Functional Role of Cerebellar Gamma Frequency in Motor Sequences Learning: a tACS Study.

Although the role of the cerebellum in motor sequences learning is widely established, the specific function of its gamma oscillatory activity still remains unclear. In the present study, gamma (50 Hz)-or delta (1 Hz)-transcranial alternating current stimulation (tACS) was applied to the right cerebellar cortex while participants performed an implicit serial reaction time task (SRTT) with their right hand. The task required the execution of motor sequences simultaneously with the presentation of a series of visual stimuli. The same sequence was repeated across multiple task blocks (from blocks 2 to 5 and from blocks 7 to 8), whereas in other blocks, new/pseudorandom sequences were reproduced (blocks 1 and 6). Task performance was examined before and during tACS. To test possible after-effects of cerebellar tACS on the contralateral primary motor cortex (M1), corticospinal excitability was assessed by examining the amplitude of motor potentials (MEP) evoked by single-pulse transcranial magnetic stimulation (TMS). Compared with delta stimulation, gamma-tACS applied during the SRTT impaired participants' performance in blocks where the same motor sequence was repeated but not in blocks where the new pseudorandom sequences were presented. Noteworthy, the later assessed corticospinal excitability was not affected. These results suggest that cerebellar gamma oscillations mediate the implicit acquisition of motor sequences but do not affect task execution itself. Overall, this study provides evidence of a specific role of cerebellar gamma oscillatory activity in implicit motor learning.

Prism adaptation in patients with unilateral lesion of the parietal or cerebellar cortex: A pilot study on two single cases using a concurrent exposure procedure.

Neuroimaging studies showed that prism adaptation (PA), a widely used tool for the rehabilitation of neglect, involves a wide network of brain regions including the parietal cortex and the cerebellum. In particular, the parietal cortex has been suggested to mediate the initial stage of PA through conscious compensatory mechanisms as a reaction to the deviation induced by PA. The cerebellum, on the other side, intervenes in sensory errors prediction to update internal models in later stages. It has been suggested that two mechanisms may underlie PA effects: recalibration, a strategic cognitive process occurring in the initial stages of PA, and realignment, a fully automatic reorganization of spatial maps emerging later and more slowly in time. The parietal lobe has been proposed to be involved mainly in the recalibration whereas the realignment would be carried over by the cerebellum. Previous studies have investigated the effects of a lesion involving either the cerebellum or the parietal lobe in PA taking into account both realignment and recalibration processes. Conversely, no studies have compared the performance of a patient with a cerebellar lesion to that of a patient with a parietal lesion. In the present study, we used a recently developed technique for digital PA to test for differences in visuomotor learning after a single session of PA in a patient with parietal and a patient with cerebellar lesions, respectively. The PA procedure, in this case, includes a digital pointing task based on a concurrent exposure technique, which allows patients to fully see their arm during the pointing task. This procedure has been shown to be as effective as the terminal exposure condition in neglect rehabilitation albeit different processes take place during concurrent exposure condition compared to the most used terminal exposure (allowing to see only the final part of the movement). Patients' performances were compared to that of a control group. A single session of PA was administered to 1) a patient (BC) with left parieto-occipital lesion involving superior parietal lobe (SPL) and inferior parietal lobe (IPL), 2) a patient (TGM) with a stroke in the territory sub-served by the superior cerebellar artery (SCA) , and 3) 14 healthy controls (HC). The task included three conditions: before wearing prismatic goggles (pre-exposure), while wearing prisms (exposure) and after removing the goggles (post-exposure). Mean deviations were calculated for the following phases: pre-exposure, early-exposure, late-exposure, post-exposure. The presence of after-effect was calculated as the difference between pre-exposure and post-exposure conditions. For each of these conditions, patients' performance was compared to that of the control group by using a modified Crawford t-test. We found that the patient with the parietal lesion had a significantly different performance in the late-exposure and in the post-exposure compared to both HC and the patient with the cerebellar lesion. Conversely, no differences were observed between TGM and HC across all the conditions. Our results show an increase in the magnitude of the adaptation during the late stage of PA in the patient with the parietal lesion whereas no differences in the performance between the cerebellar patient and the controls were found. These results confirm previous studies suggesting that the parietal cortex is an important node of a wider network involved in PA effect. Furthermore, results concerning the cerebellar patient suggest that visuomotor learning is not affected by lesions of the SCA territory when a concurrent exposure is used as, in such case, it less relies on sensory errors prediction to update internal models. Results are discussed considering the novelty of the applied PA technique.

