Traumatic axonal injury influences the cognitive effect of non-invasive brain stimulation
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Non-invasive brain stimulation has been widely investigated for as a potential
treatment for a range of neurological and psychiatric conditions, including brain
injury. However, the behavioural effects of brain stimulation are very variable, for
reasons that are poorly understood. This is a particular challenge for traumatic brain
injury, where patterns of damage and their clinical effects are heterogenous. Here we
test the hypothesis that the response to transcranial direct current stimulation
following traumatic brain injury is dependent on white matter damage within the
stimulated network. We used a novel simultaneous stimulation-MRI protocol
applying anodal, cathodal and sham stimulation to 24 healthy and 35 moderate/severe
traumatic brain injury patients. Stimulation was applied to the right inferior frontal
gyrus/anterior insula node of the Salience Network, which was targeted because our
previous work had shown its importance to executive function. Stimulation was
applied during performance of the Stop Signal Task, which assesses response
inhibition, a key component of executive function. Structural MRI was used to assess
the extent of brain injury, including diffusion MRI assessment of post-traumatic
axonal injury. Functional MRI, which was simultaneously acquired to delivery of
stimulation, assessed the effects of stimulation on cognitive network function. Anodal
stimulation improved response inhibition in control participants, an effect that was not
observed in the patient group. The extent of traumatic axonal injury within the
Salience Network strongly influenced the behavioural response to stimulation.
Increasing damage to the tract connecting the stimulated right inferior frontal
gyrus/anterior insula to the rest of the SN was associated with reduced beneficial
effects of stimulation. In addition, anodal stimulation normalised Default Mode
Network activation in patients with poor response inhibition, suggesting that
stimulation modulates communication between the networks involved in supporting
cognitive control. These results demonstrate an important principle: that white matter
structure of the connections within a stimulated brain network influences the
behavioural response to stimulation. This suggests that a personalised approach to
non-invasive brain stimulation is likely to be necessary, with structural integrity of the
targeted brain networks an important criteria for patient selection and an
individualised approach to the selection of stimulation parameters.
treatment for a range of neurological and psychiatric conditions, including brain
injury. However, the behavioural effects of brain stimulation are very variable, for
reasons that are poorly understood. This is a particular challenge for traumatic brain
injury, where patterns of damage and their clinical effects are heterogenous. Here we
test the hypothesis that the response to transcranial direct current stimulation
following traumatic brain injury is dependent on white matter damage within the
stimulated network. We used a novel simultaneous stimulation-MRI protocol
applying anodal, cathodal and sham stimulation to 24 healthy and 35 moderate/severe
traumatic brain injury patients. Stimulation was applied to the right inferior frontal
gyrus/anterior insula node of the Salience Network, which was targeted because our
previous work had shown its importance to executive function. Stimulation was
applied during performance of the Stop Signal Task, which assesses response
inhibition, a key component of executive function. Structural MRI was used to assess
the extent of brain injury, including diffusion MRI assessment of post-traumatic
axonal injury. Functional MRI, which was simultaneously acquired to delivery of
stimulation, assessed the effects of stimulation on cognitive network function. Anodal
stimulation improved response inhibition in control participants, an effect that was not
observed in the patient group. The extent of traumatic axonal injury within the
Salience Network strongly influenced the behavioural response to stimulation.
Increasing damage to the tract connecting the stimulated right inferior frontal
gyrus/anterior insula to the rest of the SN was associated with reduced beneficial
effects of stimulation. In addition, anodal stimulation normalised Default Mode
Network activation in patients with poor response inhibition, suggesting that
stimulation modulates communication between the networks involved in supporting
cognitive control. These results demonstrate an important principle: that white matter
structure of the connections within a stimulated brain network influences the
behavioural response to stimulation. This suggests that a personalised approach to
non-invasive brain stimulation is likely to be necessary, with structural integrity of the
targeted brain networks an important criteria for patient selection and an
individualised approach to the selection of stimulation parameters.
Date Issued
2019-10-01
Date Acceptance
2019-06-25
Citation
Brain, 2019, 142 (10), pp.3280-3293
ISSN
1460-2156
Publisher
Oxford University Press (OUP)
Start Page
3280
End Page
3293
Journal / Book Title
Brain
Volume
142
Issue
10
Copyright Statement
© (2019) The Author(s). Published by Oxford University Press on behalf of the Guarantors of Brain.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse,
distribution, and reproduction in any medium, provided the original work is properly cited.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse,
distribution, and reproduction in any medium, provided the original work is properly cited.
Sponsor
Wellcome Trust
Imperial College Healthcare NHS Trust- BRC Funding
Imperial College Healthcare NHS Trust- BRC Funding
Wellcome Trust
Imperial College Healthcare NHS Trust- BRC Funding
Imperial College Healthcare NHS Trust- BRC Funding
National Institute for Health Research
Wellcome Trust
Wellcome Trust
Grant Number
103429/Z/13/Z
RDA03
RDC04 79560
103429/Z/13/Z
RDA03_79560
RDC04
NIHR-RP-011-048
103045/Z/13/Z
103045/Z/13/Z
Subjects
axonal injury
brain stimulation
response inhibition
salience network
traumatic brain injury
11 Medical and Health Sciences
17 Psychology and Cognitive Sciences
Neurology & Neurosurgery
Publication Status
Published
Date Publish Online
2019-08-30