Transcranial magnetic stimulation in mild to severe hemiparesis early after stroke: a proof of principle and novel approach to improve motor function

Low-frequency repetitive transcranial magnetic stimulation (rTMS) of the unaffected hemisphere can enhance function of the paretic hand in patients with mild motor impairment. Effects of low-frequency rTMS to the contralesional motor cortex at an early stage of mild to severe hemiparesis after stroke are unknown. In this pilot, randomized, double-blind clinical trial we compared the effects of low-frequency rTMS or sham rTMS as add-on therapies to outpatient customary rehabilitation, in 30 patients within 5-45 days after ischemic stroke, and mild to severe hand paresis. The primary feasibility outcome was compliance with the interventions. The primary safety outcome was the proportion of intervention-related adverse events. Performance of the paretic hand in the Jebsen-Taylor test and pinch strength were secondary outcomes. Outcomes were assessed at baseline, after ten sessions of treatment administered over 2 weeks and at 1 month after end of treatment. Baseline clinical features were comparable across groups. For the primary feasibility outcome, compliance with treatment was 100% in the active group and 94% in the sham group. There were no serious intervention-related adverse events. There were significant improvements in performance in the Jebsen-Taylor test (mean, 12.3% 1 month after treatment) and pinch force (mean, 0.5 Newtons) in the active group, but not in the sham group. Low-frequency rTMS to the contralesional motor cortex early after stroke is feasible, safe and potentially effective to improve function of the paretic hand, in patients with mild to severe hemiparesis. These promising results will be valuable to design larger randomized clinical trials.

Cerebral blood flow identifies responders to transcranial magnetic stimulation in auditory verbal hallucinations

Auditory hallucinations comprise a critical domain of psychopathology in schizophrenia. Repetitive transcranial magnetic stimulation (TMS) has shown promise as an intervention with both positive and negative reports. The aim of this study was to test resting-brain perfusion before treatment as a possible biological marker of response to repetitive TMS. Twenty-four medicated patients underwent resting-brain perfusion magnetic resonance imaging with arterial spin labeling (ASL) before 10 days of repetitive TMS treatment. Response was defined as a reduction in the hallucination change scale of at least 50%. Responders (n=9) were robustly differentiated from nonresponders (n=15) to repetitive TMS by the higher regional cerebral blood flow (CBF) in the left superior temporal gyrus (STG) (P<0.05, corrected) before treatment. Resting-brain perfusion in the left STG predicted the response to repetitive TMS in this study sample, suggesting this parameter as a possible bio-marker of response in patients with schizophrenia and auditory hallucinations. Being noninvasive and relatively easy to use, resting perfusion measurement before treatment might be a clinically relevant way to identify possible responders and nonresponders to repetitive TMS.

One-Hertz transcranial magnetic stimulation over the frontal eye field induces lasting inhibition of saccade triggering

The aim of the study was to examine the effect of low-frequency repetitive transcranial magnetic stimulation on saccade triggering. In five participants, a train of 600 pulses with a frequency of 1 Hz was applied over the right frontal eye field and--as control condition--over the vertex. After repetitive transcranial magnetic stimulation application, oculomotor performance was evaluated with an overlap paradigm. The results show that the repetitive transcranial magnetic stimulation effect was specific for frontal eye field stimulation. Saccade latencies were found to be increased bilaterally for several minutes after the stimulation, and the time course of recovery was different for the ipsilateral and contralateral sides. The results are discussed in the light of possible local and remote repetitive transcranial magnetic stimulation effects on the oculomotor network.

Time course of blood oxygenation level-dependent signal response after theta burst transcranial magnetic stimulation of the frontal eye field

The aim of the current study was to examine the effect of theta burst repetitive transcranial magnetic stimulation (rTMS) on the blood oxygenation level-dependent (BOLD) activation during repeated functional magnetic resonance imaging (fMRI) measurements. Theta burst rTMS was applied over the right frontal eye field in seven healthy subjects. Subsequently, repeated fMRI measurements were performed during a saccade-fixation task (block design) 5, 20, 35, and 60 min after stimulation. We found that theta burst rTMS induced a strong and long-lasting decrease of the BOLD signal response of the stimulated frontal eye field at 20 and 35 min. Furthermore, less pronounced alterations of the BOLD signal response with different dynamics were found for remote oculomotor areas such as the left frontal eye field, the pre-supplementary eye field, the supplementary eye field, and both parietal eye fields. Recovery of the BOLD signal changes in the anterior remote areas started earlier than in the posterior remote areas. These results show that a) the major inhibitory impact of theta burst rTMS occurs directly in the stimulated area itself, and that b) a lower effect on remote, oculomotor areas can be induced.

