Anatomical measurements and field modeling to assess transcranial magnetic stimulation motor and non-motor effects.

OBJECTIVE: Explore how anatomical measurements and field modeling can be leveraged to improve investigations of transcranial magnetic stimulation (TMS) effects on both motor and non-motor TMS targets. METHODS: TMS motor effects (targeting the primary motor cortex [M1]) were evaluated using the resting motor threshold (rMT), while TMS non-motor effects (targeting the superior temporal gyrus [STG]) were assessed using a pain memory task. Anatomical measurements included scalp-cortex distance (SCD) and cortical thickness (CT), whereas field modeling encompassed the magnitude of the electric field (E) induced by TMS. RESULTS: Anatomical measurements and field modeling values differed significantly between M1 and STG. For TMS motor effects, rMT was correlated with SCD, CT, and E values at M1 (p < 0.05). No correlations were found between these metrics for the STG and TMS non-motor effects (pain memory; all p-values > 0.05). CONCLUSION: Although anatomical measurements and field modeling are closely related to TMS motor effects, their relationship to non-motor effects - such as pain memory - appear to be much more tenuous and complex, highlighting the need for further advancement in our use of TMS and virtual lesion paradigms.

Impact of follow ups, time interval and study duration in diffusion & myelin MRI clinical study in MS.

It is currently unknown how quantitative diffusion and myelin MRI designs affect the results of a longitudinal study. We used two independent datasets containing 6 monthly MRI measurements from 20 healthy controls and 20 relapsing-remitting multiple sclerosis (RR-MS) patients. Six designs were tested, including 3 MRI acquisitions, either over 6 months or over a shorter study duration, with balanced (same interval) or unbalanced (different interval) time intervals between MRI acquisitions. First, we show that in RR-MS patients, the brain changes over time obtained with 3 MRI acquisitions were similar to those observed with 5 MRI acquisitions and that designs with an unbalanced time interval showed the highest similarity, regardless of study duration. No significant brain changes were found in the healthy controls over the same periods. Second, the study duration affects the sample size in the RR-MS dataset; a longer study requires more subjects and vice versa. Third, the number of follow-up acquisitions and study duration affect the sensitivity and specificity of the associations with clinical parameters, and these depend on the white matter bundle and MRI measure considered. Together, this suggests that the optimal design depends on the assumption of the dynamics of change in the target population and the accuracy required to capture these dynamics. Thus, this work provides a better understanding of key factors to consider in a longitudinal study and provides clues for better strategies in clinical trial design.

Relationship between Motor Corticospinal System, Endogenous Pain Modulation Mechanisms and Clinical Symptoms in Patients with Knee Osteoarthritis: New Perspectives on an Old Disease.

Knee osteoarthritis (OA) is a painful condition characterized by joint and bone changes. A growing number of studies suggest that these changes only partially explain the pain experienced by individuals with OA. The purpose of the current study was to evaluate if corticospinal and bulbospinal projection measurements were interrelated in patients with knee OA, and to explore the relationship between these neurophysiological measures and temporal summation (excitatory mechanisms of pain) on one hand, and clinical symptoms on the other. Twenty-eight (28) patients with knee OA were recruited. Corticospinal projections were measured using transcranial magnetic stimulation, while bulbospinal projections were evaluated with a conditioned pain modulation (CPM) protocol using a counter-irritation paradigm. Validated questionnaires were used to document clinical and psychological manifestations. All participants suffered from moderate to severe pain. There was a positive association between corticospinal excitability and the effectiveness of the CPM (rs = 0.67, p = 0.01, n = 13). There was also a positive relationship between pain intensity and corticospinal excitability (rs = 0.45, p = 0.03, n = 23), and between pain intensity and temporal summation (rs = 0.58, p = 0.01, n = 18). The results of this study highlight some of the central nervous system changes that could be involved in knee OA and underline the importance of interindividual variability to better understand and explain the semiology and pathophysiology of knee OA.

Relieving Chronic Musculoskeletal Pain in Older Adults Using Transcranial Direct Current Stimulation: Effects on Pain Intensity, Quality, and Pain-Related Outcomes.

