Biomedical subjects

Stewart Denslow

Publications and source records attributed to Stewart Denslow.

9 recordsLinked to original sources

PubMed2005

Cortical and subcortical brain effects of transcranial magnetic stimulation (TMS)-induced movement: an interleaved TMS/functional magnetic resonance imaging study.

BACKGROUND: To date, interleaved transcranial magnetic stimulation and functional magnetic resonance imaging (TMS/fMRI) studies of motor activation have not recorded whole brain patterns. We hypothesized that TMS would activate known motor circuitry with some additional regions plus some areas dropping out. METHODS: We used interleaved TMS/fMRI (11 subjects, three scans each) to elucidate whole brain activation patterns from 1-Hz TMS over left primary motor cortex. RESULTS: Both TMS (110% motor threshold) and volitional movement of the same muscles excited by TMS caused blood oxygen level-dependent (BOLD) patterns encompassing known motor circuitry. Additional activation was observed bilaterally in superior temporal auditory areas. Decreases in BOLD signal with unexpected post-task "rebounds" were observed for both tasks in the right motor area, right superior parietal lobe, and in occipital regions. Paired t test of parametric contrast maps failed to detect significant differences between TMS- and volition-induced effects. Differences were detectable, however, in primary data time-intensity profiles. CONCLUSIONS: Using this interleaved TMS/fMRI technique, TMS over primary motor cortex produces a whole brain pattern of BOLD activation similar to known motor circuitry, without detectable differences from mimicked volitional movement. Some differences may exist between time courses of BOLD intensity during TMS circuit activation and volitional circuit activation.

Adult↗

PubMed2005

An increased precision comparison of TMS-induced motor cortex BOLD fMRI response for image-guided versus function-guided coil placement.

OBJECTIVE: To examine with high precision the differences between function-guided and image-guided transcranial magnetic stimulation (TMS). METHOD: Using a calibrated TMS coil holder/positioner, interleaved TMS/functional magnetic resonance imaging (fMRI), and individualized anatomy-based regional normalization, we conducted a two-phase study of TMS coil positioning guided by either function (elicited thumb motion) or image-based targeting of the "hand knob," the anatomy associated with fMRI activation during thumb motion. RESULTS: In every case, image-guided TMS coil placement produced a thumb movement response at thresholds similar to those found under function guidance. Unexpectedly, function-guided coil locations clustered bimodally over central and precentral sulci. Image-guided locations clustered as anticipated toward the targeted gyral crown. Despite these differences, blood oxygenation level-dependent (BOLD) activation locations and magnitude for the two methods displayed no consistent differences in mean or variance between or within subjects. Image guidance produced more consistent coil placement from subject to subject relative to targeted anatomy. Surprisingly, BOLD time courses from image-guided experiments showed significantly slower return to baseline after TMS than was observed under function guidance. CONCLUSIONS: The results demonstrate the effectiveness and precision of image-guided positioning of TMS coils combined with a precisely adjustable holder/positioner and regional normalization. Image guidance provides an accurate TMS placement relative to individual anatomy when no external sign is available.

Adult↗

PubMed2004

Acute vagus nerve stimulation using different pulse widths produces varying brain effects.

BACKGROUND: Vagus nerve stimulation (VNS) is an approved treatment for epilepsy and has been investigated in clinical trials of depression. Little is known about the relationship of VNS parameters to brain function. Using the interleaved VNS /functional magnetic resonance imaging (fMRI) technique, we tested whether variations of VNS pulse width (PW) would produce different immediate brain activation in a manner consistent with single neuron PW studies. METHODS: Twelve adult patients with major depression, treated with VNS, underwent three consecutive VNS/fMRI scans, each randomly using one of three PWs (130 micros, 250 micros, or 500 micros). The data were analyzed with SPM2. RESULTS: Global activations induced by PWs 250 and 500 were both significantly greater than that induced by PW 130 but not significantly different from each other. For global deactivation, PWs 130 and 250 were both significantly greater than PW 500 but not significantly different from each other. Regional similarities and differences were also seen with the various PWs. CONCLUSIONS: The data confirm our hypothesis that VNS at PW 500 globally produces no more activation than does PW 250, and PW 130 is insufficient for activation of some regions. These data suggest that PW is an important variable in producing VNS brain effects.

