondage and discipline, dominance and submission, sadism and masochism, enacted by power exchanges between consensual partners. In recent years, attention has shifted from the idea of BDSM as a pathological and tabooed niche practice towards viewing BDSM as a healthy form of intimacy. This systematic review brings together all existing literature on the biology of BDSM and places it in a broader biological context. A systematic search was conducted on PubMed, Web of Science and PsycARTICLES, of which 10 articles are included and discussed in this systematic review. There is evidence for cortisol changes in submissives as a result of a BDSM interaction, suggesting involvement of the physiological stress system. Endocannabinoid changes implicate the pleasure and reward system. In dominants, this biologically measured pleasure seemed to be dependent on power play rather than pain play. Testosterone and oxytocin are also implicated in BDSM, though their role is less evident. Research into brain region activity patterns related to BDSM interest suggests a role for the parietal operculum and ventral striatum in the context of the pleasure and reward system, the primary and secondary somatosensory cortex in the context of pain perception, empathy-related circuits such as the anterior insula, anterior midcingulate cortex and sensorimotor cortex and the left frontal cortex in the context of social and sexual interactions. Pain thresholds are shown to be higher in submissive individuals and a BDSM interaction may cause pain thresholds to rise in submissives as well. BDSM interactions are complex and influenced by several psychological, social and biological processes. Though research is limited, there is emerging evidence for an interaction between several biological systems involved in these types of interests and activities. This means there is an important role for future research to replicate and supplement current results.