Long-term in vivo regeneration of peripheral nerves through bioengineered nerve grafts.

Although autologous nerve graft is still the first choice strategy in nerve reconstruction, it has the severe disadvantage of the sacrifice of a functional nerve. Cell transplantation in a bioartificial conduit is an alternative strategy to improve nerve regeneration. Nerve fibrin conduits were seeded with various cell types: primary Schwann cells (SC), SC-like differentiated bone marrow-derived mesenchymal stem cells (dMSC), SC-like differentiated adipose-derived stem cells (dASC). Two further control groups were fibrin conduits without cells and autografts. Conduits were used to bridge a 1 cm rat sciatic nerve gap in a long term experiment (16 weeks). Functional and morphological properties of regenerated nerves were investigated. A reduction in muscle atrophy was observed in the autograft and in all cell-seeded groups, when compared with the empty fibrin conduits. SC showed significant improvement in axon myelination and average fiber diameter of the regenerated nerves. dASC were the most effective cell population in terms of improvement of axonal and fiber diameter, evoked potentials at the level of the gastrocnemius muscle and regeneration of motoneurons, similar to the autografts. Given these results and other advantages of adipose derived stem cells such as ease of harvest and relative abundance, dASC could be a clinically translatable route towards new methods to enhance peripheral nerve repair.

Chronic low-frequency rTMS of primary motor cortex diminishes exercise training-induced gains in maximal voluntary force in humans.

Although there is consensus that the central nervous system mediates the increases in maximal voluntary force (maximal voluntary contraction, MVC) produced by resistance exercise, the involvement of the primary motor cortex (M1) in these processes remains controversial. We hypothesized that 1-Hz repetitive transcranial magnetic stimulation (rTMS) of M1 during resistance training would diminish strength gains. Forty subjects were divided equally into five groups. Subjects voluntarily (Vol) abducted the first dorsal interosseus (FDI) (5 bouts x 10 repetitions, 10 sessions, 4 wk) at 70-80% MVC. Another group also exercised but in the 1-min-long interbout rest intervals they received rTMS [Vol+rTMS, 1 Hz, FDI motor area, 300 pulses/session, 120% of the resting motor threshold (rMT)]. The third group also exercised and received sham rTMS (Vol+Sham). The fourth group received only rTMS (rTMS_only). The 37.5% and 33.3% gains in MVC in Vol and Vol+Sham groups, respectively, were greater (P = 0.001) than the 18.9% gain in Vol+rTMS, 1.9% in rTMS_only, and 2.6% in unexercised control subjects who received no stimulation. Acutely, within sessions 5 and 10, single-pulse TMS revealed that motor-evoked potential size and recruitment curve slopes were reduced in Vol+rTMS and rTMS_only groups and accumulated to chronic reductions by session 10. There were no changes in rMT, maximum compound action potential amplitude (M(max)), and peripherally evoked twitch forces in the trained FDI and the untrained abductor digiti minimi. Although contributions from spinal sources cannot be excluded, the data suggest that M1 may play a role in mediating neural adaptations to strength training.

Neurophysiological changes during shortening osteotomies of the spine.

