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The functional correlates of anatomical derangements are of interest to the neurological clinician. Diffusion tensor tractography (DTT) is a relatively new tool in the arsenal of functional neuroimaging, by which to assess white matter tracts in the brain. While much import has been given to tracking corticospinal tracts in neurological disease, studying language pathway interconnections using DTT has largely remained in the research realm. Hardware and software advances have allowed this tool to ease into clinical practice, with several radiologists, neurologists, and neurosurgeons now familiar with its applications. DTT images, although visually appealing, are founded in mathematical equations and assumptions, and require a more than basic understanding of principles and limitations before they can be integrated into routine clinical practice. Cognitive pathways like that of language, that are normally hard to assess and especially more so when pathologically affected, have been at the receiving end of several opposing and often controversial hypotheses, and the past decade has seen the clarification, validation or rejection of several of these by the in vivo charting of functional connectivity using DTT. The focus of this review is to illustrate DTT of the language pathways with emphasis on practical considerations, clinical applications, and limitations., (© 2013 Wiley Periodicals, Inc.)

Traumatic brain injury (TBI) is a major health concern in industrialised countries. Sleep and wake disturbances are among the most persistent and disabling sequelae after TBI. Yet, despite the widespread complaints of post-TBI sleep and wake disturbances, studies on their etiology, pathophysiology, and treatments remain inconclusive. This narrative review aims to summarise the current state of knowledge regarding the nature of sleep and wake disturbances following TBI, both subjective and objective, spanning all levels of severity and phases post-injury. A second goal is to outline the various causes of post-TBI sleep-wake disturbances. Globally, although sleep-wake complaints are reported in all studies and across all levels of severity, consensus regarding the objective nature of these disturbances is not unanimous and varies widely across studies. In order to optimise recovery in TBI survivors, further studies are required to shed light on the complexity and heterogeneity of post-TBI sleep and wake disturbances, and to fully grasp the best timing and approach for intervention., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Obstructive sleep apnea (OSA) is characterised by repetitive cessation or reduction of airflow due to upper airway obstructions. These respiratory events lead to chronic sleep fragmentation and intermittent hypoxemia. Several studies have shown that OSA is associated with daytime sleepiness and cognitive dysfunctions, characterized by impairments of attention, episodic memory, working memory, and executive functions. This paper reviews the cognitive profile of adults with OSA and discusses the relative role of altered sleep and hypoxemia in the aetiology of these cognitive deficits. Markers of cognitive dysfunctions such as those measured with waking electroencephalography and neuroimaging are also presented. The effects of continuous positive airway pressure (CPAP) on cognitive functioning and the possibility of permanent brain damage associated with OSA are also discussed. Finally, this paper reviews the evidence suggesting that OSA is a risk factor for developing mild cognitive impairment and dementia in the aging population and stresses the importance of its early diagnosis and treatment., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

The sensory input that we experience is highly patterned, and we are experts at detecting these regularities. Although the extraction of such regularities, or statistical learning (SL), is typically viewed as a cortical process, recent studies have implicated the medial temporal lobe (MTL), including the hippocampus. These studies have employed fMRI, leaving open the possibility that the MTL is involved but not necessary for SL. Here, we examined this issue in a case study of LSJ, a patient with complete bilateral hippocampal loss and broader MTL damage. In Experiments 1 and 2, LSJ and matched control participants were passively exposed to a continuous sequence of shapes, syllables, scenes, or tones containing temporal regularities in the co-occurrence of items. In a subsequent test phase, the control groups exhibited reliable SL in all conditions, successfully discriminating regularities from recombinations of the same items into novel foil sequences. LSJ, however, exhibited no SL, failing to discriminate regularities from foils. Experiment 3 ruled out more general explanations for this failure, such as inattention during exposure or difficulty following test instructions, by showing that LSJ could discriminate which individual items had been exposed. These findings provide converging support for the importance of the MTL in extracting temporal regularities.

Introduction: Most of the people who have survived a lateralized brain injury have sequelae components affecting sensorimotor, cognitive or behavioral. These deficits affect the proper execution of daily living activities. The aim of this study is to analyze and compare the occupational profile of people with unilateral acquired brain injury, both people with traumatic brain injury (TBI) and cerebrovascular accidents (CVA), with functional independence, ability, participation and the quality of performance of everyday activities, before and after a multidisciplinary treatment., Patients and Methods: Cohort quasi-experimental design with pre-cutting measures after treatment with a sample of 58 people, 28 TBI and 30 CVA, both lateralized. The measures used were the FIM+FAM, ICF, and AMPS., Results: Considering the groups analyzed (lateralized full sample, sample diagnosis) analysis results indicate the existence of significant differences and a moderate effect size in the two cross-sectional estimates, providing greater levels of independence to injuries occurring in the right hemisphere (p < 0.001). However, when it is divided the sample by diagnosis appears no significant differences, except in motor skills, where higher scores for TBI are showed (p < 0,05)., Conclusions: We suggest that this justifies the differences is not the mode of injury (TBI or CVA), but the hemispheric location. Therefore, it is suggested that people with acquired brain injury in the left hemisphere require more intensive intervention.

Hierarchical models of visual processing assume that global pattern recognition is contingent on the progressive integration of local elements across larger spatial regions, operating from early through intermediate to higher-level cortical regions. Here, we present results from neuropsychological fMRI that refute such models. We report two patients, one with lesions to intermediate ventral regions and the other with damage around the intraparietal sulcus (IPS). The patient with ventral damage showed normal behavioral and BOLD responses to global Glass patterns. The patient with IPS damage was impaired in discriminating global patterns and showed a lack of significant responses to these patterns in intermediate visual regions spared by the lesion. However, this patient did show BOLD activity to translational patterns, where local element relations are important. These results suggest that activation of intermediate ventral regions is not necessary to code global patterns; instead global patterns are coded in a heterarchical fashion. High-level regions of dorsal cortex are necessary to generate global pattern coding in intermediate ventral regions; in contrast, local integration processes are not sufficient.

