A Novel Paired Somatosensory-Cerebellar Stimulation Induces Plasticity on Cerebellar-Brain Connectivity.

The cerebellum receives and integrates a large amount of sensory information that is important for motor coordination and learning. The aim of the present work was to investigate whether peripheral nerve and cerebellum paired associative stimulation (cPAS) could induce plasticity in both the cerebellum and the cortex. In a cross-over design, we delivered right median nerve electrical stimulation 25 or 10 ms before applying transcranial magnetic stimulation over the cerebellum. We assessed changes in motor evoked potentials (MEP), somatosensory evoked potentials (SEP), short-afferent inhibition (SAI), and cerebellum-brain inhibition (CBI) immediately, and 30 min after cPAS. Our results showed a significant reduction in CBI 30 minutes after cPAS, with no discernible changes in MEP, SEP, and SAI. Notably, cPAS10 did not produce any modulatory effects on these parameters. In summary, cPAS25 demonstrated the capacity to induce plasticity effects in the cerebellar cortex, leading to a reduction in CBI. This novel intervention may be used to modulate plasticity mechanisms and motor learning in healthy individuals and patients with neurological conditions.

Short-term transcutaneous trigeminal nerve stimulation does not affect visual oddball task and paired-click paradigm ERP responses in healthy volunteers.

Recent research suggests that transcutaneous trigeminal nerve stimulation (TNS) may positively affect cognitive function. However, no clear-cut evidence is available yet, since the majority of it derives from clinical studies, and the few data on healthy subjects show inconsistent results. In this study, we report the effects of short-term TNS on event-related potentials (ERP) recorded during the administration of a simple visual oddball task and a paired-click paradigm, both considered useful for studying brain information processing functions. Thirty-two healthy subjects underwent EEG recording before and after 20 min of sham- or real-TNS, delivered bilaterally to the infraorbital nerve. The amplitude and latency of P200 and P300 waves in the simple visual oddball task and P50, N100 and P200 waves in the paired-click paradigm were measured before and after treatment. Our results show that short-term TNS did not alter any of the ERP parameters measured, suggesting that in healthy subjects, short-term TNS may not affect brain processes involved in cognitive functions such as pre-attentional processes, early allocation of attention and immediate memory. The perspective of having an effective, non-pharmacological, non-invasive, and safe treatment option for cognitive decline is particularly appealing; therefore, more research on the positive effects on cognition of TNS is definitely needed.

Is it possible to compare inhibitory and excitatory intracortical circuits in face and hand primary motor cortex?

Face muscles are important in a variety of different functions, such as feeding, speech and communication of non-verbal affective states, which require quite different patterns of activity from those of a typical hand muscle. We ask whether there are differences in their neurophysiological control that might reflect this. Fifteen healthy individuals were studied. Standard single- and paired-pulse transcranial magnetic stimulation (TMS) methods were used to compare intracortical inhibitory (short interval intracortical inhibition (SICI); cortical silent period (CSP)) and excitatory circuitries (short interval intracortical facilitation (SICF)) in two typical muscles, the depressor anguli oris (DAO), a face muscle, and the first dorsal interosseous (FDI), a hand muscle. TMS threshold was higher in DAO than in FDI. Over a range of intensities, resting SICF was not different between DAO and FDI, while during muscle activation SICF was stronger in FDI than in DAO (P = 0.012). At rest, SICI was stronger in FDI than in DAO (P = 0.038) but during muscle contraction, SICI was weaker in FDI than in DAO (P = 0.034). We argue that although many of the difference in response to the TMS protocols could result from the difference in thresholds, some, such as the reduction of resting SICI in DAO, may reflect fundamental differences in the physiology of the two muscle groups. KEY POINTS: Transcranial magnetic stimulation (TMS) single- and paired-pulse protocols were used to investigate and compare the activity of facilitatory and inhibitory intracortical circuits in a face (depressor anguli oris; DAO) and hand (first dorsal interosseous; FDI) muscles. Several TMS intensities and interstimulus intervals were tested with the target muscles at rest and when voluntarily activated. At rest, intracortical inhibitory activity was stronger in FDI than in DAO. In contrast, during muscle contraction inhibitory activity was stronger in DAO than in FDI. As many previous reports have found, the motor evoked potential threshold was higher in DAO than in FDI. Although many of the differences in response to the TMS protocols could result from the difference in thresholds, some, such as the reduction of resting short interval intracortical inhibition in DAO, may reflect fundamental differences in the physiology of the two muscle groups.

