Restorative Neurology and Neuroscience - Volume 28, issue 4

Authors: Platz, Thomas | Rothwell, John C.

Article Type: Research Article

Abstract: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive method of stimulating the brain that changes excitability at the site of stimulation as well as at distant anatomically connected sites. Since the effects can outlast the period of stimulation for minutes or hours and are thought to be depend, at least in part, on changes in the efficiency of synaptic connections in the cortex, the method has generated much interest as a potential therapeutic intervention in a …wide range of neurological and psychiatric conditions. A symposium on brain stimulation and brain recovery was held in Greifswald (Germany) in 2010 to exchange of state-of-the-art knowledge about rTMS effects from animal experiments to clinical trials in conditions such as stroke, Parkinson disease, and depression. There was enormous interest in the effects of rTMS and signs of therapeutic success in mainly small clinical trials. However, it was also clear that some of our models of the effects of rTMS, such as upregulation or downregulation of specific brain areas may need further development if they are to account for all the observations that have been made so far. The results of the symposium are made available by lab reviews of members of the symposium's faculty. This editorial provides an overview. Show more

DOI: 10.3233/RNN-2010-0570

Citation: Restorative Neurology and Neuroscience, vol. 28, no. 4, pp. 387-398, 2010

Authors: Funke, Klaus | Benali, Alia

Article Type: Research Article

Abstract: Transcranial magnetic stimulation (TMS) can be used in two different ways to manipulate cortical information processing, either by applying a single pulse around the time point of expected task processing or by persistently shifting cortical excitability by repetitive stimulation (rTMS). Single pulses applied when specific cortical processing takes place always impair cortical function due to increased noise or enhanced inhibition, both resulting in decreased signal-to-noise ratio, while repetitive stimulation may allow to …weaken or improve cortical processing depending on the type of stimulation. The opposite effects of low- (∼1 Hz) and high-frequency rTMS (5–20 Hz), as well as the opposing effects of continuous versus intermittent theta-burst trains, lowering or raising cortical excitability respectively, have mainly been attributed to synaptic plasticity. As reviewed in this article, in a series of electrophysiological, immunohistochemical and molecular-biological animal experiments we obtained evidence for modulation of inhibitory cortical activity as a further reason of changing cortical excitability following rTMS. Show more

DOI: 10.3233/RNN-2010-0566

Citation: Restorative Neurology and Neuroscience, vol. 28, no. 4, pp. 399-417, 2010

Authors: Hamada, Masashi | Ugawa, Yoshikazu

Article Type: Research Article

Abstract: A new patterned repetitive transcranial magnetic stimulation (rTMS) protocol, quadripulse stimulation (QPS), can produce a broad range of motor cortical plasticity ranging from MEP suppression to MEP facilitation depending on the interval of the pulses within a burst. In addition to inducing lasting cortical plastic changes, QPS can also be used to evaluate priming effects: when used as a priming stimulation, which does not induce an LTP- or LTD-like phenomena itself, it can nevertheless change the …threshold for LTP- or LTD-like plasticity caused by a consecutive stimulation. This enables us to examine metaplasticity theory in more details in humans. Another application of QPS might be to induce symptomatic relief in patients with neurological or psychiatric disorders, such as Parkinson's disease, depression, or intractable pain. Show more

Keywords: Repetitive transcranial magnetic stimulation (rTMS), motor cortex, supplementary motor area, metaplasticity, LTP, LTD

DOI: 10.3233/RNN-2010-0564

Citation: Restorative Neurology and Neuroscience, vol. 28, no. 4, pp. 419-424, 2010

Authors: Stagg, Charlotte J. | O'Shea, Jacinta | Johansen-Berg, Heidi

Article Type: Research Article

Abstract: Repetitive Transcranial Magnetic Stimulation (rTMS) paradigms are showing increasing promise as tools for neurorehabilitation in a variety of chronic neurological and psychiatric conditions. However, the mechanisms by which they modulate cortical activation are still not completely understood. In this review we summarize what non-invasive magnetic resonance imaging techniques can tell us about the cortical effects of rTMS – from changes at a cellular level within the stimulated motor cortex, to modulating activation …patterns within the wider motor network. We discuss how variation in these effects in stroke patients may inform our understanding of how rTMS could improve function in these patients. Show more

Keywords: Repetitive transcranial magnetic stimulation, motor cortex, stroke, functional magnetic resonance imaging, magnetic resonance spectroscopy

