Patients with neuropathic pain from lumbosacral radiculopathy demonstrate similar pressure pain thresholds and conditioned pain modulation to those with fibromyalgia

ObjectiveThe purpose of the study was to evaluate pain thresholds, impairment of the endogenous pain modulatory system, and self-reported cognitive-emotional and central sensitization-related symptoms among three subject groups: a rarely studied patient cohort with neuropathic pain from lumbosacral radiculopathy (NPLSR), patients with fibromyalgia (FM) and healthy controls (HC).MethodsPatient-reported pain-related symptomology was evaluated with psychometricallyvalidated questionnaires. Pressure pain threshold (PPT), heat pain threshold (HPT), and cold pain threshold (CPT) were assessed in the low back and contralateral forearm. Conditioned pain modulation (CPM) was evaluated with a recently introduced methodology that accounts for a standard error of measurement.ResultsCompared to the HC subjects, the FM and NPLSR subjects had significantly lower pain thresholds and more CPM impairment. No significant differences in PPT and CPM were observed between the FM and NPLSR groups. Significant group differences were found in self-reported symptoms of depression, anxiety, stress, and central sensitization. Self-reported symptom severity increased in a stair-step fashion, with the HC group scoring lowest and FM group scoring highest.ConclusionThe NPLSR group manifested CPM dysfunction and pressure hyperalgesia at similar levels to the FM group, indicating that these two chronic pain syndromes, likely based on different pathophysiological mechanisms, in fact share some common pain processing features. However, though both patient groups demonstrated similarities in pain processing, self-reported cognitive-emotional and central sensitization-related symptom severity was significantly higher in the FM cohort, which distinguished them from the chronic NPLSR cohort.     

Nocturnal sleep,daytime sleepiness and fatigue in fibromyalgia patients compared to rheumatoid arthritis patients and healthy controls: A preliminary study

ObjectiveFibromyalgia (FM) and rheumatoid arthritis (RA) are pain disorders, both of which are associated with complaints of sleep disturbance, non-refreshing sleep, and daytime sleepiness and fatigue. Given the putative differential central versus peripheral nervous system involvement in these disorders, subjective and objective measures of nocturnal sleep, daytime sleepiness, fatigue and pain were compared between patient groups and to healthy controls (HC).MethodsFifty women (18 with FM, 16 with RA, and 16 HC) completed an 8 h nocturnal polysomnogram (NPSG), Multiple Sleep Latency Test (MSLT) the following day, and self-reports of sleepiness, fatigue, and pain.ResultsFM and RA patients were similar to each other and had less total sleep time than HC, primarily due to more wake after sleep onset. In an analysis of sleep and wake bouts, both patient groups had longer duration of wake bouts than HC. Nocturnal sleep was judged to be non-restorative for both patient groups. Although reporting the greatest subjective sleepiness and fatigue, FM patients had less objective (MSLT) daytime sleepiness than HC, whereas RA patients were intermediate in objective sleepiness. Unlike the RA and HC, FM patients also showed no association between their subjective and objective sleepiness.ConclusionsWomen with FM have similar nocturnal sleep disturbance as those with RA, but FM patients report greater self-rated daytime sleepiness and fatigue than RA and HC, which did not correspond to the relatively low level of objectively determined daytime sleepiness of FM patients. These findings suggest a generalized hyperarousal state in FM.     

Functional Magnetic Resonance Imaging Signal Variability Is Associated With Neuromodulation in Fibromyalgia

