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.

Role of cutaneous and proprioceptive inputs in sensorimotor integration and plasticity occurring in the facial primary motor cortex.

KEY POINTS: Previous studies investigating the effects of somatosensory afferent inputs on cortical excitability and neural plasticity often used transcranial magnetic stimulation (TMS) of hand motor cortex (M1) as a model, but in this model it is difficult to separate out the relative contribution of cutaneous and muscle afferent input to each effect. In the face, cutaneous and muscle afferents are segregated in the trigeminal and facial nerves, respectively. We studied their relative contribution to corticobulbar excitability and neural plasticity in the depressor anguli oris M1. Stimulation of trigeminal afferents induced short-latency (SAI) but not long-latency (LAI) afferent inhibition of face M1, while facial nerve stimulation evoked LAI but not SAI. Plasticity induction was observed only after a paired associative stimulation protocol using the facial nerve. Physiological differences in effects of cutaneous and muscle afferent inputs on face M1 excitability suggest they play separate functional roles in behaviour. ABSTRACT: The lack of conventional muscle spindles in face muscles raises the question of how sensory input from the face is used to control muscle activation. In 16 healthy volunteers, we probed sensorimotor interactions in face motor cortex (fM1) using short-afferent inhibition (SAI), long-afferent inhibition (LAI) and LTP-like plasticity following paired associative stimulation (PAS) in the depressor anguli oris muscle (DAO). Stimulation of low threshold afferents in the trigeminal nerve produced a clear SAI (P < 0.05) when the interval between trigeminal stimulation and transcranial magnetic stimulation (TMS) of fM1 was 15-30 ms. However, there was no evidence for LAI at longer intervals of 100-200 ms, nor was there any effect of PAS. In contrast, facial nerve stimulation produced significant LAI (P < 0.05) as well as significant facilitation 10-30 minutes after PAS (P < 0.05). Given that the facial nerve is a pure motor nerve, we presume that the afferent fibres responsible were those activated by the evoked muscle twitch. The F-wave in DAO was unaffected during both LAI and SAI, consistent with their presumed cortical origin. We hypothesize that, in fM1, SAI is evoked by activity in low threshold, presumably cutaneous afferents, whereas LAI and PAS require activity in (higher threshold) afferents activated by the muscle twitch evoked by electrical stimulation of the facial nerve. Cutaneous inputs may exert a paucisynaptic inhibitory effect on fM1, while proprioceptive information is likely to target inhibitory and excitatory polysynaptic circuits involved in LAI and PAS. Such information may be relevant to the physiopathology of several disorders involving the cranio-facial system.

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.

Happy faces selectively increase the excitability of cortical neurons innervating frowning muscles of the mouth.

Although facial muscles are heavily involved in emotional expressions, there is still a lack of evidence about the role of face primary motor cortex (face M1) in the processing of facial recognition and expression. This work investigated the effects of the passive viewing of different facial expressions on face M1 and compared data with those obtained from the hand M1. Thirty healthy subjects were randomly assigned to two groups undergoing transcranial magnetic stimulation (TMS) of face or hand M1. In both groups, short-latency intracortical inhibition (SICI) and intracortical facilitation (ICF) were probed in the depressor anguli oris (DAO) and first dorsal interosseous (FDI) muscles 300 ms after presentation of a picture of a face that expressed happy, sad or neutral emotions. Statistical analysis of SICI showed a non-significant effect of muscle (F1,28 = 1.903, p = 0.179), but a significant effect of emotion (F2,56 = 6.860, p = 0.004) and a significant interaction between muscle and emotion (F2,56 = 5.072, p = 0.015). Post hoc analysis showed that there was a significant reduction of SICI in the DAO muscle after presentation of a face with a happy expression compared with a neutral face (p < 0.001). In the FDI, a significant difference was observed between neutral and sad expressions (p = 0.010) No clear differences in ICF were detected. The different responses of face and hand muscles to emotional stimuli may be due to their functional roles in emotional expression versus protection of the body.

Enhancing research quality of studies on VEMPs in central neurological disorders: a scoping review.

