bluuebunny/crossref_metadata_2025 huggingface dataset:
Anosognosia for motor and sensory deficits after unilateral brain	damage: A review
Authors: Vallar Giuseppe , Ronchi Roberta
Published: December 2024

Purpose: The syndrome of unawareness (anosognosia) for sensory and motor neurological deficits (hemiplegia, hemianaesthesia, and hemianopia), contralateral to the side of a hemispheric lesion, is reviewed.

Content: Main topics include: basic historical facts; the types of patient's interview and specific questions used to reveal the deficits; the clinical patterns of presentation; the associations and dissociations of the different anosognosic manifestations, and their relationships with associated disorders of sensory, memory, and executive-intellectual functions; the hemispheric asymmetry of anosognosia, that, as the syndrome of unilateral spatial neglect, is more frequent and severe after damage to the right cerebral hemisphere; the relationships between spatial neglect and the anosognosias, and their neural correlates; the effects of lateralized sensory stimulations on defective awareness of neurological impairments.

Conclusions: The argument is made that anosognosia for sensory and motor neurological deficits should be considered as a multi-component syndrome, including a number of specific disorders that are due to the impairment of discrete monitoring systems, specific for the different supervised functions. The putative causal role of associated deficits of other parts of the sensory-motor or cognitive (e.g., memory, general intelligence) system is critically discussed. These specific control processes may be physically implemented in brain areas anatomically (and functionally) close to those subserving the monitored function.
Repetitive optokinetic stimulation induces lasting recovery from	visual neglect
Authors: Kerkhoff G. , Keller I. , Ritter V. , Marquardt C.
Published: December 2024

Purpose: To evaluate whether repetitive optokinetic stimulation with active pursuit eye movements leads to substantial and greater recovery from visual neglect as compared to conventional visual scanning training.

Methods: Two groups of five patients with leftsided hemineglect were consecutively collected and matched for clinical and demographic variables as well as neglect severity. One group received five treatment sessions of repetitive optokinetic stimulation (R-OKS) within one week, while the other group received the same amount of conventional visual scanning training (VST) using identical visual stimuli and setup. All patients were treated in a single-subject baseline design with treatment-free intervals before (14 days) and after specific neglect therapy (14 days). Dependent variables were the improvements in digit cancellation, visuoperceptual and visuomotor line bisection and visual size distortion during treatment. The transfer of treatment effects was assessed by a paragraph reading test.

Results: The results showed superior effects of OKS treatment in all five patients which generalized across all tasks administered and remained stable at follow-up. In contrast, no significant improvements were obtained after VST training in any of these tasks, except in line bisection.

Conclusion: We conclude that the presentation of moving visual stimulus displays with active smooth pursuit eye movements can be more efficient than conventional visual scanning training using static visual displays.
Prism adaptation first among equals in alleviating left neglect: A	review
Authors: Luauté Jacques , Halligan Peter , Rode Gilles , Jacquin-Courtois Sophie , Boisson Dominique
Published: December 2024

Purpose: The current paper was designed to provide a critical overview on the different methods proposed for the rehabilitation of left spatial neglect.

Methods: On the basis of a previous systematic review of the literature, we analyzed all articles available aiming at reducing left spatial neglect which included a long term functional assessment.

Results: The aim of most early rehabilitation approaches, such as visuo-scanning training, was to re-orient visual scanning toward the neglected side. This review confirmed the utility of this method for rehabilitation purposes. More recent – theory driven – procedures, also based on a training approach, include limb activation, mental imagery training and video-feedback training. Although there is ground for optimism, the functional effectiveness of these methods still relies on few single-case studies. Newer methods have tried to stimulate automatic orientation of gaze or attention towards neglected space in a bottom-up fashion. Sensory stimulations can remove most of the classical signs of left neglect but their effects are short-lived. Such stimulations are not functionally relevant for rehabilitation except for trunk rotation or repeated neck muscle vibrations if they are associated with an extensive training program. A more promising intervention is prism adaptation given the growing evidence of relatively long-term functional gains from comparatively short term usage.