A questionnaire to collect unintended effects of transcranial magnetic stimulation: A consensus based approach.

Transcranial magnetic stimulation (TMS) has been widely used in both clinical and research practice. However, TMS might induce unintended sensations and undesired effects as well as serious adverse effects. To date, no shared forms are available to report such unintended effects. This study aimed at developing a questionnaire enabling reporting of TMS unintended effects. A Delphi procedure was applied which allowed consensus among TMS experts. A steering committee nominated a number of experts to be involved in the Delphi procedure. Three rounds were conducted before reaching a consensus. Afterwards, the questionnaire was publicized on the International Federation of Clinical Neurophysiology website to collect further suggestions by the wider scientific community. A last Delphi round was then conducted to obtain consensus on the suggestions collected during the publicization and integrate them in the questionnaire. The procedure resulted in a questionnaire, that is the TMSens_Q, applicable in clinical and research settings. Routine use of the structured TMS questionnaire and standard reporting of unintended TMS effects will help to monitor the safety of TMS, particularly when applying new protocols. It will also improve the quality of data collection as well as the interpretation of experimental findings.

[The support of the ultrasonography of the shoulder in the diagnosis of polymyalgia rheumatica with normal erythrocyte sedimentation rate]. / L'ausilio dell'ecografia della spalla nella diagnosi della polimialgia reumatica con velocità di eritrosedimentazione normale.

Polymyalgia rheumatica (PMR) is a chronic inflammatory syndrome that affects the elderly population and whose diagnosis is mainly based on clinical criteria taking little advantage of the latest innovatory methods of diagnostic imaging, for instance ultrasonography. Although it is generally characterised by increasing of inflammation values as well as pain and stiffness on the shoulder and pelvic girdles, there is a significant percentage of patients with PMR whose erythrocyte sedimentation rate (ESR) is normal; in this case to make a diagnosis is difficult. The purpose of our study is to demonstrate how useful ultrasound investigations on the shoulders joints could be in order to make a diagnosis of PMR, especially for those patients with atypical normal ESR. Our case control study included 23 patients with atypical PMR and 88 patients with standard symptomatic PMR; both groups underwent shoulder ultrasound scans before receiving steroid therapy. As it has been previously shown, the ultrasound method is able to detect distinctive aspects in the joints and tissues of the patients with PMR; so that we could find that 90% of the patients with PMR of both groups suffered from bilateral subdeltoid bursitis. This disorder is seldom found in healthy people and consequently its presence could be considered a useful diagnostic test/check for/of PMR independently from ESR values.

Effects of low-gamma tACS on primary motor cortex in implicit motor learning.

In the primary motor cortex (M1), rhythmic activity in the gamma frequency band has been found during movement planning, onset and execution. Although the role of high-gamma oscillatory activity in M1 is well established, the contribution of low-gamma activity is still unexplored. In this study, transcranial alternating current stimulation (tACS) was used with the aim to specifically modulate low-gamma frequency band in M1, during an implicit motor learning task. A 40 Hz-tACS was applied over the left M1 while participants performed a serial reaction time task (SRTT) using their right hand. The task required the repetitive execution of sequential movements in response to sequences of visual stimuli. Sequential blocks were interleaved by a random block, which served as interference to sequence learning. Sham and 1 Hz tACS were used as control. Task performance was examined before, during and after tACS (pre-, online- and post-phase, respectively). Furthermore, cortical reactivity of M1 was assessed in the pre- and post-tACS phases, by measuring motor-evoked potentials (MEPs) elicited by single-pulse transcranial magnetic stimulation (TMS). Compared to sham and pre-tACS, the 40 Hz stimulation applied during SRTT slowed down response times in blocks that required retrieving previously learned sequences, after performing the random block. In addition, M1 cortical reactivity was selectively inhibited following 40 Hz-tACS, as quantified by reduced MEP amplitude. These results show that low-gamma tACS delivered over M1 during motor learning enhanced susceptibility to interference generated by the random sequence (i.e., proactive interference effect). Importantly, only low-gamma stimulation produced long-lasting effects on M1 cortical reactivity.

