Restorative Neurology and Neuroscience - Volume 36, issue 6

Authors: Kusch, M. | Schmidt, C.C. | Göden, L. | Tscherpel, C. | Stahl, J. | Saliger, J. | Karbe, H. | Fink, G.R. | Weiss, P.H.

Article Type: Research Article

Abstract: Background and Objective: Apraxia is a deficit of motor cognition leading to difficulties in actual tool use, imitation of gestures, and pantomiming object use. To date, little data exist regarding the recovery from apraxic deficits after stroke, and no statistical lesion mapping study investigated the neural correlate of recovery from apraxia. Accordingly, we here examined recovery from apraxic deficits, differential associations of apraxia task (imitation vs. pantomime) and effector (bucco-facial vs. limb apraxia) with recovery, and the underlying neural correlates. Methods: We assessed apraxia in 39 patients with left hemisphere (LH) stroke both at admission and approximately 11 …days later. Furthermore, we collected clinical imaging data to identify brain regions associated with recovery from apraxic deficits using voxel-based lesion-symptom mapping (VLSM). Results: Between the two assessments, a significant recovery from apraxic deficits was observed with a tendency of enhanced recovery of limb compared to bucco-facial apraxia. VLSM analyses revealed that within the lesion pattern initially associated with apraxia, lesions of the left insula were associated with remission of apraxic deficits, whereas lesions to the (inferior) parietal lobe (IPL; supramarginal and angular gyrus) and the superior longitudinal fasciculus (SLF) were associated with persistent apraxic deficits. Conclusions: Data suggest that lesions affecting the core regions (and white matter) of the fronto-parietal praxis network cause more persistent apraxic deficits than lesions affecting other regions (here: the left insula) that also contribute to motor cognition and apraxic deficits. Show more

Keywords: Stroke, neurorehabilitation, aphasia, VLSM, insular cortex

DOI: 10.3233/RNN-180815

Citation: Restorative Neurology and Neuroscience, vol. 36, no. 6, pp. 669-678, 2018

Authors: Werth, Reinhard

Article Type: Research Article

Abstract: Background: Reading disability is termed “dyslexia” if it is much lower than other cognitive abilities according to the intelligence quotient (IQ). This means that dyslexia is caused by an impairment of abilities other than those which the IQ requires. Therefore, reading performance should improve immediately if these impairments are either eliminated or compensated. Objective: The experiments explore conditions under which these impairments are compensated and dyslexic children's poor reading ability immediately improve. Methods: Experiment 1 examined if reducing the number of letters in pseudowords, prolonging the time interval during which the gaze is directed to pseudowords, …reducing the amplitude of saccades and prolonging the time interval that elapsed between the beginning of the presentation of a pseudoword and the beginning of the pronunciation of that word influences childrens’ reading performance. A group of 100 German children (71 boys and 29 girls) aged 8 to 13 years, who suffered from dyslexia according to the Zuerich Reading Test, were divided into a training group (n  = 50) and an age-matched control group (n  = 50) and tested. Both groups participated in experiment 1. Only the children in the training group participated in experiment 2, in which the children learned a compensatory reading strategy. The age - matched control group did not learn the compensatory reading strategy. In the training group, reading performance was tested before and after having learned the new reading strategy. Results: Conditions were found under which all children were able to read 95% of the pseudowords correctly. After having learned a compensatory reading strategy, a mean 58.9% decrease in words read incorrectly was found after a single training session. The difference between the number of reading mistakes before and after the training session was highly significant (Wicoxon Test: p  <  0.00001). The effect size showed that the compensatory reading strategy was highly effective (Hedges g  = 1.7). The reading ability of an age-matched dyslexic control group showed no improvement. Conclusions: Dyslexic subjects’ reading performance improves significantly when they learn a new reading strategy. Show more

Keywords: Dyslexia, diagnosis, therapy, word recognition, segmentation, fixation time, eye movements, speech onset latency

