Restorative Neurology and Neuroscience - Volume 30, issue 4

Authors: Bashir, Shahid | Vernet, Marine | Yoo, Woo-Kyoung | Mizrahi, Ilan | Theoret, Hugo | Pascual-Leone, Alvaro

Article Type: Research Article

Abstract: Purpose: Even after a mild traumatic brain injury (TBI) symptoms may be long lasting and never resolve completely. The neurophysiologic substrate for such lasting deficits remains unclear. There is a lack of objective measures of early brain abnormalities following mild TBI, which could shed light on the genesis of these lasting impairments. Methods: Here we report findings in a previously healthy man tested 2 and 6 weeks after a well-documented concussion. Findings were compared with 12 control subjects. All subjects underwent brain magnetic resonance imaging (MRI) and diffusion-tensor imaging (DTI). Testing included neuropsychological evaluation and physiological assessment with TMS and …EEG, excitatory/inhibitory balance and brain plasticity. Results: While the MRI, DTI and neuropsychological evaluations showed no abnormalities, neurophysiologic tests revealed subclinical abnormalities in our patient: (1) Significantly higher intracortical facilitation than the control group at both time points; (2) Intracortical inhibition presumably mediated by GABAB receptors was absent at week 2, but returned to normal value at week 6; (3) Abnormal mechanisms of plasticity at week 2, that normalize at week 6. Conclusions: These findings demonstrate a transient alteration of brain cortical physiology following concussion independent of anatomical findings and neuropsychological function. This case study suggests that TMS measures may serve as sensitive biomarkers of physiologic brain abnormalities after concussion. Show more

Keywords: Theta burst stimulation, motor cortex, excitability, EEG

DOI: 10.3233/RNN-2012-110207

Citation: Restorative Neurology and Neuroscience, vol. 30, no. 4, pp. 277-282, 2012

Authors: Menniti, Frank S. | Ren, JingMei | Sietsma, Dana K. | Som, Angel | Nelson, Fredrick R. | Stephenson, Diane T. | Tate, Barbara A. | Finklestein, Seth P.

Article Type: Research Article

Abstract: Purpose: Phosphodiesterase 5A (PDE5A) inhibitors improve functional recovery in experimental models of stroke in rats when treatment is delayed and without effect on infarct volume. PDE5A is expressed to only a very limited extent in forebrain tissues, raising the possibility that the locus of effect for the inhibitors is outside the brain. To start to address this question, we determined whether PDE5A inhibitors must have the ability to cross the blood brain barrier to improve recovery. Method: After permanent middle cerebral artery occlusion in rats, PF-5 and UK-489,791, PDE5A inhibitors that do or do not pass the blood brain barrier, …were administered starting 24 h after occlusion and continued for 1 week. Motor function was assessed at intervals to 28 days using body swing and limb placement measures. Results: Both PF-5 and UK-489,791 produced improvement in motor scores over 28 days that were significantly greater than in vehicle treated animals. There was no difference in efficacy between the two PDE5A inhibitors. Conclusions: Brain penetrability appears not to be critical to the ability of a PDE5A inhibitor to improve functional recovery after experimental stroke in rats. This finding is discussed with regard to the cellular target(s) for PDE5A inhibitors mediating this effect. Show more

Keywords: Phosphodiesterase 5A, PDE5A, stroke recovery, PF-5, PF-489,791, brain penetration

DOI: 10.3233/RNN-2012-110187

Citation: Restorative Neurology and Neuroscience, vol. 30, no. 4, pp. 283-289, 2012

Authors: Vonder Haar, Cole | Emery, Michael A. | Hoane, Michael R.

Article Type: Research Article

Abstract: Purpose: Traumatic brain injury (TBI) is a major health concern today and effective treatments must be developed in order to combat the numerous TBIs that occur each year. Multiple b-vitamins have been shown to have neuroprotective effects, however, folic acid (B9 ) has not been widely studied. The current study examined two different doses in a rodent model of controlled cortical impact (CCI) TBI. Methods: Sham procedures or a unilateral parietal controlled cortical impact injury was induced. Rats were administered either vehicle or folic acid in an 80 μg/kg or 800 μg/kg dose. Rats were tested on the bilateral tactile …adhesive removal task, rotarod task and the Morris water maze. Brains were examined to determine lesion size and neuronal loss. Results: Neither of the folic acid-treated groups showed improvement on any behavioral task or anatomical measure post-CCI and the high dose group had increased neuronal loss compared to the vehicle. Administration of the high dose in sham animals resulted in some behavioral dysfunction and significant neuronal loss. Conclusions: The results from this study suggest that folic acid may not represent an effective avenue for treatment and that higher doses may actually be detrimental following TBI. Show more

