BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation

The effect of right vagus nerve stimulation on focal cerebral ischemia: an experimental study in the rat

Zhenghui Sun, Wesley Baker, Teruyuki Hiraki, Joel H. Greenberg — 2011-02-23

Background: The aim of this study was to determine the effect of vagus nerve stimulation (VNS) on infarct size after transient and after permanent focal cerebral ischemia in rats and to test the hypothesis that VNS-induced neuroprotection is due to changes in cerebral blood flow.Methods: Ischemia was produced by either temporary proximal middle cerebral artery occlusion (TMCAO) or permanent distal middle cerebral artery occlusion (PMCAO). Stimulating electrodes were implanted on the cervical part of the right vagus nerve, and electrical stimulation was initiated 30 minutes after the induction of ischemia and delivered for 30 seconds every 5 minutes for 1 hour. All the procedures were duplicated but no stimulus was delivered in control groups. Cerebral blood flow in the MCA territory was continuously monitored with laser speckle contrast imaging. A neurologic evaluation was undertaken after 24 hours of ischemia, and animals were euthanized and neuronal damage evaluated.Results: Ischemic lesion volume was smaller in VNS-treated animals in both the temporary and permanent ischemic groups (P < .01). VNS-treated animals in TMCAO had better functional scores at 24 hours as compared with control animals (P < .01), but there were no statistically significant differences in the neurobehavioral scores in PMCAO (P = .089). Cerebral blood flow changes in the MCA territory during ischemia did not differ between the VNS-treated animals and control animals in either group.Conclusions: VNS offers neuroprotection against stroke in both temporary and permanent ischemia. Although the precise mechanism of this effect remains to be determined, alterations in cerebral blood flow do not appear to play a role. VNS could readily be translated to clinical practice.

The involvement of posterior parietal cortex and frontal eye fields in spatially primed visual search

Alison R. Lane, Daniel T. Smith, Thomas Schenk, Amanda Ellison — 2011-02-08

Background: Right posterior parietal cortex (rPPC) and frontal eye fields (FEF) are known to be involved in processing visuospatial attention. However, the functional involvement of these areas in spatial priming in complex conjunction visual search has yet to be determined.Objective: This study aimed to examine the roles of rPPC and bilateral FEF in conjunction search when spatial ambiguity was reduced by priming the target location.Methods: Participants completed a conjunction search task whereby the target location was random or else repeated from the previous trial. Transcranial magnetic stimulation was delivered to each one of the three sites of interest at a time, and task performance was compared with a sham condition.Results: Spatial priming occurred for all conditions: search times were faster for primed relative to nonprimed trials. When the target appeared at a nonprimed location, stimulation over any of the three sites increased reaction times relative to the sham condition. However, when the target location was repeated, reaction time was only significantly increased by stimulation over the right FEF.Conclusions: rPPC and left FEF are only involved when the target location is random, suggesting that these areas are essential for resolving spatial ambiguity to localize targets. Conversely, right FEF contributes equally to visual search regardless of spatial priming. We propose that right FEF has a role in the integration of bottom up saliency and top down expectancy signals and is the node at which rPPC and/or left FEF is either recruited or not.

Episode length and mixed features as predictors of ECT nonresponse in patients with medication-resistant major depression

