Shortening of simple reaction time by peripheral electrical and submotor-threshold magnetic cortical stimulation

Subthreshold transcranial magnetic stimulation (TMS) over the motor cortex can shorten the simple reaction time in contralateral arm muscles if the cortical shock is given at about the same time as the reaction stimulus. The present experiments were designed to investigate whether this phenomenon is due to a specific facilitatory effect on cortical circuitry. The simple visual reaction time was shortened by 20-50 ms when subthreshold TMS was given over the contralateral motor cortex. Reaction time was reduced to the same level whether the magnetic stimulus was given over the bilateral motor cortices or over other points on the scalp (Cz, Pz). Indeed, similar effects could be seen with conventional electrical stimulation over the neck, or even when the coil was discharged (giving a click sound) near the head. We conclude that much of the effect of TMS on simple reaction time is due to intersensory facilitation, although part of it may be ascribed to a specific effect on the excitability of motor cortex.     

Precentral glioma location determines the displacement of cortical hand representation

OBJECTIVE: Low-grade brain tumors may remain asymptomatic in contrast to malignant gliomas. The mechanisms underlying the preservation of cerebral function in such gliomas are not well understood. METHODS: We used positron emission tomography and transcranial magnetic stimulation for presurgical monitoring of motor hand function in six patients with gliomas of the precentral gyrus. All patients were able to perform finger movements of the contralesional hand. RESULTS: Movement-related increases of the regional cerebral blood flow occurred only outside the tumor in surrounding brain tissue. Compared with the contralateral side, these activations were shifted by 20 +/- 13 mm (standard deviation) within the dorsoventral dimension of the precentral gyrus. This shift of cortical hand representation could not be explained by the deformation of the central sulcus as determined from the spatially aligned magnetic resonance images but was closely related to the location of the maximal tumor growth. Dorsal tumor growth resulted in ventral displacement of motor hand representation, leaving the motor cortical output system unaffected, whereas ventral tumor growth leading to dorsal displacement of motor hand representation compromised the motor cortical output, as evident from transcranial magnetic stimulation. In two patients, additional activation of the supplementary motor area was present. CONCLUSION: Our data provide evidence for the reorganization of the human motor cortex to allow for preserved hand function in Grade II astrocytomas.     

Multi-modality mapping of motor cortex: comparing echoplanar BOLD fMRI and transcranial magnetic stimulation. Short communication

Multiple non-invasive methods of imaging brain function are now available for presurgical planning and neurobiological research. As these new methods become available, it is important to understand their relative advantages and liabilities, as well as how the information gained compares across different methods. A current and future trend in neurobiological studies as well as presurgical planning is to combine information from different imaging techniques. Multi-modal integration may perhaps give more powerful information than each modality alone, especially when one of the methods is transcranial magnetic stimulation (TMS), with its ability to non-invasively activate the brain. As an initial venture in cross comparing new imaging methods, we performed the following 2 studies, locating motor cortex with echoplanar BOLD fMRI and TMS. The two methods can be readily integrated, with concurring results, although each have important limitations.     

Corticospinal direct response to transcranial magnetic stimulation in humans

The corticospinal motor evoked potential (MEP) response to transcranial magnetic stimulation of the motor cortex was investigated in comparison with the direct (D) response to electrical stimulation of the exposed motor cortex from the spinal epidural space in 7 neurologically normal patients during brain tumor surgery. The D response during operation was obtained by transcranial magnetic stimulation of the scalp over the areas of the cerebral motor cortex, the hand or arm areas. The magnetic induced D response showed a conduction velocity of 50.5-72.7 m/sec and was resistant to anesthesia and unaffected by muscle relaxants and tolerant to high frequency (500 Hz) paired magnetic stimulus, and the latencies of magnetic MEPs corresponded to those with direct electrical stimulation. Thus, recordings of the D response by transcranial magnetic stimulation are useful for not only identifying the location of the motor cortex during intracranial surgery but also for non-invasive recording of pyramidal tract activity during extracranial surgery under general anesthesia.     

Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation

We studied the effects of low-frequency transcranial magnetic stimulation (TMS) on motor cortex excitability in humans. TMS at 0.1 Hz for 1 hour did not change cortical excitability. Stimulation at 0.9 Hz for 15 minutes (810 pulses), similar to the parameters used to induce long-term depression (LTD) in cortical slice preparations and in vivo animal studies, led to a mean decrease in motor evoked potential (MEP) amplitude of 19.5%. The decrease in cortical excitability lasted for at least 15 minutes after the end of the 0.9 Hz stimulation. The mechanism underlying this decrease in excitability may be similar to LTD. TMS-induced reduction of cortical excitability has potential clinical applications in diseases such as epilepsy and myoclonus. Spread of excitation, which may be a warning sign for seizures, occurred in one subject and was not accompanied by increased MEP amplitude, suggesting that spread of excitation and amplitude changes are different phenomena and also indicating the need for adequate monitoring even with stimulations at low frequencies.     

Mechanisms of cortical reorganization in lower-limb amputees

The human motor system undergoes reorganization after amputation, but the site of motor reorganization and the mechanisms involved are unknown. We studied the site and mechanisms of motor reorganization in 16 subjects with traumatic lower-limb amputation. Stimulation at different levels in the CNS was used to determine the site of reorganization. The mechanisms involved were evaluated by measuring the thresholds for transcranial magnetic stimulation (TMS) and by testing intracortical inhibition and facilitation. With TMS, the threshold for muscle activation on the amputated side was lower than that of the intact side, but with transcranial electrical stimulation there was no difference in motor threshold between the two sides. TMS at the maximal output of the stimulator activated a higher percentage of the motor neuron pool (%MNP) on the amputated side than on the intact side. The %MNP activated by spinal electrical stimulation was similar on the two sides. Paired TMS study showed significantly less intracortical inhibition on the amputated side. Our findings suggest that motor reorganization after lower-limb amputation occurs predominately at the cortical level. The mechanisms involved are likely to include reduction of GABAergic inhibition.     

Fulminant hepatitis complicated by small intestine infection and massive hemorrhage

OBJECT: The purpose of this study was to evaluate the efficacy of noninvasive preoperative functional imaging data used in an interactive fashion in the operating room. The authors describe a method of registering preoperative functional magnetic resonance (fMR) imaging localization of sensorimotor cortex with a frameless stereotactic surgical navigation device. METHODS: The day before surgery, patients underwent blood oxygen level-dependent fMR imaging while performing a finger-tapping motor paradigm. Immediately afterward an anatomical stereotactic MR image was acquired. Raw fMR imaging data were analyzed offline at a separate workstation, and the resulting functional maps were registered to a high-resolution anatomical scan. The fused functional-anatomical images were then downloaded onto a surgical navigation computer via an ethernet connection. At surgery, the brain was exposed in the standard fashion, and the sensorimotor cortex was identified by direct cortical stimulation, the use of somatosensory evoked potentials, or both. This localization was then compared with that predicted by the registered fMR study. Thirteen procedures were performed in 12 patients. The mean registration error was 2.2 mm. The predicted location of motor and/or sensory cortex matched that found on intraoperative mapping in all 12 patients tested. Maximal tumor resection was accomplished in each case and no new permanent neurological deficits resulted. CONCLUSIONS: Compared with conventional brain mapping techniques, fMR image-guided surgery may allow for smaller brain exposures, localization of the language cortex with the patient under general anesthesia, and the mapping of multiple functional sites. The scanning equipment used in this method may be more readily available than for other functional imaging techniques such as positron emission tomography or magnetoencephalography.     

