Left dorsolateral prefrontal cortex repetitive transcranial magnetic stimulation reduces the development of long-term muscle pain

The left dorsolateral prefrontal cortex (DLPFC) is involved in the experience and modulation of pain, and may be an important node linking pain and cognition. Repetitive transcranial magnetic stimulation (rTMS) to the left DLPFC can reduce chronic and experimental pain. However, whether left DLPFC rTMS can influence the development of chronic pain is unknown. Using repeated intramuscular injection of nerve growth factor to induce the development of sustained muscle pain (lasting weeks), 30 healthy individuals were randomized to receive 5 consecutive daily treatments of active or sham left DLPFC rTMS, starting before the first nerve growth factor injection on day 0. Muscle soreness and pain severity were collected daily for 14 days and disability on every alternate day. Before the first and 1 day after the last rTMS session, anxiety, depression, affect, pain catastrophizing, and cognitive performance on the attention network test were assessed. Left DLPFC rTMS treatment compared with sham was associated with reduced muscle soreness, pain intensity, and painful area (P < 0.05), and a similar trend was observed for disability. These effects were most evident during the days rTMS was applied lasting up to 3 days after intervention. Depression, anxiety, pain catastrophizing, and affect were unchanged. There was a trend toward improved cognitive function with rTMS compared with sham (P = 0.057). These data indicate that repeated left DLPFC rTMS reduces the pain severity in a model of prolonged muscle pain. The findings may have implications for the development of sustained pain in clinical populations

High frequency repetitive transcranial magnetic stimulation to the left dorsolateral prefrontal cortex modulates sensorimotor cortex function in the transition to sustained muscle pain

Based on reciprocal connections between the dorsolateral prefrontal cortex (DLPFC) and basal-ganglia regions associated with sensorimotor cortical excitability, it was hypothesized that repetitive transcranial magnetic stimulation (rTMS) of the left DLPFC would modulate sensorimotor cortical excitability induced by muscle pain. Muscle pain was provoked by injections of nerve growth factor (end of Day-0 and Day-2) into the right extensor carpi radialis brevis (ECRB) muscle in two groups of 15 healthy participants receiving 5 daily sessions (Day-0 to Day-4) of active or sham rTMS. Muscle pain scores and pressure pain thresholds (PPTs) were collected (Day-0, Day-3, Day-5). Assessment of motor cortical excitability using TMS (mapping cortical ECRB muscle representation) and somatosensory evoked potentials (SEPs) from electrical stimulation of the right radial nerve were recorded at Day-0 and Day-5. At Day-0 versus Day-5, the sham compared to active group showed: Higher muscle pain scores and reduced PPTs (P < 0.04); decreased frontal N30 SEP (P < 0.01); increased TMS map volume (P < 0.03). These results indicate that muscle pain exerts modulatory effects on the sensorimotor cortical excitability and left DLPFC rTMS has analgesic effects and modulates pain-induced sensorimotor cortical adaptations. These findings suggest an important role of prefrontal to basal-ganglia function in sensorimotor cortical excitability and pain processing

Changes in Oceanic Radiocarbon and CFCs Since the 1990s

Anthropogenic perturbations from fossil fuel burning, nuclear bomb testing, and chlorofluorocarbon (CFC) use have created useful transient tracers of ocean circulation. The atmospheric 14C/C ratio (∆14C) peaked in the early 1960s and has decreased now to pre‐industrial levels, while atmospheric CFC‐11 and CFC‐12 concentrations peaked in the early 1990s and early 2000s, respectively, and have now decreased by 10%–20%. We present the first analysis of a decade of new observations (2007 to 2018–2019) and give a comprehensive overview of the changes in ocean ∆14C and CFC concentration since the WOCE surveys in the 1990s. Surface ocean ∆14C decreased at a nearly constant rate from the 1990–2010s (20‰/decade). In most of the surface ocean ∆14C is higher than in atmospheric CO2 while in the interior ocean, only a few places are found to have increases in ∆14C, indicating that globally, oceanic bomb 14C uptake has stopped and reversed. Decreases in surface ocean CFC‐11 started between the 1990 and 2000s, and CFC‐12 between the 2000–2010s. Strong coherence in model biases of decadal changes in all tracers in the Southern Ocean suggest ventilation of Antarctic Intermediate Water was enhanced from the 1990 to the 2000s, whereas ventilation of Subantarctic Mode Water was enhanced from the 2000 to the 2010s. The decrease in surface tracers globally between the 2000 and 2010s is consistently stronger in observations than in models, indicating a reduction in vertical transport and mixing due to stratification

Differential corticomotor excitability responses to hypertonic saline-induced muscle pain in forearm and hand muscles

Experimental muscle pain inhibits corticomotor excitability (CE) of upper limb muscles. It is unknown if this inhibition affects overlapping muscle representations within the primary motor cortex to the same degree. This study explored CE changes of the first dorsal interosseus (FDI) and extensor carpi radialis (ECR) muscles in response to muscle pain. Participants (n=13) attended two sessions (≥48 hours in-between). Hypertonic saline was injected in the ECR (session one) or the FDI (session two) muscle. CE, assessed by transcranial magnetic stimulation (TMS) motor-evoked potentials (MEPs), was recorded at baseline, during pain, and twenty minutes postinjection together with pain intensity ratings. Pain intensity ratings did not differ between the two pain sites (p=0.19). In response to FDI muscle pain, the MEPs of the FDI muscle were reduced at 2 and 4 min postinjection (p≤0.03), but not after ECR muscle pain. No significant MEP change was detected for the ECR muscle (p=0.62). No associations between MEPs and pain intensity were found (p>0.2). The present results indicate that the output from overlapping cortical representations of two muscles differentially adapts to acute muscle pain