With increasing public education in basic life support and with the widespread use of automated defibrillators, post-cardiac arrest comatose patients represent a growing part of ICU admissions. However the prognosis remains very poor and only a very low proportion of these resuscitated patients will recover and will leave the hospital without major neurological impairments. Neurological dysfunction predominantly includes disorders of consciousness, and may also include other manifestations such as seizures, myoclonus status epilepticus and other forms of movement disorders including post-anoxic myoclonus. In the most severe cases, coma may be irreversible or evolve towards a minimally conscious state, a vegetative state or even brain death. These severe conditions represent by far the leading cause of mortality and disability in such patients. Currently, early use of mild therapeutic hypothermia is the only treatment that demonstrated its ability to decrease neurological consequences and to improve the prognosis. Prognostication outcome is still mainly based on a rigorous clinical evaluation coupled with neuro-physiological investigations, but brain functional imaging could become a valuable tool in the near future. Clinical research focusing on survivors should be strongly encouraged in order to assess the mid- and long-terms outcome of survivors and to evaluate the impact of new treatments or strategies., (Copyright © 2013 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.)

Introduction: Predicting the neurological outcome after cardiopulmonary resuscitation (CPR) is extremely difficult. We tested the hypothesis whether monitoring of bispectral index (BIS) and suppression ratio (SR) could serve as an early prognostic indicator of neurological outcomes after CPR., Methods: Cerebral monitoring (BIS, SR) was started as soon as possible after initiation of CPR and was continued for up to 72h. The functional neurological outcome was measured on day 3, day 7 and again one month after CPR via a clinical examination and assessment according to the cerebral performance category score (CPC)., Results: In total 79 patients were included. Of these, 26 patients (32.9%) survived the observation period of one month; 7 of them (8.9%) showed an unfavourable neurological outcome. These 7 patients had significantly lower median BIS values (25 [21;37] vs. 61 [51;70]) and higher SR (56 [44;64] vs. 7 [1;22]) during the first 4h after the initiation of CPR. Using BIS<40 as threshold criteria, unfavourable neurological outcome was predicted with a specificity of 89.5% and a sensitivity of 85.7%. The odds ratio for predicting an unfavourable neurological outcome was 0.921 (95% CI 0.853-0.985). The likelihood to remain in a poor neurological condition decreased by 7.9% for each additional point of BIS, on average., Conclusion: Our results suggest that BIS and SR are helpful tools in the evaluation of the neurological outcomes of resuscitated patients. Nevertheless, therapeutic decisions have to be confirmed through further examinations due to the far-ranging consequences of false positive results., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Loss of cognitive function is one the most devastating manifestations of ageing and vascular disease. Cognitive decline is rapidly becoming an important cause of disability worldwide and contributes significantly to increased mortality. There is growing evidence that hypertension is the most important modifiable vascular risk factor for development and progression of both cognitive decline and dementia. High blood pressure contributes to cerebral small and large vessel disease resulting in brain damage and dementia. A decline in cerebrovascular reserve capacity and emerging degenerative vascular wall changes underlie complete and incomplete brain infarcts, haemorrhages and white matter hyperintensities. This review discusses the complexity of factors linking hypertension to brain functional and structural changes, and to cognitive decline and dementia. The evidence for possible clinical markers useful for prevention of decreased cognitive ability, as well as recent data on vascular mechanism in the pathogenesis of cognitive decline, and the role of antihypertensive therapies in long-term prevention of late-life cognitive decline will be reviewed.

Pantomimes of object use require accurate representations of movements and a selection of the most task-relevant gestures. Prominent models of praxis, corroborated by functional neuroimaging studies, predict a critical role for left parietal cortices in pantomime and advance that these areas store representations of tool use. In contrast, lesion data points to the involvement of left inferior frontal areas, suggesting that defective selection of movement features is the cause of pantomime errors. We conducted a large-scale voxel-based lesion-symptom mapping analyses with configural/spatial (CS) and body-part-as-object (BPO) pantomime errors of 150 left and right brain-damaged patients. Our results confirm the left hemisphere dominance in pantomime. Both types of error were associated with damage to left inferior frontal regions in tumor and stroke patients. While CS pantomime errors were associated with left temporoparietal lesions in both stroke and tumor patients, these errors appeared less associated with parietal areas in stroke than in tumor patients and less associated with temporal in tumor than stroke patients. BPO errors were associated with left inferior frontal lesions in both tumor and stroke patients. Collectively, our results reveal a left intrahemispheric dissociation for various aspects of pantomime, but with an unspecific role for inferior frontal regions.

Functional reorganization of language was investigated in a group of eleven non-fluent aphasic patients after linguistic recovery and in a group of matched healthy adults. The ElectroEncephaloGram (EEG) was recorded from 38 scalp electrodes and high-beta band (21-28 Hz), an index of cognitive cortical arousal, was computed as normalized percentage across 0-100 Hz spectral range in six electrode clusters during three linguistic tasks: Phonological, Semantic and Orthographic/visuo-perceptual. During the Phonological task, controls showed greater beta activation on left versus right central cluster, whereas aphasic patients exhibited an inverted pattern of lateralization. In addition, patients' left central cluster, located over the core lesion, showed reduced beta activity with respect to controls. A similar inhibited activation was found in aphasics' left posterior cluster located over undamaged areas. At left anterior locations, aphasics, unlike controls, exhibited larger left versus right beta activity during both Phonological and Orthographic/visuo-perceptual tasks. Results point to substantial reorganization of language in recovered non-fluent aphasics at left prefrontal sites located anterior to the damaged Broca's area and inhibited language-related activation in left posterior undamaged, but disconnected, regions., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Patients with acute lung injury or acute respiratory distress syndrome (ARDS) admitted to the ICU present neuropsychological alterations, which in most cases extend beyond the acute phase and have an important adverse effect upon quality of life. The aim of this review is to deepen in the analysis of the complex interaction between lung and brain in critically ill patients subjected to mechanical ventilation. This update first describes the neuropsychological alterations occurring both during the acute phase of ICU stay and at discharge, followed by an analysis of lung-brain interactions during mechanical ventilation, and finally explores the etiology and mechanisms leading to the neurological disorders observed in these patients. The management of critical patients requires an integral approach focused on minimizing the deleterious effects over the short, middle or long term., (Copyright © 2012 Elsevier España, S.L. y SEMICYUC. All rights reserved.)

