http://nnr.sagepub.com/content/30/4/339.full
- Suzanne J. Ackerley, PhD1
- Winston D. Byblow, PhD1
- P. Alan Barber, FRACP1,2
- Hayley MacDonald1
- Andrew McIntyre-Robinson1
- Cathy M. Stinear, PhD1⇑
- Cathy M. Stinear, PhD, Centre for Brain Research, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand. Email: c.stinear@auckland.ac.nz
Abstract
Background. Recovery of upper limb function is important for regaining independence after stroke.
Objective.
To test the effects of priming upper limb physical therapy with
intermittent theta burst stimulation (iTBS), a form of noninvasive
brain stimulation.
Methods. Eighteen
adults with first-ever chronic monohemispheric subcortical stroke
participated in this randomized, controlled,
triple-blinded trial. Intervention consisted of
priming with real or sham iTBS to the ipsilesional primary motor cortex
immediately
before 45 minutes of upper limb physical therapy,
daily for 10 days. Changes in upper limb function (Action Research Arm
Test
[ARAT]), upper limb impairment (Fugl-Meyer Scale),
and corticomotor excitability, were assessed before, during, and
immediately,
1 month and 3 months after the intervention.
Functional magnetic resonance images were acquired before and at one
month after
the intervention.
Results. Improvements in
ARAT were observed after the intervention period when therapy was
primed with real iTBS, but not sham, and
were maintained at 1 month. These improvements were
not apparent halfway through the intervention, indicating a dose
effect.
Improvements in ARAT at 1 month were related to
balancing of corticomotor excitability and an increase in ipsilesional
premotor
cortex activation during paretic hand grip.
Conclusions.
Two weeks of iTBS-primed therapy improves upper limb function at the
chronic stage of stroke, for at least 1 month postintervention,
whereas therapy alone may not be sufficient to
alter function. This indicates a potential role for iTBS as an adjuvant
to
therapy delivered at the chronic stage.
Introduction
Upper limb (UL) impairment is common after stroke and recovery of function is important for regaining independence in activities
of daily living.1 Rehabilitation of the UL involves repetitive motor practice to promote use-dependent neuroplasticity and functional recovery,
and primarily occurs in the first 6 months after stroke.2⇓-4 Whether further gains are possible beyond this time has been a matter of ongoing debate.5 Therapy may need to be primed in order to realize the potential for further gains in function at the chronic stage.6
Noninvasive brain stimulation techniques can be used to prime the motor
cortex by promoting long-term potentiation–like plasticity7
and rendering the primary motor cortex (M1) more receptive to input
from other cortical areas for a greater response to therapy.8⇓⇓-11
In healthy individuals, the balance of
excitability between the 2 cerebral hemispheres is symmetric. At the
chronic stage
after stroke, the ipsilesional M1 is typically
underexcitable and interhemispheric inhibition between the hemispheres
is asymmetric,
reinforcing an imbalance in corticomotor
excitability between hemispheres.12,13 Better clinical outcomes for the affected hand and arm are seen when asymmetry of corticomotor excitability is reduced.14
Noninvasive brain stimulation techniques
that increase the excitability of the ipsilesional motor cortex may
promote reorganization
within ipsilesional M1 and improve the symmetry of
corticomotor excitability between hemispheres.9,10 A protocol of repetitive transcranial magnetic stimulation (rTMS), called intermittent theta burst stimulation (iTBS), may
act as a priming stimulus to facilitate excitability and promote use-dependent plasticity.15,16 Ipsilesional M1 iTBS followed by a single dose of UL practice at the chronic stage after stroke is more beneficial than UL
practice alone.17,18 However, one study has investigated the effects of multiple sessions combining iTBS with UL therapy in chronic stroke patients,
with a negative result.19 There was no difference between real and sham treatment groups for any hand function outcome measure.
The aim of this study was to examine the
effects of priming UL physical therapy with iTBS of ipsilesional M1 in
subcortical
stroke patients at the chronic stage. We
hypothesized that UL function would be improved immediately and one
month after intervention
in the PRIMED group (receiving real iTBS and
physical therapy) and exceed any benefit made by the CONTROL group
(receiving
sham iTBS and physical therapy). We also
hypothesized improved UL function may be associated with balancing of
cortical activity
toward symmetry between the hemispheres, assessed
with neurophysiology and neuroimaging measures.
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