Test–retest reliability of regional electroencephalogram (EEG) and cardiovascular measures in social anxiety disorder (SAD)

International Journal of Psychophysiology 84 (2012) 65–73

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Test–retest reliability of regional electroencephalogram (EEG) and cardiovascular measures in social anxiety disorder (SAD) Louis A. Schmidt a, b,⁎, Diane L. Santesso a, g, Vladimir Miskovic b, Karen J. Mathewson a, Randi E. McCabe c, d, Martin M. Antony e, David A. Moscovitch f,⁎⁎ a

Department of Psychology, Neuroscience & Behaviour, McMaster University, Canada McMaster Integrative Neuroscience Discovery and Study, McMaster University, Canada Anxiety Treatment and Research Centre, St. Joseph's Healthcare, Hamilton, Canada d Department of Psychiatry and Behavioural Neurosciences, McMaster University, Canada e Department of Psychology, Ryerson University, Canada f Department of Psychology, University of Waterloo, Canada g Centre for Arts and Technology, University of Waterloo, Canada b c

a r t i c l e

i n f o

Article history: Received 3 September 2011 Received in revised form 7 January 2012 Accepted 9 January 2012 Available online 24 January 2012 Keywords: Test–retest reliability Frontal EEG asymmetry Cardiac vagal tone Social anxiety disorder Psychometrics Stability

a b s t r a c t Although the search for psychophysiological manifestations of social anxiety has a rich history, there appear to be no published reports examining the reliability of continuous electrocortical measures that putatively index stress vulnerability and stress reactivity in socially anxious individuals. We examined the 1-week test–retest reliability of regional electroencephalogram (EEG) alpha asymmetry and power, respiratory sinus arrhythmia (RSA), heart period, and heart period variability measures at rest and during anticipation of an impromptu speech in 26 adults diagnosed with social anxiety disorder (SAD). Across the 1-week time period, we found medium-to-large correlations for regional EEG asymmetry and large correlations for regional EEG alpha power, RSA, heart period, and heart period variability measures at rest and during speech anticipation, before and after accounting for age and medication status. These results are similar to patterns observed in nonclinical samples and appear to provide the first documented evidence of test–retest reliability of psychophysiological measures that index central nervous system activity in socially anxious individuals. These findings also provide support for the notion that resting frontal EEG asymmetry and RSA constitute relatively stable individual differences in this clinical population. © 2012 Elsevier B.V. All rights reserved.

1. Introduction Social anxiety disorder (SAD) is characterized by extreme fear and avoidance of social and performance situations (American Psychiatric Association, 2000). With a lifetime prevalence estimated to be as high as 12%, SAD is the third most common psychological disorder (Kessler, Berglund, Demler, Jin, Merikangas, & Walters, 2005). SAD has an early onset, a chronic course, and a debilitating impact on quality of life in interpersonal, emotional, and occupational domains (Ledley and Heimberg, 2005). Similar to other anxiety disorders, SAD has been examined in terms of its behavioral, cognitive/affective, and physiological correlates. Although the search for psychophysiological manifestations of social anxiety has a long and rich history, this work has traditionally involved the collection of peripheral nervous system measures. These measures

⁎ Correspondence to: L.A. Schmidt, Department of Psychology, Neuroscience & Behaviour, McMaster University, Canada. ⁎⁎ Corresponding author. E-mail addresses: [email protected] (L.A. Schmidt), [email protected] (D.A. Moscovitch). 0167-8760/$ – see front matter © 2012 Elsevier B.V. All rights reserved. doi:10.1016/j.ijpsycho.2012.01.011

have included heart rate (Beidel et al., 1985, 1989; Borkovec et al., 1974; Cuthbert et al., 2003; Edelmann and Baker, 2002; Hofmann et al., 1995, 2006; Turner et al., 1986; Weerts and Lang, 1978; Wieser et al., 2009), skin conductance (Abrams and Wilson, 1979; Eckman and Shean, 1997; Cuthbert et al., 2003; Edelmann and Baker, 2002; Hofmann et al., 2006; Lader, 1967; Mauss et al., 2003; Werts and Lang, 1978; Wieser et al., 2009), startle EMG reactivity (Blumenthal et al., 1995; Cornwell et al., 2006; Hermann et al., 2002; Cuthbert et al., 2003; Panayiotou and Vrana, 1998) and blush/facial temperature (Edelmann and Baker, 2002; Hofmann et al., 2006) measured in clinical and nonclinical socially anxious adult populations. Overall, these studies have shown increased autonomic arousal at rest and during evaluative situations in this population. More recent studies have examined measures of central nervous system functioning, in addition to peripheral measures, including measures of regional EEG asymmetry (Beaton et al., 2008; Davidson et al., 2000; Schmidt, 1999; Schmidt and Fox, 1994), cross-frequency EEG coupling (Miskovic et al., 2010; Miskovic et al., 2011) and eventrelated potentials (ERPs) (Jetha et al., 2012; Kolassa and Miltner, 2006; Mueller et al., 2009; Sachs et al., 2004) in clinical and nonclinical populations of socially anxious adults and related profiles (see Miskovic

