Inhibition of muscle sympathetic nerve activity in pre-menopausal women: responses to sudden sensory stimuli predict responses to mental stress.

Muscle sympathetic nerve responses to sudden sensory stimuli have been elucidated in several studies on young healthy men, showing reproducible interindividual differences ranging from varying degrees of inhibition to no significant change, with very few subjects showing significant excitation. These individual response patterns have been shown to predict the neural response to mental stress, and coupled blood pressure responses. The aim of this study was to investigate whether pre-menopausal healthy women show similar neural and blood pressure responses. Muscle sympathetic nerve recordings from the peroneal nerve were performed in 34 healthy women (mean age 27±8 years) during sudden sensory stimuli (electrical stimuli to a finger) and 3 minutes of mental stress (forced arithmetics). After sensory stimuli 18 women showed varying degrees of inhibition of muscle sympathetic nerve activity (burst amplitude mean reduction 60%, range 34 to 100%). The remaining 16 showed no inhibition (mean 5%, range -31 to 28%; one subject exhibiting excitation). During 3 minutes of mental stress the normalized change in burst incidence for muscle sympathetic nerve activity correlated with the percentage change of muscle sympathetic nerve activity induced by the sensory stimulation protocol (r=0.64, p=0.0042). In contrast to men, the neural responses did not predict changes in blood pressure. Thus, pre-menopausal females show a similar range of individual differences in defence-related muscle sympathetic neural responses as men, but no associated differences in blood pressure responses. Whether these patterns are unchanged after menopause remains to be investigated.

From MEG to clinical EEG: evaluating a promising non-invasive estimator of defense-related muscle sympathetic nerve inhibition.

Sudden, unexpected stimuli can induce a transient inhibition of sympathetic vasoconstriction to skeletal muscle, indicating a link to defense reactions. This phenomenon is relatively stable within, but differs between, individuals. It correlates with blood pressure reactivity which is associated with cardiovascular risk. Inhibition of muscle sympathetic nerve activity (MSNA) is currently characterized through invasive microneurography in peripheral nerves. We recently reported that brain neural oscillatory power in the beta spectrum (beta rebound) recorded with magnetoencephalography (MEG) correlated closely with stimulus-induced MSNA inhibition. Aiming for a clinically more available surrogate variable reflecting MSNA inhibition, we investigated whether a similar approach with electroencephalography (EEG) can accurately gauge stimulus-induced beta rebound. We found that beta rebound shows similar tendencies to correlate with MSNA inhibition, but these EEG data lack the robustness of previous MEG results, although a correlation in the low beta band (13-20 Hz) to MSNA inhibition was found (p = 0.021). The predictive power is summarized in a receiver-operating-characteristics curve. The optimum threshold yielded sensitivity and false-positive rate of 0.74 and 0.33 respectively. A plausible confounder is myogenic noise. A more complicated experimental and/or analysis approach is required for differentiating MSNA-inhibitors from non-inhibitors based on EEG, as compared to MEG.

Brain structural and functional correlates to defense-related inhibition of muscle sympathetic nerve activity in man.

An individual's blood pressure (BP) reactivity to stress is linked to increased risk of hypertension and cardiovascular disease. However, inter- and intra-individual BP variability makes understanding the coupling between stress, BP reactivity, and long-term outcomes challenging. Previous microneurographic studies of sympathetic signaling to muscle vasculature (i.e. muscle sympathetic nerve activity, MSNA) have established a neural predictor for an individual's BP reactivity during short-lasting stress. Unfortunately, this method is invasive, technically demanding, and time-consuming and thus not optimal for widespread use. Potential central nervous system correlates have not been investigated. We used MagnetoEncephaloGraphy and Magnetic Resonance Imaging to search for neural correlates to sympathetic response profiles within the central autonomic network and sensorimotor (Rolandic) regions in 20 healthy young males. The main correlates include (a) Rolandic beta rebound and an anterior cingulate cortex (ACC) response elicited by sudden stimulation and (b) cortical thickness in the ACC. Our findings highlight the involvement of the ACC in reactions to stress entailing peripheral sympathetic responses to environmental stimuli. The Rolandic response furthermore indicates a surprisingly strong link between somatosensory and autonomic processes. Our results thus demonstrate the potential in using non-invasive neuroimaging-based measures of stress-related MSNA reactions, previously assessed only using invasive microneurography.