BACKGROUND CONTEXT: Kyphotic deformities with sagittal imbalance of the spine can be treated with spinal osteotomies. Those procedures are known to have a high incidence of neurological complications, in particular at the thoracic level. Motor evoked potentials (MEPs) have been widely used in helping to avoid major neurological deficits postoperatively. Previous reports have shown that a significant proportion of such cases present with important transcranial MEP (Tc-MEP) changes during surgery with some of them being predictive of postoperative deficits. PURPOSE: Our aim was to study Tc-MEP changes in a consecutive series of patients and correlate them with clinical parameters and radiological changes. STUDY DESIGN/SETTING: Retrospective case notes study from a prospective patient register. PATIENT SAMPLE: Eighteen patients undergoing posterior shortening osteotomies (nine at thoracic and nine at lumbar levels) for kyphosis of congenital, degenerative, inflammatory, or post-traumatic origin were included. OUTCOME MEASURES: Loss of at least 80% of Tc-MEP signal expressed as the area under the curve percentual change, of at least one muscle. METHODS: We studied the relation between outcome measure (80% Tc-MEP loss in at least one muscle group) and amount of posterior vertebral body shortening as well as angular correction measured on computed tomography scans, occurrence of postoperative deficits, intraoperative blood pressure at the time of the osteotomy, and hemoglobin (Hb) change. RESULTS: All patients showed significant Tc-MEP changes. In particular, greater than 80% MEP loss in at least one muscle group was observed in five of nine patients in the thoracic group and four of nine patients in the lumbar group. No surgical maneuver was undertaken as a result of this loss in an effort to improve motor responses other than verifying the stability of the construct and the extent of the decompression. Four patients developed postoperative deficits of radicular origin, three of them recovering fully at 3 months. No relation was found between intraoperative blood pressure, Hb changes, and Tc-MEP changes. Severity of Tc-MEP loss did not correlate with postoperative deficits. Shortening of more than 10 mm was linked to more severe Tc-MEP changes in the thoracic group. CONCLUSIONS: Transcranial MEP changes during spinal shortening procedures are common and do not appear to predict severe postoperative deficits. Total loss of Tc-MEP (not witnessed in our series) might require a more drastic approach with possible reversal of the correction and wake-up test.

EEG windowed statistical wavelet scoring for evaluation and discrimination of muscular artifacts

EEG recordings are usually corrupted by spurious extra-cerebral artifacts, which should be rejected or cleaned up by the practitioner. Since manual screening of human EEGs is inherently error prone and might induce experimental bias, automatic artifact detection is an issue of importance. Automatic artifact detection is the best guarantee for objective and clean results. We present a new approach, based on the time–frequency shape of muscular artifacts, to achieve reliable and automatic scoring. The impact of muscular activity on the signal can be evaluated using this methodology by placing emphasis on the analysis of EEG activity. The method is used to discriminate evoked potentials from several types of recorded muscular artifacts—with a sensitivity of 98.8% and a specificity of 92.2%. Automatic cleaning ofEEGdata are then successfully realized using this method, combined with independent component analysis. The outcome of the automatic cleaning is then compared with the Slepian multitaper spectrum based technique introduced by Delorme et al (2007 Neuroimage 34 1443–9).

Location-independent and location-linked representations of sound objects.

For the recognition of sounds to benefit perception and action, their neural representations should also encode their current spatial position and their changes in position over time. The dual-stream model of auditory processing postulates separate (albeit interacting) processing streams for sound meaning and for sound location. Using a repetition priming paradigm in conjunction with distributed source modeling of auditory evoked potentials, we determined how individual sound objects are represented within these streams. Changes in perceived location were induced by interaural intensity differences, and sound location was either held constant or shifted across initial and repeated presentations (from one hemispace to the other in the main experiment or between locations within the right hemispace in a follow-up experiment). Location-linked representations were characterized by differences in priming effects between pairs presented to the same vs. different simulated lateralizations. These effects were significant at 20-39 ms post-stimulus onset within a cluster on the posterior part of the left superior and middle temporal gyri; and at 143-162 ms within a cluster on the left inferior and middle frontal gyri. Location-independent representations were characterized by a difference between initial and repeated presentations, independently of whether or not their simulated lateralization was held constant across repetitions. This effect was significant at 42-63 ms within three clusters on the right temporo-frontal region; and at 165-215 ms in a large cluster on the left temporo-parietal convexity. Our results reveal two varieties of representations of sound objects within the ventral/What stream: one location-independent, as initially postulated in the dual-stream model, and the other location-linked.