Even though it is known that neonatal seizures are associated with acute brain lesions, the relationship of electroencephalographic (EEG) seizures to acute perinatal brain lesions visible on magnetic resonance imaging (MRI) has not been objectively studied. EEG source localization is successfully used for this purpose in adults, but it has not been sufficiently explored in neonates. Therefore, we developed an integrated method for ictal EEG dipole source localization based on a realistic head model to investigate the utility of EEG source imaging in neonates with postasphyxial seizures. We describe here our method and compare the dipole seizure localization results with acute perinatal lesions seen on brain MRI in 10 full-term infants with neonatal encephalopathy. Through experimental studies, we also explore the sensitivity of our method to the electrode positioning errors and the variations in neonatal skull geometry and conductivity. The localization results of 45 focal seizures from 10 neonates are compared with the visual analysis of EEG and MRI data, scored by expert physicians. In 9 of 10 neonates, dipole locations showed good relationship with MRI lesions and clinical data. Our experimental results also suggest that the variations in the used values for skull conductivity or thickness have little effect on the dipole localization, whereas inaccurate electrode positioning can reduce the accuracy of source estimates. The performance of our fused method indicates that ictal EEG source imaging is feasible in neonates and with further validation studies, this technique can become a useful diagnostic tool., (Copyright © 2012 Wiley Periodicals, Inc.)

We examined the relations between texture segregation and contour integration in patients with deficits in spatial attention leading to left or right hemisphere extinction. Patients and control participants were presented with texture and contour stimuli consisting of oriented elements. We induced regularity in the stimuli by manipulating the element orientations resulting in an implicit texture border or explicit contour. Participants had to discriminate curved from straight shapes without making eye movements, while the stimulus presentation time was varied using a QUEST procedure. The results showed that only patients with right hemisphere extinction had a spatial bias, needing a longer presentation time to determine the shape of the border or contour on the contralesional side, especially for borders defined by texture. These results indicate that texture segregation is modulated by attention-related brain areas in the right posterior parietal cortex.

It remains unclear to what extent retinotopic maps can undergo large-scale plasticity following damage to human visual cortex. The literature has predominately focused on retinotopic changes in patients with retinal pathologies or congenital brain malformations. Yet, damage to the adult visual cortex itself is common in cases such as stroke, tumor, or trauma. To address this issue, we used a unique database of fMRI vision maps in patients with adult-onset (n=25) and congenital (n=2) pathology of the visual cortex. We identified atypical retinotopic organization in three patients (two with adult-onset, and one with congenital pathology) consisting of an expanded ipsilateral field representation that was on average 3.2 times greater than healthy controls. The expanded representations were located at the vertical meridian borders between visual areas such as V1/V2. Additionally, two of the three patients had apparently an ectopic (topographically inconsistent) representation of the ipsilateral field within lateral occipital cortex that is normally associated with visual areas V3/V3A (and possibly other areas). Both adult-onset cases had direct damage to early visual cortex itself (rather than to the afferent drive only), resulting in a mostly nonfunctional hemisphere. The congenital case had severe cortical malformation of the visual cortex and was acallosal. Our results are consistent with a competitive model in which unilateral damage to visual cortex or disruption of the transcallosal connections removes interhemispheric suppression from retino-geniculate afferents in intact visual cortex that represent the vertical meridian and ipsilateral visual field.

Purpose of Review: Early prognostication in acute brain damage remains a challenge in the realm of critical care. There remains controversy over the most optimal methods that can be utilized to predict outcome. The utility of recently reported prognostic biomarkers and clinical methods will be reviewed., Recent Findings: Recent guidelines touch upon prognostication techniques as part of management recommendations. In addition to novel laboratory values, there have been few reports on the use of clinical parameters, diagnostic imaging techniques, and electrophysiological techniques to assist in prognostication., Summary: Although encouraging, newer markers are not capable of providing accurate estimates on outcomes in acute injuries of the central nervous system. Traditional markers of prognostication may not be applicable in the light of newer and effective therapies (i.e. hypothermia). Substantial research in the field of outcome determination is in progress, but these studies need to be interpreted with caution.

Cognitive impairment is the most frequent cause of disability in humans following brain damage, yet the behavioral tasks used to assess cognition in rodent models of brain injury is lacking. Borrowing from the operant literature our laboratory utilized a basic scent discrimination paradigm in order to assess deficits in frontally-injured rats. Previously we have briefly described the Dig task and demonstrated that rats with frontal brain damage show severe deficits across multiple tests within the task. Here we present a more detailed protocol for this task. Rats are placed into a chamber and allowed to discriminate between two scented sands, one of which contains a reinforcer. The trial ends after the rat either correctly discriminates (defined as digging in the correct scented sand), incorrectly discriminates, or 30 sec elapses. Rats that correctly discriminate are allowed to recover and consume the reinforcer. Rats that discriminate incorrectly are immediately removed from the chamber. This can continue through a variety of reversals and novel scents. The primary analysis is the accuracy for each scent pairing (cumulative proportion correct for each scent). The general findings from the Dig task suggest that it is a simple experimental preparation that can assess deficits in rats with bilateral frontal cortical damage compared to rats with unilateral parietal damage. The Dig task can also be easily incorporated into an existing cognitive test battery. The use of more tasks such as this one can lead to more accurate testing of frontal function following injury, which may lead to therapeutic options for treatment. All animal use was conducted in accordance with protocols approved by the Institutional Animal Care and Use Committee.

Childhood trauma due to physical abuse, neglect, or sexual abuse is a serious problem in the United States. Trauma can result in disruption or injury to the developing brain and lead to neurodevelopmental deficits that affect a child's functioning and can result in lifelong problems. Research has provided insight into how early childhood maltreatment affects brain development. This article examines the research on trauma, its effects on the brain, and evidence-based interventions. An overview of normal brain functioning and posttraumatic stress disorder is presented. Implications for social work practice with children who have experienced child maltreatment are discussed.

