Clinical Psychology and Special Education
2020. Vol. 9, no. 3, 105–126
doi:10.17759/cpse.2020090308
ISSN: 2304-0394 (online)
Case Series of Transcranial Direct Current Stimulation as an Augmentation Strategy for Attention Bias Modification Treatment in Adolescents with Anxiety Disorders
Abstract
General Information
Keywords: anxiety, adolescents, attention bias modification, transcranial direct current stimulation, neuromodulation, electroencephalography (EEG), event related potential (ERP)
Journal rubric: Empirical Research
Article type: scientific article
DOI: https://doi.org/10.17759/cpse.2020090308
Funding. The reported study was funded by the National Institutes of Health (R25 GM061347, UH2 MH101470, and R01 MH119299). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health
Acknowledgements. The authors gratefully acknowledge Dr. Greg Hajcak for his contributions to this study
For citation: Vaclavik D., Bechor M., Foster A., Gralnik L.M., Bar-Haim Y., Pine D.S., Bikson M., Silverman W.K., Reeb-Sutherland B.C., Pettit J.W. Case Series of Transcranial Direct Current Stimulation as an Augmentation Strategy for Attention Bias Modification Treatment in Adolescents with Anxiety Disorders [Elektronnyi resurs]. Klinicheskaia i spetsial'naia psikhologiia = Clinical Psychology and Special Education, 2020. Vol. 9, no. 3, pp. 105–126. DOI: 10.17759/cpse.2020090308.
Full text
Introduction
Despite the established efficacy of cognitive behavioral therapy (CBT) and antidepressant medications for the treatment of anxiety disorders in adolescents, treatment protocols are lengthy, and up to one-half of anxious adolescents do not respond well to treatment [15; 53; 59]. This highlights the need for alternative, brief, and efficacious treatments. In this case series, we present data on Attention Bias Modification Treatment (ABMT) augmented with transcranial Direct Current Stimulation (tDCS) as an alternative, brief treatment for anxiety in adolescents.
Behavioral and neuroscience research
extensively documents that adolescents with anxiety disorders show heightened
attention to threat such as angry faces [3; 17; 59]. Neural regions
corresponding to attentional processes develop rapidly during adolescence,
suggesting a developmental window of opportunity for delivering treatments that
target these neural regions subserving attention to threat. The most commonly
used paradigm for assessing attention to threat has been through behavioral
responses (i.e., reaction times) to a visual probe dot-probe task. Research
using behavioral responses to the dot-probe task provides support for an
association between attention bias to threat and anxiety (for reviews see [24;
37]); however, behavioral responses calculated from reaction times are
a distal measure of attention, evidenced by poor internal consistency and
test-retest reliability [10; 29; 45; 48]. Event-related potentials (ERPs), the
neural activation in response to a discrete event, are a common measure for
assessing the chronometry
of neural activity in relation to attention [54] and provide a more proximal
measure of attention to threat than traditional behavioral reaction time
measures [36].
Evidence supports ERP components P1, P2, and P3
as potential neural measures of attention to threat [2; 19; 41; 54; 57]. P1 and
P2 represent early stage processes involved in attention orienting and
detection of threat [27; 31], whereas P3 represents later
stage processes involved in the strategic regulation of attention (i.e.,
attentional control [18; 26; 49]).
ABMT is the translational treatment implication of heightened attention to threat that shows promise for reducing anxiety and its disorders (e.g., [21; 32; 35], including in adolescents [34; 39; 42; 44]. Despite the promise of ABMT, effect sizes on changes in attention to threat and anxiety symptom severity are usually small to medium in samples of children and adolescents with anxiety disorders (for reviews see [32; 34; 37; 46]). These small to medium effect sizes highlight the critical need for novel therapeutics that could be used as augmentation strategies to reduce attention to threat and enhance the anxiety reducing effects of ABMT.