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and Schmidt, 2012, for a recent review). For example, increased right anterior EEG activity and heart rate during anticipation of public speaking has been reported in adults diagnosed with social anxiety (Davidson et al., 2000) and in a nonclinical sample of extremely shy children (Schmidt et al., 1999). Schmidt and his colleagues have also found that extremely shy and socially anxious individuals (without a clinical diagnosis) exhibited relatively greater right frontal EEG activity at rest (Beaton et al., 2008; Schmidt, 1999), greater relative left parietal EEG activity and lower heart period variability (e.g., lower RSA) in response to an anticipated unfamiliar social interaction (Schmidt and Fox, 1994) than their nonshy counterparts. In the present study, we were interested in establishing the test– retest reliability of regional EEG alpha asymmetry and power measures, particularly in the frontal region, at rest and during speech anticipation in adults with SAD. If greater relative right frontal EEG activity at rest and during evaluative situations is a valid putative measure of stress vulnerability (e.g., Schmidt, 1999) or stress reactivity (Davidson et al., 2000; Schmidt and Fox, 1994) in socially anxious adults (Davidson et al., 2000; Schmidt, 1999; Schmidt and Fox, 1994) and children (Schmidt et al., 1999), then these metrics should show acceptable levels of test–retest reliability within the same individuals at different testing points. Although the test–retest reliability of regional EEG alpha asymmetry and power measures has been well documented in nonclinical adult samples across time (McEvoy et al., 2000; Salinsky et al., 1991; Tomarken et al., 1992), across different contexts (Schmidt et al., 2003), and in some clinical populations, including adults with schizophrenia (Jetha et al., 2009) and depression (Allen et al., 2004; Vuga et al., 2006), the test–retest reliability of regional EEG alpha asymmetry and power measures in a clinical sample of socially anxious individuals has not been published to date. A second goal was to examine the test–retest reliability of multiple cardiac measures, including respiratory sinus arrhythmia (RSA), heart period, and heart period variability in SAD. Cardiac regulation may be assessed in terms of heart period (HP), heart period variability (HPV), and respiratory sinus arrhythmia (RSA). HP (the inverse of heart rate) is the net physiological outcome of competing innervation of the heart by the sympathetic and parasympathetic branches of the autonomic nervous system. HPV (the standard deviation of heart period) reflects the total combined output of multiple factors that influence chronotropic cardiac control—autonomic, endocrine, thermoregulatory, postural, etc. A large portion of HPV is attributable to RSA, a high-frequency irregularity that is centrally coordinated with respiratory cycles and reflected in cardiac vagal control (at typical breathing rates). When assessed during rest in nonclinical samples, measures of HPV index trait-like individual differences in basal autonomic control that are reproducible across time (Pitzalis et al., 1996). Higher resting HPV has been associated with optimal self-regulatory behavior (Porges, 1992; Thayer and Lane, 2000), cognitive performance (Thayer et al., 2009; Mathewson et al., 2010) and emotional regulation (Brosschot et al., 2007), whereas lower levels of resting HPV tend to be associated with less adaptive functioning (e.g., Friedman and Thayer, 1998; Hansen et al., 2004). Given the role of cardiac activity in stress vulnerability and reactivity in typical populations (e.g., Brosschot et al., 2006; Porges, 1995), clinical (e.g., Friedman, 2007; Thayer et al., 1996) and subsyndromal populations of socially anxious adults (Schmidt and Fox, 1994), we were particularly interested in determining whether RSA, which is commonly used to index phasic cardiac vagal control, was reliable in adults with SAD. Similar to the frontal EEG measures, if RSA is a valid putative measure of stress vulnerability and stress reactivity in social anxiety, then this metric should show acceptable test– retest reliability within the same individuals across time. Although the reliability of the RSA metric has been established in nonclinical adult samples (e.g., Kleiger et al., 1991), its reliability has not been established in SAD, although the reliability of other cardiac measures has been reported previously (Beidel et al., 1989; Borkovec et al.,