ObjectivesAlthough primary motor cortex (M1) transcranial direct current stimulation (tDCS) has an analgesic effect in fibromyalgia (FM), its neural mechanism remains elusive. We investigated whether M1-tDCS modulates a regional temporal variability of blood-oxygenation-level-dependent (BOLD) signals, an indicator of the brain's flexibility and efficiency and if this change is associated with pain improvement.Materials and MethodsIn a within-subjects cross-over design, 12 female FM patients underwent sham and active tDCS on five consecutive days, respectively. Each session was performed with an anode placed on the left M1 and a cathode on the contralateral supraorbital region. The subjects also participated in resting-state functional magnetic resonance imaging (fMRI) at baseline and after sham and active tDCS. We compared the BOLD signal variability (SD_BOLD), defined as the standard deviation of the BOLD time-series, between the tDCS conditions. Baseline SD_BOLD was compared to 15 healthy female controls.ResultsAt baseline, FM patients showed reduced SD_BOLD in the ventromedial prefrontal cortex (vmPFC), lateral PFC, and anterior insula and increased SD_BOLD in the posterior insula compared to healthy controls. After active tDCS, compared to sham, we found an increased SD_BOLD in the left rostral anterior cingulate cortex (rACC), lateral PFC, and thalamus. After sham tDCS, compared to baseline, we found a decreased SD_BOLD in the dorsomedial PFC and posterior cingulate cortex/precuneus. Interestingly, after active tDCS compared to sham, pain reduction was correlated with an increased SD_BOLD in the rACC/vmPFC but with a decreased SD_BOLD in the posterior insula.ConclusionOur findings suggest that M1-tDCS might revert temporal variability of fMRI signals in the rACC/vmPFC and posterior insula linked to FM pain. Changes in neural variability would be part of the mechanisms underlying repetitive M1-tDCS analgesia in FM.     

CNS BOLD fMRI Effects of Sham-Controlled Transcutaneous Electrical Nerve Stimulation in the Left Outer Auditory Canal – A Pilot Study

BackgroundIt has recently been shown that electrical stimulation of sensory afferents within the outer auditory canal may facilitate a transcutaneous form of central nervous system stimulation. Functional magnetic resonance imaging (fMRI) blood oxygenation level dependent (BOLD) effects in limbic and temporal structures have been detected in two independent studies. In the present study, we investigated BOLD fMRI effects in response to transcutaneous electrical stimulation of two different zones in the left outer auditory canal. It is hypothesized that different central nervous system (CNS) activation patterns might help to localize and specifically stimulate auricular cutaneous vagal afferents.Methodology16 healthy subjects aged between 20 and 37 years were divided into two groups. 8 subjects were stimulated in the anterior wall, the other 8 persons received transcutaneous vagus nervous stimulation (tVNS) at the posterior side of their left outer auditory canal. For sham control, both groups were also stimulated in an alternating manner on their corresponding ear lobe, which is generally known to be free of cutaneous vagal innervation. Functional MR data from the cortex and brain stem level were collected and a group analysis was performed.ResultsIn most cortical areas, BOLD changes were in the opposite direction when comparing anterior vs. posterior stimulation of the left auditory canal. The only exception was in the insular cortex, where both stimulation types evoked positive BOLD changes. Prominent decreases of the BOLD signals were detected in the parahippocampal gyrus, posterior cingulate cortex and right thalamus (pulvinar) following anterior stimulation. In subcortical areas at brain stem level, a stronger BOLD decrease as compared with sham stimulation was found in the locus coeruleus and the solitary tract only during stimulation of the anterior part of the auditory canal.ConclusionsThe results of the study are in line with previous fMRI studies showing robust BOLD signal decreases in limbic structures and the brain stem during electrical stimulation of the left anterior auditory canal. BOLD signal decreases in the area of the nuclei of the vagus nerve may indicate an effective stimulation of vagal afferences. In contrast, stimulation at the posterior wall seems to lead to unspecific changes of the BOLD signal within the solitary tract, which is a key relay station of vagal neurotransmission. The results of the study show promise for a specific novel method of cranial nerve stimulation and provide a basis for further developments and applications of non-invasive transcutaneous vagus stimulation in psychiatric patients.     

FMRI of spinal and supra‐spinal correlates of temporal pain summation in fibromyalgia patients