G. Perugi, P. Medda, S. Zanello, C. Toni, G.B. Cassano — 2011-03-21

Objectives: This study aimed to ascertain predictors of nonresponse to electroconvulsive therapy (ECT) in a large sample of major depressive patients resistant to pharmacologic treatment.Methods: A total of 208 depressive patients (31 with major depression [UP], 101 with bipolar disorder II [BP II], and 76 with bipolar disorder I [BP I] according to DSM-IV criteria) were included in the study and treated with bilateral ECT on a twice-a-week schedule. The patients were assessed before (baseline) and a week after the ECT course (final score) using the Hamilton Rating Scale for Depression-17 items (HAM-D-17), the Young Mania Rating Scale (YMRS), the Brief Psychiatric Rating Scale (BPRS), and the Clinical Global Improvement (CGI). Responders were defined as those patients with a reduction of at least 50% in HAM-D-17 score and a rating of 2 (“much improved”) or 1 (“very much improved”) in the CGI-Improvement subscale.Results: At the end of the ECT course, 152 patients (64%) were classified as responders and 56 patients (36%) were classified as nonresponders. On backward stepwise logistic regression, bipolar subtype (odds ratio [OR] = 17.85; 95% confidence level [CL] = 1.786-178.407), higher mean baseline YMRS scores (OR = 1.094; 95% CL = 1.025-1.166), lower mean baseline HAM-D-17 scores (OR = 0.928; 95% CL = 0.860-1.002), and length of current episode (OR = 1.047; 95% CL = 1.009-1.086) were identified as statistically significant predictors of nonresponse.Conclusions: ECT was an effective treatment for approximately two-thirds of the patients with medication-resistant depression who were included in this study. ECT nonresponse was associated with bipolar subtype, presence of manic symptoms during depression, slightly less severe depressive symptomatology, and protracted duration of the episode.

Transient increase of plasma concentrations of amyloid β peptides after electroconvulsive therapy

2011-02-08

Background: Electroconvulsive therapy (ECT) is applied to effectively treat depressive episodes, and it can be considered an ideal model of generalized seizures induced and performed under precisely controllable conditions.Objective: We hypothesize that ECT causes a transiently increased blood-brain barrier permeability.Methods: We measured plasma concentrations of amyloid β (Aβ) peptides: 1-42, 1-40, x-42, and x-40 before ECT, within 30 minutes after 2, and 24 hours after ECT treatment in 33-36 sessions of n = 13 different patients.Results: We observed a significant increase of the plasma concentrations of all four peptides within 30 minutes after the ECT, followed by the normalization of the peptides concentrations 2 hours after the ECT.Conclusion: Different physiologic phenomena may be responsible for the transient increase of the Aβ peptides concentrations in plasma shortly after ECT session, and further studies are necessary to explain these mechanisms. For example, decreased integrity of the blood-brain barrier permeability, an increased release from neurons due to their activation or increased release from peripheral sources, like thrombocytes or muscles, or a combination of different factors must be taken into consideration.

Repetitive transcranial magnetic stimulation (rTMS) improves movement-related cortical potentials in autism spectrum disorders

2011-03-07

Background: Motor impairments are common in autism spectrum disorders (ASD). Electrophysiologic studies reveal abnormalities in the preparation of movement; repetitive transcranial magnetic stimulation (rTMS) to key motor cortical sites may therefore be a useful technique for improving motor function in ASD.Objective: To examine whether rTMS can improve electrophysiologic and behavioral indices of motor activity.Methods: Eleven participants with ASD completed three sessions in which they were administered one of three rTMS conditions (left M1, supplementary motor area [SMA], sham) at 1 Hz for 15 minutes. Movement-related cortical potentials (MRCPs) were assessed before and after rTMS.Results: rTMS to the SMA was associated with a gradient increase to the early component of MRCPs, whereas rTMS to left M1 produced a stronger gradient in the late component.Conclusions: rTMS appears to improve movement-related electrophysiologic activity in ASD, perhaps through an influence on cortical inhibitory processes.

A sham controlled study of repetitive transcranial magnetic stimulation for posttraumatic stress disorder

Bradley V. Watts, Barbara Landon, Alicia Groft, Yinong Young-Xu — 2011-03-07

Background: Posttraumatic stress disorder (PTSD) is a commonly occurring and often debilitating psychiatric condition. There currently is not definitive information regarding the efficacy of repetitive transcranial magnetic stimulation (rTMS) for PTSD.Objective: This study seeks to examine the efficacy of rTMS for PTSD.Methods: Twenty subjects with PTSD were randomly assigned to receive either 10 rTMS sessions delivered at 1 Hz to the right dorsolateral prefrontal cortex (DLPRC) or 10 sham rTMS sessions to the same area. A blinded rater assessed PTSD, depressive, anxiety, and neurocognitive symptoms before treatment, after the treatment series, and during a 2-month follow-up period.Results: Trancranial magnetic stimulation delivered at 1 Hz to the right DLPRC resulted in statistically and clinically significant improvements in core PTSD symptoms and depressive symptoms compared with sham treatments. The effectiveness showed some degradation during the 2 months after treatments were stopped.Conclusions: This blinded sham controlled trial supports the efficacy of 10 sessions of right DLPRC rTMS delivered at 1 Hz for the treatment of PTSD symptoms.

