CMC is more than a measure of corticospinal tract integrity in acute stroke patients.

In healthy subjects, motor cortex activity and electromyographic (EMG) signals from contracting contralateral muscle show coherence in the beta (15-30 Hz) range. Corticomuscular coherence (CMC) is considered a sign of functional coupling between muscle and brain. Based on prior studies, CMC is altered in stroke, but functional significance of this finding has remained unclear. Here, we examined CMC in acute stroke patients and correlated the results with clinical outcome measures and corticospinal tract (CST) integrity estimated with diffusion tensor imaging (DTI). During isometric contraction of the extensor carpi radialis muscle, EMG and magnetoencephalographic oscillatory signals were recorded from 29 patients with paresis of the upper extremity due to ischemic stroke and 22 control subjects. CMC amplitudes and peak frequencies at 13-30 Hz were compared between the two groups. In the patients, the peak frequency in both the affected and the unaffected hemisphere was significantly (p < 0.01) lower and the strength of CMC was significantly (p < 0.05) weaker in the affected hemisphere compared to the control subjects. The strength of CMC in the patients correlated with the level of tactile sensitivity and clinical test results of hand function. In contrast, no correlation between measures of CST integrity and CMC was found. The results confirm the earlier findings that CMC is altered in acute stroke and demonstrate that CMC is bidirectional and not solely a measure of integrity of the efferent corticospinal tract.

Patients with complex regional pain syndrome overestimate applied force in observed hand actions.

BACKGROUND: Movement accuracy is ensured by interaction between motor, somatosensory, and visual systems. In complex regional pain syndrome (CRPS), this interaction is disturbed. To explore CRPS patients' visual perception of actions, we investigated how these patients evaluate the applied force in observed hand actions of another person. METHODS: Nineteen patients suffering from unilateral upper-limb CRPS and 19 healthy control subjects viewed six different videos of left- and right-hand actions. They were asked to evaluate the applied force in each hand action, as well as their subjective sensations of unpleasantness and pain during the observation. RESULTS: The patients overestimated the force applied in the videos: the ratings were two times as large as in the control subjects for actions performed with the hand corresponding to the patients' affected hand, and 1.5 times as large for actions corresponding to their healthy hand. The control subjects considered the stimuli neutral and painless, whereas the patients rated them unpleasant. Moreover, the patients felt increased pain during viewing actions performed with the hand corresponding to their affected side. The overestimation of force was related to the elicited unpleasantness and pain, but not to the patients' muscle strength. CONCLUSIONS: We propose that the overestimation of force is explained both by the pain elicited by the observation and by the abnormal sensorimotor integration that is associated with perception of increased effort. This visually elicited unpleasantness and painfulness may promote avoidance of viewing own actions, further impairing the patients' motor performance.

Normal laser-evoked cortical responses in patients with chronic hemibody pain.

BACKGROUND: Patients with widespread unilateral chronic pain associated with recurrent herpes simplex virus (HSV) infections show functional and/or structural changes in the insula, anterior cingulate cortex, frontal and prefrontal cortices, as well as the thalamus, suggesting central dysfunction of the pain system in these patients. Central pain has been associated with attenuated laser-evoked cortical responses. We aimed to clarify whether the observed deficient activation of these areas to acute nociceptive stimuli is due to a lesion at a lower level of pain processing pathways. METHODS: We explored the functional integrity of the ascending nociceptive pathways by recording the cortical-evoked responses to noxious laser stimulation using magnetoencephalography and electroencephalography in eight patients (age 41-51 years, mean 46) with recurrent HSV infections and a history of chronic, spontaneous, widespread unilateral pain, and in nine age-matched healthy control subjects. RESULTS: The cortical-evoked fields of the HSV patients originating from the secondary somatosensory and posterior parietal cortices, as well as the evoked potentials recorded from the midline, did not differ from those of the control subjects, indicating functionally intact ascending nociceptive pathways. CONCLUSIONS: The present results show that our patients with chronic hemibody pain do not show signs of spinothalamic tract lesion. This indicates normal processing of sensory aspects of painful stimuli, while higher pain processing areas show altered activation. We conclude that normal laser-evoked magnetic fields (LEF) or laser-evoked potentials (LEP) may not exclude central pain condition.

