Transcranial Direct Current Stimulation of the Frontal Eye Field
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Transcranial Direct Current Stimulation of the Frontal Eye Field to Modulate Eye Movements Faculty of Social and Behavioural Sciences, Psychology Master Thesis Psychology, Brain and Cognition Name: Floris Jan Frederik Willem Roelofs Student NumBer: 10212434 Supervisor: Leon Reteig Date: 18/07/2017 Word count: 5119 Abstract The main focus of this study is to validate the results presented By Kanai et al. (2012). In their study they have found indicative data for a modulatory role of the Frontal Eye Fields (FEF) induced By transcranial direct current stimulation (tDCS) on saccade latencies. Because the data did not fully suBstantiate the hypothesised results and the effect sizes Were mild, the aim of this study is to find more conclusive evidence on the modulatory role of the FEF and the influence of tDCS. By taking the design from Kanai et al. (2012) as reference, suBjects received Both anodal and cathodal stimulation during a prosaccade task over the course of two sessions in Which saccade latency Was measured. To estimate the effects of tDCS over time, Baseline measurements Were compared to suBsequent stimulation and post stimulation Blocks. A repeated measure ANOVA over 18 suBjects revealed no significant effects of stimulation on saccade latency and accuracy. It seems like the data does not support the findings of Kanai et al. (2012) in Which tDCS stimulation successfully reached and influenced the FEF. Implications for future research are discussed, as Well as shortcomings and alternative theoretical interpretations of the current data. Introduction With the rising interest and applicability of transcranial direct current stimulation (tDCS), much research arises on the effects of tDCS on different Brain regions. Most of this research has Been centered on the effects of stimulating the motor cortex and prefrontal cortex (PFC), Both in experimental as Well as clinical setting (Nitsche & Paulus, 2000, 2001; Boggio et al., 2006; Berryhill & Jones, 2012). tDCS applies electrical current at targeted areas of the Brain through two sorts of electrodes, a positive anodal electrode and a negative cathodal electrode. The electrode that is not placed over a target area is called the reference electrode, usually placed on the opposite forehead in respect to the target area or the shoulder (Filmer, Dux & Mattingley, 2014). By stimulating the underlying cortex With the anodal electrode, the resting potential of the memBrane can Be depolarised, Which loWers the firing threshold. In contrast, By inhiBiting the underlying cortex With the cathodal electrode, the memBrane Will Be Brought in a hyperpolarising state, resulting in an increased firing threshold (Medeiros et al., 2012). Conceptually, one can think of the effects of depolarisation and hyperpolarisation caused By anodal and cathodal tDCS as modulations that make it more or less likely, respectively, that a stimulated neuron Will produce an action potential (Filmer et al., 2014). After prolonged stimulation of the cortex, the effects can still Be apparent after the stimulation (Nitsche et al., 2008; Zheng, Alsop & Schlaug, 2011; Brunoni et al., 2012) due to plasticity concepts of long-term potentiation (LTP) and long-term depression (LTD) caused By the alteration of synaptic transmission By tDCS. In the present study We are interested if tDCS is able to reach and modulate the Frontal Eye Fields (FEF). The FEF is located in the dorsal prefrontal cortex and is involved With detecting stimuli Within the visual field, controlling selective attention and initiating target orientated saccades (RoBinson & Fuchs, 1969; Bruce & GoldBerg, 1985; Paus, 1996; Moore, Armstrong & Fallah, 2003; Schall, 2009). A transcranial magnetic stimulation (TMS) study in 2006 shoWed that stimulation of the FEF (versus vertex) enhanced perceived contrast for peripheral relative to central visual stimuli (Ruff et al., 2006). Such an enhancement may play a functional role during saccade planning and execution and is in accordance With the perceived role of the FEF. In addition, the planning role of the FEF finds support By many fMRI studies in Which FEF activity Was shoWn prior to saccadic movements (BroWn, Goltz, Vilis, Ford & Everling, 2006; Connolly, Goodale, Menon & Munoz, 2002; Sweeney, Luna, Keedy, McDoWell & Clementz, 2007). Also, numerous studies on the effects of micro stimulation to the FEF have Been puBlished. For example, Moore and Fallah (2004) shoWed that electrical micro stimulation of the FEF resulted in an increased sensitivity to targets Within the stimulation site, demonstrating that improvements in the deployment of covert spatial attention can Be oBtained By micro stimulation of FEF sites from Which saccadic eye movements