Fibromyalgia syndrome (FM) is a debilitating chronic pain condition, which afflicts primarily females. Although the etiology of this illness is not completely understood, FM pain is thought to rely on enhanced pain sensitivity maintained by central mechanisms. One of these mechanisms is central pain amplification, which is characterized by altered temporal summation of second pain (TSSP). Here we use a TSSP paradigm and functional MRI (fMRI) of the spinal cord, brainstem, and brain to noninvasively examine the central nervous system contributions to TSSP in FM patients and normal controls (NC). Functional MRI of pain‐free female adults (N = 15) and FM patients (N = 14) was conducted while brief, repetitive heat pain stimuli (0.33 Hz) were applied to the thenar eminence of the hand (C6 dermatome). The stimulus intensity was adjusted to each participant's heat pain sensitivity to achieve moderate pain. Data were analyzed by means of a General Linear Model and region‐of‐interest analyses. All participants demonstrated significant pain summation in the TSSP condition. FM subjects, however, required significantly lower stimulus intensities than NC to achieve similar TSSP. fMRI analyses of perceptually equal TSSP identified similar brain activity in NC and FM subjects; however, multiple areas in the brainstem (rostral ventromedial medulla and periaqueductal grey region) and spinal cord (dorsal horn) exhibited greater activity in NC subjects. Finally, increased after‐sensations and enhanced dorsal horn activity was demonstrated in FM patients. In conclusion, the spinal and brainstem BOLD responses to TSSP are different between NC and FM patients, which may indicate alterations to descending pain control mechanisms suggesting contributions of these mechanisms to central sensitization and pain of FM patients. Hum Brain Mapp 37:1349‐1360, 2016. © 2016 Wiley Periodicals, Inc.     

Cerebral processing of social rejection in patients with borderline personality disorder

An intense fear of abandonment or rejection is a central feature of social relationships for individuals with borderline personality disorder (BPD). A total of 20 unmedicated BPD patients and 20 healthy participants (HC, matched for age and education) played a virtual ball-tossing game including the three conditions: exclusion, inclusion and a control condition with predefined game rules, whereas cerebral activity was assessed using functional magnetic resonance imaging. Subjective experiences of exclusion were assessed after each blocked condition. Both groups felt similarly excluded during the exclusion condition; however, BPD subjects felt more excluded than HC during the inclusion and control conditions. In all three conditions, BPD patients showed a stronger engagement of the dorsal anterior cingulate and medial prefrontal cortex. For HC, activation in several cerebral regions such as the insula and the precuneus differed depending on the interaction situation, whereas for BPD subjects activation in these regions was not modulated by experimental conditions. Subjects with BPD differed from HC in both their subjective reactions to and their neural processing of social interaction situations. Our data suggest that individuals with BPD have difficulty in discriminating between social situations, and tend to hypermentalize during social encounters that are not determined by the intentions of others.     

Paired inhibitory stimulation and gait training modulates supplemental motor area connectivity in freezing of gait

IntroductionFreezing of gait (FOG) is a debilitating feature of Parkinson's disease (PD). Evidence suggests patients with FOG have increased cortical control of gait. The supplementary motor area (SMA) may be a key structure due to its connectivity with locomotor and cognitive networks. The objectives of this study were to determine (1) if SMA connectivity is disrupted in patients with FOG and (2) if “inhibitory” repetitive transcranial magnetic stimulation can decrease maladaptive SMA connectivity.MethodsTwo experiments were performed. In experiment 1 resting-state (T2* BOLD imaging) was compared between 38 PD freezers and 17 PD controls. In experiment 2, twenty PD patients with FOG were randomized to either 10 sessions of real or sham rTMS to the SMA (1 Hz, 110% motor threshold, 1200 pulses/session) combined with daily gait training.Results(Experiment 1) Freezers had increased connectivity between the left SMA and the vermis of the cerebellum and decreased connectivity between the SMA and the orbitofrontal cortex (p_FDR-corr <0.05). (Experiment 2) 10 sessions of active TMS reduced SMA connectivity with the anterior cingulate, angular gyrus and the medial temporal cortex, whereas sham TMS did not reduce SMA connectivity. From a behavioral perspective, both groups showed nFOG-Q improvements (F(4, 25.7) = 3.87, p = 0.014).ConclusionsThe SMA in freezers is hyper-connected to the cerebellum, a key locomotor region which may represent maladaptive compensation. In this preliminary study, 1 Hz rTMS reduced SMA connectivity however, this was not specific to the locomotor regions. Intervention outcomes may be improved with subject specific targeting of SMA.     

