Finally putting the horse before the cart?

Transcranial magnetic stimulation

A review of low-intensity focused ultrasound pulsation

To prospectively demonstrate anterior mesiotemporal lobe (MTL) activation in healthy volunteers by using a semirandom memory-encoding paradigm and to prospectively compare lateralized functional magnetic resonance (MR) imaging activation with intracarotid amobarbital procedure (IAP) memory test results in patients with temporal lobe epilepsy (TLE) who were scheduled to undergo surgery. The study was approved by a local ethics committee, and written informed consent was obtained from all subjects. Eight healthy volunteers and 18 patients with TLE who were scheduled for surgery were included in the functional MR imaging study involving the use of a memory-encoding paradigm with variable epoch lengths. Subjects were instructed to memorize new pictures that were mixed among pictures that they had seen before. Data analysis entailed computations of the contrast between the MTL activation induced by the new pictures and the MTL activation induced by the old pictures and of the lateralization index, defined as the relative difference in the number of activated voxels between the left and right MTLs. Lateralization indexes were compared between the patients and the volunteers and statistically correlated with the patients' IAP memory test results. To study deviations from perfect correspondence between the functional MR imaging- and IAP-derived lateralization indexes, orthogonal regression analysis was applied. Proportional relations for the patients with left-sided TLE and for those with right-sided TLE were calculated separately. The memory paradigm consistently activated the posterior and anterior MTL structures in both the healthy volunteers and the patients. Regression analysis revealed that functional MR imaging activation was stronger than the IAP results when it was lateralized to the contralateral MTL. This analysis also revealed a significant (P < .001) correlation between the functional MR imaging results and the IAP results in the patients with right-sided TLE but not in those with left-sided TLE (P > .1). The functional MR imaging memory-encoding paradigm consistently yielded MTL activation in the volunteers and the patients with TLE, but lateralized functional MR imaging activation was in concordance with the IAP results in only those patients with right-sided TLE.

Comparison of representational maps using functional magnetic resonance imaging and transcranial magnetic stimulation.

*Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin, U.S.A.; †University Hospital Gent, Gent, Belgium; ‡Departments of Diagnostic Radiology and Neurosurgery, Yale University, New Haven, Connecticut; §Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania; Clinical Epilepsy Section, National Institutes of Health, Bethesda, Maryland; ¶Department of Radiology, Mayo Clinic, Rochester, Minnesota; and **Department of Neurology, Medical College of Georgia, Augusta, Georgia, U.S.A.

Motor training consisting of voluntary movements leads to performance improvements and results in characteristic reorganizational changes in the motor cortex. It has been proposed that repetition of passively elicited movements could also lead to improvements in motor performance. In this study, we compared behavioural gains, changes in functional MRI (fMRI) activation in the contralateral primary motor cortex (cM1) and in motor cortex excitability measured with transcranial magnetic stimulation (TMS) after a 30 min training period of either voluntarily (active) or passively (passive) induced wrist movements, when alertness and kinematic aspects of training were controlled. During active training, subjects were instructed to perform voluntary wrist flexion-extension movements of a specified duration (target window 174-186 ms) in an articulated splint. Passive training consisted of wrist flexion- extension movements elicited by a torque motor, of the same amplitude and duration range as in the active task. fMRI activation and TMS parameters of motor cortex excitability were measured before and after each training type. Motor performance, measured as the number of movements that hit the target window duration, was significantly better after active than after passive training. Both active and passive movements performed during fMRI measurements activated cM1. Active training led to more prominent increases in (i) fMRI activation of cM1; (ii) recruitment curves (TMS); and (iii) intracortical facilitation (TMS) than passive training. Therefore, a short period of active motor training is more effective than passive motor training in eliciting performance improvements and cortical reorganization. This result is consistent with the concept of a pivotal role for voluntary drive in motor learning and neurorehabilitation.

