Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation

“At the motor cortices, these can be detected as suppression or facilitation of corticospinal excitability (Pascual-Leone et al., 1994; Chen et al., 1997; Wolters et al., 2003; Huang et al., 2005).”

“[39] demonstrated that low-frequency (0.”

“Conversely, low-frequency rTMS (at a rate of around 1 Hz) produces a lasting suppression of corticospinal excitability at suprathreshold (Chen et al. 1997) or subthreshold intensities of stimulation (Touge et al.”

“, 1998; Wassermann, 1998), while low frequency stimulation at 1 Hz and less can reduce excitability in underlying cortex (Chen et al., 1997).”

“Low-frequency (1 Hz) rTMS has been shown to decrease excitability of the motor system (Pascual-Leone et al., 1995; Chen et al., 1997; Gerschlager et al., 2001; van der Werf and Paus, 2002; Chouinard et al., 2003), and has also been used to investigate brain– behaviour relationships [e.g. (Kosslyn…”

“Neuropsychopharmacology lasting beyond the time of stimulation (Wassermann et al, 1996; Chen et al, 1997), but was not supported by Siebner et al (1999).”

“This way the interpulse interval was 10 s, thereby avoiding changes in motor excitability due to TMS per se (Chen et al., 1997).”

“2 Hz), which has been shown not to modify cortical excitability (Chen et al. 1997).”

“For example, stimulation for 15 min at 1 Hz in normal subjects reduces cortical excitability as demonstrated by an increase in resting motor threshold (RMT) levels and decreased motor-evoked potential (MEP) size (Chen et al., 1997; Fitzgerald et al., 2002a,b).”

“In general, high-frequency rTMS transiently facilitates cortical responses (Pascual-Leone et al. 1994) while low-frequency rTMS inhibits cortical excitability (Chen et al. 1997).”

“…frequency TMS ( 1 Hz) given at subthreshold ( 95% resting threshold) or suprathreshold ( 110% resting threshold) intensity produce a transient decrease in corticomotor excitability that lasts seconds to minutes (Chen et al., 1997; Maeda et al., 2000; Muellbacher et al., 2000; Touge et al., 2001).”

“Chen et al. (1997a) have demonstrated that low frequency rTMS stimulation for a period of approximately 15 min induces a transient inhibition of the cortex, thus providing a mechanism to address the right-sided hyperfunction found in depression.”

“However, the physiological mechanisms of this modulation were obscure. rTMS over M1 can modulate the ipsilateral sensory information processing (Enomoto et al., 2001; Tsuji and Rothwell, 2002) as well as motor cortical excitability (Chen et al., 1997; Pascual-Leone et al., 1994b).”

“Low-frequency rTMS (≤1 Hz) inhibits the cortical excitability and leads to a weakening of the transfer at the synapses [”

“…while higher frequency (> 5 Hz) rTMS increases neuronal activity and cortical excitability and increases relative regional cerebral blood flow (Chen et al., 1997; Pascual-Leone et al., 1994). rTMS could stimulate not only local but related far cortical and subcortical function, and the…”

“Moreover, transcranial brain stimulation at frequencies similar to ours, but with TMS, have been shown to reduce cortical excitability in humans (Chen et al., 1997).”

“One prominent notion, derived from motor cortex stimulation, is that fast rTMS induces neuronal excitation and slow rTMS neuronal inhibition of the target region (Pascual-Leone et al., 1994; Chen et al., 1997).”

“2–1 Hz produces a period of cortical inhibition (Chen et al., 1997; Maeda et al., 2000; Hallett, 2007) and is often used to deactivate a brain region temporarily to examine its direct causal contribution to a particular percept or behavior (Hallett, 2007; Wassermann and Zimmermann, 2012).”

“In this study we investigated in a group of healthy volunteers the effect of an rTMS protocol (1 Hz), which usually reduces motor cortical excitability (e.g. Chen et al., 1997; Maeda et al., 2000), on evoked MEPs and on the amplitude of TEPs evoked by single pulse TMS over the same area.”

“This is because 1 Hz rTMS is associated with a decrease in cortical excitability [28] and anodal tDCS is associated with an increase in cortical excitability [26].”

“Stimulation near 1 Hz has been demonstrated to have an inhibiting effect on brain excitability [22].”

“During the past decade, high-frequency rTMS has been shown to induce facilitatory effects on the human motor cortex (Pascual- Leone et al., 1994; Chen et al., 1997b; Berardelli et al., 1998; Maeda et al., 2000; Baumer et al., 2003; Peinemann et al., 2004).”