How the brain is lateralised for emotion processing remains a key question in contemporary neuropsychological research. The right hemisphere hypothesis asserts that the right hemisphere dominates emotion processing, whereas the valence hypothesis holds that positive emotion is processed in the left hemisphere and negative emotion is controlled by the right hemisphere. A meta-analysis was conducted to assess unilateral brain-damaged individuals' performance on tasks of facial emotion perception according to valence. A systematic search of the literature identified seven articles that met the conservative selection criteria and could be included in a meta-analysis. A total of 12 meta-analyses of facial expression perception were constructed assessing identification and labelling tasks according to valence and the side of brain damage. The results demonstrated that both left and right hemisphere damage leads to impairments in emotion perception (identification and labelling) irrespective of valence. Importantly, right hemisphere damage prompted more pronounced emotion perception impairment than left hemisphere damage, across valence, suggesting right hemisphere dominance for emotion perception. Furthermore, right hemisphere damage was associated with a larger tendency for impaired perception of negative than positive emotion across identification and labelling tasks. Overall the findings support Adolphs, Jansari, and Tranel (2001) model whereby the right hemisphere preferentially processes negative facial expressions and both hemispheres process positive facial expressions.

Background: There is a growing interest in therapies that may augment motor recovery that could be initiated in the acute stroke unit and maintained through the rehabilitation period. Homogenization of the currently fragmented stroke clinicometrics is necessary before such multidisciplinary trials can be conducted. The supplementary motor scale of the NIH Stroke Scale (SMS-NIHSS) is a simple and reliable scale for assessing proximal and distal motor function in the upper and lower extremities. We hypothesized that the currently underutilized SMS-NIHSS is a valid tool for assessing motor recovery with prognosticative value., Methods: We performed an analysis of SMS-NIHSS scores recorded in 1,281 patients enrolled in the Trial of ORG 10172 in Acute Stroke Treatment (TOAST). We plotted the probability of a favorable outcome (FO) and very favorable outcome (VFO) at 3 months based on the baseline SMS-NIHSS scores. In order to better study the relationship between SMS-NIHSS and 3-month functional outcome, we performed multivariate logistic regression analyses using both FO and VFO as outcome measures. Analyses were adjusted for potential confounders such as age, sex, side of the lesion, time from symptom onset to emergency room arrival, temperature, systolic blood pressure, blood glucose level and treatment group assignment (ORG 10172 vs. placebo). We also calculated the Spearman correlation coefficient between the SMS-NIHSS, Barthel Index (BI) and Glasgow Outcome Score (GOS) obtained at the 3-month visit., Results: The mean SMS-NIHSS scores were 8.18 at baseline and 4.68 at 3 months. The SMS-NIHSS scores showed a gradual improvement during the first 3 months after stroke. There was a linear relationship between the baseline SMS-NIHSS scores and the probability of an FO or VFO at 3 months. The SMS-NIHSS baseline score was an independent predictor of FO (OR = 0.86; 95% CI 0.84-0.87; p < 0.0001) and VFO (OR = 0.85; 95% CI 0.84-0.87; p < 0.0001) at 3 months after adjusting for confounders. The degree of improvement in the SMS-NIHSS scores from baseline to 3 months was also independently associated with FO and VFO (p < 0.0001). At 3 months, SMS-NIHSS scores showed a strong correlation with the BI (r = -0.70; p < 0.0001) and GOS (r = 0.73; p < 0.0001)., Conclusions: The SMS-NIHSS is a valid scale for assessing motor recovery with prognosticative value, and may be sensitive to changes during recovery. Given that the SMS-NIHSS is an extension of the widely accepted NIHSS, it could be easily implemented in trials conducted in a variety of clinical research settings, including acute stroke hospitals and rehabilitation units., (Copyright © 2013 S. Karger AG, Basel.)

Objective: To describes socio-demographic and clinical features of adults and children in vegetative state (VS) and minimally conscious state (MCS)., Design: Observational cross-sectional study., Methods: Demographic, aetiological and clinical data were collected, together with patients' management procedures. Mann-Whitney U-test was used for continuous variables and chi-squared test for categorical variables., Results: Six hundred patients (69.7% in VS; 6% children) were enrolled. No difference regarding age at enrolment, age at acute event and disease duration was observed between VS and MCS. Disease duration was superior to 10 years for 3.3% of the whole sample and 64.3-77% of cases had a non-traumatic aetiology. Mean number of drugs per adult patient was four and decreased consistently with increased disease duration., Discussion: Patients with VS and MCS were similar for age at acute event and at enrolment, both over 50 years, as well as for the frequency of non-traumatic aetiology. Disease duration was similar for both conditions and 2.6% of VS and 4.8% of MCS patients survived for more than 10 years. Finally care and treatment needs are similar and not related to diagnosis.

In this experiment we studied statistical learning, inter-trial priming, and visual attention. We assessed healthy controls and right brain damaged (RBD) patients with and without neglect, on a simple visual discrimination task designed to measure priming effects and probability learning. All participants showed a preserved priming effect for item color. Contrary to healthy controls and RBD participants without neglect, RBD participants with neglect did not show positional priming and both RBD groups learned the underlying spatial probability distribution of target locations to a lesser degree. To see if the latter deficiency could be improved, we tested a patient with long standing chronic spatial neglect on three separate days and observed improved identification times for left sided, high probability, targets. In summary, we found preservation of priming per se in people with spatial neglect. However, this was only clearly demonstrable for color priming and not for positional priming. Associated with this impairment was a difficulty in learning the overall statistical structure of target locations. In a patient with severe persistent neglect we were able to demonstrate that the deficit in statistical learning was not absolute, as this subject improved his identification times for targets appearing in high probability regions of the test display., (Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.)

