Improvement Of Frontal Lobe Dysfunction And White Matter Integrity By rTMS In Treatment-Resistant Depression

Figures & data

Figure 1 Oval regions of interest (ROIs) of identical size (20 mm²) were used to measure fractional anisotropy (FA) values. The same ROI was used for both measures, and all ROIs were placed on axial slices. Bilateral superior gyri and middle frontal gyri ROIs were placed halfway between the precentral sulcus and anterior boundary of the brain, on the most inferior slice where both gyri were visible as separate structures. a: the right middle frontal gyrus, b: the left middle frontal gyrus, c: the right superior frontal gyrus, d: the left superior frontal gyrus.

Table 1 Participant Characteristics (N = 12)

Age, M (SD) (years)	52.8 (17.8)
Gender (Male/Female) (n)	5/7
Onset age, M (SD) (year)	46.9 (19.6)
Last duration of illness, M (SD) (year)	4.0 (4.7)
Number of episodes, M (SD)	1.3 (0.6)
Number of antidepressant, M (SD)	2.9 (1.2)

Abbreviations: M, mean; SD, standard deviation.

Table 2 Changes In Depressive Symptoms And Frontal Lobe Function Induced By rTMS

	n	Pre		Post		t	p
		Mean	SD	Mean	SD
HAMD	12	20.33	6.87	13.17	8.98	−5.00	0.00
BDI	12	26.33	10.73	19.50	11.97	−2.44	0.03
WCST CA	12	4.58	2.11	4.33	2.35	−0.67	0.52
TE	12	14.41	4.76	14.00	7.37	−0.35	0.74
PEN	12	1.67	1.61	1.67	3.08	0.00	1.00
DMS	12	1.17	1.95	1.58	2.23	0.86	0.41
WFT phoneme	12	25.25	7.21	25.58	7.83	0.35	0.73
Category	12	36.25	7.20	39.42	6.47	2.40	0.04
CST part1	12	16.47	5.46	14.54	1.45	−1.40	0.19
Part2	12	21.67	6.40	19.40	3.29	−1.55	0.15
Part3	12	29.00	7.65	25.76	5.28	−2.34	0.04
Responders
	n	Pre		Post		t	p
		Mean	SD	Mean	SD
WCST CA	4	3.00	2.94	3.00	2.58	0.00	1.00
TE	4	18.75	5.38	18.25	7.50	−0.32	0.77
PEN	4	3.00	2.16	3.75	4.35	0.48	0.66
DMS	4	2.50	3.00	2.50	2.65	0.00	1.00
WFT phoneme	4	23.00	7.12	21.25	5.19	−0.78	0.49
Category	4	35.00	4.24	36.50	5.32	1.19	0.32
CST part1	4	20.20	8.74	15.01	1.50	−1.37	0.27
Part2	4	26.33	9.32	20.71	1.92	−1.48	0.23
Part3	4	33.14	8.11	27.07	2.32	−1.68	0.19
Non-responders
	n	Pre		Post		t	p
		Mean	SD	Mean	SD
WCST CA	8	5.38	1.06	5.00	2.07	−0.81	0.44
TE	8	12.25	2.66	11.88	6.77	−0.22	0.83
PEN	8	1.00	0.76	0.63	1.77	−0.55	0.60
DMS	8	0.50	0.76	1.13	2.03	1.17	0.28
WFT phoneme	8	26.38	7.46	27.75	8.29	1.82	0.11
Category	8	36.88	8.51	40.88	6.81	2.15	0.07
CST part1	8	14.61	1.46	14.30	1.46	−0.59	0.57
Part2	8	19.33	2.91	18.75	3.73	−0.67	0.52
Part3	8	26.93	7.00	25.10	6.33	−1.95	0.09

Notes: Paired t-tests analyzing the pre- and post-treatment difference revealed significant decreases in HAM-D and BDI scores (p = 0.0004 and p = 0.03, respectively). rTMS treatment significantly improved Category scores in the word fluency test (WFT) (p = 0.04, n = 12) and part 3 of the color Stroop test (CST) scores (p = 0.04, n = 12). In rTMS-responders (n = 4) or rTMS-non-responders (n = 8), rTMS treatment did not significantly improve any frontal lobe function.