Crossed and direct effects of digital nerves stimulation on motor evoked potential: a study with magnetic brain stimulation

We studied the influence of contralateral and ipsilateral cutaneous digital nerve stimulation on motor evoked potentials (MEPs) elicited in hand muscles by transcranial magnetic stimulation (TMS). We tested the effect of different magnetic stimulus intensities on MEPs recorded from the thenar eminence (TE) muscles of the right hand while an electrical conditioning stimulus was delivered to the second finger of the same hand with an intensity four times above the sensory threshold. Amplitude decrement of conditioned MEPs as a function of magnetic stimulus intensity was observed. The lowest TMS stimulus intensity produced the largest decrease in conditioned MEPs. Moreover, we investigated the effects of ipsilateral and contralateral electrical digital stimulation on MEPs elicited in the right TE and biceps muscle using an intensity 10% above the threshold. Marked MEP inhibition in TE muscles following both ipsilateral and contralateral digital stimulation is the main finding of this study. The decrease in conditioned MEP amplitude to ipsilateral stimulation reached a level of 50% of unconditioned MEP amplitude with the circular coil and 30% with the focal coil. The amplitude of conditioned MEPs to contralateral digital stimulation showed a decrease of 60% with the circular coil and more than 50% with the focal coil. The onset of the inhibitory effect of contralateral stimulation using the focal coil occurred at a mean of 15 ms later than that of ipsilateral stimulation. No MEP inhibition was observed when recording from proximal muscles. Ipsilateral and contralateral digital stimulation had no effect on F wave at appropriate interstimulus intervals, where the main MEP suppression was noted. We stress the importance of selecting an appropriate test stimulus intensity to evaluate MEP inhibition by digital nerves stimulation. Spinal and cortical sites of sensorimotor integration are adduced to explain the direct and crossed MEP inhibition following digital nerves stimulation.     

Magnetoencephalographic mapping: basic of a new functional risk profile in the selection of patients with cortical brain lesions

OBJECTIVE: Surgical management of cortical lesions adjacent to or within the eloquent cerebral cortex requires a critical risk: benefit analysis of the procedure before intervention. This study introduced a measure of surgical risk, based on preoperative magnetoencephalographic (MEG) sensory and motor mapping, and tested its value in predicting surgical morbidity. METHODS: Forty patients (21 men and 19 women; mean age, 36.5 yr) with cortical lesions (12 arteriovenous malformations and 28 tumors) in the vicinity of the sensorimotor cortex were classified into high-, medium-, or low-risk categories by using the MEG-defined functional risk profile (FRP). This was based on the minimal distance between the lesion margin and the sensory and motor MEG sources, superimposed on a magnetic resonance imaging scan. Case management decisions were based on the MEG mapping-derived FRP in combination with biopsy pathological findings, radiographic findings, and anatomic characteristics of the lesion. A recently developed protocol was used to transform MEG source locations into the stereotactic coordinate system. This procedure provided intraoperative access to MEG data in combination with stereotactic anatomic data displays routinely available on-line during surgery. RESULTS: It was determined that 11 patients diagnosed as having gliomas had high FRPs. The margin of the lesion was less than 4 mm from the nearest MEG dipole or involved the central sulcus directly. A nonoperative approach was used for six patients of this group, based on the MEG mapping-derived FRP. In the group with arteriovenous malformations, 6 of 12 patients with high or medium FRPs underwent nonoperative therapy. The remaining 28 patients, whose lesions showed satisfactory FRPs, underwent uneventful lesion resection, without postoperative neurological deficits. CONCLUSION: Our results suggest that MEG mapping-derived FRPs can serve as powerful tools for use in presurgical planning and during surgery.     

Intracranial neurosurgery guided by functional imaging

Neurosurgery on eloquent cortex entails important risks of functional deficits complicating aggressive lesion resection. In this study, advanced biomagnetic functional imaging of somatosensory and motor cortex combined with surface rendered magnetic resonance imaging displays including vascular anatomy were used in conjunction with a new nonintrusive intraoperative guided instrumentation system to resect a tumor in eloquent cortex. Intraoperative verification of the accuracy of pre-operative motor localization demonstrated highly accurate results comparing direct stimulation and noninvasive presurgical mapping. The applicability of surface rendered combined functional and anatomic maps of cortex is directly evident on comparison of preoperative computer images and intraoperative pictures. This combination of new technologies has a significant potential for reduced risk and improved outcome in neurosurgery of eloquent cortex.     