“Highfrequency TMS in the 5- to 20-Hz range temporarily increases the excitability of the motor cortex,(29,30) whereas low-frequency rTMS with stimulation rates of less than or equal to 1 Hz appears to temporarily decrease corticospinal excitability.(31) Whenever possible, we will try in this review identify which type…”

“Supporting this concept, several studies have now shown that chronic lowfrequency stimulation of the motor cortex can produce inhibitory intermediate-term effects (lasting for several minutes) after stimulation (34).”

“rTMS over the motor cortex at low frequency ( 1 Hz) decreases neuronal excitability of the stimulated brain area (Chen et al., 1997), whereas rTMS at highfrequency ranges (>5 Hz) increases neuronal excitability (Pascual-Leone, Valls-Sole, Wassermann, & Hallett, 1994).”

“It has been suggested that they resemble long-term potentiation (LTP) and long-term depression in animal models (Chen et al., 1997) which can induce early genes, e.g. c-fos, leading to protein synthesis.”

“Les post-effets induits par l’application d’une ou plusieurs sessions de rTMS dépendent de la fréquence de stimulation, ( à 1 Hz : diminution de l’excitabilité [37] ; > 5 Hz : augmentation de l’excitabilité [38]) du nombre de chocs (600–2000), de la longueur du train, de l’intensité de stimulation, du site de stimulat…”

“1–1 Hz) rTMS induces cortical inhibition, while high-frequency (5–20 Hz) rTMS induces cortical facilitation at the target ROI [160, 161].”

“1 Hz for 1 h having been shown to have no subsequent effect on excitability (Chen et al., 1997).”

“Magnetic pulses delivered repetitively (rTMS) and at low frequencies tend to inhibit neural activity (5) whereas high-frequency stimulation tends to facilitate neural activity (6,7).”

“In normal subjects, rTMS tonically applied over M1 at low frequency (1 Hz or less) reduces motor corticospinal output as demonstrated by post-rTMS decrease in motor-evoked potential amplitude [19], whereas the reverse is induced by rTMS bursts delivered at high frequency (5 Hz and higher) [87].”

“rTMS could modulate cortical excitability; specifically, high-frequency rTMS (ie, ≥5Hz) enhances motor cortex excitability,(9) whereas low-frequency rTMS (≤1Hz) downregulates cortical excitability.(10) The approach of neuromodulation offers a promising rationale in potentiating the efficacy of motor training by primin…”

“In fact, TMS can create temporary functional changes, by activating cells and removing them from participation in their normal function in a network.(1,2) With the variables used in the present study, we found no long-lasting antitremor effect.”

“Low frequency rTMS (~1 Hz) inhibits cerebral cortex [82,87,88].”

“Studies that have explored the physiological effects of low-frequency rTMS have predominately used 0.9-1.0 Hz stimulation which has been shown to produce a reduction in the excitability of local cortical regions (e.g. Chen et al., 1997 ; Chen and Seitz, 2001; Fitzgerald et al., 2002).”

“It has been reported that low-frequency rTMS of ≤ 1 Hz suppresses while high-frequency rTMS of ≥ 5 Hz activates local neural activities [1-4].”

“The choice of the duration of this inter-trial interval was based on research [58] that showed no change in cortico-spinal excitability after repetitive TMS at 0.”

“…to cortical excitation, as evidenced by increased amplitude of the TMS-induced motorevoked potential (MEP) (Pascual-Leone et al. 1994), whereas low-frequency rTMS, that is, very near 1 Hz, leads to cortical inhibition as evidenced by decreased amplitude of the TMS-induced MEP (Chen et al. 1997).”

“, 1997, 1999) and physiological levels (Chen et al., 1997; Klein et al., 1999; Tergau et al., 1999; Hoffman et al., 2000).”

“5e1 Hz) reducing cortical excitability and high-frequency rTMS (>2 Hz) increasing it [1,2].”

“Slow rTMS, where one magnetic pulse is applied every second (1 Hz), delivered to the motor cortex can give rise to a lasting decrease in corticospinal excitability (Chen et al., 1997; Maeda et al., 2000; Pascual-Leone et al., 2000).”

“which suppresses motor excitability for up to 20 min after the end of stimulation (Chen et al. 1997; Möttönen and Watkins 2009).”