Conclusion: Overall, there is now evidence for several clinically relevant long-term benefits in the case of visual scanning training, mental imagery training, video feedback training, neck muscle vibration and trunk rotation if associated with visual scanning training and prism adaptation. However, the amount of evidence is still limited to a small number of relevant published articles and it is mandatory to continue the research in this field. In this review, the possible routes for new rehabilitation procedures are discussed on the basis of the actual knowledge regarding the neuro-cognitive mechanisms underlying the therapeutic effect of prism adaptation.
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.
Stimulus- and goal-driven biases of selective attention following	unilateral brain damage: Implications for rehabilitation of spatial neglect and	extinction
Authors: Snow Jacqueline C. , Mattingley Jason B.
Published: December 2024

In this review we address the question of whether selective attentional mechanisms within the ipsilesional field are intact in unilateral lesion patients with spatial neglect and extinction. We consider how a lesion-induced bias in the neural representation of salience critically disrupts the integration of goal-driven and stimulus-driven prioritization signals. This has important consequences for selectivity both within the 'impaired' contralesional field within the 'intact' ipsilesional field. Examples are drawn from the neuropsychological literature and recent experiments conducted within our own laboratory. The implications of ipsilesional spatial selection deficits for rehabilitation are discussed.
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.
End-to-side nerve repair: Review of the literature
Authors: Pannucci Christopher , Myckatyn Terence M. , Mackinnon Susan E. , Hayashi Ayato
Published: December 2024

End-to-side (ETS) nerve repair, in which the distal stump of a transected nerve is coapted to the side of an uninjured donor nerve, offers a technique for repair of peripheral nerve injuries where the proximal nerve stump is unavailable or a significant nerve gap exists. Details of animal models are explored including motor and sensory regeneration to further clarify the mechanism of collateral sprouting while eliminating false positive results from contaminating axons. Some experimental studies support the conclusion that sensory or motor reinnervation may be derived from collateral sprouting while others suggest that reinnervation requires an injury to the donor nerve. Clinical experience with ETS neurorrhaphy includes management of upper extremity nerve injury, facial reanimation, reconstruction following tumor ablation, and the prevention of neuroma formation. Our interpretation of the ETS literature suggests that sensory axons may sprout without deliberately attempting to injure them, while motor axons regenerate only in response to a deliberate injury. Experimental and clinical experience with ETS neurorrhaphy has rendered mixed results. Our interpretation of the literature suggests that the success of this technique is dependent upon axonal injury of motor and possibly sensory nerves. While continued clinical and laboratory experimentation with ETS nerve repair is warranted, it should not yet replace more established techniques of nerve repair.
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.
ERP effects of meaningful and non-meaningful sound processing in anterior temporal patients
Authors: Kotz Sonja A. , Opitz Bertram , Friederici Angela D.
Published: December 2024

Purpose: The contribution of the anterior temporal lobe to the processing of environmental sounds was investigated in patients with primary lesions in the anterior portion of the left (ATL) and right (ATR) temporal lobe in comparison to healthy controls. Two controversial questions were addressed: (1) whether environmental sounds are processed similarly for meaning as language, and (2) whether task-dependent lateralized semantic and perceptual effects observed in earlier studies persist when testing environmental sounds independent of task.

Methods: In an event-related brain potential (ERP) experiment we examined the effect of meaningful and non-meaningful novel sound processing in a novelty oddball paradigm.

Results: Healthy controls and both patient groups displayed a normal target P3b as well as a novelty P3a. In addition, while healthy controls differentiated non-meaningful and meaningful novel sounds in the novelty P3a at posterior lateral and midline electrode-sites, all patients showed this effect only at midline sites. Lastly, the P3a effect was followed by a larger N400 amplitude rise for meaningful compared to non-meaningful novel sounds in healthy controls, but not in either patient group.

