Restorative Neurology and Neuroscience - Volume 30, issue 3

Authors: Chang, Won Hyuk | Kim, Yun-Hee | Yoo, Woo-Kyoung | Goo, Kyoung-Hyup | Park, Chang-hyun | Kim, Sung Tae | Pascual-Leone, Alvaro

Article Type: Research Article

Abstract: Background and purpose: Repetitive transcranial magnetic stimulation (rTMS) may enhance plastic changes in the human cortex and modulation of behavior. However, the underlying neural mechanisms have not been sufficiently investigated. We examined the clinical effects and neural correlates of high-frequency rTMS coupled with motor training in patients with hemiparesis after stroke. Methods: Twenty-one patients were randomly divided into two groups, and received either real or sham rTMS. Ten daily sessions of 1,000 pulses of real or sham rTMS were applied at 10 Hz over the primary motor cortex of the affected hemisphere, coupled with sequential finger motor training of the …paretic hand. Functional MRIs were obtained before and after training using sequential finger motor tasks, and performances were assessed. Results: Following rTMS intervention, movement accuracy of sequential finger motor tasks showed significantly greater improvement in the real group than in the sham group (p < 0.05). Real rTMS modulated areas of brain activation during performance of motor tasks with a significant interaction effect in the sensorimotor cortex, thalamus, and caudate nucleus. Patients in the real rTMS group also showed significantly enhanced activation in the affected hemisphere compared to the sham rTMS group. Conclusion: According to these results, a 10 day course of high-frequency rTMS coupled with motor training improved motor performance through modulation of activities in the cortico-basal ganglia-thalamocortical circuits. Show more

Keywords: Stroke, repetitive transcranial magnetic stimulation, functional MRI, motor function, cortico-basal ganglia-thalamocortical circuits

DOI: 10.3233/RNN-2012-110162

Citation: Restorative Neurology and Neuroscience, vol. 30, no. 3, pp. 179-189, 2012

Authors: Schade, Sebastian | Moliadze, Vera | Paulus, Walter | Antal, Andrea

Article Type: Research Article

Abstract: Purpose: Transcranial direct current stimulation (tDCS) has proven to be a useful tool for fundamental brain research as well as for attempts in therapy of neurological and psychiatric diseases by modulating neuronal plasticity. Little is understood about the effects of tDCS are influenced by hemispheric dominance, even less in terms of handedness. The aim of our pilot study was to investigate whether tDCS induced neuroplastic changes may be different in right- and left-handed individuals due to existing differences in hemispheric lateralisation. Methods: We measured changes in motor evoked potentials (MEPs) after application of tDCS in 8 right-handers, 8 left-handers and …8 mixed-handers according to the Edinburgh Handedness Inventory (EHI). In double-blind sessions, we applied either anodal or cathodal tDCS for 5 minutes for each hemisphere. Results: While motor thresholds (MT) seem to be not influenced by handedness significantly, in right-handed subjects we reproduced the well-known effects of tDCS: anodal stimulation increased while cathodal stimulation decreased MEP amplitudes. However, left-and mixed-handed subjects differed from right-handed subjects. After anodal stimulation of the left hemisphere the increase of the MEP amplitudes was stronger in right handed subjects than in left and mixed handed subjects. Interestingly, after cathodal stimulation of the left hemisphere this difference was less marked. The stimulation of the right hemisphere showed the same tendency, but results were not significant. Conclusions: For the first time, we are able to demonstrate that the modulating effects of tDCS on corticospinal excitability differ moderately in the left-and mixed-handed population compared to right-handed subjects. The shown differences according to handedness should be taken into account in further studies. Show more

Keywords: Hemispheric asymmetry, handedness, Edinburgh Handedness Inventory (EHI), motor thresholds (MTs), motor evoked potentials (MEPs), transcranial direct current stimulation (tDCS)

DOI: 10.3233/RNN-2012-110175

Citation: Restorative Neurology and Neuroscience, vol. 30, no. 3, pp. 191-198, 2012

Authors: Platz, Thomas | Roschka, Sybille | Christel, Marianne I. | Duecker, Felix | Rothwell, John C. | Sack, Alexander T.