A wearable microwave instrument can detect and monitor traumatic abdominal injuries in a porcine model.

Abdominal injury is a frequent cause of death for trauma patients, and early recognition is essential to limit fatalities. There is a need for a wearable sensor system for prehospital settings that can detect and monitor bleeding in the abdomen (hemoperitoneum). This study evaluates the potential for microwave technology to fill that gap. A simple prototype of a wearable microwave sensor was constructed using eight antennas. A realistic porcine model of hemoperitoneum was developed using anesthetized pigs. Ten animals were measured at healthy state and at two sizes of bleeding. Statistical tests and a machine learning method were used to evaluate blood detection sensitivity. All subjects presented similar changes due to accumulation of blood, which dampened the microwave signal ([Formula: see text]). The machine learning analysis yielded an area under the receiver operating characteristic (ROC) curve (AUC) of 0.93, showing 100% sensitivity at 90% specificity. Large inter-individual variability of the healthy state signal complicated differentiation of bleedings from healthy state. A wearable microwave instrument has potential for accurate detection and monitoring of hemoperitoneum, with automated analysis making the instrument easy-to-use. Future hardware development is necessary to suppress measurement system variability and enable detection of smaller bleedings.

Cutaneous warmth, but not touch, increases muscle sympathetic nerve activity during a muscle fatigue hand-grip task.

In homeostasis, somatosensory C fibre afferents are hypothesised to mediate input to the brain about interactions with external stimuli and sympathetic efference provides the output that regulates bodily functions. We aimed to test this hypothesis and whether different types of innocuous somatosensory input have differential effects. Healthy volunteers performed a muscle fatigue (hand-grip) task to exhaustion, which produces increased muscle sympathetic nerve activity (MSNA), as measured through microneurography. Participants completed the muscle fatigue task without concurrent cutaneous sensory stimulation (control) or we applied skin warming (heat pack) as a C fibre stimulation, slow brush stroking as C and Aß fibre stimulation, or vibration as Aß fibre stimulation, to the participant's forearm. We also measured heart rate, the duration of the hand-grip task, and ratings of pain at the end of the task. Concurrent skin warming showed increased MSNA compared to the other conditions. Tactile stimuli (brushing, vibration) were not significantly different to the control (no intervention) condition. Warming increased the pain from the muscle contraction, whereas the tactile stimuli did not. We interpret the effect of warming on MSNA as providing relevant afferent information during muscle contraction, which needed to be counteracted via vasoconstriction to maintain homeostasis. Brushing and vibration were less homeostatically relevant stimuli for the muscle contraction and hence had no significant effect. The findings add sensory specificity to our current understanding of homeostatic regulation through somatosensory afferent and sympathetic efferent pathways.

Cortical mapping of receptive language processing in children using navigated transcranial magnetic stimulation.

We used a stepwise process to develop a new paradigm for preoperative cortical mapping of receptive language in children, using temporary functional blocking with transcranial magnetic stimulation (TMS). The method combines short sentences with a lexical decision task in which children are asked to point at a picture that fits a short sentence delivered aurally. This was first tested with 24 healthy children aged 4-16 years. Next, 75 sentences and 25 slides were presented to five healthy children in a clinical setting without TMS. Responses were registered on a separate computer, and facial expressions and hand movements were filmed for later offline review. Technical adjustments were made to combine these elements with the existing TMS equipment. The audio-recorded sentences were presented before the visual stimuli. Sentence lists were constructed to avoid similar stimuli in a row. Two different baseline lists were used before the TMS registration; the second baseline resulted in faster responses and was chosen as the reference for possible response delays induced by TMS. Protocols for offline reviews were constructed. No response, incorrect response, self-correction, delayed response, and perseveration were considered clear stimulation effects, while poor attention, discomfort, and other events were regarded as unclear. Finally, three children (6:2, 14:0, 14:10 years) with epilepsy and expected to undergo neurosurgery were assessed using TMS (left hemisphere in one; both hemispheres in the other two). In the two assessed bilaterally, TMS effects indicated bilateral language processing. Delayed response was the most common error. This is a first attempt to develop a new TMS paradigm for receptive language mapping, and further evaluation is suggested.

