Mathias Lüthi

Repetitive TMS over the human oculomotor cortex: Comparison of 1-Hz and theta burst stimulation

The aim of the study was to compare the effect duration of two different protocols of repetitive transcranial magnetic stimulation (rTMS) on saccade triggering. In four experiments, two regions (right frontal eye field (FEF) and vertex) were stimulated using a 1-Hz and a theta burst protocol (three 30Hz pulses repeated at intervals of 100ms). The same number of TMS pulses (600 pulses) was applied with stimulation strength of 80% of the resting motor threshold for hand muscles. Following stimulation the subjects repeatedly performed an oculomotor task using a modified overlap paradigm, and saccade latencies were measured over a period of 60min. The results show that both 1-Hz and theta burst stimulation had inhibitory effects on saccade triggering when applied over the FEF, but not over the vertex. One-hertz rTMS significantly increased saccade latencies over a period of about 8min. After theta burst rTMS, this effect lasted up to 30min. Furthermore, the decay of rTMS effects was protocol-specific: After 1-Hz stimulation, saccade latencies returned to a baseline level much faster than after theta burst stimulation. We speculate that these time course differences represent distinct physiological mechanisms of how TMS interacts with brain function.

Extending lifetime of plastic changes in the human brain

The ability of the brain to adjust to changing environments and to recover from damage rests on its remarkable capacity to adapt through plastic changes of underlying neural networks. We show here with an eye movement paradigm that a lifetime of plastic changes can be extended to several hours by repeated applications of theta burst transcranial magnetic stimulation to the frontal eye field of the human cortex. The results suggest that repeated application of the same stimulation protocol consolidates short‐lived plasticity into long‐lasting changes.

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.

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.

Size matters: saccades during scene perception.

We investigated the effect of image size on saccade amplitudes. First, in a meta-analysis, relevant results from previous scene perception studies are summarised, suggesting the possibility of a linear relationship between mean saccade amplitude and image size. Forty-eight observers viewed 96 colour scene images scaled to four different sizes, while their eye movements were recorded. Mean and median saccade amplitudes were found to be directly proportional to image size, while the mode of the distribution lay in the range of very short saccades. However, saccade amplitudes expressed as percentages of image size were not constant over the different image sizes; on smaller stimulus images, the relative saccades were found to be larger, and vice versa. In sum, and as far as mean and median saccade amplitudes are concerned, the size of stimulus images is the dominant factor. Other factors, such as image properties, viewing task, or measurement equipment, are only of subordinate importance. Thus, the role of stimulus size has to be reconsidered, in theoretical as well as methodological terms.

When left becomes right and vice versa: mirrored vision after cerebral hypoxia.

The combination of acquired mirror writing and reading is an extremely rare neurological disorder. It is encountered when brain damaged patients prefer horizontally mirrored over normal script in writing and reading. Previous theories have related this pathology to a disinhibition of mirrored engrams in the non-dominant hemisphere, possibly accompanied by a reversal of the preferred scanning direction. Here, we report the experimental investigation of PR, a patient who developed pronounced mirror writing and reading following septic shock that caused hypoxic brain damage. A series of five oculomotor experiments revealed that the patients preferred scanning direction was indeed reversed. However, PR showed striking scanpath abnormalities and mirror reversals that cannot be explained by previous theories. Considered together with mirror phenomena she displayed in neuropsychological tasks and everyday activities, our findings suggest a horizontal reversal of visual information on a perceptual level. In addition, a systematic manipulation of visual variables within two further experiments had dramatic effects on her mirror phenomena. When confronted with moving, flickering or briefly presented stimuli, PR showed hardly any left-right reversals. Not only do these findings underline the perceptual nature of her disorder, but also allow interpretation of the pathology in terms of a dissociation between visual subsystems. We speculate that early visual cortices are crucially involved in this dissociation. More generally, her mirrored vision may represent an extreme clinical manifestation of the relative instability of the horizontal axis in spatial vision.

In your eyes only: deficits in executive functioning after frontal TMS reflect in eye movements

This study investigated the roles of the right and left dorsolateral prefrontal (rDLPFC, lDLPFC) and the medial frontal cortex (MFC) in executive functioning using a theta burst transcranial magnetic stimulation (TMS) approach. Healthy subjects solved two visual search tasks: a number search task with low cognitive demands, and a number and letter search task with high cognitive demands. To observe how subjects solved the tasks, we assessed their behavior with and without TMS using eye movements when subjects were confronted with specific executive demands. To observe executive functions, we were particularly interested in TMS-induced changes in visual exploration strategies found to be associated with good or bad performance in a control condition without TMS stimulation. TMS left processing time unchanged in both tasks. Inhibition of the rDLPFC resulted in a decrease in anticipatory fixations in the number search task, i.e., a decrease in a good strategy in this low demand task. This was paired with a decrease in stimulus fixations. Together, these results point to a role of the rDLPFC in planning and response selection. Inhibition of the lDLPFC and the MFC resulted in an increase in anticipatory fixations in the number and letter search task, i.e., an increase in the application of a good strategy in this task. We interpret these results as a compensatory strategy to account for TMS-induced deficits in attentional switching when faced with high switching demands. After inhibition of the lDLPFC, an increase in regressive fixations was found in the number and letter search task. In the context of high working memory demands, this strategy appears to support TMS-induced working memory deficits. Combining an experimental TMS approach with the recording of eye movements proved sensitive to discrete decrements of executive functions and allows pinpointing the functional organization of the frontal lobes.