Targeting of White Matter Tracts with Transcranial Magnetic Stimulation

BackgroundTMS activations of white matter depend not only on the distance from the coil, but also on the orientation of the axons relative to the TMS-induced electric field, and especially on axonal bends that create strong local field gradient maxima. Therefore, tractography contains potentially useful information for TMS targeting.Objective/methodsHere, we utilized 1-mm resolution diffusion and structural T1-weighted MRI to construct large-scale tractography models, and localized TMS white matter activations in motor cortex using electromagnetic forward modeling in a boundary element model (BEM).ResultsAs expected, in sulcal walls, pyramidal cell axonal bends created preferred sites of activation that were not found in gyral crowns. The model agreed with the well-known coil orientation sensitivity of motor cortex, and also suggested unexpected activation distributions emerging from the E-field and tract configurations. We further propose a novel method for computing the optimal coil location and orientation to maximally stimulate a pre-determined axonal bundle.ConclusionsDiffusion MRI tractography with electromagnetic modeling may improve spatial specificity and efficacy of TMS.     

Evoking highly focal percepts in the fingertips through targeted stimulation of sulcal regions of the brain for sensory restoration

BackgroundParalysis and neuropathy, affecting millions of people worldwide, can be accompanied by significant loss of somatosensation. With tactile sensation being central to achieving dexterous movement, brain-computer interface (BCI) researchers have used intracortical and cortical surface electrical stimulation to restore somatotopically-relevant sensation to the hand. However, these approaches are restricted to stimulating the gyral areas of the brain. Since representation of distal regions of the hand extends into the sulcal regions of human primary somatosensory cortex (S1), it has been challenging to evoke sensory percepts localized to the fingertips.Objective/hypothesisTargeted stimulation of sulcal regions of S1, using stereoelectroencephalography (SEEG) depth electrodes, can evoke focal sensory percepts in the fingertips.MethodsTwo participants with intractable epilepsy received cortical stimulation both at the gyri via high-density electrocorticography (HD-ECoG) grids and in the sulci via SEEG depth electrode leads. We characterized the evoked sensory percepts localized to the hand.ResultsWe show that highly focal percepts can be evoked in the fingertips of the hand through sulcal stimulation. fMRI, myelin content, and cortical thickness maps from the Human Connectome Project elucidated specific cortical areas and sub-regions within S1 that evoked these focal percepts. Within-participant comparisons showed that percepts evoked by sulcal stimulation via SEEG electrodes were significantly more focal (80% less area; p = 0.02) and localized to the fingertips more often, than by gyral stimulation via HD-ECoG electrodes. Finally, sulcal locations with consistent modulation of high-frequency neural activity during mechanical tactile stimulation of the fingertips showed the same somatotopic correspondence as cortical stimulation.ConclusionsOur findings indicate minimally invasive sulcal stimulation via SEEG electrodes could be a clinically viable approach to restoring sensation.     

Short-Latency Artifacts Associated with Concurrent TMS–EEG

BackgroundConcurrent transcranial magnetic stimulation and electroencephalography (TMS–EEG) is an emerging method for studying cortical network properties. However, various artifacts affect measurement of TMS-evoked cortical potentials (TEPs), especially within 30 ms of stimulation.Objective/hypothesisThe aim of this study was to assess the origin and recovery of short-latency TMS–EEG artifacts (<30 ms) using different stimulators and under different experimental conditions.MethodsEEG was recorded during TMS delivered to a phantom head (melon) and 12 healthy volunteers with different TMS machines, at different scalp positions, at different TMS intensities, and following paired-pulse TMS. Recovery from the TMS artifact and other short-latency artifacts were compared between conditions.ResultsFollowing phantom stimulation, the artifact resulting from different TMS machines (Magstim 200, Magventure MagPro R30 and X100) and pulse shapes (monophasic and biphasic) resulted in different artifact profiles. After accounting for differences between machines, TMS artifacts recovered within ～12 ms. This was replicated in human participants, however a large secondary artifact (peaks at 5 and 10 ms) became prominent following stimulation over lateral scalp positions, which only recovered after ～25–40 ms. Increasing TMS intensity increased secondary artifact amplitude over both motor and prefrontal cortex. There was no consistent modulation of the secondary artifact following inhibitory paired-pulse TMS (interstimulus interval = 100 ms) over motor cortex.ConclusionsThe secondary artifact observed in humans is consistent with activation of scalp muscles following TMS. TEPs can be recorded within a short period of time (10–12 ms) following TMS, however measures must be taken to avoid muscle stimulation.     