Stimulus predictability moderates the withdrawal strategy in response to repetitive noxious stimulation in humans

Nociceptive withdrawal reflex (NWR) is a protective reaction to a noxious stimulus, resulting in withdrawal of the affected area and thus preventing potential tissue damage. This involuntary reaction consists of neural circuits, biomechanical strategies, and muscle activity that ensure an optimal withdrawal. Studies of lower limb NWR indicate that the amplitude of the NWR is highly modulated by extrinsic and intrinsic factors, such as stimulation site, intensity, frequency, and supraspinal activity, among others. Whether the predictability of the stimulus has an effect on the biomechanical strategies is still unclear. This study aimed to evaluate how the predictability of impending noxious stimuli modulate the NWR reaction in the lower limb. NWR was evoked on fifteen healthy participants by trains of electrical stimuli on the sole of the foot and was measured in one distal (tibialis anterior) and one proximal (biceps femoris) muscle. The predictability was manipulated by giving participants prior information about the onset of the stimulus trains and the number of delivered stimuli per train. Results showed that the predictability of the incoming stimuli differentially modulates the muscle activity involved in the NWR reaction. For the most unpredictable stimulus train, larger NWR at distal muscles were evoked. Furthermore, the stereotyped temporal summation profile to repeated stimulation was observed when the stimulus train was completely predictable, while it was disrupted in proximal muscles in unpredictable conditions. It is inferred that the reflex response is shaped by descending control, which dynamically tunes the activity of the muscles involved in the resulting reaction. NEW & NOTEWORTHY Innate defensive behaviors such as reflexes are found across all species, constituting preprogrammed responses to external threats that are not anticipated. Previous studies indicated that the excitability of the reflex arcs like spinal nociceptive withdrawal reflex (NWR) pathways in humans are modulated by several cognitive factors. This study assesses how the predictability of a threat affects the biomechanical pattern of the withdrawal response, showing that distal and proximal muscles are differentially modulated by descending control.Fil: Jure, Fabricio A.. Aalborg University; DinamarcaFil: Arguissain, Federico G.. Aalborg University; DinamarcaFil: Biurrun Manresa, José Alberto. Universidad Nacional de Entre Ríos. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia de Entre Ríos. Universidad Nacional de Entre Ríos. Centro de Investigaciones y Transferencia de Entre Ríos; Argentina. Aalborg University; DinamarcaFil: Graven Nielsen, Thomas. Aalborg University; DinamarcaFil: Andersen, Ole Kæseler. Aalborg University; Dinamarc

Corticomotor excitability reduction induced by experimental pain remains unaffected by performing a working memory task as compared to staying at rest

Experimental pain inhibits primary motor cortex (M1) excitability. Attenuating pain-related inhibition of M1 excitability may be useful during rehabilitation in individuals with pain. One strategy to attenuate M1 excitability is to influence prefrontal and premotor cortex activity. Working memory tasks, e.g. the two-back task (TBT), engage prefrontal and premotor cortices and may influence M1 excitability. We hypothesized that performing the TBT during pain would influence pain-related changes in M1 excitability. Participants (n = 28) received rigorous training in the TBT before baseline testing. Experimental pain was induced by injecting hypertonic saline into the first dorsal interosseous (FDI) muscle. Participants rated pain intensity on a 0–10 numerical rating scale (NRS) every second min until pain-resolved (PR) during the performance of the TBT (n = 14) or during REST (n = 14). In the TBT, letters were presented pseudo-randomly, and accuracy and reaction time to identified letters corresponding to letters shown two times back were recorded. M1 excitability was assessed using transcranial magnetic stimulation. Motor-evoked potentials (MEPs) were recorded at baseline, and at PR, PR + 10, PR + 20, and PR + 30 min. Four minutes after hypertonic saline injection, the pain NRS scores were higher in the TBT group than the REST group (p = 0.009). No time x group interaction was found for MEPs (p = 0.73), but a main effect of time (p < 0.0005) revealed a reduction of MEPs at PR up until PR + 30 (p < 0.008). The TBT accuracy improved at PR + 30 in both groups (p = 0.019). In conclusion, the pain-induced reduction in corticomotor excitability was unaffected by performing a working memory task, despite greater pain in the TBT group

Resisting the desire for the unambiguous: productive gaps in researcher, teacher and student interpretations of a number story task

This article offers reflections on task design in the context of a Grade R (reception year) in-service numeracy project in South Africa. The research explores under what conditions, and for what learning purpose, a task designed by someone else may be recast and how varying given task specifications may support or inhibit learning, as a result of that recasting. This question is situated within a two-pronged task design challenge as to emerging gaps between the task designer’s intentions and teacher’s actions and secondly between the teachers’ intentions and students’ actions. Through analysing two teachers and their respective Grade R students’ interpretations of a worksheet task, provided to teachers in the project, we illuminate the way explicit constraints, in the form of task specifications, can be both enabling and constraining of learning. In so doing we recast this ‘double gap’ as enabling productive learning spaces for teacher educators, teachers and students