Introduction: Brain ischemia and reperfusion produce alterations in the microenvironment of the parenchyma, including ATP depletion, ionic homeostasis alterations, inflammation, release of multiple cytokines and abnormal release of neurotransmitters. As a consequence, the induction of proliferation and migration of neural stem cells towards the peri-infarct region occurs., Development: The success of new neurorestorative treatments for damaged brain implies the need to know, with greater accuracy, the mechanisms in charge of regulating adult neurogenesis, both under physiological and pathological conditions. Recent evidence demonstrates that many neurotransmitters, glutamate in particular, control the subventricular zone, thus being part of the complex signalling network that influences the production of new neurons., Conclusion: Neurotransmitters provide a link between brain activity and subventricular zone neurogenesis. Therefore, a deeper knowledge of the role of neurotransmitters systems, such as glutamate and its transporters, in adult neurogenesis, may provide a valuable tool to be used as a neurorestorative therapy in this pathology.

To determine the areas involved in reorganization of language to the right hemisphere after early left hemisphere injury, we compared fMRI activation patterns during four production and comprehension tasks in post-surgical epilepsy patients with either left (LH) or right hemisphere (RH) speech dominance (determined by Wada testing) and healthy controls. Patient groups were carefully matched for IQ, lesion location and size. RH patients' activation across all tasks was greatest in right hemisphere areas homotopic to areas activated by LH and control participants. Differences in right vs. left dominant hemisphere activation were limited to homologous areas typically activated by language tasks, supporting the hypothesis that language localization following transfer to the RH is the mirror-image of localization in the absence of transfer. The similarity of these findings to those in patients with larger, peri-sylvian lesions suggests that these areas in both hemispheres may be uniquely predisposed to subserve various language functions., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Aim: Early sucking and swallowing problems may be potential markers of neonatal brain injury and assist in identifying those infants at increased risk of adverse outcomes, but the relation between early sucking and swallowing problems and neonatal brain injury has not been established. The aim of the review was, therefore, to investigate the relation between early measures of sucking and swallowing and neurodevelopmental outcomes in infants diagnosed with neonatal brain injury and in infants born very preterm (<32wks) with very low birthweight (<1500g), at risk of neonatal brain injury., Method: We conducted a systematic review of English-language articles using CINAHL, EMBASE, and MEDLINE OVID (from 1980 to May 2011). Additional studies were identified through manual searches of key journals and the works of expert authors. Extraction of data informed an assessment of the level of evidence and risk of bias for each study using a predefined set of quality indicators., Results: A total of 394 abstracts were generated by the search but only nine studies met the inclusion criterion. Early sucking and swallowing problems were present in a consistent proportion of infants and were predictive of neurodevelopmental outcome in infancy in five of the six studies reviewed., Limitations: The methodological quality of studies was variable in terms of research design, level of evidence (National Health and Medical Research Council levels II, III, and IV), populations studied, assessments used and the nature and timing of neurodevelopmental follow-up., Conclusions: Based upon the results of this review, there is currently insufficient evidence to clearly determine the relation between early sucking and swallowing problems and neonatal brain injury. Although early sucking and swallowing problems may be related to later neurodevelopmental outcomes, further research is required to delineate their value in predicting later motor outcomes and to establish reliable measures of early sucking and swallowing function., (© The Authors. Developmental Medicine & Child Neurology © 2012 Mac Keith Press.)

Background: Specific language impairment (SLI) is a primary developmental disorder in which language is significantly more impaired than other developmental domains. Abnormal electroencephalographic recordings without clinical seizures are often observed. The aim of this retrospective study was to characterize the frequency of these abnormalities, to describe them and to analyze their association with anamnestic, clinical, paraclinical and evolution characteristics., Methods: The cases of 35 children with a diagnosis of SLI, who also underwent electroencephalography and MRI, were systematically reviewed retrospectively., Results: In this population, aged between 4 and 7 years, 49% (n=17) of patients exhibited a specific expressive language disorder and 51% (n=18) a specific receptive disorder. Forty-nine percent of the children featured abnormal electroencephalography results. Abnormalities were essentially localized on the left side of the brain and in two specific regions: the temporo-occipital (60%) and the frontorolandic (30%) regions. The groups with and without abnormalities were compared statistically with each other in terms of clinical, paraclinical and evolution characteristics. Evolution data were available for 24 patients through a telephone interview and for nine patients through a new complete language evaluation. The comparison of the two groups showed significant differences in terms of severity of the phonological disorder, a higher number of delayed acquisition of walking and cleanliness and a higher range of non specific psychomotor difficulties., Discussion: A large proportion of children suffering from SLI present abnormal electroencephalography recordings with no clinical seizures. This rate is much higher than in the general population and the abnormalities are essentially localized on the left side of the brain in regions known for their specific role in language development. These abnormalities are more frequent in children with a severe phonological disorder, suggesting that they may share common pathophysiological features with SLI., Conclusion: The presence of EEG abnormalities in a large group of patients suffering from SLI associated with minor neurological abnormalities suggests a possible theoretical neurodevelopmental model. Minor neurodevelopmental abnormalities, genetically transmitted or acquired during the pre- or perinatal period, may create vulnerability towards SLI. This vulnerability, in conjunction with environmental influences such as family environment, linguistic stimuli, exposure to multiple languages, or transitory hearing loss, might take the form of SLI. This hypothesis underlines the importance of prevention and early detection of SLI when identifying vulnerable subjects. Monitoring the family early through parental guidance and early school support would facilitate the acquisition of language., (Copyright © 2012 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Dichotic listening test can estimate hemispheric dominance for language., Aim: To study the usefulness of a new set of dichotic pairs of Spanish stimuli in middle childhood., Subjects and Methods: The stratified control group comprised 40 healthy, right-handed children, aged 3.5- 7.5 years, of both sexes, with average ability at speaking Spanish. The clinical sample comprised 12 children with right spastic hemi-paretic cerebral palsy, average general intelligence and sentence repetition index over -2z. Each listening series is composed of 20 age-appropriate dichotic pairs: one syllable, word, or number; or trains of two or three syllables or numbers. Voice onset time, duration and stress of stimuli were balanced. Hemispheric dominance index (HDI) for language was calculated using a formula with the scores of stimuli from right or left ears. Statistical analysis evaluated the age-related accuracy and discriminant power of each HDI., Results: In the non-forced attention paradigm, the range of HDI is 0-200. Values of HDI ≥ 112 indicate left hemisphere dominance for language, whereas values of HDI ≤ 88 indicate right hemisphere dominance. All 40 typical subjects showed left HDI for language, without influence of age and sex. In contrast, ten out of twelve (83%) right hemiparetic children had right HDI., Conclusions: The results show that this new set of dichotic pairs is useful in the initial assessment of cerebral dominance for language and valid for use in Spanish speaking children aged 3.5 years or more.

