bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined transcranial direct current stimulation and	robot-assisted arm training in subacute stroke patients: A pilot study
Authors: Hesse S. , Werner C. , Schonhardt E.M. , Bardeleben A. , Jenrich W. , Kirker S.G.B. 
Published: December 2024

Background and Purpose: Preliminary reports suggest that central stimulation may enhance the effect of conventional physical therapies after stroke. This pilot study examines the safety and methodology of using transcranial direct stimulation (tDCS) with robot-assisted arm training (AT), to inform planning a larger randomised controlled trial. Subjects: Ten patients, after an ischaemic stroke 4–8 weeks before study onset, no history of epilepsy, participated. Eight had a cortical lesion and 2 had subcortical lesions: all had severe arm paresis and, co-incidentally, 5 had severe aphasia. Methods: Over six weeks, they received thirty 20 min-sessions of AT. During the first 7 minutes, 1.5mA of tDCS was applied, with the anode over the lesioned hemisphere and the cathode above the contralateral orbit. Arm and language impairment were assessed with the Fugl-Meyer motor score (FM, full range 0–66) and the Aachener Aphasie Test. Results: No major side effects occurred. Arm function of three patients (two with a subcortical lesion) improved significantly, with FM scores increasing from 6 to 28, 10 to 49 and 11 to 48. In the remaining seven patients, all with cortical lesions, arm function changed little, FM scores did not increase more than 5 points. Unexpectedly, aphasia improved in 4 patients. Conclusions: These procedures are safe, and easy to use in a clinical setting. In future studies, patients should be stratified by degree of arm weakness and lesion site, also the unexpected aphasia improvement warrants following-up.
The novel antiepileptic agent RWJ-333369-A, but not its analog	RWJ-333369, reduces regional cerebral edema without affecting neurobehavioral	outcome or cell death following experimental traumatic brain injury
Authors: Keck Carrie A. , Thompson Hilaire J. , Pitkänen Asla , LeBold David G. , Morales Diego M. , Plevy Jamie B. , Puri Rishi , Zhao Boyu , Dichter Marc , McIntosh Tracy K. 
Published: December 2024

Purpose: To evaluate the therapeutic efficacy of two antiepileptic compounds, RWJ-333369 and RWJ-333369-A in a well-established experimental model of lateral fluid percussion (FP) traumatic brain injury (TBI) in the rat. Methods: Anethestized Male Sprague-Dawley rats (n=227) were subjected to lateral FP brain injury or sham-injury. Animals were randomized to receive treatment with RWJ-333369 (60 mg/kg, p.o.) or its analog RWJ-333369-A (60 mg/kg, p.o.), or vehicle (equal volume) at 15 minutes, 4, 8, and 24 hours post-injury. In Study I, animals were assessed at 48 hours for acute motor and cognitive function and then sacrificed to evaluate regional cerebral edema. In Study II, animals were evaluated post-injury for motor function at 48 hours and weekly thereafter from 1 to 4 weeks. Post-traumatic learning ability was assessed 4 weeks post-injury, followed by evaluation of hemispheric tissue loss. Results: In Study I, no improvement in acute memory or motor function was observed following administration of either RWJ-333369 or RWJ-333369-A in brain-injured animals compared to vehicle-treated, brain-injured animals. However, brain-injured animals receiving treatment with RWJ-333369-A had a significant reduction in post-traumatic cerebral edema in both injured and contralateral hippocampus compared to brain-injured, vehicle-treated controls (p<0.05). In Study II, treatment with either compound did not result in any improvement of neuromotor function, learning ability or change in lesion volume following brain injury.
Auditory temporal-order thresholds show no gender	differences
Authors: van Kesteren Marlieke T.R. , Wiersinga-Post J. Esther C. 
Published: December 2024