Advances in the neural underpinnings of attention to threat
and attention training suggest that tDCS of the dorsolateral prefrontal cortex
(dlPFC) may enhance the effects of ABMT [14; 24; 25]. tDCS is a noninvasive
technique that facilitates spontaneous neuronal activity and plasticity in
specific areas of the brain by applying electrical current to corresponding
regions of the scalp [7; 13]. Heightened attention to threat signals
corresponds to perturbations in amygdala-prefrontal cortex (PFC) circuitry. The
amygdala facilitates vigilance through rapid threat processing, whereas the
ventro- and
dorsolateral PFC (vlPFC and dlPFC) facilitate regulation of attentional
deployment to threat [20; 22; 23; 56]. ABMT targets neural circuitry subserving
attention to threat [9; 11; 55; 60], and tDCS of the dlPFC enhances neuronal
activity and plasticity [7; 28; 50]. Thus, it is reasonable to expect that tDCS
of the dlPFC during ABMT (ABMT + tDCS) would enhance ABMT’s effects.
Data from two studies support this expectation [14; 24]. In Clarke et al., 77 nonreferred college students with trait anxiety in the middle quartiles of a sample distribution were randomly assigned to either anodal tDCS of the dlPFC or sham stimulation while completing a single ABMT session [14]. Participants who received active stimulation showed significant changes in attention to threat in the expected direction compared to participants who received sham stimulation. In Heeren et al., 56 nonreferred college students with elevated trait anxiety were randomly assigned to anodal tDCS of the dlPFC, cathodal tDCS to inhibit activity of the dlPFC, or sham stimulation while completing a single ABMT session [24]. Compared to participants who received cathodal or sham stimulation, participants who received anodal tDCS of the dlPFC displayed significant reductions in attention to threat. Together these data from single sessions in nonreferred samples show that stimulation of the dlPFC enhances ABMT effects on attention to threat. However, neither of these studies used a sample of clinic-referred adolescents with anxiety disorders, used a standard multi-session protocol of ABMT, or reported on anxiety outcomes.
The purpose of the present case series was to examine the feasibility, acceptability, and clinical promise of tDCS of the dlPFC as an augmentation strategy for a standard multi-session ABMT protocol in referred adolescents who met criteria for anxiety disorder diagnoses. We hypothesized that participants and their parents would find the treatment acceptable and that participants would experience reductions in anxiety severity and attention to threat, as indicated by lower amplitudes on P1, P2, and P3 ERP components during the presentation of angry faces on the dot-probe task. Such data lay the groundwork for further testing and clinical administration of ABMT + tDCS.
Research Program
Participants
For study inclusion, participants had to be between the ages of 13 and 17 and were required to meet criteria for a primary Diagnostic and Statistical Manual of Mental Disorders-4th Edition (DSM-IV [1]) diagnosis of Social Phobia/Anxiety Disorder (SOP) or Generalized Anxiety Disorder (GAD) using the Anxiety Disorders Interview Schedule for Children (Child and Parent Versions; ADIS-IV:C/P [52]). Exclusionary criteria were (1) organic mental disorders, psychotic disorders, pervasive developmental disorders or attention deficit hyperactivity disorder, (2) severe risk of suicide, (3) serious and uncorrected vision problems, (4) physical disability that would interfere with ability to perform the dot probe task, (5) left-handedness or ambidexterity, (6) current psychotropic medication, and (7) seizure disorder or recent traumatic brain injury.
Participants were recruited from a university-based outpatient clinic specializing in the treatment of child and adolescent anxiety in a large urban area. Ten families on the clinic’s waitlist were identified and contacted by telephone to share information about this study. The parents of all 10 adolescents expressed interest in participating. One adolescent declined due to distance and travel time, and three adolescents declined without providing a reason. These four adolescents also declined clinical services unrelated to a research study (i.e., cognitive behavioral therapy) and never came to our clinic for an intake assessment. The remaining six families consented to participate (i.e., parents provided informed consent and adolescents provided assent) and completed the pretreatment assessment. Age, sex, and diagnoses for each participant are provided in Table 1. Four participants identified as white Hispanic/Latino and two identified as non-Hispanic white.