1974). For example, Borkovec and his colleagues noted medium-tolarge correlations in ECG responses across 2 to 4 weeks in a nonclinical sample of socially anxious males in response to interacting with a female confederate (Borkovec et al., 1974). In a clinical sample of adults with social anxiety disorder, Beidel et al. (1989) found medium-to-large correlations for baseline pulse rate and blood pressure measured separately between two time points across 1 week. We examined the test–retest reliability of regional EEG alpha asymmetry and power, RSA, heart period, and heart period variability at rest and during anticipation of an impromptu speech in a sample of adults diagnosed with SAD. We predicted that regional EEG alpha asymmetry and power, RSA, heart period, and heart period variability would all remain stable over a 1-week period during resting baseline and the impromptu speech. Demonstrating within-subject stability serves as an important source of validation that these measures do indeed reflect meaningful individual differences that may be of interest to clinical and personality research. 2. Method 2.1. Overview and participants The present study was part of a larger project examining the psychophysiology of cognitive behavioral therapy (CBT) in patients with SAD, in which we previously examined regional EEG coupling (see Miskovic et al., 2011) and asymmetry (see Moscovitch et al., 2011) changes during CBT. Here we examined and report the test– retest reliability of regional EEG alpha power and asymmetry and the three cardiac measures during two pre-treatment visits. Thirty-three, right-handed Caucasian outpatients (18 males, M = 36.3 years, SD = 15.1; 15 females, M = 33.4 years, SD = 11.2) from a large anxiety treatment clinic at an urban Canadian hospital participated in this study. All participants received a principal DSM-IV-TR (American Psychiatric Association, 2000) diagnosis of SAD (generalized subtype), as determined by trained clinicians on the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders-4th Edition (SCID-IV; First et al., 2001). Exclusion criteria included current mania, psychosis, significant suicidality, and organic brain disorders. Patients with current substance dependence were excluded if they could not agree to refrain from using substances prior to and during treatment and experimental protocols, were deemed by the clinical team to be unsuitable for group CBT targeting SAD, or required treatment for substance abuse. Clinical severity ratings (CSRs) were assigned on a 0 to 8 scale, with CSRs of 4 and above representing increasing levels of clinically significant interference and distress associated with the principal diagnosis. The CSRs for SAD diagnoses in the present sample ranged from 4 to 7 (M = 5.40, SD = 1.02). Patients were also assessed at Time 1 and Time 2 using the Social Phobia Inventory (SPIN; Connor et al., 2000), a 17-item self-report instrument measuring symptoms of social fear, avoidance and arousal, and the second edition of the Beck Depression Inventory II (BDI-II; Beck et al., 1996), a 21-item selfreport measure of common emotional and physiological symptoms of depression. Importantly, social anxiety symptom scores on the SPIN and depression scores on the BDI-II remained highly stable from Time 1 to Time 2, rSPIN (25) = 0.83, p b 0.001, and rBDI (25) = 0.90, p b 0.001, respectively. At Time 1 and Time 2, 58% (19/33) of the patients were receiving antidepressant and/or anti-anxiety medications, as patients were recruited from a community outpatient clinic situated within a hospital. 2.2. Procedure Participants completed two psychophysiological assessments as part of their pretreatment battery approximately 1 week (M = 7.7 days) apart. Procedures were identical across the two

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laboratory visits. Upon arrival at the laboratory, participants were given several minutes to acclimate to the testing environment, were briefed about the procedures, and written informed consent was obtained. Participants' EEG and ECG measures were then collected continuously during 6 min of rest, consisting of alternating three 1-minute eyes open and three 1-minute eyes closed epochs. Following the resting recording, participants were then given 3 min to prepare an impromptu speech on controversial topics that were relevant to the Canadian political context (e.g., capital punishment, same-sex marriage, funding of religious schools), and participants were informed that the speech was to be given in front of two female observers and recorded by a video camera. EEG and ECG were recorded (eyes open) during this 3-minute anticipatory period. Participants were next provided with the set of three predetermined speech topics, and they performed the public speaking task on any one or more of these topics for a maximum of 3 min. The participants were given different topics at each visit to eliminate practice effects. EEG and ECG were not collected during the speech itself. All laboratory procedures were conducted under the supervision of trained research staff and approved by the Hamilton Health Sciences and University of Waterloo Research Ethics Committees. 2.3. Psychophysiological data collection 2.3.1. EEG recording Regional EEG was recorded using a Lycra stretch cap (Electro-Cap International, Eaton, OH). Electrodes were positioned according to the International 10/20 Electrode System (Jasper, 1958). The experimenter used the blunt end of a cotton swab in combination with an abrasive gel to gently abrade the scalp at each electrode site. An electrolyte gel was applied to each site to act as a conductor. Electrode impedances were all below 10,000 Ω within and 500 Ω between homologous sites. EEG was recorded from 8 locations: left and right midfrontal (F3, F4), central (C3, C4), parietal (P3, P4), and occipital (O1, O2) regions. As the occipital EEG data were not the focus of our reliability analyses, these data were not analyzed. Electrodes were referenced to the central vertex (Cz) during recording. The signals were amplified using SA Instrumentation Bioamplifiers and bandpass filtered between 1 Hz (high pass) and 100 Hz (low pass). The signal from each channel was digitized on-line at a sampling rate of 512 Hz. 2.3.2. ECG recording ECG was recorded using two disposable electrodes placed on the participant's chest simultaneously with EEG. The ECG signal was amplified by an individual SA Instrumentation Bioamplifier. The ECG data were recorded at a sampling rate of 512 Hz and filtered between 0.1 Hz (high pass) and 1000 Hz (low pass). 2.4. Psychophysiological data reduction and analyses 2.4.1. EEG data reduction and analysis EEG data were visually scored for artifact due to eyeblinks, eye movements, and other movements using software developed by the James Long Company (EEG Analysis Program, Caroga Lake, NY). All artifact-free data were analyzed using a discrete Fourier transform (DFT), with Hanning window of 1 s width, with a 50% overlap. Regional EEG power (in μV 2) was derived in the alpha (8 to 13 Hz) frequency band separately for the EO and EC conditions. It is well documented that EEG alpha activity in frontal sites is linked to individual differences in stress reactivity and vulnerability (see Coan and Allen, 2004; Davidson, 2000). We included EEG activity in the central and parietal sites for purposes of regional comparison and because these sites, to a lesser extent, have also been linked to individual differences in affective style (Davidson et al., 1985; Henriques and Davidson, 1990; Schmidt and Fox, 1994; Theall-Honey and Schmidt,