Purpose: Several studies on auditory temporal-order processing showed gender differences. Women needed longer inter-stimulus intervals than men when indicating the temporal order of two clicks presented to the left and right ear. In this study, we examined whether we could reproduce these results in order to further investigate the differences in auditory processing between men and women. Methods: Neurologically healthy subjects (13 males and 13 females, age range: 19 to 37 years) had to identify the temporal order of two clicks, presented monaurally to the left and right ear. Thresholds for the inter-stimulus intervals between the clicks were determined using a three step transformed up-down procedure. Results: The results show no influence of gender in the auditory temporal-order task. Inter-individual differences were, however, large, ranging from a threshold of around 15 ms to around 90 ms. Conclusion: Contrary to what was found in previous studies, no significant gender difference was measured in temporal-processing abilities using a task with monaurally presented clicks.
Repeated sessions of noninvasive brain DC stimulation is	associated with motor function improvement in stroke patients
Authors: Boggio Paulo S. , Nunes Alice , Rigonatti Sergio P. , Nitsche Michael A. , Pascual-Leone Alvaro , Fregni Felipe 
Published: December 2024

Purpose: Recent evidence has suggested that a simple technique of noninvasive brain stimulation – transcranial direct current stimulation (tDCS) – is associated with a significant motor function improvement in stroke patients. Methods: We tested the motor performance improvement in stroke patients following 4 weekly sessions of sham, anodal- and cathodal tDCS (experiment 1) and the effects of 5 consecutive daily sessions of cathodal tDCS (experiment 2). A blinded rater evaluated motor function using the Jebsen-Taylor Hand Function Test. Results: There was a significant main effect of stimulation condition (p=0.009) in experiment 1. Furthermore there was a significant motor function improvement after either cathodal tDCS of the unaffected hemisphere (p=0.016) or anodal tDCS of the affected hemisphere (p=0.046) when compared to sham tDCS. There was no cumulative effect associated with weekly sessions of tDCS, however consecutive daily sessions of tDCS (experiment 2) were associated with a significant effect on time (p< 0.0001) that lasted for 2 weeks after treatment. Conclusions: The findings of our study support previous research showing that tDCS is significantly associated with motor function improvement in stroke patients; and support that consecutive daily sessions of tDCS might increase its behavioral effects. Because the technique of tDCS is simple, safe and non-expensive; our findings support further research on the use of this technique for the rehabilitation of patients with stroke.
Heterotopic, not homotopic, fetal occipital allografts in adult	hosts project to visual-related extracortical targets
Authors: Gaillard Frédéric 
Published: December 2024

Purpose: Fetal occipital allografts implanted into the posterior cortex of adult mice project massively throughout the ipsilateral pallium of the host, but rarely outside this domain (Gaillard et al., 2004). The present study was undertaken to examine in detail whether this pattern is specific to graft location. Methods: Cortical fragments corresponding to presumptive occipital areas were harvested from E15 mice fetuses expressing ubiquitously the eGFP protein, and implanted in correct (homotopic) and incorrect (heterotopic) cortical loci in wild-type adults. Two months later, efferents were detected by immunohistochemistry and quantified on selected DAB-treated sections. Results: The present findings show (i) that robust projections are present in the ipsilateral host cortex regardless of the graft location; (ii) that 55% the grafts located in parietal and frontal cortices have obvious but sparse callosal and subcortical projections; and (iii) that grafts placed in occipital areas never contact ipsilateral subcortical targets, likely because graft-related axons are unable to cross obliquely the thalamocortical fascicles in the underlying white matter. Conclusions: These puzzling results question the use of transplantation strategies for repairing damaged networks in adults where rewiring involves complex white matter trajectories.
Environmental enrichment improves functional and neuropathological	indices following stroke in young and aged rats
Authors: Buchhold B. , Mogoanta L. , Suofu Y. , Hamm A. , Walker L. , Kessler Ch. , Popa-Wagner A. 
Published: December 2024

