Sujesh Sreedharan1, Arun K. M.1, Sylaja P. N.2, Ranaganatha Sitaram3, and Kesavadas C.1
1Imaging Sciences and Interventional Radiology, SCTIMST, Trivandrum, India, 2Neurology, SCTIMST, Trivandrum, India, 3Department of Psychiatry and Division of Neuroscience, Pontificia Universidad Católica de Chile, Santiago, Chile
Synopsis
Recovery from stroke
to lead an improved life is one of the most sought after rehabilitation
programs around the globe. Various factors are involved in the process of
restoration of an impaired function. The study examined the functional network
disruption due to stroke and the network changes happening during the real-time
fMRI based neurofeedback training for aphasic stroke survivors to retrain the
language areas. The results show that though the contralateral hemisphere for
test group has strong connections when compared with controls, and with
training the ipsilateral connections are strengthened and are recovering
through alternate connections.
Introduction
Rehabilitation in stroke helps survivors relearn
skills that are lost when part of the brain is damaged1,2. A carefully directed, well-focused,
repetitively practiced rehabilitation regime is highly desired for the
compensation or recovery from the deficits3. A real-time fMRI (rt-fMRI) based
neuro-feedback training was performed to modulate neural activity of language
areas in post-stroke aphasic patients. The effect of this intervention is
studied using the functional connectivity (FC) changes in the network of
language areas and the associated structures. The objective was to
study: (i) the effect of stroke on FC in a limited area of the brain including
language areas, (ii) the alteration of brain networks during up-regulation
activity during training, and (iii) the brain networks strengthened due to the
training and associated language recovery.Methods
Twelve
subjects were recruited for the study. The subject group included four
experimental and four control patients, all with Broca’s aphasia and four
healthy volunteers. The study was designed as sessions having alternating
baseline and up-regulation epochs. The first session is a pre-test session
which also includes a naming task after each baseline and up-regulation epoch.
The next four sessions are neuro-feedback
training sessions which do not have any testing task. The last session is a
post-test session which is a repetition of the pre-test. For controls the
experiment is conducted having only the pre-training and post-training sessions
and skipping the four training sessions.
The regions of-
interest (ROIs) chosen for the study included the Broca’s and Wernicke’s areas
and its right homologues, and eleven other ROIs surrounding the Broca’s and
Wernicke’s areas (restricted to each patient’s active region during an SPM
T-statistic map of p <0.01).The connectivity analysis was performed on data
preprocessed using SPM8 toolbox. The preprocessing involved realignment,
coregistration of anatomical scan, normalization and smoothing. This data was
then analyzed using the CONN toolbox4. The measure used for functional
connectivity is the bivariate correlation between ROIs. The connectivity matrix
obtained for the healthy group is then analyzed for modularity and subsequently
grouped into the six modules in the left hemisphere as shown in Figure 1. These
modules are restricted to the left hemisphere (LH) and six other analogous
modules are generated for the right hemisphere (RH) as well using the AAL
markers. Table 1 describes the areas covered in each module. Twelve modules so
generated are analyzed for functional connectivity changes. The inter-modular
connections are found by summing the connectivity from each ROI of one module
to that of the other module. The modular connectivity is then plotted for
various conditions using BrainNet viewer.Results and Discussion
The
study evaluated inter subject group and inter condition comparisons in the
functional connectivity changes among the modules defined above. Inter modular
connections for the test group is compared with the control groups as well as healthy
volunteers to understand the changes in network organization.
Healthy
volunteers at rest when compared to test patients have shown a stronger
inter-hemispheric connection between CO modules and between FL and TL modules
in the LH. They are indicative of weakened connections due to aphasic stroke
for the test group. In healthy group the FL and TL module connections are observed
to strengthen most due to neurofeedback training over the sessions (Figure 2).
In
the test patient group the intra-hemispheric connections involving FL, SP, CO
and TL modules are getting strengthened over the training sessions. Connections
to right hemispheric SP and CO modules are also seen. TL module is not directly
connected to FL module in the LH, and only indirectly through CO and SP modules
as opposed to direct connection in case of healthy volunteers. The effect of
training in test patients was further studied by comparing the final sessions
of the study with control group. The connections in RH are seen to strengthen most
in addition to the LH connections involving FP, FL, TL and SP modules (Figure 3a
& 3c).Conclusion
The results of the study explored the effect of
stroke on FC in the language areas. The test patients when compared to normal have
disrupted connections between the temporal and frontal language modules. The
resting and language active connections are stronger on the contralateral
hemisphere when compared to controls. Up regulation through neuro-feedback has
been shown to increase the strength of left hemispheric connections which were
disrupted due to stroke, through alternate pathwaysAcknowledgements
No acknowledgement found.References
- Smith,
L. N. et al. Rehabilitation of patients with stroke: summary of SIGN
guidance. BMJ 340, c2845 (2010).
- Carey, L. M. Stroke Rehabilitation:
Insights from Neuroscience and Imaging. (OUP USA, 2012).
- Woldag, H. & Hummelsheim, H.
Evidence-based physiotherapeutic concepts for improving arm and hand function
in stroke patients: a review. J. Neurol. 249, 518–528 (2002).
- Whitfield-Gabrieli, S. &
Nieto-Castanon, A. Conn: A Functional Connectivity Toolbox for Correlated and
Anticorrelated Brain Networks. Brain Connect. 2, 125–141 (2012).