DOI: 10.3233/RNN-180829

Citation: Restorative Neurology and Neuroscience, vol. 36, no. 6, pp. 679-691, 2018

Authors: Washabaugh, Edward P. | Treadway, Emma | Gillespie, R. Brent | Remy, C. David | Krishnan, Chandramouli

Article Type: Research Article

Abstract: Background: Robotic rehabilitation is a highly promising approach to recover lost functions after stroke or other neurological disorders. Unfortunately, robotic rehabilitation currently suffers from “motor slacking”, a phenomenon in which the human motor system reduces muscle activation levels and movement excursions, ostensibly to minimize metabolic- and movement-related costs. Consequently, the patient remains passive and is not fully engaged during therapy. To overcome this limitation, we envision a new class of body-powered robots and hypothesize that motor slacking could be reduced if individuals must provide the power to move their impaired limbs via their own body (i.e., through the motion of …a healthy limb). Objective: To test whether a body-powered exoskeleton (i.e. robot) could reduce motor slacking during robotic training. Methods: We developed a body-powered robot that mechanically coupled the motions of the user’s elbow joints. We tested this passive robot in two groups of subjects (stroke and able-bodied) during four exercise conditions in which we controlled whether the robotic device was powered by the subject or by the experimenter, and whether the subject’s driven arm was engaged or at rest. Motor slacking was quantified by computing the muscle activation changes of the elbow flexor and extensor muscles using surface electromyography. Results: Subjects had higher levels of muscle activation in their driven arm during self-powered conditions compared to externally-powered conditions. Most notably, subjects unintentionally activated their driven arm even when explicitly told to relax when the device was self-powered. This behavior was persistent throughout the trial and did not wane after the initiation of the trial. Conclusions: Our findings provide novel evidence indicating that motor slacking can be reduced by self-powered robots; thus demonstrating promise for rehabilitation of impaired subjects using this new class of wearable system. The results also serve as a foundation to develop more sophisticated body-powered robots (e.g., with controllable transmissions) for rehabilitation purposes. Show more

Keywords: Rehabilitation robotics, hemiparesis, active engagement, EMG, metabolic cost, wearable, cable robot

DOI: 10.3233/RNN-180830

Citation: Restorative Neurology and Neuroscience, vol. 36, no. 6, pp. 693-708, 2018

Authors: Tramontano, Marco | Martino Cinnera, Alex | Manzari, Leonardo | Tozzi, Federico Francesco | Caltagirone, Carlo | Morone, Giovanni | Pompa, Alessandra | Grasso, Maria Grazia

Article Type: Research Article

Abstract: Background: Balance disorders are present in patients with Multiple Sclerosis and part of these disorders could be of vestibular origin. Vestibular Rehabilitation was found to be effective in improving balance in patients with central vestibular dysfunction. Objective: To investigate the clinical effects of vestibular rehabilitation on balance skills and secondly on fatigue and activity of daily living in highly disabled multiple sclerosis people. Methods: Thirty hospitalized participants with severe multiple sclerosis (EDSS 6-7) were randomly assigned to the experimental group (15 patients -9F-; mean age 50.64±11.73) and the control group (15 patients -8F-; mean age 45.77±10.91). …All patients were evaluated before and after treatment with the Expanded Disability Status Scale, Barthel Index Tinetti Balance and Gait scale, Berg Balance Scale, Fatigue Severity Scale, Two Minute Walking Test and Timed 25-foot walk test. Two follow-ups (i.e., at 30 and 60 days after treatment) were carried out with Barthel Index. Results: Significant improvement was found in the experimental group with respect to the control group (p  <  0,05) in balance, fatigue perception, activities of daily living and short distance gait. No significant improvements were found for gait endurance as measured by Two Minute Walking Test. Conclusions: Four weeks of Vestibular Rehabilitation training results in less fatigue, improved balance and performance of the activities of daily living in patients with severe Multiple Sclerosis. Show more