Faces emotional expressions: from perceptive to motor areas in aged and young subjects.

The role of age in perception and production of facial expressions is still unclear. Therefore, this work compared, in aged and young subjects, the effects of passive viewing of faces expressing different emotions on perceptive brain regions, such as occipital and temporal cortical areas and on the primary motor cortex (M1) innervating lower face muscles. Seventeen young (24.41 ± 0.71 yr) and seventeen aged (63.82 ± 0.99 yr) subjects underwent recording of event-related potentials (ERP), of motor potentials evoked by transcranial magnetic stimulation of face M1 in the depressor anguli oris muscle and reaction time assessment. In both groups, the P100 and N170 waves, as well as short-latency intracortical inhibition (SICI) and intracortical facilitation (ICF) were probed in face M1 after 300 ms from the presentation of images reporting faces expressing happy, sad, and neutral emotions. ERP data evidenced a major involvement of the right hemisphere in perceptual processing of faces, regardless of age. Compared with young subjects, the aged group showed a delayed N170 wave and a smaller P100 wave following the view of sad but not happy or neutral expressions, along with less accuracy and longer reaction times for recognition of the emotion expressed by faces. Aged subjects presented less SICI than young subjects, but facial expressions of happiness increased the excitability of face M1 with no differences between groups. In conclusion, data suggest that encoding of sad face expressions is impaired in the aged compared with the young group, whereas perception of happiness and its excitatory effects on face M1 remains preserved.NEW & NOTEWORTHY This study shows that aged subjects have less visual attention and impaired perception for sad, but not for happy, face expressions. Conversely, the view of happy, but not sad, faces increases excitability in face M1 bilaterally, regardless of age. The impaired attention for sad expressions, the preserved perception of faces expressing happiness, along with the enhancing effects of the latter on face M1 excitability, likely makes the aged subjects more motivated in approaching positive emotions.

The vestibulo-masseteric reflex and the acoustic-masseteric reflex: a reliability and responsiveness study in healthy subjects.

The vestibulo-masseteric reflex (VMR or p11 wave), the acoustic-masseteric reflex (AMR or p1/n21 wave) and the mixed vestibulo-cochlear p11/n21 potential are responses of masseter muscles to sound that can be employed to evaluate brainstem function. This study was aimed at establishing the test-retest reliability and responsiveness of these reflex parameters according to the type of electrode configuration. Twenty-two healthy volunteers (M:F = 11:11; mean age 25.3 ± 5.2 years) participated in two testing sessions separated by one week. Zygomatic and mandibular montages were compared following unilateral and bilateral stimulations. For reliability purposes, intraclass correlation coefficient (ICC), coefficient of variation of the method error (CVME) and standard error of measurement (SEM) were calculated. The minimal detectable difference (MDD) was also determined as a measure of responsiveness. Both VMR (p11 wave) and AMR could be consistently evoked from test to retest, although the frequency rate was significantly higher (all p values ≤ 0.009) with zygomatic (VMR: 97.7-100%; AMR: 86.9-97.6%) than mandibular montage (VMR: 84.7-89.8%; AMR: 65.0-67.8%), with no significant differences between unilateral and bilateral stimulations. Good-to-excellent reliability and responsiveness (high ICC, low CVME, SEM and MDD scores) were detected for corrected amplitudes and peak latencies for all reflex responses, whereas raw amplitudes were associated to poor reliability. The reliability of the zygomatic montage proved superior to the mandibular montage for all reflex responses. Given their high test-retest consistency and capability to study different features of the reflex arch, both peak latencies and corrected amplitudes should be reported and considered in the interpretation of reflex testing results.

Sensorimotor integration in cranial muscles tested by short- and long-latency afferent inhibition.