Introduction: Chronic pain is a significant health problem and is particularly prevalent amongst the elderly. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that has been proposed to reduce chronic pain. The aim of this study was to evaluate and compare the efficacy of active and sham tDCS in reducing pain in older individuals living with chronic musculoskeletal pain. Materials and Methods: Twenty-four older individuals (mean age: 68 ± 7 years) suffering from chronic musculoskeletal pain were randomized to receive either anodal tDCS over the contralateral motor cortex (2 mA, 20 min; n = 12) or sham tDCS (20 min; n = 12) for five consecutive days. Pain logbooks were used to measure pain intensity. Questionnaires (McGill Pain Questionnaire, Brief Pain Inventory, Beck Depression Inventory [BDI], Beck Anxiety Inventory, Pain Catastrophizing Scale [PCS], and Margolis Pain Drawing and Scoring System [MPDSS]) were also used to assess pain in its globality. Results: Analysis of pain logbooks revealed that active tDCS led to a reduction in daily average pain intensity (all p ≤ 0.04), while sham tDCS did not produce any change (p = 0.15). Between-group comparisons for change in pain intensity reduction between active and sham tDCS showed a trend during treatment (p = 0.08) which was significant at the follow-up period (p = 0.02). Active tDCS also improved scores of all questionnaires (all p ≤ 0.02), while sham tDCS only reduced MPDSS scores (p = 0.04). Between-group comparisons for the pain-related outcomes showed significant differences for BDI et PCS after the last tDCS session. Conclusions: These results suggest that anodal tDCS applied over the primary motor cortex is an effective modality to decrease pain in older individuals. tDCS can also improve other key outcomes, such as physical and emotional functioning, and catastrophic thinking.

Combining Transcranial Direct Current Stimulation and Transcutaneous Electrical Nerve Stimulation to Relieve Persistent Pain in a Patient Suffering from Complex Regional Pain Syndrome: A Case Report.

PURPOSE: Complex regional pain syndrome (CRPS) is a rare neuropathic pain condition characterized by sensory, motor and autonomic alterations. Previous investigations have shown that transcranial direct current stimulation (tDCS) and transcutaneous electrical nerve stimulation (TENS) can alleviate pain in various populations, and that a combination of these treatments could provide greater hypoalgesic effects. In the present case report, we describe the effect of tDCS and TENS treatment on pain intensity and unpleasantness in a patient suffering from chronic CRPS. RESULTS: The patient was a 37-year-old woman, suffering from left lower limb CRPS (type I) for more than 5 years. Despite medication (pregabalin, tapentadol, duloxetine), rehabilitation treatments (sensorimotor retraining, graded motor imagery) and spinal cord stimulation (SCS), the participant reported moderate to severe pain. Treatments of tDCS alone (performed with SCS turned off during tDCS application, 1 session/day, for 5 consecutive days) did not significantly decrease pain. Combining tDCS with TENS (SCS temporarily turned off during tDCS, 1 session/day, for 5 consecutive days) slightly reduced pain intensity and unpleasantness. DISCUSSION: Our results suggest that combining tDCS and TENS could be a therapeutic strategy worth investigating further to relieve pain in chronic CRPS patients. Future studies should examine the efficacy of combined tDCS and TENS treatments in CRPS patients, and other chronic pain conditions, with special attention to the cumulative and long-term effects and its effect on function and quality of life.

Perturbing the activity of the superior temporal gyrus during pain encoding prevents the exaggeration of pain memories: A virtual lesion study using single-pulse transcranial magnetic stimulation.

BACKGROUND: Past studies have shown that pain memories are often inaccurate, a phenomenon known as mnemonic pain bias. Pain memories are thought to play an important role on how future pain is felt. Recent evidence from our laboratory suggests that individuals who exaggerate past pain display increased superior temporal gyrus (STG) activity during the encoding of experimental painful stimulations, suggesting that this brain structure plays an important role in pain memories. OBJECTIVE: /hypothesis. To determine whether a virtual lesion paradigm, targeting the STG during pain encoding, can affect long-lasting pain memories. We hypothesized that interfering with the activity of the STG would attenuate mnemonic bias. METHODS: Randomized double-blind study with two parallel groups. Participants received either sham (n = 21) or real (n = 21) transcranial magnetic stimulation (TMS - virtual lesion paradigm) over the STG during pain encoding (milliseconds after the administration of a painful stimuli). Pain intensity and unpleasantness were evaluated using a visual analog scale (VAS; 0 to 10) immediately after the painful event, and at recall, 2 months later. The mnemonic pain bias (calculated by subtracting the pain scores obtained at recall from the pain score obtained during encoding) was compared between the two groups for both pain intensity and unpleasantness. RESULTS: Participants in both groups did not differ in terms of age and gender (real TMS = 27 years ±â€¯9, 43% female; sham TMS = 25 years ±â€¯4, 49% female; p > 0.64). The mnemonic bias related to pain intensity was similar in both groups (p = 0.83). However, the mnemonic bias related to pain unpleasantness was lower in the real TMS group (p = 0.04). CONCLUSIONS: Our results provide the first evidence that the STG, is causally involved in the formation of biased memories of pain unpleasantness.

