The role of the primary motor cortex in motor imagery: A theta burst stimulation study.

While mentally simulated actions activate similar neural structures to overt movement, the role of the primary motor cortex (PMC) in motor imagery remains disputed. The aim of the study was to use continuous theta burst stimulation (cTBS) to modulate corticospinal activity to investigate the putative role of the PMC in implicit motor imagery in young adults with typical and atypical motor ability. A randomized, double blind, sham-controlled, crossover, offline cTBS protocol was applied to 35 young adults. During three separate sessions, adults with typical and low motor ability (developmental coordination disorder [DCD]), received active cTBS to the PMC and supplementary motor area (SMA), and sham stimulation to either the PMC or SMA. Following stimulation, participants completed measures of motor imagery (i.e., hand rotation task) and visual imagery (i.e., letter number rotation task). Although active cTBS significantly reduced corticospinal excitability in adults with typical motor ability, neither task performance was altered following active cTBS to the PMC or SMA, compared to performance after sham cTBS. These results did not differ across motor status (i.e., typical motor ability and DCD). These findings are not consistent with our hypothesis that the PMC (and SMA) is directly involved in motor imagery. Instead, previous motor cortical activation observed during motor imagery may be an epiphenomenon of other neurophysiological processes and/or activity within brain regions involved in motor imagery. This study highlights the need to consider multi-session theta burst stimulation application and its neural effects when probing the putative role of motor cortices in motor imagery.

Do gaze behaviours during action observation predict interpersonal motor resonance?

Interpersonal motor resonance (IMR) is a common putative index of the mirror neuron system (MNS), a network containing specialised cells that fire during both action execution and observation. Visual content inputs to the MNS, however, it is unclear whether visual behaviours mediate the putative MNS response. We aimed to examine gaze effects on IMR during action observation. Neurotypical adults (N = 99; 60 female) underwent transcranial magnetic stimulation, electromyography, and eye-tracking during the observation of videos of actors performing grasping actions. IMR was measured as a percentage change in motor evoked potentials (MEPs) of the first dorsal interosseous muscle during action observation relative to baseline. MEP facilitation was observed during action observation, indicating IMR (65.43%, SE = 11.26%, P < 0.001). Fixations occurring in biologically relevant areas (face/hand/arm) yielded significantly stronger IMR (81.03%, SE = 14.15%) than non-biological areas (63.92%, SE = 14.60, P = 0.012). This effect, however, was only evident in the first of four experimental blocks. Our results suggest that gaze fixation can modulate IMR, but this may be affected by the salience and novelty of the observed action. These findings have important methodological implications for future studies in both clinical and healthy populations.

Is there a relationship between EEG and sTMS neurophysiological markers of the putative human mirror neuron system?

The mirror neuron system (MNS) has been theorized to play a neurobiological role in a number of social cognitive abilities and is commonly indexed putatively in humans via interpersonal motor resonance (IMR) and mu suppression. Although both indices are thought to measure similar neuronal populations (i.e., "mirror neurons"), it has been suggested that these methods are unrelated, and therefore, incompatible. However, prior studies reporting no relationships were typically conducted in small and underpowered samples. Thus, we aimed to investigate this potential association in a large sample of neurotypical adults (N = 116; 72 females). Participants underwent transcranial magnetic stimulation (TMS), electromyography (EMG), and electroencephalography (EEG) during the observation of videos of actors performing grasping actions in order to index IMR and mu suppression (in beta, lower alpha, and upper alpha bandwidths). A series of linear regressions revealed no associations between IMR and each of the mu suppression bandwidths. Supplementary Bayesian analyses provided further evidence in favor of the null (B01  = 8.85-8.93), providing further support for no association between the two indices of MNS activity. Our findings suggest that these two measures may indeed be unrelated indices that perhaps assess different neurophysiological aspects of the MNS. These results have important implications for future studies examining the MNS.

Repetitive transcranial magnetic stimulation (rTMS) in autism spectrum disorder: protocol for a multicentre randomised controlled clinical trial.

INTRODUCTION: There are no well-established biomedical treatments for the core symptoms of autism spectrum disorder (ASD). A small number of studies suggest that repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation technique, may improve clinical and cognitive outcomes in ASD. We describe here the protocol for a funded multicentre randomised controlled clinical trial to investigate whether a course of rTMS to the right temporoparietal junction (rTPJ), which has demonstrated abnormal brain activation in ASD, can improve social communication in adolescents and young adults with ASD. METHODS AND ANALYSIS: This study will evaluate the safety and efficacy of a 4-week course of intermittent theta burst stimulation (iTBS, a variant of rTMS) in ASD. Participants meeting criteria for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ASD (n=150, aged 14-40 years) will receive 20 sessions of either active iTBS (600 pulses) or sham iTBS (in which a sham coil mimics the sensation of iTBS, but no active stimulation is delivered) to the rTPJ. Participants will undergo a range of clinical, cognitive, epi/genetic, and neurophysiological assessments before and at multiple time points up to 6 months after iTBS. Safety will be assessed via a structured questionnaire and adverse event reporting. The study will be conducted from November 2020 to October 2024. ETHICS AND DISSEMINATION: The study was approved by the Human Research Ethics Committee of Monash Health (Melbourne, Australia) under Australia's National Mutual Acceptance scheme. The trial will be conducted according to Good Clinical Practice, and findings will be written up for scholarly publication. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12620000890932).