Nutritional strategies for psoriasis: current scientific evidence in clinical trials.

OBJECTIVE: Several nutritional strategies for the management of psoriasis are promising. Even if recent data support that nutrition may play a pivotal role in prevention and co-treatment and despite patient's concerns regarding the best nutritional habits, the consensus regarding the nutritional strategies to be adopted lacks in clinical settings. In this manuscript, the effects of several nutritional strategies for psoriasis patients such as hypocaloric diet, vitamin D, fish oil, selenium, and zinc supplementation were systematically reviewed. Randomized controlled trials (RCTs) on beneficial botanical oral supplements were also included in the analysis. MATERIALS AND METHODS: For each topic, a search was conducted in MEDLINE electronic databases for articles published in English between January 1, 1990 and September 2018. Two independent reviewers assessed and extracted the data. Only controlled clinical trials were selected. RESULTS: The evidence regarding the current nutritional strategies for psoriasis patients were summarized and translated into a global, comprehensible recommendation. CONCLUSIONS: Weight loss combined with a healthy lifestyle was shown to be very beneficial for patients with moderate to severe disease with a significant reduction of the Psoriasis Area and Severity Index (PASI) score. Currently, oral vitamin D supplementation for prevention or treatment of psoriasis in adults with normal vitamin D levels is not recommended; however, psoriasis patients with a deficit in plasma vitamin D levels are advised to complement with oral supplements to prevent psoriasis-related comorbidities. Instead of zinc, selenium, and omega 3 supplements have been proven beneficial for psoriasis patients. Among botanical species, Dunaliella bardawil (D. bardawil), Tripterygium wilfordii (T. wilfordii), Azadirachta indica (A. indica), Curcuma longa (C. longa), and HESA-A are the most beneficial. In conclusion, a close cooperation between nutritionists and dermatologists may be useful for the management of psoriasis.

The time course of idiom processing.

Recent neuropsychological and neurophysiological studies have suggested that the neural correlates of idiom processing are predominantly located in the left Brodmann's area (BA) 22 and, to some extent, in the prefrontal cortex. The present study explores the temporal dynamics of left prefrontal and temporal cortex in idiom processing by using repetitive transcranial magnetic stimulation (rTMS) in normal subjects. Forty-five opaque highly familiar idioms and 45 literal sentences were used. Forty-three subjects completed 5 blocks of 18 trials (9 idioms, 9 literal sentences) corresponding to 4 stimulation conditions (left prefrontal, left temporal, vertex, no-stimulation baseline). Each subject was assigned to one of three groups, which differed in the timing of stimulation delivery. A selective impairment in accuracy for idioms was found when rTMS was applied to the prefrontal and temporal cortex 80ms after picture presentation, confirming the role of these regions in this task. Moreover, rTMS to the prefrontal cortex, but not to the temporal cortex, continued to affect the performance with idiomatic sentences at the later time of 120ms. The results seem to suggest that the prefrontal region is involved in both the retrieval of the figurative meaning from semantic memory and the monitoring of the response by inhibiting alternative interpretations when a picture-matching task is used.

[Therapy of rheumatic polymyalgia: the pathophysiologic management]. / Trattamento della polimialgia reumatica: l'approccio fisiopatologico.

