Secondary Somatosensory Cortex Research Articles

Pain-Discriminating Information Decoded From Spatiotemporal Patterns of Hemodynamic Responses Measured by fMRI in the Human Brain.

Functional magnetic resonance imaging (fMRI) has been widely used in studying the neural mechanisms of pain in the human brain, primarily focusing on where in the brain pain-elicited neural activities occur (i.e., the spatial distribution of pain-related brain activities). However, the temporal dynamics of pain-elicited hemodynamic responses (HDRs) measured by fMRI may also contain information specific to pain processing but have been largely neglected. Using high temporal resolution fMRI (TR = 0.8 s) data acquired from 62 healthy participants, in the present study we aimed to test whether pain-distinguishing information could be decoded from the spatial pattern of the temporal dynamics (i.e., the spatiotemporal pattern) of HDRs elicited by painful stimuli. Specifically, the peak latency and the response duration were used to characterize the temporal dynamics of HDRs to painful laser stimuli and non-painful electric stimuli, and then were compared between the two conditions (i.e., pain and no-pain) using a voxel-wise univariate analysis and a multivariate pattern analysis. Furthermore, we also tested whether the two temporal characteristics of pain-elicited HDRs and their spatial patterns were associated with pain-related behaviors. We found that the spatial patterns of HDR peak latency and response duration could successfully discriminate pain from no-pain. Interestingly, we also observed that the Pain Vigilance and Awareness Questionnaire (PVAQ) scores were correlated with the average response duration in bilateral insula and secondary somatosensory cortex (S2) and could also be predicted from the across-voxel spatial patterns of response durations in the middle cingulate cortex and middle frontal gyrus only during painful condition but not during non-painful condition. These findings indicate that the spatiotemporal pattern of pain-elicited HDRs may contain pain-specific information and highlight the importance of studying the neural mechanisms of pain by taking advantage of the high sensitivity of fMRI to both spatial and temporal information of brain responses.

Fatty acid-binding protein 7 gene deletion promotes decreases in brain cannabinoid type 1 receptor binding.

Fatty acid-binding protein 7 (FABP7) aids in the intracellular transport of endogenous cannabinoids and is involved in regulating the stress response system. This study examined the role of FABP7 in chronic stress exposure through the binding of CB1 receptors. Adult male FABP7+/+ and FABP7-/- mice were treated with the unpredictable chronic mild stress (UCMS) procedure. After 28 days of treatment, mice were euthanized, and CB1 was measured with in vitro autoradiography using [3H] SR141716A. FABP7-/- mice, irrespective of stress treatment, showed reduced [3H] SR141716A binding in the amygdala, secondary somatosensory cortex, and ventral caudate putamen compared with the FABP7+/+ mice. Additionally, FABP7-/- mice treated with UCMS exhibited a reduction in CB1 binding in the globus pallidus and ventral caudate putamen compared with UCMS-treated FABP7+/+ mice. Genetic deletion of FABP7 can decrease CB1 expression in various brain regions; however, the underlying mechanism remains unclear.

Pain Catastrophizing and Functional Activation During Occlusion in TMD Patients-An Interventional Study.

In temporomandibular disorder (TMD), the effects of standard interventions such as using an occlusal splint and its impact on pain relief and pain catastrophizing are poorly understood. Earlier work pointed to a crucial role of insula activation with changes in pain relief by occlusal splint treatment. We performed a functional imaging study using specially developed splint systems to allow for a placebo-controlled longitudinal design. Using functional MRI we examined 20 TMD patients during repetitive occlusal movements at baseline and over the course of splint therapy and also collected self-reported pain catastrophizing. For balancing performance between baseline and after intervention we used occlusion force measures in an individualized fMRI-splint system. Splint therapy lasted for approximately 7 weeks with one group selected by randomization wearing a palatine placebo splint over the first 3 weeks (delayed start; 11 individuals). As expected, fMRI activation in areas involved in pain processing (insula, primary and secondary somatosensory cortex) decreased with intervention. At baseline a positive correlation between activation of the left anterior insula and pain catastrophizing was present. Both parameters decreased over intervention while associations were primarily observable for patients with rather mild TMD.

