How does experience outside the present moment become part of living matter? Mental travel, which is both creative and low-carbon, is an experience that anyone can enjoy without needing to abstract from immediacy and project themselves beyond reality. The possibility of such a virtual journey has long fascinated philosophers and then scientists. What does mental travel actually involve? Which neural circuits are engaged? What are the conditions that take us on a hallucinatory journey, deprive us of it, or enable us to control it? What are the adaptive advantages of this imaginary journey? Is it present in other living beings and in our "intelligent" machines?

How does experience outside the present moment become part of living matter? Mental travel, which is both creative and low-carbon, is an experience that anyone can enjoy without needing to abstract from immediacy and project themselves beyond reality. The possibility of such a virtual journey has long fascinated philosophers and then scientists. What does mental travel actually involve? Which neural circuits are engaged? What are the conditions that take us on a hallucinatory journey, deprive us of it, or enable us to control it? What are the adaptive advantages of this imaginary journey? Is it present in other living beings and in our "intelligent" machines?

Objectives: Complex regional pain syndrome (CRPS) is a chronic pain condition involving autonomic dysregulation. In this study, we report the results of an ancillary study to a larger clinical trial investigating the treatment of CRPS by neuromodulation. This ancillary study, based on functional magnetic resonance imaging (fMRI), evaluated the neural correlates of pain in patients with CRPS in relation to the sympathetic nervous system and for its potential relief after repetitive transcranial magnetic stimulation of the motor cortex. Materials and Methods: Eleven patients with CRPS at one limb (six women, five men, aged 52.0 +/- 9.6 years) were assessed before and one month after the end of a five-month repetitive transcranial magnetic stimulation (rTMS) therapy targeting the motor cortex contralateral to the painful limb, by means of electrochemical skin conductance (ESC) measurement, daily pain intensity scores on a visual numerical scale (VNS), and fMRI with motor tasks (alternation of finger movements and rest). The fMRI scans were analyzed voxelwise using ESC and VNS pain score as regressors to derive their neural correlates. The criterion of response to rTMS therapy was defined as >= 30% reduction in VNS pain score one month after treatment compared with baseline. Results: At baseline, ESC values were reduced in the affected limb vs the nonaffected limb. There was a covariance of VNS with brain activation in a small region of the primary somatosensory cortex (S1) contralateral to the painful side on fMRI investigation. After rTMS therapy on motor cortex related to the painful limb, the VNS pain scores significantly decreased by 22% on average. The criterion of response was met in six of 11 patients (55%). In these responders, at one month after treatment, ESC value increased and returned to normal in the CRPS-affected limb, and overall, the increase in ESC correlated with the decrease in VNS after motor cortex rTMS therapy. At one month after treatment, there also was a covariance of both variables (ESC and VNS) with fMRI activation of the S1 region previously mentioned. The fMRI activation of other brain regions (middle frontal gyrus and temporo-parietal junction) showed correlation with ESC values before and after treatment. Finally, we found a positive correlation at one month after treatment (not at baseline) between VNS pain score and fMRI activation in the temporo-parietal junction contralateral to painful side. Conclusions: This study first shows a functional pain-autonomic coupling in patients with CRPS, which could involve a specific S1 region. However, the modulation of sympathetic sudomotor activities expressed by ESC changes was rather correlated with functional changes in other brain regions. Finally, the pain relief observed at one month after rTMS treatment was associated with a reduced activation of the temporo-parietal junction on the side in which rTMS was performed. These findings open perspectives to define new targets or biomarkers for using rTMS to treat CRPS-associated pain. Clinical

The aim of the present study was to compare the analgesic effect of motor cortex stimulation using high-frequency repetitive transcranial magnetic stimulation or transcranial direct current stimulation and transcutaneous spinal direct current stimulation in patients with complex regional pain syndrome. Thirty-three patients with complex regional pain syndrome were randomized to one of the three treatment groups (repetitive transcranial magnetic stimulation, n = 11; transcranial direct current stimulation, n = 10; transcutaneous spinal direct current stimulation, n = 12) and received a series of 12 sessions of stimulation for 3 weeks (induction phase) and 11 sessions for 4 months (maintenance therapy). The primary end-point was the mean pain intensity assessed weekly with a visual numerical scale during the month prior to treatment (baseline), the 5-month stimulation period and 1 month after the treatment. The weekly visual numerical scale pain score was significantly reduced at all time points compared to baseline in the transcutaneous spinal direct current stimulation group, at the last two time points in the repetitive transcranial magnetic stimulation group (end of the 5-month stimulation period and 1 month later), but at no time point in the transcranial direct current stimulation group. A significant pain relief was observed at the end of induction phase using transcutaneous spinal direct current stimulation compared to repetitive transcranial magnetic stimulation (P = 0.008) and to transcranial direct current stimulation (P = 0.003). In this trial, transcutaneous spinal direct current stimulation was more efficient to relieve pain in patients with complex regional pain syndrome compared to motor cortex stimulation techniques (repetitive transcranial magnetic stimulation, transcranial direct current stimulation). This efficacy was found during the induction phase and was maintained thereafter. This study warrants further investigation to confirm the potentiality of transcutaneous spinal direct current stimulation as a therapeutic option in complex regional pain syndrome.