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2006). A natural log (ln) transformation was performed on the EEG power values in order to reduce skewness. Because EEG power in the EO and EC conditions was highly correlated for each of the sites (rs > 0.89, ps b 0.001), a composite measure of resting EEG alpha power was computed separately for each EEG site by averaging power in the EO and EC conditions. This aggregate measure is known to produce a more reliable estimate of EEG power and asymmetry than separate EO and EC conditions (see Tomarken et al., 1992). 2.4.2. ECG data reduction and RSA quantification The eyes-open and eyes-closed segments of the resting condition were aggregated. A file of interbeat intervals (IBIs) was created on each participant for the 6-minute resting condition and the 3-minute speech anticipation condition, using James Long Company Software (IBI Analysis Program). The IBI data were visually edited for artifact (missing or spurious R-waves) and analyzed using the ECG Analysis software. This program also calculated the mean heart period and the standard deviation of the mean heart period (i.e., global heart period variability measures). We employed a spectral analysis approach in order to isolate RSA of cardiovascular function (Task Force of the European Society of Cardiology, 1996). The prorated time-series IBI data were detrended using a high-pass filter with a period of 10 s. A DFT analysis, with a 32-second Hanning window and 50% consecutive overlap, was then applied to quantify the amount of variability (ms 2) within the 0.12 to 0.40 Hz range (Berntson et al., 1997). This range reflects both peripheral vagal efferent activity and central respiratory control mechanisms (Berntson et al., 1997; Berntson et al., 1993) and is commonly used to assess high-frequency heart rate variability in adolescents and adults. High-frequency power values were transformed using a natural log (ln) transform to normalize the distribution, yielding estimates of RSA. The three-minute anticipation condition in our study was comparable to recordings used in some other studies (e.g., Berntson et al., 1996), where RSA was assessed during one-minute rest periods and one-minute on-task trials. 2.5. Data analyses In order to assess test–retest reliability for the individual EEG and ECG measures during resting baseline and speech anticipation, we performed four analyses: First, we computed separate matched-pair t-tests to compare the mean values on each EEG and ECG measures between Time 1 and Time 2. Second, we computed separate Pearson correlations on each EEG and ECG measure between Time 1 and Time 2. Third, we computed separate intraclass correlations on each EEG and ECG measure between Time 1 and Time 2. Intraclass correlations are sensitive to differences in rank order across the two time points, in addition to within-subject differences in absolute scores. Fourth, we computed correlations between Time 1 and Time 2, while controlling age and medication status by grouping those individuals who were taking medication versus those who were not, dummy coding medication status and partialling it out of the analyses. Age and medication were controlled because increased adult age is generally associated with reduced heart rate variability (Antelmi et al., 2004; Byrne et al., 1996). As well, evidence suggests that some medications for depression and anxiety may influence the pattern of regional brain activity in human and nonhuman primates. Davidson et al. (1992) reported reductions in EEG power particularly in the left frontal region in rhesus monkeys treated with diazepam, with good test–retest stability of EEG asymmetry measures between two testing periods separate by three months. Furmark et al. (2002) reported reductions in regional cerebral blood flow (rCBF) in the amygdala bilaterally and other limbic regions in response to public speaking in patients with social phobia who were treated with

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Table 1 Patient profiles (N = 26). Characteristic

Frequencies

Sex (M/F) Psychotropic medication (no/yes)

13/13 11/15 Mean (SD) range

Age SPIN (Time 1) SPIN (Time 2) BDI-II (Time 1) BDI-II (Time 2)

33.3 47.2 44.8 25.7 23.0

(11.0) (10.4) (10.6) (9.3) (10.1)

19 to 59 24 to 64 16 to 61 3 to 44 1 to 45

Note: SPIN = Social Phobia Inventory; BDI-II = Beck Depression Inventory (2nd ed); one participant was missing SPIN and BDI-II data at Time 1.