Neglect-like visual exploration behaviour after theta burst transcranial magnetic stimulation of the right posterior parietal cortex

The right posterior parietal cortex (PPC) is critically involved in visual exploration behaviour, and damage to this area may lead to neglect of the left hemispace. We investigated whether neglect-like visual exploration behaviour could be induced in healthy subjects using theta burst repetitive transcranial magnetic stimulation (rTMS). To this end, one continuous train of theta burst rTMS was applied over the right PPC in 12 healthy subjects prior to a visual exploration task where colour photographs of real-life scenes were presented on a computer screen. In a control experiment, stimulation was also applied over the vertex. Eye movements were measured, and the distribution of visual fixations in the left and right halves of the screen was analysed. In comparison to the performance of 28 control subjects without stimulation, theta burst rTMS over the right PPC, but not the vertex, significantly decreased cumulative fixation duration in the left screen-half and significantly increased cumulative fixation duration in the right screen-half for a time period of 30 min. These results suggest that theta burst rTMS is a reliable method of inducing transient neglect-like visual exploration behaviour.

Theta burst transcranial magnetic stimulation for the treatment of auditory verbal hallucinations: results of a randomized controlled study

One Hertz (1 Hz) repetitive transcranial magnetic stimulation (rTMS) is an effective therapy for auditory verbal hallucinations (AVH). Theta burst protocols (TBS) show longer after-effects. This single-blind, randomized controlled study compared continuous TBS with 1Hz rTMS in a 10-day treatment. Patients were diagnosed with schizophrenia or schizoaffective disorder. TBS demonstrated equal clinical effects compared to 1Hz TMS.

Suppressing versus releasing a habit: frequency-dependent effects of prefrontal transcranial magnetic stimulation.

When subjects are required to generate a random sequence of numbers they typically produce too many forward and backward 'counts' (e.g. 5-6, 4-3). This counting bias is interpreted as the consequence of an interference by overlearned tendencies to arrange numbers according to their natural order. Inhibition of such well-learned routines is known to rely on frontal lobe functioning. We examined differential effects of slow (1 Hz) and fast (10 Hz) repetitive transcranial magnetic stimulation (rTMS) over the left or right dorsolateral prefrontal cortex (DLPFC) on random number generation (RNG) performance. Eighteen healthy men performed an RNG task. Those subjects stimulated over the left DLPFC showed a frequency-dependent rTMS effect: counting bias was significantly reduced after the 1 Hz stimulation compared with baseline, but significantly exaggerated after the 10 Hz stimulation compared with 1 Hz stimulation. In contrast, the sequences of the subjects stimulated over the right DLPFC showed the well-known excess of counting in all conditions (i.e. baseline, 1 Hz and 10 Hz). These findings confirm the functional importance of specifically the left DLPFC in sequential response production and show, for the first time, that rTMS affects cognitive processing in a frequency-dependent manner.

Transcranial magnetic stimulation to right parietal cortex modifies the attentional blink

The 'attentional blink' (AB) reflects a limitation in the ability to identify multiple items in a stream of rapidly presented information. Repetitive transcranial magnetic stimulation (rTMS), applied to a site over the right posterior parietal cortex, reduced the magnitude of the AB to visual stimuli, whilst no effect of rTMS was found when stimulation took place at a control site. The data confirm that the posterior parietal cortex may play a critical role in temporal as well as spatial aspects of visual attention.

Psychobiophysics of transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) is a technique that stimulates the brain using a magnetic coil placed on the scalp. Since it is applicable to humans non-invasively, directly interfering with neural electrical activity, it is potentially a good tool to study the direct relationship between perceptual experience and neural activity. However, it has been difficult to produce a clear perceptible phenomenon with TMS of sensory areas, especially using a single magnetic pulse. Also, the biophysical mechanisms of magnetic stimulation of single neurons have been poorly understood.