Neural activity within HVC (proper name), a premotor nucleus of the songbird telencephalon analogous to premotor cortical regions in mammals, controls the temporal structure of learned song in male zebra finches (Taeniopygia guttata). HVC is composed of a superficially isomorphic neuronal mosaic, implying that song is encoded in a distributed network within HVC. Here, we combined HVC microlesions (10% focal ablation) with singing-driven immediate-early gene (IEG) labeling to explore the network architecture of HVC during singing. Microlesions produce a transient disruption of HVC activity that results in a temporary (≈ 1 week) loss of vocal patterning. Results showed an asymmetrical reduction in the density of IEG-labeled cells 3-5 d after microlesions: swaths of unlabeled cells extended rostrally and/or caudally depending on the position of the HVC microlesion. Labeling returned once birds recovered their songs. Axial swaths of unlabeled cells occurred whether microlesions were located at rostral or caudal poles of HVC, indicating that the localized reduction in IEG labeling could not be attributable solely to transection of afferents that enter HVC rostrally. The asymmetrical pattern of reduced IEG labeling could be explained if synaptic connectivity within HVC is organized preferentially within the rostrocaudal axis. In vivo retrograde tracer injections and in vitro stimulation and recording experiments in horizontal slices of HVC confirmed a rostrocaudal organization of HVC neural connectivity. Our findings suggest that HVC contains an axially organized network architecture that may encode the temporal structure of song.

This study investigated the requirements for restoring motor function after corticospinal (CS) system damage during early postnatal development. Activity-dependent competition between the CS tracts (CSTs) of the two hemispheres is imperative for normal development. Blocking primary motor cortex (M1) activity unilaterally during a critical period [postnatal week 5 (PW5) to PW7] produces permanent contralateral motor skill impairments, loss of M1 motor map, aberrant CS terminations, and decreases in CST presynaptic sites and spinal cholinergic interneuron numbers. To repair these motor systems impairments and restore function, we manipulated motor experience in three groups of cats after this CST injury produced by inactivation. One group wore a jacket restraining the limb ipsilateral to inactivation, forcing use of the contralateral, impaired limb, for the month after M1 inactivation (PW8-PW13; "restraint alone"). A second group wore the restraint during PW8-PW13 and was also trained for 1 h/d in a reaching task with the contralateral forelimb ("early training"). To test the efficacy of intervention during adolescence, a third group wore the restraint and received reach training during PW20-PW24 ("delayed training"). Early training restored CST connections and the M1 motor map, increased cholinergic spinal interneurons numbers on the contralateral, relative to ipsilateral, side, and abrogated limb control impairments. Delayed training restored CST connectivity and the M1 motor map but not contralateral spinal cholinergic cell counts or motor performance. Restraint alone only restored CST connectivity. Our findings stress the need to reestablish the integrated functions of the CS system at multiple hierarchical levels in restoring skilled motor function after developmental injury.

Background: The neurorehabilitation of the patient with cerebral damage implies the reestablishment of the visual functions. Botulinum toxin can be considerate as a less invasive alternative for treatment., Objective: to demonstrate the answer to the treatment using botulinum toxin of the visual motor alterations in patients with cerebral damage., Methods: Descriptive study of patients with visual alterations associated to cerebral damage. The visual treatment included three areas: sensorial, refracting and motor under quimiodenervation with botulinum toxin, of May 2009 to May 2010., Results: 48 patients were studied, age 22,4 years ± 23. The strabismus were: esotropia 52%, exotropia 39,5%, vertical 8%, nystagmus 4%. 50% of the patients had psychomotor delay. Some of the most important causes of cerebral damage were: Down syndrome, epilepsy, tumor, hydrocephalus, neuroinfection, infantile cerebral paralysis, multiple sclerosis, metabolic syndrome, cranial trauma, congenital cardiopathy, ventricular hemorrhage, cerebrovascular stroke. The dose of botulinum toxin was 8,1 UI ± 3. We registered good results in 56.5%, regular 23,9% and bad 19,5%. The global percentage of rehabilitation was 69% of correction with a r of Pearson of 0,5., Discussion: Patients with cerebral damage have diverse types of visuomotor alterations, strabismus and nystagmus.Use of botulinum toxin as a paralytic muscle agent is a good alternative in these cases., Conclusion: The botulinum toxin is an effective option for the visual rehabilitation in patients with cerebral damage and prevents the progression of more cerebral changes secondary to strabismus.

Aim: To characterize early amplitude-integrated electroencephalogram (aEEG) and single-channel EEG (aEEG/EEG) in very preterm (VPT) infants for prediction of long-term outcome., Patients: Forty-nine infants with median (range) gestational age of 25 (22-30) weeks., Methods: Amplitude-integrated electroencephalogram/EEG recorded during the first 72 h and analysed over 0-12, 12-24, 24-48 and 48-72 h, for background pattern, sleep-wake cycling, seizures, interburst intervals (IBI) and interburst percentage (IB%). In total, 2614 h of single-channel EEG examined for seizures. Survivors were assessed at 2 years corrected age with a neurological examination and Bayley Scales of Infant Development-II. Poor outcome was defined as death or survival with neurodevelopmental impairment. Good outcome was defined as survival without impairment., Results: Thirty infants had good outcome. Poor outcome (n = 19) was associated with depressed aEEG/EEG already during the first 12 h (p = 0.023), and with prolonged IBI and higher IB% at 24 h. Seizures were present in 43% of the infants and associated with intraventricular haemorrhages but not with outcome. Best predictors of poor outcome were burst-suppression pattern [76% correctly predicted; positive predictive value (PPV) 63%, negative predictive value (NPV) 91%], IBI > 6 sec (74% correctly predicted; PPV 67%, NPV 79%) and IB% > 55% at 24 h age (79% correctly predicted; PPV 72%, NPV 80%). In 35 infants with normal cerebral ultrasound during the first 3 days, outcome was correctly predicted in 82% by IB% (PPV 82%, NPV 83%)., Conclusion: Long-term outcome can be predicted by aEEG/EEG with 75-80% accuracy already at 24 postnatal hours in VPT infants, also in infants with no early indication of brain injury., (© 2012 The Author(s)/Acta Paediatrica © 2012 Foundation Acta Paediatrica.)