Mental rotation performance in young adults with and without developmental coordination disorder.

While there have been consistent behavioural reports of atypical hand rotation task (HRT) performance in adults with developmental coordination disorder (DCD), this study aimed to clarify whether this deficit could be attributed to specific difficulties in motor imagery (MI), as opposed to broad deficits in general mental rotation. Participants were 57 young adults aged 18-30 years with (n = 22) and without DCD (n = 35). Participants were compared on the HRT, a measure of MI, and the letter number rotation task (LNRT), a common visual imagery task. Only participants whose behavioural performance on the HRT suggested use of a MI strategy were included in group comparisons. Young adults with DCD were significantly less efficient compared to controls when completing the HRT yet showed comparable performance on the LNRT relative to adults with typical motor ability. Our data are consistent with the view that atypical HRT performance in adults with DCD is likely to be attributed to specific difficulties engaging in MI, as opposed to deficits in general mental rotation. Based on the theory that MI provides insight into the integrity of internal action representations, these findings offer further support for the internal modelling deficit hypothesis of DCD.

Is the Putative Mirror Neuron System Associated with Empathy? A Systematic Review and Meta-Analysis.

Theoretical perspectives suggest that the mirror neuron system (MNS) is an important neurobiological contributor to empathy, yet empirical support is mixed. Here, we adopt a summary model for empathy, consisting of motor, emotional, and cognitive components of empathy. This review provides an overview of existing empirical studies investigating the relationship between putative MNS activity and empathy in healthy populations. 52 studies were identified that investigated the association between the MNS and at least one domain of empathy, representing data from 1044 participants. Our results suggest that emotional and cognitive empathy are moderately correlated with MNS activity, however, these domains were mixed and varied across techniques used to acquire MNS activity (TMS, EEG, and fMRI). Few studies investigated motor empathy, and of those, no significant relationships were revealed. Overall, results provide preliminary evidence for a relationship between MNS activity and empathy. However, our findings highlight methodological variability in study design as an important factor in understanding this relationship. We discuss limitations regarding these methodological variations and important implications for clinical and community translations, as well as suggestions for future research.

High-definition tDCS to the right temporoparietal junction modulates slow-wave resting state power and coherence in healthy adults.

The right temporoparietal junction (rTPJ) is a multisensory integration hub that is increasingly utilized as a target of stimulation studies exploring its rich functional network roles and potential clinical applications. While transcranial direct current stimulation (tDCS) is frequently employed in such studies, there is still relatively little known regarding its local and network neurophysiological effects, particularly at important nonmotor sites such as the rTPJ. The current study applied either anodal, cathodal, or sham high-definition tDCS to the rTPJ of 53 healthy participants and used offline EEG to assess the impacts of stimulation on resting state (eyes open and eyes closed) band power and coherence. Temporoparietal and central region delta power was increased after anodal stimulation (the latter trend only), whereas cathodal stimulation increased frontal region delta and theta power. Increased coherence between right and left temporoparietal regions was also observed after anodal stimulation. All significant effects occurred in the eyes open condition. These findings are discussed with reference to domain general and mechanistic theories of rTPJ function. Low-frequency oscillatory activity may exert long-range inhibitory network influences that enable switching between and integration of endogenous/exogenous processing streams.NEW & NOTEWORTHY Through the novel use of high-definition transcranial direct current stimulation (tDCS) and EEG, we provide evidence that both anodal and cathodal stimulation of the right temporoparietal junction selectively modulate slow-wave power and coherence in distributed network regions of known relevance to proposed temporoparietal junction functionality. These results also provide direct evidence of the ability of tDCS to modulate oscillatory activity at a long-range network level, which may have explanatory power in terms of both neurophysiological and behavioral effects.

Intra- and Inter-Regional Priming of Ipsilateral Human Primary Motor Cortex With Continuous Theta Burst Stimulation Does Not Induce Consistent Neuroplastic Effects.

Human responses to non-invasive brain stimulation (NIBS) techniques can be highly variable. Recently, priming protocols involving a conditioning round of NIBS applied to a target brain region prior to the application of a test protocol have shown promise in inducing more reliable effects. We investigated whether intra- or inter-regional priming of the left primary motor cortex (M1) using continuous theta burst stimulation (cTBS) can induce consistent, and reliable modulation of corticospinal excitability. Twenty healthy adults (six males) underwent four cTBS protocols. For intra-regional priming, cTBS was applied twice to the left M1 (M1-M1). For inter-regional M1 priming, cTBS was applied to the ipsilateral (left) dorsal premotor cortex (dPMC-M1), and ipsilateral (left) dorsolateral prefrontal cortex (DLPFC-M1). In the control condition, sham stimulation was applied to left M1, followed by active cTBS also applied to the left M1 (sham-M1). Each round of cTBS was separated by 10 min. Neuroplastic responses were indexed using motor evoked potentials (MEPs) elicited from the left M1 hand region, and measured from the contralateral first dorsal interosseous (right hand). MEP measurements were taken before the first round of cTBS priming, then immediately, 10, 20 and 30 min after the second test round of cTBS. The primary two-way repeated measures ANOVA revealed no significant differences in MEP responses across each condition (no main effects or interaction). Intra- and inter-regional priming of the left M1 using cTBS does not induce consistent neuroplastic effects. Further work is required to identify factors which contribute to such variability in human responses to NIBS.