Lateralization of forelimb motor evoked potentials by transcranial magnetic stimulation in rats

ObjectivesTo approximate methods for human transcranial magnetic stimulation (TMS) in rats, we tested whether lateralized cortical stimulation resulting in selective activation of one forelimb contralateral to the site of stimulation could be achieved by TMS in the rat.MethodsMotor evoked potentials (MEP) were recorded from the brachioradialis muscle bilaterally in adult male anesthetized rats (n = 13). A figure-of-eight TMS coil was positioned lateral to midline. TMS intensity was increased stepwise from subthreshold intensities to maximal machine output in order to generate input–output curves and to determine the motor threshold (MT) for brachioradialis activation.ResultsIn 100% of the animals, selective activation of the contralateral brachioradialis, in the absence of ipsilateral brachioradialis activation was achieved, and the ipsilateral brachioradialis was activated only at TMS intensities exceeding contralateral forelimb MT. With increasing TMS intensity, the amplitudes of both the ipsilateral and contralateral signals increased in proportion to TMS strength. However, the input–output curves for the contralateral and ipsilateral brachioradialis were significantly different (p < 0.001) such that amplitude of the ipsilateral MEP was reliably lower than the contralateral signal.ConclusionsWe demonstrate that lateralized TMS leading to asymmetric brachioradialis activation is feasible with conventional TMS equipment in anesthetized rats.SignificanceThese data show that TMS can be used to assess the unilateral excitability of the forelimb descending motor pathway in the rat, and suggest that rat TMS protocols analogous to human TMS may be applied in future translational research.     

Simulation of transcranial magnetic stimulation in head model with morphologically-realistic cortical neurons

BackgroundTranscranial magnetic stimulation (TMS) enables non-invasive modulation of brain activity with both clinical and research applications, but fundamental questions remain about the neural types and elements TMS activates and how stimulation parameters affect the neural response.ObjectiveTo develop a multi-scale computational model to quantify the effect of TMS parameters on the direct response of individual neurons.MethodsWe integrated morphologically-realistic neuronal models with TMS-induced electric fields computed in a finite element model of a human head to quantify the cortical response to TMS with several combinations of pulse waveforms and current directions.ResultsTMS activated with lowest intensity intracortical axonal terminations in the superficial gyral crown and lip regions. Layer 5 pyramidal cells had the lowest thresholds, but layer 2/3 pyramidal cells and inhibitory basket cells were also activated at most intensities. Direct activation of layers 1 and 6 was unlikely. Neural activation was largely driven by the field magnitude, rather than the field component normal to the cortical surface. Varying the induced current direction caused a waveform-dependent shift in the activation site and provided a potential mechanism for experimentally observed differences in thresholds and latencies of muscle responses.ConclusionsThis biophysically-based simulation provides a novel method to elucidate mechanisms and inform parameter selection of TMS and other cortical stimulation modalities. It also serves as a foundation for more detailed network models of the response to TMS, which may include endogenous activity, synaptic connectivity, inputs from intrinsic and extrinsic axonal projections, and corticofugal axons in white matter.     