Table 1
Demographic, diagnostic, and symptom data
Sex |
Age |
DSM-IV-TR Diagnoses |
ADIS Impairment Ratings |
PARS |
SCARED |
CSQ |
|||||||||
|
|
|
Parent |
Parent |
Child |
Child |
|
Parent |
Parent |
Child |
Child |
Parent |
Child |
||
|
|
PRE |
POST |
PRE |
POST |
PRE |
POST |
PRE |
POST |
PRE |
POST |
PRE |
POST |
POST |
POST |
F |
14 |
SAD |
SAD |
6 |
4 |
6 |
4 |
14 |
12 |
10 |
10 |
60 |
37 |
31 |
16 |
F |
16 |
GAD |
GAD |
5 |
- |
7 |
4 |
17 |
14 |
37 |
13 |
42 |
44 |
32 |
26 |
F |
15 |
SAD |
SAD |
4 |
4 |
4 |
- |
13 |
10 |
5 |
12 |
21 |
24 |
29 |
28 |
M |
16 |
GAD |
No Dx |
- |
- |
7 |
- |
22 |
9 |
26 |
15 |
46 |
34 |
31 |
32 |
F |
16 |
SAD |
SAD |
6 |
8 |
7 |
7 |
23 |
19 |
53 |
60 |
68 |
56 |
19 |
18 |
F |
14 |
SAD |
SAD |
8 |
6 |
7 |
7 |
25 |
24 |
45 |
39 |
41 |
52 |
29 |
18 |
Notes. SAD – Social Anxiety Disorder; GAD – Generalized Anxiety Disorder; No Dx – diagnosis was not endorsed by neither parent nor child. ADIS – Anxiety Disorders Interview Schedule for Children; PARS – Pediatric Anxiety Rating Scale; SCARED – Screen for Child Anxiety Related Emotional Disorders; CSQ – Client Satisfaction Questionnaire. F – Female; M – Male. PRE – pretreatment; POST – posttreatment.
Procedures
This study was conducted as approved by the
Institutional Review Board. Participants were compensated for their time
completing the assessments. Participants completed a pretreatment assessment to
determine anxiety diagnosis and severity, as well as to obtain a baseline
measure of attention bias to threat. Participants then completed four weekly
treatment sessions (ABMT + tDCS; described below), and a posttreatment
assessment conducted one week after treatment sessions finished, all at the
university clinic. Acceptability, feasibility, and satisfaction were measured
by the (1) number of eligible families who consented to participate, (2) number
of adolescent participants who completed the study, (3) adverse effects and
acclimation to stimulation, and (4) adolescent and parent ratings of
satisfaction with treatment. Neural resources allocated to nonthreatening and
threatening stimuli (i.e., attention to threat) were measured using event
related potentials (ERPs) during an emotional faces dot-probe task [5; 19;
54].
A multi-informant anxiety outcome assessment was conducted, which included
clinician-, parent-, and adolescent self-ratings of anxiety symptom severity
and impairment.
Attention Bias Modification Treatment (ABMT). The ABMT protocol (TAU-NIMH ABMT initiative) was the same as has been used in previous studies of ABMT in children and adolescents [42; 43]. The training protocol is identical to the attention to threat measurement (i.e., dot-probe) task with three exceptions: (1) a different set of faces was used during treatment than during measurement; (2) each block consisted of 160 trials instead of 240 during measurement, presenting 120 angry–neutral and 40 neutral–neutral combinations, with two consecutive blocks completed per treatment session; and (3) the probe replaced the neutral face on 100% of trials to establish a training contingency between neutral face location and probe location. On average, completion of the training protocols took participants 15 minutes.
