Anthony T. Barker

Transcranial Magnetic Stimulation

Abstract. To investigate the mechanism of transcranial magnetic stimulation (TMS), we compared the directional effects of two stimulators (Magstim 200 and Magstim Super Rapid). First, stimulating visual cortex and facial nerve with occipital mid-line TMS, we found that, for a particular coil orientation, these two stimulators affected a particular neural structure in opposite hemispheres and that, to affect a particular neural structure in a particular hemisphere, these two stimulators required opposite coil orientations. Second, stimulating a membrane-simulating circuit, we found that, for a particular coil orientation, these two stimulators resulted in a peak induced current of the same polarity but in a peak induced charge accumulation of opposite polarity. We suggest that the critical parameter in TMS is the amplitude of the induced charge accumulation rather than the amplitude of the induced current. Accordingly, TMS would be elicited just before the end of the first (Magstim 200) and second (Magstim Super Rapid) phase of the induced current rather than just after the start of the first phase of the induced current.

Where does transcranial magnetic stimulation (TMS) stimulate? Modelling of induced field maps for some common cortical and cerebellar targets

Computational models have been be used to estimate the electric and magnetic fields induced by transcranial magnetic stimulation (TMS) and can provide valuable insights into the location and spatial distribution of TMS stimulation. However, there has been little translation of these findings into practical TMS research. This study uses the International 10-20 EEG electrode placement system to position a standard figure-of-eight TMS coil over 13 commonly adopted targets. Using a finite element method and an anatomically detailed and realistic head model, this study provides the first pictorial and numerical atlas of TMS-induced electric fields for a range of coil positions. The results highlight the importance of subject-specific gyral folding patterns and of local thickness of subarachnoid cerebrospinal fluid (CSF). Our modelling shows that high electric fields occur primarily on the peaks of those gyri which have only a thin layer of CSF above them. These findings have important implications for inter-individual generalizability of the TMS-induced electric field. We propose that, in order to determine with accuracy the site of stimulation for an individual subject, it is necessary to solve the electric field distribution using subject-specific anatomy obtained from a high-resolution imaging modality such as MRI.

Effect of 900 MHz Electromagnetic Fields on Nonthermal Induction of Heat-Shock Proteins in Human Leukocytes

Abstract Lim, H. B., Cook, G. G., Barker, A. T. and Coulton, L. A. Effect of 900 MHz Electromagnetic Fields on Nonthermal Induction of Heat-Shock Proteins in Human Leukocytes. Radiat. Res. 163, 45–52 (2005). Despite many studies, the evidence as to whether radiofrequency fields are detrimental to health remains controversial, and the debate continues. Cells respond to some abnormal physiological conditions by producing cytoprotective heat-shock (or stress) proteins. The aim of this study was to determine whether exposure to mobile phone-type radiation causes a nonthermal stress response in human leukocytes. Human peripheral blood was sham-exposed or exposed to 900 MHz fields (continuous-wave or GSM-modulated signal) at three average specific absorption rates (0.4, 2.0 and 3.6 W/kg) for different durations (20 min, 1 h and 4 h) in a calibrated TEM cell placed in an incubator to give well-controlled atmospheric conditions at 37°C and 95% air/5% CO2. Positive (heat-stressed at 42°C) and negative (kept at 37°C) control groups were incubated simultaneously in the same incubator. Heat caused an increase in the number of cells expressing stress proteins (HSP70, HSP27), measured using flow cytometry, and this increase was dependent on time. However, no statistically significant difference was detected in the number of cells expressing stress proteins after RF-field exposure. These results suggest that mobile phone-type radiation is not a stressor of normal human lymphocytes and monocytes, in contrast to mild heating.

Transcranial magnetic theta-burst stimulation of the human cerebellum distinguishes absolute, duration-based from relative, beat-based perception of subsecond time intervals.

