bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neglect and prism adaptation: A new therapeutic tool for spatial	cognition disorders
Authors: Rode Gilles , Klos Thomas , Courtois-Jacquin Sophie , Rossetti Yves , Pisella Laure 
Published: December 2024

Purpose: A large proportion of right-hemisphere stroke patients show unilateral neglect, a neurological deficit of perception, attention, representation, and/or performing actions within their left-sided space, inducing many functional debilitating effects on everyday life, and responsible for poor functional recovery and ability to benefit from treatment. This spatial cognition disorder affects the orientation of behaviour with a shift of proprioceptive representations toward the lesion side. Methods: This shift can be reduced after a prism adaptation period to a right lateral displacement of visual field (induced by a simple target-pointing task with base-left wedge prisms). The modification of visuo-motor or sensory-motor correspondences induced by prism adaptation involves improvement of different symptoms of neglect. Results: Classical visuo-motor tests could be improved for at least 2h after adaptation, but also non-motor and non-visual tasks. In addition, cross-modal effects have been described (tactile extinction and dichotic listening), mental imagery tasks (geographic map, number bisection) and even visuo-constructive disorders. These cognitive effects are shown to result from indirect bottom-up effects of the deeper, adaptive realignment component of the reaction to prisms. Lesion studies and functional imaging data evoke a cerebello-cortical network in which each structure plays a specific role and not all structures are crucial for adaptation ability. Conclusions: These cognitive effects of prism adaptation suggest that prism adaptation does not act specifically on the ipsilesional bias characteristic of unilateral neglect but rehabilitates more generally the visuo-spatial functions attributed to the right cortical hemisphere. These results reinforce the idea that the process of prism adaptation may activate brain functions related to multisensory integration and higher spatial representations and show a generalization at a functional level. Prism adaptation therefore appears as a new powerful therapeutic tool for spatial cognition disorders.
Alertness-training in neglect: Behavioral and imaging	results
Authors: Sturm W. , Thimm M. , Küst J. , Karbe H. , Fink G.R. 
Published: December 2024

Purpose: It has been proposed that the right hemisphere alerting network co-activates, either directly or via the brainstem, the spatial attention system in the parietal cortex. The observation that measures of impaired alertness and sustained attention can be used to predict the outcome of neglect might suggest such a relationship, too. The aim of the present study was to investigate the effects of alertness training on hemispatial neglect. Method: A three-week computerised alertness training was applied to patients with chronic (> 3 months) stable visuospatial hemineglect. Training effects were investigated both in a single case and in a group of 7 patients by means of neuropsychological tests and functional magnetic resonance imaging (fMRI). Results: After the training, the patients showed a significant improvement in a neglect test battery above any natural fluctuation during a three-week baseline phase. Improvements in the neglect tasks were accompanied by an increase of both right and left hemisphere frontal, anterior cingulate and superior parietal activation, areas known to be associated with both alertness and spatial attention. Four weeks after the end of the training, the patients' neglect test performance had mostly returned to baseline. Despite decreases of activation in some of the initially reactivated areas, increases in neural activity bilaterally in frontal areas, in the right anterior cingulate cortex, the right angular gyrus and in the left temporoparietal cortex remained. An Optokinetic Stimulation Training (OKS) in a control group of another 7 neglect patients led to comparable behavioral results. After the training, however, there was a reactivation mainly in posterior parts of both hemispheres suggesting training specific functional reorganization. Conclusion: The limited stability of the behavioral and reactivation results over time demonstrates that a three-week alertness or OKS training alone does not result in long lasting behavioral improvements and stable reactivation patterns in every patient. We rather suggest that combining alertness and spatial attention oriented training procedures might lead to a more stable amelioration of neglect symptoms.
Experimental intracerebral hematoma in the rat
Authors: Barth Alain , Guzman Raphael , Andres Robert H. , Mordasini Pasquale , Barth Laurence , Widmer Hans R. 
Published: December 2024