Abbreviations: HAM-D, Hamilton Depressive Rating Scale; BDI, Beck Depression Inventory; WCST, Wisconsin Card Sorting Test; CA, categories achieved; TE, total errors; PEN, the Perseverative Errors of Nelson; DMS, Difficulties of Maintaining Set; WFT, Word Fluency Test; CST, Color Stroop Test.

Table 3 Changes In FA Values Induced By rTMS

	n	Pre		Post		t	p
		Mean	SD	Mean	SD
FA in the left middle frontal gyrus	12	0.588	0.094	0.581	0.080	−0.563	0.585
In the right middle frontal gyrus	12	0.558	0.081	0.588	0.061	1.427	0.181
In the left superior frontal gyrus	12	0.616	0.062	0.606	0.055	−0.871	0.403
In the right superior frontal gyrus	12	0.562	0.070	0.587	0.072	3.512	0.005
Responders
	n	Pre		Post		t	p
		Mean	SD	Mean	SD
FA in the left middle frontal gyrus	4	0.532	0.090	0.546	0.073	0.486	0.660
In the right middle frontal gyrus	4	0.551	0.084	0.576	0.064	0.439	0.690
In the left superior frontal gyrus	4	0.608	0.086	0.587	0.069	−1.478	0.236
In the right superior frontal gyrus	4	0.513	0.100	0.533	0.094	1.035	0.377
Non-responders
	n	Pre		Post		t	p
		Mean	SD	Mean	SD
FA in the left middle frontal gyrus	8	0.616	0.089	0.599	0.081	−1.449	0.191
In the right middle frontal gyrus	8	0.562	0.085	0.594	0.063	1.829	0.110
In the left superior frontal gyrus	8	0.620	0.052	0.615	0.049	−0.297	0.775
In the right superior frontal gyrus	8	0.587	0.037	0.615	0.042	4.328	0.003

Notes: The region of interest (ROI) approach (n = 12) revealed that white matter fractional anisotropy (FA) in the right superior frontal gyri was significantly increased by rTMS (p = 0.004). In rTMS-responders (n = 4), the ROI approach did not reveal significantly increased white matter FA in any region by rTMS. In rTMS-non-responders (n = 8), the ROI approach revealed that rTMS significantly increased white matter FA in the right superior frontal gyrus.

Abbreviation: FA, fractional anisotropy.

Table 4 Correlation Between Changes In FA Values And Frontal Lobe Function As Well As Changes In FA Values And Depressive Symptoms (N=12)

		HAM-D	BDI	WCST				WFT		CST
				CA	TE	PEN	DMS	Phoneme	Category	Part1	Part2	Part3
FA in the left middle frontal gyrus	Pearson’s correlation	−0.451	−0.204	0.030	0.391	0.471	0.012	−0.757	−0.290	−0.658	−0.715	−0.668
	p	0.141	0.524	0.926	0.209	0.123	0.971	0.004	0.360	0.020	0.009	0.018
FA in the right middle frontal gyrus	Pearson’s correlation	0.154	0.151	0.191	0.081	0.115	−0.328	−0.698	−0.154	−0.629	−0.516	−0.679
	p	0.633	0.639	0.552	0.803	0.722	0.298	0.012	0.632	0.028	0.086	0.015
FA in the left superior frontal gyrus	Pearson’s correlation	−0.005	0.183	−0.021	0.226	0.405	0.067	0.000	−0.320	0.167	−0.039	0.182
	p	0.988	0.570	0.949	0.481	0.192	0.837	0.999	0.310	0.605	0.905	0.571
FA in the right superior frontal gyrus	Pearson’s correlation	−0.265	−0.201	0.533	0.025	0.126	−0.548	−0.138	−0.146	−0.403	−0.538	−0.232
	p	0.405	0.532	0.074	0.939	0.697	0.065	0.670	0.652	0.194	0.071	0.468

Notes: In the region of interest (ROI) analysis, none of the fractional anisotropy (FA) increases in any region were correlated with increases in HAM-D scores, BDI scores, or the improvement of any frontal lobe function (n = 12). The amount of changes in FA values and frontal lobe function was calculated by post-pre comparisons.

Abbreviations: HAMD, Hamilton Depressive Rating Scale; BDI, Beck Depression Inventory; WCST, Wisconsin Card Sorting Test; CA, categories achieved; TE, total errors; PEN, the Perseverative Errors of Nelson; DMS, Difficulties of Maintaining Set; WFT, Word Fluency Test; CST, Color Stroop Test; FA, fractional anisotropy.