Keywords: Vitamin-therapy, traumatic brain injury, neurotoxicity, therapeutic, recovery of function

DOI: 10.3233/RNN-2012-110196

Citation: Restorative Neurology and Neuroscience, vol. 30, no. 4, pp. 291-302, 2012

Authors: Yang, Eun Joo | Baek, So-Ra | Shin, Joonho | Lim, Jong Youb | Jang, Hye Jin | Kim, Yu Kyeong | Paik, Nam-Jong

Article Type: Research Article

Abstract: Purpose: Transcranial direct current stimulation (tDCS) combined with swallowing training might improve swallowing function in patients with post-stroke dysphagia. We investigate the effects of transcranial direct current stimulation (tDCS) combined with swallowing training on post-stroke dysphagia. Methods: Sixteen patients with post-stroke dysphagia, diagnosed using video fluoroscopic swallowing (VFSS), were randomly assigned into two groups: (1) anodal tDCS group (1 mA for 20 min), or (2) sham group (1 mA for 30 s). Patients received anodal tDCS or sham over the pharyngeal motor cortex of the affected hemisphere during 30 min of conventional swallowing training for 10 days. Functional dysphagia scale …(FDS) scores based on VFSS were measured at baseline and immediately and 3 months after the intervention. The effect of tDCS on dysphagia was analyzed using a generalized linear model (GLM) with repeated measures. Results: After the intervention, FDS scores improved in both groups without significant differences. However, 3 months after the intervention, anodal tDCS elicited greater improvement in terms of FDS compared to the sham group (β = −7.79, p = 0.041) after controlling for age, National Institutes of Health Stroke Scale (NIHSS) score, lesion size, baseline FDS score, and time from stroke onset. Conclusions: Anodal tDCS applied over the affected pharyngeal motor cortex can enhance the outcome of swallowing training in post-stroke dysphagia. Our results suggest that non-invasive cortical stimulation has a potential role as an adjuvant strategy during swallowing training in patients with post-stroke dysphagia. Show more

Keywords: Dysphagia, stroke, cortical stimulation, transcranial direct current stimulation

DOI: 10.3233/RNN-2012-110213

Citation: Restorative Neurology and Neuroscience, vol. 30, no. 4, pp. 303-311, 2012

Authors: Levy-Tzedek, S. | Hanassy, S. | Abboud, S. | Maidenbaum, S. | Amedi, A.

Article Type: Research Article

Abstract: Purpose: Visual sensory substitution devices (SSDs) use sound or touch to convey information that is normally perceived by vision. The primary focus of prior research using SSDs was the perceptual components of learning to use SSDs and their neural correlates. However, sensorimotor integration is critical in the effort to make SSDs relevant for everyday tasks, like grabbing a cup of coffee efficiently. The purpose of this study was to test the use of a novel visual-to-auditory SSD to guide a fast reaching movement. Methods: Using sound, the SSD device relays location, shape and color information. Participants were asked to make …fast reaching movements to targets presented by the SSD. Results: After only a short practice session, blindfolded sighted participants performed fast and accurate movements to presented targets, which did not differ significantly from movements performed with visual feedback in terms of movement time, peak speed, and path length. A small but significant difference was found between the endpoint accuracy of movements under the two feedback conditions; remarkably, in both cases the average error was smaller than 0.5 cm. Conclusions: Our findings combine with previous brain-imaging studies to support a theory of a modality-independent representation of spatial information. Task-specificity, rather than modality-specificity, of brain functions is crucially important for the rehabilitative use of SSDs in the blind and the visually impaired. We present the first direct comparison between movement trajectories performed with an SSD and ones performed under visual guidance. The accuracy level reached in this study demonstrates the potential applicability of using the visual-to-auditory SSD for performance of daily tasks which require fast, accurate reaching movements, and indicates a potential for rehabilitative use of the device. Show more

Keywords: Sensory substitution, motor control, vision rehabilitation, spatial processing, visual impairment, blindness, sensorimotor integration, perception and action

DOI: 10.3233/RNN-2012-110219

Citation: Restorative Neurology and Neuroscience, vol. 30, no. 4, pp. 313-323, 2012

Authors: Crane, Andrew T. | Fink, Kyle D. | Smith, Jeffrey S.