Auditory stimulation does not induce implicit memory during anaesthesia

Background and aim of the study: Formation of implicit memory during general anaesthesia is still debated. Perceptual learning is the ability to learn to perceive. In this study, an auditory perceptual learning paradigm, using frequency discrimination, was performed to investigate the implicit memory. It was hypothesized that auditory stimulation would successfully induce perceptual learning. Thus, initial thresholds of the frequency discrimination postoperative task should be lower for the stimulated group (group S) compared to the control group (group C). Material and method: Eighty-seven patients ASA I-III undergoing visceral and orthopaedic surgery during general anaesthesia lasting more than 60 minutes were recruited. The anaesthesia procedure was standardized (BISR monitoring included). Group S received auditory stimulation (2000 pure tones applied for 45 minutes) during the surgery. Twenty-four hours after the operation, both groups performed ten blocks of the frequency discrimination task. Mean of the thresholds for the first three blocks (T1) were compared between groups. Results: Mean age and BIS value of group S and group C are respectively 40 } 11 vs 42 } 11 years (p = 0,49) and 42 } 6 vs 41 } 8 (p = 0.87). T1 is respectively 31 } 33 vs 28 } 34 (p = 0.72) in group S and C. Conclusion: In our study, no implicit memory during general anaesthesia was demonstrated. This may be explained by a modulation of the auditory evoked potentials caused by the anaesthesia, or by an insufficient longer time of repetitive stimulation to induce perceptual learning.

Neural plasticity associated with recently versus often heard objects.

In natural settings the same sound source is often heard repeatedly, with variations in spectro-temporal and spatial characteristics. We investigated how such repetitions influence sound representations and in particular how auditory cortices keep track of recently vs. often heard objects. A set of 40 environmental sounds was presented twice, i.e. as prime and as repeat, while subjects categorized the corresponding sound sources as living vs. non-living. Electrical neuroimaging analyses were applied to auditory evoked potentials (AEPs) comparing primes vs. repeats (effect of presentation) and the four experimental sections. Dynamic analysis of distributed source estimations revealed i) a significant main effect of presentation within the left temporal convexity at 164-215ms post-stimulus onset; and ii) a significant main effect of section in the right temporo-parietal junction at 166-213ms. A 3-way repeated measures ANOVA (hemisphere×presentation×section) applied to neural activity of the above clusters during the common time window confirmed the specificity of the left hemisphere for the effect of presentation, but not that of the right hemisphere for the effect of section. In conclusion, spatio-temporal dynamics of neural activity encode the temporal history of exposure to sound objects. Rapidly occurring plastic changes within the semantic representations of the left hemisphere keep track of objects heard a few seconds before, independent of the more general sound exposure history. Progressively occurring and more long-lasting plastic changes occurring predominantly within right hemispheric networks, which are known to code for perceptual, semantic and spatial aspects of sound objects, keep track of multiple exposures.

Glutathione deficit in schizophrenia: strategies to increase glutathione levels in " in vitro " and clinical studies

