Preconditioning of low-frequency repetitive transcranial magnetic stimulation with transcranial direct current stimulation: evidence for homeostatic plasticity in the human motor cortex

Recent experimental work in animals has emphasized the importance of homeostatic plasticity as a means of stabilizing the properties of neuronal circuits. Here, we report a phenomenon that indicates a homeostatic pattern of cortical plasticity in healthy human subjects. The experiments combined two techniques that can produce long-term effects on the excitability of corticospinal output neurons: transcranial direct current stimulation (TDCS) and repetitive transcranial magnetic stimulation (rTMS) of the left primary motor cortex. "Facilitatory preconditioning" with anodal TDCS caused a subsequent period of 1 Hz rTMS to reduce corticospinal excitability to below baseline levels for >20 min. Conversely, "inhibitory preconditioning" with cathodal TDCS resulted in 1 Hz rTMS increasing corticospinal excitability for at least 20 min. No changes in excitability occurred when 1 Hz rTMS was preceded by sham TDCS. Thus, changing the initial state of the motor cortex by a period of DC polarization reversed the conditioning effects of 1 Hz rTMS. These preconditioning effects of TDCS suggest the existence of a homeostatic mechanism in the human motor cortex that stabilizes corticospinal excitability within a physiologically useful range

Transcranial magnetic stimulation

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenTranscranial Magnetic Stimulation (TMS) is a new non-invasive method to investigate the central nervous system. Initially it was used to assess the functional integrity of the pyramidal pathways but more recently various other aspects of brain function have been studied including cortical excitability. By localised interference with brain function, it is possible to use TMS to assess the relationship between various brain regions and cognitive functions. The therapeutic effect of TMS has been explored in the treatment of neurological diseases and psychiatric disorders such as epilepsy, cerebellar ataxia and depressive illness.Segulörvun heila í gegnum höfuðkúpu er notuð til rannsókna á miðtaugakerfi. Upphaflega var þessi aðferð þróuð til að meta starfsemi og ástand hreyfitauga­brauta milli heila og mænu, en er nú einnig notuð til margvíslegra rannsókna á heilastarfsemi. Meta má hömlunar- og örvunarástand heilabarkar sem getur breyst vegna heilasjúkdóma og við lyfjagjöf. Með staðbundinni truflun á starfsemi taugafrumna eftir segulörvun hefur verið hægt að kanna tengsl milli heilasvæða og hugrænna ferla. Í ljós hefur komið möguleg notkun segulörvunar í meðferð taugasjúkdóma og geðraskana. Rannsóknir hvað þetta varðar hafa meðal annars beinst að flogaveiki, mænu- og hnykilhrörnun og djúpri geðlægð

Terapia experimental da epilepsia com estimulação magnética transcraniana : ausência de melhora adicional com tratamento prolongado

Objetivo: investigar o efeito de três meses de estimulação magnética transcraniana repetitiva (EMTr) de baixa freqüência, na epilepsia de difícil controle. Método: Cinco pacientes (quatro homens, uma mulher, idades entre 6 e 50 anos), participaram do estudo; suas crises epilépticas não puderam ser controlados por tratamento medicamentoso e não tinham indicação cirúrgica; a EMTr foi realizada duas vezes por semana durante três meses, sendo que os pacientes anotaram o número diário de crises neste período, assim como nos três meses anteriores e posteriores ao tratamento. A aplicação da EMTr foi feita no vértex com bobina circular, com intensidade 5% abaixo do limiar motor. Durante as sessões de EMTr, 100 estímulos (5 séries de 20 estímulos, com um minuto de intervalo entre as séries) foram realizadas na freqüência de 0,3 Hz. Resultados: A média diária de crises (MDC) decresceu em três pacientes e aumentou em dois durante o uso da EMTr; um destes casos foi tratado somente por um mês; o melhor resultado foi encontrado em um paciente com displasia cortical focal (redução de 43,09% na MDC). Em todo o grupo de pacientes, houve decréscimo significativo na MDC de 22,8% (p<0,01). Conclusão: Embora o tratamento prolongado com a EMTr seja seguro e tenha sido registrado decréscimo moderado da MDC em um grupo de pacientes com epilepsia de difícil controle, respostas individuais de pacientes foram imprevisíveis e a relevância clínica deste método é provavelmente baixa. Nossos dados sugerem, contudo, que pacientes com lesões corticais focais podem ser beneficiar deste novo tipo de tratamento. Estudos futuros devem se concentrar neste grupo de pacientes.OBJECTIVE: To investigate the effect of three months of low-frequency repetitive transcranial magnetic stimulation (rTMS) treatment in intractable epilepsy. METHODS: Five patients (four males, one female; ages 6 to 50 years), were enrolled in the study; their epilepsy could not be controlled by medical treatment and surgery was not indicated. rTMS was performed twice a week for three months; patients kept records of seizure frequency for an equal period of time before, during, and after rTMS sessions. rTMS was delivered to the vertex with a round coil, at an intensity 5 % below motor threshold. During rTMS sessions, 100 stimuli (five series of 20 stimuli, with one-minute intervals between series) were delivered at a frequency of 0.3 Hz. RESULTS: Mean daily number of seizures (MDNS) decreased in three patients and increased in two during rTMS- one of these was treated for only one month; the best result was achieved in a patient with focal cortical dysplasia (reduction of 43.09 % in MDNS). In the whole patient group, there was a significant (p<0.01) decrease in MDNS of 22.8 %. CONCLUSION: Although prolonged rTMS treatment is safe and moderately decreases MDNS in a group of patients with intractable epilepsy, individual patient responses were mostly subtle and clinical relevance of this method is probably low. Our data suggest, however, that patients with focal cortical lesions may indeed benefit from this novel treatment. Further studies should concentrate on that patient subgroup

