Somatosensory evoked magnetic fields from the primary somatosensory cortex (SI) in acute stroke.

We recorded somatosensory evoked magnetic fields (SEFs) to median nerve stimulation from 15 patients in the acute stage (1-15 days from the onset of the symptoms) of their first-ever unilateral stroke involving sensorimotor cortical and/or subcortical structures in the territory of the middle cerebral artery (MCA). Neuronal activity corresponding to the peaks of the N20m, P35m and P60m SEF deflections from the contralateral primary somatosensory cortex (SI) was modelled with equivalent current dipoles (ECDs), the locations and strengths of which were compared with those of an age-matched normal population. Four patients with pure motor stroke had symmetric SEFs. In one of the 4 patients with pure sensory stroke, and in 5 of the 7 patients with sensorimotor paresis, the SEFs were markedly attenuated or missing. All except one patient with abnormal SEFs had deficient two-point discrimination ability; especially the attenuation of N20m was more clearly correlated with two-point discrimination than with joint-position or vibration senses. Of the different SEF deflections, P35m and P60m were slightly more sensitive indicators of abnormality than N20m, the former being affected in two patients with symmetric N20m. Three patients with pure sensory stroke and lesions in the opercular cortex had normal SEFs from SI. We conclude that the SEF deflections N20m, P35m and P60m from SI are related to cutaneous sensation, in particular discriminative to touch. The results also demonstrate that basic somatosensory perception can be affected by lesions in the opercular cortex in patients with functionally intact SI.     

Magnetoencephalographic study of giant somatosensory evoked responses in patients with rolandic epilepsy

We report five patients with rolandic epilepsy associated with giant somatosensory responses to median nerve stimulation, in whom we analyzed the pathophysiologic relationship between rolandic discharges and the somatosensory responses using magnetoencephalography. Four of the five patients showed giant P30m, the current source of which was localized in the primary somatosensory cortex, while the first cortical response, N20m, was not enhanced, except in one patient. The current source of the giant middle-latency component, N70m, was localized posterior to that of N20m, possibly in the posterior parietal cortex, in all patients. The initial positive peak and large negative peak of rolandic discharges were identical to P30m and N70m with respect to the current source localization, wave form, topographic pattern, and time relationship in the electroencephalogram and magnetoencephalogram, and somatosensory evoked magnetic field and somatosensory evoked potential records, respectively. In addition, the secondary sensory cortex was considered to be the generator of the middle-latency component in one patient. In one patient, the current intensity of the N70m was normalized along with clinical improvement and the disappearance of rolandic discharges, whereas those of other somatosensory evoked magnetic field components remained unchanged. Our data suggest that the rolandic discharge generator mechanism in these patients could be closely related to the developmental alteration of excitability in the primary somatosensory cortex, posterior parietal cortex, and secondary somatosensory cortex, which decreased with age, and it could share a common neuronal pathway, at least in part, with the giant P30m-N70m (N90m) in the somatosensory evoked magnetic field through the sequential and parallel processing of somatosensory information.     

Cerebral magnetic fields to lingual stimulation.

We recorded cerebral magnetic fields to electric stimulation of the tongue in 7 healthy adults. The two main deflections of the response peaked around 55 msec (P55m) and 140 msec (N140m). During both of them the magnetic field pattern, determined with a 7- or 24-channel SQUID magnetometer, suggested a dipolar current source. The topography of P55m can be explained by a tangential dipole at the first somatosensory cortex (SI) in the posterior wall of the central sulcus. The equivalent source of N140m is, on average, about 1 cm lateral to the source of P55m. The reported method allows non-invasive determination of the cortical tongue representation area.     

Interaction of afferent impulses in the human primary sensorimotor cortex.