OBJECTIVE: To compressively investigate sensorimotor integration in the cranial-cervical muscles in healthy adults. METHODS: Short- (SAI) and long-latency afferent (LAI) inhibition were probed in the anterior digastric (AD), the depressor anguli oris (DAO) and upper trapezius (UT) muscles. A transcranial magnetic stimulation pulse over primary motor cortex was preceded by peripheral stimulation delivered to the trigeminal, facial and accessory nerves using interstimulus intervals of 15-25 ms and 100-200 ms for SAI and LAI respectively. RESULTS: In the AD, both SAI and LAI were detected following trigeminal nerve stimulation, but not following facial nerve stimulation. In the DAO, SAI was observed only following trigeminal nerve stimulation, while LAI depended only on facial nerve stimulation, only at an intensity suprathreshold for the compound motor action potential (cMAP). In the UT we could only detect LAI following accessory nerve stimulation at an intensity suprathreshold for a cMAP. CONCLUSIONS: The results suggest that integration of sensory inputs with motor output is profoundly influenced by the type of sensory afferent involved and by the functional role played by the target muscle. SIGNIFICANCE: Data indicate the importance of taking into account the sensory receptors involved as well as the function of the target muscle when studying sensorimotor integration, both in physiological and neurological conditions.

Face emotional expressions influence interhemispheric inhibition.

The processing of face expressions is a key ability to perform social interactions. Recently, it has been demonstrated that the excitability of the hand primary motor cortex (M1) increases following the view of negative faces expressions. Interhemispheric interactions and sensory-motor integration are cortical processes involving M1, which are known to be modulated by emotional and social behaviors. Whether these processes may mediate the effects of face emotional expressions on M1 excitability is unknown. Therefore, the aim of this study was to investigate the influence of the passive viewing of face emotional expressions on M1 interhemispheric connections and sensory-motor integration using standardized transcranial magnetic stimulation (TMS) protocols. Nineteen healthy subjects participated in the study. Interhemispheric inhibition (IHI) and short-afferent inhibition (SAI) were probed in the right first dorsal interosseous (FDI) muscle 300 ms after the randomized presentation of seven different face expressions (neutral, sadness, fear, disgust, surprise and happiness). Results showed a significantly reduced IHI following the passive viewing of fearful faces compared to neutral (p = .001) and happy (p = .035) faces and following the view of sad faces compared to neutral faces (p = .008). No effect of emotional faces was detected on SAI. Data suggest that sensory-motor integration process does not mediate the increased excitability of M1 induced by the view of negative face expressions. By contrast, it may be underpinned by a depression of IHI, which from a functional point of view may promote symmetrical avoiding movements of the hands in response to aversive stimuli.

Abnormalities in the face primary motor cortex in oromandibular dystonia.

OBJECTIVE: To comprehensively investigate excitability in face and hand M1 and sensorimotor integration in oromandibular dystonia (OMD) patients. METHODS: Short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), short (SAI) and long (LAI) afferent inhibition were investigated in face and hand M1 using transcranial magnetic stimulation protocols in 10 OMD patients. Data were compared with those obtained in 10 patients with focal hand dystonia (FHD), in 10 patients with blepharospasm (BSP), and 10 matched healthy subjects (HS). RESULTS: Results demonstrated that in OMD patients SICI was reduced in face M1 (p < 0.001), but not in hand M1, compared to HS. In FHD, SICI was significantly impaired in hand M1 (p = 0.029), but not in face M1. In BSP, SICI was normal in both face and hand M1 while ICF and LAI were normal in all patient groups and cortical area tested. SAI was significantly reduced (p = 0.003) only in the face M1 of OMD patients. CONCLUSIONS: In OMD, SICI and SAI were significantly reduced. These abnormalities are specific to the motor cortical area innervating the muscular district involved in focal dystonia. SIGNIFICANCE: In OMD, the integration between sensory inflow and motor output seem to be disrupted at cortical level with topographic specificity.

Emotional Face Expressions Influence the Delay Eye-blink Classical Conditioning.

Recent evidence raised the importance of the cerebellum in emotional processes, with specific regard to negative emotions. However, its role in the processing of face emotional expressions is still unknown. This study was aimed at assessing whether face emotional expressions influence the cerebellar learning processes, using the delay eyeblink classical conditioning (EBCC) as a model. Visual stimuli composed of faces expressing happy, sad and neutral emotions were used as conditioning stimulus in forty healthy subjects to modulate the cerebellum-brainstem pathway underlying the EBCC. The same stimuli were used to explore their effects on the blink reflex (BR) and its recovery cycle (BRRC) and on the cerebellar-brain inhibition (CBI). Data analysis revealed that the learning component of the EBCC was significantly reduced following the passive view of sad faces, while the extinction phase was modulated by both sad and happy faces. By contrast, BR, BRRC and CBI were not significantly affected by the view of emotional face expressions. The present study provides first evidence that the passive viewing of faces displaying emotional expressions, are processed by the cerebellum, with no apparent involvement of the brainstem and the cerebello-cortical connection. In particular, the view of sad faces, reduces the excitability of the cerebellar circuit underlying the learning phase of the EBCC. Differently, the extinction phase was shortened by both happy and sad faces, suggesting that different neural bases underlie learning and extinction of emotions expressed by faces.