Two cases of food-borne botulism in Finland caused by conserved olives, October 2011.

In October 2011 in Finland, two persons fell ill with symptoms compatible with botulism after having eaten conserved olives stuffed with almonds. One of these two died. Clostridium botulinum type B and its neurotoxin were detected in the implicated olives by PCR and mouse bioassay, respectively. The olives were traced back to an Italian manufacturer and withdrawn from the market. The public and other European countries were informed through media and Europe-wide notifications.

Activation of the human posterior parietal and temporoparietal cortices during audiotactile interaction.

We recorded cortical-evoked responses with a whole-scalp neuromagnetometer to study human brain dynamics associated with audiotactile interaction. The subjects received unilateral auditory (A) or tactile (T) stimuli, or both stimuli simultaneously (AT), alternating to the left and right side. Responses to AT stimuli differed significantly from the algebraic sum of responses to A and T stimuli (A + T) at 75-85 and 105-130 ms and indicated suppressive audiotactile interaction. Source modeling revealed that the earlier interaction occurred in the contralateral posterior parietal cortex and the later interaction in the contralateral parietal opercula between the SII cortex and the auditory cortex. The interaction was significantly stronger in the left than the right hemisphere. In most subjects, AT responses were far more similar to T than to A responses, suggesting suppression of auditory processing during the spatially and temporally concordant audiotactile stimuli in which the tactile component was subjectively more salient.

Dorsal penile nerve stimulation elicits left-hemisphere dominant activation in the second somatosensory cortex.

Activation of peripheral mixed and cutaneous nerves activates a distributed cortical network including the second somatosensory cortex (SII) in the parietal operculum. SII activation has not been previously reported in the stimulation of the dorsal penile nerve (DPN). We recorded somatosensory evoked fields (SEFs) to DPN stimulation from 7 healthy adults with a 122-channel whole-scalp neuromagnetometer. Electrical pulses were applied once every 0.5 or 1.5 sec to the left and right DPN. For comparison, left and right median and tibial nerves were stimulated alternatingly at 1.5-sec intervals. DPN stimuli elicited weak, early responses in the vicinity of responses to tibial nerve stimulation in the primary somatosensory cortex. Strong later responses, peaking at 107-126 msec were evoked in the SII cortices of both hemispheres, with left-hemisphere dominance. In addition to tactile processing, SII could also contribute to mediating emotional effects of DPN stimuli.

Oscillatory cortical drive to isometrically contracting muscle in Unverricht-Lundborg type progressive myoclonus epilepsy (ULD).

OBJECTIVE: We investigated with whole-scalp magnetoencephalography (MEG) oscillatory cortical drive to isometrically contracting muscle in 8 genetically verified, and thus etiologically homogeneous, Unverricht-Lundborg type progressive myoclonus epilepsy (ULD) patients suffering from cortical myoclonus and generalized tonic-clonic seizures. The results were compared with those of 8 healthy control subjects. METHODS: Cortical MEG signals were measured simultaneously with surface electromyography (EMG) during isometric contraction of the left and right first dorsal interosseus muscles. Cortex-muscle coherence and cross-correlograms between MEG and EMG signals were calculated as indicators of oscillatory cortical drive to muscle. The cortical areas involved in the maximum cortex-muscle coherence were also identified. RESULTS: In patients, the strengths of the dominant coherent peaks were 2-4 fold compared with the healthy controls. Whereas the coherence was found strictly in the contralateral primary motor cortex in controls, additional coherent activity was observed ipsilaterally in 5 out of 8 patients. CONCLUSIONS: The remarkably increased MEG-EMG coherence in ULD patients suggests altered oscillatory cortical drive to the muscle during isometric contraction. We suggest that the enhanced cortex-muscle coherence in ULD patients reflects reduced inhibition in the motor cortex, and may contribute to disturbed voluntary movements.

Functional characterization of human second somatosensory cortex by magnetoencephalography.