Unaltered neurocardiovascular reactions to mental stress after renal sympathetic denervation.

Background: The impact of renal denervation (RDN) on muscle sympathetic nerve activity (MSNA) at rest remains controversial. Mental stress (MS) induces transient changes in sympathetic nerve activity, heart rate (HR) and blood pressure (BP). It is not known whether RDN modifies these changes.Purpose: The main objective was to assess the effect of RDN on MSNA and BP alterations during MS.Methods: In 14 patients (11 included in analysis) with resistant hypertension multi-unit MSNA, BP (Finometer ®) and HR were assessed at rest and during forced arithmetics at baseline and 6 months after RDN.Results: Systolic office BP decreased significantly 6 months after RDN (185 ± 29 vs.175 ± 33 mmHG; p = 0.04). No significant changes in MSNA at rest (68 ± 5 vs 73 ± 5 bursts/100hb; p = 0.43) were noted and no significant stress-induced change in group averaged sympathetic activity was found pre- (101 ± 24%; p = 0.9) or post-intervention (108 ± 26%; p = 0.37). Stress was associated with significant increases in mean arterial BP (p < 0.01) and HR (p < 0.01) at baseline, reactions which remained unaltered after intervention. We did not note any correlation between sympathetic nerve activity and BP changes after RDN.Conclusion: Thus, in our group of resistant hypertensives we find no support for the hypothesis that the BP-lowering effect of RDN depends on altered neurovascular responses to stress.

3D Simulations of Intracerebral Hemorrhage Detection Using Broadband Microwave Technology.

Early, preferably prehospital, detection of intracranial bleeding after trauma or stroke would dramatically improve the acute care of these large patient groups. In this paper, we use simulated microwave transmission data to investigate the performance of a machine learning classification algorithm based on subspace distances for the detection of intracranial bleeding. A computational model, consisting of realistic human head models of patients with bleeding, as well as healthy subjects, was inserted in an antenna array model. The Finite-Difference Time-Domain (FDTD) method was then used to generate simulated transmission coefficients between all possible combinations of antenna pairs. These transmission data were used both to train and evaluate the performance of the classification algorithm and to investigate its ability to distinguish patients with versus without intracranial bleeding. We studied how classification results were affected by the number of healthy subjects and patients used to train the algorithm, and in particular, we were interested in investigating how many samples were needed in the training dataset to obtain classification results better than chance. Our results indicated that at least 200 subjects, i.e., 100 each of the healthy subjects and bleeding patients, were needed to obtain classification results consistently better than chance (p < 0.05 using Student's t-test). The results also showed that classification results improved with the number of subjects in the training data. With a sample size that approached 1000 subjects, classifications results characterized as area under the receiver operating curve (AUC) approached 1.0, indicating very high sensitivity and specificity.

Testing a linear time invariant model for skin conductance responses by intraneural recording and stimulation.

Skin conductance responses (SCR) are increasingly analyzed with model-based approaches that assume a linear and time-invariant (LTI) mapping from sudomotor nerve (SN) activity to observed SCR. These LTI assumptions have previously been validated indirectly, by quantifying how much variance in SCR elicited by sensory stimulation is explained under an LTI model. This approach, however, collapses sources of variability in the nervous and effector organ systems. Here, we directly focus on the SN/SCR mapping by harnessing two invasive methods. In an intraneural recording experiment, we simultaneously track SN activity and SCR. This allows assessing the SN/SCR relationship but possibly suffers from interfering activity of non-SN sympathetic fibers. In an intraneural stimulation experiment under regional anesthesia, such influences are removed. In this stimulation experiment, about 95% of SCR variance is explained under LTI assumptions when stimulation frequency is below 0.6 Hz. At higher frequencies, nonlinearities occur. In the intraneural recording experiment, explained SCR variance is lower, possibly indicating interference from non-SN fibers, but higher than in our previous indirect tests. We conclude that LTI systems may not only be a useful approximation but in fact a rather accurate description of biophysical reality in the SN/SCR system, under conditions of low baseline activity and sporadic external stimuli. Intraneural stimulation under regional anesthesia is the most sensitive method to address this question.