citalopram, and reductions of rCBF in the right hemisphere in treatment responders versus nonresponders. Heart rate variability is also known to be influenced by psychotropic medication status (e.g., Licht et al., 2009). Although age and medication status remained stable from Time 1 to Time 2, we took a conservative approach and removed any variance associated with these factors. Overall, the results remained the same with and without partialling age and medication status, both for the regional EEG alpha power and asymmetry measures and the three cardiovascular measures. All findings were reported on the basis of two-tailed tests. 2.6. Data loss Of the 33 patients tested, data from one patient were excluded because of a significant medication change between Time 1 and Time 2, and from another participant who was prescribed beta blockers, as these medications would be expected to influence ANS

functioning. An additional five patients were missing RSA data from the baseline condition due to the electrodes becoming detached, not enough artifact free useable data, and/or the participant refused the speech, leaving 26 participants with complete baseline EEG and ECG data to be included in the analyses. All remaining patients adhered to identical medications and dosages at Time 1 and Time 2. The proportion of patients receiving medications remained the same as the larger sample: 58% (15/26) of them were taking psychotropic medications at the beginning of treatment, with an average of 1.12 (SD = 1.4) medications per patient. Some patients (42%; 11/26) were taking selective serotonin reuptake inhibitors (SSRI) alone or in combination with other medications such as benzodiazepines or antipsychotic medications. Patient information for the analyzed sample is presented in Table 1. 3. Results 3.1. Test–retest reliability of regional EEG alpha power and asymmetry The matched-paired t-tests revealed that there were no statistically significant changes in mean values for the left and right frontal, central, and parietal EEG alpha power measures (ps > 0.05), nor frontal, central, or parietal alpha asymmetry measures (ps > 0.05) over the 1-week period for the resting baseline (see Table 2A) and speech anticipation (see Table 2B) conditions. These findings suggest that, overall, absolute EEG alpha power and asymmetry mean values remained stable across the 1-week period for resting baseline and speech anticipation conditions. The Pearson and ICC correlations revealed that there was excellent stability in absolute left and right frontal, central, and parietal EEG alpha power for the resting baseline (rs = 0.86 to 0.96, ps b 0.001; ICCs = 0.86 to 0.95, ps b 0.001; see Table 2A) and speech anticipation (rs = 0.85 to 0.91, ps b 0.001; ICCs = 0.85 to 0.91, ps b 0.001; see

Table 2 Mean (SD) and test–retest reliability coefficients across 1 week for left and right EEG alpha power and asymmetry measures in the frontal, central, and parietal regions during (A) resting baseline (i.e., eyes open and closed aggregated) and (B) speech anticipation (eyes open) conditions. Region/measure (A) Resting baseline Frontal F3 F4 Asymmetry Central C3 C4 Asymmetry Parietal P3 P4 Asymmetry (B) Speech anticipation Frontal F3 F4 Asymmetry Central C3 C4 Asymmetry Parietal P3 P4 Asymmetry

Time 1 mean (SD)

Time 2 mean (SD)

T1 to T2 t-value

Pearson correlation

Intraclass correlation

Partial correlation

0.95 (1.37) 0.93 (1.37) − 0.02 (0.11)

0.73 (1.31) 0.75 (1.26) 0.02 (0.13)

1.62 1.30 − 1.69

0.87⁎⁎⁎ 0.86⁎⁎⁎ 0.45⁎

0.86⁎⁎⁎ 0.86⁎⁎⁎ 0.42⁎

0.87⁎⁎⁎ 0.87⁎⁎⁎ 0.40⁎

0.44 (1.42) 0.53 (1.39) 0.09 (0.29)

0.29 (1.36) 0.40 (1.31) 0.11 (0.20)

1.57 1.37 − 0.42

0.94⁎⁎⁎ 0.94⁎⁎⁎ 0.51⁎⁎

0.94⁎⁎⁎ 0.93⁎⁎⁎ 0.49⁎⁎

0.94⁎⁎⁎ 0.94⁎⁎⁎ 0.52⁎⁎

1.34 (1.33) 1.50 (1.33) 0.16 (0.29)

1.19 (1.29) 1.35 (1.27) 0.16 (0.28)

1.89 1.78 0.07

0.96⁎⁎⁎ 0.95⁎⁎⁎ 0.68⁎⁎⁎

0.95⁎⁎⁎ 0.94⁎⁎⁎ 0.69⁎⁎⁎

0.96⁎⁎⁎ 0.95⁎⁎⁎ 0.64⁎⁎⁎

0.82 (1.37) 0.82 (1.32) 0.003 (0.12)

0.63 (1.34) 0.66 (1.29) 0.03 (0.15)

1.34 1.13 − 0.75

0.87⁎⁎⁎ 0.85⁎⁎⁎ 0.26

0.87⁎⁎⁎ 0.85⁎⁎⁎ 0.27

0.88⁎⁎⁎ 0.86⁎⁎⁎ 0.25

0.35 (1.36) 0.43 (1.31) 0.08 (0.24)

0.23 (1.40) 0.32 (1.31) 0.09 (0.21)

0.97 1.01 − 0.18

0.90⁎⁎⁎ 0.91⁎⁎⁎ 0.49⁎

0.90⁎⁎⁎ 0.91⁎⁎⁎ 0.50⁎⁎

0.90⁎⁎⁎ 0.91⁎⁎⁎ 0.50⁎

1.00 (1.21) 1.13 (1.21) 0.12 (0.22)

0.94 (1.29) 1.03 (1.26) 0.09 (0.22)

0.52 0.79 0.85

0.89⁎⁎⁎ 0.89⁎⁎⁎ 0.67⁎⁎⁎

0.89⁎⁎⁎ 0.89⁎⁎⁎ 0.67⁎⁎⁎

0.89⁎⁎⁎ 0.89⁎⁎⁎ 0.66⁎⁎⁎

Note: N = 26; all power values are natural log transformed; asymmetry = ln right hemisphere minus ln left hemisphere; t-value is reported for tests of differences between Time 1 and Time 2; intraclass correlation confidence interval = 95%; in partial correlations, variance attributable to medication status was removed. One participant was missing EEG Speech Anticipation data at Time 1. All correlations are two-tailed. ⁎⁎⁎ p b 0.001. ⁎⁎ p b 0.01. ⁎ p b 0.05.

