Normalization of Fronto-Parietal Activation by Cognitive-Behavioral Therapy in Unmedicated Pediatric Patients With Anxiety Disorders
Abstract
Objective:
Methods:
Results:
Conclusions:
Methods
Participants
Characteristic | Anxiety Group (N=69) | Control Group (N=62) | ||
---|---|---|---|---|
| Mean | SD | Mean | SD |
Age (years) | 12.79 | 2.98 | 13.66 | 2.23 |
IQ | 114.36 | 13.79 | 111.72 | 12.02 |
| N | % | N | % |
Maleb | 23 | 33.33 | 30 | 48.39 |
Raceb | | | | |
Asian | 1 | 2 | 3 | 5 |
American Indian or Alaskan Native | 1 | 2 | 0 | 0 |
Black or African American | 1 | 2 | 14 | 23 |
Multiple races | 10 | 14 | 6 | 10 |
Native Hawaiian or Other Pacific Islander | 1 | 2 | 0 | 0 |
White | 50 | 73 | 19 | 31 |
Unknown or undeclared | 5 | 8 | 19 | 31 |
Ethnicity | | | | |
Latino or Hispanic | 9 | 13 | 2 | 3 |
Not Latino or Hispanic | 56 | 81 | 42 | 68 |
Unknown or undeclared | 4 | 6 | 18 | 29 |
Combined family income | | | | |
<$25,000 | 5 | 7 | 3 | 5 |
$25,000–$39,999 | 1 | 2 | 3 | 5 |
$40,000–59,999 | 1 | 2 | 4 | 7 |
$60,000–89,999 | 5 | 7 | 2 | 3 |
$90,000–$179,999 | 26 | 38 | 18 | 29 |
≥$180,000 | 29 | 42 | 11 | 18 |
Unknown or undeclared | 2 | 2 | 21 | 34 |
| Mean | SD | | |
Pretreatment PARS total score | 15.40 | 3.75 | | |
Posttreatment CGI-I score | 3.12 | 0.88 | | |
| N | % | | |
Current anxiety diagnoses | | | | |
Generalized anxiety | 55 | 78 | | |
Social anxiety | 43 | 62 | | |
Separation anxiety | 19 | 28 | | |
Specific phobia | 20 | 30 | | |
Panic disorder | 1 | 2 | | |
Treatment and Measures
Threat Attention Task
fMRI Data Acquisition and Preprocessing
Statistical Analysis
Results
Demographic Characteristics and Treatment Effects
![](/cms/10.1176/appi.ajp.20220449/asset/images/large/appi.ajp.20220449f1.jpeg)
Behavioral Effects
Whole-Brain Analyses
Pre- to posttreatment change.
Region | k | mm3 | CM LR | CM PA | CM IS | Mean | SEM | Anxiety-Control Difference Value | t | p | | | | | | | | | |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
R precentral gyrus | 93 | 1453 | 40.9 | −20.8 | 55.6 | 17.39 | 0.30 | 0.06 | 4.73 | <0.001 | | | | | | | | | |
L precentral gyrus | 88 | 1375 | −35.1 | −28 | 62.9 | 16.21 | 0.23 | 0.06 | 4.70 | <0.001 | | | | | | | | | |
R parahippocampal gyrus/amygdala | 76 | 1188 | 23.3 | −11.6 | −18.8 | 16.92 | 0.28 | 0.04 | 6.44 | <0.001 | | | | | | | | | |