Purpose: Aging is associated with a temporally dysregulated cellular response to ischemia as well as poor functional recovery. While environmental enrichment has been shown to improve the behavioral outcome of stroke in young animals, the effect of an enriched environment on behavioral and neuropathological recovery in aged animals is not known. Methods: Focal cerebral ischemia was produced by electrocoagulation of the right middle cerebral artery in 3 month- and 20 month-old male Sprague-Dawley rats. The functional outcome was assessed in neurobehavioral tests conducted over a period of 28 days following surgery. Brain tissue was then immunostained for proliferating astrocytes and the infarct and scar tissue volumes were measured. Results: Aged rats showed more severe behavioral impairments and diminished functional recovery compared to young rats. Most infarcted animals had disturbances of sensorimotor function, with recovery beginning later, progressing more slowly, and reaching a lower functional endpoint in aged animals. However, the enriched environment significantly improved the rate and extent of recovery in aged animals. Correlation analysis revealed that the beneficial effect of the enriched environment on recovery, both in young and aged rats, correlated highly with a reduction in infarct size, in the number of proliferating astrocytes, and in the volume of the glial scar. Conclusions: These results suggest that temporally modulating astrocytic proliferation and the ensuing scar formation might be a fruitful approach to improving functional recovery after stroke in aged rats.
The novel substituted pyrimidine, KP544, reduces motor deficits in	the R6/2 transgenic mouse model of Huntington's disease
Authors: Dey Nicholas D. , Boersen Angela J. , Myers Rebecca A. , York Lynae R. , Bombard Matthew C. , Lu Ming , Sandstrom Michael I. , Hulce Verne D. , Lescaudron Laurent , Dunbar Gary L. 
Published: December 2024

Purpose: The purpose of this study was to test the potential therapeutic effects of the substituted pyrimidine, KP544, which has been shown to amplify the effects of nerve growth factor in vitro, on motor deficits in the R6/2 transgenic mouse model of Huntington's disease (HD). Methods: Young, female R6/2 mice were given daily oral intubation of either 10 mg/kg KP544 or vehicle (0.5% methylcellulose) at 6 weeks of age and tested from postnatal weeks 8 through 12 on a battery of motor tasks, including assessments of clasping (drawing of the limbs to the torso when suspended by the tail), motor coordination on the rotarod, and spontaneous motor activity in the open-field. Following testing, the mice were sacrificed and the brains were sectioned and stained with cresyl violet for histological examination. Results: KP544 treatment decreased balance deficits on the rotarod task, reduced clasping, delayed the onset of hypoactivity, and reduced enlargement of the lateral ventricles in R6/2 mice. Conclusion: These results suggest that KP544 can reduce motor deficits and anatomical alterations in R6/2 mice. Further research into the use of KP544 as a potential pharmacotherapy HD is warranted.
Axonal rearrangement without reexpression of a growth associated	marker: Evidence from the compression of the retinotectal system in adult	goldfish
Authors: Si Keyuan , Miotke Jill A. , Meyer Ronald L. , Wang Ziren 
Published: December 2024

Purpose: Growing axons express a number of proteins associated with axonal growth which are thought to be critical for regeneration and sprouting. Whether these proteins are expressed during injury-induced axonal remodeling is tested in this paper. Methods: The posterior half of the adult goldfish tectum was removed leaving the anterior half intact. This causes optic fibers from nasal retina, which project to posterior tectum, to displace temporal fibers from the anterior remnant and form a compressed retinotopic projection of the entire retina onto the anterior tectum. Immunohistochemistry using an antibody shown here to recognize growing and regenerating fibers in goldfish was used to monitor optic fibers. Results: As expected, surgery induced reactivity in the axotomized nasal axons peaking at 1 month which returned to normal at 2 months when compression was completed. Unexpectedly, axons from temporal retina showed no detectable reactivity even though they were induced to grow anteriorly by the invading nasal fibers. Conclusions: Extensive axonal remodeling and synaptic rearrangement can occur without reentering the growth state associated with axonal growth and regeneration.
Effects of single versus combinatorial treatment strategies on	beta II-tubulin gene expression in axotomized hamster rubrospinal motoneurons
Authors: DeLucia Tracey A. , Alexander Thomas D. , Fargo Keith N. , Jones Kathryn J. 
Published: December 2024