Severe traumatic brain injury can lead to transient or even chronic disorder of consciousness. To increase diagnosis and prognosis accuracy of disorder of consciousness, functional neuroimaging is recommended 1 month post-injury. Here, we investigated brain networks remodelling on longitudinal data between 1 and 3 months post severe traumatic brain injury related to change of consciousness. Thirty-four severe traumatic brain-injured patients were included in a cross-sectional and longitudinal clinical study, and their MRI data were compared to those of 20 healthy subjects. Long duration resting-state functional MRI were acquired in minimally conscious and conscious patients at two time points after their brain injury. The first time corresponds to the exit from intensive care unit and the second one to the discharge from post-intensive care rehabilitation ward. Brain networks data were extracted using graph analysis and metrics at each node quantifying local (clustering) and global (degree) connectivity characteristics. Comparison with brain networks of healthy subjects revealed patterns of hyper- and hypo-connectivity that characterize brain networks reorganization through the hub disruption index, a value quantifying the functional disruption in each individual severe traumatic brain injury graph. At discharge from intensive care unit, 24 patients’ graphs (9 minimally conscious and 15 conscious) were fully analysed and demonstrated significant network disruption. Clustering and degree nodal metrics, respectively, related to segregation and integration properties of the network, were relevant to distinguish minimally conscious and conscious groups. At discharge from post-intensive care rehabilitation unit, 15 patients’ graphs (2 minimally conscious, 13 conscious) were fully analysed. The conscious group still presented a significant difference with healthy subjects. Using mixed effects models, we showed that consciousness state, rather than time, explained the hub disruption index differences between minimally conscious and conscious groups. While severe traumatic brain-injured patients recovered full consciousness, regional functional connectivity evolved towards a healthy pattern. More specifically, the restoration of a healthy brain functional segregation could be necessary for consciousness recovery after severe traumatic brain injury. For the first time, extracting the hub disruption index directly from each patient’s graph, we were able to track the clinical alteration and subsequent recovery of consciousness during the first 3 months following a severe traumatic brain injury.

While high-frequency transcranial magnetic stimulation (HF-rTMS) is now included in the armamentarium to treat chronic neuropathic pain (NP), direct-current anodal stimulation (a-tDCS) to the same cortical targets may represent a valuable alternative in terms of feasibility and cost. Here we performed a head-to-head, randomized, single-blinded, cross-over comparison of HF-rTMS versus a-tDCS over the motor cortex in 56 patients with drug-resistant NP, who received 5 daily sessions of each procedure, with a washout of at least 4 weeks. Daily scores of pain, sleep, and fatigue were obtained during 5 consecutive weeks, and functional magnetic resonance imaging (fMRI) to a motor task was performed in a subgroup of 31 patients. The percentage of responders, defined by a reduction in pain scores of > 2 SDs from pre-stimulus levels, was similar to both techniques (42.0% vs. 42.3%), while the magnitude of “best pain relief” was significantly skewed towards rTMS. Mean pain ratings in responders decreased by 32.6% (rTMS) and 29.6% (tDCS), with half of them being sensitive to only one technique. Movement-related fMRI showed significant activations in motor and premotor areas, which did not change after 5 days of stimulation, and did not discriminate responders from non-responders. Both HF-rTMS and a-tDCS showed efficacy at 1 month in drug-resistant NP, with magnitude of relief slightly favoring rTMS. Since a significant proportion of patients responded to one procedure only, both modalities should be tested before declaring a patient as unresponsive.