R superior temporal gyrus | 40 | 625 | 56.1 | −9.3 | −10.8 | 18.20 | 0.47 | 0.06 | 4.93 | <0.001 | | | | | | | | | |
L postcentral gyrus | 30 | 469 | −46 | −18.9 | 50 | 16.53 | 0.42 | 0.05 | 4.74 | <0.001 | | | | | | | | | |
L middle frontal gyrus | 24 | 375 | −26.8 | 51.4 | 8.6 | 16.18 | 0.41 | 0.03 | 4.64 | <0.001 | | | | | | | | | |
R inferior frontal gyrus | 22 | 344 | 35.9 | 32.6 | −13.4 | 17.47 | 0.57 | 0.04 | 5.08 | <0.001 | | | | | | | | | |
R inferior frontal gyrus | 21 | 328 | 45.4 | 19.5 | 26 | 16.26 | 0.37 | 0.05 | 4.44 | <0.001 | | | | | | | | | |
Region | k | mm3 | CM LR | CM PA | CM IS | Mean | SEM | Anxiety: Time 1–Time 2 | t | p | Control: Time 1–Time 2 | t | p | Anxiety>Control, Time 1 | t | p | Anxiety>Control, Time 2 | t | p |
R lingual gyrus | 535 | 8359 | 3.6 | −77.8 | 10.2 | 21.42 | 0.30 | −0.03 | −4.07 | <0.001 | 0.04 | 4.95 | <0.001 | −0.02 | −0.98 | 0.76 | 0.06 | 2.53 | 0.06 |
R middle frontal gyrus | 434 | 6781 | 33.3 | 2.2 | 53.5 | 22.07 | 0.40 | 0.04 | 8.50 | <0.001 | −0.01 | −2.24 | 0.11 | 0.03 | 3.91 | <0.001 | −0.02 | −2.26 | 0.11 |
R superior parietal lobule | 264 | 4125 | 19.2 | −69.2 | 53.4 | 19.85 | 0.31 | 0.07 | 10.25 | <0.001 | 0.00 | 0.09 | 1.00 | 0.04 | 2.90 | 0.02 | −0.03 | −2.50 | 0.06 |
R superior temporal gyrus | 256 | 4000 | 55.7 | −41.8 | 20.8 | 22.61 | 0.59 | 0.05 | 10.75 | <0.001 | 0.00 | −0.82 | 0.84 | 0.03 | 3.30 | 0.01 | −0.02 | −2.34 | 0.10 |
R inferior temporal gyrus | 215 | 3359 | 43.7 | −64.4 | −7.9 | 19.08 | 0.31 | 0.06 | 11.09 | <0.001 | 0.00 | 0.40 | 0.98 | 0.03 | 2.06 | 0.17 | −0.04 | −2.96 | 0.02 |
L precentral gyrus | 189 | 2953 | −31.5 | −1.4 | 53.9 | 18.96 | 0.35 | 0.04 | 8.76 | <0.001 | −0.01 | −1.26 | 0.59 | 0.02 | 1.88 | 0.24 | −0.03 | −3.49 | 0.00 |
L inferior parietal lobule | 180 | 2813 | −21.7 | −55.2 | 47.7 | 21.35 | 0.53 | 0.03 | 9.19 | <0.001 | −0.01 | −2.03 | 0.18 | 0.01 | 1.30 | 0.56 | −0.03 | −4.31 | <0.001 |
L middle occipital gyrus | 171 | 2672 | −46.4 | −70.3 | 2.2 | 19.87 | 0.33 | 0.06 | 10.57 | <0.001 | 0.01 | 1.43 | 0.48 | 0.03 | 2.12 | 0.15 | −0.03 | −1.79 | 0.28 |
L supplementary motor area | 135 | 2109 | 1.3 | 10.6 | 46 | 18.93 | 0.40 | 0.03 | 5.44 | <0.001 | −0.02 | −3.46 | 0.00 | 0.03 | 2.55 | 0.06 | −0.03 | −2.60 | 0.05 |
R putamen | 123 | 1922 | 31.1 | 8 | −0.7 | 19.37 | 0.38 | 0.02 | 4.51 | <0.001 | −0.19 | −4.64 | <0.001 | 0.02 | 3.46 | 0.00 | −0.02 | −2.56 | 0.06 |
