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De Martino, E.

Publications and source records attributed to De Martino, E..

6 recordsLinked to original sources

REDUCED ALPHA-BAND PHASE COHERENCE AND CORTICAL COMPLEXITY IN FIBROMYALGIA: A TMS-EEG EXPLORATORY STUDY

ObjectivesCortico-spinal excitability of the primary motor cortex (M1) is reduced in fibromyalgia, and repetitive transcranial magnetic stimulation (TMS) targeting M1 normalizes these changes and relieves symptoms. TMS combined with electroencephalography (TMS-EEG) allows the measurement of M1 excitability and its connectivity to other regions, which may help clarify neurophysiological effects in fibromyalgia. We assessed cortical excitability, oscillatory activity, and complexity in individuals with fibromyalgia compared to pain-free healthy controls. MethodsGlobal and local mean field power, peak-to-peak amplitude, event-related spectral perturbation, intertrial coherence (ITC), natural frequency, and perturbational complexity index (PCIst) of the EEG response after left-M1 TMS were compared between groups (n=18 fibromyalgia; n=15 controls). Pain intensity, interference, relief of current therapy, mood, and quality of life were assessed in individuals with fibromyalgia. ResultsCompared with controls, individuals with fibromyalgia showed a reduction in the alpha-band ITC in middle and right parieto-occipital areas (P<0.05). Middle-parieto-occipital ITC negatively correlated with reported pain relief (rho=-0.552, p=0.019). The PCIst was lower in fibromyalgia compared with controls (P<0.01) and correlated with higher pain interference in general activity (rho=-0.486, p=0.042). ConclusionIndividuals with fibromyalgia showed abnormal cortical connectivity compared with asymptomatic controls. SignificanceTMS-EEG measurements may provide insights on brain connectivity relevant for therapy.

neuroscience↗

Extracting Reproducible Components from Electroencephalographic Responses to Transcranial Magnetic Stimulation with Group Task-Related Component Analysis

Transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) is a powerful technique for investigating human cortical circuits. However, characterizing TMS-evoked potentials (TEPs) at the group level typically relies on grand averaging across stimulus repetitions (trials) and subjects - an approach that assumes a level of spatial and temporal consistency that is often lacking in TEPs. Here, we introduce an adaptation of Group Task-Related Component Analysis (gTRCA), a novel multivariate signal decomposition method, to automatically extract TEP components that are maximally reproducible across both trials and subjects. Following the validation of a new permutation-based statistical test for gTRCA using simulated data, the method was applied to two independent TMS-EEG datasets, in which stimulation was targeted to the primary motor cortex (M1) in cohorts of 16 and 22 healthy participants. We found that gTRCA reliably identified TEP components that were reproducible at the group level. Notably, the main gTRCA component captured the key spatial, temporal, and spectral features of motor TEPs, remained robust despite reduced number of stimuli and participants, and was consistent across different recordings. These findings demonstrate that gTRCA affords a more reliable characterization of TEPs at the group level, thereby facilitating the translation of TMS-EEG research into clinical practice.

neuroscience↗

Prior use-dependent plasticity triggers different individual corticomotor responses during persistent musculoskeletal pain

Movement repetition is crucial for pain interventions. It facilitates the rehabilitation of motor patterns, the acquisition of motor skills and the genesis of adaptive use-dependent plasticity. However, the influence of prior motor experience and pre-existing use-dependent plasticity on pain severity and progression remains poorly investigated. This study investigated the effects of pre-existing use-dependent plasticity during the development of prolonged experimental musculoskeletal pain. Using transcranial magnetic stimulation, corticospinal excitability was assessed by measuring the rest-motor thresholds (RMTs), motor-evoked potential (MEP), representational area of the motor map, volume, and center of gravity of the first dorsal interosseous (FDI) muscle in musicians (n=19), a well-known ecological model of use-dependent plasticity, and in non-musicians (n=20). All participants attended three sessions (Day1, Day3, Day8). Prolonged pain for several days was induced by intramuscular injection of nerve growth factor (NGF) into the right FDI muscle at the end of Day1. Compared to Day1, prolonged pain uniquely led to reduced motor map volume in non-musicians on Day3 (p=0.004), who also showed higher NGF-related pain intensity compared to musicians. The motor maps of musicians, which were already smaller in pain-free conditions (Day1) compared to non-musicians (p=0.021), remained non-significantly different across days. Notably, corticomotor responses (map volume, MEP amplitude, and RMTs) at Day1 were correlated to weekly and accumulated musical training. These findings demonstrate that pre-existing use-dependent plasticity associated with motor training may counteract the effects of prolonged pain in the motor system. Moreover, it confirms that prior motor experience acts as a source of individual variability to pain.

