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Sindhurakar A.,Burke Cornell Medical Research Institute | Bradley N.S.,University of Southern California
PLoS ONE | Year: 2012

Chicks are bipedal precocious vertebrates that achieve adaptive locomotor skill within hours after hatching. Development of limb movement has been extensively studied in the chicken embryo, but few studies have focused on the preparations leading to precocious locomotor skill. Chicks typically hatch after 21 days of incubation, and recent studies provided evidence that the neural circuits for intralimb control of stepping are established between embryonic days (E) 18-20. It has also been shown that variations in light exposure during embryogenesis can accelerate or delay the onset of hatching and walking by 1 to 2 days. Our earlier work revealed that despite these differences in time to hatch, chicks incubated in different light conditions achieved similar locomotor skill on the day of hatching. Results suggested to us that light exposure during incubation may have accelerated development of locomotor circuits in register with earlier hatching. Thus, in this study, embryos were incubated in 1 of 3 light conditions to determine if development of interlimb coordination at a common time point, 19 days of incubation, varied with light exposure during embryogenesis. Leg muscle activity was recorded bilaterally and burst analyses were performed for sequences of spontaneous locomotor-related activity in one or more ankle muscles to quantify the extent of interlimb coordination in ovo. We report findings indicating that the extent of interlimb coordination varied with light exposure, and left-right alternating steps were a more reliable attribute of interlimb coordination for embryos incubated in constant bright light. We provide evidence that morphological development of the leg varied with light exposure. Based on these findings, we propose that light can accelerate the development of interlimb coordination in register with earlier hatching. Our results lead us to further propose that alternating left-right stepping is the default pattern of interlimb coordination produced by locomotor circuits during embryogenesis. © 2012 Sindhurakar, Bradley.


Ma T.C.,Columbia University | Willis D.E.,New York Medical College | Willis D.E.,Burke Cornell Medical Research Institute
Frontiers in Molecular Neuroscience | Year: 2015

Regenerative failure remains a significant barrier for functional recovery after central nervous system (CNS) injury. As such, understanding the physiological processes that regulate axon regeneration is a central focus of regenerative medicine. Studying the gene transcription responses to axon injury of regeneration competent neurons, such as those of the peripheral nervous system (PNS), has provided insight into the genes associated with regeneration. Though several individual “regeneration-associated genes” (RAGs) have been identified from these studies, the response to injury likely regulates the expression of functionally coordinated and complementary gene groups. For instance, successful regeneration would require the induction of genes that drive the intrinsic growth capacity of neurons, while simultaneously downregulating the genes that convey environmental inhibitory cues. Thus, this view emphasizes the transcriptional regulation of gene “programs” that contribute to the overall goal of axonal regeneration. Here, we review the known RAGs, focusing on how their transcriptional regulation can reveal the underlying gene programs that drive a regenerative phenotype. Finally, we will discuss paradigms under which we can determine whether these genes are injury-associated, or indeed necessary for regeneration. © 2015 Ma and Willis.


Ferre C.,Columbia University | Bleyenheuft Y.,University for Professionals for Pediatric Physical Therapy | Hung Y.-C.,Catholic University of Louvain | Friel K.,Queens College, City University of New York | Gordon A.M.,Burke Cornell Medical Research Institute
Neurorehabilitation and Neural Repair | Year: 2014

Background. High-intensity training aims to improve hand function in children with unilateral spastic cerebral palsy (USCP). However, the extent to which skill training is required is not known. Objectives. To compare the effects of intensive bimanual training with and without structured progression of skill difficulty, on manual dexterity, bimanual hand use, daily functioning, and functional goals in children with USCP. Method. Twenty-two children were randomized to structured practice group (SPG) or unstructured practice group (UPG), and received 6 h/d training during 15 days. Children from the SPG were engaged in fine and gross motor bimanual activities, with skill progression and goal training. Children from UPG performed the same activities without skill progression or goal training. Participants were evaluated before, immediately and 6 months after training by a physical therapist blinded to group allocation. The primary outcomes were the Jebsen-Taylor Test of Hand Function (JTTHF) and Assisting Hand Assessment (AHA). Secondary outcomes included the Canadian Occupational Performance Measure (COPM), Pediatric Evaluation of Disability Inventory (PEDI), and ABILHAND-Kids. Results. Both groups showed similar improvements in the JTTHF, AHA, ABILHAND-Kids, COPM-satisfaction, and PEDI (P < .05). A significant interaction in the COPM-performance scale (P = .03) showed superior improvements of the SPG immediately, but not 6 months, after the intervention. Conclusions: Children from both groups demonstrated improvements in dexterity and functional hand use. This suggests that for intensive bimanual approaches, intensive training at such high doses may not require structured practice to elicit improvements. However, there may be immediate added benefit of including goal training. © The Author(s) 2013.