Altered Spinal Excitability in Patients with Primary Fibromyalgia: A Case-Control Study

Background and PurposeAbnormal excitability of the central nervous system, both spinal and supraspinal, has previously been described as a pathophysiological plastic mechanism for chronic pain syndromes. Primary fibromyalgia (FM) as one extreme of this spectrum of diseases. This case-control study aimed to determine the changes in the spinal excitability by investigating the Hoffman reflex (H-reflex) in patients with FM.MethodsThirty-eight patients with FM and 30 healthy controls participated in this case-control study. We measured the H-reflex bilaterally in the upper limbs (flexor carpi radialis) and the lower limbs (gastrocnemius and soleus). Moreover, pain-related variables were measured, including pain severity (using a visual analogue scale), pain duration, Widespread Pain Index, and the score on the Symptom Severity Scale. Various psychiatric comorbidities and quality-of-life parameters were measured for each patient, including scores on the Hamilton Depression Rating Scale, Taylor''s Manifest Anxiety Scale, and the Revised Fibromyalgia Impact Questionnaire.ResultsA significant increase in the ratio of the maximum baseline-to-peak amplitudes of H and M waves (H_max/M_max) but not in the H-wave minimum latency was found in patients with FM compared with healthy controls. There were no significant correlations between this ratio in both muscles and the various pain-related measures, psychiatric comorbidity, and quality of life in patients with FM. Patients with FM suffered more depression and anxiety than did the controls.ConclusionsWe found increased spinal excitability in patients with FM, which was not confined to the site of maximum pain. This information may help in the diagnosis of FM and supports the hypothesis of central sensitization.     

Fibromyalgia patients make scarce reference to pain in self-defining memories

ObjectiveSelf-defining memories (SDMs) are vivid, emotionally intense and well-rehearsed autobiographical memories that provide fundamental information about one's cognitive affective motivational representation of self. Exploring SDMs in fibromyalgia (FM) is of interest for understanding the psychopathology of this disorder and improving clinical interventions. Our aim was to compare patients and healthy controls (HC) on SDM characteristics.MethodWe included 25 patients with FM and 24 HC matched for age, sex and education level. Each participant described five SDMs, which were coded for content, specificity, integration, tension, redemption, contamination, affective response, date, and reference to pain. We statistically controlled our results for the most plausible confounding factors related to FM that could affect SDM recall, namely depression, anxiety, cognitive inhibition, pain severity and medication.ResultsCompared with HC, patients retrieved less specific SDMs with a more negative emotional valence but less tension. They reported more relationship-related memories, and fewer redemptive ones, with less meaning-making. The number of memories referring to physical or psychological pain did not differ between groups. None of the confounding factors we analysed could explain (either alone or in combination) the statistical differences between groups for SDMs characteristics.ConclusionWe discuss functional avoidance and alexithymia as two main factors for poor reference to pain in patients' SDMs that further reveal affective dysregulation in FM. In clinical practice, remediating the way in which pain is integrated into SDMs in FM may help to mitigate its negative impact on everyday life.     

Articulatory network reorganization in Parkinson's disease as assessed by multimodal MRI and acoustic measures

IntroductionHypokinetic dysarthria (HD) is common in Parkinson's disease (PD). Our objective was to evaluate articulatory networks and their reorganization due to PD pathology in individuals without overt speech impairment using a multimodal MRI protocol and acoustic analysis of speech.MethodsA total of 34 PD patients with no subjective HD complaints and 25 age-matched healthy controls (HC) underwent speech task recordings, structural MRI, and reading task-induced and resting-state fMRI. Grey matter probability maps, task-induced activations, and resting-state functional connectivity within the regions engaged in speech production (ROIs) were assessed and compared between groups. Correlation with acoustic parameters was also performed.ResultsPD patients as compared Tto HC displayed temporal decreases in speech loudness which were related to BOLD signal increases in the right-sided regions of the dorsal language pathway/articulatory network. Among those regions, activation of the right anterior cingulate was increased in PD as compared to HC. We also found bilateral posterior superior temporal gyrus (STG) GM loss in PD as compared to HC that was strongly associated with diadochokinetic (DDK) irregularity in the PD group. Task-induced activations of the left STG were increased in PD as compared to HC and were related to the DDK rate control.ConclusionsThe results provide insight into the neural correlates of speech production control and distinct articulatory network reorganization in PD apparent already in patients without subjective speech impairment.     

