Original articleAcute left prefrontal transcranial magnetic stimulation in depressed patients is associated with immediately increased activity in prefrontal cortical as well as subcortical regions
Section snippets
Subjects
Fifteen subjects who met diagnostic criteria for a major depressive episode (Structure Clinical Interview for DSM-IV; First et al 1995) signed a written informed consent form approved by the local institutional review board (IRB) to participate in this TMS/fMRI study. Eleven subjects had participated in previous TMS antidepressant treatment studies (George et al 2000, Nahas et al 2003) but had not had a TMS treatment for at least 3 months. Four TMS-naive subjects were recruited from the Medical
Subjects
Of 19 subjects screened and 15 subjects scanned, 14 subjects had data suitable for final analysis. Their demographics and stable maintenance medications are listed in Table 1. In subjects who had been treated with TMS previously, at least 3 months had lapsed since their most recent TMS exposure (range 3–58 months).
Safety, tolerability, and side effects
One subject developed claustrophobia within the scanner and could not be studied. The other subjects reported no side effects and tolerated the stimulation in the scanner with no problems.
Regional changes in BOLD functional MRI
Relative to baseline, 1-Hz TMS delivered to prefrontal cortex induced activation in several brain regions in the 14 subjects (Figure 1, Figure 2; Table 2). In addition to the significant increases directly underneath or near the coil, the following regions also demonstrated significant activation: ipsilateral hippocampus, bilateral thalamus (ipsilateral mediodorsal, bilateral pulnivar, anterior nucleus), bilateral putamen, bilateral parietal lobes and insula, right orbitofrontal cortex, left
Network analysis
Principal components analysis was performed on the average percent signal change from the 147 time points in the 12 ROIs derived from the group statistical map of TMS–rest. The two PCs accounted for 84.20% of the variance (first component 68.43%, second 15.77%). The PCs represent underlying processes that are believed to have created the correlations among the variables (Mosier and Bereznaya 2001).
Table 3 and Figure 3 show clustering of the data along the two PCs. The loading factors indicate
Discussion
Our findings demonstrate that 21 sec of 1-Hz rTMS at 100% MT over the left prefrontal cortex in depressed patients significantly increases blood flow in bilateral prefrontal regions (underneath the coil more than contralaterally) and in the ipsilateral hippocampus, bilateral putamen, bilateral thalamus, bilateral insula, bilateral temporal gyrus, and right lateral orbitofrontal cortex. These data thus provide indirect evidence supporting the initial hypothesis in 1994 regarding using prefrontal
Acknowledgements
This work was supported in part by grants from the National Alliance for Research in Schizophrenia and Depression (Independent Investigator Award to MSG), the Borderline Personality Disorder Research Foundation, National Institute of Mental Health Grant No. R01 RR 14080-02 (DEB), the Stanley Foundation (MSG), National Institute on Alcohol Abuse and Alcoholism Grant No. 2 P50 AA10761-03 (MSG), National Institute of Mental Health Grant No. R01 RR14080-01 (MSG), National Institute of Neurological
References (72)
- et al.
A combined TMS/fMRI study of intensity-dependent TMS over motor cortex
Biol Psychiatry
(1999) - et al.
SPECT mapping of cerebral activity changes induced by repetitive transcranial magnetic stimulation in depressed patients. A pilot study
Psychiatry Res
(2001) Neuroimaging studies of mood disorders
Biol Psychiatry
(2000)- et al.
A controlled trial of daily left prefrontal cortex TMS for treating depression
Biol Psychiatry
(2000) - et al.
The navigation of transcranial magnetic stimulation
Psychiatry Res
(2001) - et al.
Electrical stimulation of rat medial prefrontal cortex enhances forebrain serotonin outputImplications for electroconvulsive therapy and transcranial magnetic stimulation in depression
Neuropsychopharmacology
(1999) - et al.
Left prefrontal-repetitive transcranial magnetic stimulation (rTMS) and regional cerebral glucose metabolism in normal volunteers
Psychiatry Res
(2002) - et al.
Frequency dependence of antidepressant response to left prefrontal repetitive transcranial magnetic stimulation (rTMS) as a function of baseline cerebral glucose metabolism
Biol Psychiatry
(1999) - et al.
Transcranial magnetic stimulation and antidepressive drugs share similar cellular effects in rat hippocampus
Neuropsychopharmacology
(2001) - et al.
Aging affects transcranial magnetic modulation of hippocampal evoked potentials
Neurobiol Aging
(2001)