Common pitfalls in vestibular-evoked myogenic potential (VEMP) recording methods have been extensively outlined by several reviews. Conversely, the robustness of research methodology employed for the design and conduct of VEMP studies has never been appraised. To fill this void, we conducted a scoping review to map and evaluate the overall quality of the existing literature on VEMPs in central neurological disorders. Five databases were searched from inception to October 2018 for case-control studies on multiple sclerosis (MS), cerebellar and/or brainstem strokes, Parkinson's disease (PD), migraine, and tumors of the cerebellopontine angle. Study quality was assessed using the Agency for Healthcare Research and Quality criteria (AHRQ). The 11-criteria AHRQ scoring system revealed that PD studies achieved a score of 5/11, migraine and cerebellar and/or brainstem stroke a score of 4/11, MS and tumors of the cerebellopontine angle a score of 3/11. Age was found to be one of the main sources of case-control imbalance: compared with controls, cases were significantly older with a 3.6-yr difference in MS studies, 6 yr in PD, up to 12 yr in stroke and tumors. Regardless of pathological condition, case-control groups were found unmatched also by gender. Post hoc power calculations revealed that 53% of the studies achieved the minimum statistical power of 80%. This scoping review revealed low research quality across the literature on VEMPs in central neurological disorders. Scoping lines are provided on actions to be undertaken in future studies to establish a common methodological platform and enhance the quality of research in this field.NEW & NOTEWORTHY Robust methodology is a prerequisite for any type of research, particularly for observational designs such as those employed in vestibular-evoked myogenic potential (VEMP) research. On these premises, this scoping review provides methodological guidelines to improve validity, accuracy and consistency of clinical outcomes from VEMP studies involving central nervous system disorders. In fact, the high risk for bias that is inherent to poor methodology threatens the validity of the findings of works that are technically sound but methodologically flawed.

Effects of acute trigeminal nerve stimulation on rest EEG activity in healthy adults.

Trigeminal nerve stimulation (TNS) is a non-invasive neuromodulation method which is increasingly used for its beneficial effects on symptoms of several neuropsychiatric disorders such as drug-resistant epilepsy. Sites and mechanisms of its action are still unknown. The present study was aimed at investigating the physiological effects of acute TNS on rest electroencephalographic (EEG) activity. EEG was recorded with a 19-channel EEG system from 18 healthy adults who underwent 20 min of sham- and real-TNS (cycles of 30 s ON and 30 s OFF) in two separate sessions. EEG was continuously acquired in the 10-min preceding TNS, during TNS in the "OFF" period and throughout 10 min after TNS. Mean frequency, total power over the 0.5-48 Hz frequency range and absolute power for delta, theta, alpha, beta and gamma bands were analyzed by a discrete Fast Fourier Transform algorithm. Interhemispheric and intrahemispheric coherences were also analyzed for each band at different time points. Intra- and interhemispheric coherences were significantly reduced for the beta frequencies only during real-TNS (p = 0.002 and p = 0.006, respectively). No TNS effect on the power spectra of any band was detected. A trend of increase in the mean EEG frequency total power during real-TNS (p = 0.03) and of decrease in interhemispheric gamma coherence after real-TNS (p = 0.01) was observed. Acute TNS may induce a spatially diffuse desynchronization of fast EEG rhythms in healthy adults, this desynchronization may underpin the antiepileptic effect of TNS described by clinical studies.

Short-term trigeminal neuromodulation does not alter sleep latency in healthy subjects: a pilot study.

It has been reported that during and/or after acute trigeminal nerve stimulation (TNS) a state of sedation, decreased attention and vigilance, with a tendency to fall asleep, occurs. Whether these effects are due to a hypnotic action of TNS is yet to be demonstrated. This pilot study investigates whether acute TNS affects the latency of sleep using the Multiple Sleep Latency Test (MSLT) in healthy subjects. MSLT was performed in 14 healthy subjects after 20 min of real- and a sham-TNS, delivered in two different sessions. Mean latency of sleep across the five naps accorded and the latency of sleep for each nap was determined. All subjects reported a state of relaxation or drowsiness after the real-TNS session. Repeated-measures ANOVA showed no significant differences in sleep latency between the real and sham conditions. The sedative effects of acute TNS do not seem associated to a hypnotic effect.

Cerebellar Theta-Burst Stimulation Impairs Memory Consolidation in Eyeblink Classical Conditioning.