Keywords: Multiple sclerosis, vestibular rehabilitation, rehabilitation, balance, fatigue, gait, activities of daily living

DOI: 10.3233/RNN-180850

Citation: Restorative Neurology and Neuroscience, vol. 36, no. 6, pp. 709-718, 2018

Authors: Qadri, Rizwana | Namdeo, Manju | Behari, Madhuri | Goyal, Vinay | Sharma, Subhadra | Mukhopadhyay, Asok Kumar

Article Type: Research Article

Abstract: Background: Progressive apoptosis in the dopaminergic neurons of substantia nigra lead to Parkinson’s disease. Since neurons require substantially higher supply of energy, their mitochondria have a pivotal status in neuronal survival. These organelles have a key role to play in apoptosis and any impairment thereof may lead to apoptosis mediated cell death. Objectives: To evaluate and compare the mitochondrial membrane potential (Δψ) in Parkinson’s disease patients and healthy controls. Methods: We evaluated the mitochondrial membrane potential (Δψ) in the peripheral blood mononuclear cells by Flow cytometry using a lipophillic cationic dye JC-1 in Parkinson’s disease patients …(N = 61) and healthy controls (N = 37). Results: JC-1 fluorescence was measured and represented as percentage positivity i.e., Mean±SEM in FL-2 (representing non-apoptotic aggregates) and FL-1 (indicating apoptotic cell population having depolarized or damaged mitochondria) channels. The ratio of % FL-2 and % FL-1, which is an indicator of cellular mitochondrial membrane potential, was found to be significantly higher in healthy controls (Mean±SEM = 60.48±18.42) as compared to patients (Mean±SEM = 24.30±4.671) in both stimulated and unstimulated conditions. Conclusions: Mitochondrial membrane potential is altered and hence its evaluation in peripheral blood mononuclear cells may serve as an early marker of apoptosis in PD and, therefore, may pave way for early interventions. Since Δψ has a role in the maintenance of electrochemical gradient, the disruption of which may lead to neuronal apoptosis, Δψ is intricately nested within etiopathogenesis of PD and may prove to be useful in design of diagnostics, prognostics and therapeutics for PD. Show more

Keywords: Mitochondrial membrane potential, apoptosis, Parkinson’s disease, movement disorder

DOI: 10.3233/RNN-180852

Citation: Restorative Neurology and Neuroscience, vol. 36, no. 6, pp. 719-727, 2018

Authors: Dang, Ge | Chen, Xinran | Zhao, Yuhui | Chen, Yicong | Ouyang, Fubing | Liang, Jiahui | Guo, Yi | Zeng, Jinsheng

Article Type: Research Article

Abstract: Backgrounds: Cerebral infarction does not only cause focal injury in the ischemic site, but also secondary non-ischemic damage at the remote areas of nervous system associated with the primary focus. Objective: This study investigated the changes in the spinal cord and ventral root after middle cerebral artery occlusion (MCAO) in cynomolgus monkeys (Macaca fascicularis). Methods: Adult male cynonolgus monkeys (4–5 years, 5.5–7.5 kg) were subjected to MCAO (n  = 6) or sham surgery (n  = 4). After 12 weeks, spinal cords and the ventral roots were harvested. Morphometric alterations in the spinal cord were detected at C5 and L5 …levels via immunofluorescence. The profiles of C5 and L5 ventral roots were displayed by toluidine blue staining and transmission electron microscopic examination. Results: Significant axonal loss in the contralateral corticospinal tract and abnormally enlarged axons in the ipsilateral were observed in monkeys with MCAO. The number of neurons in the contralateral ventral horn got declined while that in the ipsilateral was almost unaffected after MCAO compared with sham controls. Glial activation post-MCAO was observed in the bilateral corticospinal tract and the ventral horn. Aberrant nerve fibers appeared frequently in the contralateral ventral roots of MCAO monkey but rarely in the ipsilateral. Conclusions: These results indicate that focal cerebral infarction leads to pathological alterations in the spinal cord and ventral roots in non-human primates. Show more