We present a neural network model of learning and processing the English past tense that is based on the notion that experience-dependent cortical development is a core aspect of cognitive development. During learning the model adds and removes units and connections to develop a task-specific final architecture. The model provides an integrated account of characteristic errors during learning the past tense, adult generalization to pseudoverbs, and dissociations between verbs observed after brain damage in aphasic patients. We put forward a theory of verb inflection in which a functional processing architecture develops through interactions between experience-dependent brain development and the structure of the environment, in this case, the statistical properties of verbs in the language. The outcome of this process is a structured processing system giving rise to graded dissociations between verbs that are easy and verbs that are hard to learn and process. In contrast to dual-mechanism accounts of inflection, we argue that describing dissociations as a dichotomy between regular and irregular verbs is a post hoc abstraction and is not linked to underlying processing mechanisms. We extend current single-mechanism accounts of inflection by highlighting the role of structural adaptation in development and in the formation of the adult processing system. In contrast to some single-mechanism accounts, we argue that the link between irregular inflection and verb semantics is not causal and that existing data can be explained on the basis of phonological representations alone. This work highlights the benefit of taking brain development seriously in theories of cognitive development., (Copyright 2012 APA, all rights reserved.)

Research is inconclusive on whether gender differences exist in cognitive function in persons who sustain a mild-to-moderate traumatic brain injury (TBI). Furthermore, it is also unclear whether there is a relationship between chronic stress and cognitive function in these persons. The purpose of this integrative review is to determine whether gender differences exist in cognitive function, neurobehavioral symptoms, and chronic stress levels after a mild-to-moderate TBI. Participants (n = 72) were recruited from eight outpatient rehabilitation centers. Participants completed the demographic questions, the Immediate Postconcussion Assessment Cognitive Testing neurocognitive test battery, the Perceived Stress Scale-14, and the Neurobehavioral Functioning Inventory (NFI). Gender differences were present on verbal memory composite scores (p = .033), with women performing worse than men. There were no other between-gender differences on cognitive tasks, neurobehavioral symptoms, or chronic stress. Higher chronic stress levels result in a decrease in verbal memory (p = .015) and motor processing speed (p = .006) and slower reaction time (p = .007) for women. As male NFI cognition scores increased, motor processing speed scores decreased (p = .012) and reaction time got slower (p = .019), whereas women exhibited decreased verbal memory (p = .017) and slower reaction time (p = .034). As NFI motor symptoms increased, men exhibited decreased verbal memory (p = .005), visual memory (p = .002), and motor processing speed (p = .002) and slower reaction time (p = .002). Overall, this study only found gender differences on verbal memory composite scores, whereas the remaining cognitive tasks, neurobehavioral symptoms, and chronic stress did not indicate gender differences. Correlations between chronic stress, neurobehavioral symptoms, and cognitive function differed in both men and women with TBI. Persons in the chronic phase of recovery from a TBI may benefit from training in compensatory strategies for verbal memory deficits and stress management.

Object: Oligodendrogliomas that enhance on MR images are associated with poor prognosis. However, the importance of the volume of enhancing tumor tissue, and the extent of its resection, is uncertain. The authors examined the prognostic significance of preoperative and residual postoperative enhancing tissue volumes in a large single-center series of patients with oligodendroglioma. They also examined the relationship between enhancement and characteristic genetic signatures in oligodendroglial tumors, specifically deletion of 1p and 19q (del 1p/19q)., Methods: The authors retrospectively analyzed 100 consecutive cases of oligodendroglioma involving patients who had undergone T1-weighted gadolinium-enhanced MRI at diagnosis and immediately after initial surgical intervention. The presence of preoperative enhancement was determined by consensus. Preoperative and residual postoperative volumes were measured using a quantitative, semiautomated method by a single blinded observer. Intrarater reliability for preoperative volumes was confirmed by remeasurement in a subset of patients 3 months later. Intrarater and interrater reliability for residual postoperative volumes was confirmed by remeasurement of these volumes by both the original and a second blinded observer. Multivariate analysis was used to assess the influence of contrast enhancement at diagnosis and the volume of pre- and postoperative contrast-enhancing tumor tissue on time to relapse (TTR) and overall survival (OS), while controlling for confounding clinical, pathological, and genetic factors., Results: Sixty-three of 100 patients had enhancing tumors at initial presentation. Presence of contrast enhancement at diagnosis was related to reduced TTR and OS on univariate analysis but was not significantly related on multivariate analysis. In enhancing tumors, however, greater initial volume of enhancing tissue correlated with shortened TTR (p = 0.00070). Reduced postoperative residual enhancing volume and a relatively greater resection of enhancing tissue correlated with longer OS (p = 0.0012 and 0.0041, respectively). Interestingly, patients in whom 100% of enhancing tumor was resected had significantly longer TTR (174 vs 64 weeks) and OS (392 vs 135 weeks) than those with any residual enhancing tumor postoperatively. This prognostic benefit was not consistently maintained with greater than 90% or even greater than 95% resection of enhancing tissue. There was no relationship between presence or volume of enhancement and del 1p/19q., Conclusions: In enhancing oligodendrogliomas, completely resecting enhancing tissue independently improves outcome, irrespective of histological grade or genetic status. This finding supports aggressive resection and may impact treatment planning for patients with these tumors.