L middle occipital gyrus | 98 | 1531 | −28 | −72.2 | 29.1 | 20.71 | 0.62 | 0.04 | 8.30 | <0.001 | 0.00 | −0.11 | 1.00 | 0.01 | 1.01 | 0.74 | −0.03 | −2.48 | 0.07 |
R caudate nucleus | 89 | 1391 | 15 | −5.1 | 17.5 | 20.84 | 0.55 | 0.02 | 2.78 | 0.03 | −0.04 | −5.71 | <0.001 | 0.05 | 4.69 | <0.001 | −0.01 | −1.11 | 0.68 |
R middle frontal gyrus | 61 | 953 | 29.6 | 44.3 | 34.3 | 19.40 | 0.57 | 0.01 | 1.89 | 0.23 | −0.04 | −6.23 | <0.001 | 0.03 | 3.67 | 0.00 | −0.02 | −1.76 | 0.30 |
L middle frontal gyrus | 57 | 891 | −35.8 | 48.8 | 2 | 19.29 | 0.65 | −0.03 | −4.94 | <0.001 | 0.02 | 3.28 | 0.01 | −0.01 | −0.97 | 0.77 | 0.04 | 4.82 | <0.001 |
L middle cingulate cortex | 54 | 844 | −10.1 | 12.7 | 36.1 | 18.80 | 0.63 | 0.02 | 4.07 | <0.001 | −0.02 | −3.81 | <0.001 | 0.03 | 3.27 | 0.01 | −0.01 | −1.77 | 0.29 |
R middle occipital gyrus | 53 | 828 | 34.1 | −68.7 | 36.5 | 18.75 | 0.49 | 0.04 | 7.94 | <0.001 | 0.00 | −0.11 | 1.00 | 0.03 | 3.36 | 0.01 | −0.01 | −1.43 | 0.48 |
R precuneus | 53 | 828 | 6.8 | −44.1 | 53.3 | 19.33 | 0.75 | 0.01 | 2.39 | 0.08 | −0.04 | −5.66 | <0.001 | 0.04 | 3.52 | 0.00 | −0.01 | −0.59 | 0.93 |
R inferior parietal lobule | 52 | 813 | 31.7 | −54.4 | 47.6 | 16.75 | 0.35 | 0.05 | 9.64 | <0.001 | 0.01 | 2.06 | 0.04 | 0.01 | 1.02 | 0.74 | −0.03 | −2.74 | 0.04 |
R Rolandic operculum | 49 | 766 | 46.4 | −12.6 | 12.3 | 18.41 | 0.62 | −0.04 | −7.07 | <0.001 | 0.01 | 1.80 | 0.28 | −0.01 | −0.59 | 0.93 | 0.05 | 4.72 | <0.001 |
L superior parietal lobule | 43 | 672 | −21 | −73 | 45.8 | 20.46 | 0.80 | 0.05 | 7.74 | <0.001 | 0.00 | −0.74 | 0.88 | 0.03 | 1.72 | 0.32 | −0.03 | −1.78 | 0.29 |
L precuneus | 42 | 656 | −14.4 | −71.4 | 59.1 | 21.68 | 1.15 | 0.08 | 8.44 | <0.001 | −0.01 | −0.65 | 0.92 | 0.02 | 1.10 | 0.69 | −0.06 | −3.14 | 0.01 |
R thalamus | 40 | 625 | 6.6 | −26.6 | 16.2 | 16.97 | 0.47 | 0.02 | 2.34 | 0.09 | −0.04 | −5.20 | <0.001 | 0.04 | 3.33 | 0.01 | −0.02 | −1.55 | 0.41 |
R middle occipital gyrus | 40 | 625 | 36.7 | −77.9 | 18.7 | 19.24 | 0.70 | 0.05 | 8.35 | <0.001 | 0.00 | 0.49 | 0.96 | 0.02 | 1.58 | 0.40 | −0.03 | −1.79 | 0.28 |
R superior frontal gyrus | 38 | 594 | 28.4 | 56.7 | 15.1 | 19.96 | 0.77 | 0.02 | 3.22 | 0.01 | −0.04 | −4.51 | <0.001 | 0.05 | 3.93 | <0.001 | −0.01 | −0.63 | 0.92 |
L superior temporal gyrus | 37 | 578 | −59.2 | −45.7 | 19.4 | 19.55 | 0.59 | 0.04 | 7.71 | <0.001 | −0.01 | −2.22 | 0.12 | 0.03 | 3.85 | 0.00 | −0.01 | −1.44 | 0.48 |