Summary: Decrease in glutathione (GSH) levels was observed in cerebrospinal fluid, prefrontal cortex and post-mortem striatum of schizophrenia patients. Evidences suggest a defect in GSH synthesis at the levels of the rate-limiting synthesizing enzyme, glutamate cysteine ligase (GCL). Indeed, polymorphisms in the gene of the modifier subunit of GCL (GCLM) was shown to be associated with the disease in three different populations, GCLM gene expression is decreaséd in fibroblasts from patients and the increase in GCL activity induced by an oxidative stress is lower in patients' fibroblasts compared to controls. GSH being a major antioxydant and redox regulator, its presence is of high importance for protecting cells against oxidative stress. The aim of the present work was to use various substances to increase GSH levels by diverse strategies. Since the synthesizing enzyme GCL is defective, bypassing this enzyme was the first strategy we used. GSH ethyl ester (GSHEE), a membrane permeable analog of GSH, succeeded in replenishing GSH levels in cultured neurons and astrocytes previously depleted in GSH by L-buthionine-(S,R)-sulfoximine (BSO), an inhibitor of GCL. GSHEE also abolished dopamine-induced decrease of NMDA-mediated calcium response observed in BSO-treated neurons. y-Glutamylcysteine ethyl ester (GCSE), a membrane permeable analog of the product of GCL, increased GSH levels only in astrocytes. The second strategy was to boost the defective enzyme GCL. While quercetin (flavonoid) could increase GSH levels only in astrocytes, curcumin (polyphenol) and tertbutylhydroquinone (quinone) were successful in both neurons and astrocytes, via an increase in the gene expression of the two subunits of GCL and, consequently, an increase in the activity of the enzyme. However, FK506, an immunosupressant, was unefficient. Treating astrocytes from GCLM KO mice showed that the modulatory subunit is necessary for the action of the substances. Finally, since cysteine is the limiting precursor in the synthesis of GSH, we hypothesized that we could increase GSH levels by providing more of this precursor. N-acetyl-cysteine (NAC), a cysteine donor, was administered to schizophrenia patients, using adouble-blind and cross-over protocol. NAC significantly improved the mismatch negativity (MMN), a component of the auditory evoked potentials, thought to reflect selective current flowing through open, unblocked NMDA channels. Considering that NMDA function is reduced when GSH levels are low, increasing these levels with NAC could improve NMDA function as reflected by the improvement in the generation of the MMN. Résumé: Les taux de glutathion (GSH) dans le liquide céphalo-rachidien, le cortex préfrontal ainsi que le striatum post-mortem de patients schizophrènes, sont diminués. L'enzyme limitante dans la synthèse du GSH, la glutamyl-cysteine ligase (GCL), est défectueuse. En effet, des polymorphismes dans le gène de la sous-unité modulatrice de GCL (GCLM) sont associés à la maladie, l'expression du gène GCLM est diminuée dans les fibroblastes de patients et, lors d'un stress oxidative, l'augmentation de l'activité de GCL est plus faible chez les patients que chez les contrôles. Le GSH étant un important antioxydant et régulateur du status redox, sa présence est primordiale afin de protéger les cellules contre les stress oxydatifs. Au cours du présent travail, une variété de substances ont été utilisées dans le but d'augmenter les taux de GSH. Passer outre l'enzyme de synthèse GCL qui est défectueuse fut la première stratégie utilisée. L'éthylester de GSH (GSHEE), un analogue du GSH qui pénètre la membrane cellulaire, a augmenté les taux de GSH dans des neurones et des astrocytes déficitaires en GSH dû au L-buthionine-(S,R)-sulfoximine (BSO), un inhibiteur du GCL. Dans ces neurones, le GSHEE a aussi aboli la diminution de la réponse NMDA, induite parla dopamine. L'éthyl-ester de y-glutamylcysteine (GCEE), un analogue du produit de la GCL qui pénètre la membrane cellulaire, a augmenté les taux de GSH seulement dans les astrocytes. La seconde stratégie était d'augmenter l'activité de l'enzyme GCL. Tandis que la quercétine (flavonoïde) n'a pu augmenter les taux de GSH que dans les astrocytes, la curcumin (polyphénol) et le tert-butylhydroquinone (quinone) furent efficaces dans les deux types de cellules, via une augmentation de l'expression des gènes des deux sous-unités de GCL et de l'activité de l'enzyme. Le FK506 (immunosupresseur) n' a démontré aucune efficacité. Traiter des astrocytes provenant de souris GCLM KO a permis d'observer que la sous-unité modulatoire est nécessaire à l'action des substances. Enfin, puisque la cysteine est le substrat limitant dans la synthèse du GSH, fournir plus de ce présurseur pourrait augmenter les taux de GSH. Nacétyl-cystéine (NAC), un donneur de cystéine, a été administrée à des schizophrènes, lors d'une étude en double-aveugle et cross-over. NAC a amélioré le mismatch negativity (MMN), un composant des potentials évoqués auditifs, qui reflète le courant circulant via les canaux NMDA. Puisque la fonctionnalité des R-NMDA est diminuée lorsque les taux de GSH sont bas, augmenter ces taux avec NAC pourrait améliorer la fonction des R-NMDA, réflété par une augmentation de l'amplitude du MMN.

From bird to sparrow: Learning-induced modulations in fine-grained semantic discrimination.