Cerebellar functions in two types of perceptual timing were assessed: the absolute (duration-based) timing of single intervals and the relative (beat-based) timing of rhythmic sequences. Continuous transcranial magnetic theta-burst stimulation (cTBS) was applied over the medial cerebellum and performance was measured adaptively before and after stimulation. A large and significant effect was found in the TBS (n = 12) compared to the SHAM (n = 12) group for single-interval timing but not for the detection of a regular beat or a deviation from it. The data support the existence of distinct perceptual timing mechanisms and an obligatory role of the cerebellum in absolute interval timing with a functional dissociation from relative timing of interval within rhythmic sequences based on a regular beat.

The role of the cerebellum in sub-and supraliminal error correction during sensorimotor synchronization: Evidence from fmri and tms

Our ability to interact physically with objects in the external world critically depends on temporal coupling between perception and movement (sensorimotor timing) and swift behavioral adjustment to changes in the environment (error correction). In this study, we investigated the neural correlates of the correction of subliminal and supraliminal phase shifts during a sensorimotor synchronization task. In particular, we focused on the role of the cerebellum because this structure has been shown to play a role in both motor timing and error correction. Experiment 1 used fMRI to show that the right cerebellar dentate nucleus and primary motor and sensory cortices were activated during regular timing and during the correction of subliminal errors. The correction of supraliminal phase shifts led to additional activations in the left cerebellum and right inferior parietal and frontal areas. Furthermore, a psychophysiological interaction analysis revealed that supraliminal error correction was associated with enhanced connectivity of the left cerebellum with frontal, auditory, and sensory cortices and with the right cerebellum. Experiment 2 showed that suppression of the left but not the right cerebellum with theta burst TMS significantly affected supraliminal error correction. These findings provide evidence that the left lateral cerebellum is essential for supraliminal error correction during sensorimotor synchronization.

Effect of 50 Hz Electromagnetic Fields on the Induction of Heat-Shock Protein Gene Expression in Human Leukocytes

Abstract Coulton, L. A., Harris, P. A., Barker, A. T. and Pockley, A. G. Effect of 50 Hz Electromagnetic Fields on the Induction of Heat-Shock Protein Gene Expression in Human Leukocytes. Radiat. Res. 161, 430–434 (2004). Although evidence is controversial, exposure to environmental power-frequency magnetic fields is of public concern. Cells respond to some abnormal physiological conditions by producing cytoprotective heat-shock (or stress) proteins. In this study, we determined whether exposure to power-frequency magnetic fields in the range 0–100 μT rms either alone or concomitant with mild heating induced heat-shock protein gene expression in human leukocytes, and we compared this response to that induced by heat alone. Samples of human peripheral blood were simultaneously exposed to a range of magnetic-field amplitudes using a regimen that was designed to allow field effects to be distinguished from possible artifacts due to the position of the samples in the exposure system. Power-frequency magnetic-field exposure for 4 h at 37°C had no detectable effect on expression of the genes encoding HSP27, HSP70A or HSP70B, as determined using reverse transcriptase-PCR, whereas 2 h at 42°C elicited 10-, 5- and 12-fold increases, respectively, in the expression of these genes. Gene expression in cells exposed to power-frequency magnetic fields at 40°C was not increased compared to cells incubated at 40°C without field exposure. These findings and the extant literature suggest that power-frequency electromagnetic fields are not a universal stressor, in contrast to physical agents such as heat.

Biophysical determinants of transcranial magnetic stimulation: effects of excitability and depth of targeted area.

Safe and effective transcranial magnetic stimulation (TMS) requires accurate intensity calibration. Output is typically calibrated to individual motor cortex excitability and applied to nonmotor brain areas, assuming that it captures a site nonspecific factor of excitability. We tested this assumption by correlating the effect of TMS at motor and visual cortex. In 30 participants, we measured motor threshold (MT) and phosphene threshold (PT) at the scalp surface and at coil-scalp distances of 3.17, 5.63, and 9.03 mm. We also modeled the effect of TMS in a simple head model to test the effect of distance. Four independent tests confirmed a significant correlation between PT and MT. We also found similar effects of distance in motor and visual areas, which did not correlate across participants. Computational modeling suggests that the relationship between the effect of distance and the induced electric field is effectively linear within the range of distances that have been explored empirically. We conclude that MT-guided calibration is valid for nonmotor brain areas if coil-cortex distance is taken into account. For standard figure-of-eight TMS coils connected to biphasic stimulators, the effect of cortical distance should be adjusted using a general correction factor of 2.7% stimulator output per millimeter.