Objective: To assess the prophylactic effect of anodal tDCS of the left motor cortex in patients with resistant chronic migraine (CM) and its long-term maintenance. Methods: In a patient-assessor blinded, sham-controlled trial, 36 patients were randomized to receive anodal tDCS (active group, n = 18) or sham tDCS (sham group, n = 18). The studied population was characterized by a previous failure of at least 3 classes of preventive drugs and a mean duration of migraine history of 26 years. The tDCS procedure consisted of an induction phase of 5 consecutive daily sessions (week 1) followed by a maintenance phase of 1 weekly session during the next 4 weeks and two bimonthly sessions in the next month, for a total of 11 sessions during 2 months. Anodal tDCS was delivered at 2 mA intensity for 20 min over the left motor cortex. The primary endpoint was the reduction in the monthly number of migraine attacks from baseline to each period of follow-up (months 1, 2, 3, 5) between the active and sham groups. Results: The monthly number of migraine attacks expressed as the percentage of reduction from baseline was significantly reduced in the active versus the sham group, from the end of first month (-21% +/- 22 vs. -2% +/- 25, p = 0.019) to the end of follow-up (3-month post-treatment) (-32% +/- 33 vs. -6% +/- 39, p = 0.011). At this time, the rate of responders, defined as a reduction of the monthly number of migraine attacks >= 30% from baseline, was significantly higher in the active group than in the sham group (50% vs. 14%, p = 0.043). Conclusion: Our results show a marked prophylactic effect of anodal tDCS of the left motor cortex in resistant CM extending several months after the stimulation period, and suggest that this neuromodulatory approach may be part of the prophylactic alternatives available for CM. (C) 2022 The Authors. Published by Elsevier Inc.

In tinnitus literature, researchers have increasingly been advocating for a clearer distinction between tinnitus perception and tinnitus-related distress. In non-bothersome tinnitus, the perception itself can be more specifically investigated: this has provided a body of evidence, based on resting-state and activation fMRI protocols, highlighting the involvement of regions outside the conventional auditory areas, such as the right parietal operculum. Here, we aim to conduct a review of available investigations of the human parietal operculo–insular subregions conducted at the microscopic, mesoscopic, and macroscopic scales arguing in favor of an auditory–somatosensory cross-talk. Both the previous literature and new results on functional connectivity derived from cortico–cortical evoked potentials show that these subregions present a dense tissue of interconnections and a strong connectivity with auditory and somatosensory areas in the healthy brain. Disrupted integration processes between these modalities may thus result in erroneous perceptions, such as tinnitus. More precisely, we highlight the role of a subregion of the right parietal operculum, known as OP3 according to the Jülich atlas, in the integration of auditory and somatosensory representation of the orofacial muscles in the healthy population. We further discuss how a dysfunction of these muscles could induce hyperactivity in the OP3. The evidence of direct electrical stimulation of this area eliciting auditory hallucinations further suggests its involvement in tinnitus perception. Finally, a small number of neuroimaging studies of therapeutic interventions for tinnitus provide additional evidence of right parietal operculum involvement.

Subjective tinnitus is a symptom characterized by the perception of sound with no external acoustic source, most often accompanied by co-morbidities. To date, the specific role of white matter abnormalities related to tinnitus reaches no consensus in the literature. The goal of this study was to explore the structural connectivity related to tinnitus percept per se, thus focusing on a specific population presenting chronic non-bothersome tinnitus of similar etiology (noise induced) without co-morbidities. We acquired diffusion-weighted images with high angular resolution in a homogeneous group of mildly impacted tinnitus participants (n = 19) and their matched controls (n = 19). We focused the study on two subsets of fiber bundles of interest: on one hand, we extracted the acoustic radiation and further included any intersecting fiber bundles; on the other hand, we explored the tracts related to the limbic system. We modeled the diffusion signal using constrained spherical deconvolution. We conducted a deep-learning based tractography segmentation and mapped Apparent Fiber Density (AFD) on the bundles of interest. C, as well as Fractional Anisotropy (FA) and FOD peak amplitude for comparison. Between group statistical comparison was performed along the 27 tracts of interest controlling for confounding hearing loss, tinnitus severity, and duration since onset. We tested a potential correlation with hearing loss, tinnitus duration and tinnitus handicap score along these tracts. In the tinnitus group, we observed increased AFD related to chronic tinnitus percept after acoustic trauma in two main white matter regions. First, in the right hemisphere, in the isthmus between inferior temporal and inferior frontal cortices, in the uncinate fasciculus (UF), and in the inferior fronto-occipital bundle (IFO). Second, in the left hemisphere, underneath the superior parietal region in the thalamo parietal tract and parieto-occipital pontine tract. Between-group differences in the acoustic radiations were not significant with AFD but were with FA. Furthermore, significant correlations with hearing loss were found in the left hemisphere in the inferior longitudinal fasciculus and in the fronto-pontine tract. No additional correlation was found with tinnitus duration nor with tinnitus handicap, as reflected by THI scores. The regions that displayed tinnitus related increased AFD also displayed increased FA. The isthmus of the UF and IFO in the right hemisphere appear to be involved with a number of neuropsychiatric and traumatic disorders confirming the involvement of the limbic system even in chronic non-bothersome tinnitus subjects, potentially suggesting a common pathway between these pathologies. White matter changes underneath the superior parietal cortex found here in tinnitus participants supports the implication of an auditory-somatosensory pathway in tinnitus perception.

