Background: Major Depressive Disorder is a common psychiatric disorder characterized by defects in affective processing and self-perception.Wide variety of neurobiological models of depression has been proposed,however reports on psychotherapy induced effects were rare.We conducted a longitudinal study to explore the underlying brain mechanism of guided-imagery psychotherapy in MDD.Methods: A total of 23 MDD patients and 20 age-,sex-,and education-matched healthy controls were enrolled.Resting-state magnetic resonance and anatomical date were acquired.The psycho-therapist administered guided-imagery psychotherapy therapy to all 23 patients.Then we presented a longitudinal study union the voxel-based morphometry(VBM)method and the amplitude of low-frequency fluctuation(ALFF)method in a guided-imagery psychotherapy research of MDD to evaluate regional gray matter structural and functional activity alterations in MDD corresponding with the neurological impairment and early-stage therapeutic reaction Results: Compared with healthy control group,patients showed increased fALFF values but lower GMV in bilateral orbitofrontal cortex(OFC).After therapy we observed significant decreased spontaneous activity of frontocingulate area including dorsal(dACC)and subgenual anterior cingulate(sgACC),moreover,the post-treatment fALFF of sgACC was negatively correlated with symptom improvement.Functional connectivity analysis presented increased connectivity between the dACC and dorsolateral prefrontal cortex(DLPFC),as well as the sgACC and left supplementary motor area(SMA).Conclusion: The successful treatment did not operate by normalizing the regionally disruptions directly but modulate the activity of sgACC to regulate cortical-limbic connectivity and remodel the global emotion-related functional loop.The sgACC served as a bridge and initial trigger point in the psychological intervention procedure and it could be a key hub of all kinds of antidepressive therapy.In addition even though the striatum retained in a normal level both in functional and structural date,the pre-treatment striatal activity exhibited most highly correlation with the symptom remission and prognosis,enlightened that the depression is a synthetical disorder involved multiple protective and aggressive factors in its neural mechanisms.Striatal function may contribute indirectly to maintain the normal state of mind and could be an independent protective factor of depression.