Differential effects of deep TMS of the prefrontal cortex on apathy and depression.

BACKGROUND: Apathy is one hallmark of major depression (MDD). It is distinguished by lack of emotion, whereas other aspects of depression involve considerable emotional distress. Investigating both apathy and depression may increase the degree of treatment efficacy for both ailments together and apart. OBJECTIVE: Evaluate the differential effects of deep transcranial magnetic stimulation (DTMS) over the prefrontal cortex (PFC) on apathy and other aspects of depression in patients suffering from a depressive episode. METHODS: Fifty-four treatment-resistant MDD patients were evaluated with the Hamilton Rating Scale for Depression (HRSD), and then treated with DTMS. Apathy-related items from HRSD (ApHRSD) were compared with the remaining items from HRSD (DepHRSD). Antidepressant medications were withdrawn and active DTMS treatment was administered at 20 Hz, 5 days a week for 4 weeks. Changes in HRSD were recorded. Primary efficacy time point was 1 week after the end of active treatment. RESULTS: At screening, ApHRSD distribution was unimodal (moderate apathy), with low correlation (r = 0.17) between ApHRSD and DepHRSD. After treatment, a third had remitted apathy, and the correlation between ApHRSD and DepHRSD had dramatically increased (r = 0.83). Severe ApHRSD (≥ 7) at screening correlated with nonremission for both ApHRSD (R(2) = 0.1993, P = .0012) and DepHRSD (R(2) = 0.0860, P = .0334). CONCLUSIONS: DTMS over the PFC improved both apathy and depression similarly. However, DTMS did not lead to MDD remission if ApHRSD at screening was ≥ 7 of 12. Further investigation using a larger sample will determine whether screening apathy at baseline could be used to predict efficacy of DTMS in MDD patients.

Deep transcranial magnetic stimulation over the prefrontal cortex: evaluation of antidepressant and cognitive effects in depressive patients.

BACKGROUND: Electroconvulsive therapy (ECT) is an effective alternative for pharmacotherapy in treatment-resistant depressive patients, but the side effects limit its use. Transcranial magnetic stimulation (TMS) has been proposed as a refined alternative, but most studies do not indicate that TMS is as effective as ECT for severe depression. OBJECTIVE: We propose that the limited effectiveness of standard TMS resides in its superficial effect on the cortex, although much of the pathophysiology of depression is associated with deeper and larger brain regions implicated in the reward system. Herein, we tested the effectiveness and safety of a novel TMS coil, the "H-coil," which enables direct stimulation of deeper brain regions, at the expense of focality. METHODS: We have studied the antidepressant and cognitive effects induced by 4 weeks of high-frequency (20 Hz) repeated deep TMS (DTMS) over the prefrontal cortex (PFC) of 65 medication-free depressive patients, who have failed to benefit from prior medications. Patients were randomly assigned to various treatment configurations, differing in stimulation intensity and laterality. Effects were assessed by the 24-item Hamilton depression rating scale (HDRS-24) and several secondary outcome measures. RESULTS: A significant improvement in HDRS scores was found when high, but not low, stimulation intensity was used. Several cognitive improvements were evident, and no treatment-related serious adverse events were observed. CONCLUSIONS: DTMS over the PFC was found safe and effective in alleviating depression. The results accentuate the significance of deep, high-intensity stimulation over low, and serve as the first study to indicate the potential of DTMS in psychiatric and neurologic disorders.

A randomized controlled feasibility and safety study of deep transcranial magnetic stimulation.

OBJECTIVE: The H-coils are a new development in transcranial magnetic stimulation (TMS) research, allowing direct stimulation of deeper neuronal pathways than does standard TMS. This study assessed possible health risks, and some cognitive and emotional effects, of two H-coil versions designed to stimulate deep portions of the prefrontal cortex, using several stimulation frequencies. METHODS: Healthy volunteers (n=32) were randomly assigned to one of four groups: each of two H-coil designs (H1/H2), standard figure-8 coil, and sham-coil control. Subjects were tested in a pre-post design, during three increasing (single pulses, 10 Hz, and 20 Hz) stimulation sessions, as well as 24-36 h after the last stimulation. RESULTS: The major finding of the present study is that stimulation with the novel H-coils was well tolerated, with no adverse physical or neurological outcomes. Computerized cognitive tests found no deterioration in cognitive functions, except for a transient short-term effect of the H1-coil on spatial recognition memory on the first day of rTMS (but not in the following treatment days). On the other hand, spatial working memory was transiently improved by the H2-coil treatment. Finally, the questionnaires showed no significant emotional or mood alterations, except for reports on 'detachment' experienced by subjects treated with the H1-coil. CONCLUSIONS: This study provides additional evidence for the feasibility and safety of the two H-coil designs (H1/H2). SIGNIFICANCE: The H-coils offer a safe new tool with potential for both research and clinical applications for psychiatric and neurological disorders associated with dysfunctions of deep brain regions.