Article Type: Research Article

Abstract: Purpose: To examine whether motor performance and motor learning in healthy subjects can be segregated into a number of distinct motor abilities which are linked to intact processing in different motor-related brain regions (M1, S1, SMA, PMC) early during learning. Methods: Seven young healthy subjects trained in eight motor arm tasks (Arm Ability Training, AAT) once a day for 5 days using their left non-dominant arm. Except for day 1 (baseline), training was performed before and after applying an inhibitory form of repetitive transcranial magnetic stimulation (cTBS, continuous theta burst) to either M1, S1, SMA, or PMC. Results: A principal …component analysis of the motor behaviour data suggested four independent motor abilities: aiming, speed, steadiness, and visuomotor tracking. AAT induced substantial motor learning across abilities. Within session effects of cTBS revealed that activity in primary somatosensory cortex (S1) was relevant for motor performance and learning across all tasks whereas M1 was specifically involved in rapid tapping movements, PMC in ballistic arm navigation in extra-personal space; performance on a non-trained motor tasks was not affected by cTBS. Conclusions: Cortical sensory and motor areas including S1, M1, and PMC functionally contribute to early motor learning in a differential manner across motor abilities. Show more

Keywords: Motor practice, learning, cortex, plasticity, transcranial magnetic stimulation

DOI: 10.3233/RNN-2012-110204

Citation: Restorative Neurology and Neuroscience, vol. 30, no. 3, pp. 199-211, 2012

Authors: Platz, Thomas | Roschka, Sybille | Doppl, Karla | Roth, Charlotte | Lotze, Martin | Sack, Alexander T. | Rothwell, John C.

Article Type: Research Article

Abstract: Purpose: To assess the behavioural effects of prolonged motor practice in healthy volunteers, and the specific impact of inhibiting different motor-related brain regions in the late phase of motor learning using continuous theta burst transcranial magnetic stimulation (cTBS). Methods: Twelve subjects trained their non-dominant arm in eight arm motor tasks (Arm Ability Training, AAT) once a day for three weeks (16 sessions). During the last four days, training was performed before and after applying cTBS to either M1, S1, SMA, or PMC. Results: The AAT induced substantial and robust motor learning for the trained arm with variations across tasks. Considerable …motor learning was also observed in the non-trained dominant arm with remarkably similar variations across tasks, suggesting that practise improved common underlying sensorimotor capacities (abilities) in addition to effector-specific effects. When applied after prolonged training, inhibitory cTBS showed no detrimental effects on motor performance/learning; M1 cTBS even improved performance in a labyrinth task. Conclusions: Prolonged training with the non-dominant arm led to profound motor learning across abilities with transfer to the non-trained dominant arm. Unlike during early stages of motor learning, no detrimental effect of cTBS over M1, S1, PMC, or SMA could be substantiated after prolonged motor practice. Show more

Keywords: Motor practice, learning, cortex, plasticity, transcranial magnetic stimulation

DOI: 10.3233/RNN-2012-110205

Citation: Restorative Neurology and Neuroscience, vol. 30, no. 3, pp. 213-224, 2012

Authors: Tornøe, Jens | Torp, Malene | Jørgensen, Jesper Roland | Emerich, Dwaine F. | Thanos, Chris | Bintz, Briannan | Fjord-Larsen, Lone | Wahlberg, Lars U.

Article Type: Research Article

Abstract: Purpose: Encapsulated cell (EC) biodelivery is a promising, clinically relevant technology platform to safely target the delivery of therapeutic proteins to the central nervous system. The purpose of this study was to evaluate EC biodelivery of the novel neurotrophic factor, Meteorin, to the striatum of rats and to investigate its neuroprotective effects against quinolinic acid (QA)-induced excitotoxicity. Methods: Meteorin-producing ARPE-19 cells were loaded into EC biodelivery devices and implanted into the striatum of rats. Two weeks after implantation, QA was injected into the ipsilateral striatum followed by assessment of neurological performance two and four weeks after QA administration. Results: Implant-delivered …Meteorin effectively protected against QA-induced toxicity, as manifested by both near-normal neurological performance and reduction of brain cell death. Morphological analysis of the Meteorin-treated brains showed a markedly reduced striatal lesion size. The EC biodelivery devices produced stable or even increasing levels of Meteorin throughout the study over 6 weeks. Conclusions: Stereotactically implanted EC biodelivery devices releasing Meteorin could offer a feasible strategy in the treatment of neurological diseases with an excitotoxic component such as Huntington's disease. In a broader sense, the EC biodelivery technology is a promising therapeutic protein delivery platform for the treatment of a wide range of diseases of the central nervous system. Show more