“In normal subjects, low-frequency rTMS at 1 Hz causes a lasting decrease of cortical excitability [5], whereas we found that low-frequency rTMS at 0.”

“Repetitive transcranial magnetic stimulation (rTMS) over the motor cortex is known to produce changes in cortical excitability that outlast the period of stimulation by several minutes (Pascual-Leone et al. 1994; Chen et al. 1997; Maeda et al. 2000; Muellbacher et al. 2000; Touge et al. 2001).”

“Conversely, low-frequency rTMS, defined as a stimulation rate less than or equal to 1 Hz, depresses excitability.(5) Interhemispheric inhibition (IHI) is a normal physiological interaction between the two hemispheres of the brain.”

“These stimulation parameters suppress activity in the targeted brain region in most subjects as evidenced by studies in humans and animal models (Chen et al., 1997; Maeda et al., 2000; Valero-Cabre et al., 2007, 2005).”

“At the beginning, TMS was almost exclusively applied to spinal roots, and cranial and peripheral nerves([15]).”

“Different frequencies of TMS can both decrease and increase motor cortical excitability (Chen et al., 1997; Pascual– Leone et al., 1998; Wu et al., 2000) and exert differential effects on cerebral activity (Kimbrell et al., 1999; Post et al., 1999a).”

“1 Hz frequency did not induce any change in motor excitability [17].”

“We used trains of pulses at 1 Hz frequency, which are known to reduce the excitability of the targeted region, and so to interfere with cognitive processing beyond the duration of the train itself (Koch, Oliveri, Torriero, & Caltagirone, 2003; Hilgetag, Theoret, & Pascual-Leone, 2001; Shapiro, Pascual-Leone, Mottaghy,…”

“…rTMS increase cortical excitability, at least when applied to the primary motor 974 Eur J Pain 16 (2012) 974–982 © 2012 European Federation of International Association for the Study of Pain Chapters cortex (M1) in healthy subjects (Chen et al., 1997; Maeda et al., 2000; Nitsche and Paulus, 2000).”

“At first sight, this seems difficult to reconcile with studies showing a decrease in cortical excitability after long-train low-frequency rTMS ( Chen et al., 1997; Gerschlager et al., 2001; Kosslyn et al., 1999; Maeda et al., 2000; Muellbacher et al., 2000; Wassermann et al., 1998).”

“In particular, low-frequency rTMS over the motor (Chen et al. 1997) and visual cortex (Boroojerdi et al.”

“On the first day, subjects completed a training session that also served for target titration but did not include TMS.”

“The choice of the intertrial interval was based on research by Chen et al. (1997) that showed no change in corticospinal excitability with repetitive TMS at 0.1 Hz for 1 h.”

“First, unlike depotentiation 1 Hz rTMS applied during rest has been shown to elicit cortical inhibition (Chen et al., 1997; Gangitano et al., 2002; Romero et al., 2002) as well as widespread, nonsynaptic specific motor cortex excitability changes (Ziemann et al., 1998; Trippe et al., 2009).”

“Our results indicate that low-frequency rTMS in the range of 1 Hz, which has been shown to reduce the excitability of the motor cortex (Chen et al., 1997), is unable to influence linguistic function.”

“…Medical School, Boston, Massachusetts Address reprint requests to Donald C. Goff, M.D., Department of Psychiatry, Massachussetts General Hospital, 25 Staniford Street, Boston, MA 02114; or Alvaro Pascual-Leone, M.D., Ph.D., Behavioral Neurology Unit, Beth Israel Deaconess Medical Center, 330…”

“particular, it is known that low-frequency TMS decreases cortical excitability of the targeted brain areas for several minutes beyond the end of stimulation (Chen et al. 1997).”

“Given this evidence of deficient motor inhibitory control in OCD, the use of low-frequency repetitive TMS (rTMS) to enhance inhibition in motor circuits (Chen et al., 1997) may be a fruitful avenue to explore as a putative treatment.”

“4B-C) (Chen et al. 1997).”

“This was accounted for by lower accuracy in the early (150 ms) relative to the late (300 ms) temporal condition (mean % of correct responses ±SD: 92.8 % ± 4.0 vs 95.8 % ± 2.9, p = 0.0006) found in Exp1M1right only.”

“This way the inter-pulse interval was>10 s, thereby avoiding changes in motor excitability due to TMS per se [37].”

“5 Hz and greater enhance motor cortex excitability [6], whereas rTMS at frequencies of 1 Hz and lower depresses the cortical excitability [7].”