Introduction: Disordered brain connectivity, generally defined as failure of effective functional integration within/between brain areas, is thought to be the core deficit in several mental health disorders. Functional connectivity is the term used to define the temporal synchrony or correlation among signals of two or more segregated regions. Most methods for assessing functional connectivity within EEG analysis investigate the phase-relationships between the signals from different scalp electrodes. The main drawback of most previous methods, however, is that volume conduction of the signal through cortical membranes, scalp and skin may introduce noise in the signal and bias accurate assessment of connectivity. The phase-lag index (PLI) is a new assessment method that discards volume conduction noise. The aim of this study was to investigate EEG functional connectivity, measured by PLI, in a large well-characterized population of patients with cirrhosis. Methods: The study population comprised of 268 patients with cirrhosis (174 men: 94 women: mean [range] age 55.3 [24-81] yr; 67% alcohol-related). The reference population comprised of 137 healthy individuals (73 men: 94 women; mean age 39.2 [17-75] years). Psychometric performance was assessed using the PHES battery. The raw PHES data were adjusted and scored using UK normative values and patients ranked by their composite final score into the following groups: PHES >0; PHES -2 to -0; PHES -4 to -2; and PHES <-4; composite scores of <2SD below mean reference values were considered abnormal. EEG recordings were undertaken for 10 minutes in a state of eyes-closed, relaxed, wakefulness. The PLI was calculated and divided into standardized frequency bands viz.: delta (1–4 Hz), theta (4–8 Hz), alpha (8–12 Hz) and beta (12–32 Hz), employing the implementation from The Neurophysiological Biomarker Toolbox (NBT) (http://www.nbtwiki.net/). Results: Significant EEG changes were observed in patients in whom the PHES would ordinarily be considered normal viz. PHES scores -2 to 0, compared to the reference population: Delta (0.139 ± 0.014 vs. 0.144 ± 0.014; P < 0.01), Alpha (0.141 ± 0.036 vs. 0.154 ± 0.036; P < 0.01) and Beta (0.065 ± 0.008 vs. 0.069 ± 0.011; P < 0.05). More pronounced changes, were observed with increasing psychometric impairment; viz. PHES scores -4 to -2: Delta (0.138 ± 0.012 vs. 0.144 ± 0.014; P < 0.01), Theta (0.117 ± 0.018 vs. 0.103 ± 0.009; P < 0.0001): Alpha (0.124 ± 0.026 vs. 0.154 ± 0.036; P < 0.0001) and Beta (0.062 ± 0.006 vs. 0.069 ± 0.011; P < 0.0001). No significant differences were observed, by cirrhosis aetiology. Significant correlations were observed between the results of the individual psychometric tests and functional connectivity in all but the delta band. Conclusion: Cortical connectivity is disturbed in patients with cirrhosis even when neuropsychometric performance is unimpaired. These finding attests to the spectral nature of the neuropsychiatric changes in this patient population and may provide a new and objective mean for assessments and early identification of clinically relevant hepatic encephalopathy; further validation is needed. The authors have none to declare.
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