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Table 2B) conditions. These findings also suggest that individuals' left and right regional EEG alpha power scores and ranking remained stable across the week for resting baseline and speech anticipation conditions. Additional Pearson and ICC correlations revealed that there was also good stability in frontal, central, and parietal EEG alpha asymmetry at resting baseline (rs = 0.45 to 0.68, ps b 0.05 to b0.001; ICCs = 0.42 to 0.69, ps b 0.05 to b0.001; see Table 2A) and good stability in central and parietal EEG alpha asymmetry during the speech anticipation condition (rs = 0.49 and 0.67, ps b 0.05 and b0.001, respectively; ICCs = 0.50 and 0.67, ps b 0.01 and b0.001, respectively; see Table 2B) over the 1-week period. These findings suggest that individuals' regional EEG alpha asymmetry scores and

(A) Baseline (EOC)

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ranking remained stable for resting baseline, although frontal measures of asymmetry were relatively less reliable during speech anticipation across the 1-week period. We also examined the zero order correlations for the regional EEG alpha power and asymmetry measures from Time 1 to Time 2, controlling for medication status. The partial correlations for regional EEG alpha power and asymmetry measures from Time 1 to Time 2 for the resting baseline and speech anticipation conditions are presented in Table 2A and B, respectively. The partial correlations for the regional EEG alpha asymmetry measures from Time 1 to Time 2 for the resting baseline and speech anticipation conditions are also illustrated in Fig. 1A and B, respectively.

(B) Anticipation (EO)

pr(23) = .40, p < .05

pr(22) = .25, p > .20

pr(23) = .52, p < .01

pr(22) = .50, p < .05

pr(23) = .64, p < .001

pr(22) = .66, p < .001

Fig. 1. Scatterplots of the relations between regional (frontal, central, parietal) EEG asymmetry at Time 1 and Time 2 separately for baseline resting (eyes open/eyes closed [EOC]) and speech anticipation (eyes open [EO]) conditions, with medication status covaried out. Note: EEG data from the anticipation condition at Time 1 were unavailable for one participant.

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As can be seen in Fig. 1A and B, the pattern of regional EEG alpha asymmetry remained stable across the two time points after controlling for medication status, with the notable exception of frontal EEG alpha asymmetry in response to the speech task.

3.2. Test–retest reliability of RSA, heart period, heart period variability The matched-paired t-tests revealed that there were no changes in mean values for the RSA and heart period variability measures (ps > 0.15) across the 1-week period for both the resting baseline (see Table 3A) and speech anticipation (see Table 3B) conditions. However, heart period was reduced (i.e., heart rate was increased) at Time 2 for both conditions (ps b 0.02). These findings suggest that the mean RSA and heart period variability values remained stable over the 1-week period for resting baseline and speech anticipation conditions, but appeared to be less reliable for heart period. To interpret the condition effect for HP, we carried out three more comparisons. At Time 1, as expected, HP declined significantly from baseline (M = 848 ms, SD = 131) to the speech anticipation condition (M = 839 ms, SD = 143), t(24) = 2.11, p b 0.05. However, at Time 2, there was no such decline in HP between conditions, t(25) = 0.76, p > 0.45. Moreover, baseline HP at Time 2 (M = 792 ms, SD = 126) was marginally shorter than HP during the speech anticipation condition at Time 1, t(24) = − 1.89, p b 0.08. This pattern of findings suggests that at Time 2, socially anxious participants may have anticipated the upcoming speech even during the resting baseline. In contrast to the t-tests, the Pearson and ICC correlations revealed that there was good to excellent reliability in RSA, heart period, and heart period variability for the resting baseline (rs = 0.70 to 0.86, ps b 0.001; ICCs = 0.63 to 0.85, ps b 0.001; see Table 3A) and speech anticipation (rs = 0.78 to 0.87, ps b 0.001; ICCs = 0.72 to 0.87, ps b 0.001; see Table 3B) conditions over the 1-week period. These findings suggest that the scores and ranking of all three autonomic variables remained stable over the 1-week period for resting baseline and speech anticipation. We also examined the zero order correlations for the three autonomic measures from Time 1 to Time 2, controlling for age and medication status. The partial correlations for RSA, heart period, and heart period variability from Time 1 to Time 2 for the resting baseline and speech anticipation conditions are presented in Table 3A and B, respectively. The partial correlations for the three autonomic measures from Time 1 to Time 2 for the resting baseline and speech anticipation conditions are also illustrated in Fig. 2A and B, respectively. As can be seen in Fig. 2A and B, the pattern of RSA, heart period, and heart period variability remained stable across the two time points after controlling for age and medication status.