Experience with transcranial magnetic stimulation in cortical mapping

Abstract

Seventeen subjects underwent transcranial magnetic stimulation (TMS) toward cortical mapping. Cortical mapping produced scalp representations of five upper extremity muscles and their spatial orientation tended to support an expected anatomic pattern. Muscle map locations and map areas showed trends across musical skill and hand dominance as well. No subject experienc.ed adverse effects during the study. TMS promises to be an effective tool for noninvasive cortical mapping. [Neural Res 1997; 19: 435-440]     

Functional MRI-navigated Repetitive Transcranial Magnetic Stimulation Over Supplementary Motor Area in Chronic Tic Disorders

BackgroundOpen label studies have shown repetitive transcranial magnetic stimulation to be effective in reducing tics.ObjectivesTo determine whether 8 sessions of continuous theta burst stimulation (cTBS) over supplementary motor area (SMA) given over 2 days may reduce tics and motor cortical network activity in Tourette syndrome/chronic tic disorders.MethodsThis was a randomized (1:1), double-blind, sham-controlled trial of functional MRI (fMRI)-navigated, 30 Hz cTBS at 90% of resting motor threshold (RMT) over SMA in 12 patients ages 10–22 years. Comorbid ADHD (n = 8), OCD (n = 8), and stable concurrent medications (n = 9) were permitted. Neuro-navigation utilized each individual's event-related fMRI signal. Primary clinical and cortical outcomes were: 1) Yale Global Tic Severity Scale (YGTSS) at one week; 2) fMRI event-related signal in SMA and primary motor cortex (M1) during a finger-tapping motor task.ResultBaseline characteristics were not statistically different between groups (age, current tic/OCD/ADHD severities, tic-years, number of prior medication trials, RMT). Mean YGTSS scores decreased in both active (27.5 ± 7.4 to 23.2 ± 9.8) and sham (26.8 ± 4.8 to 21.7 ± 7.7) groups. However, no significant difference in video-based tic severity rating was detected between the two groups. Two-day post-treatment fMRI activation during finger tapping decreased significantly in active vs. sham groups for SMA (P = 0.02), left M1 (P = 0.0004), and right M1 (P < 0.0001). No serious adverse events occurred.ConclusionActive, fMRI-navigated cTBS administered in 8 sessions over 2 days to the SMA induced significant inhibition in the motor network (SMA, bilateral M1). However, both groups on average experienced tic reduction at 7 days. Larger sample size and protocol modifications may be needed to produce clinically significant tic reduction beyond placebo effect.     

Meditation-Related Increases in GABAB Modulated Cortical Inhibition

BackgroundRecent reports suggest meditation practice improves attentional performance and emotional regulation. The process of meditation apparently increases activation in the prefrontal cortex (PFC) and stimulates the reticular nucleus of the thalamus, implicating the production and delivery of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). GABAergic inhibitory interneurons have a central role in cortical inhibition (CI), modulating cortical excitability and neural plasticity.Objective/hypothesisChanges in CI, after completion of a single meditation session, were investigated and compared to a non-meditating control activity.MethodsTranscranial magnetic stimulation (TMS), a non-invasive method of examining CI, was used to evaluate changes before and after a 60 min meditation session. Seventy right-handed healthy subjects (n = 35 meditators, n = 35 non-meditators) were assessed using TMS related measures of cortical silent period (CSP) and short intra cortical inhibition (SICI), with stimulation of the motor cortex coordinated with EMG recording of peripheral hand muscles.ResultsFor the meditators, CSP and SICI were measured before and after meditation sessions while age–sex matched healthy control subjects were identically assessed after a non-meditating activity (television watching). The meditators showed a statistically significant increase in CSP after meditation compared to non-meditators after an equivalent period of television watching (P = 0.02) while no significant between-group differences were observed in the SICI.ConclusionThese findings indicate meditation processes are linked to GABAergic cortical inhibition, a mechanism previously implicated in improved cognitive performance and enhanced emotional regulation.     