Cerebellar lobule VIIIa | 36 | 563 | −1 | −74.9 | −39.8 | 19.81 | 0.79 | 0.04 | 6.55 | <0.001 | −0.02 | −2.17 | 0.13 | 0.04 | 3.25 | 0.01 | −0.02 | −1.83 | 0.27 |
L inferior occipital gyrus | 34 | 531 | −24 | −95.9 | −6.1 | 21.00 | 1.01 | 0.04 | 4.23 | 0.00 | −0.04 | −4.04 | <0.001 | 0.07 | 2.90 | 0.02 | −0.01 | −0.44 | 0.97 |
Cerebellar vermis, 4/5 | 31 | 484 | 1.8 | −61.1 | −14.9 | 20.15 | 1.17 | 0.02 | 5.41 | <0.001 | −0.01 | −2.75 | 0.03 | 0.02 | 3.04 | 0.02 | −0.01 | −1.85 | 0.25 |
R supplementary motor area | 30 | 469 | 11 | 0.4 | 72.4 | 21.00 | 1.11 | 0.06 | 8.20 | <0.001 | 0.00 | −0.41 | 0.98 | 0.04 | 2.76 | 0.03 | −0.02 | −1.31 | 0.56 |
R superior temporal gyrus | 29 | 453 | 45.1 | −31 | 13.7 | 23.76 | 1.44 | −0.04 | −5.90 | <0.001 | 0.02 | 2.52 | 0.06 | 0.00 | −0.16 | 1.00 | 0.06 | 4.63 | <0.001 |
R middle cingulate cortex | 29 | 453 | 6.6 | 24.1 | 30.8 | 16.46 | 0.42 | 0.02 | 2.95 | 0.02 | −0.03 | −3.83 | <0.001 | 0.03 | 2.80 | 0.30 | −0.02 | −1.72 | 0.32 |
R postcentral gyrus | 29 | 453 | 46.4 | −34.9 | 59.8 | 19.21 | 0.77 | 0.07 | 6.66 | <0.001 | −0.01 | −1.17 | 0.65 | 0.06 | 2.77 | 0.03 | −0.02 | −0.99 | 0.76 |
R hippocampus | 28 | 438 | 24.4 | −32.9 | 6.2 | 20.11 | 0.99 | 0.01 | 4.14 | <0.001 | −0.02 | −4.83 | <0.001 | 0.03 | 5.38 | <0.001 | 0.00 | −0.90 | 0.81 |
R fusiform gyrus | 27 | 422 | 43.3 | −39.3 | −18.3 | 20.79 | 0.92 | 0.04 | 7.34 | <0.001 | −0.01 | −0.99 | 0.76 | 0.03 | 3.32 | 0.01 | −0.01 | −0.88 | 0.82 |
L superior temporal gyrus | 26 | 406 | −41.6 | −37.4 | 19.3 | 19.09 | 0.83 | −0.03 | −3.93 | <0.001 | 0.02 | 3.57 | 0.00 | −0.01 | −1.04 | 0.73 | 0.04 | 3.28 | 0.01 |
L lingual gyrus | 22 | 344 | −8.5 | −67.2 | −3 | 22.03 | 1.64 | −0.05 | −4.12 | <0.001 | 0.03 | 2.82 | 0.03 | −0.04 | −1.47 | 0.46 | 0.04 | 1.38 | 0.51 |
Cerebellar vermis, 8 | 21 | 328 | −0.9 | −57.8 | −29.2 | 19.98 | 1.29 | −0.03 | −3.85 | <0.001 | 0.03 | 4.24 | <0.001 | −0.04 | −4.37 | <0.001 | 0.02 | 1.89 | 0.24 |
![](/cms/10.1176/appi.ajp.20220449/asset/images/large/appi.ajp.20220449f2.jpeg)
Associations between pretreatment activation patterns and treatment response.
Discussion
Baseline Differences in Fronto-Parietal Networks
Fronto-Parietal Networks and Treatment-Related Change
Pretreatment Activation Patterns and Treatment Response
Strengths and Limitations
Conclusions
Acknowledgments
Supplementary Material
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