Transcranial Direct Current Stimulation (tDCS). tDCS was administered using a Soterix 1X1 tDCS Limited Total Energy (LTE) Stimulator while adolescent participants completed the ABMT protocol at each session. Direct current was transferred via two 5 cm x 5 cm conductive silicone electrodes each within a disposable 5 cm x 7 cm saline-soaked (6 ml per side) sponge pouch. The anodal (active) electrode was secured over the left dlPFC, localized using F3 on the 10/20 international EEG system, and the cathodal (reference) electrode was secured over the contralateral supra-orbital area [24]. The intensity of tDCS was 1 mA with a 30 sec ramp up/down time. Stimulation began two minutes before the initiation of the ABMT protocol to allow for a ramp up period and acclimation to stimulation before training began. Stimulation was administered continuously for 20 minutes after ramp up. Once the full intensity (1 mA) was reached and adolescents had two minutes to acclimate, the ABMT protocol began. In cases where adolescents reported adverse effects/discomfort that did not abate during the two-minute period, we extended the acclimation period until discomfort ceased or an additional five minutes had passed. At the end of the additional five minutes, the ABMT protocol was initiated and tDCS was administered at 1 mA or the maximum intensity tolerable to the adolescents (e.g., 0.8 mA). Participants were instructed that they could discontinue at any time.
Measures
Anxiety Diagnosis, Impairment,
and Symptom Severity.Youth anxiety disorders were assessed using the
Anxiety Disorders Interview Schedule for Children, Child /Parent Versions
(ADIS-IV: C/P [51]). The ADIS was administered independently to parent and
adolescent. Anxiety-related impairment was assessed using a severity/impairment
rating scale as reported by each informant, scored from 0 to 8. A
severity/impairment rating
≥ 4 was used as a clinical cutoff of impairment for diagnosis. Youth anxiety
symptom severity was assessed using clinician ratings on the Pediatric Anxiety
Rating Scale (PARS [47]) and adolescent and parent ratings on the Screen for
Child Anxiety Related Emotional Disorders – Child/Parent Versions (SCARED-C/P
[8]). All anxiety measures were administered by trained and supervised
psychology doctoral students.
tDCS Adverse Effects.
Adverse effects were assessed using the tDCS Adverse Effects Questionnaire
[12], a clinician-administered rating scale that assesses the severity of ten
adverse effects on a 4-point likert scale (1 – “absent”, 2 – “mild”, 3 –
“moderate”,
4 – “severe”). It was administered at each session immediately before
stimulation, to obtain a baseline measurement, and immediately after the end of
stimulation, to compare to baseline and determine if adverse effects were
related to stimulation (1 – “none”,
2 – “remote”, 3 – “possible”, 4 – “probable”, 5 – “definite”). A score ≥ 3
indicated an adverse effect of stimulation.
Client Satisfaction.
Satisfaction with treatment was assessed using the Client Satisfaction
Questionnaire-8 (CSQ-8 [30]). Adolescents and parents independently rated the
quality of and satisfaction with treatment on a 4-point likert scale (1 –
“poor/quite dissatisfied”, 2 – “fair/indifferent or mildly dissatisfied”, 3 –
“good/mostly satisfied”,
4 – “excellent/very satisfied”). Overall satisfaction ratings were categorized
as ‘‘poor’’
(8–13), ‘‘fair’’ (14–19), ‘‘good’’ (20–25), and ‘‘excellent’’
(26–32).
Attention to Threat.
Consistent with prior research, the angry/neutral faces dot-probe task
(TAU-NIMH ABMT initiative; http://people.socsci.tau.ac.il/mu/anxietytrauma/
research/) was used while EEG/ERP data were collected to obtain a measure of
attention to threat [6; 19; 54]. In the task, participants are presented with
240 trials. In each trial,
a white fixation cross appears in the center of the screen for 500 milliseconds
(ms), followed by a pair of faces of the same actor for 500 ms, arranged
vertically (one above the other). In each trial, the faces display one of three
combinations: neutral-angry, angry-neutral, or neutral-neutral. This is
immediately followed by a visual probe (“<” or “>”) replacing either the
top or bottom face. Participants are asked to respond as fast as possible and
indicate the orientation of the probe by clicking the left or right mouse
button (left for “<” and right for “>”) using their dominant hand. The
probe remains on the screen until participants respond, and the next trial
starts immediately. Angry-face location, probe location, probe type, and actor
are fully counterbalanced.