Polymyalgia rheumatica (PMR) is an inflammatory syndrome affecting older people whose prevalence has increased in recent years. The suppression of the hypothalamic-pituitary-adrenal axis (HPA) and ageing may contribute to the pathogenesis of PMR. Chronic stress (i.e. interpersonal, chronic infections etc.) in elderly people may represent a risk factor for the development of PMR. In fact, elderly represent per se a condition of endocrine senescence including adrenal hypofunction, in addition chronic stress represents a further harmful stimulus to seriously compromise endogenous glucocorticoid production. Synovitis and vasculitis characterize the majority of the patients. Serum cytokine and steroidal hormone patterns suggest that patients with PMR have an intensive inflammatory reaction. As a matter of fact, glucocorticoids represent the most useful temporary "replacement" treatment during the active phase of PMR. The use of modified-release glucocorticoids that might induce higher levels during the night (circadian rhythms as in physiological conditions), will represent another important approach to optimize PMR treatment and reduce the side effects. Combination therapy between glucocorticoids and inhibitors of pro-inflammatory cytokines should be tested in large studies and early cases of PMR.

High prevalence of secondary hyperparathyroidism due to hypovitaminosis D in hospitalized elderly with and without hip fracture.

OBJECTIVES: To determine and compare the prevalence of secondary hyperparathyroidism (HPTH) in a population of community-dwelling and institutionalized older adults hospitalized with and without hip fracture, and to evaluate factors correlated with secondary HPTH in this population. METHODS: Circulating concentrations of serum intact PTH, 25-hydroxyvitamin D [25(OH)D] total serum calcium and albumin were measured in 160 subjects with an osteoporotic fracture of the proximal femur and in 160 matched controls hospitalized for a disease unrelated to bone status. Patients with secondary causes of bone loss and taking medications affecting bone metabolism were excluded. Age, sex, place of residence and the ability to perform basic activities of daily living (BADL) two weeks before hospital admission were recorded at baseline. RESULTS: Patients were comparable with regard to the baseline demographic, biochemical and functional characteristics. The overall prevalence of secondary hyperparathyroidism was 51.2%, without significant differences between hip fractured patients and controls (50.6 vs 51.9%, p=0.911). In bivariate analysis only the age and functional status (BADL) demonstrated a significant relationship with secondary HPTH, while sex and place of residence were not significant. These results were also confirmed in multivariate analysis. Particularly, the risk of secondary HPTH increased with age and with the number of functions lost in BADL: patients fully dependent showed a 3 times as high risk (odd ratio 3.07, 95% confidence interval 1.73 to 5.46, p=0.000) compared to patients independent in BADL, and subject aged >88 yr had a twice as high risk of developing secondary HPTH compared to younger ones (odd ratio 2.28, 95% confidence interval 1.20 to 4.32, p=0.012). CONCLUSION: These results show that secondary HPTH due to hypovitaminosis D is a frequent disorder in hospitalized elderly, strongly correlated with the functional status, irrespective of sex and place of residence.

IFN-gamma low production capacity in type 1 diabetes mellitus patients at onset of disease.

In type 1 diabetes mellitus (T1DM), cytokines can be directly cytotoxic to beta-cells, and/or play an indirect role influencing some cells of the immune system. Since several factors could impair cytokine serum levels, the purpose of our study was to longitudinally evaluate intracellular cytokines, in T1DM patients, and in subject at risk, by flow cytometry analysis. At T1DM onset we observed significantly lower percentage of peripheral CD4 + and CD8 + cells producing IFN-gamma in patients compared to controls and subjects at risk. The 15-month follow-up patients showed significantly lower percentage of CD4 + and CD8 + cells producing IFN-gamma compared to the other groups. At 8-year follow-up no significant differences were observed among the groups in the percentage of cells producing cytokines. We could have considered "exhausted cells" or these T cell subsets may be migrated from peripheral blood to pancreas. On the other hand, our results are in agreement with those reported in literature: in animal model the absence of IFN-gamma production makes beta-cells highly susceptible to viral infection and subsequent attack by natural killer cells, which lead to hyperglycaemia and diabetes mellitus.

Effect of IL-6 on IGF binding protein-3: a study in IL-6 transgenic mice and in patients with systemic juvenile idiopathic arthritis.