Clinical Evaluation of a Microwave-Based Device for Detection of Traumatic Intracranial Hemorrhage.

Traumatic brain injury (TBI) is the leading cause of death and disability among young persons. A key to improve outcome for patients with TBI is to reduce the time from injury to definitive care by achieving high triage accuracy. Microwave technology (MWT) allows for a portable device to be used in the pre-hospital setting for detection of intracranial hematomas at the scene of injury, thereby enhancing early triage and allowing for more adequate early care. MWT has previously been evaluated for medical applications including the ability to differentiate between hemorrhagic and ischemic stroke. The purpose of this study was to test whether MWT in conjunction with a diagnostic mathematical algorithm could be used as a medical screening tool to differentiate patients with traumatic intracranial hematomas, chronic subdural hematomas (cSDH), from a healthy control (HC) group. Twenty patients with cSDH and 20 HC were measured with a MWT device. The accuracy of the diagnostic algorithm was assessed using a leave-one-out analysis. At 100% sensitivity, the specificity was 75%-i.e., all hematomas were detected at the cost of 25% false positives (patients who would be overtriaged). Considering the need for methods to identify patients with intracranial hematomas in the pre-hospital setting, MWT shows promise as a tool to improve triage accuracy. Further studies are under way to evaluate MWT in patients with other intracranial hemorrhages.

Sympathetic Nerve Activity in Monozygotic Twins: Identical at Rest but Not During Arousal.

Microneurographic recordings of human muscle sympathetic nerve activity responses to sudden sensory stimuli (ie, arousal) have revealed 2 intraindividually reproducible response profiles in healthy young males that predict different neural and blood pressure responses to more sustained stress. Approximately 50% of subjects inhibit muscle sympathetic nerve activity during arousal, whereas the remaining 50% do not, and the latter group displays a markedly greater blood pressure increase in response to arousal, as well as during and after 3 minutes of mental arithmetic. Studying a group of monozygotic twins (10 pairs, 2 excluded from analysis), the aim of the present study was to evaluate the degree of genetic determination of these sympathetic response profiles. Muscle sympathetic burst incidence at rest was similar in twins, with a within-pair burst incidence ratio of 0.87±0.02 (SEM) compared with 0.73±0.07 found in unrelated pairs (P=0.002), confirming a previous study from our laboratory. In contrast, the sympathetic responses to arousal showed large twin within-pair variance (arousal inhibition ratio 0.56±0.11), which did not significantly differ (P=0.939) from the variance in pairs of unrelated subjects (0.46±0.11). The finding that human muscle sympathetic nerve responses to arousal are less determined by genotype than the resting level of corresponding sympathetic nerve activity suggests that the arousal response pattern is more prone to be altered by environmental factors. This raises the possibility that these intraindividually reproducible sympathetic neural response profiles can be modified in a positive direction from a cardiovascular risk perspective.

Microwave technology for detecting traumatic intracranial bleedings: tests on phantom of subdural hematoma and numerical simulations.

Traumatic brain injury is the leading cause of death and severe disability for young people and a major public health problem for elderly. Many patients with intracranial bleeding are treated too late, because they initially show no symptoms of severe injury and are not transported to a trauma center. There is a need for a method to detect intracranial bleedings in the prehospital setting. In this study, we investigate whether broadband microwave technology (MWT) in conjunction with a diagnostic algorithm can detect subdural hematoma (SDH). A human cranium phantom and numerical simulations of SDH are used. Four phantoms with SDH 0, 40, 70 and 110 mL are measured with a MWT instrument. The simulated dataset consists of 1500 observations. Classification accuracy is assessed using fivefold cross-validation, and a validation dataset never used for training. The total accuracy is 100 and 82-96 % for phantom measurements and simulated data, respectively. Sensitivity and specificity for bleeding detection were 100 and 96 %, respectively, for the simulated data. SDH of different sizes is differentiated. The classifier requires training dataset size in order of 150 observations per class to achieve high accuracy. We conclude that the results indicate that MWT can detect and estimate the size of SDH. This is promising for developing MWT to be used for prehospital diagnosis of intracranial bleedings.