Recognition of environmental sounds is believed to proceed through discrimination steps from broad to more narrow categories. Very little is known about the neural processes that underlie fine-grained discrimination within narrow categories or about their plasticity in relation to newly acquired expertise. We investigated how the cortical representation of birdsongs is modulated by brief training to recognize individual species. During a 60-minute session, participants learned to recognize a set of birdsongs; they improved significantly their performance for trained (T) but not control species (C), which were counterbalanced across participants. Auditory evoked potentials (AEPs) were recorded during pre- and post-training sessions. Pre vs. post changes in AEPs were significantly different between T and C i) at 206-232ms post stimulus onset within a cluster on the anterior part of the left superior temporal gyrus; ii) at 246-291ms in the left middle frontal gyrus; and iii) 512-545ms in the left middle temporal gyrus as well as bilaterally in the cingulate cortex. All effects were driven by weaker activity for T than C species. Thus, expertise in discriminating T species modulated early stages of semantic processing, during and immediately after the time window that sustains the discrimination between human vs. animal vocalizations. Moreover, the training-induced plasticity is reflected by the sharpening of a left lateralized semantic network, including the anterior part of the temporal convexity and the frontal cortex. Training to identify birdsongs influenced, however, also the processing of C species, but at a much later stage. Correct discrimination of untrained sounds seems to require an additional step which results from lower-level features analysis such as apperception. We therefore suggest that the access to objects within an auditory semantic category is different and depends on subject's level of expertise. More specifically, correct intra-categorical auditory discrimination for untrained items follows the temporal hierarchy and transpires in a late stage of semantic processing. On the other hand, correct categorization of individually trained stimuli occurs earlier, during a period contemporaneous with human vs. animal vocalization discrimination, and involves a parallel semantic pathway requiring expertise.

Potenciales evocados como marcadores de riesgo al alcoholismo

En este informe se presenta una revisión de trabajos acerca de la utilización de distintos componentes de los potenciales evocados como marcadores de riesgo para desarrollar alcoholisrno. Los jóvenes procedentes de familias con antecedentes de alcoholismo presentan anomalías en la amplitud de P3 semejantes a las observadas en alcohólicos crónicos abstinentes. La infuencia de factores genéticos sobre las características de este componente y sobre la aparición de la adicción, hacen de P3 un posible marcador genético de riesgo. También se discute la posible utilidad de otros componentes y de la respuesta de aumento/reducción.

Coma post-anoxique après arrêt cardiaque et hypothermie, peut-on encore prédire le pronostic en 2014 ?

