Brain Stimulation and Vision Testing

Objective

An influential model of cortical organization proposes that the primate visual system is divided into two functionally distinct pathways (Ungerleider \& Mishkin, 1982). The ventral or what visual pathway, which projects from occipital cortex into the ventral temporal cortex, is principally used for object recognition and identification. The dorsal or where pathway, which projects from occipital cortex into the parietal cortex, is principally used for locating the position of objects in the visual field and for action planning. In the proposed series of experiments we will investigate how neural representations in the ventral and dorsal pathways contribute to a range of cognitive tasks including object and scene recognition, attentional selection and face processing. These experiments will principally use transcranial magnetic stimulation (TMS) or transcranial electrical stimulation (tES) in combination with functional magnetic resonance imaging (fMRI).

TMS and tES provide unique experimental tools for studies of human cognitive function because they can be used to transiently and safely disrupt or enhance the neural processing in a targeted cortical region while subjects perform concurrent behavioral tasks that depend on the operations of that region. Furthermore TMS and tES can be combined with neuroimaging techniques such as fMRI to examine the remote effects of the induced neural disruption in other task-dependent regions distributed across cortex. We plan to use TMS and tES to address unanswered questions concerning the functioning of the distributed neural networks for different categories of object recognition and in the attention network of the human brain.

Study Population

We plan to test 665 neurologically normal subjects aged between 18 and 50 years old. Subjects will also take part in an fMRI experiment prior to any subsequent TMS or tES experiments in order to localize the stimulation sites of interest.

Design

The aim of the proposed series of experiments is to examine the effects of the TMS and tES induced neural disruption or enhancement on behavioral task performance and the neural correlates of the impaired performance as measured with fMRI. Broadly these experiments can be divided into studies that use online and offline TMS or tES. In on-line experiments, TMS or tES will be applied during behavioral tasks. In off-line experiments, theta burst stimulation (TBS) or tES will be delivered before the experimental task and off-line experiments may combine TBS or tES with fMRI.

1. TMS or tES target site localization

Prior to both online and offline studies subjects will take part in an fMRI experiment designed to localize particular cortical regions of interest (ROIs). The fMRI experiment will require the subject to view either a series of different object categories (e.g. faces, bodies, scenes) or flickering sections of black and white checkerboards in the fMRI scanner. The results of these fMRI experiments will be used to identify regions of cortex that will then be targeted with TMS or tES. We will identify TMS and tES target sites using the stereotaxic Brainsight co-registration software and the scalp location will be marked individually on each subject. 2. Online behavioral TMS experiments

Online TMS experiments are designed to address the direct effects of the induced neural disruption on the targeted TMS site only. TMS is delivered during every trial to assess the effects on concurrent task performance. Subjects will perform a range of visual behavioral tasks while online TMS is delivered over the cortical region of interest or over control sites (e.g. vertex). Repetitive TMS will be delivered at a frequency of 10Hz for 500ms. In some experiments we will alternatively deliver double-pulse TMS at different latencies after stimulus onset to assess when the targeted region is likely to be involved in task performance. 3. Offline TBS experiments

Offline thetaburst (TBS) experiments are also designed to assess the effects of the induced disruption in the stimulated region. However, rather than delivering TMS during every experimental trial Thetaburst TMS (TBS) is delivered over the targeted region of interest (ROI) for latencies up to 60 seconds prior to the subject performing any behavioral task. The neural effects of this induced disruption have then been shown to last for up to 30 minutes (Huang et al., 2005). In the offline TBS experiments we propose to deliver 60 seconds of the TBS over the stimulated ROI. In some of the proposed experiment participants will then be placed in an fMRI scanner before and after TBS stimulation. During both fMRI sessions subjects will perform a series of visual discrimination tasks to assess the effects of TBS disruption both on their behavior and on activity in remote cortical areas as measured with BOLD activation. 4. Online \& offline tES experiments

Behavioral impact of tES can be recorded both online and offline simultaneously within the same session and using the same protocol. Online tES examines the direct effect of neural stimulation whilst a participant is performing a task (Tyler et al., 2018). Unlike TMS, online tES is possible as the subcutaneous stimulation effects are minor or unperceived, have no auditory impact, and require no experimenter involvement. Once the surface electrodes are in place, the participant is free to act independently. Offline tES examines the time-course of behavioral impact after stimulation. The offline effects of tES last up to 60 minutes after stimulation (Terney et al., 2008; Herpich et al., 2019). We may deliver either direct or alternating current tES for a maximum of 20 minutes, at an intensity under 4mA (Antal et al., 2017; Rossi \& Antal, 2020).

Outcome measures

The dependent variables in the online behavioral TMS or tES experiments will be performance accuracy, sensitivity (d ) and reaction time (RT) measures collected during the concurrently performed behavioral tasks. Dependent variables in the offline fMRI-TBS or fMRI-tES experiments will be task performance as well as reduced neuronal activity as measured by decreased BOLD activation in the targeted and remote ROIs.