Reduced negative BOLD responses in the default-mode network and increased self-focus in depression

Abstract

Objectives. Functional imaging studies in major depressive disorder (MDD) indicate abnormal resting state neural activity and negative blood oxygenation level-dependent (BOLD) responses (NBRs) in regions of the default-mode network (DMN). Methods. Since activity in DMN regions has been associated with self-relatedness, we investigated neural activity in these regions during self-related emotional judgement and passive picture viewing in 25 patients with MDD and 25 healthy controls in an event-related fMRI design. Results. Behaviourally, MDD subjects showed significantly higher ratings of self-relatedness that also correlated with depression symptoms such as hopelessness. Neuroimaging results in MDD patients showed significantly lower negative BOLD responses (NBRs) in anterior medial cortical regions during judgement of self-relatedness while posterior medial regions showed increased NBRs. Unlike in healthy subjects, the anterior medial cortical NBRs were no longer parametrically modulated by the degree of self-relatedness in MDD patients. Conclusions. Our findings suggest that reduced NBRs in the anterior regions of the default-mode network may signify decoupling from self-relatedness in MDD patients with the consecutive abnormal increase of self-focus.     

EEG changes reflecting pain: is alpha suppression better than gamma enhancement?

ObjectiveSuppression of alpha and enhancement of gamma electroencephalographic (EEG) power have both been suggested as objective indicators of cortical pain processing. While gamma activity has been emphasized as the best potential marker, its spectral overlap with pain-related muscular responses is a potential drawback. Since muscle contractions are almost universal concomitants of physical pain, here we investigated alpha and gamma scalp-recorded activities during either tonic pain or voluntary facial grimaces mimicking those triggered by pain.MethodsHigh-density EEG (128 electrodes) was recorded while 14 healthy participants either underwent a cold pressor test (painful hand immersion in 10 °C water) or produced stereotyped facial/nuchal contractions (grimaces) mimicking those evoked by pain. The scalp distribution of spectral EEG changes was quantified via vector-transformation of maps and compared between the pain and grimacing conditions by calculating the cosine of the angle between the two corresponding topographies.ResultsPainful stimuli significantly enhanced gamma power bilaterally in fronto-temporal regions and decreased alpha power in the contralateral central scalp. Sustained cervico-facial contractions (grimaces) gave also rise to significant gamma power increase in fronto-temporal regions but did not decrease central scalp alpha. While changes in alpha topography significantly differed between the pain and grimace situations, the scalp topography of gamma power was statistically indistinguishable from that occurring during grimaces.ConclusionGamma power induced by painful stimuli or voluntary facial-cervical muscle contractions had overlapping topography. Pain-related alpha decrease in contralateral central scalp was less disturbed by muscle activity and may therefore prove more discriminant as an ancillary pain biomarker.     

Self-referential processing influences functional activation during cognitive control: an fMRI study

Rostral anterior cingulate cortex (rACC) plays a central role in the pathophysiology of major depressive disorder (MDD). As we reported in our previous study (Wagner et al., 2006), patients with MDD were characterized by an inability to deactivate this region during cognitive processing leading to a compensatory prefrontal hyperactivation. This hyperactivation in rACC may be related to a deficient inhibitory control of negative self-referential processes, which in turn may interfere with cognitive control task execution and the underlying fronto-cingulate network activation. To test this assumption, a functional magnetic resonance imaging study was conducted in 34 healthy subjects. Univariate and functional connectivity analyses in statistical parametric mapping software 8 were used. Self-referential stimuli and the Stroop task were presented in an event-related design. As hypothesized, rACC was specifically engaged during negative self-referential processing (SRP) and was significantly related to the degree of depressive symptoms in participants. BOLD signal in rACC showed increased valence-dependent (negative vs neutral SRP) interaction with BOLD signal in prefrontal and dorsal anterior cingulate regions during Stroop task performance. This result provides strong support for the notion that enhanced rACC interacts with brain regions involved in cognitive control processes and substantiates our previous interpretation of increased rACC and prefrontal activation in patients during Stroop task.     