Electrophysiological Recording
and Processing. Participants were fitted with
a 64-channel Geodesic Sensor Net (Electrical Geodesics Inc., Eugene, OR)
previously soaked in a non-toxic, potassium chloride solution for 10 minutes.
The raw EEG signal was amplified using an high-impedance EGI NetAmps 400
amplifier and sampled at 1000 Hz. Impedance values were checked and adjusted to
be below 50 kΩ prior to data collection. EEG was recorded continuously during
the completion of the dot-probe task and was referenced to Cz after artifact
rejection. Continuous raw EEG was processed using EEGLab [16] and ERPLab [33].
Offline, data were resampled to 512 Hz and filtered using a high pass filter of
.1 Hz and a low pass filter of 30 Hz. Data was segmented into epochs with a 200
ms baseline period and 500 ms post-face stimulus onset period. Data were
baseline corrected to the average voltage during the 200 ms prior to stimulus
onset. Epochs were processed for artifacts using a voltage threshold of ± 75
μV. Remaining epochs were visually inspected for ocular and motor artifacts. Of
the trials not rejected, individual bad channels were identified and replaced
using spherical spline interpolation. Individual subject averages were
constructed separately for neutral-neutral (NN) and neutral-threat (NT)
stimuli.
Stimulus-Evoked ERP
Components.ERP neural activity was time-locked to the onset of the face
stimuli. Specific components of interest were P1, P2, and P3. In line with
previous studies, P1 and P2 components were examined at midline occipital sites
(Oz or E37 [4; 19; 38; 40]), and the P3 component was examined at frontal sites
(Fz or E4 [18]). ERP latency windows were determined by visually inspecting
grand average waves. Peak and mean amplitudes for P1 (0-100 ms), P2 (150-250
ms), and P3 (280-400 ms) were generated separately for NN and NT trials in
ERPLAB and data were imported into SPSS version 22.0 [53] for final statistical
analysis. In addition, for each ERP component at pretreatment and again at
POST, we computed ΔNT-NN scores as the difference between the amplitudes
for NT and NN trials. ΔNT-NN scores indicate the relative allocation of neural
resources when
a threat stimulus is present (NT trials) versus when only neutral stimuli are
present
(NN trials). We examined pretreatment to posttreatment changes in ΔNT-NN scores
for each component.
Results
Feasibility, Acceptability, and Satisfaction
All contacted parents expressed interest in participating. All six remaining adolescents completed all four treatment sessions as well as pretreatment and posttreatment assessments. Treatment satisfaction ratings by adolescents and their parents appear in Table 1. Five parents rated satisfaction as Excellent and one as Fair. Three adolescents rated satisfaction as Excellent and three as fair.
Adverse Effects and Dosage Toleration
Figure displays rates of specific adverse effects at each of the four sessions reported in the tDCS Adverse Effects Questionnaire. Excluded adverse effects that were also assessed but not endorsed include: neck pain, scalp pain, burning sensation, and sudden mood change. Following stimulation, the most common adverse effects were mild skin redness, itching, and sleepiness. In session one, three adolescents displayed mild redness, two reported mild itching, one reported mild tingling, and two reported mild sleepiness. In session two, two adolescents displayed mild redness, one reported mild itching, and one reported mild headache. In session three, two adolescents displayed mild redness and one reported mild sleepiness. In session four, three adolescents displayed mild redness, one reported mild itching, one reported mild headache, and four reported mild sleepiness. Moreover, one adolescent reported moderate tingling and a moderate hot sensation in session one. No adolescent reported a severe adverse effect. Adolescents stated that adverse effects decreased during stimulation, and attributed sleepiness to boredom with the procedures.
