Changes in dorsolateral prefrontal connectivity after rTMS in treatment-resistant depression: a brain perfusion SPECT study.
OBJECTIVE
Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive and safe alternative to electroconvulsive therapy for treatment-resistant depression (TRD). After rTMS, changes in brain SPECT perfusion have been remotely identified within medial temporal limbic areas, while no local effects have been found within the left dorsolateral prefrontal cortex (DLPFC)-i.e. under the coil. Functional changes in connectivity may underlie these remote effects. Interestingly, functional connectivity has been recently investigated using perfusion SPECT, and abnormalities identified in TRD patients. The aim of the present study is to evaluate perfusion and connectivity SPECT changes in TRD patients after rTMS of the left DLPFC. We hypothesize that changes in DLPFC networks may explain remote hypoperfusions found after rTMS.


METHODS
Fifty-eight TRD patients underwent a brain SPECT before and after high-frequency rTMS of the left DLPFC. Whole-brain voxel-based changes in perfusion were evaluated with SPM8, and inter-regional correlation analysis performed to study left DLPFC functional connectivity (p < 0.005, corrected for cluster volume).


RESULTS
After rTMS, patients were significantly improved on Beck Depression Inventory score (p < 0.0001). Considering a 50% reduction threshold, 27 patients were identified as responders (47%). After rTMS, perfusion changes were not found locally within the left DLPFC, but remotely within the bilateral temporal lobes, including limbic areas. Inter-regional correlation SPECT analysis brings out a decrease of connectivity between the left DLPFC and both the cingulate/medial frontal cortex and bilateral medial temporal limbic areas, in relation with the clinical response.


CONCLUSIONS
rTMS of DLPFC in TRD patients leads to remote temporal hypoperfusions in relation with changes in functional connectivity between the DLPFC and the default mode network, especially including medial temporal limbic areas.
Department of Psychiatry, La Conception University Hospital, 13005, Marseille, France.|EA 3279 - Self-perceived Health Assessment Research Unit, Aix-Marseille Univ, 13005, Marseille, France.
Raphaëlle
R
Richieri
Service Central de Biophysique et Médecine Nucléaire, Hôpital de la Timone, APHM, 264 rue Saint Pierre, 13005, Marseille, France.
Damien
D
Jouvenoz
Department of Nuclear Medicine & Nancyclotep Imaging Platform, 54000, Nancy, France.|IADI, INSERM U947, 54000, Nancy, France.
Antoine
A
Verger
Department of Psychiatry, La Conception University Hospital, 13005, Marseille, France.|EA 3279 - Self-perceived Health Assessment Research Unit, Aix-Marseille Univ, 13005, Marseille, France.
Patrick
P
Fiat
EA 3279 - Self-perceived Health Assessment Research Unit, Aix-Marseille Univ, 13005, Marseille, France.|Department of Public Health, Assistance Publique - Hôpitaux de Marseille, Marseille, France.
Laurent
L
Boyer
Department of Psychiatry, La Conception University Hospital, 13005, Marseille, France.|EA 3279 - Self-perceived Health Assessment Research Unit, Aix-Marseille Univ, 13005, Marseille, France.
Christophe
C
Lançon
Service Central de Biophysique et Médecine Nucléaire, Hôpital de la Timone, APHM, 264 rue Saint Pierre, 13005, Marseille, France. eric.guedj@ap-hm.fr.|Aix-Marseille Univ, INT, CNRS UMR 7289, 13005, Marseille, France. eric.guedj@ap-hm.fr.|Aix-Marseille Univ, CERIMED, 13005, Marseille, France. eric.guedj@ap-hm.fr.
Eric
http://orcid.org/0000-0003-1912-6132
E
Guedj
D061218:Depressive Disorder, Treatment-Resistant / Q000000981:diagnostic imaging* / Q000503:physiopathology / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000000981:diagnostic imaging* / Q000503:physiopathology; D055420:Perfusion Imaging; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging* / Q000503:physiopathology; D012189:Retrospective Studies; D015899:Tomography, Emission-Computed, Single-Photon; D050781:Transcranial Magnetic Stimulation
Connectivity; Repetitive transcranial magnetic stimulation (rTMS); SPM; Single-photon emission computed tomography (SPECT); Treatment-resistant depression