Deconinck F.J.A.,Ghent University | Deconinck F.J.A.,Manchester Metropolitan University | Smorenburg A.R.P.,Burke Cornell Medical Research Institute | Benham A.,Bradford Institute for Health Research | And 3 more authors.
Neurorehabilitation and Neural Repair | Year: 2015

Background. Mirror visual feedback (MVF), a phenomenon where movement of one limb is perceived as movement of the other limb, has the capacity to alleviate phantom limb pain or promote motor recovery of the upper limbs after stroke. The tool has received great interest from health professionals; however, a clear understanding of the mechanisms underlying the neural recovery owing to MVF is lacking. Objective. We performed a systematic review to assess the effect of MVF on brain activation during a motor task. Methods. We searched PubMed, CINAHL, and EMBASE databases for neuroimaging studies investigating the effect of MVF on the brain. Key details for each study regarding participants, imaging methods, and results were extracted. Results. The database search yielded 347 article, of which we identified 33 suitable for inclusion. Compared with a control condition, MVF increases neural activity in areas involved with allocation of attention and cognitive control (dorsolateral prefrontal cortex, posterior cingulate cortex, S1 and S2, precuneus). Apart from activation in the superior temporal gyrus and premotor cortex, there is little evidence that MVF activates the mirror neuron system. MVF increases the excitability of the ipsilateral primary motor cortex (M1) that projects to the "untrained" hand/arm. There is also evidence for ipsilateral projections from the contralateral M1 to the untrained/affected hand as a consequence of training with MVF. Conclusion. MVF can exert a strong influence on the motor network, mainly through increased cognitive penetration in action control, though the variance in methodology and the lack of studies that shed light on the functional connectivity between areas still limit insight into the actual underlying mechanisms. © The Author(s) 2014.


Bashir S.,Harvard University | Edwards D.,Harvard University | Edwards D.,Burke Cornell Medical Research Institute | Edwards D.,University of Western Australia | And 2 more authors.
Brain Topography | Year: 2011

Low-frequency repetitive transcranial magnetic stimulation (rTMS) can exert local and inter-hemispheric neuromodulatory effects on cortical excitability. These physiologic effects can translate into changes in motor behavior, and may offer valuable therapeutic interventions in recovery from stroke. Neuronavigated TMS can maximize accurate and consistent targeting of a given cortical region, but is a lot more involved that conventional TMS. We aimed to assess whether neuronavigation enhances the physiologic and behavioral effects of low-frequency rTMS. Ten healthy subjects underwent two experimental sessions during which they received 1600 pulses of either navigated or non-navigated 1 Hz rTMS at 90% of the resting motor threshold (RMT) intensity over the motor cortical representation for left first dorsal interosseous (FDI) muscle. We compared the effects of navigated and non-navigated rTMS on motor-evoked potentials (MEPs) to single-pulse TMS, intracortical inhibition (ICI) and intracortical facilitation (ICF) by paired-pulse TMS, and performance in various behavioral tasks (index finger tapping, simple reaction time and grip strength tasks). Following navigated rTMS, the amplitude of MEPs elicited from the contralateral (unstimulated) motor cortex was significantly increased, and was associated with an increase in ICF and a trend to decrease in ICI. In contrast, non-navigated rTMS elicited nonsignificant changes, most prominently ipsilateral to rTMS. Behaviorally, navigated rTMS significantly improved reaction time RT and pinch force with the hand ipsilateral to stimulation. Non-navigated rTMS lead to similar behavioral trends, although the effects did not reach significance. In summary, navigated rTMS leads to more robust modulation of the contralateral (unstimulated) hemisphere resulting in physiologic and behavioral effects. Our findings highlight the spatial specificity of inter-hemispheric TMS effects, illustrate the superiority of navigated rTMS for certain applications, and have implications for therapeutic applications of rTMS. © 2010 Springer Science+Business Media, LLC.

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