Transcranial Magnetic Stimulation Measures in the Elderly: Reliability, Smallest Detectable Change and the Potential Influence of Lifestyle Habits.

Background: Transcranial magnetic stimulation (TMS) is a non-invasive technique that can be used to evaluate cortical function and corticospinal pathway in normal and pathological aging. Yet, the metrologic properties of TMS-related measurements is still limited in the aging population. Objectives: The aim of this cross-sectional study was to document the reliability and smallest detectable change of TMS measurements among community-dwelling seniors. A secondary objective was to test if TMS measurements differ between elders based on lifestyle, medical and socio-demographic factors. Methods: Motor evoked potentials (MEPs) elicited by single-pulse TMS were recorded in the first dorsal interosseous (FDI) in 26 elderly individuals (mean age = 70 ± 3.8 years). Resting motor threshold (rMT), MEP amplitudes and contralateral silent period (cSP) were measured on two separate occasions (1-week interval), and the standard error of the measurement (SEMeas), intraclass correlation coefficient (ICC), and smallest detectable change in an individual (SDCindv) were calculated. Lifestyle, medical and socio-demographic factors were collected using questionnaires. TMS-related outcomes were compared using independent sample t-test based on the presence of chronic health diseases, chronic medication intake, obesity, history of smoking, physical activity levels, gender, and level of education. Results: rMT and cSP measures were the most reliable outcomes, with the lowest SEMeas and highest ICCs, whereas MEP amplitude-related measures were less reliable. SDCindv levels were generally high, even for rMT (7.29 %MSO) and cSP (43.16-50.84 ms) measures. Although not systematically significant, results pointed toward a higher corticospinal excitability in elderly individuals who were regularly active, who had no chronic medical conditions and who did not take any medication. Conclusion: Even though SDCindv levels were relatively high, these results show that rMT and cSP are the most reliable outcomes to investigate age-related changes in the corticomotor system and suggest that the influence of factors such as lifestyle habits and medications on TMS measures should be investigated further.

Evidence of motor system reorganization in complex regional pain syndrome type 1: A case report.

BACKGROUND: Central nervous system reorganization, particularly in networks devoted to somatosensation, is thought to be a significant feature of complex regional pain syndrome (CRPS). AIMS: In the present case report, we evaluated the corticomotor system of a woman suffering from CRPS, as she started and completed her rehabilitation, in order to explore whether CRPS could also be linked to changes in motor networks. METHODS: The patient, a 58-year-old woman, was diagnosed with right-hand CRPS. Transcranial magnetic stimulation measures, reflecting the strength of the corticospinal projections, were evaluated before, during, and after an 8-week graded motor imagery (GMI) program. RESULTS: Before treatment, the patient reported significant pain and disability, and the strength of the corticospinal projections of the first dorsal interosseous of the affected hand was reduced compared to the healthy, unaffected hand. Pain and disability decreased as the patient completed the GMI program. These changes were paralleled by an increase in the strength of the corticospinal projections. CONCLUSIONS: These observations suggest that corticomotor changes can be observed in individuals suffering from CRPS and that some of the clinical manifestations observed in these patients (e.g., pain, disability) could possibly be linked to these neurophysiological changes.

Contexte: La réorganisation du système nerveux central des réseaux cérébraux, en particulier ceux liés à la somatosensation, est connue comme une caractéristique importante du syndrome douloureux régional complexe (SDRC).But: Dans la présente étude de cas, nous avons évalué le système corticomoteur d'une femme souffrant du SDRC, du début à la fin de sa réadaptation, afin de déterminer si le SDRC pouvait aussi être lié à des changements dans les réseaux moteurs.Méthode: La patiente, une femme âgée de 58 ans, avait reçu un diagnostic de SDRC au niveau de la main droite. Des mesures de stimulation magnétique transcrânienne reflétant la force des projections corticospinales ont été évaluées avant, pendant et après un programme d'imagerie motrice progressive (IMP) d'une durée de huit semaines.Résultats: Avant le traitement, la patiente rapportait douleur et une incapacité importantes, et la force de ses projections corticospinales du premier interosseux dorsal de la main affectée, comparativement à la main saine, non affectée était réduite. La douleur et l'incapacité ont diminué pendant le programme d'IMP. Parallèllement à ces changements, une augmentation de la force des projections corticospinales a été observée.Conclusions: Ces observations suggèrent que des changements corticomoteurs peuvent être observés chez des individus souffrant de SDRC, et que certaines manifestations cliniques observées chez ces patients (ex.: la douleur, l'incapacité) pourraient être liées à ces changements neurophysiologiques.

