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Assessing the Functional Role of Frontal Eye Fields in Voluntary and Reflexive Saccades Using Continuous Theta Burst Stimulation.

ABSTRACT: The frontal eye fields (FEFs) are core nodes of the oculomotor system contributing to saccade planning, control, and execution. Here, we aimed to reveal hemispheric asymmetries between left and right FEF in both voluntary and reflexive saccades toward horizontal and vertical targets. To this end, we applied fMRI-guided continuous theta burst stimulation (cTBS) over either left or right FEF and assessed the consequences of this disruption on saccade latencies. Using a fully counterbalanced within-subject design, we measured saccade latencies before and after the application of cTBS in eighteen healthy volunteers. In general, saccade latencies on both tasks were susceptible to our experimental manipulations, that is, voluntary saccades were slower than reflexive saccades, and downward saccades were slower than upward saccades. Contrary to our expectations, we failed to reveal any TMS-related effects on saccade latencies, and Bayesian analyses provided strong support in favor of a TMS null result for both tasks. Keeping in mind the interpretative challenges of null results, we discuss possible explanations for this absence of behavioral TMS effects, focusing on methodological differences compared to previous studies (task parameters and online vs. offline TMS interventions). We also speculate about what our results might reveal about the functional role of FEF.

SUBMITTER: Gurel SC

PROVIDER: S-EPMC6302006 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Project description:IntroductionRepetitive transcranial magnetic stimulation (rTMS) may have anti-epileptic effects, especially in patients with neocortical lesions. Initial clinical trials demonstrated that the duration of the seizure reducing effect is relatively short-lived. In the context of a chronic condition like epilepsy, theta burst stimulation (TBS) may represent a potential solution in optimizing treatment practicality and durability as it was demonstrated to be associated with longer-lasting after-effects. TBS has been studied extensively in diverse neuropsychiatric conditions, but a therapeutic TBS protocol has not previously been applied in epilepsy patients.Materials and methodsWe performed a prospective open-label pilot study of 4-day accelerated continuous TBS (cTBS) treatment in patients with neocortical drug-resistant epilepsy (DRE). A treatment session consisted of 5 cTBS trains, each comprising 600 pulses presented in 50 Hz triplet bursts every 200 ms, delivered at 10-min intertrain-intervals, targeted over the epileptic focus (EF) using a neuronavigation-guided figure-of-8 coil. Safety and feasibility, and seizure frequency were assessed as primary and secondary endpoints, respectively, over a 4-week baseline period, a 1-week treatment period and a 7-week follow-up period, using adverse event logging, electro-encephalography, cognitive, and psychological questionnaires and a seizure diary kept by the patients and/or caregivers.ResultsSeven subjects (4M:3F; median age 48, interquartile ranges 25) underwent the treatment protocol. Adverse events were reported in all subjects but were mild and transient. No clinical or electrographic seizures were evoked during or immediately following stimulation. No deterioration was found in cognition nor in psycho-emotional well-being following treatment. Treatment burden was acceptable, but seems to depend on clinical effect, duration of ongoing effect and stimulation site. Median weekly seizure frequency and ratio of seizure-free weeks did not change significantly in this small patient cohort.ConclusionWe report the results of the first ever trial of cTBS as a treatment for neocortical DRE. A 4-day accelerated cTBS protocol over the EF appears safe and feasible. Although the design and sample size of this open-label pilot study is unfit to reliably identify a therapeutic effect, results encourage further exploration of cTBS as an anti-epileptic treatment and potential optimization compared to conventional rTMS in a dedicated randomized controlled trial. (clinicaltrials.gov: NCT02635633).

Project description:Learning regularities that exist in the environment can help the visual system achieve optimal efficiency while reducing computational burden. Using a pro- and anti-saccade task, studies have shown that probabilistic information regarding spatial locations can be a strong modulator of frontal eye fields (FEF) activities and consequently alter saccadic behavior. One recent study has also shown that FEF activities can be modulated by transcranial direct current stimulation, where anodal tDCS facilitated prosaccades but cathodal tDCS prolonged antisaccades. These studies together suggest that location probability and tDCS can both alter FEF activities and oculomotor performance, yet how these two modulators interact with each other remains unclear. In this study, we applied anodal or cathodal tDCS over right FEF, and participants performed an interleaved pro- and anti-saccade task. Location probability was manipulated in prosaccade trials but not antisaccade trials. We observed that anodal tDCS over rFEF facilitated prosaccdes toward low-probability locations but not to high-probability locations; whereas cathodal tDCS facilitated antisaccades away from the high-probability location (i.e., same location as the low-probability locations in prosaccades). These observed effects were specific to rFEF as tDCS over the SEF in a separate control experiment did not yield similar patterns. These effects were also more pronounced in low-performers who had slower saccade reaction time. Together, we conclude that (1) the overlapping spatial endpoint between prosaccades (i.e., toward low-probability location) and antisaccades (i.e., away from high-probability location) possibly suggest an endpoint-selective mechanism within right FEF, (2) anodal tDCS and location probability cannot be combined to produce a bigger facilitative effect, and (3) anodal rFEF tDCS works best on low-performers who had slower saccade reaction time. These observations are consistent with the homeostasis account of tDCS effect and FEF functioning.

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Assessing the Functional Role of Frontal Eye Fields in Voluntary and Reflexive Saccades Using Continuous Theta Burst Stimulation.

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