Diana J. Vincent

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.

Prefrontal repetitive transcranial magnetic stimulation (rTMS) changes relative perfusion locally and remotely

Although transcranial magnetic stimulation has been used as a stand‐alone brain mapping tool, relatively few studies have attempted to couple TMS with functional brain imaging to understand the neurobiological effects of TMS. Technical problems of placing a TMS coil in a PET or MRI scanner have hampered previous efforts at imaging the immediate effects of TMS. Perfusion SPECT offers the advantage of tracer injection away from the camera, with later image development. We wondered if perfusion SPECT could be used to visualize brain changes during rTMS over the left prefrontal cortex—a region where rTMS has been shown to cause changes in mood or working memory. Eight healthy adult subjects were scanned with brain SPECT scintigraphy using 30 mCi (1110 MBq) Neurolite® (DuPont Pharma) on a triple‐headed Picker camera. Each subject had three scans: (1) baseline, (2) bolus tracer injection during seconds 10–20 of a train of 2 min of left prefrontal rTMS (10 Hz; 60% motor threshold (MT); 10 s on/off, 600 stimuli) (2MIN), and (3) exactly as in the 2MIN, but immediately after subjects had received 18 min of high frequency stimulation (20 Hz; 80% MT; 2 s on/28 s off, 1440+600=2040 total stimuli) (20MIN). Scans were linearly transformed into Talairach space using SPM96b and compared across conditions (p<0·05 for display). Contrary to our prestudy hypothesis, there was no relative increase at the coil site during the 2 min or the 20 min scan compared to baseline. In fact, at the 20 min comparison perfusion was relatively decreased in the right prefrontal cortex, bilateral anterior cingulate, and anterior temporal cortex. Also, relative perfusion was significantly increased in the orbitofrontal cortex (L>R) and hypothalamus at 20 min and at 2 min, with thalamic increases occurring at the 20 min scan compared to baseline. There was an apparent TMS dose effect with twice as many decreases at 20 min than 2 min. Directly comparing the 20 min to the 2 min scans demonstrated opposite hemisphere decreases and relative increases in the ipsilateral (left) hemisphere as a function of more TMS stimuli. Full interpretation of these results is hampered by incomplete knowledge of the effect of the relative amount of stimulation to rest during tracer uptake, pharmacokinetics of tracer uptake, and depth and intensity of the magnetic field. Nevertheless, coupling rTMS with split‐dose perfusion SPECT appears to be a promising method for understanding the brain changes associated with rTMS, and for directly visualizing neural circuits. We have demonstrated that prefrontal rTMS at high frequencies has both local and remote effects. These imaging results may help explain the cognitive and behavioural effects demonstrated in other prefrontal rTMS studies involving mood and working memory. Copyright

Comparison of Functional Magnetic Resonance Imaging for Language Localization and Intracarotid Speech Amytal Testing in Presurgical Evaluation for Intractable Epilepsy

A comparison is made between the results of standard intracarotid speech amytal testing and a new methodology, echoplanar blood-oxygen-level-dependent functional magnetic resonance imaging (BOLD fMRI), in patients undergoing presurgical evaluation for intractable epilepsy. Of the 15 patients entered in the study, all had fMRIs while performing a verbal fluency task. Twelve of these patients also underwent standard intracarotid sodium amytal testing for speech and memory. Results of the fMRIs as compared to the intracarotid speech amytal testing are discussed, including agreement and disagreement between studies. Potential reasons for poor concordance are discussed, including complexity of the verbal fluency task, and motion and technical issues in MRI scan acquisition and data analysis.

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

SummaryMultiple 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.

The Range of Motor Activation in the Normal Human Cortex Using Bold fMRI

SummaryUnderstanding and documenting the nature of normal human brain functional motor activation using functional Magnetic Resonance Imaging (fMRI) is necessary, if valid statements are to be made about normal and disease functional states using fMRI activation maps. The present study examines activation maps in ’normal‘ adults. Six healthy adult volunteers performed three motor tasks isolating the tongue, non-dominant foot, and non-dominant thumb during a single magnetic resonance imaging (MRI)/(fMRI) scanning session. Group maps demonstrated discrete areas of activation that were task dependent. The degree of variability between the anatomical central location of global maximum intensity for each individual may mean extra care should be applied when using the global maximum to define the area of activation. These differences may represent anatomical variability among individuals, task complexity, paradigm design, data analysis techniques or a combination thereof, which form the basis of our ongoing research endeavors. Standard notions of strongly associated functions as related to anatomic foci may need to be revised.

BOLD fMRI response to direct stimulation (transcranial magnetic stimulation) of the motor cortex shows no decline with age.