Stunted growth is a common complication of childhood diseases characterized by chronic inflammation or infections. We previously demonstrated that NSE/hIL-6 transgenic mice, overexpressing the inflammatory cytokine IL-6 since early phase of life, showed a marked growth defect associated with decreased IGF-I levels, suggesting that IL-6 is one of the factors involved in stunted growth complicating chronic inflammation in childhood. Here we show that NSE/hIL-6 mice have normal liver IGF-I production, decreased levels of IGF binding protein-3 (IGFBP-3) and increased serum IGFBP-3 proteolysis. Reduced IGFBP-3 levels results in a marked decrease in the circulating 150-kDa ternary complex, even in the presence of normally functional acid labile subunit. Pharmacokinetic studies showed that NSE/hIL-6 mice have accelerated IGF-I clearance. Patients with systemic juvenile idiopathic arthritis (s-JIA), a chronic inflammatory disease characterized by prominent IL-6 production and complicated by stunted growth associated with low IGF-I levels, have markedly decreased IGFBP-3 levels, increased serum IGFBP-3 proteolysis and normal acid labile subunit levels. Our data show that chronic overproduction of IL-6 causes decreased IGFBP-3 levels, resulting in a decreased association of IGF-I in the 150-kDa complex. Decreased levels of IGF-I appear to be secondary to increased clearance.

Pharmacokinetics and pharmacodynamics of ranitidine after burn injury.

The pharmacokinetics and pharmacodynamics of ranitidine were studied in 10 hypermetabolic burned patients with normal creatinine clearance and compared with healthy volunteers. Ranitidine was administered as a single 50 mg intravenous bolus and multiple blood samples were obtained up to 10 hours after the dose for determination of plasma ranitidine concentrations. Gastric pH in burned patients was monitored by way of a nasogastric tube. Burned patients exhibited significantly higher (p less than 0.01) ranitidine clearance (mean +/- SD; 10.80 +/- 2.38 versus 7.53 +/- 1.71 ml/min/kg) and steady-state distribution volume (1.63 +/- 0.13 versus 1.16 +/- 0.33 L/kg). Within an hour of administration of drug the gastric pH was greater than or equal to 4.0 in all but one patient. This pH was maintained for at least 6 hours. In five patients the pH was greater than or equal to 4.0 throughout the 10-hour study. Thus, despite increased ranitidine clearance, the recommended dose of ranitidine maintained gastric pH greater than or equal to 4.0 throughout the normal dosing interval in the majority of patients. Dosage adjustment reported for many other drugs after burn injury may not be necessary for ranitidine.

rTMS of the unaffected hemisphere transiently reduces contralesional visuospatial hemineglect.

To verify the role of interhemispheric influences on manifestations of neglect, the authors investigated the effects of a transient repetitive transcranial magnetic stimulation (rTMS)-induced disruption of the unaffected hemisphere on contralesional visuospatial neglect in two left- and five right-brain-damaged patients. Parietal rTMS of the unaffected hemisphere during the execution of a computerized task of bisected line's length judgment transiently decreased the magnitude of neglect as expressed in the number of errors.

Effects of motor imagery on motor cortical output topography in Parkinson's disease.

BACKGROUND: The motor impairment in Parkinson's disease (PD) could partly reflect a failure to activate processes of motor imagery. OBJECTIVE: To verify any selective changes of motor output during motor imagery, lateralized to the hemisphere contralateral to the clinically affected side of hemiparkinsonian patients. METHODS: Transcranial magnetic stimulation (TMS) was used to map the cortical representations of the contralateral abductor digiti minimi muscle (ADM) during rest, contraction, and motor imagery in a group of patients with hemi-PD and in a group of healthy volunteers. Seven patients with hemi-PD and seven healthy subjects were examined. Focal TMS was applied over a grid of 20 scalp positions on each hemiscalp. Maps were characterized by area (number of excitable positions), volume (the sum of motor evoked potential amplitudes at all scalp positions), and center of gravity (a map position representing an amplitude-weighted calculation of the excitable area). RESULTS: In healthy control subjects, the area of cortical representation of ADM was symmetrically increased in both hemispheres by mental simulation of movement and real muscle contraction. In patients with hemi-PD, there was a hemispheric asymmetry in the area of cortical representation elicited by motor imagery. The area was reduced in the clinically affected hemisphere. The volume of cortical representation was increased under all conditions and in both hemispheres in patients with PD. However, largely because the volume was so high at rest in patients, the increment in volume associated with contraction was smaller than in control subjects. CONCLUSION: This study demonstrates the presence of a tonic hyperactivation of motor cortical circuitry in PD in conjunction with an abnormality of either motor imagery or the process by which motor imagery engages the sensorimotor cortices in the clinically affected hemisphere.

