Ananda Shastri

A combined TMS/fMRI study of intensity-dependent TMS over motor cortex.

BACKGROUND Transcranial magnetic stimulation (TMS) allows noninvasive stimulation of neurons using time-varying magnetic fields. Researchers have begun combining TMS with functional imaging to simultaneously stimulate and image brain activity. Recently, the feasibility of interleaving TMS with functional magnetic resonance imaging (fMRI) was demonstrated. This study tests this new method to determine if TMS at different intensities shows different local and remote activation. METHODS Within a 1.5 Tesla (T) MRI scanner, seven adults were stimulated with a figure-eight TMS coil over the left motor cortex for thumb, while continuously acquiring blood oxygen level dependent (BOLD) echoplanar images. TMS was applied at 1 Hz in 18-second long trains delivered alternately at 110% and 80% of motor threshold separated by rest periods. RESULTS Though the TMS coil caused some artifacts and reduced the signal to noise ratio (SNR), higher intensity TMS caused greater activation than lower, both locally and remotely. The magnitude (approximately 3% increase) and temporal onset (2 to 5 sec) of TMS induced blood flow changes appear similar to those induced using other motor and cognitive tasks. CONCLUSIONS Though work remains in refining this potentially powerful method, combined TMS/fMRI is both technically feasible and produces measurable dose-dependent changes in brain activity.

Unilateral left prefrontal transcranial magnetic stimulation (TMS) produces intensity-dependent bilateral effects as measured by interleaved BOLD fMRI

Transcranial magnetic stimulation (TMS) administered over the prefrontal cortex has been shown to subtly influence neuropsychological tasks, and has antidepressant effects when applied daily for several weeks. Prefrontal TMS does not, however, produce an immediate easily observable effect, making it hard to determine if one has stimulated the cortex. Most prefrontal TMS studies have stimulated using intensity relative to the more easily determined motor threshold (MT) over motor cortex. Five healthy adults were studied in a 1.5 T MRI scanner during short trains of 1 Hz TMS delivered with a figure eight MR compatible TMS coil followed by rest epochs. In a randomized manner, left prefrontal TMS was delivered at 80%, 100% and 120% of MT interleaved with BOLD fMRI acquisition. Compared to rest, all TMS epochs activated auditory cortex, with 80% MT having no other areas of significant activation. 100% MT showed contralateral activation and 120% MT showed bilateral prefrontal activation. Higher intensity TMS, compared to lower, in general produced more activity both under the coil and contralaterally. Higher prefrontal TMS stimulation intensity produces greater local and contralateral activation. Importantly, unilateral prefrontal TMS produces bilateral effects, and TMS at 80% MT produces only minimal prefrontal cortex activation.

The transcranial magnetic stimulation motor threshold depends on the distance from coil to underlying cortex: a replication in healthy adults comparing two methods of assessing the distance to cortex

Using transcranial magnetic stimulation (TMS), a handheld electrified copper coil against the scalp produces a powerful and rapidly oscillating magnetic field, which in turn induces electrical currents in the brain. The amount of electrical energy needed for TMS to induce motor movement (called the motor threshold [MT]), varies widely across individuals. The intensity of TMS is dosed relative to the MT. Kozel et al observed in a depressed cohort that MT increases as a function of distance from coil to cortex. This article examines this relationship in a healthy cohort and compares the two methods of assessing distance to cortex. Seventeen healthy adults had their TMS MT determined and marked with a fiducial. Magnetic resonance images showed the fiducials marking motor cortex, allowing researchers to measure distance from scalp to motor and prefontal cortex using two methods: 1) measuring a line from scalp to the nearest cortex and 2) sampling the distance from scalp to cortex of two 18-mm-square areas. Confirming Kozels previous finding, we observe that motor threshold increases as distance to motor cortex increased for both methods of measuring distance and that no significant correlation exists between MT and prefontal cortex distance. Distance from TMS coil to motor cortex is an important determinant of MT in healthy and depressed adults. Distance to prefontal cortex is not correlated with MT, raising questions about the common practice of dosing prefontal stimulation using MT determined over motor cortex.

Feasibility of Vagus Nerve Stimulation-Synchronized Blood Oxygenation Level-Dependent Functional MRI

Bohning DE, Lomarev MP, Denslow S, et al. Feasibility of vagus nerve stimulation–synchronized blood oxygenation level– dependent functional MRI. Invest Radiol 2001;36:470–479. rationale and objectives. Left cervical vagus nerve stimulation (VNS) by use of an implanted neurocybernetic prosthesis (NCP) system is effective in treating epilepsy, with open data suggesting effectiveness in depression, yet the mechanisms of action are unknown. Our objective was to develop a methodology for performing VNS-synchronized functional magnetic resonance imaging (VNS-fMRI) and then to demonstrate its feasibility for studying VNS effects. methods.In nine patients implanted for treatment of intractable depression, a Macintosh computer was used to detect the signal from the implanted VNS stimulator and then to synchronize fMRI image acquisition with its regular firing. results.With our VNS-fMRI methodology, the blood oxygenation level–dependent response to VNS was shown in brain regions regulated by the vagus nerve: orbitofrontal and parieto-occipital cortex bilaterally, left temporal cortex, the hypothalamus, and the left amygdala. conclusions.Vagus nerve stimulation pulses from an NCP system can be detected externally to determine its firing pattern, thus allowing VNS-fMRI studies of VNS-induced brain activity.

BOLD-f MRI response to single-pulse transcranial magnetic stimulation (TMS).