Associative learning of sensorimotor contingences, as it occurs in eyeblink classical conditioning (EBCC), is known to involve the cerebellum, but its mechanism remains controversial. EBCC involves a sequence of learning processes which are thought to occur in the cerebellar cortex and deep cerebellar nuclei. Recently, the extinction phase of EBCC has been shown to be modulated after one week by cerebellar continuous theta-burst stimulation (cTBS). Here, we asked whether cerebellar cTBS could affect retention and reacquisition of conditioned responses (CRs) tested immediately after conditioning. We also investigated a possible lateralized cerebellar control of EBCC by applying cTBS on both the right and left cerebellar hemispheres. Both right and left cerebellar cTBSs induced a statistically significant impairment in retention and new acquisition of conditioned responses (CRs), the disruption effect being marginally more effective when the left cerebellar hemisphere was stimulated. These data support a model in which cTBS impairs retention and reacquisition of CR in the cerebellum, possibly by interfering with the transfer of memory to the deep cerebellar nuclei.

Resistance Training for Muscle Weakness in Multiple Sclerosis: Direct Versus Contralateral Approach in Individuals With Ankle Dorsiflexors' Disparity in Strength.

OBJECTIVE: To compare effects of contralateral strength training (CST) and direct strength training of the more affected ankle dorsiflexors on muscle performance and clinical functional outcomes in people with multiple sclerosis (MS) exhibiting interlimb strength asymmetry. DESIGN: Randomized controlled trial. SETTING: University hospital. PARTICIPANTS: Individuals with relapsing-remitting MS (N=30) and mild-to-moderate disability (Expanded Disability Status Scale score ≤6) presenting with ankle dorsiflexors' strength disparity. INTERVENTIONS: Participants were randomly assigned to a CST (n=15) or direct strength training (n=15) group performing 6 weeks of maximal intensity strength training of the less or more affected dorsiflexors, respectively. MAIN OUTCOME MEASURES: Maximal strength, endurance to fatigue, and mobility outcomes were assessed before, at the intervention end, and at 12-week follow-up. Strength and fatigue parameters were measured after 3 weeks of training (midintervention). RESULTS: In the more affected limb of both groups, pre- to postintervention significant increases in maximal strength (P≤.006) and fatigue endurance (P≤.04) were detected along with consistent retention of these improvements at follow-up (P≤.04). At midintervention, the direct strength training group showed significant improvements (P≤.002), with no further increase at postintervention, despite training continuation. Conversely, the CST group showed nonsignificant strength gains, increasing to significance at postintervention (P≤.003). In both groups, significant pre- to postintervention improvements in mobility outcomes (P≤.03), not retained at follow-up, were observed. CONCLUSIONS: After 6 weeks of training, CST proved as effective as direct strength training in enhancing performance of the more affected limb with a different time course, which may have practical implications in management of severely weakened limbs where direct strength training is not initially possible.

Transcutaneous trigeminal nerve stimulation induces a long-term depression-like plasticity of the human blink reflex.

The beneficial effects of trigeminal nerve stimulation (TNS) on several neurological disorders are increasingly acknowledged. Hypothesized mechanisms include the modulation of excitability in networks involved by the disease, and its main site of action has been recently reported at brain stem level. Aim of this work was to test whether acute TNS modulates brain stem plasticity using the blink reflex (BR) as a model. The BR was recorded from 20 healthy volunteers before and after 20 min of cyclic transcutaneous TNS delivered bilaterally to the infraorbital nerve. Eleven subjects underwent sham-TNS administration and were compared to the real-TNS group. In 12 subjects, effects of unilateral TNS were tested. The areas of the R1 and R2 components of the BR were recorded before and after 0 (T0), 15 (T15), 30 (T30), and 45 (T45) min from TNS. In three subjects, T60 and T90 time points were also evaluated. Ipsi- and contralateral R2 areas were significantly suppressed after bilateral real-TNS at T15 (p = 0.013), T30 (p = 0.002), and T45 (p = 0.001), while R1 response appeared unaffected. The TNS-induced inhibitory effect on R2 responses lasted up to 60 min. Real- and sham-TNS protocols produced significantly different effects (p = 0.005), with sham-TNS being ineffective at any time point tested. Bilateral TNS was more effective (p = 0.009) than unilateral TNS. Acute TNS induced a bilateral long-lasting inhibition of the R2 component of the BR, which resembles a long-term depression-like effect, providing evidence of brain stem plasticity produced by transcutaneous TNS. These findings add new insight into mechanisms of TNS neuromodulation and into physiopathology of those neurological disorders where clinical benefits of TNS are recognized.