The impact of baroreflex function on endogenous pain control: a microneurography study.

The interaction between sympathetic vasoconstrictor activity to muscles [muscle sympathetic nerve activity (MSNA), burst frequency (BF) and burst incidence (BI)] and different stress and somatosensory stimuli is still unclear. Eighteen healthy men (median age 28 years) underwent microneurography recordings from the peroneal nerve. MSNA was recorded during heat pain (HP) and cold pain (CP) alone as well as combined with different stress tasks (mental arithmetic, singing, giving a speech). An additional nine healthy men (median age 26 years) underwent the stimulation protocol with an additional control task (thermal pain combined with listening to music) to evaluate possible attentional confounders. MSNA was significantly increased by CP and HP. CP-evoked responses were smaller. The diastolic blood pressure followed the time course of MSNA while heart rate remained unchanged. The mental stress tasks further increased MSNA and were sufficient to reduce pain while the control task had no effect. MSNA activity correlated negatively with pain intensity and positively with analgesia. High blood pressure values were associated with lower pain intensity. Our study indicates an impact of central sympathetic drive on pain and pain control.

Microwave-based stroke diagnosis making global prehospital thrombolytic treatment possible.

Here, we present two different brain diagnostic devices based on microwave technology and the associated two first proof-of-principle measurements that show that the systems can differentiate hemorrhagic from ischemic stroke in acute stroke patients, as well as differentiate hemorrhagic patients from healthy volunteers. The system was based on microwave scattering measurements with an antenna system worn on the head. Measurement data were analyzed with a machine-learning algorithm that is based on training using data from patients with a known condition. Computer tomography images were used as reference. The detection methodology was evaluated with the leave-one-out validation method combined with a Monte Carlo-based bootstrap step. The clinical motivation for this project is that ischemic stroke patients may receive acute thrombolytic treatment at hospitals, dramatically reducing or abolishing symptoms. A microwave system is suitable for prehospital use, and therefore has the potential to allow significantly earlier diagnosis and treatment than today.

Neurochemical evidence of potential neurotoxicity after prophylactic cranial irradiation.

PURPOSE: To examine whether cerebrospinal fluid biomarkers for neuroaxonal damage, neuroglial activation, and amyloid ß-related processes could characterize the neurochemical response to cranial radiation. METHODS AND MATERIALS: Before prophylactic cranial irradiation (PCI) of patients with small cell lung cancer, each patient underwent magnetic resonance imaging of the brain, lumbar puncture, and Mini-Mental State Examination of cognitive function. These examinations were repeated at approximately 3 and 12 months after radiation. RESULTS: The major findings were as follows. (1) Cerebrospinal fluid markers for neuronal and neuroglial injury were elevated during the subacute phase after PCI. Neurofilament and T-tau increased 120% and 50%, respectively, after PCI (P<.05). The same was seen for the neuroglial markers YKL-40 and glial fibrillary acidic protein, which increased 144% and 106%, respectively, after PCI (P<.05). (2) The levels of secreted amyloid precursor protein-α and -ß were reduced 44% and 46%, respectively, 3 months after PCI, and the levels continued to decrease as long as 1 year after treatment (P<.05). (3) Mini-Mental State Examination did not reveal any cognitive decline, indicating that a more sensitive test should be used in future studies. CONCLUSION: In conclusion, we were able to detect radiation therapy-induced changes in several markers reflecting neuronal injury, inflammatory/astroglial activation, and altered amyloid precursor protein/amyloid ß metabolism, despite the low number of patients and quite moderate radiation doses (20-30 Gy). These changes are hypothesis generating and could potentially be used to assess the individual risk of developing long-term symptoms of chronic encephalopathy after PCI. This has to be evaluated in large studies with extended clinical follow-up and more detailed neurocognitive assessments.