Purpose: Current models of intracerebral hematoma are difficult to use for neurotransplantation studies because of high mortality and important variations of morphology, size and location of blood deposits. We propose a modification of the autologous blood infusion technique in rats to reduce these limitations. Methods: The modification consisted in a mechanical microlesion preceding blood infusion. A canula was stereotactically introduced into the striatum of adult rats. Subsequently, a parenchyma lesion was created by a rotating microcatheter coaxially inserted through the canula, followed by slow infusion of 30 μl autologous blood during 5 minutes. Controls included canula insertion only and canula + microlesion. Hematoma volume/morphology were quantified and the animals behaviorally analysed using standardized tests. Results: Surgical mortality was 0/54 rats. One animal died during follow-up. Hematoma volume was constant and significantly higher (15.20 ± 0.60 mm $^3$ ) than control lesions (canula: 0.11 ± 0.01 mm $^3$ ; canula + trauma: 0.51 ± 0.01 mm $^3$ ). Hematoma edges were sharply delineated and the perihematomal region histologically preserved. Rats with hematoma showed initially a reduced spontaneous rotational behaviour. They also showed persisting deficits of forelimb placing ability. Conclusions: The advantages of this model include a systematic control of all steps of hematoma production, high reproducibility of volume, size, and location of blood deposits, preservation of perihematomal brain tissue, and quantifiable neurological deficits.
Widespread cellular proliferation and focal neurogenesis after	traumatic brain injury in the rat
Authors: Urrea Carlos , Castellanos Daniel A. , Sagen Jacqueline , Tsoulfas Pantelis , Bramlett Helen M. , Dietrich W. Dalton 
Published: December 2024

Purpose: A proliferation of stem/progenitor cells is observed after brain injury. We examined the regional and temporal profile of mitotically active cells to determine whether traumatic brain injury (TBI) would increase neurogenesis in selective brain regions. Methods: Male Sprague-Dawley rats received injections (IP) of 5-bromo-deoxyuridine (BrdU), a compound used to detect mitotic cells, before and after fluid-percussion brain injury. At 3 hr, 1, 2, 3, 7, and 14 days after moderate fluid percussion, brains were processed for immunocytochemical and confocal analysis. Sections were double-labeled for markers selective for neurons (NeuN), astrocytes (GFAP), olidgodendrocytes (CNPase and MBP) and macrophage/microglia (ED1). Results: At 3 hr post-trauma, the majority of BrdU labeled cells were associated with the subventricular zone of the traumatized hemisphere. At later time points, a significant increase in BrdU positive cells was observed throughout the traumatized cerebral cortex, hippocampus, white matter structures, and some contralateral regions. BrdU labeled cells were observed as late as 14 days post-injury. Double-label studies with confocal microscopy demonstrated that cell phenotypes including astrocytes, macrophage/microglia, oligodendrocytes, and neurons were BrdU positive with the majority of cells appearing glial in nature. Evidence for neurogenesis was seen in the granular cell layer of the hippocampus. Conclusion: These findings indicate that TBI stimulates widespread cellular proliferation for days after injury and results in focal neurogenesis in the dentate gyrus of the hippocampus. These cellular responses to injury may participate in brain repair and functional recovery.
A golgi analysis of cortical pyramidal cells in the unilateral	parkinson rat: Absence of change in the affected hemisphere vs hypertrophy in	the intact hemisphere
Authors: Miklyaeva Elena I. , Whishaw Ian Q. , Kolb Bryan 
Published: December 2024

Purpose: Unilateral dopamine (DA) depletion in the rat provides an analog of human Parkinson's disease. The classic view of DA loss is that it produces changes in the activity of striatal-cortical circuitry that results in reduced frontal cortex neural activity. This "functional deafferent" view is consistent with findings that animals display sensorimotor deficits in the contralateral-to-lesion side of the body and compensatory behavior adjustments in the ipsilateral-to-lesion side of the body. The present study examined how DA depletion and the associated sensorimotor changes affect the morphology of the ipsilateral or contralateral neocortex neurons as assessed by dendritic morphology in Golgi-stained tissue. Method: Rats were given unilateral 6-hydroxydopamine (6-OHDA) or sham lesions in the nigrostriatal bundle. Lesion success was confirmed by enduring bilateral motor impairments in a skilled-reaching task, compensatory use of the ipsilateral-to-lesion limbs, and by increases in amphetamine and apomorphine-induced rotational behavior. Results: Brains processed for Golgi-Cox staining at 1, 3, 8, or 24 months after the lesion showed no changes in dendritic arborization or synapse number in layer V pyramidal cells of motor cortex ipsilateral to the 6-OHDA lesion (DA-depleted hemisphere) at any postsurgical recovery stage. There was an increase in dendritic arborization in all lesion groups in the hemisphere contralateral to the lesion (good hemisphere). Conclusion: The results are inconsistent with the classical view of frontal cortex functional deafferentiation due to DA loss but do suggest that compensatory behavior leads to dendritic hypertrophy in the good hemisphere.
Predicting improvement in the upper paretic limb after stroke: A	longitudinal prospective study
Authors: Kwakkel Gert , Kollen Boudewijn 
Published: December 2024