Physiological Differences in Hand and Face Areas of the Primary Motor Cortex in Skilled Wind and String Musicians.

The process of learning and playing a musical instrument modulates the structural and functional organization of cortical motor networks. In the present study the excitability and short-term functional plasticity of face and hand areas of primary motor cortex (M1) were compared in woodwind musicians (WM), string musicians (SM) and non-musicians (NM) to test the hypothesis that neurophysiological adaptations to the long-term experience of playing a musical instrument are site-specific and related to the particular physiological properties of the representation area in M1. Twenty-two musicians (11 SM, 11 WM) and 11 NM participated in the study. Transcranial magnetic stimulation (TMS) was used to probe rest and active short-latency intracortical inhibition (SICI), interhemispheric inhibition (IHI) and response to paired associative stimulation (PAS). TMS-induced motor evoked potentials (MEP) were recorded from the depressor anguli oris (DAO) and the first dorsal interosseous (FDI) muscles, respectively. Rest and active SICI were the same in all groups (all p > 0.05). WM exhibited significant IHI in the DAO (p = 0.031), in contrast to its absence in SM and NM. Compared with NM and WM, the PAS-induced increase in MEP amplitude in SM was significantly larger in hand M1 (p = 0.008) but not in face M1. In conclusion, neurophysiological adaptations differ between WM, in whom control of the embouchure is highly important, and SM who perform a large range of sequential finger movements and are site-specific in M1.

Reporting quality of TMS studies in neurological conditions: A critical appraisal of the main gaps, challenges and clinical implications.

Transparent reporting of study methods and findings can dramatically expand the reliability and impact of health research. Evidence-based reporting checklists and guidelines, such as those hosted by the EQUATOR network, provide a framework for summarizing statistics, methods and data presentation. While being increasingly used in several research fields, such trend toward better control seems in its infancy in the field of transcranial magnetic stimulation (TMS). By the present work we aimed at assessing the quality of methodological and statistical reporting of TMS-based investigations in individuals with neurological motor impairments. We completed a methodological survey of all the studies conducted in the last two decades on the application of TMS to evaluate motor impairments in individual with neurological conditions. The pre-planned literature search of three major biomedical databases resulted in 1109 articles retrieved, 571 of which satisfied the eligibility criteria. The survey revealed that most of the studies suffered from relevant methodological and statistical issues, which potentially affect data interpretation and usability. Among these, sample size calculation, indices of change other than p values, reproducibility and clinical relevance/responsiveness emerged as those elements most commonly neglected. To increase research reliability of TMS data, we recommend adhering to international initiatives like the EQUATOR, that can impact clinical research by promoting adequate reporting. In particular, we advocate an update of the submission policies of the journals active in this field in line with adjacent areas, such as neurorehabilitation, that require the uploading of completed checklists that rationalize reporting.

Transcutaneous trigeminal nerve stimulation modulates the hand blink reflex.

The hand-blink reflex (HBR) is a subcortical response, elicited by the electrical stimulation of the median nerve, whose magnitude is specifically modulated according to the spatial properties of the defensive peripersonal space (DPPS) of the face. For these reasons, the HBR is commonly used as a model to assess the DPPS of the face. Little is known on the effects induced by the activation of cutaneous afferents from the face on the DPPS of the face. Therefore, we tested the effect of non-painful transcutaneous trigeminal nerve stimulation (TNS) on the amplitude of the HBR. Fifteen healthy participants underwent HBR recording before and after 20 min of sham- and real-TNS delivered bilaterally to the infraorbital nerve in two separate sessions. The HBR was recorded bilaterally from the orbicularis oculi muscles, following non-painful median nerve stimulation at the wrist. The HBR amplitude was assessed in the "hand-far" and "hand-near" conditions, relative to the hand position in respect to the face. The amplitudes of the hand-far and hand-near HBR were measured bilaterally before and after sham- and real-TNS. Real-TNS significantly reduced the magnitude of the HBR, while sham-TNS had no significant effect. The inhibitory effect of TNS was of similar extent on both the hand-far and hand-near components of the HBR, which suggests an action exerted mainly at brainstem level.