Triad-conditioning Transcranial Magnetic Stimulation in Parkinson's Disease

BackgroundTranscranial magnetic stimulation (TMS) has been used to reveal excitability changes of the primary motor cortex (M1) in Parkinson's disease (PD). Abnormal rhythmic neural activities are considered to play pathophysiological roles in the motor symptoms of PD. The cortical responses to external rhythmic stimulation have not been studied in PD. We recently reported a new method of triad-conditioning TMS to detect the excitability changes after rhythmic conditioning stimuli, which induce facilitation by 40-Hz stimulation in healthy volunteers.ObjectiveWe applied a triad-conditioning TMS to PD patients to reveal the motor cortical response characteristics to rhythmic TMS.MethodsThe subjects included 13 PD patients and 14 healthy volunteers. Three conditioning stimuli over M1 at an intensity of 110% active motor threshold preceded the test TMS at various inter-stimulus intervals corresponding to 10–200 Hz.ResultsThe triad-conditioning TMS at 40 Hz induced no MEP enhancement in PD patients in either the On or Off state, in contrast to the facilitation observed in the normal subjects. Triad-conditioning TMS at 20–33 Hz in the beta frequency elicited significant MEP suppression in PD patients. The amount of suppression at 20 Hz positively correlated with the UPDRS III score.ConclusionWe observed abnormal M1 responses to rhythmic TMS in PD. The suppression induced by beta frequency stimulation and no facilitation by 40-Hz stimulation may be related to abnormal beta and gamma band activities within the cortical-basal ganglia network in PD patients. The motor cortical response to rhythmic TMS may be an additional method to detect physiological changes in humans.     

Disentangling EEG responses to TMS due to cortical and peripheral activations

Backgroundthe use of combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) for the functional evaluation of the cerebral cortex in health and disease is becoming increasingly common. However, there is still some ambiguity regarding the extent to which brain responses to auditory and somatosensory stimulation contribute to the TMS-evoked potential (TEP).Objective/Hypothesisto measure separately the contribution of auditory and somatosensory stimulation caused by TMS, and to assess their contribution to the TEP waveform, when stimulating the motor cortex (M1).Methods19 healthy volunteers underwent 7 blocks of EEG recording. To assess the impact of auditory stimulation on the TEP waveform, we used a standard figure of eight coil, with or without masking with a continuous noise reproducing the specific time-varying frequencies of the TMS click, stimulating at 90% of resting motor threshold. To further characterise auditory responses due to the TMS click, we used either a standard or a sham figure of eight coil placed on a pasteboard cylinder that rested on the scalp, with or without masking. Lastly, we used electrical stimulation of the scalp to investigate the possible contribution of somatosensory activation.Resultsauditory stimulation induced a known pattern of responses in electrodes located around the vertex, which could be suppressed by appropriate noise masking. Electrical stimulation of the scalp alone only induced similar, non-specific scalp responses in the in the central electrodes. TMS, coupled with appropriate masking of sensory input, resulted in specific, lateralized responses at the stimulation site, lasting around 300 ms.Conclusionsif careful control of confounding sources is applied, TMS over M1 can generate genuine, lateralized EEG activity. By contrast, sensory evoked responses, if present, are represented by non-specific, late (100–200 ms) components, located at the vertex, possibly due to saliency of the stimuli. Notably, the latter can confound the TEP if masking procedures are not properly used.     

Differentiating transcranial magnetic stimulation cortical and auditory responses via single pulse and paired pulse protocols: A TMS-EEG study