Does sedentary time and physical activity predict chronic back pain and morphological brain changes? A UK biobank cohort study in 33,402 participants

BackgroundThe relationship between sedentary time, physical activity, and chronic back pain remains unclear. The study aims to investigate whether sedentary time and physical activity predict chronic back pain and morphological brain changes.MethodsThis cohort study recruited adults aged 37–73 years enrolled between 2006 and 2010, with follow-up until 2014. The total cohort comprised 33,402 participants (mean age: 54.53). Data were collected on daily sedentary time, physical activity, lifestyle factors, and health outcomes.ResultsAfter nearly 8-year follow-up, 3,006 individuals (9.00%) reported chronic back pain in total. Individuals with daily sedentary time exceeding 6 h had a 33% higher risk of chronic back pain compared to those with sedentary time of 2 h or less (RR, 1.33, 95%CI, 1.17–1.52). Sedentary time was also associated with decreased grey matter volume in several brain regions, including bilateral primary somatosensory cortex (S1), secondary somatosensory cortex, putamen, primary motor cortex (M1), insula, hippocampus, amygdala, as well as right supplementary motor area, left medial frontal cortex, and right anterior cingulate cortex (FDR-corrected p-value < 0.05). Compared to individuals who sat for more than 6 h with light physical activity, those engaging in moderate physical activity with sedentary time of 2 h or less (RR, 0.71, 95%CI, 0.52–0.99) exhibited a significant decrease in chronic back pain risk. In addition, replacing sedentary time with equivalent amount of physical activity also demonstrated a reduction in the risk of chronic back pain (RR, 0.87, 95%CI, 0.77–0.99) and increased the reginal grey matter volumes including the amygdala, insula, M1, putamen and S1.ConclusionsProlonged sedentary time is associated with heightened risks of chronic back pain and deterioration in brain health.

Resting-state functional connectivity involved in tactile orientation processing

BackgroundGrating orientation discrimination (GOD) is commonly used to assess somatosensory spatial processing. It allows discrimination between parallel and orthogonal orientations of tactile stimuli applied to the fingertip. Despite its widespread application, the underlying mechanisms of GOD, particularly the role of cortico-cortical interactions and local brain activity in this process, remain elusive. Therefore, we aimed to investigate how a specific cortico-cortical network and inhibitory circuits within the primary somatosensory cortex (S1) and secondary somatosensory cortex (S2) contribute to GOD. MethodsIn total, 51 healthy young adults were included in our study. We recorded resting-state magnetoencephalography (MEG) and somatosensory-evoked magnetic field (SEF) in participants with open eyes. We converted the data into a source space based on individual structural magnetic resonance imaging. Next, we estimated S1- and S2-seed resting-state functional connectivity (rs-FC) at the alpha and beta bands through resting-state MEG using the amplitude envelope correlation method across the entire brain (i.e., S1/S2-seeds × 15,000 vertices × two frequencies). We assessed the inhibitory response in the S1 and S2 from SEFs using a paired-pulse paradigm. We automatically measured the GOD task in parallel and orthogonal orientations to the index finger, applying various groove widths with a custom-made device. ResultsWe observed a specific association between the GOD threshold (all P < 0.048) and the alpha rs-FC in the S1–superior parietal lobule and S1–adjacent to the parieto-occipital sulcus (i.e., lower rs-FC values corresponded to higher performance). In contrast, no association was observed between the local responses and the threshold. DiscussionThe results of this study underpin the significance of specific cortico-cortical networks in recognizing variations in tactile stimuli.