Congenital erythropoietic porphyria: skeletal manifestations and effect of pamidronate treatment.

Congenital erythropoietic porphyria (CEP) is a rare disorder of heme biosynthesis. Skeletal abnormalities have been described in patients with this disease. We report a 25-year-old woman with osteodystrophy from CEP. On examination, mild hepatosplenomegaly, multiple hyperpigmented scars, hypertrichosis, erythrodontia and red coloration of urine were found. Biochemical studies showed increased serum levels of alkaline phosphatase, fasting and total 24-h urinary calcium excretion. Serum 250H vitamin-D concentration was low due to avoidance of sun exposure. Skeletal radiographs disclosed marked vertical and horizontal trabecular pattern and biconcavity of most of the dorsal and lumbar vertebral bodies. Several round sclerotic lesions (1-3 cm in diameter) were seen in the skull, pelvis and one lumbar vertebrae. The sclerotic lesions were augmented in size and number compared to X-rays obtained 8 years before. Bone mineral density (evaluated by DEXA) was markedly reduced at the spine and moderately diminished at the proximal femur and total skeleton. Treatment for 11 months with pamidronate (and the addition of hydrochlorotiazide for the last 6 months) reduced to normal values the serum levels of alkaline phosphatase and fasting urinary calcium. The 24-h urinary excretion of calcium and hydroxyproline were also decreased. The BMD increased in all the skeletal areas with presumably hyperactive bone marrow: spine, head, ribs and pelvis (and total skeleton), but did not change at the extremities and diminished at the femoral neck. Patients with CEP may present osteodystrophy characterized by sclerotic lesions and osteopenia, most likely due to accelerated bone turnover in areas of active bone marrow.(ABSTRACT TRUNCATED AT 250 WORDS)

Timing of right parietal and frontal cortex activity in visuo-spatial perception: a TMS study in normal individuals.

In a recent study we showed that repetitive transcranial magnetic stimulation (rTMS) with train duration of 400 ms over right frontal and right posterior parietal cortices gives rise to transitory contralateral visuo-spatial neglect in normal subjects. In the present experiment we investigated whether using single-pulse TMS it is possible to obtain information about the timing of cortical activity related to spatial cognition. Nine healthy subjects performed in baseline condition and during TMS a tachistoscopic task, requiring a forced-choice estimation of the length of the two segments of prebisected horizontal lines. Single-pulse TMS was triggered at various time intervals (150 ms, 225 ms, 300 ms) after visual stimulus onset with a focal coil over P6 and F4 (according to 10/20 EEG system). Relative transitory rightward bias was observed only when parietal TMS was delivered 150 ms after visual stimulus presentation. Frontal stimulation induced no effect on visuo-spatial perception with the time intervals explored.

Modulation of spinal cord excitability by subthreshold repetitive transcranial magnetic stimulation of the primary motor cortex in humans.

Repetitive transcranial magnetic stimulation (rTMS) allows the modulation of intra-cortical excitability and may therefore affect the descending control of spinal excitability. We applied rTMS at subthreshold intensity and 1 Hz frequency for 10 min to the left primary motor cortex representation of the flexor carpi radialis muscle (FCR) in 10 subjects and assessed the H and M responses to median nerve stimulation before and after the rTMS. Following rTMS, H wave thresholds significantly reduced by approximately 20%. Maximal H but not M wave amplitude significantly increased over the baseline, so that H/M amplitude ratio was increased by 41%. Sham stimulation did not induce any noticeable change in M or H waves. Slow rTMS might facilitate monosynaptic spinal cord reflexes by inhibiting the cortico-spinal projections modulating spinal excitability.