ObjectiveWe measured the neurophysiological responses of both active and sham transcranial magnetic stimulation (TMS) for both single pulse (SP) and paired pulse (PP; long interval cortical inhibition (LICI)) paradigms using TMS-EEG (electroencephalography).MethodsNineteen healthy subjects received active and sham (coil 90° tilted and touching the scalp) SP and PP TMS over the left dorsolateral prefrontal cortex (DLPFC). We measured excitability through SP TMS and inhibition (i.e., cortical inhibition (CI)) through PP TMS.ResultsCortical excitability indexed by area under the curve (AUC_(25-275ms)) was significantly higher in the active compared to sham stimulation (F(1,18) = 43.737, p < 0.001, η² = 0.708). Moreover, the amplitude of N100-P200 complex was significantly larger (F(1,18) = 9.118, p < 0.01, η² = 0.336) with active stimulation (10.38 ± 9.576 µV) compared to sham (4.295 ± 2.323 µV). Significant interaction effects were also observed between active and sham stimulation for both the SP and PP (i.e., LICI) cortical responses. Finally, only active stimulation (CI = 0.64 ± 0.23, p < 0.001) resulted in significant cortical inhibition.ConclusionThe significant differences between active and sham stimulation in both excitatory and inhibitory neurophysiological responses showed that active stimulation elicits responses from the cortex that are different from the non-specific effects of sham stimulation.SignificanceOur study reaffirms that TMS-EEG represents an effective tool to evaluate cortical neurophysiology with high fidelity.     

TMS brain mapping of the pharyngeal cortical representation in healthy subjects

BackgroundBrain mapping is fundamental to understanding brain organization and function. However, a major drawback to the traditional Brodmann parcellation technique is the reliance on the use of postmortem specimens. It has therefore historically been difficult to make any comparison regarding functional data from different regions or hemispheres within the same individual. Moreover, this method has been significant limited by subjective boundaries and classification criteria and therefore suffer from reproducibility issues. The development of transcranial magnetic stimulation (TMS) offers an alternative approach to brain mapping, specifically the motor cortical regions by eliciting quantifiable functional reactions.ObjectiveTo precisely describe the motor cortical topographic representation of pharyngeal constrictor musculature using TMS and to further map the brain for use as a tool to study brain plasticity.Methods51 healthy subjects (20 male/31 female, 19–26 years old) were tested using single-pulse TMS combined with intraluminal catheter-guided high-resolution manometry and a standardized grid cap. We investigated various parameters of the motor-evoked potential (MEP) that include the motor map area, amplitude, latency, center of gravity (CoG) and asymmetry index.ResultsCortically evoked response latencies were similar for the left and right hemispheres at 6.79 ± 0.22 and 7.24 ± 0.27 ms, respectively. The average scalp positions (relative to the vertex) of the pharyngeal motor cortical representation were 10.40 ± 0.19 (SE) cm medio-lateral and 3.20 ± 0.20 (SE) cm antero-posterior in the left hemisphere and 9.65 ± 0.24 (SE) cm medio-lateral and 3.18 ± 0.23 (SE) cm antero-posterior in the right hemisphere. The mean motor map area of the pharynx in the left and right hemispheres were 9.22 ± 0.85(SE) cm²and 10.12 ± 1.24(SE) cm², respectively. The amplitudes of the MEPs were 35.94 ± 1.81(SE)uV in the left hemisphere and 34.49 ± 1.95(SE)uV in the right hemisphere. By comparison, subtle but consistent differences in the degree of the bilateral hemispheric representation were also apparent both between and within individuals.ConclusionThe swallowing musculature has a bilateral motor cortical representation across individuals, but is largely asymmetric within single subjects. These results suggest that TMS mapping using a guided intra-pharyngeal EMG catheter combined with a standardized gridded cap might be a useful tool to localize brain function/dysfunction by linking brain activation to the corresponding physical reaction.     

Motor activation in patients with Pantothenate-Kinase Associated Neurodegeneration: A functional magnetic resonance imaging study