Article Type: Research Article

Abstract: Purpose: Traumatic brain injury (TBI) produces significant deficits in executive function, sensory-motor function, and on spatial learning tasks. We wish to study if recovery from TBI can be benefited by voluntary exercise. Methods: A variation of the stop-signal reaction time (SSRT) task was employed to measure rats ability to obtain maximum reinforcers in a complex behavioral task. A 2 × 2 (lesion × treatment) experimental design was constructed with 31 weight restricted male Long-Evans rats which received either bilateral cortical contusions to the medial frontal cortex or sham preparations following the acquisition of the SSRT task (matched based on pre-surgical …performance). Following surgery, rats were randomly assigned to either an environment with free access to running wheels or traditional single housing without running wheels. Results: Rats receiving a bilateral TBI performed significantly worse than sham operated rats on a complex task. Contrary to our original hypothesis, acute exercise following injury exacerbated the deficits in the complex task that did not return to levels of the injured rats without access to running wheels until post-TBI day 13. Conclusion: We found a significant interaction between severe bilateral TBI and the introduction of voluntary exercise immediately post-injury. In this paradigm, voluntary wheel running exacerbated the TBI-induced deficit, rather than reducing it. Show more

Keywords: Traumatic brain injury, physiotherapy, executive function

DOI: 10.3233/RNN-2012-120232

Citation: Restorative Neurology and Neuroscience, vol. 30, no. 4, pp. 325-333, 2012

Authors: Liu, Ling | Qian, Xin-Hong | Feng, Guo-Dong | Wu, Ming-Mei | Yang, An-An | Jiao, Xi-Ying | You, Si-Wei | Ju, Gong

Article Type: Research Article

Abstract: Purpose: To compare neuroprotection and therapeutic time windows of two diazepam regimens on retinal ganglion cells (RGCs) after rat optic nerve transection (ONT). Methods: Adult rats received initial intraperitoneal diazepam injections 30 minutes before left ONT, followed by daily diazepam (Regimen-A) or every 8 hours for 3 days (Regimen-B) until they were killed at Day 7 or 14. Initial diazepam in Regimen-A and Regimen-B was delayed to 3, 6, 7, 9, 10, 12 and 6, 7, 8, 9, 10, 12 hours after ONT and these animals survived for 7 days. The effect of daily combinational uses of diazepam and bicuculline …was assayed at 7 days. Results: Regimen-A induced higher RGC densities than those in control and Regimen-B groups at Day 7, but lower density than Regimen-B did at Day 14. When initial diazepam was delayed beyond 6 or 8 hours after ONT with Regimen-A and Regimen-B, the promoting effects of diazepam on RGC densities disappeared. Bicuculline completely inhibited the protection of diazepam. Conclusions: Prolonged neuroprotection on RGCs at Day 14 and extended therapeutic time window for 8 hours can be achieved by Regimen-B, while Regimen-A induces a stronger neuroprotection at Day 7. Diazepam neuroprotection is mediated through GABAA receptor. Show more

Keywords: Diazepam, optic nerve transection, retinal ganglion cells, neuroprotection, GABA receptor, rat

DOI: 10.3233/RNN-2012-110216

Citation: Restorative Neurology and Neuroscience, vol. 30, no. 4, pp. 335-343, 2012

Authors: Vallence, Ann-Maree | Reilly, Karen | Hammond, Geoff

Article Type: Research Article

Abstract: Purpose: The primary motor cortex is capable of rapid, reversible plastic changes and longer-term, more permanent reorganization. Ischemic nerve block (INB) is a model of deafferentation-induced short-term plasticity. We used transcranial magnetic stimulation to examine whether changes in the excitability of short- and/or long-interval intracortical inhibitory (SICI, LICI) or short-interval intracortical facilitatory (SICF) circuits underlie the corticospinal excitability increases observed during INB. Methods: SICI and LICI recruitment curves, obtained by varying conditioning stimulus intensity, and SICF were measured at multiple inter-stimulus intervals (ISIs). Results: Forearm flexor MEP amplitude increased during INB at the wrist; this was not accompanied by changes …in SICI at ISIs of 1 or 2 ms, in SICF at ISIs of 1.2, 2.7, or 4.4 ms, or in LICI at an ISI of 80 ms, but was accompanied by an increase in LICI at an ISI of 150 ms. Conclusions: The results suggest that (1) the increased excitability of forearm flexors is not due to reduced SICI or LICI or increased SICF, and (2) LICI measured at ISIs of 80 and 150 ms are distinct processes. We discuss the importance of identifying distinct processes of LICI and speculate regarding other mechanisms that could potentially underlie INB-induced plasticity. Show more

Keywords: Ischemic nerve block, transcranial magnetic stimulation, short-interval intracortical inhibition, long-interval intracortical inhibition, short-interval intracortical facilitation, primary motor cortex, cortical plasticity

DOI: 10.3233/RNN-2012-110198

Citation: Restorative Neurology and Neuroscience, vol. 30, no. 4, pp. 345-354, 2012