L'encéphalopathie post-anoxique après arrêt cardiaque (AC) est une cause féquente d'admission pour coma en réanimation. Depuis les recommandations de 2003, l'hypothermie thérapeutique (HT) est devenue un standard de traitement après AC et est à l'origine de l'amélioration du pronostic au cours de cette derniere décennie. Les élements prédicteurs de pronostic validés par l'Académie Américaine de Neurologie avant l'ère de l'HT sont devenus moins précis. En effet, l'HT et la sédation retardent la reprise de la réponse motrice et peuvent altérer la valeur prédictive des réflexes du tronc cérébral. Une nouvelle approche est nécessaire pour établir un pronostic après AC et HT. L'enregistrement (pendant l'HTou peu après) d'une activité électroencéphalographique réactive et/ou continue est un bon prédicteur de récupération neurologique favorable après AC. Au contraire, la présence d'un tracé non réactif ou discontinu de type burst-suppression, avec une réponse N20 absente bilatérale aux potentiels évoqués somatosensoriels, sont presqu'à 100 % prédictifs d'un coma irréversible déjà à 48 heures après AC. L'HT modifie aussi la valeur prédictive de l'énolase neuronale spécifique (NSE), principal biomarqueur sérique de la lésion cérébrale post-anoxique. Un réveil avec bonne récupération neurologique a été récemment observé par plusieurs groupes chez des patients présentant des valeurs de NSE>33 μg/L à 48-72 heures : ce seuil ne doit pas être utilisé seul pour guider le traitement. L'imagerie par résonance magnétique de diffusion peut aider à prédire les séquelles neurologiques à long terme. Un réveil chez les patients en coma post-anoxique est de plus en plus observé, malgré l'absence précoce de signes moteurs et une élévation franche des biomarqueurs neuronaux. En 2014, une nouvelle approche multimodale du pronostic est donc nécessaire, pour optimiser la prédiction d'une évolution clinique favorable après AC. Hypoxic-ischemic encephalopathy after cardiac arrest (CA) is a frequent cause of intensive care unit (ICU) admission. Incorporated in all recent guidelines, therapeutic hypothermia (TH) has become a standard of care and has contributed to improve prognosis after CA during the past decade. The accuracy of prognostic predictors validated in 2006 by the American Academy of Neurology before the era of TH is less accurate. Indeed, TH and sedation may delay the recovery of motor response and alter the predictive value of brainstem reflexes. A new approach is needed to accurately establish prognosis after CA and TH. A reactive and/or continuous electroencephalogram background (during TH or shortly thereafter) strongly predicts good outcome. On the contrary, unreactive/spontaneous burst-suppression electroencephalogram pattern, together with absent N20 on somatosensory evoked potentials, is almost 100% predictive of irreversible coma. TH also affects the predictive value of neuronspecific enolase (NSE), the main serum biomarker of postanoxic injury. A good outcome can occur despite NSE levels >33 μg/L, so this cutoff value should not be used alone to guide treatment. Diffusion magnetic resonance imagery may help predict long-term neurological sequelae. Awakening from postanoxic coma is increasingly observed, despite the absence of early motor signs and pathological elevation of NSE. In 2014, a multimodal approach to prognosis is recommended to optimize the prediction of outcome after CA.

Morphological priming in Spanish verb forms: an ERP repetition priming study

The ERP repetition priming paradigm has been shown to be sensitive to the processing differences between regular and irregular verb forms in English and German. The purpose of the present study is to extend this research to a language with a different inflectional system, Spanish. The design (delayed visual repetition priming) was adopted from our previous study on English, and the specific linguistic phenomena we examined are priming relations between different kinds of stem (or root) forms. There were two experimental conditions: In the first condition, the prime and the target shared the same stem form, e.g., "ando-andar" [I walk-to walk], whereas in the second condition, the prime contained a marked (alternated) stem, e.g., "duermo-dormir" [I sleep-to sleep]. A reduced N400 was found for unmarked (nonalternated) stems in the primed condition, whereas marked stems showed no such effect. Moreover, control conditions demonstrated that the surface form properties (i.e., the different degree of phonetic and orthographic overlap between primes and targets) do not explain the observed priming difference. The ERP priming effect for verb forms with unmarked stems in Spanish is parallel to that found for regularly inflected verb forms in English and German. We argue that effective priming is possible because prime target pairs such as "ando-andar" access the same lexical entry for their stems. By contrast, verb forms with alternated stems (e.g., "duermo") constitute separate lexical entries, and are therefore less powerful primes for their corresponding base forms.

Nucleus accumbens is involved in human action monitoring: evidence from invasive electrophysiological recordings

The Nucleus accumbens (Nacc) has been proposed to act as a limbic-motor interface. Here, using invasive intraoperative recordings in an awake patient suffering from obsessive-compulsive disease (OCD), we demonstrate that its activity is modulated by the quality of performance of the subject in a choice reaction time task designed to tap action monitoring processes. Action monitoring, that is, error detection and correction, is thought to be supported by a system involving the dopaminergic midbrain, the basal ganglia, and the medial prefrontal cortex. In surface electrophysiological recordings, action monitoring is indexed by an error-related negativity (ERN) appearing time-locked to the erroneous responses and emanating from the medial frontal cortex. In preoperative scalp recordings the patient's ERN was found to be signifi cantly increased compared to a large (n = 83) normal sample, suggesting enhanced action monitoring processes. Intraoperatively, error-related modulations were obtained from the Nacc but not from a site 5 mm above. Importantly, crosscorrelation analysis showed that error-related activity in the Nacc preceded surface activity by 40 ms. We propose that the Nacc is involved in action monitoring, possibly by using error signals from the dopaminergic midbrain to adjust the relative impact of limbic and prefrontal inputs on frontal control systems in order to optimize goal-directed behavior.