DOI: 10.3233/RNN-2010-0553

Citation: Restorative Neurology and Neuroscience, vol. 28, no. 4, pp. 425-436, 2010

Authors: Kobayashi, Masahito

Article Type: Research Article

Abstract: Background: Disruption of a cortical region can paradoxically improve behavior. After unilateral damage to the primary motor cortex (M1), increased excitability of the unaffected M1 has been shown. The M1 plays a critical role in motor performance and also early aspects of motor skill learning. Repetitive transcranial magnetic stimulation (rTMS) of one motor cortex can lead a temporary reduction in cortical excitability. We hypothesize that unilateral suppression of one M1 by rTMS may increase excitability of …the unaffected motor cortex and thus improve motor performance and motor skill learning with the ipsilateral hand by releasing the contralateral motor cortex from transcallosal inhibition. Methods: Forty healthy volunteers participated in our study; 16 for the experiment I and 24 for the experiment II. In the experiment I, after practicing a sequential simple key-pressing task with the index finger, their motor performance was monitored before and after slow-frequency (1Hz) rTMS, applied on the M1 ipsilateral or contralateral to the hand, ipsilateral premotor area or vertex (Cz). In the experiment II, participants were randomly divided into three stimulation groups: i) ipsilateral M1; ii) contralateral M1; and iii) Cz. rTMS was applied before the initiation of practice and learning of a simple motor skill. Mean execution time and error rate were recorded in 4 sessions distributed over 2 days. Results: In experiment I: rTMS of M1 shortened execution time of the motor task with the ipsilateral hand, without affecting performance with the contralateral hand. This effect outlasted rTMS by at least 10 min, and was most prominent for M1 stimulation. In experiment II, disruption of M1 with rTMS slowed down skill acquisition with the contralateral hand, but paradoxically accelerated learning with the ipsilateral hand. This effect was evident during the first of 2 days of practice in the group with rTMS over the ipsilateral M1 compared to the other two groups (Cz and contralateral M1). Conclusions: Our results support the notion of an interhemispheric competition, and demonstrate the utility of rTMS to explore the functional facilitation of the un-stimulated counterpart M1 with effects on motor execution and learning, which may have implications for neurorehabilitation. Show more

Keywords: Ipsilateral motor area, transcranial magnetic stimulation, motor learning, interhemispheric inhibition

DOI: 10.3233/RNN-2010-0562

Citation: Restorative Neurology and Neuroscience, vol. 28, no. 4, pp. 437-448, 2010

Authors: Huang, Ying-Zu

Article Type: Research Article

Abstract: Repetitive electrical stimulation has been applied to induce long-term changes in synaptic strength in animal preparations. It is generally believed that such changes in synapses form the basis of neural plasticity. Recently, several techniques, including repetitive transcranial magnetic stimulation (rTMS), have been developed to attempt to replicate similar plasticity effects in the brains of conscious humans. However, traditional paradigms of rTMS usually require lengthy stimulation and relatively high stimulus intensity. In light …of these problems, a novel rTMS paradigm- theta burst stimulation (TBS) – was developed. TBS is able to produce plasticity-like effects more efficiently and powerfully than traditional protocols. The excitability of circuits within the motor cortex can be modified not only by TBS over the primary motor cortex but also when it is delivered to the premotor area. Moreover, TBS over the premotor cortex modifies aspects of spinal reflexes. Studies using TBS over the motor and premotor cortices provide further understanding of dystonia, and the results also distinguish the different mechanisms of the effects of TBS given to the primary motor and premotor cortices. In addition, some data also support the hypothesis that TBS is a potential candidate technique to help restore damaged motor functions through brain stimulation. Show more

Keywords: Motor, premotor, plasticity, transcranial magnetic stimulation, theta burst stimulation, TBS, dystonia

DOI: 10.3233/RNN-2010-0554

Citation: Restorative Neurology and Neuroscience, vol. 28, no. 4, pp. 449-457, 2010

Authors: Todd, G. | Ridding, M.C.

Article Type: Research Article

Abstract: Non-invasive brain stimulation techniques, such as repetitive transcranial magnetic stimulation (rTMS), can modify cortical excitability in a lasting fashion. The modification can be bi-directional in nature and holds considerable therapeutic promise for a number of neurological conditions. However, the effectiveness of these techniques is currently limited by large intra- and inter-subject variability in the response. A number of factors that contribute to response variability have now been identified, with one of the …most important being the history of synaptic activity within the cortical region being targeted by stimulation. In this review we discuss what is currently known about the influence of behaviourally, or experimentally, induced changes in synaptic activity in the cortical (or interconnected) region being targeted by stimulation on the response to rTMS techniques. Understanding such influences is a critical step in the development of effective therapeutic paradigms employing such techniques. Show more

DOI: 10.3233/RNN-2010-0565

Citation: Restorative Neurology and Neuroscience, vol. 28, no. 4, pp. 459-467, 2010

Authors: Lotze, M.