Can we improve pain and sleep in elderly individuals with transcranial direct current stimulation? - Results from a randomized controlled pilot study.

BACKGROUND: The prevalence of chronic pain and sleep disturbances substantially increases with age. Pharmacotherapy remains the primary treatment option for these health issues. However, side effects and drug interactions are difficult to control in elderly individuals. AIMS: The objective of this study was to assess the feasibility of conducting a randomized sham-controlled trial and to collect preliminary data on the efficacy of transcranial direct current stimulation (tDCS) to reduce pain and improve sleep in older adults suffering from chronic pain. METHODS: Fourteen elderly individuals (mean age 71±7 years) suffering from chronic pain and sleep complaints were randomized to receive either anodal tDCS, applied over the primary motor cortex (2 mA, 20 minutes), or sham tDCS, for 5 consecutive days. Pain was measured with visual analog scales, pain logbooks and questionnaires, while sleep was assessed with actigraphy, sleep diaries and questionnaires. RESULTS: There were no missing data for pain and sleep measures, except for actigraphy, that generated several missing data. Blinding was maintained throughout the study, for both the evaluator and participants. Active but not sham tDCS significantly reduced pain (P<0.05). No change was observed in sleep parameters, in both the active and sham tDCS groups (all P≥0.18). CONCLUSION: The present study provides guidelines for the implementation of future tDCS studies in larger populations of elderly individuals. M1 anodal tDCS in this population appears to be effective to reduce pain, but not to improve sleep.

Unravelling the effect of experimental pain on the corticomotor system using transcranial magnetic stimulation and electroencephalography.

The interaction between pain and the motor system is well-known, with past studies showing that pain can alter corticomotor excitability and have deleterious effects on motor learning. The aim of this study was to better understand the cortical mechanisms underlying the interaction between pain and the motor system. Experimental pain was induced on 19 young and healthy participants using capsaicin cream, applied on the middle volar part of the left forearm. The effect of pain on brain activity and on the corticomotor system was assessed with electroencephalography (EEG) and transcranial magnetic stimulation (TMS), respectively. Compared to baseline, resting state brain activity significantly increased after capsaicin application in the central cuneus (theta frequency), left dorsolateral prefrontal cortex (alpha frequency), and left cuneus and right insula (beta frequency). A pain-evoked increase in the right primary motor cortex (M1) activity was also observed (beta frequency), but only among participants who showed a reduction in corticospinal output (as depicted by TMS recruitment curves). These participants further showed greater beta M1-cuneus connectivity than the other participants. These findings indicate that pain-evoked increases in M1 beta power are intimately tied to changes in the corticospinal system, and provide evidence that beta M1-cuneus connectivity is related to the corticomotor alterations induced by pain. The differential pattern of response observed in our participants suggest that the effect of pain on the motor system is variable from on individual to another; an observation that could have important clinical implications for rehabilitation professionals working with pain patients.

Does Age Affect the Relationship Between Pain and Disability? A Descriptive Study in Individuals Suffering From Chronic Low Back Pain.

BACKGROUND: Previous studies have revealed a weak to moderate relationship between pain and disability in individuals suffering from low back pain (LBP). However, to our knowledge, no studies have evaluated if this relationship is different between young and older adults. PURPOSE: The objective of this descriptive, cross-sectional study was to determine whether the relationship between LBP intensity and physical disability is different between young and older adults. METHODS: Pain intensity (measured with a visual analog scale) and physical disability scores (measured with the Oswestry Disability Index) were collected from the medical files of 164 patients with LBP. Separate Pearson correlation coefficients were calculated between these 2 variables for young (mean age 40 ± 6 years, n = 82) and older (62 ± 9 years, n = 82) individuals and a Fisher r-to-z transformation was used to test for group differences in the strength of the relationship. Linear regression analyses were also performed to determine whether the slope of the association was different between the 2 groups. RESULTS: A significant and positive association was found between pain intensity and disability for both young and older individuals. However, the correlation was stronger in the young group (r = 0.66; P < .01) than in the older group (r = 0.44; P < .01) (Fisher Z = 2.03; P < .05). The linear regression model also revealed that the slope of the relationship was steeper in the young group (P < .05). CONCLUSION: Although both young and older individuals showed a significant association between pain intensity and disability, the relationship between these 2 variables was more tenuous in older individuals than in young patients. Future research is essential to identify the factors underlying this age-related difference.