Article

Frequency dependence of antidepressant response to left prefrontal repetitive transcranial magnetic stimulation (rTMS) as a function of baseline cerebral glucose metabolism

Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
Biological Psychiatry (Impact Factor: 10.26). 12/1999; 46(12):1603-13. DOI: 10.1016/S0006-3223(99)00195-X
Source: PubMed

ABSTRACT

Recent studies suggest that both high frequency (10-20 Hz) and low frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) have an antidepressant effect in some individuals. Electrophysiologic data indicate that high frequency rTMS enhances neuronal firing efficacy and that low frequency rTMS has the opposite effect.
We investigated the antidepressant effects of 10 daily left prefrontal 1 Hz versus 20 Hz rTMS with the hypothesis that within a given subject, antidepressant response would differ by frequency and vary as a function of baseline cerebral glucose metabolism. After baseline PET scans utilizing [18F]-Fluorodeoxyglucose, thirteen subjects participated in a randomized crossover trial of 2 weeks of 20 Hz paired with 2 weeks 1 Hz or placebo rTMS.
We found a negative correlation between degree of antidepressant response after 1 Hz compared to 20 Hz rTMS (r = -0.797, p < .004). Additionally, better response to 20 Hz was associated with the degree of baseline hypometabolism, whereas response to 1 Hz rTMS tended to be associated with baseline hypermetabolism.
These preliminary results suggest that antidepressant response to rTMS might vary as a function of stimulation frequency and may depend on pretreatment cerebral metabolism. Further studies combining rTMS and functional neuroimaging are needed.

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    • "Although we have not compared to such samples, our results add that higher cerebellar CMRglc may be indicative for beneficial response to HF-rTMS treatment , even when controlled for the number of sessionsSpeer et al. 2009) found that the degree of antidepressant response to 1-Hz rTMS correlated with the initial degree of hyperperfusion (H 2 15 O PET) in particular in the cerebellum. This association however was not found with a high frequency approach and 99m Tc-ECD SPECT (Richieri et al. 2011Richieri et al. , 2015), and even a reversed pattern was found (Kimbrell et al. 1999). Methodological differences in stimulation protocol, patient inclusion, and brain imaging method may to some extent be responsible for the discrepant results. "
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    ABSTRACT: Repetitive transcranial magnetic stimulation (rTMS) is an evidence based neurostimulation modality used to treat patients with Major Depressive Disorder (MDD). In spite that the duration of current a depressive episode has been put forward as a negative predictor for clinical outcome, little is known about the underlying neurobiological mechanisms of this phenomenon. To address this important issue, in a sample of 43 melancholic stage III treatment resistant antidepressant-free refractory MDD patients, we reanalysed regional cerebral glucose metabolism (CMRglc) before high frequency (HF)-rTMS treatment, applied to the left dorsolateral prefrontal cortex (DLPFC). Besides that a lower baseline cerebellar metabolic activity indicated negative clinical response, a longer duration of the depressive episode was a negative indicator for recovery and negatively influenced cerebellar CMRglc. This exploratory 18FDG PET study is the first to demonstrate that the clinical response of HF-rTMS treatment in TRD patients may depend on the metabolic state of the cerebellum. Our observations could imply that for left DLPFC HF-rTMS non-responders other brain localisations for stimulation, more specifically the cerebellum, may be warranted.
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    • "The PFC-thalamo-limbic (e.g., amygdala) pathway is one of the key circuits implicated in depression [11] and its disruption may be specific to refractory MDD. High-frequency prefrontal rTMS has been reported to enhance cortical excitability/activity [5], [12], [13] and to improve PFC inhibitory functions through enhanced GABA-mediated inhibitory neurotransmission [14], and therefore normalizes the PFC-limbic dys-regulation of the depressive circuit [7], [15]. The amygdala is a major structure in the emotional limbic system of human subjects with depression [16]. "
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    • "Repetitive TMS (rTMS) has been found to exert excitatory or inhibitory modulation on brain activity, depending on the stimulation frequency. High-frequency rTMS (Ͼ10 Hz) has been posited to increase regional brain activity and facilitate synaptic potentiation , whereas low-frequency rTMS (Ͻ1 Hz) downregulates and inhibits brain activity (Kimbrell et al., 1999; George and Belmaker, 2000; Maeda et al., 2000; Speer et al., 2000; Fitzgerald et al., 2006). rTMS has been investigated as a potential treatment for PTSD in several clinical trials (Grisaru et al., 1998; McCann et al., 1998; Rosenberg et al., 2002; Cohen et al., 2004). "
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