Summary.Previous studies using BOLD fMRI to examine age-related changes in cortical activation used tasks that relied on peripheral systems to activate the brain. They were unable to distinguish between alterations due to age-related changes in the periphery and actual changes in cortical physiology. Transcranial magnetic stimulation (TMS), which allows direct, noninvasive stimulation of cortical neurons, was interleaved with BOLD fMRI to study 6 young and 5 old subjects. Three different tasks were compared: direct stimulation by TMS, indirect active stimulation produced by a motor task, and indirect passive stimulation produced by hearing the TMS coil discharge.Direct neuronal stimulation by TMS produced similar fMRI signal increases in both groups, suggesting that cortical physiology itself may not necessarily decline with age.

Image processing of head CT images using neuro best contrast (NBC) and lesion detection performance

Purpose: The purpose of this study was to objectively compare lesion detection performance of head CT images reconstructed using filtered back projection (FBP) algorithms with those reconstructed using NBC. Method: The observer study was conducted using the 2-AFC methodology. An AFC experiment consists of 128 observer choices and permits the computation of the intensity needed to achieve 92% correct (I92%). High values of I92% corresponds to a poor level of detection performance, and vice versa. Head CT images were acquired at an x-ray tube voltage of 120 kVp with a CTDIvol value of 75 mGy in a helical scan. Nine randomly selected normal images from three patients and at three anatomical head locations were reconstructed using filtered back projection (FBP) and neuro-best-contrast (NBC) processing. Circular lesions were generated by projecting spheres onto the image plane, followed by blurring function, with lesion sizes of 2.8 mm, 6.5 mm and 9.8 mm used in these experiments. Four readers were used, with 18 experiments performed by each observer (2 processing techniques × 3 lesion sizes × 3 repeats). The experimental order of the 18 experiments was randomized to eliminate learning curve and/or observer fatigue. The ratio R of the I92% value for NBC to the corresponding I92% value for FBP was calculated for each observer and each lesion size. Values of R greater than unity indicate that NBC is inferior to FBP, and vice versa. Results: Analysis of data from each observer showed that a total of four data points had R less than unity, and eight data points were greater than unity. Eleven of the twelve individual observer R values with one standard deviation of unity. When data for the four observers were pooled, the resultant average R values were 0.98 ± 0.38, 0.96 ± 0.33 and 1.15 ± 0.45, for the 2.8 mm, 6.5 mm and 9.8 mm lesions respectively. The overall average R for all three lesions sizes was 1.03 ± 0.67. Conclusion: Our AFC investigation has shown no evidence that use of Neuro Best Contrast to process head CT images improves detection of circular, low contrast lesions less than 10 mm.

SU‐E‐I‐118: Differential Analysis (DA) ‐ A New Approach for Evaluating the Clinical Utility of Image Processing Algorithms

Purpose: To describe a new method, called Differential Analysis (DA), of evaluating image processing algorithms in radiological imaging. Methods: Thirty head CTimages which showed abnormal findings were selected. Each abnormal image was paired with a normal head CTimage at the same anatomical location. All images were processed using standard filtered back projection (FBP) and a new algorithm called iterative reconstruction in image space (IRIS). Three experienced neuroradiologists evaluated the image pairs and assigned a score from 1 to 10, based on how easy / difficult it was to differentiate between normal and abnormal findings. A score of 1 would indicate a barely visible lesion, implying that the processing allows poor differentiation between abnormal and normal pathology, whereas a score of 10 indicated a readily visible lesion, implying excellent differentiation. All evaluations were performed independently and in a random order. The results permitted a differential score “delta” (i.e., IRIS score minus FBP score) to be obtained, with positive values showing IRIS to be superior to FBP, and vice versa. Results: Two observers had positive to negative delta ratios of 3 to 2, and one observer had a positive to negative delta ratio of 1. The ratio of positive to negative delta values for all observers was 2.5. Pooled delta scores showed 18 values less than −1, 38 values between −1 and +1, and 34 values greater than +1. Overall, twice as many images processed using IRIS showed improvements in the differential score as compared with filtered back projection. Conclusions: We describe here a new method to evaluate image processing algorithms in radiological imaging which we propose to call Differential Analysis. Application of this method to a new Iterative Reconstruction algorithm (IRIS) showed improved visibility of brain lesions on CT.

A functional neuroimaging study of speech recognition in noise

Few studies have examined brain activity in response to auditory stimuli using functional magnetic resonance imaging (fMRI) due to the inherent loudness of the scanner noise. Here, the scanner noise has been incorporated into the design of a speech recognition in noise task. Normal‐hearing subjects were scanned on a Picker EDGE 1.5‐T MR scanner; structural and functional images were acquired for 15 coronal slices. In one active task, sentences included contextual information so that the final words were highly predictable from the other words in the sentence (PH); in the other active task, sentences had no contextual information so that the same final words were not predictable (PL). Using nonmetallic noise‐reduction earphones, sentences were presented to subjects’ right ears for 1‐min blocks, alternating with 1‐min blocks with no speech stimuli. Using a multiple subtraction technique, activation during rest was subtracted from activation in response to both low‐context sentences (PL‐rest) and high‐contex...