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Peak alpha frequency is not significantly altered by five days of experimental pain and repetitive transcranial stimulation of the left dorsolateral prefrontal cortex

Repetitive transcranial magnetic stimulation (rTMS) holds promise as a non-invasive pain treatment. Given the link between individual peak alpha frequency (PAF) of resting-state electroencephalographic recordings and pain sensitivity, and the potential for rTMS to modulate PAF, we investigated these relationships through a secondary analysis of established rTMS-induced analgesia in an experimental model of sustained muscle pain. In a randomised, single-blind, sham-controlled experiment, 30 healthy adults underwent either active (n=15) or sham (n=15) high-frequency rTMS (20 min) to the left dorsolateral prefrontal cortex for five consecutive days following induction of sustained experimental pain by nerve growth factor (NGF) injected into the right extensor carpi radialis brevis muscle. The pain intensity was assessed daily for 14 days on a numerical rating scale (NRS). PAF of the resting state electroencephalography (5 min) was assessed before and one day after the five rTMS treatment days. The pre-registered analysis revealed no significant changes in PAF following five consecutive days of active (from 9.90{+/-}0.39 Hz to 9.95{+/-}0.38 Hz) or sham (from 9.86{+/-}0.44 Hz to 9.81{+/-}0.35 Hz) rTMS, suggesting that the impact of rTMS on NGF-induced pain is independent of PAF modulation. However, exploratory analysis indicated an association between a larger absolute difference in baseline PAF to 10 Hz (i.e. the rTMS frequency) and higher NRS pain ratings at Day 5 in participants receiving active rTMS. This suggests rTMS is more efficient when delivered close to individual PAF or for those with PAF around 10 Hz, necessitating further exploration of PAFs role in rTMS-induced pain relief.

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POSTERIOR-SUPERIOR INSULA REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION REDUCES EXPERIMENTAL TONIC PAIN AND PAIN-RELATED CORTICAL INHIBITION IN HUMANS

High frequency repetitive transcranial magnetic stimulation (rTMS) to the posterosuperior insula (PSI) may produce analgesic effects. However, the neuroplastic changes behind PSI-rTMS analgesia remain poorly understood. The present study aimed to determine whether tonic capsaicin-induced pain and cortical inhibition (indexed using TMS-electroencephalography) are modulated by PSI-rTMS. Twenty healthy volunteers (10 females) attended two sessions randomized to active or sham rTMS. Experimental pain was induced by capsaicin administered to the forearm for 90 minutes, with pain ratings collected every 5 minutes. Left PSI-rTMS was delivered (10Hz, 100 pulses per train, 15 trains) [~]50 minutes post-capsaicin administration. TMS-evoked potentials (TEPs) and thermal sensitivity were assessed at baseline, during capsaicin pain prior to rTMS and after rTMS. Bayesian evidence of reduced pain scores and increased heat pain thresholds were found following active rTMS, with no changes occurring after sham rTMS. Pain (prior to active rTMS) led to an increase in the frontal negative peak [~]45 ms (N45) TEP relative to baseline. Following active rTMS, there was a decrease in the N45 peak back to baseline levels. In contrast, following sham rTMS, the N45 peak was increased relative to baseline. We also found that the reduction in pain NRS scores following active vs. sham rTMS was partially mediated by decreases in the N45 peak. These findings provide evidence of the analgesic effects of PSI-rTMS and suggest that the TEP N45 peak is a potential marker and mediator of both pain and analgesia.

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Acute pain drives different effects on local and global cortical excitability in motor and prefrontal areas: Insights into interregional and interpersonal differences in pain processing

Pain-related depression of motor cortico-spinal excitability has been explored using transcranial magnetic stimulation (TMS)-based motor evoked potentials. Recently, TMS combined with concomitant high-density electroencephalography (TMS-EEG) enabled cortical excitability (CE) assessments in non-motor areas, offering novel insights into CE changes during pain states. Here, pain-related CE changes were explored in the primary motor cortex (M1) and dorsolateral prefrontal cortex (DLPFC). CE was recorded in 24 healthy participants before (Baseline), during painful heat (Acute Pain), and non-painful warm (Non-noxious warm) stimulation for eight minutes at the right forearm in a randomized sequence, followed by a pain-free stimulation measurement. Local CE was measured as peak-to-peak amplitude of the early latencies of the TMS-evoked potential (<120 ms) on each target. Furthermore, global-mean field power (GMFP) was used to measure global excitability. Relative to the Baseline, Acute Pain induced a decrease of -9.9{+/-}8.8% in the peak-to-peak amplitude in M1 and -10.2{+/-}7.4% in DFPFC, while no significant differences were found for Non-noxious warm (+0.6{+/-}8.0% in M1 and +3.4{+/-}7.2% in DLPFC; both P<0.05). A reduced GMFP of - 9.1{+/-}9.0% was only found in M1 during Acute Pain compared with Non-noxious warm (P=0.003). Participants with the largest reduction in local CE under Acute Pain showed a negative correlation between DLPFC and M1 local CE (r=-0.769; P=0.006). Acute experimental pain drove differential pain-related effects on local and global CE changes in motor and non-motor areas at a group level while also revealing different interindividual patterns of CE changes, which can be explored when designing personalized treatment plans. SUMMARYCortical motor and prefrontal areas present reduced excitability during acute pain, but they occur in different patterns across individuals and present distinct impacts on global connectivity.

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