Cognitive control networks in OCD: A resting-state connectivity study in unmedicated patients with obsessive-compulsive disorder and their unaffected relatives

Figures & data

Figure 1. Seed regions are depicted on the left side. The fronto-parietal network consisted of four seed regions, the cingulo-opercular network of three regions, and the the fronto-parietal network of on seed region (subgenual ACC). On the right side the connectivity from each network seed with the rest of the brain is displayed for each group separately.

Table 1. Demographic and clinical characteristics of OCD patients and healthy controls.

	OCD patients (N = 39)		Healthy controls (N = 36)		Statistical analysis
	Mean	SD/%	Mean	SD/%	t	df	P value
Demographic measures
Age (years)	38.0	9.7	39.4	11.3	–0.6	73	0.55
Gender (female: male)	21:18	54%	19:17	53%	χ^2 = 0.9		0.56
Handedness (right: left)	33:6	85%	31:5	86%	χ^2 = 0.03		0.86
Estimated verbal IQ	98	12.9	96	8.1	0.7	63	0.50
Education (years)	12.6	3.2	12.9	3.2	–0.4	73	0.71
Number of patients with a co-morbid axis I disorders	21^a	54%	—
Clinical measures
Y-BOCS severity (points)	21.3	6.3	0	0	n.a.
OCI-R, total (points)	23.7	12.8	2.6	3.4	9.9	43	0.000
OCI-R, checking (points)	5.8	3.8	0.5	0.9	8.5	43	0.000
OCI-R, washing (points)	3.3	4.0	0.3	0.6	4.6	40	0.000
OCI-R, symmetry (points)	4.6	4.0	0.6	0.9	6.1	43	0.000
MADRS (points)	10.7	8.0	0.9	1.5	7.6	41	0.000
BAI (points)	14.3	9.9	2.0	2.8	7.5	45	0.000

OCD: obsessive-compulsive disorder; Y-BOCS: Yale-Brown Obsessive-Compulsive Scale; OCI-R: Obsessive-compulsive Inventory-Revised; BAI: Beck Anxiety Inventory; MADRS: Montgomery–Åsberg Depression Rating Scale; n.a.: not applicable.

^a Nine mood disorders (current depressive episodes), 19 anxiety disorders, two eating disorders, three tic disorders, one somatoform disorder, one alcohol dependence in partial remission. Total number is higher than 21 because of patients with more than one co-morbid disorder.

Table 2. The matched group of OCD patients, unaffected siblings and healthy controls.

	OCD patients (N = 16)		Unaffected siblings^a (N = 16)		Healthy controls (N = 16)		Statistical analysis
							Value
	Mean	SD	Mean	SD	Mean	SD	F	df	P value
Demographic measures
Age (years)	37	11	37	12	37	12	0.01	2,45	0.9
Gender (female: male)	7:9	44%	5:11	31%	5:11	31%	χ^2 = 0.7		0.7
Handedness (right: left)	13:3	81%	11:5	68%	13:3	81%	χ^2 = 0.9		0.6
Estimated IQ	100	12.5	97	10.4	93	8.1	1.6	2,45	0.2
Clinical measures
Y-BOCS	20.3	5.5	0.06	0.25	0	0	n.a.
OCI-R, total	20.6	8.6	2.6	2.6	2.5	3.3	58	2,45	0.000*
OCI-R, check	5.6	4.2	0.4	0.7	0.4	0.8	144	2,45	0.000*
OCI-R, wash	3.1	4.0	0.3	0.4	0.2	0.4	45	2,45	0.001*
OCI-R, symm	3.1	3.7	0.4	0.7	0.8	0.9	36	2,45	0.002*
MADRS	8.1	6.2	1.6	3.6	0.7	1.2	14.7	2,44	0.000*
BAI	11.9	9.6	3.1	3.7	1.5	2.1	13.9	2,45	0.000*

OCD: obsessive-compulsive disorder; Y-BOCS: Yale-Brown Obsessive-Compulsive Scale; OCI-R: Obsessive-compulsive Inventory-Revised; BAI: Beck Anxiety Inventory; MADRS: Montgomery–Åsberg Depression Rating Scale; n.a.: not applicable.

* For all post-hoc tests OCD patients differed significantly from siblings and controls, but siblings and controls were not significantly different.

^a One sibling was diagnosed with specific phobia, no other psychiatric disorders were present in the siblings.

Table 3. Averaged (z transformed) correlation coefficients between the time courses of the seed maps of each network as a measure of within-network connectivity: t-test between average (z transformed) correlations for OCD patients and controls.