We recorded somatosensory evoked magnetic fields (SEFs) over the hand area of the primary sensorimotor cortex (SMI) in 6 healthy adults in 2 sets of experiments to study interaction of afferent impulses. In experiment 1, SEFs were elicited by contralateral median nerve (MC) stimuli presented alone and 40 msec after a conditioning stimulus to the contralateral ulnar (UC), ipsilateral median (MI) or contralateral tibial (TC) nerve. N20m, P30m and P60m deflections to MC stimulation were markedly attenuated by preceding UC stimulation whereas N40m was enhanced, and a novel P80m emerged. In contrast, MI or TC stimulation did not affect the responses to MC. In experiment 2, the time course of recovery of N20m to median nerve stimuli was studied after stimulation of the adjacent ulnar and of the same median nerve. The recovery curves were similar for both conditioning stimuli with nearly full recovery of N20m at 120 msec. The results indicate marked interaction of impulses from ipsilateral median and ulnar nerves in human SMI, but no evidence was found of interaction from the two hands or from ipsilateral hand and foot.     

Afferent excitation of human motor cortex as revealed by enhancement of direct cortico-spinal actions on motoneurones

Changes in motor cortex excitability induced by somatosensory afferences were evaluated in 5 subjects by testing how the short-latency cortico-spinal effects evoked by transcranial magnetic stimulation in flexor carpi radialis (FCR) motoneurones were influenced by volleys in median nerve afferent fibres. Transcranial magnetic stimulation induced two facilitatory peaks on FCR H reflex, the first at a conditioning-test interval of about −3 msec and the second at 0 msec, separated by a phase of inhibition. If an electric shock to the median nerve at the wrist, 0.8-1 × motor threshold (MT) for thenar muscles, preceded the cortical stimulus by 18–25 msec, an increase in size of both facilitatory peaks was observed. The increase was partly due to a direct action of the median nerve volley on motoneurones. When this contribution was subtracted, two peaks of additional facilitation resulted as the effect of combined conditioning. Additional facilitation was present even during the short-lasting phase ascribed to monosynaptic cortico-spinal excitation of motoneurones, i.e., the first millisecond of the earliest facilitatory peak. This result indicates that cortical responsiveness to magnetic stimulation had been enhanced by the peripheral stimulus. The time course of the excitability changes in motor cortex was compared with the cortical somatosensory evoked potentials (SEPs) induced by the same peripheral stimulus. Additional facilitation was present immediately after the N20 peak of SEPs and lasted 8–10 msec. Additional facilitation had the same threshold as N20 (0.6 × MT) and grew in parallel with it when grading the afferent stimulus up to 1 MT.     

Cortical somatosensory magnetic responses in multiple sclerosis.

Somatosensory evoked magnetic fields (SEFs) to contralateral median and ulnar nerve stimulation were analyzed in 10 patients with multiple sclerosis and in 8 healthy controls. SEFs were recorded with a 24-channel SQUID gradiometer over both hemispheres. Seven patients showed abnormally large-amplitude SEF deflections at 60-80 msec; 5 of them had multiple lesions around lateral ventricles in magnetic resonance imaging. In 2 patients with plaques at the level of 3rd and 4th ventricles and medulla, the 30 msec responses were enlarged. The equivalent sources of 20 msec and 30-80 msec responses were in the primary hand sensorimotor cortex both in patients and in control subjects. The results suggest that early and middle-latency SEFs reflect parallel processing of somatosensory input. Recording of middle-latency evoked responses, electric or magnetic, may give additional information about the somatosensory function in multiple sclerosis.     

Early deflections of cerebral magnetic responses to median nerve stimulation

We have recorded early components of somatosensory evoked magnetic fields with a sensitive 7-channel first-order gradiometer using a wide recording passband (0.05-2000 Hz) and high sampling frequency (8000 Hz). The left median nerve was stimulated at the wrist and responses were recorded over the right hemisphere. The responses typically consisted of a N20m peaking at 18-20 msec, a small P22m peaking at 21-23 msec and a P27m peaking at 29-31 msec. The topography of N20m could be explained by a tangential current dipole in the posterior wall of the central sulcus (probably in area 3b). The equivalent dipoles of P27m were located on average 10 mm antero-medially to the sources of N20m. This suggests that P27m may get a contribution from the anterior wall of the central sulcus. An increase of stimulus repetition rate from 2 to 5 Hz decreased the amplitude of P27m more than that of N20m, which implies that these two deflections are generated by different neural networks.     