Adult↗

PubMed2004

A high resolution assessment of the repeatability of relative location and intensity of transcranial magnetic stimulation-induced and volitionally induced blood oxygen level-dependent response in the motor cortex.

OBJECTIVE: Using functional magnetic resonance imaging, we assessed variation in location and intensity of blood oxygen level-dependent contrast associated with movements induced by transcranial magnetic stimulation or volition. BACKGROUND: Anatomic location and within-subject repeatability of blood oxygen level-dependent responses induced by transcranial magnetic stimulation comprise critical information to the use of interleaved transcranial magnetic stimulation/functional magnetic resonance imaging as a neuroscience tool. METHODS: Eleven healthy adults were scanned 3 times each at 1.5 T. Interleaved with functional magnetic resonance imaging, 1-Hz transcranial magnetic stimulation was applied over motor cortex. VOL was alternated with transcranial magnetic stimulation over the scans. RESULTS: Intra-subject standard deviations in blood oxygen level-dependent locations ranged between 3 and 6 millimeters, allowing localization to subregions of the motor strip. Coil placement relative to blood oxygen level-dependent location varied more than blood oxygen level-dependent location (sdx = 9.5mm, sdy = 8.7 mm, sdz = 9.0mm) with consistent anterior displacement (dy = 21.8 mm, P = <0.025). Analysis of variance did not detect significant differences between transcranial magnetic stimulation and VOL blood oxygen level-dependent locations or intensities, in contrast to significant intensity differences detected in auditory blood oxygen level dependence. CONCLUSION: The high repeatability of location of transcranial magnetic stimulation-induced blood oxygen level-dependent activation suggests that transcranial magnetic stimulation/functional magnetic resonance imaging stimulation can be used as a precise tool in investigation of cortical mechanisms. The similarity between VOL and transcranial magnetic stimulation suggests that transcranial magnetic stimulation may act through natural brain movement circuits.

Adult↗

PubMed2003

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

OBJECTIVE: To 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. BACKGROUND: Transcranial 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. METHODS: Within 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. RESULTS: No significant qualitative apparent diffusion coefficient differences were observed before and after 1 Hertz transcranial magnetic stimulation underneath the coil. CONCLUSIONS: One 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.

Adolescent↗

PubMed2002

Cellular changes in experimental left heart hypoplasia.

Hypoplastic left heart syndrome (HLHS) is a rare but deadly congenital malformation, which can be created experimentally in the chick embryo by left atrial ligation (LAL). The goal of this study was to examine the cellular changes leading to the profound remodeling of ventricular myocardial architecture that occurs in this model. Hypoplasia of left heart structures was produced after 3H-thymidine prelabeling by partial LAL at stage 24, thereby reducing its volume, and redistributing blood preferentially to the developing right ventricle (RV). Controls included both sham-operated and intact stage-matched embryos. Survivors were studied 4 days after the ligation, when the heart organogenesis was essentially complete. Paraffin sections of the hearts were subjected to autoradiography and immunohistochemistry to detect changes in history of cell proliferation and expression of myosin, and growth factors implicated in cardiomyocyte proliferation. Sampling for apoptosis detection using TUNEL assay was done at stages 29 and 34. LAL resulted in decreased levels of proliferation in the left ventricular compact layer and trabeculae. The right ventricular compact layer also showed a slight decrease, but the trabeculae showed no differences. Anti-myosin staining was significantly reduced in all compartments. The expression levels of growth factors were altered as well. Apoptosis was increased in the right atrioventricular mesenchyme, with no changes in the working myocardium. These data suggest that changes in cardiomyocyte proliferation play a significant role in the pathogenesis of HLHS.