Different pain types may be encoded in different brain circuits. Here, we examine similarities and differences in brain processing of visceral and somatic pain. We analyze data from seven fMRI studies ( N = 165) and five types of pain and discomfort (esophageal, gastric, and rectal distension, cutaneous thermal stimulation, and vulvar pressure) to establish and validate generalizable pain representations. We first evaluate an established multivariate brain measure, the Neurologic Pain Signature (NPS), as a common nociceptive pain system across pain types. Then, we develop a multivariate classifier to distinguish visceral from somatic pain. The NPS responds robustly in 98% of participants across pain types, correlates with perceived intensity of visceral pain and discomfort, and shows specificity to pain when compared with cognitive and affective conditions from twelve additional studies ( N = 180). Pre-defined signatures for non-pain negative affect do not respond to visceral pain. The visceral versus the somatic classifier reliably distinguishes somatic (thermal) from visceral (rectal) stimulation in both cross-validation and independent cohorts. Other pain types reflect mixtures of somatic and visceral patterns. These results validate the NPS as measuring a common core nociceptive pain system across pain types, and provide a new classifier for visceral versus somatic pain.

Background:Tinnitus and its mechanisms are an ongoing subject of interrogation in the neuroscientific community. Although most current models agree that it encompasses multiple structures within and outside the auditory system, evidence provided in the literature suffers from a lack of convergence. To further our understanding of contributions to tinnitus lying outside the auditory system, we explored a new model based on a proprioceptive hypothesis specifically in subjects experiencing chronic nonbothersome tinnitus due to acoustic trauma. The present study addresses the role of the right operculum 3 (OP3) involved in this model. It also investigates classical models of tinnitus. Methods:A seed-based resting-state magnetic resonance imaging study explored the functional connectivity in an acoustic trauma group presenting slight to mild nonbothersome chronic tinnitus and compared it with a control group. Results:Group differences were found with two networks: with the sensorimotor-auditory and the frontoparietal, but not with the default mode network nor the limbic regions. In the auditory pathway, the inferior colliculus displayed group differences in connectivity with the right superior parietal lobule. Exploratory analysis elicited a significant increase in connectivity between two seeds in the right OP3 and two mirror regions of the dorsal prefrontal cortex, thought to correspond to the human homologue of the premotor ear-eye field bilaterally and the inferior parietal lobule involved in proprioception, in the tinnitus group. Conclusions:These new findings support the view that acoustic trauma tinnitus could bear a proprioceptive contribution and that a permanent cognitive control is required to filter out this chronic phantom percept.

