Restorative Neurology and Neuroscience - Volume 28, issue 4

Authors: Cazzoli, Dario | Müri, René M. | Hess, Christian W. | Nyffeler, Thomas

Article Type: Research Article

Abstract: Hemispatial neglect – defined as the failure to attend, explore, and act upon the contralesional side of space – is a frequent and disabling neurological syndrome. Interhemispheric rivalry is considered as a major pathophysiological mechanism underlying hemispatial neglect. According to this account, the contralesional, intact hemisphere undergoes a pathological hyperactivity due to a deficient transcallosal inhibition from the damaged hemisphere. This model offers a framework for possible therapeutic interventions with repetitive transcranial …magnetic stimulation (rTMS), i.e. a reduction of the pathological hyperactivity with a rTMS protocol that has lasting inhibitory effects. In the present work, we will first review evidence for the interhemispheric rivalry account coming from animals and humans. We will then describe studies showing the possibility to perturb and to restore interhemispheric balance in healthy subjects as a proof of concept for therapeutic rTMS application. Finally, we will consider studies applying rTMS as a therapeutic approach in hemispatial neglect. We conclude that rTMS is a promising approach to reduce the interhemispheric imbalance in neglect patients and to ameliorate symptoms. Newly developed protocols such as Theta Burst Stimulation (TBS) – with short stimulation times and long offline effects – seem to be particularly convenient. However, future studies should assess stimulation effects not only in clinical testing, but also on disability, considering combination with traditional therapies as well. Show more

Keywords: Hemispatial neglect, experimental therapy, interhemispheric balance, visuospatial attention, repetitive transcranial magnetic stimulation, Theta Burst Stimulation

DOI: 10.3233/RNN-2010-0560

Citation: Restorative Neurology and Neuroscience, vol. 28, no. 4, pp. 499-510, 2010

Authors: Naeser, Margaret A. | Martin, Paula I. | Treglia, Ethan | Ho, Michael | Kaplan, Elina | Bashir, Shahid | Hamilton, Roy | Coslett, H. Branch | Pascual-Leone, Alvaro

Article Type: Research Article

Abstract: This review of our research with rTMS to treat aphasia contains four parts: Part 1 reviews functional brain imaging studies related to recovery of language in aphasia with emphasis on nonfluent aphasia. Part 2 presents the rationale for using rTMS to treat nonfluent aphasia patients (based on results from functional imaging studies). Part 2 also reviews our current rTMS treatment protocol used with nonfluent aphasia patients, and our functional imaging results from overt naming fMRI scans, …obtained pre- and post- a series of rTMS treatments. Part 3 presents results from a pilot study where rTMS treatments were followed immediately by constraint-induced language therapy (CILT). Part 4 reviews our diffusion tensor imaging (DTI) study that examined white matter connections between the horizontal, midportion of the arcuate fasciculus (hAF) to different parts within Broca's area (pars triangularis, PTr; pars opercularis, POp), and the ventral premotor cortex (vPMC) in the RH and in the LH. Part 4 also addresses some of the possible mechanisms involved with improved naming and speech, following rTMS with nonfluent aphasia patients. Show more

DOI: 10.3233/RNN-2010-0559

Citation: Restorative Neurology and Neuroscience, vol. 28, no. 4, pp. 511-529, 2010

Authors: Nowak, Dennis A. | Bösl, Kathrin | Podubeckà, Jitka | Carey, James R.

Article Type: Research Article

Abstract: Purpose: Upper limb function is the best predictor of long-term disability after stroke. Despite extensive rehabilitation, recovery of upper limb motor function is frequently incomplete after stroke. Methods: We review the pertinent literature on functional reorganization within the cerebral motor network after stroke and noninvasive techniques to modulate brain function towards beneficial plasticity. Results: Direct current stimulation and repetitive transcranial magnetic stimulation are powerful tools to (i) modulate cortical excitability, (ii) induce …remote changes within the cortical motor system and (iii) thereby improve upper limb motor function after stroke. Today no relevant side effects have been reported. Conclusions: Neuromodulation, by means of noninvasive brain stimulation techniques, has been shown to be a safe, feasible and effective method to promote recovery of motor function after stroke. However, several methodological and theoretical issues remain to be addressed in future work. Show more

Keywords: Stroke, repetitive transcranial magnetic stimulation transcranial direct current stimulation

DOI: 10.3233/RNN-2010-0552

Citation: Restorative Neurology and Neuroscience, vol. 28, no. 4, pp. 531-544, 2010

Authors: Khedr, Eman M. | Fetoh, Noha Abo-El

Article Type: Research Article

Abstract: This review discusses the clinical results that were obtained by applying rTMS in acute and chronic ischemic stroke patients. These studies included only the recovery of motor disability and dysphagia. In summary, two approaches have been used when employing rTMS as a potential therapy for the treatment of stroke. The most direct approach involves applying rTMS directly over the affected hemisphere in an attempt to increase excitability and plasticity of damaged circuits to improve motor function. …The second approach has taken advantage of the concept of interhemispheric balance in which damage to the stroke hemisphere is exacerbated by increased inhibition from the intact non-stroke hemisphere. In this case, inhibitory rTMS is applied to the non-stroke hemisphere with the intention of reducing interhemispheric inhibition and restoring the balance of excitation between the motor cortices.The overall procedure remains to be optimized, in particular regarding the number of rTMS sessions, frequency and intensity of stimulation and the exact timing of rTMS application after stroke. Cortical stimulation is an effective method for improving functional recovery of acute and chronic stroke. Show more

Keywords: Repetitive transcranial magnetic stimulation, stroke, neuroplasticity, cortical excitability