4. Discussion We found excellent test–retest reliability in measures of regional EEG alpha power and good test–retest reliability in regional EEG asymmetry measures during baseline and speech anticipation in adults diagnosed with SAD. Our regional EEG asymmetry and power findings are consistent with other published studies examining the test–retest reliability of regional EEG alpha power and asymmetry in nonclinical adults (Tomarken et al., 1992) and clinical samples of adults with depression (Allen et al., 2004; Vuga et al., 2006) and schizophrenia (Jetha et al., 2009). The present results extend these earlier findings to a sample of adults diagnosed with social anxiety disorder. Although the pattern of resting frontal EEG alpha asymmetry remained modestly stable across the 1 week period, the pattern of frontal EEG alpha asymmetry during the speech task was not stable. There appear to be at last three plausible explanations for the lack of stability that are inter-related. One explanation is that the pattern of frontal EEG alpha asymmetry may reflect different aspects of personality and emotion depending on how it is conceptualized and measured. Resting or tonic frontal EEG alpha asymmetry has been conceptualized as more “trait-like” and is perhaps less open to change in some circumstances and individuals at least in the short-term. Henrique and Davidson (1990) found that adults with clinical depression still exhibited greater relative right frontal EEG alpha asymmetry at rest even when their depressive symptoms were in remission. On the other hand, the pattern of frontal EEG activity in response to stressors or phasic patterning may be more “state-like” and perhaps more modifiable and/or susceptible to environmental input at least in the short-term. A second possibility is that the laboratory visit at Time 2 may have been more familiar to the participants and they became more comfortable than at Time 1. Accordingly, the state-related measure of frontal EEG asymmetry at Time 2 may have reflected this familiarity. A third explanation may have been due to medication effects. Although the two visits were separated by only one week, medication type and dosage remained stable, and the anxiolytic medications are slow acting, it is possible that there are individual differences in the efficacy of these medications and different time tables to their effectiveness that might have biased state-like measures of frontal EEG during the speech, but did not have the same time course and/or effect on trait-like (i.e., baseline resting) measures of frontal EEG. We also found excellent test–retest reliability in the correlations between Time 1 and Time 2 for measures of RSA and heart period variability for both the resting baseline and a more active condition, speech anticipation. These results suggest that at the level of individual differences, all three cardiac variables were reliable. The heart

Table 3 Mean (SD) and test–retest reliability coefficients across 1 week for respiratory sinus arrhythmia (RSA, 0.12 to 0.40 Hz), heart period (HP), and heart period variability (HPV) measures during (A) resting baseline (i.e., eyes open and closed aggregated) and (B) speech anticipation (eyes open) conditions. Measure

Time 1 mean (SD)

Time 2 mean (SD)

T1 to T2 t-value

Pearson correlation

Intraclass correlation

Partial correlation

(A) Resting baseline RSA (ln ms2) HPV (ms) Heart period (ms)

6.02 (1.60) 45 (23) 848 (139)

5.82 (1.45) 42 (23) 792 (126)

1.22 1.23 2.75⁎

0.86⁎⁎⁎ 0.82⁎⁎⁎ 0.70⁎⁎⁎

0.85⁎⁎⁎ 0.82⁎⁎⁎ 0.63⁎⁎⁎

0.84⁎⁎⁎ 0.77⁎⁎⁎ 0.70⁎⁎⁎

(B) Speech anticipation RSA (ln ms2) HPV (ms) Heart period (ms)

6.09 (1.55) 53 (34) 839 (143)

5.85 (1.70) 52 (28) 791 (127)

1.43 0.33 2.64⁎

0.87⁎⁎⁎ 0.85⁎⁎⁎ 0.78⁎⁎⁎

0.87⁎⁎⁎ 0.84⁎⁎⁎ 0.72⁎⁎⁎

0.87⁎⁎⁎ 0.81⁎⁎⁎ 0.77⁎⁎⁎

Note: N = 26; RSA = Respiratory Sinus Arrhythmia; HPV = Heart Period Variability; RSA values are natural log-transformed; t-value is reported for tests of mean differences between Time 1 and Time 2; intraclass correlation confidence interval = 95%; in partial correlations, variance attributable to age and medication status was removed. One participant was missing cardiac data from the Speech Anticipation condition at Time 1. All correlations are two-tailed. ⁎⁎⁎ p b 0.001. ⁎ p b 0.05.

