Sequential Finger Opposition Research Articles

323. Can interleaved TMS and fMRI demonstrate changes in an activated circuit?

TMS, combined with fMRI, offers the potential for demonstrating functional brain circuits, as well as the changes induced by direct non-invasive stimulation (TMS). Recent human electrophysiological and imaging studies have found that 1 Hz TMS has local and remote inhibitory effects in different time domains. To test whether this inhibition occurs at time domains of several seconds and is visible with interleaved TMS/fMRI, we performed TMS within an fMRI scanner and measured blood flow. Within a 1.5 T MRI scanner, five adults were stimulated with a figure eight TMS coil over the left motor cortex. Subjects alternated between rest and a sequential finger opposition task in their left hand. On alternating movement trials, TMS was applied either at 120% motor threshold or 10% of stimulator output (below threshold for movement). Over seconds, TMS did not inhibit local or remote BOLD response during the movement. In fact, TMS over the left hemisphere caused a local 1.5% increase in blood flow in addition to the 2.5% activation caused by the complex movement. Of note, thin deactivation clusters underlying areas of activation were associated with BOLD response to motor activity and the acoustical effects of TMS. Such clusters were revealed in the motor cortex contralateral to the coil, SMA, temporal cortex.

Antipsychotic drug effects on motor activation measured by functional magnetic resonance imaging in schizophrenic patients

Brain function and laterality in schizophrenia were investigated by means of a simple motor task with a self-generated left-hand sequential finger opposition (SFO) using a whole-brain high-speed (100 ms per slice) functional imaging technique. Neuroleptic-naı̈ve, acutely ill schizophrenic patients were compared to schizophrenic patients under stable neuroleptic medication and matched controls. The goal was to evaluate both the motor function in first-episode patients and possible effects of different neuroleptic treatments on functional MRI results. Forty patients satisfying ICD 10 criteria (F20.x) for schizophrenia and sex- and age-matched healthy volunteers participated in this study. All subjects underwent fMRI examinations on a conventional 1.5 T MR unit. The primary sensorimotor cortex and the high-order supplementary motor area (SMA) were evaluated. There was a close similarity in the activation of the primary and high-order (SMA) sensorimotor areas between first-episode schizophrenic patients and controls. In contrast, a significant reduction in the overall blood oxygen level dependent (BOLD) response was seen in sensorimotor cortices (contra- and ipsilateral) in schizophrenic patients under stable medication with typical neuroleptics. This effect was not present in patients treated with atypical antipsychotics. Both antipsychotic treatments, however, led to a significant reduction in activation of the SMA region compared to controls and neuroleptic-naı̈ve subjects. Thus, the present study provides no evidence for the localized involvement of the primary motor cortex or the SMA as a relatively stable vulnerability marker in schizophrenia. There is, however, strong evidence that neuroleptics themselves influence fMRI activation patterns and that there are major differences between typical neuroleptics and atypical antipsychotics.

Bilateral representation of sequential finger movements in human cortical areas

The spatial distribution of cortical neural clusters activated during movement of either hand (‘bilateral’ population), or only of one hand, was investigated in healthy right-handed volunteers performing a sequential finger opposition task, using echo-planar functional magnetic resonance imaging. ‘Bilateral’ clusters were found in the mesial premotor, perirolandic and adjacent lateral premotor cortex of the two hemispheres, and in the left superior parietal lobule. In the precentral gyrus, their spatial extent was larger on the left hemisphere. Clusters activated exclusively during contralateral finger movements were equally distributed in the left and right perirolandic cortex. No cluster activated exclusively during ipsilateral finger movements was detected. These findings support a role of the motor/lateral premotor cortex of the dominant hemisphere in bilateral motor control.