In the psychophysical part of this thesis, perceptual phenomena induced by TMS of the human visual cortex are demonstrated as results of the interactions with visual inputs. We first introduce a method to create a hole, or a scotoma, in a flashed, large-field visual pattern using single-pulse TMS. Spatial aspects of the interactions are explored using the distortion effect of the scotoma depending on the visual pattern, which can be luminance-defined or illusory. Its similarity to the distortion of afterimages is also discussed. Temporal interactions are demonstrated in the filling-in of the scotoma with temporally adjacent visual features, as well as in the effective suppression of transient visual features. Also, paired-pulse TMS is shown to lead to different brightness modulations in transient and sustained visual stimuli.

In the biophysical part, we first develop a biophysical theory to simulate the effect of magnetic stimulation on arbitrary neuronal structure. Computer simulations are performed on cortical neuron models with realistic structure and channels, combined with the current injection that simulates magnetic stimulation. The simulation results account for general and basic characteristics of the macroscopic effects of TMS including our psychophysical findings, such as a long inhibitory effect, dependence on the background activity, and dependence on the direction of the induced electric field.

The perceptual effects and the cortical neuron model presented here provide foundations for the study of the relationship between perception and neural activity. Further insights would be obtained from extension of our model to neuronal networks and psychophysical studies based on predictions of the biophysical model.

Simultaneous transcranial magnetic stimulation and single-neuron recording in alert non-human primates.

Transcranial magnetic stimulation (TMS) is a widely used, noninvasive method for stimulating nervous tissue, yet its mechanisms of effect are poorly understood. Here we report new methods for studying the influence of TMS on single neurons in the brain of alert non-human primates. We designed a TMS coil that focuses its effect near the tip of a recording electrode and recording electronics that enable direct acquisition of neuronal signals at the site of peak stimulus strength minimally perturbed by stimulation artifact in awake monkeys (Macaca mulatta). We recorded action potentials within ∼1 ms after 0.4-ms TMS pulses and observed changes in activity that differed significantly for active stimulation as compared with sham stimulation. This methodology is compatible with standard equipment in primate laboratories, allowing easy implementation. Application of these tools will facilitate the refinement of next generation TMS devices, experiments and treatment protocols.

Determining the optimal current direction of transcranial magnetic stimulation to induce motor responses in the tongue: A preliminary study of neurologically healthy individuals

Objective
To determine the optimal transcranial magnetic stimulation (TMS) coil direction for inducing motor responses in the tongue in a group of non-neurologically impaired participants.
Methods
Single-pulse TMS was delivered using a figure-of-eight Magstim 2002 TMS coil. Study 1 investigated the effect of eight different TMS coil directions on the motor-evoked potentials elicited in the tongue in eight adults. Study 2 examined active motor threshold levels at optimal TMS coil direction compared to a customarily-used ventral-caudal direction. Study 3 repeated the procedure of Study 1 at five different sites across the tongue motor cortex in one adult.
Results
Inter-individual variability in optimal direction was observed, with an optimal range of directions determined for the group. Active motor threshold was reduced when a participant's own optimal TMS coil direction was used compared to the ventral-caudal direction. A restricted range of optimal directions was identified across the five cortical positions tested.
Conclusions
There is a need to identify each individual's own optimal TMS coil direction in investigating tongue motor cortex function. A recommended procedure for determining optimal coil direction is described.
Significance
Optimized TMS procedures are needed so that TMS can be utilized in determining the underlying neurophysiological basis of various motor speech disorders.

The role of the right parietal cortex in sound localization: a chronometric single pulse transcranial magnetic stimulation study.

Auditory spatial functions, including the ability to discriminate between the positions of nearby sound sources, are subserved by a large temporo-parieto-frontal network. With the aim of determining whether and when the parietal contribution is critical for auditory spatial discrimination, we applied single pulse transcranial magnetic stimulation on the right parietal cortex 20, 80, 90 and 150 ms post-stimulus onset while participants completed a two-alternative forced choice auditory spatial discrimination task in the left or right hemispace. Our results reveal that transient TMS disruption of right parietal activity impairs spatial discrimination when applied at 20 ms post-stimulus onset for sounds presented in the left (controlateral) hemispace and at 80 ms for sounds presented in the right hemispace. We interpret our finding in terms of a critical role for controlateral temporo-parietal cortices over initial stages of the building-up of auditory spatial representation and for a right hemispheric specialization in integrating the whole auditory space over subsequent, higher-order processing stages.