Purpose: βII-tubulin, a regeneration-associated gene, is upregulated in injured peripheral neurons, but significantly less so in injured central neurons. Using a hamster dorsal spinal cord injury (SCI), the ability of single versus combinatorial treatment strategies to alter βII-tubulin mRNA expression in rubrospinal motoneurons (RSMN) was examined. We have shown that systemic testosterone propionate (TP) treatment in combination with peripheral nerve grafting into a SCI site produces a peripheral-like pattern of βII-tubulin mRNA expression in injured RSMN. In the present study, selected single- and combinatorial-therapy strategies were tested for their ability to promote a sustained upregulation of βII-tubulin mRNA levels in injured RSMN. Methods: Single treatments of olfactory ensheathing cells (OEC), brain-derived neurotrophic factor (BDNF), or Schwann cells (SC) vs combinatorial treatments (SC + TP, OEC + TP, and OEC + BDNF) were administered to hamsters following a dorsal SCI. Quantitative in situ hybridization in conjunction with a βII-tubulin cDNA probe was accomplished. Results: All of the single-therapy treatments tested were able to prevent the downregulation of βII-tubulin mRNA that occurred a week after injury alone, but only BDNF maintained high levels of βII-tubulin mRNA. In contrast, all combinatorial treatments tested maintained the upregulation of βII-tubulin mRNA expression in injured RSMN 1 week post-SCI. Conclusions: Targeting both intrinsic and extrinsic components of CNS injury can re-program elements of the molecular response of injured central motoneurons.
Right hemisphere dominance for auditory attention and its modulation by eye position: An event related fMRI study
Authors: Petit Laurent , Simon Grégory , Joliot Marc , Andersson Frédéric , Bertin Thomas , Zago Laure , Mellet Emmanuel , Tzourio-Mazoyer Nathalie 
Published: December 2024

Purpose: Previous neuroimaging studies of oddball tasks and other paradigms measuring attention processes support right hemisphere dominance for attentional processes. Using an auditory selective attention task, we studied the functional asymmetry of the human brain in response to attended or unattended deviant tones. Secondly, we examined whether a congruency or a discrepancy between audio-spatial and visuo-spatial cued attentional resources may influence the activity elicited by an auditory selective attention task. Methods: We used event-related functional magnetic resonance imaging (fMRI) to study healthy adults as they performed an auditory oddball task in which a spatial-cued instruction indicated the ear to attend a monaural deviant tone. We addressed the question of congruency/discrepancy between attentional resources by using three different eye positions during the performance of the auditory oddball task. Results: Relative to standard tones, both attended and unattended deviant tones (DTs) presented to either ear elicit the activation of a widespread bilaterally distributed cortical and subcortical network. A subset of this network, essentially frontal and temporal areas, showed not only greater right than left activity but an enhancement of this rightward asymmetry in response to attended DTs. The only cortical region that showed a leftward asymmetry in response to attended DTs overlapped Heschl gyrus and planum temporale, unmasking a left hemisphere preference of both primary and secondary auditory cortex for processing simple attended monaural stimuli. Questioning the impact of eye position during auditory oddball task, we observed a lesser activity in right integrative crossmodal areas (superior temporal sulcus, opercular part of the inferior frontal gyrus, pre-SMA) when the eye positions were contralateral to detected DTs. These regions may be tuned to best respond when both visuo-spatial and audio-spatial attentional resources work together. Conclusion: These results support the assumption that the right hemisphere is preferentially engaged in processing audio-spatial attentional resources and underline the interest to study the crossmodal integration of attentional resources by the mean of the detection of DTs in different eye positions.
Hemispheric asymmetries in the processing of temporal acoustic cues in consonant-vowel syllables
Authors: Sandmann Pascale , Eichele Tom , Specht Karsten , Jäncke Lutz , Rimol Lars Morten , Nordby Helge , Hugdahl Kenneth 
Published: December 2024

Purpose: In order to examine auditory lateralization of prelexical speech processing, a dichotic listening task was performed with concurrent EEG measurement. Methods: Subjects were tested with dichotic pairs of six consonant-vowel (CV) syllables that initially started with a voiced (/ba/, /da/, /ga/) or a voiceless stop consonant (/pa/, /ta/, /ka/). Electrophysiological correlates were analyzed by a low resolution electromagnetic tomography (LORETA) approach to estimate the sources of N1 event-related potentials (ERP) in the 3D brain. Results: Behavioral and electrophysiological measures revealed different ear advantages and ERP amplitude measures for voiced and voiceless syllables. Fronto-central N1 amplitudes were larger for syllables with voiced than voiceless initial consonants. LORETA source estimates revealed a lateralization effect, with stronger leftward lateralization for voiced than voiceless CV syllables. Conclusions: The present study demonstrates that auditory lateralization is affected by temporal cues in CV syllables. The lateralization effect suggests that functional hemispheric differences exist at an early prelexical level of speech processing.
Induction of LTP-like changes in human auditory cortex by rapid auditory stimulation: An FMRI study
Authors: Zaehle Tino , Clapp Wesley C. , Hamm Jeff P. , Meyer Martin , Kirk Ian J. 
Published: December 2024