Map activation of various brain regions using different frequencies of electroacupuncture ST36, utilizing the FosCreER strategy

Objective: Electroacupuncture (EA) is an alternative treatment option for pain. Different frequencies of EA have different pain-relieving effects; however, the central mechanism is still not well understood. Methods: The Fos2A-iCreER (TRAP):Ai9 mice were divided into three groups (sham, 2 Hz, and 100 Hz). The mice were intraperitoneally injected with 4-hydroxytamoxifen (4-OHT) immediately after EA at Zusanli (ST36) for 30 min to record the activated neurons. One week later, the mice were sacrificed, and the number of TRAP-treated neurons activated by EA in the thalamus, amygdala, cortex, and hypothalamus was determined. Results: In the cortex, 2 Hz EA activated more TRAP-treated neurons than 100 Hz EA did in the cingulate cortex area 1 (Cg1) and primary somatosensory cortex (S1), and 2 and 100 Hz EAs did not differ from sham EA. TRAP-treated neurons activated by 2 Hz EA were upregulated in the insular cortex (IC) and secondary somatosensory cortex (S2) compared with those activated by 100 Hz and sham EA. In the thalamus, the number of TRAP-treated neurons activated by 2 Hz EA was elevated in the paraventricular thalamic nucleus (PV) compared with those activated by sham EA. In the ventrolateral thalamic nucleus (VL), the number of TRAP-treated neurons activated by 2 Hz EA was significantly upregulated compared with those activated by 100 Hz EA, and sham EA showed no difference compared with 2 or 100 Hz EA. TRAP-treated neurons were more frequently activated in the ventral posterolateral thalamic nucleus (VPL) by 2 Hz EA than by 100 Hz or sham EA. Conclusions: Low-frequency EA ST36 effectively activates neurons in the Cg1, S1, S2, IC, VPL, PV, and VL. The enhanced excitability of the aforementioned nuclei induced by low-frequency EA may be related to its superior efficacy in the treatment of neuropathological pain.

Impaired pain in mice lacking first-order posterior medial thalamic neurons.

The thalamus plays an important role in sensory and motor information processing by mediating communication between the periphery and the cerebral cortex. Alterations in thalamic development have profound consequences on sensory and motor function. In this study, we investigated a mouse model in which thalamic nuclei formation is disrupted because of the absence of Sonic hedgehog (Shh) expression from 2 key signaling centers that are required for embryonic forebrain development. The resulting defects observed in distinct thalamic sensory nuclei in Shh mutant embryos persisted into adulthood prompting us to examine their effect on behavioral responses to somatosensory stimulation. Our findings reveal a role for first-order posterior medial thalamic neurons and their projections to layer 4 of the secondary somatosensory cortex in the transmission of nociceptive information. Together, these results establish a connection between a neurodevelopmental lesion in the thalamus and a modality-specific disruption in pain perception.

Clinical utility of fMRI in evaluating of LSD effect on pain-related brain networks in healthy subjects

ObjectiveWe aimed to evaluate the effect of Lysergic acid diethylamide (LSD) on the pain neural network (PNN) in healthy subjects using functional magnetic resonance imaging (fMRI). MethodsTwenty healthy volunteers participated in a balanced-order crossover study, receiving intravenous administration of LSD and placebo in two fMRI scanning sessions. Brain regions associated with pain processing were analyzed by amplitude of low-frequency fluctuation (ALFF), independent component analysis (ICA), functional connectivity and dynamic casual modeling (DCM). ResultsALFF analysis demonstrated that LSD effectively relieves pain due to modulation in the neural network associated with pain processing. ICA analysis showed more active voxels in anterior cingulate cortex (ACC), thalamus (THL)-left, THL-right, insula cortex (IC)-right, parietal operculum (PO)-left, PO-right and frontal pole (FP)-right in the placebo session than the LSD session. There were more active voxels in FP-left and IC-left in the LSD session compared to the placebo session. Functional brain connectivity was observed between THL-left and PO-right and between PO-left with FP-left, FP-right and IC-left in the placebo session. In the LSD session, functional connectivity of PO-left with FP-left and FP-right was observed. The effective connectivity between left anterior insula cortex (lAIC)-lAIC, lAIC-dorsolateral prefrontal cortex (dlPFC) and secondary somatosensory cortex (SII)-dlPFC were significantly different. Finally, the correlation between fMRI biomarkers and clinical pain criteria was calculated. ConclusionThis study enhances our understanding of the LSD effect on the architecture and neural behavior of pain in healthy subjects and provides great promise for future research in the field of cognitive science and pharmacology.