Keywords: EC biodelivery, encapsulated cells, Meteorin, neuroprotection, neurodegeneration, quinolinic acid, excitotoxicity, Huntington's disease

DOI: 10.3233/RNN-2012-110199

Citation: Restorative Neurology and Neuroscience, vol. 30, no. 3, pp. 225-236, 2012

Authors: Chen, Hu | Dzitoyeva, Svetlana | Manev, Hari

Article Type: Research Article

Abstract: Purpose: Aging is believed to affect epigenetic marking of brain DNA with 5-methylcytosine (5mC) and possibly via the 5mC to 5-hydroxymethylcytosine (5hmC) conversion by TET (ten-eleven translocation) enzymes. We investigated the impact of aging on hippocampal DNA 5-hydroxymethylation including in the sequence of aging-susceptible 5-lipoxygenase (5-LOX) gene. Methods: Hippocampal samples were obtained from C57BL6 mice. Cellular 5hmC localization was determined by immunofluorescence. The global 5mC and 5hmC contents were measured with the corresponding ELISA. The 5-LOX 5hmC content was measured using a glucosyltransferase/enzymatic restriction digest assay. TET mRNA was measured using qRT-PCR. Results: Global hippocampal 5hmC content increased during aging …as did the 5hmC content in the 5-LOX gene. This occurred without alterations of TET1-3 mRNAs and without changes in the content of 8-hydroxy-2-deoxy-guanosine, a marker of non-enzymatic DNA oxidation. Conclusions: The aging-associated increase of hippocampal 5hmC content (global and 5-LOX) appears to be unrelated to oxidative stress. It may be driven by an altered activity but not by the increased expression of the three TET enzymes. Global 5hmC content was increased during aging in the absence of 5mC decrease, suggesting that 5hmC could act as an epigenetic marker and not only as an intermediary in DNA demethylation. Further research is needed to elucidate the functional implications of the impact of aging on hippocampal cytosine hydroxymethylation. Show more

Keywords: Epigenetic, 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), 5-lipoxygenase (5-LOX), aging, hippocampus, ten-eleven translocation (TET)

DOI: 10.3233/RNN-2012-110223

Citation: Restorative Neurology and Neuroscience, vol. 30, no. 3, pp. 237-245, 2012

Authors: Kimberley, Teresa J. | Pickett, Kristen A.

Article Type: Research Article

Abstract: Purpose: The pathophysiology of focal hand dystonia (FHD) is not clearly understood. Previous studies have reported increased and decreased cortical activity associated with motor tasks. The aim of this study was to investigate blood oxygen level dependent (BOLD) signal changes in functional magnetic resonance imaging within the hand area of primary motor cortex during cued movement of individual digits. Methods: Eight healthy individuals and five individuals with right hand FHD participated. Beta weight contrasts were examined within the hand area of the motor cortex. Results: In both groups, BOLD signal changes in the hemisphere contralateral to the moving hand were …greater in the left hemisphere than the right. Between groups, no difference was found during control of the left hand, but a significant difference was seen during right hand movement; specifically, individuals with dystonia showed increased contralateral and decreased ipsilateral cortical response associated with the affected hand as compared to healthy individuals. This suggests a similar, albeit exaggerated pattern of activation in individuals with FHD on the affected side. Conclusions: These results suggest different levels of ipsilateral and contralateral activation between healthy and dystonic individuals but also show a relative difference between symptomatic and asymptomatic control within the patient population. Show more

Keywords: Focal hand dystonia, fMRI, motor cortex

DOI: 10.3233/RNN-2012-110183

Citation: Restorative Neurology and Neuroscience, vol. 30, no. 3, pp. 247-254, 2012

Authors: Antal, Andrea | Kovács, Gyula | Chaieb, Leila | Cziraki, Csaba | Paulus, Walter | Greenlee, Mark W.