BackgroundIn a variety of dystonias, functional magnetic resonance imaging has shown deviations of cortical and basal ganglia activations within the motor network, which might cause the movement disturbances. Because these investigations have never been performed in secondary dystonia due to Pantothenate-Kinase Associated Neurodegeneration, we report our results in a small group of such patients from the Dominican Republic.MethodsFunctional magnetic resonance imaging was carried out in 7 patients with a genetically confirmed mutation of the PANK2 gene and a non-affected control group (matched pairs) using an event-related motor activation paradigm (hand movements).ResultsCompared to the control group (p ≤ 0.01), patients showed a larger amount of activated voxels starting in the contralateral cerebellum and contralateral premotor cortex 2 s before the actual hand movement. Whereas these “hyperactivations” gradually diminished over time, activations in the contralateral primary motor cortex and the supplementary motor area peaked during the next second and those of the contralateral putamen at the time of the actual hand movement. In a multiple regression analysis, all these areas correlated positively with the degree of dystonia of the contralateral arm as judged by the Burke–Fahn–Marsden-scale (p ≤ 0.001).ConclusionAs in other forms of dystonia, the increased activations of the motor system found in our patients could be related to the origin of the dystonic movements. Because in this condition the primary lesion affects the pallidum, a defect of the feed-back control mechanism between basal ganglia and cortex might be the responsible factor.     

Decreased interhemispheric connectivity and increased cortical excitability in unmedicated schizophrenia: A prefrontal interleaved TMS fMRI study

BackgroundPrefrontal abnormalities in schizophrenia have consistently emerged from resting state and cognitive neuroimaging studies. However, these correlative findings require causal verification via combined imaging/stimulation approaches. To date, no interleaved transcranial magnetic stimulation and functional magnetic resonance imaging study (TMS fMRI) has probed putative prefrontal cortex abnormalities in schizophrenia.Objective/Hypothesis: We hypothesized that subjects with schizophrenia would show significant hyperexcitability at the site of stimulation (BA9) and decreased interhemispheric functional connectivity.MethodsWe enrolled 19 unmedicated subjects with schizophrenia and 22 controls. All subjects underwent brain imaging using a 3T MRI scanner with a SENSE coil. They also underwent a single TMS fMRI session involving motor threshold (rMT) determination, structural imaging, and a parametric TMS fMRI protocol with 10 Hz triplet pulses at 0, 80, 100 and 120% rMT. Scanning involved a surface MR coil optimized for bilateral prefrontal cortex image acquisition.ResultsOf the original 41 enrolled subjects, 8 subjects with schizophrenia and 11 controls met full criteria for final data analyses. At equal TMS intensity, subjects with schizophrenia showed hyperexcitability in left BA9 (p = 0.0157; max z-score = 4.7) and neighboring BA46 (p = 0.019; max z-score = 4.47). Controls showed more contralateral functional connectivity between left BA9 and right BA9 through increased activation in right BA9 (p = 0.02; max z-score = 3.4). GM density in subjects with schizophrenia positively correlated with normalized prefrontal to motor cortex ratio of the corresponding distance from skull to cortex ratio (S-BA9/S-MC) (r = 0.83, p = 0.004).ConclusionsSubjects with schizophrenia showed hyperexcitability in left BA9 and impaired interhemispheric functional connectivity compared to controls. Interleaved TMS fMRI is a promising tool to investigate prefrontal dysfunction in schizophrenia.     

Influence of Waveform and Current Direction on Short-Interval Intracortical Facilitation: A Paired-Pulse TMS Study

BackgroundTranscranial magnetic stimulation (TMS) of the human primary motor hand area (M1-HAND) can produce multiple descending volleys in fast-conducting corticospinal neurons, especially so-called indirect waves (I-waves) resulting from trans-synaptic excitation. Facilitatory interaction between these I-waves can be studied non-invasively using a paired-pulse paradigm referred to as short-interval intracortical facilitation (SICF).Objective/hypothesisWe examined whether SICF depends on waveform and current direction of the TMS pulses.MethodsIn young healthy volunteers, we applied single- and paired-pulse TMS to M1-HAND. We probed SICF by pairs of monophasic or half-sine pulses at suprathreshold stimulation intensity and inter-stimulus intervals (ISIs) between 1.0 and 5.0 ms. For monophasic paired-pulse stimulation, both pulses had either a posterior–anterior (PA) or anterior–posterior (AP) current direction (AP–AP or PA–PA), whereas current direction was reversed between first and second pulse for half-sine paired-pulse stimulation (PA–AP and AP–PA).ResultsMonophasic AP–AP stimulation resulted in stronger early SICF at 1.4 ms relative to late SICF at 2.8 and 4.4 ms, whereas monophasic PA–PA stimulation produced SICF of comparable size at all three peaks. With half-sine stimulation the third SICF peak was reduced for PA–AP current orientation compared with AP–PA.ConclusionSICF elicited using monophasic as well as half-sine pulses is affected by current direction at clearly suprathreshold intensities. The impact of current orientation is stronger for monophasic compared with half-sine pulses. The direction-specific effect of paired-pulse TMS on the strength of early versus late SICF shows that different cortical circuits mediate early and late SICF.     