are also evoked. Given these results from previous studies, We can hypothesize What the effects of tDCS should Be on saccadic eye movements. Because the FEF is mainly involved in the initiation of saccadic movement in a contralateral manner, anodal stimulation is expected to reduce the latency time of the saccades When moving contralateral With respect to the stimulation. Anodal stimulation Will raise the resting potential in the underlying cortex, Which Will reduce the firing threshold, causing the initiation of saccades With more ease and thereBy shortening the latency time. In addition, under cathodal stimulation an increased latency time for saccadic movements is expected When moving contralateral in respect to the stimulation. This is Because, under cathodal stimulation the underlying cortex Will Be hyperpolarised, Which increases the fire threshold. This could result in an increased latency time. For saccadic movements ipsilateral in respect to the stimulation the opposite effects could Be expected. Since the FEF initiates saccadic movements in a contralateral manner, anodal stimulation could potentially increase latency time for saccadic movements toWards the stimulation site. Cathodal stimulation could in turn facilitate saccadic movements, thus decreasing latency time toWards the stimulation site. One study that has investigated this relationship Between tDCS stimulation of the FEF and latency of saccadic movements, is the study of Kanai, Muggleton and Walsh (2012). They used a pro- and antisaccade task in Which, respectively, gaze- movement had to Be directed toWards or away from a peripheral horizontal stimulus. TWo types of tDCS montages Were used: Bilateral stimulation, With anodal stimulation over one FEF and the cathodal stimulation over the other FEF, and unilateral stimulation, in Which half of the suBjects had tDCS on the right side and the other half on the left. Under Bilateral stimulation, the latency of saccades Was influenced during a prosaccade task. The effect on latency Was specific to saccades contralateral to the FEF stimulated By the anode, suggesting that anodal stimulation shortened saccade latency. No Bilateral stimulation montage in comBination With an anti-saccade task Was reported. During the prosaccade task With a unilateral montage, anodal stimulation shortened the latency of saccade contralateral to the stimulation site. HoWever, unilateral cathodal stimulation over FEF did not have any effect on saccade latency. Conversely, cathodal tDCS had an effect in the antisaccade task But no effects of anodal tDCS Were found under unilateral stimulation. Although these results reflect a modulatory role induced By tDCS, there are results missing from this study that should also confirm this hypothesis. First, importantly, cathodal stimulation should have lengthened the latency of contralateral prosaccades. Second, anodal tDCS should have shortened the latency of ipsilateral anti-saccades. As for the lack of these effects, it is possiBle that the effect size of this study Was too small to detect With their experimental procedures. Apart from that, some differences in latency time Were of such a size (~ 3 ms), that the eye-tracking device in the experiment could not distinguish accurately enough With the used sample rate of 250 Hz. The aim of this study is to find more conclusive evidence on the modulatory role of the FEF and the influence of tDCS on it By trying to validate the results presented By Kanai et al. (2012). Using their study as reference point for replication, a feW important design choices are made to Build on their study, hoping to solve the discrepancies found in their results. Because Kanai et al. (2012) reported only small effect sizes, this study is restricted only to prosaccades, using only a prosaccade task, focusing on this mechanism in more detail. Also, Duecker, Formisano and Sack (2013) have found a functional asymmetry Between the FEF, Where stimulation to the left FEF (lFEF) effected only the contralateral hemifield, But stimulation of the right FEF (rFEF) effected Both hemifields. Because of this hemispheric difference, only the rFEF Will Be stimulated in this study. To localise the rFEF, a suBject-to- suBject method is used With structural MRI scans, in comparison to Kanai et al. (2012) Where standard MNI coordinates of the FEF Were used. As for the tDCS montage, this study uses a unilateral instead of a Bilateral montage, Because anodal and cathodal stimulation in a Bilateral montage could affect each other. By also changing the reference electrode from the shoulder to the left side of the forehead, the interelectrode distance Will decrease, Which might achieve a clearer online and offline effect from the stimulation, since it could enhance the focality of the stimulation (Moliadze, Antal & Paulus, 2010; Galletta