Person:

Gersner, Roman

Background: About 25% of schizophrenia patients with auditory hallucinations are refractory to pharmacotherapy and electroconvulsive therapy. We conducted a deep transcranial magnetic stimulation (TMS) pilot study in order to evaluate the potential clinical benefit of repeated left temporoparietal cortex stimulation in these patients. The results were encouraging, but a sham-controlled study was needed to rule out a placebo effect. Methods: A total of 18 schizophrenic patients with refractory auditory hallucinations were recruited, from Beer Yaakov MHC and other hospitals outpatient populations. Patients received 10 daily treatment sessions with low-frequency (1 Hz for 10 min) deep TMS applied over the left temporoparietal cortex, using the H1 coil at the intensity of 110% of the motor threshold. Procedure was either real or sham according to patient randomization. Patients were evaluated via the Auditory Hallucinations Rating Scale, Scale for the Assessment of Positive Symptoms-Negative Symptoms, Clinical Global Impressions, and Quality of Life Questionnaire. Results: In all, 10 patients completed the treatment (10 TMS sessions). Auditory hallucination scores of both groups improved; however, there was no statistical difference in any of the scales between the active and the sham treated groups. Conclusions: Low-frequency deep TMS to the left temporoparietal cortex using the protocol mentioned above has no statistically significant effect on auditory hallucinations or the other clinical scales measured in schizophrenic patients.

Rodent models of transcranial magnetic stimulation (TMS) play a crucial role in aiding the understanding of the cellular and molecular mechanisms underlying TMS induced plasticity. Rodent-specific TMS have previously been used to deliver focal stimulation at the cost of stimulus intensity (12 mT). Here we describe two novel TMS coils designed to deliver repetitive TMS (rTMS) at greater stimulation intensities whilst maintaining spatial resolution. Two circular coils (8 mm outer diameter) were constructed with either an air or pure iron-core. Peak magnetic field strength for the air and iron-cores were 90 and 120 mT, respectively, with the iron-core coil exhibiting less focality. Coil temperature and magnetic field stability for the two coils undergoing rTMS, were similar at 1 Hz but varied at 10 Hz. Finite element modeling of 10 Hz rTMS with the iron-core in a simplified rat brain model suggests a peak electric field of 85 and 12.7 V/m, within the skull and the brain, respectively. Delivering 10 Hz rTMS to the motor cortex of anaesthetized rats with the iron-core coil significantly increased motor evoked potential amplitudes immediately after stimulation (n = 4). Our results suggest these novel coils generate modest magnetic and electric fields, capable of altering cortical excitability and provide an alternative method to investigate the mechanisms underlying rTMS-induced plasticity in an experimental setting.

Objective: Cathodal transcranial direct current stimulation (tDCS) is a focal neuromodulation technique that suppresses cortical excitability by low-amplitude constant electrical current, and may have an antiepileptic effect. Yet, tDCS has not been tested in status epilepticus (SE). Furthermore, a combined tDCS and pharmacotherapy antiseizure approach is unexplored. We therefore examined in the rat pentylenetetrazol (PTZ) SE model whether cathodal tDCS (1) suppresses seizures, (2) augments lorazepam (LZP) efficacy, and (3) enhances GABAergic cortical inhibition. Methods: Experiment 1 aimed to identify an effective cathodal tDCS intensity. Rats received intraperitoneal PTZ followed by tDCS (sham, cathodal 1 mA, or cathodal 0.1 mA; for 20 min), and then a second PTZ challenge. In Experiment 2, two additional animal groups received a subtherapeutic LZP dose after PTZ, and then verum or sham tDCS. Clinical and electroencephalography (EEG) epileptic activity were compared between all groups. In Experiment 3, we measured GABA-mediated paired-pulse inhibition of the motor evoked potential by paired-pulse transcranial magnetic stimulation (ppTMS) in rats that received PTZ or saline, and either verum or sham tDCS. Results: Cathodal 1 mA tDCS (1) reduced EEG spike bursts, and suppressed clinical seizures after the second PTZ challenge, (2) in combination with LZP was more effective in seizure suppression and improved the clinical seizure outcomes compared to either tDCS or LZP alone, and (3) prevented the loss of ppTMS motor cortex inhibition that accompanied PTZ injection. Interpretation These results suggest that cathodal 1 mA tDCS alone and in combination with LZP can suppress seizures by augmenting GABAergic cortical inhibition.