Are there differences in cortical excitability between akinetic-rigid and tremor-dominant subtypes of Parkinson's disease?

ObjectiveTo assess by transcranial magnetic stimulation (TMS) the excitability of various cortical circuits in akinetic-rigid and tremor-dominant subtypes of Parkinson's disease (PD).MethodsThe study included 92 patients with PD according to UK Brain Bank criteria, with akinetic-rigid (n = 64) or tremor-dominant (n = 28) subtype. Cortical excitability study, including resting and active motor thresholds (rMT and aMT), input—output curve of motor evoked potentials, contralateral and ipsilateral silent periods (cSP and iSP), short and long-interval intracortical inhibition (SICI and LICI), and intracortical facilitation (ICF) were measured. The results obtained were compared to a control group of 30 age- and sex-matched healthy subjects.ResultsThe patients in the tremor group had significantly lower rMT and aMT compared to controls and akinetic-rigid patients and significantly shorter iSP duration compared to akinetic-rigid patients, while iSP latency tended to be longer in akinetic-rigid patients compared to controls. There were no significant differences between the two PD subgroups regarding other cortical excitability parameters, including paired-pulse TMS parameters.ConclusionsOnly subtle differences of cortical excitability were found between patients with akinetic-rigid vs. tremor-dominant subtype of PD.SignificanceThe clinical heterogeneity of PD patients probably has an impact on cortical excitability measures, far beyond the akinetic-rigid versus tremor-dominant profile.     

The effect of modafinil on cortical excitability in patients with narcolepsy: A randomized,placebo-controlled,crossover study

ObjectiveTo investigate the effect of modafinil on cortical excitability in patients with narcolepsy using transcranial magnetic stimulation (TMS).MethodsNineteen drug-naïve narcolepsy patients with cataplexy (10 males, 9 females, and mean age 28.5 years) and 25 age- and sex-matched healthy controls were recruited. In this double-blind, randomized, crossover study, patients and controls received a single dose of 400 mg modafinil or placebo. Modafinil and placebo administrations were separated by a 2-week washout period. TMS parameters, such as resting motor thresholds (RMT), motor-evoked potential (MEP) amplitudes, cortical silent periods (CSP), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF), were measured before and 3 h after administering modafinil or placebo. The differences of TMS parameters were statistically tested between patients and controls and between before and after modafinil or placebo administration.ResultsNarcolepsy patients had significantly increased CSP durations compared to controls (independent t-test, P < 0.05), indicating decreased excitability of cortical networks in human narcolepsy. In patients after modafinil administration, MEP amplitudes, SICI, and ICF increased, and CSP duration shortened significantly, meaning enhanced motor excitability, whereas in controls modafinil did not change TMS parameters significantly. Placebo administration did not affect TMS parameters both in patients or controls.ConclusionsNarcolepsy patients with cataplexy showed decreased cortical excitability than normal healthy controls. Single dose modafinil significantly increased motor excitability in narcolepsy patients but had no effect in healthy controls.     

Do sphenoidal electrodes aid in surgical decision making in drug resistant temporal lobe epilepsy?

