Speer AM, Kimbrell TA, Wassermann EM, DR J, Willis MW, Herscovitch P et al. Opposite effects of high and low frequency rTMS on regional brain activity in depressed patients. Biol Psychiatry 48: 1133-1141
High (10-20 Hz) and low frequency (1-5 Hz) repetitive transcranial magnetic stimulation (rTMS) have been explored for possible therapeutic effects in the treatment of neuropsychiatric disorders. As part of a double-blind, placebo-controlled, crossover study evaluating the antidepressant effect of daily rTMS over the left prefrontal cortex, we evaluated changes in absolute regional cerebral blood flow (rCBF) after treatment with 1- and 20-Hz rTMS. Based on preclinical data, we postulated that high frequency rTMS would increase and low frequency rTMS would decrease flow in frontal and related subcortical circuits.
Ten medication-free, adult patients with major depression (eight unipolar and two bipolar) were serially imaged using (15)O water and positron emission tomography to measure rCBF. Each patient was scanned at baseline and 72 hours after 10 daily treatments with 20-Hz rTMS and 10 daily treatments with 1 Hz rTMS given in a randomized order. TMS was administered over the left prefrontal cortex at 100% of motor threshold (MT). Significant changes in rCBF from pretreatment baseline were determined by paired t test.
Twenty-hertz rTMS over the left prefrontal cortex was associated only with increases in rCBF. Significant increases in rCBF across the group of all 10 patients were located in the prefrontal cortex (L > R), the cingulate gyrus (L > R), and the left amygdala, as well as bilateral insula, basal ganglia, uncus, hippocampus, parahippocampus, thalamus, and cerebellum. In contrast, 1-Hz rTMS was associated only with decreases in rCBF. Significant decreases in flow were noted in small areas of the right prefrontal cortex, left medial temporal cortex, left basal ganglia, and left amygdala. The changes in mood following the two rTMS frequencies were inversely related (r = -.78, p <.005, n = 10) such that individuals who improved with one frequency worsened with the other.
These data indicate that 2 weeks of daily 20-Hz rTMS over the left prefrontal cortex at 100% MT induce persistent increases in rCBF in bilateral frontal, limbic, and paralimbic regions implicated in depression, whereas 1-Hz rTMS produces more circumscribed decreases (including in the left amygdala). These data demonstrate frequency-dependent, opposite effects of high and low frequency rTMS on local and distant regional brain activity that may have important implications for clinical therapeutics in various neuropsychiatric disorders.
"Cortical activation patterns can be selectively modified by means of repetitive transcranial magnetic stimulation (rTMS) via electromagnetic induction . This way, rTMS has been shown to modulate neurotransmitter release  and—depending on its stimulation frequency—normalise prefrontal hypoactivity . In fact, even though results are still inconsistent , rTMS has been shown to have a moderate antidepressant effect  . "
[Show abstract][Hide abstract] ABSTRACT: Objectives:
Neurobiologically, panic disorder (PD) is supposed to be characterised by cerebral hypofrontality. Via functional near-infrared spectroscopy (fNIRS), we investigated whether prefrontal hypoactivity during cognitive tasks in PD-patients compared to healthy controls (HC) could be replicated. As intermittent theta burst stimulation (iTBS) modulates cortical activity, we furthermore investigated its ability to normalise prefrontal activation.
Forty-four PD-patients, randomised to sham or verum group, received 15 iTBS-sessions above the left dorsolateral prefrontal cortex (DLPFC) in addition to psychoeducation. Before first and after last iTBS-treatment, cortical activity during a verbal fluency task was assessed via fNIRS and compared to the results of 23 HC.
At baseline, PD-patients showed hypofrontality including the DLPFC, which differed significantly from activation patterns of HC. However, verum iTBS did not augment prefrontal fNIRS activation. Solely after sham iTBS, a significant increase of measured fNIRS activation in the left inferior frontal gyrus (IFG) during the phonological task was found.
Our results support findings that PD is characterised by prefrontal hypoactivation during cognitive performance. However, verum iTBS as an "add-on" to psychoeducation did not augment prefrontal activity. Instead we only found increased fNIRS activation in the left IFG after sham iTBS application. Possible reasons including task-related psychophysiological arousal are discussed.
