• Jared L. Moreines B.S.,

    Corresponding author
    1. Medical Scientist Training Program, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
    • Correspondence to: Jared Moreines, Department of Neuroscience, University of Pittsburgh, A210 Langley Hall, Pittsburgh, PA 15260. E-mail:

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  • Shawn M. McClintock Ph.D., M.S.C.S.,

    1. Neurocognitive Research Laboratory, Division of Brain Stimulation and Neurophysiology, Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, North Carolina
    2. Department of Psychiatry, UT Southwestern Medical Center, Dallas, Texas
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  • Mary E. Kelley Ph.D.,

    1. Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia
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  • Paul E. Holtzheimer M.D.,

    1. Departments of Psychiatry and Surgery, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire
    2. Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia
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  • Helen S. Mayberg M.D.

    1. Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia
    2. Department of Neurology, Emory University School of Medicine, Atlanta, Georgia
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  • Funding for this work was provided by grants from the Dana Foundation (Dr. Mayberg), Stanley Medical Research Institute (Dr. Mayberg), Woodruff Foundation (Dr. Mayberg), Emory Healthcare (Dr. Mayberg), National Institutes of Health K23 MH077869 (Dr. Holtzheimer) and K23 MH087739 (Dr. McClintock), the Atlanta Clinical and Translational Science Initiative supported by UL1TR000454 (Mr. Moreines), the Summer Undergraduate Research at Emory program supported by Howard Hughes Medical Institute Grant No. 52005873 (Mr. Moreines), and the Scholarly Inquiry and Research at Emory program (Mr. Moreines). Devices were donated by Advanced Neuromodulation Systems/St Jude Medical Neuromodulation.



Treatment-resistant depression (TRD) is a pervasive and difficult to treat condition for which deep brain stimulation (DBS) of the subcallosal cingulate white matter (SCCwm) is an emerging therapeutic option. However, neuropsychological safety data for this novel treatment have only been published for a small number of subjects. Moreover, little is known regarding the neuropsychological profile present in TRD patients at baseline, prior to initiation of DBS therapy. This report describes the neuropsychological effects of TRD and acute and chronic DBS of the SCCwm in patients with unipolar and bipolar TRD.


Patients with TRD (N = 17) were compared to a healthy control group (N = 15) on subtests from the Cambridge Neuropsychological Test Automated Battery and the Stroop Task. Patients were then tested again at subsequent time points of 1 and 6 months following the initiation of chronic DBS of the SCCwm.


Patients with TRD showed similar levels of performance to healthy controls on most neuropsychological measures, with the exception that the TRD group had slower processing speed. Patients with bipolar TRD, relative to those with unipolar TRD, obtained lower scores on measures of executive function and memory only at baseline. With acute and chronic SCCwm DBS, neuropsychological function improved in multiple domains including processing speed and executive function (planning, set shifting, response inhibition), and memory remained stable.


Patients with TRD show slowed processing speed but otherwise largely preserved neuropsychological functioning. DBS of the SCCwm does not result in worsening of any aspect of neuropsychological function and may improve certain domains. Future research is warranted to better understand the effects of TRD and DBS on neuropsychological function.