Errores numéricos: ¿Cómo afectan a las personas con ansiedad matemática?

¿Cómo responde el cerebro de una persona con ansiedad a las matemáticas? Nuestro estudio muestra que los estudiantes con mucha ansiedad hacia las matemáticas presentan un componente llamado negatividad asociada al error (NAE) de mayor tamaño que aquellos con poca ansiedad. Esta diferencia emerge en errores en tareas numéricas, lo que sugiere que las personas con alta ansiedad son hipersensibles a la comisión de estos errores. Este hallazgo aporta nuevo conocimiento sobre las bases cerebrales de la ansiedad hacia las matemáticas y sugiere que esta hipersensibilidad al error numérico podría ser un factor determinante tanto en el origen como en el mantenimiento de esta ansiedad.

"Dov'è la sinistra?" Hemispatial neglect in stroke

As long as the incidence of stroke continues to grow, patients with large right hemisphere lesions suffering from hemispatial neglect will require neuropsychological evaluation and rehabilitation. The inability to process information especially that coming from the left side accompanied by the magnetic orientation to the ipsilesional side represents a real challenge for rehabilitation. This dissertation is concerned with crucial aspects in the clinical neuropsychological practice of hemispatial neglect. In studying the convergence of the visual and behavioural test batteries in the assessment of neglect, nine of the seventeen patients, who completed both the conventional subtests of the Behavioural Inattention Test and the Catherine Bergego Scale assessments, showed a similar severity of neglect and thus good convergence in both tests. However, patients with neglect and hemianopia had poorer scores in the line bisection test and they displayed stronger neglect in behaviour than patients with pure neglect. The second study examined, whether arm activation, modified from the Constraint Induced Movement Therapy, could be applied as neglect rehabilitation alone without any visual training. Twelve acute- or subacute patients were randomized into two rehabilitation groups: arm activation training or traditional voluntary visual scanning training. Neglect was ameliorated significantly or almost significantly in both training groups due to rehabilitation with the effect being maintained for at least six months. In studying the reflections of hemispatial neglect on visual memory, the associations of severity of neglect and visual memory performances were explored. The performances of acute and subacute patients with hemispatial neglect were compared with the performances of matched healthy control subjects. As hypothesized, encoding from the left side and immediate recall of visual material were significantly compromised in patients with neglect. Another mechanism of neglect affecting visual memory processes is observed in delayed visual reproduction. Delayed recall demands that the individual must make a match helped by a cue or it requires a search for relevant material from long-term memory storage. In the case of representational neglect, the search may succeed but the left side of the recollected memory still fails to open. Visual and auditory evoked potentials were measured in 21 patients with hemispatial neglect. Stimuli coming from the left or right were processed differently in both sensory modalities in acute and subacute patients as compared with the chronic patients. The differences equalized during the course of recovery. Recovery from hemispatial neglect was strongly associated with early rehabilitation and with the severity of neglect. Extinction was common in patients with neglect and it did not ameliorate with the recovery of neglect. The presence of pusher symptom hampered amelioration of visual neglect in acute and subacute stroke patients, whereas depression did not have any significant effect in the early phases after the stroke. However, depression had an unfavourable effect on recovery in the chronic phase. In conclusion, the combination of neglect and hemianopia may explain part of the residual behavioural neglect that is no longer evident in visual testing. Further research is needed in order to determine which specific rehabilitation procedures would be most beneficial in patients suffering the combination of neglect and hemianopia. Arm activation should be included in the rehabilitation programs of neglect; this is a useful technique for patients who need bedside treatment in the acute phase. With respect to the deficit in visual memory in association with neglect, the possible mechanisms of lateralized deficit in delayed recall need to be further examined and clarified. Intensive treatment induced recovery in both severe and moderate visual neglect long after the first two to first three months after the stroke.