All adolescents required additional acclimation
time beyond the allocated two minutes in at least one session, mostly in
earlier sessions, meaning that they requested stimulation be lowered from 1 mA,
prior to stimulation being ramped up to full intensity
(1 mA). In one session, two adolescents did not reach full intensity after an
additional five minutes; after those five minutes, the ABMT protocol was
initiated and stimulation was administered at the maximum tolerable
intensity.
Figure. Distribution of endorsed mild adverse effects per session and participant
Notes. S1, S2, S3, S4 – Sessions 1-4. Figure includes adverse effects that were endorsed for at least one participant at least once. The Adverse Effects Questionnaire was administered before stimulation to determine baseline, and immediately after stimulation. It was considered an adverse effect if it was endorsed immediately after stimulation and not present (or mildly present and increased in intensity) before stimulation (sensations present prior to stimulation were considered to be unrelated to stimulation).
Attention to Threat
Peak and mean amplitudes for ERP components are presented in Table 2. Most effects were not statistically significant, as we expected in this small feasibility study with six cases. We therefore focus our presentation of results on effect sizes. For the P1 component peak amplitude, we found a medium (d = .47) pretreatment to posttreatment decrease on neutral-threat (NT) trials (ns), a large (d = 1.58) pretreatment to posttreatment increase on neutral-neutral (NN) trials (p < .05), and a large (d = 4.17) pretreatment to posttreatment decrease in ΔNT-NN (pretreatment: NT > NN; POST: NN > NT; p < .05). For the P2 component peak amplitude, we found a large (d = 1.97) pretreatment to posttreatment decrease on NT trials (p < .05), a large (d = 1.27) pretreatment to posttreatment increase on NN trials (p < .10), and a large (d = 1.73) pretreatment to posttreatment decrease in ΔNT-NN (ns). For the P3 component peak amplitude, we found a small (d = .16) pretreatment to posttreatment increase on NT trials (ns), a small (d = .19) pretreatment to posttreatment decrease on NN trials (ns), and a large (d = 1.46) pretreatment to posttreatment increase in ΔNT-NN (pretreatment: NN > NT; POST: NT > NN; p < .05).
For P1 and P2 components mean amplitude, we
found medium to large
(ds = .61–1.99) pretreatment to posttreatment changes on NN and NT
trials (ns), in the same direction as changes in peak amplitude, and large
(ds = 1.60–1.77) pretreatment to posttreatment decreases on ΔNT-NN (ns).
For P3 mean amplitude, we found small
(ds = .21–.35) pretreatment to posttreatment changes on NN and NT trials
(ns) and a large (d = 1.27) pretreatment to posttreatment increase on
ΔNT-NN (pretreatment: NN > NT; posttreatment : NT > NN; p < .05).
Table 2
Peak and mean amplitudes for ERP components
Component |
Trial |
Pretreatment |
Posttreatment |
t |
d |
Peak Amplitude |
|||||
P1 (M, SD) |
NT |
0.95 (0.92) |
0.45 (1.19) |