Purpose: A number of longitudinal studies show that about one third of all patients regain dexterity following a stroke. However, the determinants of improvement of upper limb function are largely unknown. The aim of the present study was to investigate the longitudinal relationship of functional change in the upper paretic limb and change in time-dependent covariates in order to develop a multivariable regression model to predict improvement in dexterity. Methods: Based on 18 repeated measurements over time during the first post-stroke year, 101 stroke patients with first-ever ischemic middle cerebral artery strokes were investigated. Baseline characteristics as well as longitudinal information from Action Research Arm Test (ARAT), Fugl-Meyer arm and hand score (FM-arm and FM-hand), Motricity Index arm and leg score (MI-arm and MI-leg), letter cancellation task (LCT), Fugl-Meyer balance score (FM-balance) and progress of time were obtained prospectively. Outcome constituted of change scores on the ARAT over first year post stroke. Adjoining measurements of time-dependent variables were used to calculate time-dependent changes producing change scores. Results: In total 1570 of the 1717 change scores were available for longitudinal regression analysis. The regression model shows that FM-hand change scores was the most important relative factor in predicting improvement on ARAT (standardized β=0.357; p< 0.001) followed by change scores on FM-arm (β = 0.007; p< 0.001), whereas progress of time was significantly negatively associated with improvement on ARAT (β = −0.001; p< 0.001). Conclusions: Functional improvement of the upper paretic limb is mainly determined by improvement of the paretic hand, followed by synergistic independent movement of the paretic arm. Progress of time itself is an independent covariate that is negatively associated with upper limb function suggesting that most pronounced improvements occur earlier after stroke.
Treatment of adult neural progenitor cells prior to	transplantation affects graft survival and integration in a neonatal and adult	rat model of selective retinal ganglion cell depletion
Authors: Mellough Carla B. , Cui Qi , Harvey Alan R. 
Published: December 2024

Purpose: We tested whether microenvironmental changes surrounding apoptotic neural degeneration, cellular pre-treatment and timing of transplant can influence the survival and differentiation of transplanted cells. This was done by transplanting adult hippocampal precursor cells (AHPCs) into normal and retinal ganglion cell (RGC) depleted rat retinae. Methods: Apoptotic RGC death was induced in neonates by removal of the contralateral superior colliculus (SC) and in adults by unilateral optic nerve transection, with or without a peripheral nerve (PN) graft. AHPCs were transplanted 24 h after SC ablation, or 5, 7 or 14 days following optic nerve (ON) transection. Hosts received untreated grafts, or grafts treated by co-culture with embryonic retinal explants or the neuropeptide somatostatin. Results: AHPCs integrated within all neonatal and 65% of adult retinae. Greater numbers of AHPCs were observed within the ganglion cell layer (GCL) in SC lesioned hosts. Explant co-culture induced proliferation of grafted AHPCs within host retinae. Somatostatin-treatment resulted in reduced overall engraftment but increased integration within the GCL. In lesioned adults, greatest GCL engraftment was observed following 7 or 14 day grafts. Some AHPCs in the inner retina expressed neuronal antigens and extended processes into the ON. Conclusions: These data indicate that various factors can influence the behaviour of grafted cells and work towards encouraging the functional restoration of retinal circuitry.
Mental practice improves hand function after hemiparetic	stroke
Authors: Müller Katharina , Bütefisch C.M. , Seitz Rüdiger J. , Hömberg Volker 
Published: December 2024