High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) of the motor cortex was shown effective in treating chronic pain, in particular neuropathic pain [[1]Lefaucheur J.P. Aleman A. Baeken C. Benninger D.H. Brunelin J. Di Lazzaro V. et al.Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): an update (2014-2018).Clin Neurophysiol. 2020; 131: 474-528https://doi:10.1016/j.clinph.2019.11.002Crossref PubMed Scopus (276) Google Scholar]. A flat figure-of-8 coil is classically used, focusing cortical stimulation in the superficial layers of the motor cortex [[2]Lefaucheur J.P. Nguyen J.P. A practical algorithm for using rTMS to treat patients with chronic pain.Neurophysiol Clin. 2019; 49: 301-307https://doi:10.1016/j.neucli.2019.07.014Crossref PubMed Scopus (12) Google Scholar]. Deeper brain structures can be stimulated by other types of coils (e.g., double-cone or H-coil), but their value to modulate pain perception remains controversial [[3]Galhardoni R. Aparecida da Silva V. García-Larrea L. Dale C. Baptista A.F. Barbosa L.M. et al.Insular and anterior cingulate cortex deep stimulation for central neuropathic pain: disassembling the percept of pain.Neurology. 2019; 92: e2165-e2175https://doi:10.1212/WNL.0000000000007396PubMed Google Scholar]. In fact, these coils stimulate more deeply but also more broadly the brain. On the other hand, the B70 coil, which is an angled figure-of-8 coil consisting of two partially overlapping coils making an angle of 150°, stimulates deeply, while remaining focal [[4]Lontis E.R. Voigt M. Struijk J.J. Focality assessment in transcranial magnetic stimulation with double and cone coils.J Clin Neurophysiol. 2006; 23: 462-471https://doi:10.1097/01.wnp.0000229944.63011.a1Crossref PubMed Scopus (28) Google Scholar]. To our knowledge, the B70 coil was only used to treat neuropathic pain in the lower limbs in a single case [[5]Hodaj H. Payen J.F. Lefaucheur J.P. Therapeutic impact of motor cortex rTMS in patients with chronic neuropathic pain even in the absence of an analgesic response. A case report.Neurophysiol Clin. 2018; 48: 303-308https://doi:10.1016/j.neucli.2018.05.039Crossref PubMed Scopus (12) Google Scholar]. Compared to a flat figure-of-8 coil, the B70 coil more easily reaches the medial wall of the motor cortex bilaterally, where the pelvic muscles are represented, corresponding to the anterior extension of the paracentral lobule towards the supplementary motor area [[6]Yani M.S. Wondolowski J.H. Eckel S.P. Kulig K. Fisher B.E. Gordon J.E. et al.Distributed representation of pelvic floor muscles in human motor cortex.Sci Rep. 2018; 8: 7213https://doi: 10.1038/s41598-018-25705-0Crossref PubMed Scopus (13) Google Scholar]. In the Pain Center of Grenoble University Hospital, HF-rTMS is used for several years in clinical practice to treat various chronic pain syndromes [[7]Hodaj H. Alibeu J.P. Payen J.F. Lefaucheur J.P. Treatment of chronic facial pain including cluster headache by repetitive transcranial magnetic stimulation of the motor cortex with maintenance sessions: a naturalistic study.Brain Stimul. 2015; 8: 801-807https://doi:10.1016/j.brs.2015.01.416Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar,[8]Hodaj H. Payen J.F. Hodaj E. Dumolard A. Maindet C. Cracowski J.L. et al.Long-term treatment of chronic orofacial, pudendal, and central neuropathic limb pain with repetitive transcranial magnetic stimulation of the motor cortex.Clin Neurophysiol. 2020; 131: 1423-1432https://doi:10.1016/j.clinph.2020.03.022Crossref PubMed Scopus (1) Google Scholar]. From our last study [[8]Hodaj H. Payen J.F. Hodaj E. Dumolard A. Maindet C. Cracowski J.L. et al.Long-term treatment of chronic orofacial, pudendal, and central neuropathic limb pain with repetitive transcranial magnetic stimulation of the motor cortex.Clin Neurophysiol. 2020; 131: 1423-1432https://doi:10.1016/j.clinph.2020.03.022Crossref PubMed Scopus (1) Google Scholar], we would like to focus on the interest of applying HF-rTMS with a B70 coil in a series of 18 patients suffering from perineal pain due to pudendal nerve entrapment syndrome (13 women and 5 men, age (mean ± sd): 60.4 ± 15.9 years, pain duration: 94 ± 64.7 months). The rTMS procedure was performed using a MagPro stimulator (MagVenture, Farum, Denmark); each 10Hz-rTMS session consisted of delivering 2000 pulses in 20 minutes (40 trains of 5 sec with intertrain interval of 25 sec); the intensity of stimulation was set at 80% of the resting motor threshold; the B70 coil was held in posteroanterior orientation, centred on the vertex (Cz), without using neuronavigation for targeting. The therapeutic protocol included an induction phase: one rTMS session per day for five days during two consecutive weeks, followed by two sessions the next week (12 sessions). In patients who responded to rTMS (reduction in average daily pain intensity ≥30% on a 0–10 numerical rating scale), a maintenance phase of bi-monthly sessions for five months was undertaken (11 sessions). Compared to the baseline, a significant decrease was found at the end of the induction phase (D21) regarding the average intensity of ongoing daily pain (from 5.4 ± 1.9 to 3.7 ± 3.0, p = 0.006, Wilcoxon signed-rank test) and paroxysmal daily pain (from 8.0 ± 1.8 to 3.8 ± 3.0, p = 0.005). The average number of painful paroxysms was also reduced (from 5.7 ± 3.1 to 2.4 ± 2.5, p = 0.006). Regarding individual responses, pain reduction was ≥70% in 4 patients, between 30% and 49% in 8 patients, and <30% in 6 patients. The 12 responders (67%) entered in the maintenance phase. Six patients (33% of the initial series and 50% of the responders to the induction phase) completed the study to the end of maintenance phase (D180). They had pain reduction ≥70% (n = 1) or ranging between 50% and 69% (n = 3) or between 30% and 49% (n = 2). Overall, the average intensity of ongoing and paroxysmal daily pain intensity