Purpose: Previously we have shown that rapid sensory stimulation, in this case, auditory tone pips, can induce long-lasting plastic changes akin to Long Term Potentiation (LTP) within adult human sensory cortex. In a previous study, auditory LTP was reflected as an increase in the amplitude of the N1 component of the auditory event-related potential as measured by EEG. The goal of the present study was to investigate potential effects of LTP-like changes on the hemodynamic response of the human auditory cortex. Methods: Silent sparse-sampled fMRI recordings were obtained while subjects passively listened to tone-pips both before and after a short block of rapidly presented auditory tone-pips (auditory tetanus) was delivered. Results: The BOLD response within the primary auditory cortex was significantly enhanced after the auditory tetanus. Conclusion: This is the first study demonstrating LTP-like changes of the hemodynamic response in the auditory system, and thus supports the growing literature demonstrating LTP can be induced in adult human cortex. These results have implications in the fields of perceptual learning and rehabilitation.
Generalization of non-linguistic auditory perceptual training to syllable discrimination
Authors: Lakshminarayanan Kala , Tallal Paula 
Published: December 2024

Purpose: The generalization of non-linguistic auditory perceptual training to syllable discrimination was investigated in two experiments. Methods: Participants were divided into a control and training group. Both groups came for pre and post-testing sessions spaced ten days apart. Following pre- testing, the training group also participated for five consecutive days in non-linguistic auditory perceptual training. Training was adaptive and involved active sequencing of rising and falling frequency modulated sweeps for 30 minutes per day. Sweeps were passively varied in onset frequency, duration and rate of presentation. A syllable discrimination threshold (SDT) task was used as the pre and post-test measure. In experiment 1, a /ba/-/da/ syllable continuum was used. In experiment 2, the pre-test battery was expanded to include /ba/-/da/, /ba/-/wa/, and /sa/-/sta/ syllable continua and a tone sequencing task that mimicked other parameters of training. Results: Results of experiment 1 revealed that the training group had a significantly lowered (better) SDT following training as compared to the control group. The extent of training-driven perceptual gain was significantly correlated with pre-training performance. In experiment 2, training resulted in a significantly lowered SDT for /ba/-/da/, but not for the other syllables or the tone sequencing task. Conclusions: Results showed that task-specific attention drives generalization of auditory perceptual training from non-linguistic to linguistic contexts. Furthermore, individual differences in initial perceptual performance affect the degree of generalization following training.
Patterns of recovery following focal hemispheric lesions: Relationship between lasting deficit and damage to specialized networks
Authors: Rey Beatrice , Frischknecht Rolf , Maeder Philippe , Clarke Stephanie 
Published: December 2024

Purpose: Cognitive deficits that are present in the acute stage of a focal hemispheric lesion tend to be greater and more general than residual deficits, which persist into the chronic stage. We have investigated the patterns of recovery and the relationship between deficits and damage to specialized networks taking as model auditory cognitive functions. Evidence from human psychophysical, activation and neuropsychological studies suggests that sound recognition and sound localization are processed in anatomically and functionally distinct cortical networks, the auditory “What” and “Where” processing streams, that are each present in both hemispheres. Focal left or right hemispheric lesions centred on these networks were found to be associated, in the chronic stage, with the corresponding deficits in sound recognition and/or sound localization. Methods: We report here on recovery patterns in 24 patients who sustained focal hemispheric lesions and were deficient in sound recognition, sound localization and/or sound motion perception at a first evaluation in the acute ( n = 9), subacute ( n = 6) or early chronic stages ( n = 9). Results: All 24 patients had initially a deficit in sound localization and/or sound motion perception. In the acute stage this deficit occurred without damage to the auditory “Where” stream in almost half of the patients, a situation which was never observed in the early chronic stage. Lack of recovery tended to be associated with damage to the specialized stream plus the persistence of deficits beyond the acute stage, and was only loosely related to the size of the lesion and to the extent of damage to a specialized network. Conclusions: Our results suggest that different mechanisms underlie deficits and recovery at different time points.