Conclusion: The present data indicate that independent of task both the left and right anterior temporal lobe is crucial for lexical-semantic processing of novel sounds.
Neural correlates of rapid auditory processing are disrupted in children with developmental dyslexia and ameliorated with training: An fMRI study
Authors: Gaab N. , Gabrieli J.D.E. , Deutsch G.K. , Tallal P. , Temple E.
Published: December 2024

Purpose: Developmental dyslexia, characterized by unexpected difficulty in reading, may involve a fundamental deficit in processing rapid acoustic stimuli. Using functional magnetic resonance imaging (fMRI) we previously reported that adults with developmental dyslexia have a disruption in neural response to rapid acoustic stimuli in left prefrontal cortex. Here we examined the neural correlates of rapid auditory processing in children.

Methods: Whole-brain fMRI was performed on twenty-two children with developmental dyslexia and twenty-three typical-reading children while they listened to nonlinguistic acoustic stimuli, with either rapid or slow transitions, designed to mimic the spectro-temporal structure of consonant-vowel-consonant speech syllables.

Results: Typical-reading children showed activation for rapid compared to slow transitions in left prefrontal cortex. Children with developmental dyslexia did not show any differential response in these regions to rapid versus slow transitions. After eight weeks of remediation focused primarily on rapid auditory processing, phonological and linguistic training the children with developmental dyslexia showed significant improvements in language and reading skills, and exhibited activation for rapid relative to slow transitions in left prefrontal cortex.

Conclusion: The presence of a disruption in the neural response to rapid stimuli in children with developmental dyslexia prior to remediation, coupled with significant improvement in language and reading scores and increased brain activation after remediation, gives further support to the importance of rapid auditory processing in reading development and disorders.
Computer-based multisensory learning in children with developmental dyslexia
Authors: Kast Monika , Meyer Martin , Vögeli Christian , Gross Markus , Jäncke Lutz
Published: December 2024

Purpose: Several attempts have been made to remediate developmental dyslexia using various training environments. Based on the well-known retrieval structure model, the memory strength of phonemes and graphemes should be strengthened by visual and auditory associations between graphemes and phonemes. Using specifically designed training software, we examined whether establishing a multitude of visuo-auditory associations might help to mitigate writing errors in children with developmental dyslexia.

Methods: Forty-three children with developmental dyslexia and 37 carefully matched normal reading children performed a computer-based writing training (15–20 minutes 4 days a week) for three months with the aim to recode a sequential textual input string into a multi-sensory representation comprising visual and auditory codes (including musical tones). The study included four matched groups: a group of children with developmental dyslexia ( n = 20) and a control group ( n = 18) practiced with the training software in the first period (3 months, 15–20 minutes 4 days a week), while a second group of children with developmental dyslexia ( n = 23) (waiting group) and a second control group ( n = 19) received no training during the first period. In the second period the children with developmental dyslexia and controls who did not receive training during the first period now took part in the training.

Results: Children with developmental dyslexia who did not perform computer-based training during the first period hardly improved their writing skills (post-pre improvement of 0–9%), the dyslexic children receiving training strongly improved their writing skills (post-pre improvement of 19–35%). The group who did the training during the second period also revealed improvement of writing skills (post-pre improvement of 27–35%). Interestingly, we noticed a strong transfer from trained to non-trained words in that the children who underwent the training were also better able to write words correctly that were not part of the training software. In addition, even non-impaired readers and writers (controls) benefited from this training.

Conclusion: Three-month of visual-auditory multimedia training strongly improved writing skills in children with developmental dyslexia and non-dyslexic children. Thus, according to the retrieval structure model, multi-sensory training using visual and auditory cues enhances writing performance in children with developmental dyslexia and non-dyslexic children.
Influence of musical expertise and musical training on pitch processing in music and language
Authors: Besson Mireille , Schön Daniele , Moreno Sylvain , Santos Andréia , Magne Cyrille
Published: December 2024

Purpose: We review a series of experiments aimed at studying pitch processing in music and speech. These studies were conducted with musician and non musician adults and children. We found that musical expertise improved pitch processing not only in music but also in speech. Demonstrating transfer of training between music and language has interesting applications for second language learning. We also addressed the issue of whether the positive effects of musical expertise are linked with specific predispositions for music or with extensive musical practice. Results of longitudinal studies argue for the later. Finally, we also examined pitch processing in dyslexic children and found that they had difficulties discriminating strong pitch changes that are easily discriminate by normal readers. These results argue for a strong link between basic auditory perception abilities and reading abilities.