Impaired motor cortex inhibition in patients with amyotrophic lateral sclerosis. Evidence from paired transcranial magnetic stimulation

We investigated 14 patients with amyotrophic lateral sclerosis (ALS) by paired conditioning-test transcranial magnetic stimulation to test the hypothesis that the motor cortex is hyperexcitable in ALS. Intracortical (corticocortical) inhibition was significantly less in the ALS group than in an age-matched healthy control group (85.3 +/- 27.0% versus 45.2 +/- 15.5%, respectively; p < 0.0001). In contrast, intracortical facilitation, motor threshold, and cortical silent period duration in the ALS patients were not different from the control group. We suggest that the selective abnormality of intracortical inhibition is best compatible with an impaired function of inhibitory interneuronal circuits in the motor cortex that in turn renders the corticomotoneuron hyperexcitable.     

Comparison of magnetoencephalography, functional MRI, and motor evoked potentials in the localization of the sensory-motor cortex

To clarify the topographical relationship between peri-Rolandic lesions and the central sulcus, we carried out presurgical functional mapping by using magnetoencephalography (MEG), functional magnetic resonance imaging (f-MRI), and motor evoked potentials (MEPs) on 5 patients. The sensory cortex was identified by somatosensory evoked magnetic fields using MEG (magnetic source imaging (MSI)). The motor area of the hand region was identified using f-MRI, during a hand squeezing task. In addition, transcranial magnetic stimulation localized the hand motor area on the scalp, which was mapped onto the MRI. In all cases, the sensory cortex was easily identified by MSI and the results of MSI correlated well with the findings obtained by the intraoperative recording of somatosensory evoked potentials. In contrast, the motor cortex could not be localized by f-MRI due to either the activated signal of the large cortical vein or the lack of any functional activation in the area of peri-lesional edema. MEPs were also unable to localize the entire motor strip. Therefore, at present, MSI is considered to be the most reliable method to localize peri-Rolandic lesions [corrected].     

Optical imaging of bipolar cortical stimulation

In order to better understand the degree of cortical activation that occurs during bipolar surface stimulation, the authors stimulated monkey visual cortex while monitoring the degree of activation with optical imaging. Optical imaging of intrinsic signals in monkey visual cortex during visual stimulation resulted in functional maps of ocular dominance and orientation selectivity. After functional maps of ocular dominance and orientation preference were obtained, bipolar surface stimulation was applied to activate just the cortical areas around the bipolar electrodes. Graded responses to changes in the stimulation intensity and duration were found. These findings demonstrate the reliability of bipolar cortical surface stimulation in localizing functional regions of cortex. The area of activation, at least in the region around the bipolar stimulating electrodes, did not appear to activate nearby ocular dominance columns or orientation patches. Intraoperative bipolar surface stimulation continues to be a consistently reliable technique for localizing rolandic cortex and essential language sites.     

Correlation of functional magnetic source imaging with intraoperative cortical stimulation in neurosurgical patients

This study compared noninvasive preoperative functional imaging by using magnetoencephalography (MEG) with intraoperative direct cortical stimulation in ten patients undergoing neurosurgery. The goal was to assess the accuracy and reliability of MEG-based functional imaging in these patients as a possible replacement or adjunct for direct cortical stimulation with electrocorticography. Objective comparison of intraoperative mapping with preoperative MEG procedures was achieved by intraoperative recording of mapped cortical locations for motor responses using an interactive image-guided surgical device, the ISG viewing wand, with which mapping points could be marked on a previously acquired (MRI) set. In all ten patients, at least one stimulation site elicited a response during both MEG and intraoperative mapping. The central sulcus ipsilateral to the lesion was only directly visible on high-resolution MRIs in 3/10 cases and equivocally in 2/10. Coregistered with MRI to form magnetic source images (MSIs), MEG predictions of the postcentral gyrus were possible in all 10 cases. In all 10 cases, these were in agreement with intraoperative estimation of the precentral gyrus. Functional mapping of somatosensory cortex was achieved noninvasively in surgical patients by using MSI. The accuracy, compared with cortical stimulation, was always sufficient to define motor and somatosensory strips.     