Late pain-related magnetic fields and electric potentials evoked by intracutaneous electric finger stimulation.

Surface magnetic and electric recordings were used to localize the sources of late pain-related magnetic fields and electric potentials, evoked by painful intracutaneous electric finger stimulation. We find that the source of the P90m component of the evoked magnetic field lies in the finger area of the primary somatosensory cortex; the sources of the N150m and P250m are found to reside in the frontal operculum. These findings are unexpected from the evoked electric potential data, which suggest a central location for these sources. We also note that the interpretation of the electric data was confounded by the presence of an alpha-like oscillation, which overlapped many components of the evoked potential.     

Enlarged SI and SII somatosensory evoked responses in the CLN5 form of neuronal ceroid lipofuscinosis.

OBJECTIVES: To examine in detail the activation of the primary (SI) and secondary (SII) somatosensory cortex in CLN5, the Finnish variant of late infantile neuronal ceroid lipofuscinoses (NCL). METHODS: Somatory evoked magnetic fields were recorded with a 122-channel planar gradiometer in response to median nerve stimulation in 5 CLN5 patients (aged 8.8-16.7 years) and in 10 healthy age-matched controls. RESULTS: The first two responses from contralateral SI, N20m and P35m, were 6-20 times stronger in the patients than in the controls. The morphology of the subsequent deflections from SI was abnormal in the patients: a prominent N45m was detected, while the normally present P60m deflection was missing. In 4 patients the contra- and in two patients the ipsilateral SII responses were also enlarged. Furthermore, the SII activation was detected at shorter latency in patients than in controls. CONCLUSIONS: At SI, CLN5 is associated with a selective enhancement of the early cortical responses. We propose that the enlargement of N20m most likely reflects increased synchronous input from thalamus, whereas the altered morphology of the following responses may reflect defective interneuronal inhibition at the cortex. The enlargement of SII responses shows that the imbalance between excitation and inhibition in CLN5 extends outside the primary somatosensory areas.     

Human somatosensory cortical activation strengths: comparison between males and females and age-related changes

The amplitudes of many scalp-recorded evoked potential (EP) deflections are higher in females than in males, and in elderly than in young subjects. Since EPs critically depend on the electric conductivity of the cranium, it is not known whether these differences reflect age- and gender-dependent changes in the intensity of neuronal activation, or changes in the volume conductor. Evoked magnetic fields are not significantly affected by the conductivities of the cranial tissues and therefore reflect more directly the neuronal activation than EPs. We report here on the effects of age and gender on somatosensory evoked fields (SEFs) from the primary somatosensory cortex (SI) in 43 healthy subjects (21 males) aged from 20 to 73 years (males 51+/-18 years, females 51+/-14 years). The intensity of neuronal activation was estimated with equivalent current dipoles (ECDs) found at the peaks of the N20m, P35m and P60m deflections from the left SI after right median nerve stimulation. The peak latencies of N20m and P35m (but not of P60m) were shorter in females than in males. The N20m latency was positively correlated with age in males, but otherwise the latencies did not correlate with age. The ECD amplitudes did not differ between males and females for any of the deflections. The N20m ECD strength showed a significant positive correlation (r=0.39, p<0.01) with age while P35m and P60m ECD strengths did not. The results thus did not disclose gender differences in the activation strengths of the somatosensory cortex, implying that such differences in evoked potentials may possibly be due to gender differences in the volume conductor. On the other hand, the results suggest a slight age-related increase in cortical excitability.     

