Abnormal functional connectivity of the amygdala is associated with depressive symptoms in patients with multiple system atrophy

Figures & data

Table 1 Demographics and clinical features among DMSA, NDMSA, and HCs

Measure	DMSA	NDMSA	HCs	Statistic	P-value
					DMSA vs HCs	NDMSA vs HCs	DMSA vs NDMSA
Age	62.36±5.25	64.86±9.31	64.53±4.16	F=0.97	0.25	0.86	0.21
Sex (male/female)	12:17	18:11	19:15	F=1.59	0.19	0.63	0.08
Education (years)	10.21±3.40	11.24±3.80	11.24±2.09	F=1.03	0.20	0.99	0.22
Handedness (R/L)	28:0	29:0	34:0	F=0.00	1.00	1.00	1.00
HAMD-17	22.54±5.17	4.76±1.85	0.77±0.85	F=415.31	0.00*	0.00*	0.00*
MMSE	27.29±1.49	27.24±1.79	27.88±1.32	F=1.75	0.13	0.10	0.91
Dur (years)	3.93±2.31	3.29±1.71	NA	T=0.52	NA	NA	0.95
H-Y	2.46±0.82	2.29±0.59	NA	T=0.60	NA	NA	0.87
UMSARS	15.01±8.18	11.35±7.48	NA	T=0.89	NA	NA	0.40
LED (mg)	539.29±187.75	513.79±229.47	NA	U=347.5	NA	NA	0.34

Notes: Values are represented as mean±SD.

* Means value is less than 0.00; P<0.05 is considered as statistically significant.

Abbreviations: DMSA, MSA patients with depression; Dur, disease duration; HAMD-17, 17-item Hamilton Depression Rating Scale; HC, healthy control; H-Y, Hoehn and Yahr staging scale; LED, levodopa equivalent dose (mg); MMSE, Mini–Mental State Examination; MSA, multiple system atrophy; NA, not applicable; NDMSA, MSA patients without depression; UMSARS, Unified Multiple System Atrophy Rating Scale.

Table 2 Difference of functional connectivity between DMSA patients and HCs

Brain regions	L/R	Cluster	BA	MNI coordinates			t-value
				x	y	z
DMSA < HCs
Superior occipital gyrus	L	52	18	−18	−90	27	−4.301
Middle occipital gyrus	L	54	19	−42	−75	6	−5.102
Lingual gyrus	L	132	37	−24	−48	−3	−5.62
Middle cingulate cortex	L	24	NaN	−11	−18	45	−4.238
Fusiform	L	28	30	−19	−44	−11	−4.064
Precuneus lobe	R	191	37	24	−45	3	−5.172
Rolandic oper	L	92	48	−39	−21	21	−4.831
Paracentral lobe	L	64		−12	−33	54	−4.583
Supply motor area	R	19	4	2	−21	60	−4.118
Postcentral gyrus	L	227	3	−33	−21	45	−5.439
Superior parietal lobe	R	21	1	21	−45	72	−4.359
Parahippocampal gyrus	L	16	37	−23	−40	−3	−3.899
Cuneus lobe	L	35	19	6	−87	33	−4.263
Insula	L	78	48	−39	−18	21	−6.541
Middle temporal gyrus	L	81	21	−51	−48	15	−4.490
Frontal_Inf_Orb	L	63	11	−24	30	−12	−5.605

Abbreviations: BA, Brodmann; DMSA, multiple system atrophy patients with depression; HC, healthy control; L, left; MNI, Montreal Neurological Institute; NaN, not applicable; R, right.

Figure 1 Statistical parametric map showing the significant differences in left and right AMY FC differences between DMSA patients and HCs (left AMY, cluster size >14, P<0.001 and right AMY cluster size >9, P<0.001 AlphaSim corrected); differences between NDMSA and HC (left AMY, cluster size >47, P<0.001 and right AMY cluster size >64, P<0.001 AlphaSim corrected).

Notes: Areas in blue indicate the regions in which the former group who had decreased FC. The left side corresponds to the right hemisphere significant differences FC.
Abbreviations: AMY, amygdala; DMSA, multiple system atrophy patients with depression; FC, functional connectivity; HC, healthy control; L, left; NDMSA, multiple system atrophy patients without depression; R, right.

Table 3 Difference of functional connectivity between NDMSA patients and HCs

Brain regions	L/R	Cluster	BA	MNI coordinates			t-value
				x	y	z
NDMSA < HCs
Lingual gyrus	L	12	19	−27	−72	−6	−4.238
Middle frontal gyrus	R	225	6	41	−4	56	−5.048
Orbital gyrus	L	33	11	−21	30	−12	−5.891
Calcarine gyrus	L	170	18	−12	−70	7	−4.446
Cuneus gyrus	L	34	18	−9	−78	36	−4.252
Middle occipital gyrus	L	27	19	−42	−81	9	−4.218
Insula lobe	R	29	48	39	−27	24	−5.451
Superior temporal gyrus	L	46	48	−39	−18	21	−4.711
Middle frontal gyrus	L	18	46	−27	54	18	−4.904
Precentral gyrus	R	233	6	22	−20	73	−4.189
Postcentral gyrus	L	166	3	−43	−23	52	−4.566
Supply motor area	R	50	6	9	9	54	−4.837
Superior frontal gyrus	L	17	11	−21	30	−12	−5.891
Putamen	R	19	48	32	−6	10	−4.360
Rolandic oper	L	146	48	−42	−15	21	−4.851
Middle cingulum cortex	L	69	NaN	−8	−16	46	−4823

Abbreviations: BA, Brodmann; HC, healthy control; L, left; MNI, Montreal Neurological Institute; NaN, not applicable; NDMSA, multiple system atrophy patients without depression; R, right.

Table 4 Difference of functional connectivity between DMSA and NDMSA patients

Brain regions	L/R	Cluster	BA	MNI coordinates			t-value
				x	y	z
DMSA > NDMSA
Middle frontal gyrus	L	50	45	−39	45	9	4.5916
Middle frontal gyrus	L	46	47	−37	−45	1	3.4013
DMSA < NDMSA
Middle occipital gyrus	R	32	19	42	−81	3	−2.857

Abbreviations: BA, Brodmann; DMSA, multiple system atrophy patients depression; L, left; MNI, Montreal Neurological Institute; NaN, not applicable; NDMSA, multiple system atrophy patients depression; R, right.

Figure 2 Statistical parametric map showing the significant differences between DMSA and NDMSA patients (P<0.001, AlphaSim corrected); Blue denotes decreased FC in DMSA group than NDMSA group, red denotes increased FC in DMSA group than NDMSA group.

Notes: FC between the bilateral AMY and left middle frontal gyrus positively correlates with HAMD scores. No correlation was found between the AMY and the right middle occipital gyrus. Note that the left side corresponds to the right hemisphere significant differences FC.
Abbreviations: AMY, amygdala; DMSA, multiple system atrophy patients with depression; FC, functional connectivity; HAMD, Hamilton Depression Rating Scale; MFG, middle frontal gyrus; MOG, middle occipital gyrus; NDMSA, multiple system atrophy patients without depression.