Brain activity changes after high/low frequency stimulation in a nonhuman primate model of central post-stroke pain

Central post-stroke pain (CPSP) is a chronic pain resulting from a lesion in somatosensory pathways. Neuromodulation techniques, such as repetitive transcranial magnetic stimulation (rTMS) that target the primary motor cortex (M1), have shown promise for the treatment of CPSP. High-frequency (Hf) rTMS exhibits analgesic effects compared to low-frequency (Lf) rTMS; however, its analgesic mechanism is unknown. We aimed to elucidate the mechanism of rTMS-induced analgesia by evaluating alterations of tactile functional magnetic resonance imaging (fMRI) due to Hf- and Lf-rTMS in a CPSP monkey model. Consistent with the patient findings, the monkeys showed an increase in pain threshold after Hf-rTMS, which indicated an analgesic effect. However, no change after Lf-rTMS was observed. Compared to Lf-rTMS, Hf-rTMS produced enhanced tactile-evoked fMRI signals not only in M1 but also in somatosensory processing regions, such as the primary somatosensory and midcingulate cortices. However, the secondary somatosensory cortex (S2) was less active after Hf-rTMS than after Lf-rTMS, suggesting that activation of this region was involved in CPSP. Previous studies showed pharmacological inhibition of S2 reduces CPSP-related behaviors, and the present results emphasize the involvement of an S2 inhibitory system in rTMS-induced analgesia. Verification using the monkey model is important to elucidate the inhibition system.

Pan-cortical cellular imaging in freely behaving mice using a miniaturized micro-camera array microscope (mini-MCAM).

Understanding how circuits in the brain simultaneously coordinate their activity to mediate complex ethnologically relevant behaviors requires recording neural activities from distributed populations of neurons in freely behaving animals. Current miniaturized imaging microscopes are typically limited to imaging a relatively small field of view, precluding the measurement of neural activities across multiple brain regions. Here we present a miniaturized micro-camera array microscope (mini-MCAM) that consists of four fluorescence imaging micro-cameras, each capable of capturing neural activity across a 4.5 mm x 2.55 mm field of view (FOV). Cumulatively, the mini-MCAM images over 30 mm2 area of sparsely expressed GCaMP6s neurons distributed throughout the dorsal cortex, in regions including the primary and secondary motor, somatosensory, visual, retrosplenial, and association cortices across both hemispheres. We demonstrate cortex-wide cellular resolution in vivo Calcium (Ca 2+ ) imaging using the mini-MCAM in both head-fixed and freely behaving mice.

Brain structure alterations following neonatal exposure to low-frequency electromagnetic fields: A histological analysis.