Homeostatic metaplasticity in the human somatosensory cortex

Long-term potentiation (LTP) and long-term depression (LTD) are regulated by homeostatic control mechanisms to maintain synaptic strength in a physiological range. Although homeostatic metaplasticity has been demonstrated in the human motor cortex, little is known to which extent it operates in other cortical areas and how it links to behavior. Here we tested homeostatic interactions between two stimulation protocols -- paired associative stimulation (PAS) followed by peripheral high-frequency stimulation (pHFS) -- on excitability in the human somatosensory cortex and tactile spatial discrimination threshold. PAS employed repeated pairs of electrical stimulation of the right median nerve followed by focal transcranial magnetic stimulation of the left somatosensory cortex at an interstimulus interval of the individual N20 latency minus 15 msec or N20 minus 2.5 msec to induce LTD- or LTP-like plasticity, respectively [Wolters, A., Schmidt, A., Schramm, A., Zeller, D., Naumann, M., Kunesch, E., et al. Timing-dependent plasticity in human primary somatosensory cortex. Journal of Physiology, 565, 1039-1052, 2005]. pHFS always consisted of 20-Hz trains of electrical stimulation of the right median nerve. Excitability in the somatosensory cortex was assessed by median nerve somatosensory evoked cortical potential amplitudes. Tactile spatial discrimination was tested by the grating orientation task. PAS had no significant effect on excitability in the somatosensory cortex or on tactile discrimination. However, the direction of effects induced by subsequent pHFS varied with the preconditioning PAS protocol: After PAS(N20-15), excitability tended to increase and tactile spatial discrimination threshold decreased. After PAS(N20-2.5), excitability decreased and discrimination threshold tended to increase. These interactions demonstrate that homeostatic metaplasticity operates in the human somatosensory cortex, controlling both cortical excitability and somatosensory skill.     

Magnetic responses of the human auditory cortex to noise/square wave transitions

We recorded evoked magnetic fields from the human auditory cortex to noise/square wave sequences. Two prominent deflections were observed: one 100 msec after the noise onset (N100m) and another 100 msec after the noise/square wave transition (N100m'). The amplitude of N100m' increased with decrease in square wave frequency from 2 kHz to 0.125 kHz and with increase in square wave duration from 4 msec to 200 msec. The latency of N100m' was on the average 23 msec longer for noise durations of 60 msec than 310 msec, whereas the amplitude of N100m' did not change. Increase in interstimulus interval from 1.1 to 8.8 sec enhanced the amplitude of N100m significantly more than that of N100m'. The small interaction between N100m and N100m' and their different recovery cycles suggest that different activation patterns underlie these two 100 msec responses at the auditory cortex.     

Cortical somatosensory magnetic responses in multiple sclerosis

Somatosenosor evoked magnetic fields (SEFs) to contralateral medium and ulnnar nerve stimulation were analyzed in 10 patients with multiple sclerosis and in 8 healthy controls. SEFs were recorded with a 24-channel SQUID gradiometer over both hemispheres. Seven patients' showed abnormally large-amplitude SEF deflections at 60–80 msec; 5 of them had multiple lesions around lateral ventricles in magnetic resonance imaging. In 2 patients with plaques at the level of 3rd and 4th ventricles and medulla, the 30 msce response were enlarged. The equivalent sources of 20 msec and 30–80 msec responses were in the primary hand sensorimotor cortex both in patients and in control subjects. The results suggest that early and middle-latency SEFs reflect parallel processing of somatosensory input. Recording of middle-latency evoekd responses, electric or magnetic, may give additional information about the somatosensory function in multiple sclerosis.     

Somatosensory potentials evoked by magnetic stimulation of lumbar roots, cauda equina, and leg nerves

Cortical somatosensory evoked potentials (SEPs) were studied by noninvasive magnetic stimulation at T-10, T-12, and L-5 vertebral levels and in mid-gluteus muscle and ankle in 27 normal subjects and 7 patients with neurological diseases. Cortical components P2 and N2 were recorded in all normal subjects. The mean peak latencies of P2 were 20.3 +/- 0.9 (standard deviation), 21.1 +/- 1.2, 23.5 +/- 1.4, 27.9 +/- 2.0, and 38.1 +/- 1.8 msec at the T-10, T-12, L-5, midgluteal and ankle sites of stimulation, respectively. No substantial difference in morphology of P2 and N2 was seen between magnetic and electrical stimulation at T-12. Amplitudes of P2 and N2 were maximal after magnetic stimulation at motor threshold. P2 and N2 may originate from the sensory cortex. P2 and N2 evoked by T-10 and T-12 stimulation were normal in peak latency and morphology in patients with polyneuropathy or polyradiculoneuropathy. Peak latencies of P2 and N2 evoked by T-10 and T-12 stimulation were significantly delayed in patients with myelopathy. The patients with radiculopathy showed a delayed peak latency and conduction time of P2 evoked by L-5 stimulation. Magnetic stimulation of spinal root is able to detect lesions of spinal cord noninvasively.     

