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

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.

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 Kozel's 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.

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

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.

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.

Subcellular localization of the env-related glycoproteins in Friend erythroleukemia cells.

A scheme was developed for the subcellular fractionation of murine erythroleukemia cells transformed by Friend leukemia virus. The subcellular localization of the env-related glycoproteins was determined by immune precipitation with antiserum against gp70, the envelope glycoprotein of the helper virus, followed by gel electrophoresis. In cells labeled for 2 h with [35S]methionine, the glycoprotein encoded by the defective spleen focus-forming virus, gp55SFFV, was found primarily in the nuclear fraction and in fractions containing dense cytoplasmic membranes such as endoplasmic reticulum. A similar distribution was noted for gp85env, the precursor to gp70. The concentration of viral glycoproteins in the nuclear fraction could not be accounted for by contamination with endoplasmic reticulum. In pulse-chase experiments, neither glycoprotein underwent major redistribution. However, labeled gp85env disappeared from intracellular membranes with a half-time of 30 min to 1 h, whereas labeled gp55SFFV was stable during a 2-h chase. In plasma membrane preparations with very low levels of contamination with endoplasmic reticulum, gp70 was the major viral env-related glycoprotein detected; a minor amount of gp55SFFV and no gp85env could be detected. The unexpected result of these experiments is the amount of viral glycoproteins found in the nuclear fraction. Presence of viral proteins in the nucleus could be relevant to the mechanism of viral leukemogenesis.