Nitric oxide (NO) and electromagnetic fields (EMF) have been extensively studied for their roles in neurobiology, particularly in regulating cerebral functions and synaptic plasticity. This study investigates the impact of EMFs on NO modulation and its subsequent effects on neurodevelopment, building upon prior research examining EMF exposure's consequences on Wistar albino rats. Rats were exposed perinatally to either tap water, 1g/L of L-arginine (LA) or 0.5g/L of N-methylarginine (NMA). Half of the rats in each group were also exposed to a 7-Hz square-wave EMF at three separate intensities (5, 50 and 500 nT) for 2-14 days following birth. Animals were allowed to develop, and their brains were harvested later in adulthood (mean age = 568.17 days, SD = 162.73). Histological analyses were used to elucidate structural changes in key brain regions. All brains were stained with Toluidine Blue O (TBO), enabling the visualization of neurons. Neuronal counts were then conducted in specific regions of interest (e.g. hippocampus, cortices, amygdala and hypothalamus). Histological analyses revealed significant alterations in neuronal density in specific brain regions, particularly in response to EMF exposure and pharmacological interventions. Notable findings include a main EMF exposure effect where increased neuronal counts were observed in the secondary somatosensory cortex under low EMF intensities (p< 0.001) and sex-specific responses in the hippocampus, where a significant increase in neuronal counts was observed in the left CA3 region in female rats exposed to EMF compared to unexposed females (t(18) =2.371, p= 0.029). Additionally, a significant increase in neuronal counts in the right entorhinal cortex was seen in male rats exposed to EMF compared to unexposed males (t(18) =2.216, p= 0.040). These findings emphasize the complex interaction among sex, EMF exposure and pharmacological agents on neuronal dynamics across brain regions, highlighting the need for further research to identify underlying mechanisms and potential implications for cognitive function and neurological health in clinical and environmental contexts.

The location of pain in cluster headache: Data from the International Cluster Headache Questionnaire.

To identify the most common locations of cluster headache pain from an international, non-clinic-based survey of participants with cluster headache, and to compare these locations to other cluster headache features as well as to somatotopic maps of peripheral, brainstem, thalamic, and cortical areas. Official criteria for cluster headache state pain in the orbital, supraorbital, and/or temporal areas, yet studies have noted pain extending beyond these locations, and the occipital nerve appears relevant, given the effectiveness of suboccipital corticosteroid injections and occipital nerve stimulation. Furthermore, cranial autonomic features vary between patients, and it is not clear if the trigeminovascular reflex is dermatome specific (e.g., do patients with maxillary or V2 division pain have more rhinorrhea?). Finally, functional imaging studies show early activation of the posterior hypothalamus in a cluster headache attack. However, the first somatosensory area to be sensitized is unclear; the first area can be hypothesized based on the complete map of pain locations. The International Cluster Headache Questionnaire was an internet-based cross-sectional survey that included a clickable pain map of the face. These data were compared to several other datasets: (1) a meta-analysis of 22 previous publications of pain location in cluster headache (consisting of 6074 patients); (2) four cephalic dermatome maps; (3) participants' survey responses for demographics, autonomic features, and effective medications; and (4) previously published somatotopic maps of the brainstem, thalamus, primary somatosensory cortex, and higher order somatosensory cortex. One thousand five hundred eighty-nine participants completed the pain map portion of the survey, and the primary locations of pain across all respondents was the orbital, periorbital, and temporal areas with a secondary location in the lower occiput; these primary and secondary locations were consistent with our meta-analysis of 22 previous publications. Of the four cephalic dermatomes (V1, V2, V3, and a combination of C2-3), our study found that most respondents had pain in two or more dermatomes (range 85.7% to 88.7%, or 1361-1410 of 1589 respondents, across the four dermatome maps). Dermatomes did not correlate with their respective autonomic features or with medication effectiveness. The first area to be sensitized in the canonical somatosensory pathway is either a subcortical (brainstem or thalamus) or higher order somatosensory area (parietal ventral or secondary somatosensory cortices) because the primary somatosensory cortex (area 3b) and somatosensory area 1 have discontinuous face and occipital regions. The primary pain locations in cluster headache are the orbital, supraorbital, and temporal areas, consistent with the official International Classification of Headache Disorders criteria. However, activation of the occiput in many participants suggests a role for the occipital nerve, and the pain locations suggest that somatosensory sensitization does not start in the primary somatosensory cortex.

Secondary somatosensory and posterior insular cortices: a somatomotor hub for object prehension and manipulation movements.

