http://journal.frontiersin.org/article/10.3389/fnhum.2016.00428/full?
- 1Spaulding Neuromodulation Center, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA, USA
- 2Physical and Rehabilitation Medicine Institute of the University of São Paulo, Medical School General Hospital, São Paulo, Brazil
- 3Service of Interdisciplinary Neuromodulation, Laboratory of Neurosciences (LIM-27), Department and Institute of Psychiatry, University of São Paulo, São Paulo, Brazil
Objective: Emotional disturbance is a
common complication of stroke significantly affecting functional
recovery and quality of life. Identifying relevant neurophysiologic
markers associated with post-stroke emotional disturbance may lead to a
better understanding of this disabling condition, guiding the diagnosis,
development of new interventions and the assessments of treatment
response.
Methods: Thirty-five subjects with
chronic stroke were enrolled in this study. The emotion sub-domain of
Stroke Impact Scale (SIS-Emotion) was used to assess post-stroke mood
and emotional control. The relation between SIS-Emotion and
neurophysiologic measures was assessed by using covariance mapping and
univariate linear regression. Multivariate analyses were conducted to
identify and adjust for potential confounders. Neurophysiologic measures
included power asymmetry and coherence assessed by
electroencephalography (EEG); and motor threshold, intracortical
inhibition (ICI) and intracortical facilitation (ICF) measured by
transcranial magnetic stimulation (TMS).
Results: Lower scores on SIS-Emotion
was associated with (1) frontal EEG power asymmetry in alpha and beta
bands, (2) central EEG power asymmetry in alpha and theta bands, and (3)
lower inter-hemispheric coherence over frontal and central areas in
alpha band. SIS-Emotion also correlated with higher ICF and MT in the
unlesioned hemisphere as measured by TMS.
Conclusions: To our knowledge, this is
the first study using EEG and TMS to index neurophysiologic changes
associated with post-stroke mood and emotional control. Our results
suggest that inter-hemispheric imbalance measured by EEG power and
coherence, as well as an increased ICF in the unlesioned hemisphere
measured by TMS might be relevant markers associated with post-stroke
mood and emotional control which can guide future studies investigating
new diagnostic and treatment modalities in stroke rehabilitation.
Introduction
Emotional disturbance is a common complication of stroke (Annoni et al., 2006). About 30% of stroke survivors develop anxiety and depressive symptoms critically affecting functional recovery (Parikh et al., 1990; Hackett and Anderson, 2005) and quality of life (Robinson, 1997; Jonsson et al., 2005). Moreover, a significant number of patients remain undetected and therefore untreated due to difficulties in diagnosis (Dafer et al., 2008; El Husseini et al., 2012; Ayerbe et al., 2013).
Investigation of neurophysiological markers associated with post-stroke
mood and emotional control could have important implications in the
development of new interventions as well as the assessment of current
diagnostic and therapeutic modalities in stroke rehabilitation. For
example, neurophysiologically guided interventions, such as EEG
biofeedback entrainment, has already been shown to be effective in
stroke patients with physical and cognitive impairments (Nelson, 2007).
Similarly in depression, qEEG has been used to detect inter-hemispheric
imbalance in cortical activity that has lead to the application of new
therapeutic approaches such as TMS (transcranial magnetic stimulation)
and tDCS (transcranial direct current stimulation; Rosenfeld et al., 1996; Linden, 2014).
The exact causes of post-stroke emotional disturbance
(PS-ED) are still unknown. Different mechanisms including direct effects
of ischemia to mood regulating neural networks (Starkstein et al., 1988; Beblo et al., 1999) and a psychosocial (Gainotti et al., 1999) model have been proposed to explain PS-ED (Whyte and Mulsant, 2002).
Additionally, several factors involving the severity of injury,
cognitive impairment, pre-morbid depression, disability and localization
of the stroke have been identified as predictors of PS-ED (Robinson, 1986; Hackett and Anderson, 2005; Ayerbe et al., 2013).
However, some of these factors were inconsistent across studies. For
example, earlier studies showed that left sided lesions that are close
to the frontal lobe have been associated with depression (Robinson, 1986) whereas more recent studies showed no relation between the localization of stroke and depression after stroke (Carson et al., 2000).
Quantitative electroencephalography (qEEG) is a safe,
cost-effective technique used to assess cortical activity and has been
valuable in assessing emotion related networks. Among the qEEG
parameters, frontal alpha power asymmetry has been especially of
interest given its relation to emotional processes and pathological
conditions such as major depressive disorder (MDD) and anxiety (Coan and Allen, 2004; Thibodeau et al., 2006; Harmon-Jones et al., 2010).
Yet, it is unknown whether emotional disturbance secondary to other
neurological conditions, such as stroke, is associated with similar EEG
changes. In fact, qEEG has already been used in stroke as a predictive
measurement for prognosis and clinical management in motor recovery (Finnigan and van Putten, 2013). However, use of qEEG in non-motor outcomes of stroke is limited (Schleiger et al., 2014) and to our knowledge there is no study assessing the qEEG correlates of post-stroke depression and anxiety.
Transcranial magnetic stimulation (TMS) is another
technique that is useful in assessing cortical activity in both MDD and
stroke. TMS studies assessing changes in cortical activity in patients
with MDD have shown decreased excitability in the left hemisphere (Maeda et al., 2000; Fitzgerald et al., 2004), and decreased motor threshold in the right hemisphere (Bajbouj et al., 2006). In stroke, TMS studies demonstrated that inter-hemispheric asymmetry in cortical activity (Murase et al., 2004) is associated with functional recovery after stroke (Hendricks et al., 2002). Therefore, together with EEG, TMS could potentially help elucidate changes in cortical activity related to PS-ED.
In this cross-sectional preliminary analysis of 35 stroke
subjects we investigated the associations between the emotion
sub-domain of Stroke Impact Scale (SIS-Emotion) and several
neurophysiologic measures obtained by EEG and TMS when adjusted for
potential confounders such as age and time since stroke. Given that
hemispheric asymmetry plays an important role in both stroke and mood
disorders, we hypothesized that post-stroke changes in mood and
emotional control is associated with inter-hemispheric imbalance that
can be indexed by EEG and TMS.
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