Central correlation of muscle sympathetic nerve activation during baroreflex unloading - a microneurography-positron emission tomography study.

The baroreceptor reflex controls spontaneous fluctuations in blood pressure. One major control variable of the baroreflex is the sympathetic vasoconstrictor activity to muscles [MSNA; burst frequency (BF) and burst incidence (BI)], which can be quantitatively assessed by microneurography. We aimed to investigate the central regions involved in baroreflex regulation of MSNA. Healthy men (mean age 25 years) participated in three experimental sessions. (i) Microneurography recordings of MSNA from the left peroneal nerve during rest and baroreflex unloading, induced by lower body negative pressure (LBNP; -40 mmHg). If MSNA could be reliably recorded throughout this procedure (n = 15), the subjects entered the positron emission tomography (PET) experiments. The two PET sessions took place in a randomised order. Cerebral glucose metabolism (18-fluorodeoxyglucose) was analysed after: (ii) baroreflex unloading (LBNP); and (iii) control condition (lying in the LBNP chamber without suction). The PET data were analysed employing SPM8. LBNP elicited a significant increase in MSNA in all successfully recorded subjects (BI: P = 0.001; F = 5.54; BF: P < 0.001; F = 36.59). As compared with the control condition, LBNP was associated with increased PET regional glucose metabolism bilaterally in the orbitofrontal cortex (OFC; BA 11, 47). Related to the rise of BF, there was increased activation of the left OFC (BA 11); related to the rise of BI there was increased activation of the brainstem corresponding to the rostral ventrolateral medulla. Our data support a role for the ventrolateral medulla and the OFC in baroreflex-mediated control of MSNA in humans.

Viscerosympathetic reflexes in human spinal cord injury: relationships between detrusor pressure, blood pressure and skin blood flow during bladder distension.

Autonomic dysreflexia, a dangerous and sustained increase in blood pressure brought about by widespread, reflexly generated vasoconstriction, can be induced by visceral or somatic sensory inputs originating below the lesion following spinal cord injury (SCI). We assessed whether cutaneous vasoconstriction below the lesion could serve as a proxy marker of incipient autonomic dysreflexia during bladder distension. Skin blood flow (pulse plethysmography), sweat release, blood pressure, heart rate, bladder and rectal pressures were recorded during routine cystometry (urodynamics) in 16 patients with SCI. Eight urological patients without SCI served as control subjects. In all SCI patients, who had sustained injuries 2 months to 44 years previously at levels C3-T3, bladder filling (mean ± SD, 339 ± 132 ml) induced increases in detrusor (bladder-rectal) pressure (52 ± 25 cmH(2)O) and cutaneous vasoconstriction in the fingers, but no consistent increases in sweat release. This occurred irrespective of whether the spinal lesions were complete [American Spinal Injury Association (ASIA) grade A, n = 6] or incomplete (ASIA B-D; n = 10). Group mean blood pressure for the SCI patients increased by 17 ± 15 mmHg, but in four patients the pressure decreased or did not change. Despite similar bladder volumes (423 ± 126 ml) in the control patients, the increases in detrusor pressure (14 ± 8 cmH(2)O) and blood pressure (9 ± 12 mmHg) were significantly smaller than in the SCI patients; moreover, there were no consistent changes in skin blood flow in the control subjects. In all SCI patients, changes in finger pulse amplitudes were inversely correlated to changes in detrusor pressure (mean r = -0.62 ± 0.17). Changes in finger pulse amplitudes correlated inversely to changes in blood pressure in nine of 15 patients. It is concluded that cystometry in SCI patients is associated with detrusor and cardiovascular reflex effects that are exaggerated compared with those in intact subjects and that measurement of skin blood flow from the fingers in patients with a high spinal lesion provides a supplementary, clinically useful, non-invasive and continuous marker of spinally mediated viscerosympathetic reflex activity below the lesion in such patients.