"That result is strongly in line with the increase of the cortical excitability after the high frequency rTMS (Fitzgerald et al., 2002; Hallett and Rothwell, 2011). Our results confirm the previous findings that the decrease of the frontal hypoactivity, probably in terms of cortical activity's normalization, could represent the underlying mechanism by which not only antidepressant drugs (Baxter et al., 1989; Mayberg et al., 2000) but also high frequency TMS fosters improvements in depressive disorder, as highlighted by the higher cerebral blood flow values and the cortical excitability increase (George et al., 1999, 2000; Teneback et al., 1999; Speer et al., 2000; Nahas et al., 2001; Rossini et al., 2010). We hypothesize that the high frequency rTMS, stimulating the underlying cortical region and changing the activity of the corresponding neural tissue, could determine an up-regulation of the local activity (Chen, 2000; Fitzgerald et al., 2002). "
[Show abstract][Hide abstract] ABSTRACT: Sleep alterations are among the most important disabling manifestation symptoms of Major Depression Disorder (MDD). A critical role of sleep importance is also underlined by the fact that its adjustment has been proposed as an objective marker of clinical remission in MDD. Repetitive transcranial magnetic stimulation (rTMS) represents a relatively novel therapeutic tool for the treatment of drug-resistant depression. Nevertheless besides clinical evaluation of the mood improvement after rTMS, we have no clear understanding of what are the neurophysiological correlates of such treatment. One possible marker underlying the clinical outcome of rTMS in MDD could be cortical changes on wakefulness and sleep activity. The aim of this open-label study was to evaluate the efficacy of a sequential bilateral rTMS treatment over the dorsolateral prefrontal cortex (DLPFC) to improve the mood in MDD patients, and to determine if rTMS can induce changes on the sleep structure, and if those changes can be used as a surrogate marker of the clinical state of the patient. Ten drug-resistant depressed patients participated to ten daily sessions of sequential bilateral rTMS with a low-frequency TMS (1 Hz) over right-DLPFC and a subsequent high-frequency (10 Hz) TMS over left-DLPFC. The clinical and neurophysiological effects induced by rTMS were evaluated respectively by means of the Hamilton Depression Rating Scale (HDRS), and by comparing the sleep pattern modulations and the spatial changes of EEG frequency bands during both NREM and REM sleep, before and after the real rTMS treatment. The sequential bilateral rTMS treatment over the DLPFC induced topographical-specific decrease of the alpha activity during REM sleep over left-DLPFC, which is significantly associated to the clinical outcome. In line with the notion of a left frontal hypoactivation in MDD patients, the observed local decrease of alpha activity after rTMS treatment during the REM sleep suggests that alpha frequency.
Frontiers in Human Neuroscience 08/2013; 7:433. DOI:10.3389/fnhum.2013.00433 · 2.99 Impact Factor
"Several neuroimaging studies have confirmed activation of underlying brain areas after TMS, for example over the motor cortex7) or over the prefrontal cortex. Speer et al.8) observed increased blood flow (as measured with H2O positron emission tomography) after 10 Hz rTMS to the left dorsolateral prefrontal cortex (DLPFC), whereas 1 Hz stimulation decreased blood flow. Indeed, frequencies of 1 Hz or lower are generally considered to be inhibitory (i.e., they reduce cortical excitability of the underlying area), whereas frequencies of 5 Hz and higher are considered to be excitatory.6) "
[Show abstract][Hide abstract] ABSTRACT: The potential of noninvasive neurostimulation by repetitive transcranial magnetic stimulation (rTMS) for improving psychiatric disorders has been studied increasingly over the past two decades. This is especially the case for major depression and for auditory-verbal hallucinations in schizophrenia. The present review briefly describes the background of this novel treatment modality and summarizes evidence from clinical trials into the efficacy of rTMS for depression and hallucinations. Evidence for efficacy in depression is stronger than for hallucinations, although a number of studies have reported clinically relevant improvements for hallucinations too. Different stimulation parameters (frequency, duration, location of stimulation) are discussed. There is a paucity of research into other psychiatric disorders, but initial evidence suggests that rTMS may also hold promise for the treatment of negative symptoms in schizophrenia, obsessive compulsive disorder and post-traumatic stress disorder. It can be concluded that rTMS induces alterations in neural networks relevant for psychiatric disorders and that more research is needed to elucidate efficacy and underlying mechanisms of action.
Clinical Psychopharmacology and Neuroscience 08/2013; 11(2):53-59. DOI:10.9758/cpn.2013.11.2.53
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