	OCD patients (N = 39)		Healthy controls (N = 36)
Network	Mean	SD	Mean	SD	df	t	P
FPN	0.60	0.21	0.61	0.25	73	−0.17	0.87
CON	0.79	0.29	0.80	0.31	73	−0.14	0.89

SD: standard deviation; df: degrees of freedom.

Table 4. Averaged (z transformed) correlation coefficients between the time courses of the seed maps of each network as a measure of within-network connectivity: ANOVA with average (z transformed) correlations for OCD patients, siblings and controls.

	OCD patients (N = 16)		Unaffected siblings (N = 16)		Healthy controls (N = 16)
Network	Mean	SD	Mean	SD	Mean	SD	F(2,45)	P	Post-hoc
FPN	0.55	0.21	0.62	0.27	0.59	0.19	0.4	0.68
CON	0.71	0.28	1.00	0.18	0.85	0.29	5.1	0.01	Sib > OCD p = 0.003

SD: standard deviation; df: degrees of freedom.

Table 5. Effect of group for network to whole-brain connectivity: two-group comparison (39 OCD patients and 36 healthy controls).

		MNI coordinates			ANOVA
Seed region	Area	x	y	z	ke	Z	Post-hoc	Z
FPN	No significant group differences.						n.a.
CON	No significant group differences.						n.a.
Fronto-limbic network
	R  Caudate	21	19	10	137	3.53	OCD > HC	3.71
	R  Putamen	21	16	–6		3.36	OCD > HC	3.55
	R  Inferior frontal gyrus (BA 47)	24	29	–9		3.05	OCD > HC	3.25
	L  Hippocampus/amygdala	–29	–14	–13	177	3.89	OCD > HC	4.05
	Hippocampus/amygdala	–25	–11	–16		3.73		3.89
	L  Putamen	–16	9	–13		3.33	OCD > HC	3.52
	L  Caudate	–15	22	1		2.95	OCD > HC	3.16

Group differences are reported based on an F-test and followed-up by one-sided t-test. Results significant at post-hoc testing are shown thresholded at P < 0.05 with family-wise error correction at cluster level and P < 0.005 uncorrected at the voxel level.

BA: Brodmann area; k_e: number of voxels; OCD: obsessive-compulsive disorder; HC: healthy controls; Sib: siblings; ACC: anterior cingulate cortex; dmPFC: dorsomedial prefrontal cortex; dlPFC: dorsolateral prefrontal cortex.

Table 6. Effect of group for network to whole-brain connectivity: three-group comparison (16 OCD patients, 16 unaffected siblings and 16 healthy controls).

		MNI Coordinates			ANOVA
Seed region	Area	x	y	z	ke	Z	Post-hoc	Z
FPN
	L  ACC (BA 9)	–6	42	30	105	3.49	Sib > HC	4.01
	L  ACC (BA 10)	–6	49	7		3.45	Sib > HC	4.02
CON
	Midbrain^a	–22	–20	–6	77	3.61	Sib > OCD	4.17
	L  Putamen	–32	–17	–6		3.20	Sib > OCD	3.78
	R  dlPFC (BA 46)	54	32	10	49	3.57	Sib > OCD	3.97
		54	19	20		3.51
	L  Inferior parietal cortex (BA 40)	–58	–37	30	32	3.10	Sib > OCD	3.61
	L  Anterior insula (BA 13)	–35	9	–6	2	3.37	Sib > OCD	3.94
Fronto-limbic network	No significant group differences						n.a.

Group differences are reported based on an F-test and followed-up by one-sided t-test. Results significant at post-hoc testing are shown thresholded at P < 0.05 with family-wise error correction at cluster level and P < 0.005 uncorrected at the voxel level.

BA: Brodmann area; k_e: number of voxels; OCD: obsessive-compulsive disorder; HC: healthy controls; Sib: siblings; ACC: anterior cingulate cortex; dmPFC: dorsomedial prefrontal cortex; dlPFC: dorsolateral prefrontal cortex.

^a Bilateral midbrain area including substantia nigra, red nucleus, subthalamic nucleus, extending into the pallidum and putamen.

Figure 2. Group differences in network to whole-brain connectivity. (A and B) Areas with increased connectivity with the sgACC in OCD (n = 39) compared with healthy controls (n = 36). In (A) results are masked for the striatum and in (B) for the limbic lobe for illustration purpose and displayed at P < 0.005 uncorrected. (C) Increased connectivity between the FPN and the dACC/dmPFC in siblings vs healthy controls. (D, E, F) Increased connectivity in siblings vs OCD patients between the CON and the right dlPFC (D), the left inferior parietal cortex (E), and the midbrain areas, extending into the insular cortex (F). Plots on the right side show the response estimates for each group at the given coordinates.