Magnetoencephalographic (MEG) recordings allow noninvasive monitoring of simultaneously active brain areas with reasonable spatial and excellent temporal resolution. Whole-scalp neuromagnetic recordings show activation of contralateral primary (SI) and bilateral second (SII) somatosensory cortices to unilateral median nerve stimulation. Recent MEG studies on healthy and diseased human subjects have shown some functional characteristics of SII cortex. Besides tactile input, the SII cortex also responds to nociceptive afferents. The SII activation is differentially modulated by isometric muscle contraction of various body parts. Lesions in the SII cortex may disturb the self-perception of body scheme. Moreover, the SI and SII cortices may be sequentially activated within one hemisphere, but the SII cortex may also receive direct peripheral input on the ipsilateral side.

Cortical activation associated with passive movements of the human index finger: an MEG study.

We recorded somatosensory evoked fields to passive extensions of the left and right index fingers in eight healthy adults. A new nonmagnetic device was designed to produce calibrated extensions of 19 degrees, with a mean angular velocity of 630 degrees/s. The responses, recorded with a 306-channel neuromagnetometer, were modeled with current dipoles. The earliest activation was in the primary somatosensory cortex, with peaks at 36-58 and 30-82 ms for left and right index finger extensions, respectively. Later signals were observed in the left second somatosensory (SII) cortex in six of eight subjects at 75-175 and 75-155 ms for left- and right-sided extensions, respectively; three subjects showed bilateral SII activation in at least one condition. Our results suggest a predominant role for the human left SII cortex in proprioceptive processing.

Functional overlap of finger representations in human SI and SII cortices.

We aimed to find out to what extent functional representations of different fingers of the two hands overlap at the human primary and secondary somatosensory cortices SI and SII. Somatosensory evoked fields (SEFs) were recorded with a 306-channel neuromagnetometer from 8 subjects. Tactile stimuli, produced by diaphragms driven by compressed air, were delivered to the fingertips in three different conditions. First, the right index finger was stimulated once every 2 s. Then two other stimuli were interspersed, in different sessions, to right- or left-hand fingers (thumb, middle finger, or ring finger) between the successive right index finger stimuli. Strengths of the responses to right index finger stimuli were evaluated in each condition. Responses to right index finger stimuli were modeled by three current dipoles, located at the contralateral SI and the SII cortices of both hemispheres. The earliest SI responses, peaking around 65 ms, were suppressed by 18% (P < 0.05) when the intervening stimuli were presented to the same hand; intervening stimuli to the other hand had no effect. The SII responses were bilaterally suppressed by intervening stimuli presented to either hand: in the left SII, the suppression was 39 and 42% (P < 0.01) and in the right SII 67 and 72% (P < 0.001) during left- and right-sided intervening stimuli, respectively. Left- and right-sided intervening stimuli affected similarly the SII responses and had no effect on the response latencies. The results indicate a strong and symmetric overlap of finger representations for both hands in the human SII cortices, and a weaker functional overlap for fingers of the same hand in the SI cortex.

Temporal organization of cerebral events: neuromagnetic studies of the sensorimotor system.

Somatosensory and motor processes are closely linked to each other; smooth voluntary movements require continuous interaction of sensory and motor cortices. Sensorimotor cortical processes are readily studied with magnetoencephalography (MEG) by recording evoked responses to external stimuli or spontaneous brain oscillations. With whole-scalp coverage activation of several cortical source areas can be detected even when they are temporally overlapping. For example, electric median nerve stimuli has been shown to activate at least five different widely distributed cortical areas. With MEG recordings, temporal order of activation of different areas can be monitored to reveal functional organization of the somatosensory cortical network. Temporal resolution in millisecond scale is needed also in studies of spontaneous brain rhythms. Somatomotor mu-rhythm, with its characteristic 10 and 20Hz peaks, is typically observed over bilateral sensorimotor cortex. Mu rhythm is dampened during tactile stimulation, movement or even during action observation. Reactivity of the cortical rhythm can be quantified by temporal spectral evolution (TSE) analyses; changes in reactivity of rhythm may reveal modifications in exitatory/inhibitory balance of the sensorimotor cortex. Many neurological diseases, such as stroke and cortical myoclonus, distort activation of sensorimotor cortical network. Identification of modified activation sequences and their comparison with patients' clinical signs and symptoms may reveal pathophysiological mechanisms underlying the diseases.

