CHAPTER 3 DISCUSSION AND CONCLUSIONS
2. Alpha Rhythm Coherence
2.2. Alpha-band coherence and disease
In two groups of patients, alpha-band coherence revealed the disease-related changes of functional networks. Functional disconnections as well as pathologic increases of connectivity were identified.
The correlations of FC with behavioral test scores showed that different types of neural restructuring may take place, some of them positively and others negatively related to the functional deficits (Dubovik et al., 2012; Dubovik et al., 2013). We find that alpha-band coherence can capture network
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restructuring and might be therefore used in patients to investigate individual clinically relevant changes in functional networks. Four major observations support this statement:(1) Diffuse and focal brain lesions are associated with a disruption of cortical resting-state oscillation coherence in the alpha frequency range. In stroke patients we observed a significant decrease of alpha-band coherence in the lesioned hemisphere, while other frequency-bands remained unaffected (Figure 1 A). In patients with Alzheimer‟s disease, a decrease of alpha band connectivity corresponded to the regions known to be atrophic at early stages of the disease (Dubovik et al., 2013). These observations demonstrate that alpha coherence is particularly sensitive to functional disruptions in neural networks. In line with these observations, previous studies also reported lesion related reduction of alpha-band FC in patients with stroke (Westlake et al., 2012), tumors (Guggisberg et al., 2008; Martino et al., 2011) and in patients with Alzheimer‟s disease (Alonso et al., 2011). Specifically, studies in tumor patients showed that alpha-band coherence is able to distinguish between functional and damaged tissue in proximity of a tumor with high predictive value (Guggisberg et al., 2008; Martino et al., 2011). Together these findings indicate that alpha-band FC is a significant biological marker reflecting functional network disruptions induced by a lesion or a diffused neuronal loss.
(2) A decrease of alpha-band coherence does not simply retrace structural lesion, but captures global changes in functional network synchrony. The whole brain connectivity analyses in patients showed that alpha-band disruptions are not restricted to the lesioned area, but can also be observed in dysfunctional areas outside the lesion. Not only decreased, but also increased connectivity was found in remote from the lesion areas (Figure 2 A-B). These changes were specific to the alpha rhythm and could not be observed in other traditional frequency bands. Contralateral decreases of alpha connectivity were also reported in tumor patients (Guggisberg et al., 2008).
(3) Local changes in alpha-band coherence between a given brain area and the rest of the brain are linearly correlated with neurological deficits. A disconnection of a brain region in alpha range after stroke was a good predictor for the loss of corresponding behavior. Figure 3 demonstrates correlations of alpha band coherence with language, spatial attention, verbal memory and motor function in stroke patients (Dubovik et al., 2012). Reduced connectivity in the region was associated with the severity of the patient‟s behavioral impairment. Similar correlations were also found in our study on patients with Alzheimer‟s disease (Dubovik et al., 2013) and by other research groups in patients with schizophrenia (Hinkley et al., 2010).
Furthermore, intensive rehabilitation programs in stroke patients were shown to increase alpha band coherence between brain regions that underpin the trained function and the rest of the brain. Training-induced clinical improvements were linearly associated with corresponding increases in alpha-band coherence (Westlake et al., 2012).
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Voxel-wise linear correlation of resting-state functional connectivity of the patients with their performance in functional tests. Significant positive correlations (marked in red, p<0.05, cluster corrected) could be observed only in nodes known to be involved in the processing of the tested function (e.g., in the left inferior frontal gyrus around Broca's area for verbal fluency and verbal working memory). These positive correlations were unique to the alpha frequency band (graphs). Conversely, significant negative correlations (blue) with alpha band synchrony were found in the contralateral homologous counterparts (e.g., the right inferior frontal gyrus for verbal fluency/verbal working memory), which may be related to a reduction of interhemispheric inhibitory influences from the stroke-affected hemisphere. For correlations with the composite motor score, the maps of patients with right hemispheric lesions were flipped in order to align affected and unaffected sides, in addition to a separate analysis of right and left sided motor function of all patients.
In addition to these local decreases in alpha-band coherence, we also observed increases in the homologue contralateral counterparts. Coherence in these contralateral regions was also correlated with performance, demonstrating that this form of functional neural reconfiguration is functionally significant. Interestingly, its association with behaviour was different in stroke patients than that of the Alzheimer‟s disease patients. In patients suffering from Alzheimer‟s disease, an increase in alpha-band coherence in right inferior frontal gyrus (IFG) was beneficial for language function, whilst in stroke patients it revealed to be negatively correlated and therefore was associated with poor language performance (Figure 4 b-c). Several factors might influence this phenomenon. We can speculate that diverse natures and progressions of these diseases are responsible for this discrepancy. As a comparison, Figure 4a also demonstrates the correlation between alpha-band coherence magnitude and language fluency in healthy participants.
42 Figure 4
Voxel-wise linear correlation of resting-state FC in different groups with their performance in the verbal fluency test.
The mean FC of each voxel with all other voxels at different EEG frequencies was correlated with verbal fluency scores. Significant positive correlations (p<0.05, cluster corrected) are represented in red color, significant negative correlations in blue. The line charts on the right depict Pearson correlation coefficients of anatomical ROIs at each frequency bin. Note that peak correlations in all groups are found in the alpha frequency band. (a) In healthy participants, alpha band FC between Broca’s area (pIFG L) and the rest of the cortex correlated with high verbal fluency scores. (b) Similar positive correlation in stroke patients, but additionally negative association between mean FC of right pIFG and verbal fluency performance (c) FC maps of AD patients presented the exact opposite association with verbal fluency scores than the maps of the stroke group: high resting-state FC in Broca’s area was correlated with low test performance, while high FC values in the right pIFG corresponded to better test results.
(4) Alpha-band FC is a more relevant predictor of behavioral dysfunction than traditionally suggested variables (age, lesion size). Partial correlations in our studies confirmed that linear relationships between alpha rhythm FC and behavior were independent of demographic and clinical co-variables (Dubovik et al., 2012; Dubovik et al., 2013). Confirmative findings were also reported by other groups (Westlake et al., 2012).
Taken together, our results demonstrate an important link between resting state alpha-band FC and the neurological deficits in patients with brain pathologies. Moreover, they demonstrate that functional network restructuring taking place after brain lesions or as a result of brain disease can be studied by analysing alpha band coherence. FC in alpha frequency has the potential to serve as a reliable source of information for diagnostic and prognostic purposes.