Noradrenergic Transmission at Alpha1-Adrenergic Receptors in the Ventral Periaqueductal Gray Modulates Arousal

Background

Dysregulation of arousal is symptomatic of numerous psychiatric disorders. Previous research has shown that the activity of dopamine (DA) neurons in the ventral periaqueductal gray (vPAG) tracks with arousal state, and lesions of vPAG^DA cells increase sleep. However, the circuitry controlling these wake-promoting DA neurons is unknown.

Effect of electroconvulsive therapy on cortical excitability in patients with major depression: a transcranial magnetic stimulation study.

OBJECTIVE: The antidepressant action of electro-convulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) may be related to their ability to modulate cortical excitability. The aim of this study was to investigate changes in cortical excitability following ECT in patients with major depression (MD) and to compare therapeutic efficacy of ECT combined with rTMS to that of ECT alone. METHODS: Twenty-two patients with MD were assigned to receive ECT and right prefrontal 1 Hz rTMS (n=12) or ECT with sham rTMS (n=10). ECT was given twice weekly and rTMS was applied on the remaining 4 days, throughout 3 weeks. The resting motor threshold (rMT) and motor evoked potential (MEP)/M-wave area ratio were evaluated before and 6 h after the first, third and sixth ECT session. The active motor threshold (aMT), intra-cortical inhibition (ICI) and intra-cortical facilitation (ICF) were measured at baseline and 24 h after the last ECT. RESULTS: There were no significant differences in the degree of clinical improvement and measures of cortical excitability in the ECT+active rTMS group as compared to the ECT+sham rTMS group. Marked clinical improvement observed in 19 out of the 22 patients was associated with a significant increase of the MEP/M-wave area ratio, decrease of the aMT and reduction of the ICI in the left hemisphere. CONCLUSIONS: The antidepressant effect of ECT was associated with an enhancement of left hemispheric excitability. rTMS did not add to the beneficial effect of ECT. However, the small sample size and the robust effect of ECT might have obscured a potential therapeutic effect of rTMS. SIGNIFICANCE: Measures of cortical excitability may provide insight to our understanding of the mechanism of action of ECT and might be useful for the assessment of treatment response.     

Antidepressant effects of different schedules of repetitive transcranial magnetic stimulation vs. clomipramine in patients with major depression: relationship to changes in cortical excitability

The antidepressant effects of repetitive transcranial magnetic stimulation (rTMS) that have been demonstrated in recent studies could be related to its ability to modulate cortical excitability. Yet, the relationship between stimulus location and frequency and treatment outcome has not been established. The aim of the present study was to compare efficacy of rTMS in various configurations and clomipramine treatment in patients with major depression (MD) and to evaluate the relationship between clinical outcome and changes in cortical excitability. Fifty-nine MD patients were randomized to receive (1) left (n = 12) or right (n = 12) 3 Hz rTMS with placebo medication; (2) left (n = 10) or right (n = 9) 10 Hz rTMS with placebo medication; (3) active medication (clomipramine) with sham rTMS (n = 16). Both 3 Hz and 10 Hz rTMS were administered to the prefrontal cortex by a circular coil at an intensity of 110% and 100% of the resting motor threshold (rMT) respectively. Measurements of cortical excitability were performed prior to and 24 h after completion of 2 wk of daily rTMS or pharmacological treatments. These included the rMT, silent period threshold (SPT), inter-threshold difference (ITD), MEP/M-wave amplitude ratio and silent period duration (SPD). Severity of depression was blindly assessed by the Hamilton Depression Rating Scale (HDRS). The best improvement scores were seen in patients who received left 3 Hz rTMS. The 10 Hz rTMS treatment was less tolerated resulting in a significantly higher dropout rate. A significant increase of the MEP/M wave amplitude ratio accompanied by a shortening of the SPD was evidenced in patients who showed marked clinical improvement (reduction in HDRS by 50% or more) following left rTMS regardless of stimulation frequency. Our results suggest that 3 Hz left rTMS has a higher therapeutic efficacy and tolerability in patients with MD. The enhancement of cortical excitability may be related to the antidepressant action of rTMS.