Elevated peripheral inflammation is associated with attenuated striatal reward anticipation in major depressive disorder

BackgroundMajor depressive disorder (MDD) is the leading cause of years lived with disability worldwide, and up to 40% of individuals with MDD do not respond to current treatments. Studies suggest that peripheral inflammation plays an important role in the striatal mesolimbic dopamine pathway and corticostriatal reward circuitry in MDD. Although MDD patients show blunted striatal responses to reward, the link between degree of inflammation and attenuation of reward processing is unclear. We investigated whether MDD patients with elevated peripheral inflammation exhibit attenuated reward responses to enhance our understanding of MDD pathophysiology and develop more effective treatments for current non-responders.MethodsMDD subjects varying on serum C-reactive protein (CRP) concentrations (MDD-High CRP, >3 mg/L, n = 44; MDD-Low CRP, <3 mg/L, n = 44) and healthy comparisons (HC, n = 44) completed a monetary incentive delay (MID) task and provided blood samples to measure inflammation-related markers. MDD-High and MDD-Low were propensity score-matched on age, sex, body mass index (BMI), smoking status, exercise and MID task head motion. Percent change in blood oxygen level-dependent (BOLD) signal during anticipation of wins and losses was extracted from bilateral nucleus accumbens, dorsal caudate and dorsolateral putamen regions of interest (ROIs). A linear mixed-effects model was used to test group (MDD-High, MDD-Low and HC), condition (large-win, small-win and no win), and their interaction for these ROIs as well as whole-brain voxelwise data. Analyses also tested group differences in inflammatory mediators. Correlations were used to explore the relationship between inflammatory mediators and brain regions showing differences between MDD-High and MDD-Low.ResultsMDD-High exhibited: (a) lower BOLD signal change in dorsal caudate, thalamus, left insula and left precuneus during anticipation of small wins than MDD-Low; and (b) higher serum soluble intercellular adhesion molecule 1 (sICAM-1) and interleukin 6 (IL-6) concentrations than MDD-Low and HC. MDD as a whole, regardless of CRP-based inflammation, exhibited: (a) lower precuneus BOLD signal change to large wins than HC; and (b) higher Interleukin 1 receptor antagonist (IL-1ra), macrophage-derived chemokine (MDC) and macrophage inflammatory protein-1 alpha (MIP-1α) concentrations than HC. Higher serum sICAM-1 concentrations were associated with lower caudate BOLD signal change to small wins only within the MDD-High group.ConclusionWithin MDD patients, high inflammation (CRP, sICAM-1) was linked to reduced striatal activation recruited to discriminate intermediate reward magnitudes. These findings support an association between levels of peripheral inflammation and the degree of reward-related activation in individuals with MDD.Registration of clinical trialsThe ClinicalTrials.gov identifier for the clinical protocol associated with data published in this current paper is NCT02450240, “Latent Structure of Multi-level Assessments and Predictors of Outcomes in Psychiatric Disorders.”     

Altered cortical gray matter volume and functional connectivity after transcutaneous spinal cord direct current stimulation in idiopathic restless legs syndrome

ObjectiveTo explore the neurophysiological mechanism of clinically effective transcutaneous spinal cord direct current stimulation (tsDCS) on idiopathic restless legs syndrome (RLS), structural magnetic resonance imaging (sMRI), and resting-state functional MRI (rs-fMRI) were applied to reveal the structural and functional changes in idiopathic RLS patients after tsDCS.MethodsThirty idiopathic RLS patients and 20 gender- and age-matched healthy controls (HC) were enrolled. All patients were randomly divided into anodal treatment group and sham treatment group and were treated with tsDCS for 2 weeks. The international RLS Rating Scale (IRLS-RS) and Pittsburgh Sleep Quality Index (PSQI) were used to evaluate the severity of RLS and sleep quality respectively. The sMRI and rs-fMRI data of anodal treatment group and HC were collected. Voxel-based morphology (VBM) and resting-state functional connectivity analysis were used to assess the change of cortical gray matter volume (GMV) and corresponding functional connectivity (FC) respectively in anodal treatment group after tsDCS treatment.ResultsSham treatment group showed no significant change in IRLS-RS and PSQI scores after tsDCS, while significant decrease scores were observed in anodal treatment group, and the improvement sustained up to 2 weeks. Anodal treatment group showed significant regional decrease of GMV in bilateral cuneus compared to the HC. After tsDCS treatment, the GMV in the bilateral cuneus and left ventral post central gyrus (PoCG_L) decreased significantly. The FC between bilateral cuneus and left primary visual cortex (V1_L), and between right cuneus (Cune_R) and right lingual gyrus (LG_R) increased significantly after tsDCS, whereas the FC between PoCG_L and supplementary motor area (SMA) decreased significantly. The changed FC between PoCG_L and SMA, between Cune_R and V1_L were correlated with the changed IRLS-RS.ConclusionDisturbance of sensorimotor network and visual processing network may be involved in the pathogenesis of RLS. tsDCS probably can regulate FC in the sensorimotor cortex and visual processing cortex to relieve the symptom of RLS. Continuous tsDCS may improve the symptoms of RLS patients for a long time. tsDCS probably could provide a potential non-pharmacologic treatment for idiopathic RLS patients.     