Spatiotemporal modeling of cerebral evoked magnetic fields to median nerve stimulation.

We measured somatosensory evoked magnetic fields during median nerve stimulation in 6 normal subjects. We applied multiple dipole models to study the spatiotemporal structure of early somatosensory evoked magnetic fields (SEFs), as well as the number, 3-dimensional location and time activity of their underlying neuronal sources. Two dipole sources were necessary to model the first 40 msec of SEFs explaining 85% of the data variance. Source 1 was located deeper than source 2, showed primarily a tangential orientation, and accounted for a larger part of the variance; source 2 showed no consistent orientation across subjects. Both sources showed biphasic time activities corresponding to the previously described N20-P30 and P25-N35 components. Spatiotemporal modeling could identify sources which could not be modeled consistently above noise by single moving dipoles (P25 component), revealed small latency differences of the two sources in some subjects suggesting parallel activation of these sources, and allowed separation of sources overlapping considerably both in space and time. We conclude that spatiotemporal modeling of SEFs may be useful to study functional anatomy of human sensorimotor cortex non-invasively.     

Scalp-recorded short and middle latency peroneal somatosensory evoked potentials in normals: comparison with peroneal and median nerve SEPs in patients with unilateral hemispheric lesions

Peroneal somatosensory evoked potentials (SEPs) were performed on 23 normal subjects and 9 selected patients with unilateral hemispheric lesions involving somatosensory pathways. Recording obtained from right and left peroneal nerve (PN) stimulations were compared in all subjects, using open and restricted frequency bandpass filters. Restricted filter (100-3000 Hz) and linked ear reference (A1-A2) enhanced the detection of short latency potentials (P1, P2, N1 with mean peak latency of 17.72, 21.07, 24.09) recorded from scalp electrodes over primary sensory cortex regions. Patients with lesions in the parietal cortex and adjacent subcortical areas demonstrated low amplitude and poorly formed short latency peroneal potentials, and absence of components beyond P3 peak with mean latency of 28.06 msec. In these patients, recordings to right and left median nerve (MN) stimulation showed absence or distorted components subsequent to N1 (N18) potential. These observations suggest that components subsequent to P3 potential in response to PN stimulation, and subsequent to N18 potential in response to MN stimulation, are generated in the parietal cortical regions.     

Somatosensory evoked potentials (SEPs) and cortical single unit responses elicited by mechanical tactile stimuli in awake monkeys

The origins of surface recorded evoked potentials have been investigated by combining recordings of single unit responses and somatosensory evoked potentials (SEPs) from the postcentral gyrus of 4 alert macaque monkeys. Responses were elicited by mechanical tactile stimuli (airpuffs) which selectively activate rapidly adapting cutaneous mechanoreceptors, and permit patterned stimulation of a restricted area of skin. Epidurally recorded SEPs consisted of an early positive complex, beginning 8-10 msec after airpuff onset, with two prominent positive peaks (P15 and P25), succeeded by a large negative potential (N43) lasting 30 msec, and a late slow positivity (P70). SEPs, while consistent in wave form, varied slightly between monkeys. The amplitude of the early positive complex was enhanced by increasing the number of stimulated points, or by placing the airpuffs in the receptive fields of cortical neurons located beneath the SEP recording electrode. SEP amplitude was depressed when preceded 20-40 msec earlier by a conditioning stimulus to the same skin area. Single unit responses in areas 3b and 1 of primary somatosensory (SI) cortex consisted of a burst of impulses, beginning 11-12 msec after the airpuff onset, and lasting another 15-20 msec. Peak unitary activity occurred at 12-15 msec, corresponding to the P15 wave in the SEP. No peak in SI unit responses occurred in conjunction with the P25 wave. Although SI neurons fired at lower rates during P25, the lack of any peak in SI unit responses suggests that activity in other cortical areas, such as SII cortex, contributes to this wave. Most unit activity in SI cortex ceased by the onset of N43, and was replaced by a period of profound response depression, in which unit responses to additional tactile stimuli were reduced. We propose that the N43 wave reflects IPSPs in cortical neurons previously depolarized and excited by the airpuff stimulus. Late positive potentials (P70) in the SEP had no apparent counterpart in SI unit activity, suggesting generation at other cortical loci.     