remained stable between D21 and D180 (2.9 ± 3.0 vs. 2.8 ± 2.3, p = 0.75 and 3.8 ± 3.1 vs. 3.7 ± 3.1, p = 0.90, respectively). The average number of painful paroxysms was also stable (2.3 ± 3.0 vs. 2.9 ± 3.7, p = 0.16). In addition, compared to baseline, these patients showed a significant improvement of the Physical (but not Mental) Component Summary of the Short Form (36) Health Survey (from 33.8 ± 5.6 to 55.0 ± 15.7, p = 0.04). Regarding the other 6 patients who entered the maintenance phase, 5 patients stopped the study because of pain recurrence and one patient was lost to follow-up. A careful review of the literature only retrieved 5 articles on the use of rTMS to relieve pelvic or perineal pain, including two series of patients treated by repeated sessions [[9]Cervigni M. Onesti E. Ceccanti M. Gori M.C. Tartaglia G. Campagna G. et al.Repetitive transcranial magnetic stimulation for chronic neuropathic pain in patients with bladder pain syndrome/interstitial cystitis.Neurourol Urodyn. 2018; 37: 2678-2687https://doi:10.1002/nau.23718Crossref PubMed Scopus (20) Google Scholar,[10]Pinot-Monange A. Moisset X. Chauvet P. Gremeau A.S. Comptour A. Canis M. et al.Repetitive transcranial magnetic stimulation therapy (rTMS) for endometriosis patients with refractory pelvic chronic pain: a pilot study.J Clin Med. 2019; 8: 508https://doi:10.3390/jcm8040508Crossref Scopus (5) Google Scholar]. In 12 patients with endometriosis [[10]Pinot-Monange A. Moisset X. Chauvet P. Gremeau A.S. Comptour A. Canis M. et al.Repetitive transcranial magnetic stimulation therapy (rTMS) for endometriosis patients with refractory pelvic chronic pain: a pilot study.J Clin Med. 2019; 8: 508https://doi:10.3390/jcm8040508Crossref Scopus (5) Google Scholar], 5 sessions of HF-rTMS were applied over the left motor cortex with a flat figure-of-eight coil, leading to an average of 1-point reduction in pain intensity (from 5.1 to 4.1/10). In 13 patients with bladder pain syndrome [[9]Cervigni M. Onesti E. Ceccanti M. Gori M.C. Tartaglia G. Campagna G. et al.Repetitive transcranial magnetic stimulation for chronic neuropathic pain in patients with bladder pain syndrome/interstitial cystitis.Neurourol Urodyn. 2018; 37: 2678-2687https://doi:10.1002/nau.23718Crossref PubMed Scopus (20) Google Scholar], 10 sessions of HF-rTMS were applied over the whole motor cortex with an H-coil, leading to a more marked reduction in pain intensity (from 7.9 to 6.2/10). However, there was no previous study based on repeated sessions of HF-rTMS of the motor cortex for the treatment of pudendal neuralgia. This study shows that repeated sessions of HF-rTMS applied to the vertex using a B70 coil could produce effective and sustained pain relief in some patients with refractory pudendal neuralgia. The average reduction in ongoing pain intensity (−1.7/10 at the end of the induction phase) was similar to that previously reported with a deep H-coil [[9]Cervigni M. Onesti E. Ceccanti M. Gori M.C. Tartaglia G. Campagna G. et al.Repetitive transcranial magnetic stimulation for chronic neuropathic pain in patients with bladder pain syndrome/interstitial cystitis.Neurourol Urodyn. 2018; 37: 2678-2687https://doi:10.1002/nau.23718Crossref PubMed Scopus (20) Google Scholar] and possibly higher than using a flat figure-of-eight coil [[10]Pinot-Monange A. Moisset X. Chauvet P. Gremeau A.S. Comptour A. Canis M. et al.Repetitive transcranial magnetic stimulation therapy (rTMS) for endometriosis patients with refractory pelvic chronic pain: a pilot study.J Clin Med. 2019; 8: 508https://doi:10.3390/jcm8040508Crossref Scopus (5) Google Scholar], although it is difficult to make comparisons between these studies. If confirmed, it could mean that perineal pain can be relieved more effectively by a stimulation more appropriate to reach the medial wall of the motor cortex bilaterally in the depth of the interhemispheric fissure. Regarding the mechanisms of action, this result is in favor of specifically targeting HF-rTMS on the cortical motor zone corresponding to the painful region, although unilateral focal stimulation of the motor cortex can also be effective for diffuse pain, especially non-neuropathic pain [[1]Lefaucheur J.P. Aleman A. Baeken C. Benninger D.H. Brunelin J. Di Lazzaro V. et al.Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): an update (2014-2018).Clin Neurophysiol. 2020; 131: 474-528https://doi:10.1016/j.clinph.2019.11.002Crossref PubMed Scopus (276) Google Scholar]. From a practical point of view, the use of a “deep coil” (B70, double-cone, or H-coil) facilitates rTMS application by avoiding the need for neuronavigation. Finally, the value of such “deep coils” for treating perineal pain could be extended for pain in the lower limbs, of which cortical representation also locates in the medial wall of the motor cortex in the depth of the interhemispheric fissure [[6]Yani M.S. Wondolowski J.H. Eckel S.P. Kulig K. Fisher B.E. Gordon J.E. et al.Distributed representation of pelvic floor muscles in human motor cortex.Sci Rep. 2018; 8: 7213https://doi: 10.1038/s41598-018-25705-0Crossref PubMed Scopus (13) Google Scholar]. Some of our results support this hypothesis [[5]Hodaj H. Payen J.F. Lefaucheur J.P. Therapeutic impact of motor cortex rTMS in patients with chronic neuropathic pain even in the absence of an analgesic response. A case report.Neurophysiol Clin. 2018; 48: 303-308https://doi:10.1016/j.neucli.2018.05.039Crossref PubMed Scopus (12) Google Scholar,[8]Hodaj H. Payen J.F. Hodaj E. Dumolard A. Maindet C. Cracowski J.L. et al.Long-term treatment of chronic orofacial, pudendal, and central neuropathic limb pain with repetitive transcranial magnetic stimulation of the motor cortex.Clin Neurophysiol. 2020; 131: 1423-1432https://doi:10.1016/j.clinph.2020.03.022Crossref PubMed Scopus (1) Google Scholar]. The authors have no conflicts of interest to declare.