Motor preparation impairment in multiple sclerosis: Evidence from the Bereitschaftspotential in simple and complex motor tasks

ObjectivesMultiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, characterized by the accumulation of demyelinating lesions and axonal loss over its course. This study aimed to increase current knowledge of motor preparation in this condition, by assessing the two components of the Bereitschaftspotential (BP1 and BP2), also known as the readiness potential.MethodsTwelve patients with MS and ten age- and gender-matched healthy controls (HC) were included. Patients’ demographic and clinical data were collected. Participants were asked to perform two different tasks, a simple index extension and a Luria sequence. BP1 and BP2 values were obtained from 18 central electroencephalography electrodes and were compared between the two groups.ResultsCompared to HC, patients with MS showed earlier BP1 onset (i.e., longer latency) in almost all the analyzed scalp regions during index extension. This was also observed during the Luria sequence, but only in the centro-parietal regions. As for BP2 latency, no significant difference was noted between groups during either task. With regard to amplitudes, patients with MS had larger BP1 amplitudes in the right fronto-central area during index extension and greater BP1 and BP2 amplitudes in bilateral centro-parietal and left central regions during the Luria task. BP1 latency was also found to be significantly correlated with disease duration and performance on executive function tests (Trail Making Test).ConclusionsThis study showed, for the first time, changes in the Bereitschaftspotential in patients with MS. These data reflect prolonged movement preparation in this population and may suggest global alteration of the premotor scheme.     

Effect of experimental orthodontic pain on gray and white matter functional connectivity

AimOver 90% of patients receiving orthodontic treatment experience clinically significant pain. However, little is known about the neural correlates of orthodontic pain and which has therefore been investigated in the present study of healthy subjects using an experimental paradigm.MethodsResting‐state functional magnetic resonance imaging (rsfMRI) was performed in 44 healthy subjects 24 hours after an elastic separator had been introduced between the first and the second molar on the right side of the lower jaw and in 49 age‐ and sex‐matched healthy control (HC) subjects. A K‐means clustering algorithm was used to identify functional gray matter (GM) and white matter (WM) resting‐state networks, and differences in functional connectivity (FC) of GM and WM between the group of subjects with experimental orthodontic pain and HC were analyzed.ResultsTwelve GM networks and 14 WM networks with high stability were identified. Compared with HC, subjects with orthodontic pain showed significantly increased FC between WM12, which includes posterior thalamic radiation and posterior cingulum bundle, and most GM networks. Besides, the WM12 network showed significant differences in FC with three GM‐WM loops involving the default mode network, dorsal attention network, and salience network, respectively.ConclusionsOrthodontic pain is shown to produce an alteration of FC in networks relevant to pain processing, which may be mediated by a WM network relevant to emotion perception and cognitive processing.     

The cerebellum after trauma: Resting‐state functional connectivity of the cerebellum in posttraumatic stress disorder and its dissociative subtype