Article Type: Research Article

Abstract: Applying functional lesions using functional magnetic resonance imaging (fMRI)-navigated transcranial magnetic stimulation (TMS) is a powerful method for investigation of the functional relevance of a given activation site for motor performance in healthy individuals, and also for investigation of the temporal interactions of particular areas during movement preparation. In patients with good cognitive compliance, this procedure may be useful for detection of functional reorganisation or to plan individual therapy directions. Different protocols …for applying functional lesions are presented here and their relevance and usage in different applications are explained. Show more

DOI: 10.3233/RNN-2010-0563

Citation: Restorative Neurology and Neuroscience, vol. 28, no. 4, pp. 469-476, 2010

Authors: Antal, Andrea | Paulus, Walter

Article Type: Research Article

Abstract: Transcranial stimulation of the primary motor cortex (M1) for the treatment of pain has attracted much interest in recent years. Non-invasive low frequency and high frequency repetitive transcranial magnetic stimulation (rTMS) over the M1 was reported to reduce both experimentally induced acute and chronic pain. In this paper we summarize the results of several studies from our laboratory and report the antinociceptive effects of a special rTMS paradigm, theta-burst stimulation (TBS). We have applied excitatory (iTBS) …and inhibitory (cTBS) paradigms over two cortical locations (M1 and the primary somatosensory cortex (S1)). As evaluation criteria a pain rating scale and the recording of laser evoked potentials (LEPs) were used. Reduced subjective pain perception after cTBS could be objectified by alterations of LEPs that reflect pain related activations in the pain processing in the operculo-insular and anterior cingulate cortex. The stimulation of S1 had physiological effects (LEPs), but did not induce significant reduction in acute pain perception. We believe that the application of cTBS over M1 in pain research has a great potential and as a method it can contribute to a more efficient manipulation of the brain plasticity for therapeutic purposes, for example in chronic pain. Nevertheless, the effectiveness of other types of TBS paradigms should also be tested. Show more

Keywords: Acute pain, laser TBS, M1, S1, LEP

DOI: 10.3233/RNN-2010-0555

Citation: Restorative Neurology and Neuroscience, vol. 28, no. 4, pp. 477-484, 2010

Authors: Sack, Alexander T.

Article Type: Research Article

Abstract: Visuospatial processing refers to the spatial perception, recognition and analysis of visual input. Human functional brain imaging studies have consistently revealed the involvement of fronto-parietal brain areas during the execution of visuospatial tasks. Just as the execution of these tasks activates fronto-parietal regions in the healthy brain, lesions to those structures, e.g. after stroke or brain injury, cause specific spatial deficits. The most prominent of these is known as spatial neglect. There are …several competing theories on the neural mechanisms underlying spatial neglect. Although each of these theories postulates different underlying physiological mechanisms, they all account in their own way for the fact that the prevalence of neglect is much higher following right hemisphere lesions. This makes it difficult to distinguish between the different models at a behavioural level. Until today, it was impossible to empirically address these matters and to provide direct and conclusive empirical evidence in favour of one of the competing theories of spatial neglect. This review article describes the neural correlates of intact visuospatial processing as revealed by non-invasive functional brain imaging studies. It subsequently focuses on the approach of using the non-invasive brain inference technique of transcranial magnetic brain stimulation (TMS) to transiently and reversibly disrupt neural activity in these visuospatial processing-related brain regions. Using this approach, we can now imitate specific spatial deficits and neglect-like symptoms in healthy volunteers. Mimicking and manipulating the spatial deficits following unilateral brain lesions, under controlled experimental conditions, may allow for the development of new therapeutic interventions for parietal stroke patients suffering from real spatial neglect. The perspective is to use non-invasive brain interference to guide and promote functional recovery on a brain-system level in stroke and neglect patients, based on knowledge directly derived from fundamental brain research in healthy volunteers. Show more

DOI: 10.3233/RNN-2010-0568

Citation: Restorative Neurology and Neuroscience, vol. 28, no. 4, pp. 485-497, 2010