0.75 |
0.47 |
|
NN |
-0.20 (1.34) |
2.83 (2.36) |
-3.61* |
1.58 |
P2 (M, SD) |
NT |
1.32 (0.98) |
-1.06 (1.40) |
2.85* |
1.97 |
|
NN |
-0.13 (1.21) |
1.55 (1.43) |
-1.49 |
1.27 |
P3 (M, SD) |
NT |
1.95 (3.12) |
2.36 (1.97) |
-0.40 |
0.16 |
|
NN |
2.80 (3.49) |
2.31 (1.17) |
0.45 |
0.19 |
Peak Amplitude ΔNT-NN |
|||||
P1 (M, SD) |
|
1.15 (0.42) |
-2.38 (1.12) |
2.90* |
4.17 |
P2 (M, SD) |
|
1.44 (1.88) |
-2.61 (2.73) |
2.11 |
1.73 |
P3 (M, SD) |
|
-1.56 (2.22) |
0.96 (1.0) |
-3.59* |
1.46 |
Mean Amplitude |
|||||
P1 (M, SD) |
NT |
-0.25 (0.10) |
-0.77 (1.20) |
1.05 |
0.61 |
|
NN |
-1.80 (0.50) |
-0.60 (0.69) |
-2.11 |
1.99 |
P2 (M, SD) |
NT |
-0.61 (0.63) |
-1.87 (1.69) |
1.86 |
0.99 |
|
NN |
-1.35 (1.42) |
-0.40 (0.70) |
-1.76 |
0.85 |
P3 (M, SD) |
NT |
0.82 (2.61) |
1.29 (1.65) |
-0.55 |
0.21 |
|
NN |
1.20 (2.95) |
0.35 (1.67) |
0.81 |
0.35 |
Mean Amplitude ΔNT-NN |
|||||
P1 (M, SD) |
|
1.55 (1.15) |
-.71 (1.39) |
2.20 |
1.77 |
P2 (M, SD) |
|
0.74 (1.13) |
-1.48 (1.61) |
2.10 |
1.60 |
P3 (M, SD) |
|
-0.63 (2.34) |
1.71 (1.13) |
-3.11* |
1.27 |
Notes. M – mean; SD – standard deviation. NT – Neutral-Threat trials; NN – Neutral-Neutral trials. N = 5 (one participant did not complete posttreatment EEG due to a scheduling conflict); df = 4; * – p < .05.
Anxiety-Related Impairment and Symptom Severity
Participants’ demographic and clinical characteristics are
presented in Table 1, and pretreatment to posttreatment differences in
anxiety-related impairment and symptoms severity are presented in Table 3. Most
effects were not statistically significant, as we expected in this small
feasibility study with 6 cases. We therefore focus our presentation of results
on effect sizes. Mean adolescent impairment ratings on anxiety diagnoses
decreased from pretreatment (M = 6.50, SD = 1.38) to
posttreatment (M = 2.67, SD = 3.08), with
a large effect size (Cohen’s d = 1.60). Mean parent impairment ratings
on primary diagnosis decreased from pretreatment (M = 6.17, SD =
1.60) to posttreatment (M = 4.83, SD = 2.86), with a medium
effect size (Cohen’s d = .58). Four of six parents rated the impairment
of adolescents’ primary diagnosis lower at posttreatment than pretreatment.
Table 3
Mean scores and pretreatment to posttreatment differences
for
primary diagnoses’ impairment ratings, SCARED, and PARS scores
Pretreatment |
Posttreatment |
t |
df |
p |
d |
|
ADIS Impairment-P (M, SD) |
6.17 (1.60) |
4.83 (2.86) |
1.40 |
5 |
.221 |
0.58 |
ADIS Impairment-C (M, SD) |
6.50 (1.38) |
2.67 (3.08) |
3.01 |
5 |
.030* |
1.60 |
SCARED-P (M, SD) |
29.33 (19.19) |
24.83 (20.29) |
0.93 |
5 |
.397 |
0.23 |
SCARED-C (M, SD) |
46.33 (16.40) |
41.17 (11.91) |
1.01 |
5 |
.360 |
0.36 |
PARS (M, SD) |
19.00 (5.02) |
14.67 (5.79) |
2.43 |
5 |
.059+ |
0.80 |
Notes. ADIS – Anxiety Disorders Interview Schedule
for Children. P – parent; C – child/adolescent.
M – mean; SD – standard deviation. SCARED – Screen for Child
Anxiety Related Emotional Disorders;
PARS – Pediatric Anxiety Rating Scale. N = 6; * – p < .05; “+”
– p < .10.
