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Updated: Aug 5, 2026
MRI-guided dmPFC-rTMS as a Treatment for Treatment-resistant Major Depressive Disorder
Published on: August 11, 2015
Fractal dynamics in spontaneous motor activity associate with effective antidepressant chronotherapeutic response,
Chiara Verga1, Beatrice Bravi1, Edoardo Venturelli1,2
1Division of Neuroscience, Psychiatry and Clinical Psychobiology Unit, IRCCS San Raffaele Hospital, Milan, Italy.
Aim:
Bipolar disorder (BD) is characterized by circadian dysregulation, altered sleep-wake behaviors, and heterogeneous antidepressant response. Chronotherapeutic interventions such as total sleep deprivation combined with light therapy (TSD + LT) produce rapid antidepressant effects, but predictors of outcome are lacking. We investigated whether fractal dynamics of motor activity, indexed by the short-term scaling exponent α₁, are associated with antidepressant response, sleep-wake regulation, and structural brain measures and may serve as a biomarker of treatment responsiveness.
Methods:
Sixty-eight BD inpatients underwent three cycles of TSD + LT. Depressive symptoms were assessed with the Hamilton Depression Rating Scale (HDRS), and treatment response was defined as a post-treatment HDRS score <8. α₁ was derived from actigraphy using detrended fluctuation analysis, with values close to 1 indicating optimal fractal regulation. α₁ was computed before and after TSD + LT, and Δα₁ represented treatment-related change. Sleep-wake and circadian parameters were examined. A subsample underwent multimodal magnetic resonance imaging (MRI).
Results:
TSD + LT induced clinical improvement in 65.3% of patients. Responders showed a significant reduction in α₁ toward values close to 1, whereas nonresponders did not. Δα₁ correlated with symptom improvement (P = 0.035) and was independently associated with treatment response (P = 0.039). Baseline α₁ was associated with sleep-wake parameters, cerebellar gray matter volume, and white-matter microstructure, including cerebellar peduncles and thalamo-cortical tracts. Circadian rhythmicity increased in responders and decreased in nonresponders.
Conclusion:
Fractal motor activity tracks clinical changes during chronotherapeutic treatment in BD and may represent a candidate marker of treatment-related behavioral regulation. Its association with cerebellar and white-matter measures suggests multimodal relevance, warranting validation in larger longitudinal studies.