The secondary somatosensory cortex (SII) and posterior insular cortex (pIC) are recognized for processing touch and movement information during hand manipulation in humans and non-human primates. However, their involvement in three-dimensional (3D) object manipulation remains unclear. To investigate neural activity related to hand manipulation in the SII/pIC, we trained two macaque monkeys to grasp three objects (a cone, a plate, and a ring) and engage in visual fixation on the object. Our results revealed that 19.4% (n = 50/257) of the task-related neurons in SII/pIC were active during hand manipulations, but did not respond to passive somatosensory stimuli. Among these neurons, 44% fired before hand-object contact (reaching to grasping neurons), 30% maintained tonic activity after contact (holding neurons), and 26% showed continuous discharge before and after contact (non-selective neurons). Object grasping-selectivity varied and was weak among these neurons, with only 24% responding to fixation of a 3D object (visuo-motor neurons). Even neurons unresponsive to passive visual stimuli showed responses to set-related activity before the onset of movement (42%, n = 21/50). Our findings suggest that somatomotor integration within SII/pIC is probably integral to all prehension sequences, including reaching, grasping, and object manipulation movements. Moreover, the existence of a set-related activity within SII/pIC may play a role in directing somatomotor attention during object prehension-manipulation in the absence of vision. Overall, SII/pIC may play a role as a somatomotor hub within the lateral grasping network that supports the generation of intentional hand actions based on haptic information.

Evolutionarily conserved neural responses to affective touch in monkeys transcend consciousness and change with age

Affective touch-a slow, gentle, and pleasant form of touch-activates a different neural network than which is activated during discriminative touch in humans. Affective touch perception is enabled by specialized low-threshold mechanoreceptors in the skin with unmyelinated fibers called C tactile (CT) afferents. These CT afferents are conserved across mammalian species, including macaque monkeys. However, it is unknown whether the neural representation of affective touch is the same across species and whether affective touch's capacity to activate the hubs of the brain that compute socioaffective information requires conscious perception. Here, we used functional MRI to assess the preferential activation of neural hubs by slow (affective) vs. fast (discriminative) touch in anesthetized rhesus monkeys (Macaca mulatta). The insula, anterior cingulate cortex (ACC), amygdala, and secondary somatosensory cortex were all significantly more active during slow touch relative to fast touch, suggesting homologous activation of the interoceptive-allostatic network across primate species during affective touch. Further, we found that neural responses to affective vs. discriminative touch in the insula and ACC (the primary cortical hubs for interoceptive processing) changed significantly with age. Insula and ACC in younger animals differentiated between slow and fast touch, while activity was comparable between conditions for aged monkeys (equivalent to >70 y in humans). These results, together with prior studies establishing conserved peripheral nervous system mechanisms of affective touch transduction, suggest that neural responses to affective touch are evolutionarily conserved in monkeys, significantly impacted in old age, and do not necessitate conscious experience of touch.

Functional mapping of the somatosensory cortex using noninvasive fMRI and touch in awake dogs.

Dogs are increasingly used as a model for neuroscience due to their ability to undergo functional MRI fully awake and unrestrained, after extensive behavioral training. Still, we know rather little about dogs' basic functional neuroanatomy, including how basic perceptual and motor functions are localized in their brains. This is a major shortcoming in interpreting activations obtained in dog fMRI. The aim of this preregistered study was to localize areas associated with somatosensory processing. To this end, we touched N = 22 dogs undergoing fMRI scanning on their left and right flanks using a wooden rod. We identified activation in anatomically defined primary and secondary somatosensory areas (SI and SII), lateralized to the contralateral hemisphere depending on the side of touch, and importantly also activation beyond SI and SII, in the cingulate cortex, right cerebellum and vermis, and the sylvian gyri. These activations may partly relate to motor control (cerebellum, cingulate), but also potentially to higher-order cognitive processing of somatosensory stimuli (rostral sylvian gyri), and the affective aspects of the stimulation (cingulate). We also found evidence for individual side biases in a vast majority of dogs in our sample, pointing at functional lateralization of somatosensory processing. These findings not only provide further evidence that fMRI is suited to localize neuro-cognitive processing in dogs, but also expand our understanding of in vivo touch processing in mammals, beyond classically defined primary and secondary somatosensory cortices.