Animals↗

PubMed2002

Mechanisms and state of the art of transcranial magnetic stimulation.

In 1985, Barker et al. built a transcranial magnetic stimulation (TMS) device with enough power to stimulate dorsal roots in the spine. They quickly realized that this machine could likely also noninvasively stimulate the superficial cortex in humans. They waited a while before using their device over a human head, fearing that the TMS pulse might magnetically "erase the hard-drive" of the human brain. Almost 10 years later, in 1994, an editorial in this journal concerned whether TMS might evolve into a potential antidepressant treatment. In the intervening years, there has been an explosion of basic and clinical research with and about TMS. Studies are now uncovering the mechanisms by which TMS affects the brain. It does not "erase the hard-drive" of the brain, and it has many demonstrated research and clinical uses. This article reviews the major recent advances with this interesting noninvasive technique for stimulating the brain, critically reviewing the data on whether TMS has anticonvulsant effects or modulates cortical-limbic loops.

Animals↗

PubMedDate not supplied

Vagus nerve stimulation (VNS) synchronized BOLD fMRI suggests that VNS in depressed adults has frequency/dose dependent effects.

Stimulation of the vagus nerve in the neck can reduce seizures in epilepsy patients, and may be helpful in treating depression. PET studies have shown that vagus nerve stimulation (VNS) in epilepsy patients causes acute dose (intensity) dependent changes in regional cerebral blood flow. We sought to use the newly developed VNS synchronized fMRI technique to examine whether VNS BOLD signal changes depend on the frequency of stimulation. Six adults with recurrent depression were scanned inside a 1.5 T MR scanner. Data were acquired at rest, with the VNS device on for 7 s, and also, for comparison, while the patient listened to a tone for 7 s. In two separate back-to-back sessions, the VNS stimulation frequency was set to either 5 or 20 Hz. Data were transformed into Talairach space and then compared by condition. Compared to 5 Hz, 20 Hz VNS produced more acute activity changes from rest in regions similar to our initial VNS synchronized fMRI feasibility study in depression. Brain regions activated by hearing a tone were also greater when VNS was intermittently being applied at 20 Hz than at 5 Hz. In depressed adults, left cervical VNS causes regional brain activity changes that depend on the frequency of stimulation or total dose, or both. In addition to the acute immediate effects of VNS on regional brain activity, this study suggests further that VNS at different frequencies likely has frequency or dose dependent modulatory effects on other brain activities (e.g. hearing a tone).

Adult↗

PubMedDate not supplied

A review of functional neuroimaging studies of vagus nerve stimulation (VNS).

Vagus nerve stimulation (VNS) is a new method for preventing and treating seizures, and shows promise as a potential new antidepressant. The mechanisms of action of VNS are still unknown, although the afferent direct and secondary connections of the vagus nerve are well established and are the most likely route of VNS brain effects. Over the past several years, many groups have used functional brain imaging to better understand VNS effects on the brain. Since these studies differ somewhat in their methodologies, findings and conclusions, at first glance, this literature may appear inconsistent. Although disagreement exists regarding the specific locations and the direction of brain activation, the differences across studies are largely due to different methods, and the results are not entirely inconsistent. We provide an overview of these functional imaging studies of VNS. PET (positron emission tomography) and SPECT (single photon emission computed tomography) studies have implicated several brain areas affected by VNS, without being able to define the key structures consistently and immediately activated by VNS. BOLD (blood oxygen level dependent) fMRI (functional magnetic resonance imaging), with its relatively high spatio-temporal resolution, performed during VNS, can reveal the location and level of the brain's immediate response to VNS. As a whole, these studies demonstrate that VNS causes immediate and longer-term changes in brain regions with vagus innervations and which have been implicated in neuropsychiatric disorders. These include the thalamus, cerebellum, orbitofrontal cortex, limbic system, hypothalamus, and medulla. Functional neuroimaging studies have the potential to provide greater insight into the brain circuitry behind the activity of VNS.

Brain↗