Mean anxiety severity on clinician ratings, adolescent self-ratings, and parent ratings decreased from pretreatment to posttreatment; these decreases were large for clinician ratings (Cohen’s d = .80) and small for adolescent self-ratings (Cohen’s d = .36) and parent ratings (Cohen’s d = .23). For all six adolescents mean clinician-rated PARS ratings decreased from pretreatment (M = 19.00, SD = 5.02) to posttreatment (M = 14.67, SD = 5.79), and for one-half of parents and adolescents mean anxiety ratings on the SCARED-C/P decreased from pretreatment (P: M = 29.33, SD = 19.19; C: M = 46.33, SD = 16.40) to posttreatment (P: M = 24.83, SD = 20.29; C: M = 41.17, SD = 11.91).
Discussion
This case series presents preliminary data on the feasibility and acceptability of tDCS augmentation of ABMT in adolescents with anxiety disorders. Of the 10 families recruited, all parents agreed for their adolescent child to participate, and six adolescents agreed to participate. Adolescents tolerated treatment well and adverse effects were mild and transient. Additional acclimation time to stimulation was required for all adolescents in at least one session, and two adolescents did not reach full stimulation intensity in one session. This suggests that while adolescents with anxiety disorders can tolerate stimulation at 1 mA, tDCS protocols may need to be modified to allow for a longer ramp up period and flexibility in intensity of stimulation when working with this population. Overall, both parents and adolescents rated treatment satisfaction in the excellent to fair range, supporting the acceptability of the treatment.
With regard to anxiety reduction effects, anxiety-related impairment ratings decreased from pretreatment to posttreatment, with medium to large effect sizes. Anxiety symptom severity reduction effect sizes on rating scales ranged from large on clinician ratings to small on parent and adolescent ratings, and scores were in the moderate range for several adolescents at posttreatment. These effects, while in the expected direction, were largely not statistically significant. The direction of these effects however suggests that four sessions of tDCS augmented ABMT (ABMT + tDCS) at 1 mA may be sufficient for some but not all adolescents with anxiety disorders. Lengthier and/or higher intensity monotherapy protocols have been used in past research, including up to eight ABMT sessions and 2 mA tDCS intensity. In future studies, it will be important to investigate whether additional treatment sessions and/or higher intensity tDCS may lead to greater anxiety reduction effects, and characteristics of adolescents with anxiety disorders who are most likely to benefit from tDCS augmentation of ABMT.
With regard to the target of treatment,
attention to threat, tDCS augmentation of ABMT led to reductions in neural
resources allocated to threatening stimuli and increases in neural resources
allocated to neutral stimuli in components associated with rapidly deployed
attention orientation. This is indicated by pretreatment to posttreatment
reduction in the P1 and P2 components on NT trials and pretreatment to
posttreatment increase in the P1 and P2 components on NN trials, as well as
pretreatment to posttreatment changes in the relation between NT and NN. At
pretreatment, participants allocated relatively more neural resources at
rapidly deployed attention stages when threat stimuli were present, whereas at
posttreatment participants allocated relatively more neural resources when only
neutral stimuli were present.
tDCS augmentation of ABMT also led to reductions in neural resources allocated
to neutral stimuli and increases to threatening stimuli in the component
associated with later strategic attention regulation and effortful
disengagement from threat. This is indicated by pretreatment
to posttreatment reduction in the P3 component on NN trials and pretreatment to
posttreatment increase in the P3 component on NT trials, as well as
pretreatment
to posttreatment changes in the relation between NT and NN. At pretreatment,
participants allocated relatively more neural resources at a later stage when
only neutral stimuli were present, whereas at posttreatment participants
allocated more neural resources when threat was present.
Conclusion
Overall, these preliminary data support the feasibility, acceptability, and clinical promise of tDCS augmentation of ABMT as a treatment for adolescents with anxiety disorders. It further supports the promise to engage the treatment target by increasing attention orientation in the presence of neutral stimuli and increasing attention regulation when a threat was present. We urge caution in interpreting these results, as most effects were not statistically significant in this small feasibility case series. Future research is encouraged to investigate the optimal dosing parameters to produce adequate treatment response and examine the efficacy of tDCS augmentation of ABMT in larger samples of adolescents with anxiety disorders using a randomized controlled design.
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