Field recordings of transcranial magnetic stimulation in human brain postmortem models.

The ability of repetitive transcranial magnetic stimulation (rTMS) to deliver a magnetic field (MF) in deep brain targets is debated and poorly documented. To quantify the decay of MF in the human brain. Magnetic field was generated by single pulses of TMS delivered at maximum intensity using a flat or angulated coil. Magnetic field was recorded by a 3D-magnetic probe. Decay was measured in the air using both coils and in the head of 10 postmortem human heads with the flat coil being positioned tangential to the scalp. Magnetic field decay was interpreted as a function of distance to the coil for 6 potential brain targets of noninvasive brain stimulation: the primary motor cortex (M1, mean depth: 28.5 mm), dorsolateral prefrontal cortex (DLPFC: 28 mm), secondary somatosensory cortex (S2: 35.5 mm), posterior and anterior insulae (PI: 38.5 mm; AI: 43.5 mm), and midcingulate cortex (MCC: 57.5 mm). In air, the maximal MF intensities at coil center were 0.88 and 0.77 T for the flat and angulated coils, respectively. The maximal intracranial MF intensity in the cadaver model was 0.34 T, with a ∼50% decay at 15 mm and a ∼75% MF decay at 30 mm. The decay of the MF in air was similar for the flat coil and significantly less attenuated with the angulated coil (a ∼50% decay at 20 mm and a ∼75% MF decay at 45 mm). Transcranial magnetic stimulation coil MFs decay in brain structures similarly as in air, attenuation with distance being significantly lower with angulated coils. Reaching brain targets deeper than 20 mm such as the insula or Antérior Cingulate Cortex seems feasible only when using angulated coils. The abacus of MF attenuation provided here can be used to adjust modalities of deep brain stimulation with rTMS in future research protocols.

353 Comparison of Brain Diffusion-Weighted Imaging of Cerebral Pain Regions Using DTI and MAP to Clinical Scores of Pain in Chronic Low Back Pain Patients Implanted With Thoracic Spinal Cord Stimulation

INTRODUCTION: Thoracic spinal cord stimulation (SCS) may be an effective treatment option for patients with chronic low back pain (cLBP), and pain levels can be assessed using subjective clinical scores. The use of diffusion-derived imaging of brain regions involved in pain has yet to be studied. METHODS: DTI and MAP data was gathered from five cLBP patients (4 M, 1F) post-tSCS scanned at a 3.0T scanner. Four DTI measures and four MAP measures were extracted and registered against a pain-ROI atlas. The following clinical pain scores were assessed in the same five patients: Numerical Pain Rating Scale (NPRS), Visual Analogue Scale (VAS), Central Sensitization Inventory (CSI), Oswestry Disability Index (ODI), Pain Catastrophizing Scale (PCS), Pittsburgh Sleep Quality Index (PSQI) and Hospital Anxiety and Depression Scale (HADS). The associations between clinical scores and pain ROIs were investigated using linear regression. RESULTS: Within these eight measures, 16 significant linear associations were found between pain ROIs and clinical pain scores. The regions involved are areas of the cerebrum and thalamus involved in pain perception and processing: the secondary somatosensory cortex, the ventral posterolateral and mediodorsal nuclei of the thalamus, and the anterior long, anterior inferior, and middle short gyri of the insula. CONCLUSIONS: Diffusion-derived imaging, using DTI and AMURA/MAP techniques, shows microstructural changes in brain regions involved in pain with significant linear associations with clinical pain scores. As a result, diffusion-derived indices show potential to be used as a complementary quantitative measure to assess pain in cLBP patients receiving tSCS.