Low-frequency repetitive transcranial magnetic stimulation for seizure suppression in patients with extratemporal lobe epilepsy—A pilot study

SummaryWe evaluated the effect of low-frequency repetitive transcranial magnetic stimulation (rTMS) on seizure frequency in adult patients with medically intractable extratemporal lobe epilepsy (ETLE). Seven patients with medically intractable ETLE received low-frequency rTMS at 0.9Hz, basically two sets of 15min stimulation per day for five days in a week, with the stimulus intensity of 90% of resting motor threshold (RMT). The number of seizures during two weeks before and after the stimulation of one week was compared. Furthermore, RMT and active motor threshold (AMT) were measured before and after rTMS for each daily session. After low-frequency rTMS of one week, the frequency of all seizure types, complex partial seizures (CPSs) and simple partial seizures was reduced by 19.1, 35.9 and 7.4%, respectively. The patients with smaller difference between RMT and AMT before rTMS had higher reduction rate of CPSs. A favorable tendency of seizure reduction, though not statistically significant, during two weeks after low-frequency rTMS was demonstrated in medically intractable ETLE patients. As far as CPSs are concerned, smaller decrease of motor threshold by voluntary muscle contraction was associated with better response to rTMS

Repetitive transcranial magnetic stimulation in drug‐resistant idiopathic epilepsy of dogs : a noninvasive neurostimulation technique

Background Although repetitive transcranial magnetic stimulation (rTMS) has been assessed in epileptic humans, clinical trials in epileptic dogs can provide additional insight. Objectives Evaluate the potential antiepileptic effect of rTMS in dogs. Animals Twelve client-owned dogs with drug-resistant idiopathic epilepsy (IE). Methods Single-blinded randomized sham-controlled clinical trial (dogs allocated to active or sham rTMS) (I) and open-labeled uncontrolled clinical trial (dogs received active rTMS after sham rTMS) (II). Monthly seizure frequency (MSF), monthly seizure day frequency (MSDF), and number of cluster seizures (CS) were evaluated for a 3-month pre-TMS and post-rTMS period and safety was assessed. The lasting effect period of rTMS was assessed in each dog treated by active stimulation using the MSF ratio (proportion of post-TMS to pre-rTMS MSF) and treatment was considered effective if the ratio was No adverse effects were reported. In trial I, MSF and MSDF decreased significantly (P= .04) in the active group (n = 7). In the sham group (n = 5), no significant changes were found (P= .84 and .29, respectively). Cluster seizures did not change significantly in either group. No significant differences were detected between the groups. In trial II, previously sham-treated dogs (n = 5) received active rTMS and significant decreases in MSF and MSDF were noted (P= .03 and .008, respectively). The overall effect of rTMS lasted for 4 months; thereafter, the MSF ratio was >1. Conclusions and Clinical Importance Repetitive transcranial magnetic stimulation may be a safe adjunctive treatment option for dogs with drug-resistant IE, but large-scale studies are needed to establish firm conclusions

A pilot feasibility study of daily rTMS to modify corticospinal excitability during lower limb immobilization