Cognitive behavioral therapy-related increases in cortical inhibition in problematic perfectionists

2011-02-08

Background: Several lines of evidence suggest that cognitive behavioral therapy (CBT) is an effective treatment for depression and anxiety disorders. Evidence suggests that the therapeutic effects of CBT are related to neurophysiologic changes in the cortex, particularly γ-aminobutyric acid (GABA) potentiation. Transcranial magnetic stimulation (TMS) represents a noninvasive method of measuring cortical inhibition, which is a neurophysiologic mechanism associated with the pathophysiology of several psychiatric disorders.Objective/Hypothesis: To demonstrate the effectiveness of a 12-week CBT intervention compared with a wait list control group measuring cortical inhibition in participants with pathologic perfectionism. Participants within the CBT group would demonstrate increases in cortical inhibition and improvements on clinical outcomes relative to the wait list control group.Methods: Twenty-four right-handed perfectionists were randomly assigned to a 12-week CBT intervention or a wait list control group. Cortical inhibition was measured at pre- and postintervention with TMS paradigms specifically short-interval cortical inhibition and the cortical silent period, which index GABAA and GABAB receptor-mediated inhibitory neurotransmission, respectively.Results: The CBT group demonstrated a significant potentiation of the cortical silent period when compared with the wait list control group. The CBT group demonstrated a decrease in anxiety sensitivity and automatic thoughts relative to the control group.Conclusions: These findings demonstrate that CBT tailored for perfectionism is accompanied by an increase in cortical inhibition of the motor cortex and positive changes on clinical outcomes. These findings provide compelling evidence for an association between positive CBT effects and a potentiation of GABAergic inhibitory neurotransmission.

Time course and duration of changes in Kv7.2 and Kv11.1 mRNA expression in the hippocampus and piriform cortex following electroconvulsive stimulations

Marie-Louise Hjaeresen, Ida Hageman, Gitta Wortwein, Martin B. Jørgensen — 2011-02-08

Background: A minimum of six electroconvulsive therapy (ECT) treatments has to be delivered to achieve sustained improvement in major depression. However, the mechanisms of the therapeutic actions of ECT are still debated.Objective: We aimed to study the time course and duration of increased Kv7.2 and Kv11.1 mRNA expression in the hippocampus and piriform cortex (Pir) after electroconvulsive stimulation (ECS).Methods: Adult male Sprague-Dawley rats received three ECS per week over 1, 2, or 3 weeks and were decapitated 3 days after the last stimulus. Additional groups of rats receiving nine ECS were sacrificed 7 or 28 days after the last ECS. In situ hybridization was used to measure Kv channel mRNA expression after ECS.Results: Kv7.2 mRNA was increased in the hippocampus and Pir 3 days after both six and nine, but not after three ECS. This was also seen for Kv11.1 mRNA in Pir. These changes lasted for at least 7 days.Conclusions: These results indicate that the changes in Kv7.2 and Kv11.1 channels may contribute to the therapeutic effect of ECT. However, further research needs to be undertaken in this area to extend these findings.

2012-01-01

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2012-01-01

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BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation

The effect of right vagus nerve stimulation on focal cerebral ischemia: an experimental study in the rat

The involvement of posterior parietal cortex and frontal eye fields in spatially primed visual search

Episode length and mixed features as predictors of ECT nonresponse in patients with medication-resistant major depression

Transient increase of plasma concentrations of amyloid β peptides after electroconvulsive therapy

Repetitive transcranial magnetic stimulation (rTMS) improves movement-related cortical potentials in autism spectrum disorders

A sham controlled study of repetitive transcranial magnetic stimulation for posttraumatic stress disorder

Cognitive behavioral therapy-related increases in cortical inhibition in problematic perfectionists

Time course and duration of changes in Kv7.2 and Kv11.1 mRNA expression in the hippocampus and piriform cortex following electroconvulsive stimulations

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