Purpose: In a multiple baseline design, we tested the hypothesis that imagery of finger movements is a specific strategy to improve hand function. Methods: The effect of mental training of sequential finger movements (n=6) on hand function was compared to the repetitive execution of the same movements (n=6) and conventional physical therapy (n=5) in 17 patients after their first hemiparetic stroke. The behavioral outcome measures consisted of peak force of the pinch grip using a force transducer and manipulation functions of the upper extremity (Jebsen-test). In addition, activities of daily living (Barthel Index) were aquired to describe the population. Results: Mental training resulted in an increase in the peak force of the pinch grip and generalized in a better functionality of the upper extremity (Jebsen-test). This effect was similar to the repetitive execution of the movements and superior to conventional physiotherapy. Conclusions: Our results suggest that the control of finger movements benefits from mental training of sequential finger movements and, thus, may be employed as a strategy in post-stroke rehabilitation.
Early pubertal female rats are more resistant than males to	6-hydroxydopamine neurotoxicity and behavioural deficits: A possible role for	trophic factors
Authors: Pienaar I.S. , Schallert T. , Russell V.A. , Kellaway L.A. , Carr J.A. , Daniels W.M.U. 
Published: December 2024

Purpose: The infusion of 6-hydroxydopamine (6-OHDA) into the nigrostriatal pathway in rats is commonly used to produce an animal model of Parkinson's disease (PD). However, most studies use male adult animals only. The present study focused on possible gender differences in vulnerability to 6-OHDA during the early pubertal period when the effects exerted by gonadal steroid hormones are unpronounced. Methods: Young Sprague-Dawley rats, 35 days of age, were given a low vs. a higher dose of 6-OHDA in the medial forebrain bundle (MFB). Control rats received equivalent saline infusions. At 14 days post-surgery the rats were evaluated for forelimb akinesia. Results: For the higher dose of 6-OHDA the female rats were less impaired than males in making adjustment steps in response to a weight shift and in a vibrissae-evoked forelimb placing test. Tyrosine hydroxylase (TH) immunoreactivity was significantly higher for the female rats. Conclusion: Early gender differences in cell survival factors and/or other promoters of neuroplasticity may have contributed to the beneficial outcome in the females. For example, NGF was found to be higher in the female rats following administration of DA neurotoxin. It is unclear whether gonadal steroids are involved, and if so, whether female hormones are protective or whether male hormones are prodegenerative. Determining the mechanisms for the improved outcome in the young female rats may lead to potential treatment strategies in PD.
Lentiviral vector-mediated reporter gene expression in avulsed	spinal ventral root is short-term, but is prolonged using an immune "stealth" transgene
Authors: Hendriks William T.J. , Eggers Ruben , Carlstedt Thomas P. , Zaldumbide Arnaud , Tannemaat Martijn R. , Fallaux Frits J. , Hoeben Rob C. , Boer Gerard J. , Verhaagen Joost 
Published: December 2024