Cortical sensorimotor reorganization after spinal cord injury: an electroencephalographic study

The aim of this study was to determine if cortical motor representation and generators change after partial or complete paralysis after spinal cord injury (SCI). Previously reported evidence for a change in cortical motor function after SCI was derived from transcranial magnetic stimulation. These studies inferred a reorganization of the cortical motor system. We applied the new technique of high-resolution EEG to measure changes in cortical motor representation directly. We recorded and mapped the motor potential (MP) of the movement-related cortical potentials in 12 SCI patients and 11 control subjects. Results were analyzed using a distance metric to compare MP locations between patients and control subjects. EEG was coregistered with subject-specific MR images and a boundary element model created for dipole source analysis (DSA). When compared with normal control subjects, seven quadriparetics had posteriorly located MPs with finger movements. One paraparetic had a posterior MP with toe movements, but three who could not move the toes had normally located MPs on attempts to move. DSA confirmed the electrical field map distributions of the MPs. We are reporting a reorganization of cortical motor activity to a posterior location after SCI. These results suggest an important role of the somatosensory cortex (S1) in the recovery process after SCI.     

A comparison of transcranial magnetic stimulation with electroneuronography as a predictive test in patients with Bell's palsy

The aim of this study was to examine the neuronographic findings of electrical and transcranial magnetic stimulation of the facial nerve and to compare their ability to predict clinical recovery from idiopathic facial nerve palsy (Bell's palsy). Eighty-six patients were examined clinically and neurophysiologically immediately on presentation to Tampere University Hospital. Electroneuronography (ENoG) and transcranial magnetic stimulation (TMS) were performed 1-6 times for each patient. The time interval between each examination varied from 2 to 7 days. Seventy-eight patients were followed for a median period of 13 months after the onset of palsy. Facial nerve function was graded according to the House-Brackmann grading system. Relative amplitude differences of ENoG and TMS during the acute phase were then correlated with clinical outcome. Statistical analysis of the results showed that a TMS response elicitable during the first 5 days of the palsy was correlatable with a good prognosis. ENoG results correlated with clinical outcome at a later time from onset of symptoms. TMS was well tolerated and no adverse effects were seen. These results indicate that TMS is a useful method for the early prediction of outcome in patients with Bell's palsy.     

Modulation of plasticity in human motor cortex after forearm ischemic nerve block

Deafferentation leads to cortical reorganization that may be functionally beneficial or maladaptive. Therefore, we were interested in learning whether it is possible to purposely modulate deafferentation-induced reorganization. Transient forearm deafferentation was induced by ischemic nerve block (INB) in healthy volunteers. The following five interventions were tested: INB alone; INB plus low-frequency (0.1 Hz) repetitive transcranial magnetic stimulation of the motor cortex ipsilateral to INB (INB+rTMSi); rTMSi alone; INB plus rTMS of the motor cortex contralateral to INB (INB+rTMSc); and rTMSc alone. Plastic changes in the motor cortex contralateral to deafferentation were probed with TMS, measuring motor threshold (MT), motor evoked-potential (MEP) size, and intracortical inhibition (ICI) and facilitation (ICF) to the biceps brachii muscle proximal to the level of deafferentation. INB alone induced a moderate increase in MEP size, which was significantly enhanced by INB+rTMSc but blocked by INB+rTMSi. INB alone had no effect on ICI or ICF, whereas INB+rTMSc reduced ICI and increased ICF, and conversely, INB+rTMSi deepened ICI and suppressed ICF. rTMSi and rTMSc alone were ineffective in changing any of these parameters. These findings indicate that the deafferented motor cortex becomes modifiable by inputs that are normally subthreshold for inducing changes in excitability. The deafferentation-induced plastic changes can be up-regulated by direct stimulation of the "plastic" cortex and likely via inhibitory projections down-regulated by stimulation of the opposite cortex. This modulation of cortical plasticity by noninvasive means might be used to facilitate plasticity when it is primarily beneficial or to suppress it when it is predominately maladaptive.     