Auditory magnetic response to clicks in children and adults: its components, hemispheric lateralization and repetition suppression effect.

The auditory magnetic event-related fields (ERF) qualitatively change through the child development, reflecting maturation of auditory cortical areas. Clicks presented with long inter-stimulus interval produce distinct ERF components, and may appear useful to characterize immature EFR morphology in children. The present study is aimed to investigate morphology of the auditory ERFs in school-age children, as well as lateralization and repetition suppression of ERF components evoked by the clicks. School-age children and adults passively listened to pairs of click presented to the right ear, left ear or binaurally, with 8-11 s intervals between the pairs and a 1 s interval within a pair. Adults demonstrated a typical P50m/N100m response. Unlike adults, children had two distinct components preceding the N100m-P50m (at ~65 ms) and P100m (at ~100 ms). The P100m dominated the child ERF, and was most prominent in response to binaural stimulation. The N100m in children was less developed than in adults and partly overlapped in time with the P100m, especially in response to monaural clicks. Strong repetition suppression was observed for P50m both in children and adults, P100m in children and N100m in adults. Both children and adults demonstrated ERF amplitude and/or latency right hemispheric advantage effects that may reflect right hemisphere dominance for preattentive arousal processes. Our results contribute to the knowledge concerning development of auditory processing and its lateralization in children and have implications for investigation of the auditory evoked fields in developmental disorders.

Individual effects of varying stimulation intensity and response criteria on area of activation for different muscles in humans. A study using navigated transcranial magnetic stimulation.

BACKGROUND: When using transcranial magnetic stimulation, a stimulation intensity defined as a certain level above the threshold for activation of a hand muscle is commonly used, disregarding the fact that the areas of activation for different muscles may have varying response characteristics intra- and interindividually. OBJECTIVE: To study the response characteristics of different muscles and compare them within and between individuals. Also to investigate the effect of varying stimulation intensity (defined in two different ways) and amplitude criterion for response, on the sizes of the activation areas for different muscles. METHODS: A system of transcranial magnetic stimulation with navigation capacity where the stimulation intensity can be defined in terms of the electric field strength in the tissue was used. Four different muscles were investigated in healthy adults. The threshold for activation at rest (RMT) of the different muscles and their respective areas of activation were quantified using three different stimulus intensities (100, 110 and 120% RMT) and two criteria for response amplitude (20 and 50 µV). RESULTS: Responses could readily be determined using 20 µV as response limit. The RMTs for different muscles varied within and between individuals. The degree to which the area depended on stimulation intensity differed between muscles intra- and interindividually. All results were statistically significant (P < 0.05 or less). CONCLUSIONS: The response characteristics vary between muscles within an individual and between individuals for a certain muscle. Thus, for optimal accuracy when delineating the activation area, the investigation should be adapted to each particular muscle.

Auditory cortex responses to clicks and sensory modulation difficulties in children with autism spectrum disorders (ASD).

Auditory sensory modulation difficulties are common in autism spectrum disorders (ASD) and may stem from a faulty arousal system that compromises the ability to regulate an optimal response. To study neurophysiological correlates of the sensory modulation difficulties, we recorded magnetic field responses to clicks in 14 ASD and 15 typically developing (TD) children. We further analyzed the P100m, which is the most prominent component of the auditory magnetic field response in children and may reflect preattentive arousal processes. The P100m was rightward lateralized in the TD, but not in the ASD children, who showed a tendency toward P100m reduction in the right hemisphere (RH). The atypical P100m lateralization in the ASD subjects was associated with greater severity of sensory abnormalities assessed by Short Sensory Profile, as well as with auditory hypersensitivity during the first two years of life. The absence of right-hemispheric predominance of the P100m and a tendency for its right-hemispheric reduction in the ASD children suggests disturbance of the RH ascending reticular brainstem pathways and/or their thalamic and cortical projections, which in turn may contribute to abnormal arousal and attention. The correlation of sensory abnormalities with atypical, more leftward, P100m lateralization suggests that reduced preattentive processing in the right hemisphere and/or its shift to the left hemisphere may contribute to abnormal sensory behavior in ASD.