Suppression of cutaneous perception by magnetic pulse stimulation of the human brain.

We have demonstrated that magnetic pulse stimulation of the sensorimotor cortex suppresses perception of threshold electrical stimuli to the fingers of the contralateral hand. Maximum suppression of perception occurs when the fingers are stimulated 30-90 msec after the magnetic pulse. Thereafter, errors in perception of the cutaneous stimulus decrease to control levels by 300-400 msec after the magnetic pulse. The period of maximum suppression of perception coincides with the period during which cortically generated somatosensory evoked potentials (SEPs) are enhanced following magnetic pulse stimulation of the brain. The duration of suppression of perception, however, outlasts the duration of SEP enhancement. When the magnetic pulse is delivered after finger stimulation there is also suppression of perception. The suppression of perception is maximal when the magnetic pulse occurs 20-30 msec after finger stimulation. This interval coincides with the arrival of the afferent volley at the primary sensory cortex.     

Functional anatomy of human hand sensorimotor cortex from spatiotemporal analysis of electrocorticography.

We measured chronic electrocorticography (ECoG) of sensorimotor cortex during contralateral median nerve stimulation in 6 patients with partial seizures evaluated for surgery. We analyzed the spatiotemporal structure of the somatosensory evoked response (SER) using multiple source modeling to investigate functional anatomy of its neuronal sources. Two dipole sources in postcentral gyrus explained the large majority of the first 60 msec of the SER, indicating a subregion of hand somatosensory cortex generating this activity. The source locations agreed with normal functional anatomy from cortical stimulations, intraoperative photographs, and postoperative neurological examinations after focal excisions. The time patterns of both sources were biphasic like the previously described N20-P30 and P25-N35 peaks. The spatiotemporal patterns of both sources overlapped. Spatiotemporal analysis with multiple dipole sources appears useful to determine the number, locations, and spatiotemporal field patterns of cortical regions active during peripheral somatosensory stimulation and reveals simplicity in the macroscopic functional anatomy of dynamic human sensorimotor cortex.     

Auditory attention affects two different areas in the human supratemporal cortex.

The effect of selective attention on activity of the right human auditory cortex was studied with a 24-channel planar SQUID-gradiometer. Two conditions were used, favoring either a late attention effect following N100m, or an early effect, overlapping with N100m. In experiment 1 (15 subjects), a randomized tone sequence of 1 and 3 kHz tones was delivered to the left ear with a constant interstimulus interval (ISI) of 405 msec. The subjects' task was to count infrequent longer tones of one of these pitches among shorter standards. An attention effect, called magnetic difference (Md), was found when the responses to the irrelevant standards were subtracted from those to the relevant standards. Md peaked at about 220 msec for the 1 kHz tones and at 195 msec for the 3 kHz tones. The equivalent source of Md was in the supratemporal auditory cortex, about 1 cm anterior to the source of N100m, and in the same location as the source of P200m. In experiment 2 (8 subjects) the paradigm was similar, except that the 1 kHz and 3 kHz tones were led to different ears with a random ISI of 240-300 msec. In this case Md started already at 30-40 msec, adding to the N100m deflection, and the sources of N100m and Md overlapped. Present results show that attention can modify the activity of two different areas in the supratemporal auditory cortex. We interpret both attention effects as alterations of the exogenous evoked response components: the earlier effect as changed activity in neurons underlying N100m to relevant tones and the later effect as a modification of P200m to irrelevant tones.