Under anesthesia, systemic variables and CBF are modified. How does this alter the connectivity measures obtained with rs-fMRI? To tackle this question, we explored the effect of four different anesthetics on Long Evans and Wistar rats with multimodal recordings of rs-fMRI, systemic variables and CBF. After multimodal signal processing, we show that the blood-oxygen-level-dependent (BOLD) variations and functional connectivity (FC) evaluated at low frequencies (0.031–0.25 ​Hz) do not depend on systemic variables and are preserved across a large interval of baseline CBF values. Based on these findings, we found that most brain areas remain functionally active under any anesthetics, i.e. connected to at least one other brain area, as shown by the connectivity graphs. In addition, we quantified the influence of nodes by a measure of functional connectivity strength to show the specific areas targeted by anesthetics and compare correlation values of edges at different levels. These measures enable us to highlight the specific network alterations induced by anesthetics. Altogether, this suggests that changes in connectivity could be evaluated under anesthesia, routinely used in the control of neurological injury.

Objective: To assess the long-term analgesic effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) of the motor cortex in patients with chronic pain syndrome. Methods: The study included 57 patients (orofacial pain, n = 26, pudendal neuralgia, n = 18, and neuropathic limb pain, n = 13) with an "induction phase" of 12 daily rTMS sessions for 3 weeks, followed by a "maintenance phase" of bi-monthly sessions for the next five months. Results: All pain measures significantly decreased from baseline to the end of the induction phase. Analgesic response, defined as pain intensity decrease >= 30% compared to baseline, was observed in 39 patients (68%), who could be differentiated from non-responders from the 7th rTMS session. At the end of the maintenance phase (D180), 27 patients (47%) were still responders. Anxio-depressive symptoms and quality of life also improved. The analgesic response at the end of the induction phase was associated with lower pain score at baseline, and the response at the end of the maintenance phase was associated with lower anxio-depressive score at baseline. Conclusion: The analgesic efficacy of motor cortex rTMS can be maintained in the long term in various chronic pain conditions. Patients with high pain level and severe anxio-depressive symptoms may have a less favorable profile to respond to the procedure. Significance: The overall impact of rTMS treatment on daily life requires a multidimensional evaluation that goes beyond the analgesic effect that can be achieved. (C) 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Abstract Pain is a primary driver of motivated behavior and learning. Different varieties of pain may be encoded in different brain circuits, but the neural similarities and differences across different types of pain are not well understood. Here, we examine the similarites and differences in brain processing of visceral and somatic pain, one of the most fundamental distinctions in the pain field. We analyze data from 7 fMRI studies (N = 165) and 5 types of pain and discomfort—esophageal, gastric, and rectal distension, cutaneous thermal stimulation, and vulvar pressure—to establish and validate generalizable pain representations. We first evaluate an established multivariate brain measure, the Neurologic Pain Signature (NPS), as a potential common nociceptive pain system across all pain types. Then, we develop a multivariate classifier for visceral vs. somatic pain. The NPS (1) responded robustly in 98% of participants across all types, (2) correlated with perceived intensity of visceral pain/discomfort, and (3) showed specificity to pain when compared with non-painful cognitive and affective conditions drawn from 12 additional studies (total N = 180, AUROC 0.93). Pre-defined signatures for other types of negative affect did not respond to visceral pain. The novel visceral vs. somatic classifier reliably distinguished somatic (thermal) from visceral (rectal) stimulation in both cross-validation and independent cohorts (AUROC 0.84). Other types reflected mixtures of somatic and visceral patterns. These results validate the NPS as measuring a common core nociceptive pain system across pain types, and lay a foundation for new brain-based biomarkers for particular types of pain.