Methods: We used conjointly the behavioral method (Reaction Times and error rates) and the electrophysiological method (recording of the changes in brain electrical activity time-locked to stimulus presentation, Event-Related brain Potentials or ERPs).

Results: A set of common processes may be responsible for pitch processing in music and in speech and these processes are shaped by musical practice.

Conclusion: These data add evidence in favor of brain plasticity and open interesting perspectives for the remediation of dyslexia using musical training.
Short-term plasticity in the auditory system: Differential neural responses to perception and imagery of speech and music
Authors: Meyer Martin , Elmer Stefan , Baumann Simon , Jancke Lutz
Published: December 2024

Purpose: In this EEG study we sought to examine the neuronal underpinnings of short-term plasticity as a top-down guided auditory learning process. We hypothesized, that (i) auditory imagery should elicit proper auditory evoked effects (N1/P2 complex) and a late positive component (LPC). Generally, based on recent human brain mapping studies we expected (ii) to observe the involvement of different temporal and parietal lobe areas in imagery and in perception of acoustic stimuli. Furthermore we predicted (iii) that temporal regions show an asymmetric trend due to the different specialization of the temporal lobes in processing speech and non-speech sounds. Finally we sought evidence supporting the notion that short-term training is sufficient to drive top-down activity in brain regions that are not normally recruited by sensory induced bottom up processing.

Methods: 18 non-musicians partook in a 30 channels based EEG session that investigated spatio-temporal dynamics of auditory imagery of “consonant-vowel” (CV) syllables and piano triads. To control for conditioning effects, we split the volunteers in two matched groups comprising the same conditions (visual, auditory or bimodal stimulation) presented in a slightly different serial order. Furthermore the study presents electromagnetic source localization (LORETA) of perception and imagery of CV- and piano stimuli.

Results: Our results imply that auditory imagery elicited similar electrophysiological effects at an early stage (N1/P2) as auditory stimulation. However, we found an additional LPC following the N1/P2 for auditory imagery only. Source estimation evinced bilateral engagement of anterior temporal cortex, which was generally stronger for imagery of music relative to imagery of speech. While we did not observe lateralized activity for the imagery of syllables we noted significantly increased rightward activation over the anterior supratemporal plane for musical imagery.

Conclusions: Thus, we conclude that short-term top-down training based auditory imagery of music and speech prompts involvement of distinct neural circuits residing in the perisylvian cortex.
Effects of behaviorally active ACTH (4–10) analogue – Semax on	rat basal forebrain cholinergic neurons
Authors: Grivennikov Igor A. , Dolotov Oleg V. , Zolotarev Yuri A. , Andreeva Ludmila A. , Myasoedov Nikolai F. , Leacher Lauren , Black Ira B. , Dreyfus Cheryl F.
Published: December 2024

PURPOSE. It is well established that cholinergic neurons of the basal forebrain degenerate in Alzheimer's dementia. Although recent studies were concentrated on screening molecules that might reduce the concomitant cell loss, little is known about therapeutically promising molecules. We studied the effect of Semax (Met-Glu-His-Phe-Pro-Gly-Pro), a behaviorally active adrenocorticotropic hormone (4–10) analogue, on survival of cholinergic basal forebrain neurons in vitro. Semax is known to stimulate learning and memory and can be successfully used for treatment of ischemic stroke. METHODS. Primary cultures of neuronal and glial cells from basal forebrain of rats were used in all experiments. The stability of Semax in cell cultures was tested by HPLC analysis. Cell survival in neuronal cultures was quantitated using immocytochemical and cytochemical analyses as well as detection of choline acetyltransferase activity. RESULTS. We have shown that Semax may approximately 1.5–1.7 fold increase survival of cholinergic basal forebrain neurons in vitro. Moreover, Semax (100 nM) stimulated activity of choline acetyltransferase in dissociated basal forebrain tissue cultures. However, the numbers of GABA-ergic neurons, total neuron specific enolase neurons were not affected. In concentration from 1 nM to 10 μM, Semax did not affect proliferation of glial cells in primary cultures. CONCLUSION. Implications of these findings with respect to Alzheimer's disease remain to be clarified.
Overexpression of cellular prion protein alters postischemic	Erk1/2 phosphorylation but not Akt phosphorylation and protects against focal	cerebral ischemia
Authors: Weise Jens , Doeppner Thorsten R. , Müller Tilo , Wrede Arne , Schulz-Schaeffer Walter , Zerr Inga , Witte Otto W. , Bähr Mathias
Published: December 2024