A Direct Comparison between Whole-Brain PET and BOLD fMRI Measurements of Single-Subject Activation Response

We present the results of a direct comparison of single-subject activation using identical tasks for both functional PET and fMRI whole-brain studies. We examined the most commonly employed methods for each modality. For fMRI this is the blood oxygenation level-dependent (BOLD) contrast method with echo-planar imaging. In PET single-subject activation studies are based on the development of high sensitivity 3D imaging of regional cerebral blood flow from multiple [15O]water injections. The identical activation paradigm of a visually cued sequential finger opposition was used for PET and fMRI. For both modalities the entire brain volume difference images were smoothed to the same final resolution and the peaktvalue within the primary sensory/motor (PSM) area was then identified. All contiguous voxels in the PSM above a predetermined threshold of statistical significance were determined. Finally, the difference-weighted centroid location was calculated for the PSM region for each modality. These studies showed a very similar pattern of activation, with the volume of activation greater in fMRI and higher levels of statistical significance. The centroids of activation, however, differed by 9 ± 3 mm between the modalities, with the fMRI centroid location dorsal to that for PET. These results were stable across all processing options including differing levels of image smoothing and thresholds of statistical significance. These results are consistent with the hypothesis that draining veins contribute a substantial signal for fMRI activation studies and indicate caution for the interpretation of BOLD fMRI images with activation sites near draining veins.

Functional MRI of human primary somatosensory and motor cortex during median nerve stimulation

Objectives: Somatosensory evoked potential (SEP) studies suggested that some early cortical SEP components may be generated in the primary motor cortex (M1) rather than the primary somatosensory cortex (S1). Methods: We now used functional magnetic resonance imaging (fMRI) to study activation of S1 and M1 by electrical median nerve stimulation in healthy volunteers. Results: The hand areas of both S1 and M1 showed significant activation (correlation coefficients >0.45) in 7 of 9 subjects (activated volume S1>M1). For comparison, a sequential finger opposition task significantly activated S1 in 7 and M1 in all 9 subjects (activated volume M1>S1). Conclusions: These data show that the electrical stimuli used for SEP recording lead to a functional activation of S1 as well as M1.

Non-invasive functional mapping of the human motor cortex using near-infrared spectroscopy.

We applied non-invasive multisite near-infrared spectroscopy (NIRS) to assess oxygenation changes during performance of a sequential finger opposition task in five healthy human adults. Oxygenation response was localized anatomically using three-dimensional high-resolution magnetic resonance imaging (3D MRI). NIRS measurements showed a localized increase in [oxy-Hb] and a decrease in [deoxy-Hb] in all subjects. The largest response was obtained when the measurement position was over the primary motor and sensory cortex hand area. Interestingly, changes in [deoxy-Hb] seemed to be more localized than changes in [oxy-Hb]. We conclude that this simple, non-invasive and flexible optical bedside method may be used for functional brain mapping.

Regional cerebral blood flow during a self-paced sequential finger opposition task in patients with cerebellar degeneration.

The brain regions controlling self-paced sequential finger movements in patients with cerebellar degeneration were studied by measuring changes in regional cerebral blood flow (rCBF) in eight patients using bolus injections of H2(15)O and PET. The results were compared with those obtained in eight normal age-matched control subjects. Patients and control subjects performed a self-paced sequential finger opposition task with the right hand, completing a sequence of movements every 4-6 s. Both groups had strong increases in the adjusted rCBF contralaterally in the primary motor cortex (M1) and ventral premotor area (PMv), in the caudal supplementary motor area (SMA) and cingulate motor area (CMA), and bilaterally in the prefrontal cortex (PFC), the lobus parietalis inferior (LPI), putamen and cerebellum. The cerebellum, PMv, rostral CMA, PFC and LPI were more active in the control subjects than in the patients, and the M1, SMA, caudal CMA and putamen were more active in the patients than in the control subjects. The reduced activity of the cerebellar neurons in the patients produced a complex pattern of rCBF increases and decreases in other brain regions. Our results suggest that for the preparation and execution of sequential finger movements, patients with cerebellar degeneration use a medial premotor system, including the SMA and caudal CMA, as well as the M1 and putamen, rather than the PMv, PFC, LPI and rostral CMA.