DOI: 10.3233/RNN-2010-0558

Citation: Restorative Neurology and Neuroscience, vol. 28, no. 4, pp. 545-559, 2010

Authors: Koch, Giacomo

Article Type: Research Article

Abstract: Long-term therapy with levodopa and dopamine agonists in Parkinson's disease (PD) patients is complicated by the development of fluctuations in motor response, such as levo-dopa induced dyskinesia (LID). Repetitive Transcranial Magnetic Stimulation (rTMS) has been recently put forward as a possible therapeutic tool able to LID in PD. Trains of 1 Hz rTMS applied either over the supplementary motor area (SMA) or the primary motor cortex (M1) were able to induce a transient reduction in the …severity of LID, confirming that an over-activity of these areas plays a crucial role in the pathophysiology of LID. However, repeated sessions of rTMS were not effective in inducing persistent beneficial clinical effects. Functional or metabolic changes have been reported in the cerebellum in studies in PD patients treated with procedures known to alleviate LID, such as deep brain stimulation. Therefore, the effects of rTMS applied over the lateral cerebellum has been recently tested in patients with LID. A two-week course of bilateral cerebellar rTMS induced persistent clinical beneficial effects, reducing peak-dose LID for up to four weeks after the end of the daily stimulation period. These findings demonstrate that rTMS is a potential tool in individuating the best cortical targets and the optimal parameters of stimulation able to improve LID in dyskinetic PD patients. Show more

DOI: 10.3233/RNN-2010-0556

Citation: Restorative Neurology and Neuroscience, vol. 28, no. 4, pp. 561-568, 2010

Authors: Schönfeldt-Lecuona, C. | Cárdenas-Morales, L. | Freudenmann, R. W. | Kammer, T. | Herwig, U.

Article Type: Research Article

Abstract: Looking at novelties and advances in medicine in particular in the treatment of major depressive disorder no principally new antidepressant treatment strategy has been established in clinical routine in the last fifty years. However, regarding the considerable issue of treatment resistance in depression, new therapeutic strategies are urgently required. In this context, repetitive transcranial magnetic stimulation above the dorsolateral prefrontal cortex has been proposed as a potential new treatment option for depression; …furthermore, in October 2008 a first rTMS-device (NeuroStar TMS Therapy System™) was approved by the FDA for the treatment of treatment resistant major refractory depression in adults. Yet, despite now nearly two decades of research in this field, no final answer concerning its validity for antidepressant treatment in the clinical practice is given. Numerous studies with small sample sizes and heterogeneous designs have been performed in this field yielding to different results. These were subjected to meta-analyses, assessing the antidepressant effect of rTMS, which are briefly summarized in this article. Further, multicentre-trials with larger numbers of patients were performed, which are presented and critically discussed here in more detail. This short review shall thus provide an overview of the current status of knowledge concerning rTMS in depression and it also provides some recommendations for future research in this field. Show more

Keywords: Depression, Repetitive transcranial magnetic stimulation, meta-analysis, antidepressant treatment trial

DOI: 10.3233/RNN-2010-0561

Citation: Restorative Neurology and Neuroscience, vol. 28, no. 4, pp. 569-576, 2010

Authors: Höppner, Jacqueline | Berger, Christoph | Walter, Uwe | Padberg, Frank | Buchmann, Johannes | Herwig, Uwe | Domes, Gregor

Article Type: Research Article

Abstract: Since various studies, including multi-centre studies, investigating the effect of repetitive transcranial magnetic stimulation (rTMS) in depression have shown different results, it is now important to research, which symptoms of depression are most responsive to this kind of non-invasive brain stimulation. Furthermore, an increasing interest of rTMS as a potential tool for treatment of neurological and psychiatric disorders should be recorded. Therefore, it is critical to investigate dopaminergic functional interactions in the …prefrontal cortex, and in particular, the effect of dorsolateral prefrontal cortex stimulation on clinical symptoms depending on dopaminergic concentrations in various brain regions. This short review summarizes important preliminary data, which focus on the symptom-oriented effects of rTMS in depression. Show more

DOI: 10.3233/RNN-2010-0557

Citation: Restorative Neurology and Neuroscience, vol. 28, no. 4, pp. 577-586, 2010

Authors: Vazin, Tandis | Freed, William J.

Article Type: Research Article

Abstract: The greatest therapeutic promise of human embryonic stem cells (hESC) is to generate specialized cells to replace damaged tissue in patients suffering from various degenerative diseases. However, the signaling mechanisms involved in lineage restriction of ESC to adopt various cellular phenotypes are still under investigation. Furthermore, for progression of hESC-based therapies towards clinical applications, appropriate culture conditions must be developed to generate genetically stable homogenous populations of cells, to hinder possible adverse …effects following transplantation. Other critical challenges that must be addressed for successful cell implantation include problems related to survival and functional efficacy of the grafted cells. This review initially describes the derivation of hESC and focuses on recent advances in generation, characterization, and maintenance of these cells. We also give an overview of original and emerging differentiation strategies used to convert hESC to different cell types. Finally, we will discuss transplantation studies of hESC-derived cells with respect to safety and functional recovery. Show more

Keywords: Human, embryonic, cells, progenitors, differentiation, ectoderm, endoderm, mesoderm, karyotype, feeder-free, synthetic scaffolds, hydrogels, hyaluronic acid, hepatocyte, embryoid bodies, mesenchymal, osteocytes, chondrocytes, stromal, hematopoietic, cardiomyocytes, endothelial, epithelial, neural, neurons, motor neurons, dopaminergic neurons, oligodendrocytes, myelination, degenerative disorders, transplantation

DOI: 10.3233/RNN-2010-0543

Citation: Restorative Neurology and Neuroscience, vol. 28, no. 4, pp. 589-603, 2010