Both functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) have been used to non-invasively localize the human motor functional area. These locations can be clinically used as stimulation target of TMS treatment. However, it has been reported that the finger tapping fMRI activation and TMS hotspot were not well-overlapped. The aim of the current study was to measure the distance between the finger tapping fMRI activation and the TMS hotspot, and more importantly, to compare the network difference by using resting-state fMRI. Thirty healthy participants underwent resting-state fMRI, task fMRI, and then TMS hotspot localization. We found significant difference of locations between finger tapping fMRI activation and TMS hotspot. Specifically, the finger tapping fMRI activation was more lateral than the TMS hotspot in the premotor area. The fMRI activation peak and TMS hotspot were taken as seeds for resting-state functional connectivity analyses. Compared with TMS hotspot, finger tapping fMRI activation peak showed more intensive functional connectivity with, e.g., the bilateral premotor, insula, putamen, and right globus pallidus. The findings more intensive networks of finger tapping activation than TMS hotspot suggest that TMS treatment targeting on the fMRI activation area might result in more remote effects and would be more helpful for TMS treatment on movement disorders.

The brain is capable of large-scale reorganization in blindness or after massive injury. Such reorganization crosses the division into separate sensory cortices (visual, somatosensory...). As its result, the visual cortex of the blind becomes active during tactile Braille reading. Although the possibility of such reorganization in the normal, adult brain has been raised, definitive evidence has been lacking. Here, we demonstrate such extensive reorganization in normal, sighted adults who learned Braille while their brain activity was investigated with fMRI and transcranial magnetic stimulation (TMS). Subjects showed enhanced activity for tactile reading in the visual cortex, including the visual word form area (VWFA) that was modulated by their Braille reading speed and strengthened resting-state connectivity between visual and somatosensory cortices. Moreover, TMS disruption of VWFA activity decreased their tactile reading accuracy. Our results indicate that large-scale reorganization is a viable mechanism recruited when learning complex skills.DOI: http://dx.doi.org/10.7554/eLife.10762.001

Functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) are noninvasive techniques recently used to investigate cortical motor physiology. However, these modalities measure different phenomena, and in studies of human motor control they have given inconsistent results. We have developed a reproducible technique which co-registers TMS and fMRI, using a frameless method. In four normal subjects, the TMS map and fMRI activation were present on the primary motor cortex contralateral to the target hand, with some extension into primary sensory cortex. fMRI activation alone was also present in the medial motor cortex bilaterally and in the sensorimotor cortex ipsilateral to the target hand. This technique allows a more comprehensive evaluation of the physiologic events involved in motor control.

Bidirectional and state-dependent modulation of brain activity by transcranial focused ultrasound in non-human primates

This article reviews the four ways by which large-scale, neurobiologically realistic modeling can be used in conjunction with functional neuroimaging data, especially that obtained by functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), to help investigators understand the neural bases for sensorimotor and cognitive functions. The conceptually distinct purposes served are:(1) formulating and implementing specific hypotheses about how neuronal populations mediate a task, which will be illustrated using models of visual and auditory object processing; (2) determining how well an experimental design paradigm or analysis method works, which will be illustrated by examining event-related fMRI; (3) investigating the meaning in neural terms of macro-level concepts, which will be illustrated using functional connectivity; and (4) combining different types of macroscopic data with one another, which will be illustrated using transcranial magnetic stimulation (TMS) and PET.

Movement of an affected hand after stroke is associated with increased activation of ipsilateral motor cortical areas, suggesting that these motor areas in the undamaged hemisphere may adaptively compensate for damaged or disconnected regions. However, this adaptive compensation has not yet been demonstrated directly. Here we used transcranial magnetic stimulation (TMS) to interfere transiently with processing in the ipsilateral primary motor or dorsal premotor cortex (PMd) during finger movements. TMS had a greater effect on patients than controls in a manner that depended on the site, hemisphere, and time of stimulation. In patients with right hemiparesis (but not in healthy controls), TMS applied to PMd early (100 ms) after the cue to move slowed simple reaction-time finger movements by 12% compared with controls. The relative slowing of movements with ipsilateral PMd stimulation in patients correlated with the degree of motor impairment, suggesting that functional recruitment of ipsilateral motor areas was greatest in the more impaired patients. We also used functional magnetic resonance imaging to monitor brain activity in these subjects as they performed the same movements. Slowing of reaction time after premotor cortex TMS in the patients correlated inversely with the relative hemispheric lateralization of functional magnetic resonance imaging activation in PMd. This inverse correlation suggests that the increased activation in ipsilateral cortical motor areas during movements of a paretic hand, shown in this and previous functional imaging studies, represents a functionally relevant, adaptive response to the associated brain injury.