Abnormalities of vestibular-evoked myogenic potentials in idiopathic Parkinson's disease are associated with clinical evidence of brainstem involvement.

Brainstem degeneration in Parkinson's disease (PD) may explain the occurrence of many non-motor symptoms in this condition. Purposes of the present work were to investigate brainstem function in PD through a battery of vestibular-evoked myogenic potentials (VEMP) allowing a comprehensive brainstem exploration and to correlate VEMP findings with symptoms related to brainstem involvement. Cervical (cVEMP), masseter (mVEMP) and ocular (oVEMP) VEMPs were investigated in 24 PD patients and compared with those recorded in 24 age-matched controls. Presence of symptoms ascribable to brainstem dysfunction, such as daytime sleepiness, REM sleep behavior disorder and depression, was investigated through Epworth Sleepiness Scale, Parkinson's Disease Sleep Scale, REM Sleep Disorder Screening Questionnaire (RBD-SQ) and Geriatric Depression Scale. Postural instability was additionally assessed through mini-BESTest. The frequency of alteration of VEMPs in patients was 83.3 % when considering the whole set and 41.7 % for cVEMP, 66.7 % for mVEMP and 45.8 % for oVEMP. This was significantly different from controls, with absence being the prevalent alteration in PD. A significant inverse correlation between the number of altered VEMPs and mini-BESTest and a direct correlation with RBD-SQ were found. The VEMP battery under study allowed the identification of brainstem dysfunctions in PD patients, which correlated with clinical tests suggestive of postural and REM sleep disorders. VEMPs might represent a valuable tool of brainstem assessment in PD.

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.

Investigating the Effects of a Focal Muscle Vibration Protocol on Sensorimotor Integration in Healthy Subjects.

Background: The ability to perceive two tactile stimuli as asynchronous can be measured using the somatosensory temporal discrimination threshold (STDT). In healthy humans, the execution of a voluntary movement determines an increase in STDT values, while the integration of STDT and movement execution is abnormal in patients with basal ganglia disorders. Sensorimotor integration can be modulated using focal muscle vibration (fMV), a neurophysiological approach that selectively activates proprioceptive afferents from the vibrated muscle. Method: In this study, we investigated whether fMV was able to modulate STDT or STDT-movement integration in healthy subjects by measuring them before, during and after fMV applied over the first dorsalis interosseous, abductor pollicis brevis and flexor radialis carpi muscles. Results: The results showed that fMV modulated STDT-movement integration only when applied over the first dorsalis interosseous, namely, the muscle performing the motor task involved in STDT-movement integration. These changes occurred during and up to 10 min after fMV. Differently, fMV did not influence STDT at rest. We suggest that that fMV interferes with the STDT-movement task processing, possibly disrupting the physiological processing of sensory information. Conclusions: This study showed that FMV is able to modulate STDT-movement integration when applied over the muscle involved in the motor task. This result provides further information on the mechanisms underlying fMV, and has potential future implications in basal ganglia disorders characterized by altered sensorimotor integration.

Pathophysiological mechanisms of oromandibular dystonia.

Oromandibular dystonia (OMD) is a rare form of focal idiopathic dystonia. OMD was clinically identified at the beginning of the 20th century, and the main clinical features have been progressively described over the years. However, OMD has several peculiarities that still remain unexplained, including the high rate of oral trauma, which is often related to the onset of motor symptoms. The purpose of this paper was to formulate a hypothesis regarding the pathophysiology of OMD, starting from the neuroanatomical basis of the masticatory and facial systems and highlighting the features that differentiate this condition from other forms of focal idiopathic dystonia. We provide a brief review of the clinical and etiological features of OMD as well as neurophysiological and neuroimaging findings obtained from studies in patients with OMD. We discuss possible pathophysiological mechanisms underlying OMD and suggest that abnormalities in sensory input processing may play a prominent role in OMD pathophysiology, possibly triggering a cascade of events that results in sensorimotor cortex network dysfunction. Finally, we identify open questions that future studies should address, including the effect of abnormal sensory input processing and oral trauma on the peculiar neurophysiological abnormalities observed in OMD.

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.