Continuous theta burst stimulation over the left pre-motor cortex affects sensorimotor timing accuracy and supraliminal error correction

Adjustments to movement in response to changes in our surroundings are common in everyday behavior. Previous research has suggested that the left pre-motor cortex (PMC) is specialized for the temporal control of movement and may play a role in temporal error correction. The aim of this study was to determine the role of the left PMC in sensorimotor timing and error correction using theta burst transcranial magnetic stimulation (TBS). In Experiment 1, subjects performed a sensorimotor synchronization task (SMS) with the left and the right hand before and after either continuous or intermittent TBS (cTBS or iTBS). Timing accuracy was assessed during synchronized finger tapping with a regular auditory pacing stimulus. Responses following perceivable local timing shifts in the pacing stimulus (phase shifts) were used to measure error correction. Suppression of the left PMC using cTBS decreased timing accuracy because subjects tapped further away from the pacing tones and tapping variability increased. In addition, error correction responses returned to baseline tap-tone asynchrony levels faster following negative shifts and no overcorrection occurred following positive shifts after cTBS. However, facilitation of the left PMC using iTBS did not affect timing accuracy or error correction performance. Experiment 2 revealed that error correction performance may change with practice, independent of TBS. These findings provide evidence for a role of the left PMC in both sensorimotor timing and error correction in both hands. We propose that the left PMC may be involved in voluntarily controlled phase correction responses to perceivable timing shifts.

The Neural Correlates of Emotion Regulation by Implementation Intentions

Several studies have investigated the neural basis of effortful emotion regulation (ER) but the neural basis of automatic ER has been less comprehensively explored. The present study investigated the neural basis of automatic ER supported by ‘implementation intentions’. 40 healthy participants underwent fMRI while viewing emotion-eliciting images and used either a previously-taught effortful ER strategy, in the form of a goal intention (e.g., try to take a detached perspective), or a more automatic ER strategy, in the form of an implementation intention (e.g., “If I see something disgusting, then I will think these are just pixels on the screen!”), to regulate their emotional response. Whereas goal intention ER strategies were associated with activation of brain areas previously reported to be involved in effortful ER (including dorsolateral prefrontal cortex), ER strategies based on an implementation intention strategy were associated with activation of right inferior frontal gyrus and ventro-parietal cortex, which may reflect the attentional control processes automatically captured by the cue for action contained within the implementation intention. Goal intentions were also associated with less effective modulation of left amygdala, supporting the increased efficacy of ER under implementation intention instructions, which showed coupling of orbitofrontal cortex and amygdala. The findings support previous behavioural studies in suggesting that forming an implementation intention enables people to enact goal-directed responses with less effort and more efficiency.

The effect of static magnetic fields on the rate of calcium/calmodulin-dependent phosphorylation of myosin light chain.

This study reports an attempt to confirm a published and well-defined biological effect of magnetic fields. The biological model investigated was the phosphorylation of myosin light chain in a cell free system. The rate of phosphorylation has been reported to be affected in an approximately linear manner by static magnetic field strengths in the range 0-200 microT. We performed three series of experiments, two to test the general hypothesis and a third that was a direct replication of published work. We found no effect of static magnetic field strength on the rate of phosphorylation. Hence, we were unable to confirm that weak static magnetic fields affect the binding of calcium to calmodulin. In view of the difficulty we and other authors have had making independent verifications of claimed biological effects of magnetic fields, we would urge caution in the interpretation of published data until they have been independently confirmed. There are still few well defined biological effects of low level magnetic fields that have been successfully transferred to an independent laboratory.