Purpose: Spinal root avulsions result in paralysis of the upper and/or lower extremities. Implanting a peripheral nerve bridge or reinsertion of the avulsed roots in the spinal cord are surgical strategies that lead to some degree of functional recovery. In the current study lentiviral (LV) vector-mediated gene transfer of a green fluorescent protein (GFP) reporter gene was used to study the feasibility of gene therapy in the reimplanted root to further promote regeneration of motor axons. Methods: A total of 68 female Wistar rats underwent unilateral root avulsion of the L4, L5 and L6 ventral lumbar roots. From 23 rats intercostal nerves were dissected before ventral root avulsion surgery, injected with a lentiviral vector encoding GFP (LV-GFP) and inserted between the spinal cord and avulsed rootlet. In the remaining 45 rats, the avulsed ventral root was injected with either LV-GFP or a lentiviral vector encoding a fusion between a GlyAla repeat and GFP (LV-GArGFP), and reinserted into the spinal cord. Expression of GFP was evaluated at 1, 2, 4 and 10 weeks, and one group at 4 months. Results: LV-GFP transduction of either nerve implants or reimplanted ventral roots revealed high GFP expression during the first 2 post-lesion weeks, but virtually no expression at 4 weeks. Since this reduction coincided with the appearance of mononuclear cells at the repair site, an immune response against GFP may have occurred. In a subsequent experiment reimplanted ventral roots were transduced with a vector encoding GFP fused with the GlyAla repeat of Epstein-Barr virus Nuclear Antigen 1 known to prevent generation of antigenic peptides from transgene products. Expression of this "stealth" gene persisted for at least 4 months in the reimplanted root. Conclusion: Thus persistent transgene expression can be achieved with non-immunogenic transgene products in reimplanted ventral roots. This demonstrates the feasibility of combining neurosurgical repair with LV vector-mediated gene therapy. The current approach will be used in future experiments with LV vectors encoding neurotrophic factors to enhance the regeneration of spinal motor neurons after traumatic avulsion of spinal nerve roots.
Neuroplasticity in the processing of pitch dimensions: A multidimensional scaling analysis of the mismatch negativity
Authors: Chandrasekaran Bharath , Gandour Jackson T. , Krishnan Ananthanarayan 
Published: December 2024

Purpose: An auditory electrophysiological study was conducted to explore the influence of language experience on the saliency of dimensions underlying cortical pitch processing. Methods: Mismatch negativity (MMN) responses to Mandarin tones were recorded in Chinese and English participants ( n = 10 per group) using a passive oddball paradigm. Stimuli consisted of three tones (T1: high level; T2: high rising; T3: low falling-rising). There were three oddball conditions (standard/deviant): T1/T2, T1/T3, T2/T3. In the T1/T2 and T1/T3 conditions, each tonal pair represented a contrast between a level and a contour tone; the T2/T3 condition, a contrast between two contour tones. Twenty dissimilarity matrices were created using the MMN mean amplitude measured from the Fz location for each condition per participant, and analyzed by an individual differences multidimensional scaling model. Results: Two pitch dimensions were revealed, interpretively labeled as ‘height’ and ‘contour’. The latter was found to be more important for Chinese than English subjects. Using individual weights on the contour dimension, a discriminant function showed that 17 out of 20 participants were correctly classified into their respective language groups. Conclusions: The MMN can serve as an index of pitch features that are differentially weighted depending on a listener’s experience with lexical tones and their acoustic correlates within a particular tone space.
The processing of frequency deviations within sounds: Evidence for the predictive nature of the Mismatch Negativity (MMN) system
Authors: Grimm Sabine , Schröger Erich 
Published: December 2024

Purpose: The present study aimed at further clarifying the nature of the automatic deviance detection system indexed by the mismatch negativity (MMN) component of the event-related potential (ERP). We investigated the pre-attentive detection of a transient frequency deviance occurring within a short tone at different temporal distances relative to tone onset. It was of specific interest whether these different types of deviations were categorized as distinctive events by the MMN system or not. Methods: We compared the MMN elicited by a rare frequency deviation occurring 200 ms after tone onset among frequent standard tones without frequency deviation. In three conditions, the proportions of standards and deviants were 90-10 (90% standards, 10% frequency deviation occurring 200 ms after sound onset), 70-30 (70% standards, 30% frequency deviation), or 70-10-10-10 (70% standard, frequency deviation 10% after 100 ms, 10% after 200 ms, 10% after 300 ms). Results: We found that the MMN in the 70-10-10-10 condition resembles the MMN in the 90-10 condition, both MMNs being larger than the MMN in the 70-30 condition. In other words, although a frequency deviation in the 70-10-10-10 condition was as likely as in the 70-30 condition (i.e. 30%), it was treated as if it were as unlikely as in the 90-10 condition (i.e. 10%). Thus, the amplitude of the MMN was related to the specific temporal occurrence of the frequency deviance rather than the global probability of the frequency deviance. Conclusions: The data support the hypothesis that the MMN system was operating on the basis of a spectrotemporal representation rather than on independent feature dimensions. Results are compatible with a new theory of the MMN system according to which MMN is based on a pointwise comparison between the current sound and a model-based concrete prediction of a forthcoming sound as it evolves over time.