Although repetitive transcranial magnetic stimulation (rTMS) proved effective in treating treatment-resistant depression (TRD), including significant improvements in several subscales of frontal lobe dysfunction, no correlation was noted between improvements in frontal lobe dysfunction and improvements in white matter integrity in patients with TRD, according to a small study published in Neuropsychiatric Disease and Treatment.

Japanese researchers recruited 12 patients with unipolar depression who fulfilled the diagnostic criteria for both major depressive episode (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision) and TRDbetween August 2013 and January 2019. They treated all patients with active, high-frequency (10 Hz) rTMS and performed diffusion tensor imaging scans twice: before treatment with rTMS to obtain a baseline measure and again after 6 weeks of treatment, within 24 to 72 hours after the last session. Investigators used oval regions of interest to measure fractional anisotropy (FA) values.

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Treatment with rTMS significantly improved scores for the Hamilton depressive rating scale and the Beck depression inventory (P =.0004 and P =.03, respectively), as well as category scores in the word fluency test (P =.04) and part 3 of the color Stroop test scores (P =.04). In rTMS responders (n=4), the region of interest approach did not reveal significantly increased white matter FA in the left and right middle and superior frontal gyri. None of the FA increases in any region correlated with increases in Hamilton depressive rating scale scores, Beck depression inventory scores, or improvements in frontal lobe dysfunction.

Limitations of this study included the lack of a control condition using a sham rTMS procedure and the relatively small sample size. The negative correlation found may be caused only by this small sample size. Researchers did not conduct structured clinical interviews.

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“To our knowledge, this is the first study to investigate the relationship between rTMS-induced improvements of frontal lobe dysfunction and white matter integrity in TRD patients,” the researchers concluded. “The present results suggest that rTMS is effective for treating TRD, and that it is associated with significant improvements on several subscales of frontal lobe dysfunction. Category scores in [word fluency tests] and part 3 of the [color Stroop test] scores improved independently of the improvement of depressive symptoms. Importantly, we found no correlation between the improvement of frontal lobe dysfunction by rTMS and the improvement of white matter integrity by rTMS in TRD patients.”

Tateishi H, Nishihara M, Kawaguchi A, et al. Improvement of frontal lobe dysfunction and white matter integrity by rTMS in treatment-resistant depressionNeuropsychiatr Dis Treat. 2019;15:3079-3087.