Short term immobilization of the lower limb is associated with increased corticospinal excitability at 24 hours post cast removal. We wondered whether daily stimulation of the motor cortex might decrease brain reorganization during casting. We tested the feasibility of this approach. Using transcranial magnetic stimulation (TMS), resting motor threshold and recruitment curves were obtained at baseline in 6 healthy participants who then had leg casts placed for 10 days. On 7 of the 10 days subjects received 20 minutes of 1 Hz repetitive TMS (rTMS). TMS measures were then recorded immediately after and 24 hours post cast removal. Four of 6 subjects completed the study. At the group level there were no changes in excitability following cast removal. At the individual level, two participants did not show any change, 1 participant had higher and one lower excitability 24 hours after cast removal. Daily rTMS over motor cortex is feasible during casting and may modify neuroplastic changes occurring during limb disuse. A prospective double blind study is warranted to test whether daily rTMS might improve outcome in subjects undergoing casting, and perhaps in other forms of limb disuse such as those following brain injury or weightlessness in space flight

Blockade of in vitro ictogenesis by low-frequency stimulation coincides with increased epileptiform response latency

Low-frequency stimulation, delivered through transcranial magnetic or deep-brain electrical procedures, reduces seizures in patients with pharmacoresistant epilepsy. A similar control of ictallike discharges is exerted by low-frequency electrical stimulation in rodent brain slices maintained in vitro during convulsant treatment. By employing field and “sharp” intracellular recordings, we analyzed here the effects of stimuli delivered at 0.1 or 1 Hz in the lateral nucleus of the amygdala on ictallike epileptiform discharges induced by the K+ channel blocker 4-aminopyridine in the perirhinal cortex, in a rat brain slice preparation. We found that 1) ictal events were nominally abolished when the stimulus rate was brought from 0.1 to 1 Hz; 2) this effect was associated with an increased latency of the epileptiform responses recorded in perirhinal cortex following each stimulus; and 3) both changes recovered to control values following arrest of the 1-Hz stimulation protocol. The control of ictal activity by 1-Hz stimulation and the concomitant latency increase were significantly reduced by GABAB receptor antagonism. We propose that this frequency-dependent increase in latency represents a short-lasting, GABAB receptor-dependent adaptive mechanism that contributes to decrease epileptiform synchronization, thus blocking seizures in epileptic patients and animal models

Repetitive low-frequency stimulation reduces epileptiform synchronization in limbic neuronal networks.

Deep-brain electrical or transcranial magnetic stimulation may represent a therapeutic tool for controlling seizures in patients presenting with epileptic disorders resistant to antiepileptic drugs. In keeping with this clinical evidence, we have reported that repetitive electrical stimuli delivered at approximately 1 Hz in mouse hippocampus-entorhinal cortex (EC) slices depress the EC ability to generate ictal activity induced by the application of 4-aminopyridine (4AP) or Mg2+-free medium (Barbarosie, M., Avoli, M., 1997. CA3-driven hippocampal–entorhinal loop controls rather than sustains in vitro limbic seizures. J. Neurosci. 17, 9308–9314.). Here, we confirmed a similar control mechanism in rat brain slices analyzed with field potential recordings during 4AP (50 μM) treatment. In addition, we used intrinsic optical signal (IOS) recordings to quantify the intensity and spatial characteristics of this inhibitory influence. IOSs reflect the changes in light transmittance throughout the entire extent of the slice, and are thus reliable markers of limbic network epileptiform synchronization. First, we found that in the presence of 4AP, the IOS increases, induced by a train of electrical stimuli (10 Hz for 1 s) or by recurrent, single-shock stimulation delivered at 0.05 Hz in the deep EC layers, are reduced in intensity and area size by low-frequency (1 Hz), repetitive stimulation of the subiculum; these effects were observed in all limbic areas contained in the slice. Second, by testing the effects induced by repetitive subicular stimulation at 0.2–10 Hz, we identified maximal efficacy when repetitive stimuli are delivered at 1 Hz. Finally, we discovered that similar, but slightly less pronounced, inhibitory effects occur when repetitive stimuli at 1 Hz are delivered in the EC, suggesting that the reduction of IOSs seen during repetitive stimulation is pathway dependent as well as activity dependent. Thus, the activation of limbic networks at low frequency reduces the intensity and spatial extent of the IOS changes that accompany ictal synchronization in an in vitro slice preparation. This conclusion supports the view that repetitive stimulation may represent a potential therapeutic tool for controlling seizures in patients with pharmacoresistant epileptic disorders