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.
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.
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.
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.
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.