Purpose: The physiological function of the cellular prion protein (PrP $^{C}$ ) is still unclear. A growing body of evidence suggests that PrP $^{C}$ has neuroprotective properties and that its deletion increases susceptibility to focal cerebral ischemia. The purpose of this study was to elucidate the role of PrP $^{C}$ overexpression in ischemic brain injury in vivo.

Methods: PrP $^{C}$ overexpressing (TG35) and wild type (WT) mice were subjected to a 90-minute transient focal cerebral ischemia followed by infarct volume analysis 24 hours after lesion. To identify effects of PrP $^{C}$ overexpression on signalling pathways important for the regulation of ischemic cell death, we studied postischemic activation and expression of Akt and Erk1/2 using quantitative Western Blot analysis.

Results: TG35 mice displayed significantly smaller infarct volumes and showed reduced early postischemic Erk1/2 phosphorylation, a pathway known to exacerbate neuronal injury following transient cerebral ischemia. In contrast, PrP $^{C}$ overexpression did not change postischemic Akt phosphorylation, which acts anti-apoptotic and is reduced in PrP $^{C}$ knockout animals.

Conclusions: These results demonstrate that PrP $^{C}$ overexpression reduces deleterious Erk1/2 activation but does not affect Akt activation after transient cerebral ischemia, suggesting a role for distinct cytosolic signalling pathways in PrP $^{C}$ mediated neuroprotection.
From blindsight to sight: Cognitive rehabilitation of visual field	defects
Authors: Chokron Sylvie , Perez Celine , Obadia Michaël , Gaudry Isabelle , Laloum Laurent , Gout Olivier
Published: December 2024

Purpose: Traditionally, post-chiasmatic lesions were believed to result in complete and permanent visual loss in the topographically related areas of the visual field. However, a number of studies with monkeys, and later with humans, have demonstrated spared implicit visual functioning, referred to as 'blindsight'. The present study assessed whether training this phenomenon would induce an objective restoration of conscious vision in the blind field of hemianopic patients.

Methods: For a period of 22 weeks nine patients with unilateral occipital damage participated in several forced-choice visual tasks known to elicit blindsight: pointing to visual targets, letter recognition, visual comparison between the two hemifields, target localization, and letter identification. Before and after rehabilitation, patients were submitted to a behavioral pre- and post-test, including visual detection and letter identification as well as to automated perimetry visual field testing (Humphrey Automated 24-2 Full Threshold).

Results: An objective improvement was found in the behavioral tasks for all patients at the post-test stage as well as an objective enlargement of the contralesional visual field for all except one of the nine patients. An overall decrease is seen in the number of undetected points (out of 30) on automated perimetry visual field testing after rehabilitation (F (1, 16) = 22.57; p < 0.001) for both eyes (Right Eye, RE: T = 0; z = 2.52; p < 0.05; Left Eye, LE: T = 0, z = 2.37; p < 0.05) regardless of lesion side.

Conclusions: The results suggest that explicit (conscious) visual detection can be restored in the blind visual field by using implicit (unconscious) visual capacities. Results are discussed regarding visual field defect rehabilitation, blindsight, attention, and brain plasticity hypotheses.