Article Type: Research Article

Abstract: Purpose: Transcranial direct current stimulation (tDCS) was reintroduced about a decade ago as a tool for inducing long-lasting changes in cortical excitability. Recently it has been shown that both motor and cognitive functions can be influenced by tDCS. Here, we tested the effect of tDCS on the blood-oxygen level dependent (BOLD) signal evoked by coherent visual motion using functional magnetic resonance imaging (fMRI). Methods: The subjects underwent 10 min of cathodal and sham tDCS, applied over the right MT+. Following stimulation, random dot kinomatograms (RDK) with different percentages (10%, 30%, 50%) of coherently moving dots were presented. Results: All motion …stimuli activated MT+ in both stimulation conditions. However, cathodal stimulation led to an increase in fMRI signal in MT+ when compared to sham stimulation. This effect did not depend on the coherence level of the visual stimulus. Conclusions: Here, we show for the first time, that cathodal tDCS stimulation leads to elevated fMRI signal in the human visual cortex. Show more

Keywords: Area MT+, fMRI, motion perception, transcranial direct current stimulation (tDCS)

DOI: 10.3233/RNN-2012-110208

Citation: Restorative Neurology and Neuroscience, vol. 30, no. 3, pp. 255-263, 2012

Authors: Guzen, Fausto Pierdoná | Soares, Joacil Germano | de Freitas, Leandro Moura | Cavalcanti, José Rodolfo Lopes de Paiva | Oliveira, Francisco Gilberto | Araújo, John Fontenele | Cavalcante, Jeferson de Souza | Cavalcante, Judney Cley | Nascimento Jr., Expedito Silva do | de Oliveira Costa, Miriam Stela Maris

Article Type: Research Article

Abstract: Purpose: Failure of severed adult central nervous system (CNS) axons to regenerate could be attributed with a reduced intrinsic growing capacity. Severe spinal cord injury is frequently associated with a permanent loss of function because the surviving neurons are impaired to regrow their fibers and to reestablish functional contacts. Peripheral nerves are known as good substrate for bridging CNS trauma with neurotrophic factor addition. We evaluated whether fibroblastic growth factor 2 (FGF-2) placed in a gap promoted by complete transection of the spinal cord may increase the ability of sciatic nerve graft to enhance motor recovery and fibers regrow. Methods: …We used a complete spinal cord transection model. Rats received a 4 mm-long gap at low thoracic level and were repaired with saline (control) or fragment of the sciatic nerve (Nerve) or FGF-2 was added to nerve fragment (Nerve+FGF-2) to the grafts immediately after complete transection. The hind limbs performance was evaluated weekly for 8 weeks by using motor behavior score (BBB) and sensorimotor tests-linked to the combined behavior score (CBS), which indicate the degree of the motor improvement and the percentage of functional deficit, respectively. Neuronal plasticity were evaluated at the epicenter of the injury using MAP-2 and GAP-43 expression. Results: Spinal cord treatment with sciatic nerve and sciatic nerve plus FGF-2 allowed recovery of hind limb movements compared to control, manifested by significantly higher behavioral scores. Higher amounts of MAP-2 and GAP-43 immunoreactive fibers were found in the epicenter of the graft when FGF-2 was added. Conclusions: FGF-2 added to the nerve graft favored the motor recovery and fiber regrowth. Thus, these results encourage us to explore autologous transplantation as a novel and promising cell therapy for treatment of spinal cord lesion. Show more

Keywords: Neuroregeneration, sciatic nerve graft, spinal cord, fibroblastic growth factor-2 and motor behavior

DOI: 10.3233/RNN-2012-110184

Citation: Restorative Neurology and Neuroscience, vol. 30, no. 3, pp. 265-275, 2012