Characterization of Neural Plasticity in Monkey Models of Neuropathic Pain – A Secondary Publication

Neuropathic pain can occur as a result of injuries and diseases of the nervous system. Animal models using rodents have been developed and characterized to reveal plastic changes underlying neuropathic pain. However, structures and functions of some brain areas that are associated with pain perception differ between rodents and primates. Therefore, animal models using non-human primates, such as the macaque monkey, with brain structures and functions closer to those of humans are important for elucidating the mechanisms underlying pain in human patients. Recently, we measured brain activity using functional magnetic resonance imaging (fMRI) in a macaque model of chemotherapy-induced neuropathic pain and reported abnormal activation of pain-related brain regions including insular and secondary somatosensory cortices. In the monkey model of central post-stroke pain, moreover, the increased activation of pain-related areas as seen in the patients was confirmed by fMRI. These results indicate that fMRI measurement of brain activity combined with behavioral outcomes in macaque models could be used not only to understand the pathogenetic mechanisms but also to test therapeutic interventions for neuropathic pain.

Functional neuroanatomy of the vestibular cortex and vestibular stimulation methods for neuroimaging studies

The vestibular cortex is a distributed network of multisensory areas that plays a crucial role in balance, posture, and spatial orientation. The core region of the vestibular cortex is the parietoinsular vestibular cortex (PIVC), which is located at the junction between the posterior insula, parietal operculum, and retroinsular region. The PIVC is connected to other vestibular areas, the primary and secondary somatosensory cortices, and the premotor and posterior parietal cortices. It also sends projections to the vestibular nuclei in the brainstem. The PIVC is a multisensory region that integrates vestibular, visual, and somatosensory information to create a representation of head-in-space motion, which is used to control eye movements, posture, and balance. Other regions of the vestibular cortex include the primary somatosensory, posterior parietal, and frontal cortices. The primary somatosensory cortex is involved in processing information about touch and body position. The posterior parietal cortex is involved in integrating vestibular, visual, and somatosensory information to create a representation of spatial orientation. The frontal cortex is involved in controlling posture, and eye movements. The various methods used to stimulate the vestibular receptors in neuroimaging studies include caloric vestibular stimulation (CVS), galvanic vestibular stimulation (GVS), and auditory vestibular stimulation (AVS). CVS uses warm or cold water or air to stimulate the semicircular canals, GVS uses a weak electrical current to stimulate the vestibular nerve, and AVS uses high-intensity clicks or short tone bursts to stimulate the otolithic receptors.

Maternal prenatal depressive symptoms and child brain responses to affective touch at two years of age

BackgroundTouch is an essential form of mother-child interaction, instigating better social bonding and emotional stability. MethodsWe used diffuse optical tomography to explore the relationship between total haemoglobin (HbT) responses to affective touch in the child's brain at two years of age and maternal self-reported prenatal depressive symptoms (EPDS). Affective touch was implemented via slow brushing of the child's right forearm at 3 cm/s and non-affective touch via fast brushing at 30 cm/s and HbT responses were recorded on the left hemisphere. ResultsWe discovered a cluster in the postcentral gyrus exhibiting a negative correlation (Pearson's r = −0.84, p = 0.015 corrected for multiple comparisons) between child HbT response to affective touch and EPDS at gestational week 34. Based on region of interest (ROI) analysis, we found negative correlations between child responses to affective touch and maternal prenatal EPDS at gestational week 14 in the precentral gyrus, Rolandic operculum and secondary somatosensory cortex. The responses to non-affective touch did not correlate with EPDS in these regions. LimitationsThe number of mother-child dyads was 16. However, by utilising high-density optode arrangements, individualised anatomical models, and video and accelerometry to monitor movement, we were able to minimize methodological sources of variability in the data. ConclusionsThe results show that maternal depressive symptoms during pregnancy may be associated with reduced child responses to affective touch in the temporoparietal cortex. Responses to affective touch may be considered as potential biomarkers for psychosocial development in children. Early identification of and intervention in maternal depression may be important already during early pregnancy.