Contralateral neglect induced by right posterior parietal rTMS in healthy subjects.

We applied repetitive transcranial magnetic stimulation (rTMS) in order to induce interference on visuo-spatial perception in 11 healthy subjects. Subjects performed a visuo-spatial task requiring judgements about the symmetry of prebisected lines. Visual stimuli consisted of symmetrically or asymmetrically transected lines, tachystoscopically presented for 50 ms on a computer-monitor. Performance was examined in basal condition and during rTMS trains of 10 stimuli at 25 Hz, delivered through a focal coil over right or left posterior parietal cortex (P5 and P6 sites) and triggered synchronously with visual stimulus. Randomly intermixed sham rTMS trains were employed to control for non-specific effects. Right parietal rTMS induced a significant rightward bias in symmetry judgements as compared with basal and sham rTMS conditions. No differences emerged between other conditions.

Effect of paired transcranial magnetic stimulation on the cortical silent period.

OBJECTIVE: To investigate the behaviour of silent period (SP) during paired magnetic cortical stimulation. BACKGROUND: Paired cortical magnetic stimulation is known to inhibit or facilitate motor evoked potentials (MEPs), but no attention has been paid to its effect on SP. METHODS: SP was measured in the contracted first dorsal interosseus muscle after paired cortical stimuli at given interstimulus intervals (ISIs) in eight healthy subjects. Test stimulus intensity was fixed at 110% of resting threshold (RT), while three levels of conditioning stimulus intensities at 40%, 65% and 90% RT were separately employed. We also examined the effect of progressively increasing the test stimulus intensity (120-150 RT) on SP while maintaining stable conditioning stimulus intensity. RESULTS: 65% RT conditioning stimulus shortened the SP at 1-3 ms ISIs with MEP size reduction, and prolonged the SP at 15-20 ms ISIs without affecting MEP size. 90% RT conditioning stimulus showed only SP prolongation, while 40% RT showed only SP shortening at 1 ms ISI. The SP shortening at 2 ms ISI was the most evident with 120% RT test stimulus, but without correlation with the MEP size. The SP prolongation at 15 ms ISI was maximal with 110% RT test stimulus and then almost abolished with 150% RT. The SP shortening at short intervals might be due not only to spinal but also to suprasegmental mechanisms, conceivably mediating cortical excitatory drive to the corticospinal tract. The SP prolongation at intermediate intervals might be due to activation of slowly conducting, intra- or sub-cortical polysynaptic pathways exerting a facilitatory drive on the cortical inhibitory interneurons.

Are autonomic signals influencing cortico-spinal motor excitability? A study with transcranial magnetic stimulation.

In order to investigate the role of visceral afferent inputs flowing along autonomic fibers on corticospinal tract excitability, the variability of Motor Evoked Potentials (MEPs), elicited by Transcranial Magnetic Stimulation (TMS), was analysed during simultaneous monitoring of electrocardiogram (EKG) phases, breathing phases and sudomotor skin responses (SSRs) in a group of 10 healthy subjects. A cascade of at least 60 consecutive magnetic stimuli, with an interstimulus interval randomly varying between 20 and 40 s, was acquired. At the end of the recording session, the subject was asked to make at random five not consecutive self-paced forced inspirations. TMS was carried out at an intensity 10% above motor threshold excitability via a circular coil placed over the motor area of the right hemisphere. MEPs were recorded from the contralateral abductor digiti minimi muscle (ADM). Sudomotor Skin Responses (SSRs) were recorded on both hand palms. MEPs latency and amplitude did not show significant correlation with any of the EKG and respiratory phases. During forced inspiration, a significant latency shortening was found. TMS elicited SSRs, whose amplitudes were not correlated with MEP parameters. During forced inspiration a significant SSR amplitude increment, not correlated with MEP latency shortening, was also observed. These results assign a minor if any role to the considered autonomic parameters in modulating corticospinal motor excitability.