Evidence for a 7- to 9-Hz "sigma" rhythm in the human SII cortex.

Electrical activity of the human brain features several rhythmical components which can be readily studied with whole-scalp neuromagnetometers. We describe a new 7- to 9-Hz "sigma" rhythm in the human second somatosensory cortex, distinct from both the mu rhythm of the primary sensorimotor cortex and the tau rhythm of the supratemporal auditory cortex. Sigma shows rate-selective responsiveness to rhythmical median nerve stimulation and is enhanced by stimulation at the rhythm's dominant frequency. Single stimuli may trigger several periods of the rhythm. The functional significance of the sigma rhythm remains to be investigated.

Lack of activation of human secondary somatosensory cortex in Unverricht-Lundborg type of progressive myoclonus epilepsy.

Previous electroencephalographic and magnetoencephalographic studies have demonstrated giant early somatosensory cortical responses in patients with cortical myoclonus. We applied whole-scalp magnetoencephalography to study activation sequences of the somatosensory cortical network in 7 patients with Unverricht-Lundborg-type progressive myoclonus epilepsy diagnostically verified by DNA analysis. Responses to electric median nerve stimuli displayed 30-msec peaks at the contralateral primary somatosensory cortex that were four times stronger in patients than in control subjects. The amplitudes of 20-msec responses did not significantly differ between the groups. In contrast to control subjects, 5 patients displayed ipsilateral primary somatosensory cortex activity at 48 to 61 msec in response to both left- and right-sided median nerve stimuli. Furthermore, their secondary somatosensory cortex was not significantly activated. These abnormalities indicate altered responsiveness of the entire somatosensory cortical network outside the contralateral primary somatosensory cortex in patients with Unverricht-Lundborg-type progressive myoclonus epilepsy. The deficient activation of the secondary somatosensory cortex in Unverricht-Lundborg patients may reflect disturbed sensorimotor integration, probably related to impaired movement coordination.

Sustained activation of the human SII cortices by stimulus trains.

To compare the functional properties of neurons in the human primary (SI) and secondary (SII) cortices, we recorded somatosensory-evoked fields (SEFs) from seven healthy subjects to single electric stimuli and stimulus trains delivered to the median nerve at 8--12 Hz. The SI and SII cortices responded strikingly differently to stimulus trains: whereas SI followed each stimulus with a sharp transient response up to at least 12 Hz, the transient responses were much less prominent at SII, which mainly responded with a sustained field that returned to base level at 800--1000 ms. The different response patterns of SI and SII suggest that the inhibition, following the early excitatory responses, is weaker at SII than SI, or that inhibitory responses of these two areas differ in their relative timing.

Three-dimensional integration of brain anatomy and function to facilitate intraoperative navigation around the sensorimotor strip.

We studied 12 patients with brain tumors in the vicinity of the sensorimotor region to provide a preoperative three-dimensional visualization of the functional anatomy of the rolandic cortex. We also evaluated the role of cortex-muscle coherence analysis and anatomical landmarks in identifying the sensorimotor cortex. The functional landmarks were based on neuromagnetic recordings with a whole-scalp magnetometer, coregistred with magnetic resonance images. Evoked fields to median and tibial nerve and lip stimuli were recorded to identify hand, foot and face representations in the somatosensory cortex. Oscillatory cortical activity, coherent with surface electromyogram during isometric muscle contraction, was analyzed to reveal the hand and foot representations in the precentral motor cortex. The central sulcus was identified also by available anatomical landmarks. The source locations, calculated from the neuromagnetic data, were displayed on 3-D surface reconstructions of the individual brains, including the veins. The preoperative data were verified during awake craniotomy by cortical stimulation in 7 patients and by cortical somatosensory evoked potentials in 5 patients. Sources of somatosensory evoked fields identified correctly the postcentral gyrus in all patients. Useful corroborative information was obtained from anatomical landmarks in 11 patients and from cortex-muscle correlograms in 8 patients. The preoperative visualization of the functional anatomy of the sensorimotor strip assisted in designing the operational strategy, facilitated orientation of the neurosurgeon during the operation, and speeded up the selection of sites for intraoperative stimulation or mapping, thereby helping to prevent damage of eloquent brain areas during surgery.