Transcranial magnetic stimulation (TMS) is a newer noninvasive language mapping tool that is safe and well-tolerated by children. We examined the accuracy of TMS-derived language maps in a clinical cohort by comparing it against functional magnetic resonance imaging (MRI)-derived language map. The number of TMS-induced speech disruptions and the volume of activation during functional MRI tasks were localized to Brodmann areas for each modality in 40 patients with epilepsy or brain tumor. We examined the concordance between TMS- and functional MRI-derived language maps by deriving statistical performance metrics for TMS including sensitivity, specificity, accuracy, and diagnostic odds ratio. Brodmann areas 6, 44, and 9 in the frontal lobe and 22 and 40 in the temporal lobe were the most commonly identified language areas by both modalities. Overall accuracy of TMS compared to functional MRI in localizing language cortex was 71%, with a diagnostic odds ratio of 1.27 and higher sensitivity when identifying left hemisphere regions. TMS was more accurate in determining the dominant hemisphere for language with a diagnostic odds ratio of 6. This study is the first to examine the accuracy of the whole brain language map derived by TMS in the largest cohort examined to date. While this comparison against functional MRI confirmed that TMS reliably localizes cortical areas that are not essential for speech function, it demonstrated only slight concordance between TMS- and functional MRI-derived language areas. That the localization of specific language cortices by TMS demonstrated low accuracy reveals a potential need to use concordant tasks between the modalities and other avenues for further optimization of TMS parameters.

Uncertainty Potentiates Neural and Cardiac Responses to Visual Stimuli in Anxiety Disorders

The aim of this study was to evaluate the use of functional magnetic resonance imaging as an alternative to intraoperative electrocortical stimulation mapping for the localization of critical language areas in the temporoparietal region. We investigated several requirements that functional magnetic resonance imaging must fulfill for clinical implementation: high predictive power for the presence as well as the absence of critical language function in regions of the brain, user-independent statistical methodology, and high spatial accuracy. Thirteen patients with temporal lobe epilepsy performed four different functional magnetic resonance imaging language tasks (ie, verb generation, picture naming, verbal fluency, and sentence comprehension) before epilepsy surgery that included intraoperative electrocortical stimulation mapping. To assess the optimal statistical threshold for functional magnetic resonance imaging, images were analyzed with three different statistical thresholds. Functional magnetic resonance imaging information was read into a surgical guidance system for identification of cortical areas of interest. Intraoperative electrocortical stimulation mapping was recorded by video camera, and stimulation sites were digitized. Next, a computer algorithm indicated whether significant functional magnetic resonance imaging activation was present or absent within the immediate vicinity (<6.4mm) of intraoperative electrocortical stimulation mapping sites. In 2 patients, intraoperative electrocortical stimulation mapping failed during surgery. Intraoperative electrocortical stimulation mapping detected critical language areas in 8 of the remaining 11 patients. Correspondence between functional magnetic resonance imaging and intraoperative electrocortical stimulation mapping depended heavily on statistical threshold and varied between patients and tasks. In 7 of 8 patients, sensitivity of functional magnetic resonance imaging was 100% with a combination of 3 functional magnetic resonance imaging tasks (ie, functional magnetic resonance imaging correctly detected all critical language areas with high spatial accuracy). In 1 patient, sensitivity was 38%; in this patient, functional magnetic resonance imaging was included in a larger area found with intraoperative electrocortical stimulation mapping. Overall, specificity was 61%. Functional magnetic resonance imaging reliably predicted the absence of critical language areas within the region exposed during surgery, indicating that such areas can be safely resected without the need for intraoperative electrocortical stimulation mapping. The presence of functional magnetic resonance imaging activity at noncritical language sites limited the predictive value of functional magnetic resonance imaging for the presence of critical language areas to 51%. Although this precludes current replacement of intraoperative electrocortical stimulation mapping, functional magnetic resonance imaging can at present be used to speed up intraoperative electrocortical stimulation mapping procedures and to guide the extent of the craniotomy.