The cerebellum plays a key role not only in motor function but also in affect and cognition. Although several psychopathological disorders have been associated with overall cerebellar dysfunction, it remains unclear whether different regions of the cerebellum contribute uniquely to psychopathology. Accordingly, we compared seed‐based resting‐state functional connectivity of the anterior cerebellum (lobule IV–V), of the posterior cerebellum (Crus I), and of the anterior vermis across posttraumatic stress disorder (PTSD; n = 65), its dissociative subtype (PTSD + DS; n = 37), and non‐trauma‐exposed healthy controls (HC; n = 47). Here, we observed decreased functional connectivity of the anterior cerebellum and anterior vermis with brain regions involved in somatosensory processing, multisensory integration, and bodily self‐consciousness (temporo‐parietal junction, postcentral gyrus, and superior parietal lobule) in PTSD + DS as compared to PTSD and HC. Moreover, the PTSD + DS group showed increased functional connectivity of the posterior cerebellum with cortical areas related to emotion regulation (ventromedial prefrontal and orbito‐frontal cortex, subgenual anterior cingulum) as compared to PTSD. By contrast, PTSD showed increased functional connectivity of the anterior cerebellum with cortical areas associated with visual processing (fusiform gyrus), interoceptive awareness (posterior insula), memory retrieval, and contextual processing (hippocampus) as compared to HC. Finally, we observed decreased functional connectivity between the posterior cerebellum and prefrontal regions involved in emotion regulation, in PTSD as compared to HC. These findings not only highlight the crucial role of each cerebellar region examined in the psychopathology of PTSD but also reveal unique alterations in functional connectivity distinguishing the dissociative subtype of PTSD versus PTSD.     

Neural correlates of attentional deficits in Parkinson's disease patients with mild cognitive impairment

IntroductionDeficits in attentional processing observed in Parkinson's disease (PD) patients with mild cognitive impairment (MCI) increase risk of PD dementia. However, the neural basis of these attentional deficits are presently unknown. The present study aimed to explore the neural correlates of attention dysfunction in PD-MCI using the Attention Network Test (ANT) and functional Magnetic Resonance Imaging (fMRI).MethodFifteen (15) PD-MCI patients, 26 PD patients without MCI (PD-NC) and 22 healthy controls (HC) were scanned (3T Siemens PRISMA) whilst performing the ANT. Reaction time, accuracy and fMRI BOLD activation were compared between groups for the three attentional task components of 1) alerting, 2) orienting, and 3) executive control.ResultsPD-MCI patients showed an overall slower reaction time compared to PD-NC and HC, and showed less interference of reaction time in the orienting effect than HC. fMRI data demonstrated greater activation in the bilateral cerebellum crus 1 during the alerting attention condition in both PD-MCI and PD-NC compared to HC. However, activation was supressed in the left postcentral gyrus in PD-MCI compared to PD-NC and HC.DiscussionAlterations in the alerting attention functional network despite intact task performance in PD-MCI suggests that functional brain changes may precede cognitive changes in the attention domain. Furthermore, increased activation in the cerebellum may reflect an attentional compensatory mechanism unique to the PD pathology. Taken together, the findings suggest that PD has a complex effect on attentional ability that can, at least in part, be elucidated using functional neuroimaging.     

An fMRI Study of the Neural Correlates of Incidental Versus Directed Emotion Processing in Pediatric Bipolar Disorder

ObjectiveTo use functional neuroimaging to probe the affective circuitry dysfunctions underlying disturbances in emotion processing and emotional reactivity in pediatric bipolar disorder (PBD).MethodEqual numbers of controls (HC) and unmedicated patients with euthymia and PBD were matched for age, sex, race, socioeconomic status, and IQ (n = 10 per group; mean age 14.2 years [SD 2.0 years]). The task consisted of a “directed” emotion processing condition where subjects judged whether emotion in facial expression was positive or negative and an “incidental” condition where subjects judged whether faces expressing similar affect were older or younger than 35 years.ResultsRelative to the directed condition, the incidental condition elicited greater activation in the right amygdala and the right insula, the left middle frontal gyrus, and the left posterior cingulate cortex in patients with PBD, in contrast to the HC that showed greater activation in the right superior frontal gyrus. In both incidental and directed conditions, relative to visual fixation, patients with PBD showed less activation in the right prefrontal cortex (superior, middle, and inferior frontal gyri) and the pregenual anterior cingulate cortex and greater activation in the posterior visual and face-processing regions (i.e., right precuneus/cuneus, fusiform gyrus).ConclusionsIncreased amygdala activation observed in patients with PBD elicited by incidental emotional processing relative to directed emotional processing may indicate more intense automatic emotional reactivity. Furthermore, the right prefrontal systems that are believed to modulate affect seem to be less engaged in patients with PBD regardless of whether the emotion processing is incidental or directed, which may signify reduced top-down control of emotional reactivity in PBD.