Keywords: Cerebral infarction, secondary damage, spinal cord, ventral root, non-human primates

DOI: 10.3233/RNN-180854

Citation: Restorative Neurology and Neuroscience, vol. 36, no. 6, pp. 729-740, 2018

Authors: Gagrani, Meghal | Faiq, Muneeb A. | Sidhu, Talvir | Dada, Rima | Yadav, Raj K. | Sihota, Ramanjit | Kochhar, Kanwal P. | Verma, Rohit | Dada, Tanuj

Article Type: Research Article

Abstract: Background: Glaucoma (POAG) is a kind of neurodegenerative disease known to be closely associated with stress and adverse quality of life (QOL). Stress has also been shown to be involved in etiopathogenesis of primary open angle glaucoma (POAG). Complementary treatment in form of Meditation has been reported to improve QOL, brain oxygenation and decrease markers of stress. With this premise, a randomized controlled trial was carried out to assess the effect of Meditation on intraocular pressure, subjective QOL and objective markers of stress and brain oxygenation in patients with POAG. Methods: Sixty patients were randomized into intervention and …control groups. Intervention group underwent 45 minutes of Meditation daily for 6 weeks in addition to standard medical treatment while controls received only standard medical treatment. Inclusion criteria were patients with POAG, age >45 years, best corrected visual acuity >6/60. Patients with other ocular co-morbid conditions contributing to vision loss, systemic diseases, patients already practicing meditation in any form were excluded. An assessment of IOP, brain oxygenation using functional near infrared spectroscopy (fNIRS), QOL (WHO-BREF QOL) and stress markers in serum (cortisol, β-endorphins, interleukin-6, brain derived neurotrophic factor (BDNF), reactive oxygen species) was made at baseline and at 6 weeks. Results: 21 female and 39 male patients were enrolled with a mean age of 57.28±9.37 years. All parameters were comparable between two groups at baseline. At 6 weeks mean level of IOP decreased significantly in intervention group (15.9±1.8 mmHg to 14.4±1.21 mm Hg, p -value 0.0001) as compared to control group (15.7±1.4 mmHg to 15.65±1.41, p -value 0.41). fNIRS showed significant improvement in oxygenated hemoglobin change (Δ HbO) in intervention group in the prefrontal cortex (p- value <  0.0001) as compared to control group (p- value 0.52). WHO-BREF QOL score increased significantly in intervention group (86.6±6.16 to 93.3±5.66, p- value 0.0001) as compared to control (89±7.25 to 89.07±3.24, p- value 0.74).Mean serum cortisol decreased significantly in intervention group (497±46.37 ng/ml to 447±53.78 ng/ml, p- value 0.01) as compared to control group (519.75±24.5 to 522.58±26.63 ng/ml, p- value 0.64). Mean β-endorphin levels increased significantly (33±5.52pg/ml to 43.27pg/ml, p- value <  0.0001) as compared to control group (34.78±4.1pg/ml to 36.33pg±4.07pg/ml p- value 0.27). Interleukin-6 decreased significantly in intervention group (2.2±0.5 ng/ml to 1.35±0.32 ng/ml, p- value <  0.0001) as compared to control group (2.03±0.37 to 2.17±0.34 ng/ml p- value 0.25). BDNF increased significantly in intervention group (52.24±6.71 to 63.25±13.48 ng/ml p- value 0.004) as compared to control group (53.23±5.82 to 54.42±5.66 ng/ml p- value 0.54). ROS decreased significantly in intervention group (1596.19±179.14 to 1261±244.31 RLU/min/104 neutrophils p- value 0.0001) as compared to control group (1577.5±172.02 to 1662.5±84.75 RLU/min/104 neutrophils p- value 0.16). Conclusions: A short term course of Meditation was associated with significant improvement in brain oxygenation and QOL along with a reduction in IOP and stress markers. Meditation may be a useful as an adjunct to standard treatment in patients with POAG and potentially decrease the risk of glaucoma progression. Show more