ObjectiveThe utility of sphenoidal electrodes (SPh) in analyzing interictal epileptiform discharges (IEDs) and ictal electrography remains controversial, despite its widespread use.MethodsOne hundred and twenty-two consecutive patients with presumed temporal lobe epilepsy (TLE) who underwent presurgical evaluation were prospectively studied. SPh and Silverman’s electrodes were placed, in addition to routine electrodes in 10–20 international system. IEDs and ictal electroencephalography (EEG) were analyzed separately in bipolar and referential montages. The proportion of patients selected for surgery after adjusting for SPh placement based on the earlier ictal onset and IEDs were analyzed.ResultsOf the 8701 IEDs in SPh, only 65% were seen over the scalp bipolar montage; 1392 (16%) IEDs were confined to SPh electrodes, and were not seen at scalp bipolar montage (p < 0.001). Spike amplitudes were highest at SPh (p < 0.001). Of the 592 seizures analyzed, 62 (61%) had simultaneous SPh and scalp onset, while in 26 (25%) SPh onset preceded the scalp.ConclusionsOut of the 35 patients with unilateral mesial temporal sclerosis (MTS) with additional neocortical changes and/or non-lateralized bitemporal IEDs and/or diffuse ictal onset (group 1), 27 were selected for surgery (77%). About 7% was selected for surgery in this group by SPh placement. Also, in patients with bilateral MTS (group 2), 25% (5/20) were chosen for anterior temporal lobectomy, SPh provided an additional benefit in 11% (p < 0.001). Patients with normal magnetic resonance imaging (group 3) and temporal plus epilepsy (group 4) had a lower surgical yield, only 12% and 9.5% could undergo surgery. They were denied surgical candidacy with SPh (p < 0.001).SignificanceOne-third of patients after SPh placement were selected for resective surgery obviating the need for invasive monitoring. The maximum yield was noted in unilateral MTS (associated with additional neocortical features or non-lateralized bilateral temporal interictal IEDs or diffuse ictal onset in scalp EEG) and in bilateral MTS. Those with normal MRI/temporal plus epilepsy could be excluded from direct resective surgery.     

Measurement of voluntary activation of the back muscles using transcranial magnetic stimulation

ObjectiveTwitch interpolation using transcranial magnetic stimulation (TMS) has recently been used to measure the level of drive from the motor cortex to contracting muscles of the upper and lower limbs, termed voluntary activation. It has yet to be used to assess voluntary activation in trunk muscles. The aim of this study was to assess the feasibility of using TMS to measure voluntary activation in back muscles.MethodsSixteen healthy subjects performed a series of brief maximal and submaximal isometric contractions of the back extensors during which TMS was delivered to the motor cortex. The evoked (superimposed) twitch was measured using dynamometry and simultaneous surface electromyographic (EMG) recordings were taken from the left and right erector spinae at vertebral level T12. Voluntary activation was derived using the expression: (1-superimposed twitch amplitude/resting twitch amplitude) × 100. The resting twitch amplitude was estimated by extrapolation of the linear correlation between voluntary torque and superimposed twitch amplitude to zero torque.ResultsThe relationship between superimposed twitch size and voluntary contraction strength for contraction strengths of 50–100% MVC was linear but regression revealed variability between subjects. When data were included from those subjects with a good linear regression fit a strong linear relationship was found for the group means between voluntary contraction strength and voluntary activation (r² = 1) and superimposed twitch size (r² = 0.99) for contraction strengths of 50–100% MVC. Voluntary activation was found to be less than maximal (67.71 ± 5.22%) during maximal efforts. Time-to-peak amplitude decreased linearly with increasing voluntary torque. The amplitudes of the motor evoked potentials (MEPs) increased with increasing voluntary torque.ConclusionsTwitch interpolation using TMS can be used to quantify voluntary activation in back extensors. The results of this study reveal that neural drive to the back extensors during strong contractions is submaximal.SignificanceThe assessment of voluntary activation of the back muscles may aid our understanding of the mechanisms of alteration in control of these muscles implicated in chronic low back pain.