Five healthy volunteers were studied using interleaved transcranial magnetic stimulation/functional magnetic resonance imaging (TMS/fMRI) and an averaged single trial (AST) protocol. Blood oxygenation level‐dependent (BOLD)‐fMRI response to single TMS pulses over the motor cortex was detectable in both the ipsilateral motor cortex under the TMS coil and the contralateral motor cortex, as well as bilaterally in the auditory cortex. The associated BOLD signal increase showed the typical fMRI hemodynamic response time course. The brains response to a single TMS pulse over the motor cortex at 120% of the level required to induce thumb movement (1.0%–1.5% signal increase) was comparable in both level and duration to the auditory cortex response to the sound accompanying the TMS pulse (1.5% –2.0% signal increase). J. Magn. Reson. Imaging 2000;11:569–574.

Motor cortex brain activity induced by 1-Hz transcranial magnetic stimulation is similar in location and level to that for volitional movement.

Bohning DE, Shastri A, McGavin L, et al. Motor cortex brain activity induced by 1-Hz transcranial magnetic stimulation is similar in location and level to that for volitional movement. Invest Radiol 2000;35:676–683. RATIONALE AND OBJECTIVES.The relatively high temporal and spatial resolution of functional MR imaging was used to compare the blood oxygenation level dependent (BOLD) response associated with movement induced by transcranial magnetic stimulation (TMS) with that for a similar movement executed volitionally (VOL). METHODS.Seven healthy adults were studied in a 1.5-T MR scanner. One hertz TMS at 110% of motor threshold was applied over the motor cortex for the thumb in 21-pulse trains in alternation with VOL every 63 seconds and interleaved with functional MR imaging. RESULTS.BOLD increases in motor cortex associated with TMS and VOL movement were similar (2%–3%). Mean separation of their centers of activity was 3.7 ± 1.9 mm (mean displacement: left/right = 0.3 ± 4.1 mm; superior/inferior = 0.7 ± 1.9 mm). There was no indication of supraphysiological brain activity. CONCLUSIONS.Motor cortex BOLD response associated with thumb movement induced by 1-Hz TMS at 110% motor threshold is similar in both location and level to that caused by a similar movement executed volitionally.

BOLD-fMRI response vs. transcranial magnetic stimulation (TMS) pulse-train length: testing for linearity.

To measure motor and auditory cortex blood oxygenation level‐dependent (BOLD) functional magnetic resonance imaging (fMRI) response to impulse‐like transcranial magnetic stimulation (TMS) pulses as a function of train length.

Prefrontal cortex transcranial magnetic stimulation does not change local diffusion: a magnetic resonance imaging study in patients with depression.

ObjectiveTo determine whether transcranial magnetic stimulation over the left dorsolateral prefrontal cortex produces pathologic changes or leakage of the blood-brain barrier in patients with depression by using apparent diffusion coefficient magnetic resonance imaging. BackgroundTranscranial magnetic stimulation is a new technology for noninvasively stimulating the brain. It appears to be a relatively safe technique, with some important exceptions. Its neurobiologic mechanisms of action are poorly understood. One theory to explain its apparent antidepressant effects involves a potential change in local blood-brain barrier settings, allowing passage of peripheral substances directly into brain parenchyma. Knowing whether transcranial magnetic stimulation changes local brain diffusion is important as well from a safety perspective. To test whether transcranial magnetic stimulation changes local brain diffusion, we used apparent diffusion coefficient magnetic resonance imaging in depressed patients undergoing interleaved transcranial magnetic stimulation/functional magnetic resonance imaging over the left prefrontal cortex. MethodsWithin a 1.5 Tesla magnetic resonance imaging scanner, 14 depressed patients were stimulated with a figure-eight transcranial magnetic stimulation coil over the left prefrontal cortex. Apparent diffusion coefficient magnetic resonance imaging was acquired before, and immediately after, 1 Hertz transcranial magnetic stimulation (147 stimuli) intermittently delivered at a motor threshold of more than 7.35 minutes. Phase maps of the transcranial magnetic stimulation magnetic fields were used to guide region-of-interest placement. ResultsNo significant qualitative apparent diffusion coefficient differences were observed before and after 1 Hertz transcranial magnetic stimulation underneath the coil. ConclusionsOne Hertz transcranial magnetic stimulation over the left dorsolateral prefrontal cortex as applied in this study did not result in pathologic changes or leakage of the blood-brain barrier in patients with depression. If prefrontal transcranial magnetic stimulation at these usage parameters changes local diffusion, it is not an obvious or large effect.

A low-cost system for monitoring skin conductance during functional MRI

We built a low‐cost system for monitoring human skin conductance responses (SCRs) in a clinical magnetic resonance (MR) scanner during functional imaging. The average scanner‐induced conductance noise level was suppressed sufficiently to allow SCR measurements over the full range of SCR amplitudes, and functional image signal‐to‐noise ratio was unaffected by the skin conductance apparatus. The system may be useful for a variety of imaging studies. J. Magn. Reson. Imaging 2001;14:187–193.

The train length dependence of BOLD-fMRI response to 1 Hz transcranial magnetic stimulation (TMS) compares favorably with a finite recovery hemodynamic model for short train lengths

Introduction: It is possible to combine transcranial magnetic stimulation (TMS) with PET(l-3) or f?vlRI(4-S) to visualize regional brain activit) in response to direct non-invasive stimulation. In a PET study in which TMS was applied in high-frequency (10 H/.) 5-pulse trams (l), a negative correlation was observed between blood flow increase and the number of 5-pulse trains. The objective of this work was to use the high temporal and spatial resolution of fMR1 to measure the level and duration of the BOLD-fMRI response versus 1Hz TMS pulse train length, and, further, to compare it to the previous PET work and a finite recovery hemodynamic model.