Keywords: Glaucoma, intraocular pressure, mindfulness meditation, optic nerve head, quality of life, relaxation, stress, fNIRS, brain oxygenation, prefrontal cortex

DOI: 10.3233/RNN-180857

Citation: Restorative Neurology and Neuroscience, vol. 36, no. 6, pp. 741-753, 2018

Authors: Dumont, Laurence | El Mouderrib, Sofia | Théoret, Hugo

Article Type: Research Article

Abstract: Background: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique commonly used to modulate cognitive functions; so-called “anodal” stimulation is considered to increase cortical excitability while “cathodal” stimulation is presumed to have the opposite result. Yet, a growing number of recent studies question the robustness of this polarity-dependent effect, namely because of the important inter-individual variability with regards to tDCS modulatory effects. A plausible reason for this heterogenous response may lay in task impurity issues in the evaluation of cognitive functions. Objective: To address the question of task impurity the NIH-Examiner, a neuropsychological test battery that …uses latent variables, which assess the common variance across multiple measures of a given concept, was administered to 24 healthy individuals following tDCS. This battery contains 11 tasks and provides latent variables for general executive functioning, fluency, cognitive control and working memory. Methods: Anodal, cathodal, and sham stimulation (20 minutes, 1.5 mA) was administered over left dorsolateral prefrontal cortex and right supra-orbital area in a randomized, crossover, sham-controlled, double blind protocol. Results: Factorial scores and task performance indices of executive function were not modulated by tDCS. Conclusions: Offline tDCS has limited impact on executive functions at both the task and factorial levels. This suggests that reducing task impurity does not increase the effectiveness of tDCS in modulating cognitive functions. Show more

Keywords: Executive functions, transcranial direct current stimulation, NIH-Examiner, latent variables, frontal cortex 

DOI: 10.3233/RNN-180872

Citation: Restorative Neurology and Neuroscience, vol. 36, no. 6, pp. 755-766, 2018

Authors: Sabel, Bernhard A. | Flammer, Josef | Merabet, Lotfi B.

Article Type: Research Article

Abstract: Vision loss due to ocular diseases such as glaucoma, optic neuropathy, macular degeneration, or diabetic retinopathy, are generally considered an exclusive affair of the retina and/or optic nerve. However, the brain, through multiple indirect influences, has also a major impact on functional visual impairment. Such indirect influences include intracerebral pressure, eye movements, top-down modulation (attention, cognition), and emotionally triggered stress hormone release affecting blood vessel dysregulation. Therefore, vision loss should be viewed as the result of multiple interactions within a “brain-eye-vascular triad”, and several eye diseases may also be considered as brain diseases in disguise. While the brain is part …of the problem, it can also be part of the solution. Neuronal networks of the brain can “amplify” residual vision through neuroplasticity changes of local and global functional connectivity by activating, modulating and strengthening residual visual signals. The activation of residual vision can be achieved by different means such as vision restoration training, non-invasive brain stimulation, or blood flow enhancing medications. Modulating brain functional networks and improving vascular regulation may offer new opportunities to recover or restore low vision by increasing visual field size, visual acuity and overall functional vision. Hence, neuroscience offers new insights to better understand vision loss, and modulating brain and vascular function is a promising source for new opportunities to activate residual vision to achieve restoration and recovery to improve quality of live in patients suffering from low vision. Show more

Keywords: Glaucoma, optic neuropathy, recovery, plasticity, brain, vision restoration, vascular dysregulation

DOI: 10.3233/RNN-180880

Citation: Restorative Neurology and Neuroscience, vol. 36, no. 6, pp. 767-791, 2018