Abnormal reactivity of the approximately 20-Hz motor cortex rhythm in Unverricht Lundborg type progressive myoclonus epilepsy.

The approximately 20-Hz component of the human mu rhythm originates predominantly in the primary motor cortex. We monitored with a whole-scalp neuromagnetometer the reactivity of the approximately 20-Hz rhythm as an index of the functional state of the primary motor cortex in seven patients suffering from Unverricht-Lundborg type (ULD) progressive myoclonus epilepsy (PME) and in seven healthy control subjects. In patients, the motor cortex rhythm was on average 5 Hz lower in frequency and its strength was double compared with controls. To study reactivity of the approximately 20-Hz rhythm, left and right median nerves were stimulated alternately at wrists. In controls, these stimuli elicited a small transient decrease, followed by a strong increase ("rebound") of the approximately 20-Hz level. In contrast, the patients showed no significant rebounds of the rhythm. As the approximately 20-Hz rebounds apparently reflect increased cortical inhibition, our results indicate that peripheral stimuli excite motor cortex for prolonged periods in patients with ULD.

Characteristics of the human contra- versus ipsilateral SII cortex.

OBJECTIVES: In order to study the interaction between left- and right-sided stimuli on the activation of cortical somatosensory areas, we recorded somatosensory evoked magnetic fields (SEFs) from 8 healthy subjects with a 122 channel whole-scalp SQUID gradiometer. METHODS: Right and left median nerves were stimulated either alternately within the same run, with interstimulus intervals (ISIs) of 1.5 and 3 s, or separately in different runs with a 3 s ISI. In all conditions 4 cortical source areas were activated: the contralateral primary somatosensory cortex (SI), the contra- and ipsilateral secondary somatosensory cortices (SII) and the contralateral posterior parietal cortex (PPC). RESULTS: The earliest activity starting at 20 ms was generated solely in the SI cortex, whereas longer-latency activity was detected from all 4 source areas. The mean peak latencies for SII responses were 86-96 ms for contralateral and 94-97 ms for ipsilateral stimuli. However, the activation of right and left SII areas started at 61+/-3 and 62+/-3 ms to contralateral stimuli and at 66+/-2 and 63+/-2 ms to ipsilateral stimuli, suggesting a simultaneous commencing of activation of the SII areas. PPC sources were activated between 70 and 110 ms in different subjects. The 1.5 s ISI alternating stimuli elicited smaller SII responses than the 3 s ISI non-alternating stimuli, suggesting that a considerable part of the neural population in SII responds both to contra- and ipsilateral stimuli. The earliest SI responses did not differ between the two conditions. There were no significant differences in source locations of SII responses to ipsi- and contralateral stimuli in either hemisphere. Subaverages of the responses in sets of 30 responses revealed that amplitudes of the SII responses gradually attenuated during repetitive stimulation, whereas the amplitudes of the SI responses were not changed. CONCLUSIONS: The present results implicate that ipsi- and contralateral SII receive simultaneous input, and that a large part of SII neurons responds both to contra- and ipsilateral stimulation. The present data also highlight the different behavior of SI and SII cortices to repetitive stimuli.

Differential effects of muscle contraction from various body parts on neuromagnetic somatosensory responses.

We studied eight healthy subjects with a whole-scalp 306-channel neuromagnetometer to explore the effect of motor activity from different body parts on somatosensory responses to left median nerve stimulation. The stimuli produced clear tactile sensation without any motor movement. In the rest condition, the subject had no task. During contraction conditions, the subject had to maintain submaximal isometric contraction in masseter, left deltoid, left thenar, or left tibialis muscles. Short-latency responses from the primary somatosensory cortex did not change during contraction. Responses from both the right (contralateral) and left second somatosensory cortices (SII) were significantly enhanced during contraction of the left thenar muscles. Responses from the left SII were significantly enhanced also during contraction of the left deltoid muscles, but they were decreased during contraction of the masseter and left tibialis anterior muscles. This study implies that SII activation is modulated by motor activity and that the effect depends on the topographical proximity of the stimulated and contracted body parts.