L.A. Schmidt et al. / International Journal of Psychophysiology 84 (2012) 65–73

(A) Baseline (EOC)

pr(22) = .84, p < .001

pr(22) = .77, p < .001

pr(22) = .70, p < .001

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(B) Anticipation (EO)

pr(21) = .87, p < .001

pr(21) = .81, p < .001

pr(21) = .77, p < .001

Fig. 2. Scatterplots of the relations between autonomic variables (RSA, HPV, or HP) at Time 1 and Time 2 separately for baseline resting (eyes open/eyes closed [EOC]) and speech anticipation conditions (eyes open [EO]), with age and medication status covaried out. Note: HPV and HP data for one patient and RSA data for two patients from the anticipation condition at Time 1 were unavailable.

period findings were consistent with previous reports of stability in clinical (Beidel et al., 1989) and nonclinical (Borkovec et al., 1974) samples of socially anxious adults over 1 week and 1 month time periods. Findings of stability in HPV and RSA in adults with social anxiety complement earlier work with typically developing adults (Kleiger et al., 1991; Pitzalis et al., 1996) and are consistent with results in adults with general anxiety disorder (Thayer et al., 1996). However, while the strong correlations indicated that the rank order of HP was preserved across Time 1 and Time 2 among the individuals within our sample, HP in the group as whole decreased (heart rate was faster) in the second testing session relative to the first for both the baseline and speech anticipation conditions. These

condition effects suggested that having prepared and delivered a speech at Time 1, socially anxious patients knew what to expect and may have experienced higher arousal in anticipation of the upcoming demands of the testing session. That is, as reflected in HP, both conditions at Time 2 represented speech anticipation conditions. While measures of HP, HPV and RSA in this population appeared to be equally reliable at the level of individual differences, HP appeared to be more sensitive than the variability measures to condition effects. Inherent in the notion that resting frontal EEG asymmetry and RSA are valid indices of individual differences in affective style is the assumption that these measures remain stable within individuals across time. Therefore, the first step in addressing the validity of

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psychophysiological measures is to examine their psychometric properties to confirm their reliability (Kamarck, 1992; Strube, 1990). Previous studies have shown that measures of right frontal EEG activity (Beaton et al., 2008; Schmidt, 1999) and reduced cardiac vagal control (Brosschot et al., 2006; Porges, 1995) may reflect stress vulnerability, while increases in right frontal activity and heart rate during socially evaluative situations (Davidson et al., 2000; Schmidt and Fox, 1994; Schmidt et al., 1999) may reflect stress reactivity in socially anxious individuals. Similar to nonclinical studies, the present findings suggest that frontal EEG asymmetry and RSA at rest and frontal EEG power and RSA during speech anticipation are reliable across time in SAD. The present findings also suggest that the pattern of frontal EEG asymmetry and RSA at rest might be reliable measures of individual differences of stress vulnerability in SAD. There are also two limitations worthy of discussion. First, our findings were based on a relatively small sample. Although small samples are common with clinical studies, future work needs to replicate the present results with larger and more homogeneous sample sizes in terms of sex and age. Second, a majority of our participants were on medication. Although we did control the type and dosage of medication during the course of study and medication type and dosage remained stable, it is possible that medication may have contributed artificially to our stability and/or had a deleterious influence on it in some cases. Although drug naïve studies are difficult to do with clinical populations for obvious ethical reasons, future studies should consider enlisting and psychophysiological testing of individuals who are on the same type of medication and/or across shorter time points before the drug(s) become active. Although it has long been recognized that anxiety disorders manifest on behavioral, cognitive/subjective, and physiological levels (Beidel et al., 1985; Lang, 1977), studies involving the former two components disproportionately outnumber the latter component in empirical research. The results of the present study documenting test–retest reliability of resting frontal EEG alpha asymmetry and power and cardiac regulation and their putative role in stress vulnerability and reactivity support the use of these psychophysiological measures in future studies as meaningful individual difference factors and/or endophenotypes in understanding social anxiety (see, e.g., Segalowitz and Schmidt, 2008). Acknowledgments This research was supported by operating grants from the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Social Science and Humanities Research Council of Canada (SSHRC) awarded to Louis A. Schmidt; a Vanier doctoral scholarship from NSERC awarded to Vladimir Miskovic under the direction of Louis A. Schmidt; and an Ontario Mental Health Foundation New Investigator Fellowship and funding from the Canada Research Chairs Program awarded to David A. Moscovitch. We wish to thank Sue McKee and Jessica Senn for their help with data collection and data entry and to the clinicians and staff at the Anxiety Treatment and Research Centre at St. Joseph's Healthcare for their support. References Abrams, D.B., Wilson, G.T., 1979. Effects of alcohol on social anxiety in women: cognitive versus physiological processes. Journal of Abnormal Psychology 88, 161–173. Allen, J.J.B., Urry, H.L., Hitt, S.K., Coan, J.A., 2004. The stability of resting frontal electroencephalographic asymmetry in depression. Psychophysiology 41, 269–280. American Psychiatric Association, 2000. Diagnostic and Statistical Manual of Mental Disorders, (4th Edition Test—Revised). Author, Washington, DC. Antelmi, I., Silva da Paula, R., Shinzato, A.R., Peres, C.A., Mansur, A.J., Grupi, C.J., 2004. Influence of age, gender, body mass index, and functional capacity on heart rate variability in a cohort of subjects without heart disease. The American Journal of Cardiology 93, 381–385. Beaton, E.A., Schmidt, L.A., Ashbaugh, A.R., Santesso, D.L., Antony, M.M., McCabe, R.E., 2008. Resting and reactive frontal brain electrical activity (EEG) among a

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