ABSTRACT Tinnitus mechanisms remain poorly understood. Our previous functional MRI (fMRI) studies demonstrated an abnormal hyperactivity in the right parietal operculum 3 (OP3) in acoustic trauma tinnitus and during provoked phantom sound perceptions without hearing loss, which lead us to propose a new model of tinnitus. This new model is not directly linked with hearing loss and primary auditory cortex abnormalities, but with a proprioceptive disturbance related to middle-ear muscles. In the present study, a seed-based resting-state functional MRI method was used to explore the potential abnormal connectivity of this opercular region between an acoustic trauma tinnitus group presenting slight to mild tinnitus and a control group. Primary auditory cortex seeds were also explored because they were thought to be directly involved in tinnitus in most current models. In such a model, hearing loss and tinnitus handicap were confounding factors and were therefore regressed in our analysis. Between-groups comparisons showed a significant specific connectivity between the right OP3 seeds and the potential human homologue of the premotor ear-eye field (H-PEEF) bilaterally and the inferior parietal lobule (IPL) in the tinnitus group. Our findings suggest the existence of a simultaneous premotor ear-eye disturbance in tinnitus that could lift the veil on unexplained subclinical abnormalities in oculomotor tests found in tinnitus patients with normal vestibular responses. The present work confirms the involvement of the OP3 subregion in acoustic trauma tinnitus and provides some new clues to explain its putative mechanisms.

The idea that intelligence is embedded not only in a single brain network, but instead in a complex, well-optimized system of complementary networks, has led to the development of whole brain network analysis. Using graph theory to analyze resting-state functional MRI data, we investigated the brain graph networks (or brain networks) of high intelligence quotient (HIQ) children. To this end, we computed the "hub disruption index κ," an index sensitive to graph network modifications. We found significant topological differences in the integration and segregation properties of brain networks in HIQ compared to standard IQ children, not only for the whole brain graph, but also for each hemispheric graph, and for the homotopic connectivity. Moreover, two profiles of HIQ children, homogenous and heterogeneous, based on the differences between the two main IQ subscales [verbal comprehension index (VCI) and perceptual reasoning index (PRI)], were compared. Brain network changes were more pronounced in the heterogeneous than in the homogeneous HIQ subgroups. Finally, we found significant correlations between the graph networks' changes and the full-scale IQ (FSIQ), as well as the subscales VCI and PRI. Specifically, the higher the FSIQ the greater was the brain organization modification in the whole brain, the left hemisphere, and the homotopic connectivity. These results shed new light on the relation between functional connectivity topology and high intelligence, as well as on different intelligence profiles.