Visualization of the information flow through human oculomotor cortical regions by transcranial magnetic stimulation

We investigated the topography of human cortical activation during an antisaccade task by focal transcranial magnetic stimulation (TMS). We used a figure-eight shaped coil, with the stimulus intensity set just above the threshold for activation of the hand motor areas but weak enough not to elicit blinks. TMS was delivered at various time intervals (80, 100, and 120 ms) after target presentation over various sites on the scalp while the subjects performed the antisaccade task. It was possible to elicit a mild but significant delay in saccade onset over 1) the frontal regions (a region 2-4 cm anterior and 2-4 cm lateral to hand motor area) and 2) posterior parietal regions (6-8 cm posterior and 0-4 cm lateral to hand motor area) regardless of which hemisphere was stimulated. The frontal regions were assumed to correspond to a cortical region including the frontal eye fields (FEFs), whereas the parietal regions were assumed to represent a wide region that includes the posterior parietal cortices (PPCs). The regions inducing the delay shifted from the posterior parietal regions at an earlier interval (80 ms) to the frontal regions at a later interval (100 ms), which suggested an information flow from posterior to anterior cortical regions during the presaccadic period. At 120 ms, the effect of TMS over the frontal regions still persisted but was greatly diminished. Erroneous prosaccades to the presented target were elicited over a wide cortical region including the frontal and posterior parietal regions, which again showed a forward shift with time. However, the distribution of effective regions exhibited a clear contralateral predominance in terms of saccade direction. Our technique provides a useful method not only for detecting the topography of cortical regions active during saccadic eye movement, but also for constructing a physiological map to visualize the temporal evolution of functional activities in the relevant cortical regions.     

Intracortical inhibition of lower limb motor-evoked potentials after paired transcranial magnetic stimulation

The aim of the present study was to determine the characteristics of intracortical inhibition in the motor cortex areas representing lower limb muscles using paired transcranial magnetic (TMS) and transcranial electrical stimulation (TES) in healthy subjects. In the first paradigm (n=8), paired magnetic stimuli were delivered through a double cone coil and motor evoked potentials (MEPs) were recorded from quadriceps (Q) and tibialis anterior (TA) muscles during relaxation. The conditioning stimulus strength was 5% of the maximum stimulator output below the threshold MEP evoked during weak voluntary contraction of TA (33+/-5%). The test stimulus (67+/-2%) was 10% of the stimulator output above the MEP threshold in the relaxed TA. Interstimulus intervals (ISIs) from 1-15 ms were examined. Conditioned TA MEPs were significantly suppressed (P<0.01) at ISIs of less than 5 ms (relative amplitude from 20-50% of the control). TA MEPs tended to be only slightly facilitated at 9-ms and 10-ms ISIs. The degree of MEP suppression was not different between right and left TA muscles despite the significant difference in size of the control responses (P<0.001). Also, conditioned MEPs were not significantly different between Q and TA. The time course of TA MEP suppression, using electrical test stimuli, was similar to that found using TMS. In the second paradigm (n=2), the suppression of TA MEPs at 2, 3, and 4 ms ISIs was examined at three conditioning intensities with the test stimulation kept constant. For the pooled 2- to 4-ms ISI data, relative amplitudes were 34+/-6%, 61+/-5%, and 98+/-9% for conditioning intensities of 0.95, 0.90, and 0.85x active threshold, respectively (P<0.01). In conclusion, the suppression of lower limb MEPs following paired TMS showed similar characteristics to the intracortical inhibition previously described for the hand motor area.     

Transcranial magnetic stimulation during PET: reaching and verifying the target site

Transcranial magnetic stimulation (TMS) during positron emission tomography (PET) is a novel technique for in vivo measurements of connectivity and excitability of the human cerebral cortex. Here we describe tools that allow investigators to position the stimulating coil over a target region and to verify the actual position of the coil after the study. The former is achieved by coregistering the head of the subject with an MR image of his/her brain using frameless stereotaxy. The latter is accomplished by identifying the coil on a transmission scan and coregistering it, e.g., with a model of the electrical field induced in the brain.