Excess activation of ionotropic glutamate receptors and iron is believed to contribute to free radical production and neuronal death following hypoxic ischemia. We examined the possibility that both NMDA receptor activation and iron overload determine spatial and temporal patterns of free radical production after transient middle cerebral artery occlusion (tMCAO) in male Sprague-Dawley rats. Mitochondrial free radical (MFR) levels were maximally increased in neurons in the core at 1 h and 24 h after tMCAO. Early MFR production was blocked by administration of MK-801, an NMDA receptor antagonist, but not deferoxamine, an iron chelator. Neither MK-801 nor deferoxamine attenuated late MFR production in the core. Increased MFRs were observed in penumbral neurons within 6 h and gradually increased over 24 h after tMCAO. Slowly-evolving MFRs in the core and penumbra were accompanied by iron overload. Deferoxamine blocked iron overload but reduced MFR production only in the penumbra. Combined MK-801/deferoxamine reduced late MFR production in both core and penumbra in an additive manner. Combination therapy significantly ameliorated infarction compared with monotherapy. These findings suggest that the NMDA receptor activation and iron overload mediate late MFR production and infarction after tMCAO., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Recent rodent research has shown that the basolateral amygdala (BLA) inhibits unconditioned, or innate, fear. It is, however, unknown whether the BLA acts in similar ways in humans. In a group of five subjects with a rare genetic syndrome, that is, Urbach-Wiethe disease (UWD), we used a combination of structural and functional neuroimaging, and established focal, bilateral BLA damage, while other amygdala sub-regions are functionally intact. We tested the translational hypothesis that these BLA-damaged UWD-subjects are hypervigilant to facial expressions of fear, which are prototypical innate threat cues in humans. Our data indeed repeatedly confirm fear hypervigilance in these UWD subjects. They show hypervigilant responses to unconsciously presented fearful faces in a modified Stroop task. They attend longer to the eyes of dynamically displayed fearful faces in an eye-tracked emotion recognition task, and in that task recognize facial fear significantly better than control subjects. These findings provide the first direct evidence in humans in support of an inhibitory function of the BLA on the brain's threat vigilance system, which has important implications for the understanding of the amygdala's role in the disorders of fear and anxiety.

Background: A requisite skill for successful conversation is the ability to adjust one's language according to contextual factors., Aims: This study examined one aspect of language use in context-the use of mental-state terms, i.e. words that communicate thoughts, beliefs or feelings-in conversations between adult males with and without traumatic brain injury (TBI) and familiar partners., Methods & Procedures: Participants were five males in the chronic stage of recovery following severe TBI and five male peers matched for age, conversing with friends. Conversational context was manipulated using conversation starters that were designed to induce differing levels of self-disclosure or intimacy, with the expectation that mental-state term use would increase when participants talked about more intimate topics., Outcomes & Results: Participants in both groups used more mental-state terms in more intimate conversations; however, adults with TBI did not increase their mental-state term use to the same extent as matched peers. Adults with TBI also used a significantly different pattern of mental-state term types across intimacy levels as compared with peers., Conclusions & Implications: These quantitative and qualitative differences may contribute to social conversation problems of adults with TBI., (© 2011 Royal College of Speech and Language Therapists.)

Traumatic brain injury (TBI) and intracerebral hemorrhage (ICH) are leading causes of neurological mortality and disability in the U.S. However, therapeutic options are limited and clinical management remains largely supportive. HMG-CoA reductase inhibitors (statins) have pleiotropic mechanisms of action in the setting of acute brain injury, and have been demonstrated to improve outcomes in preclinical models of ICH and TBI. To facilitate translation to clinical practice, we now characterize the optimal statin and dosing paradigm in murine models of ICH and TBI. In a preclinical model of TBI, mice received vehicle, simvastatin, and rosuvastatin at doses of 1 mg/kg and 5 mg/kg for 5 days after the impact. Immunohistochemistry, differential gene expression, and functional outcomes (rotarod and Morris water maze testing) were assessed to gauge treatment response. Following TBI, administration of rosuvastatin 1 mg/kg was associated with the greatest improvement in functional outcomes. Rosuvastatin treatment was associated with histological evidence of reduced neuronal degeneration at 24 h post-TBI, reduced microgliosis at day 7 post-TBI, and preserved neuronal density in the CA3 region at 35 days post-injury. Administration of rosuvastatin following TBI was also associated with downregulation of inflammatory gene expression in the brain. Following ICH, treatment with simvastatin 1 mg/kg was associated with the greatest improvement in functional outcomes, an effect that was independent of hemorrhage volume. Clinically relevant models of acute brain injury may be used to define variables such as optimal statin and dosing paradigms to facilitate the rational design of pilot clinical trials.

Pedaling is widely used for rehabilitation of locomotion because it induces similar muscle activity to that observed during locomotion. However, no study has examined the effects of pedaling exercise on intracortical inhibition. The aim of the present study was to investigate the effect of pedaling exercise on short-interval intracortical inhibition (SICI) in the cortical area controlling the tibialis anterior (TA) and soleus (SOL) muscles. Ten healthy adults participated in this study and were instructed to perform 7 min of active and passive pedaling. Paired pulse transcranial magnetic stimulation (TMS) was used to investigate the SICI. Using interstimulus intervals of 2-3 ms, the SICI of TA and SOL muscles was recorded at rest before and after the pedaling and repetitive ankle dorsiflexion tasks. SICI in both TA and SOL muscles decreased immediately after active pedaling. There were no significant changes in SICI after the passive pedaling and repetitive ankle dorsiflexion. A short-term, low-intensity active pedaling exercise decreases the intracortical inhibition of the leg area of the motor cortex. Our results suggest that pedaling has the potential to restore ambulation-inducing cortical reorganization among patients with central nervous system lesions.

Following stroke, control of both the contralesional (paretic) and ipsilesional (less affected) arms is altered. The purpose of this study was to analyse the consequences of stroke on joint rotations of both shoulder girdles, that is, glenohumeral (GH) and scapula motion. Because of hemispheric specialization, we hypothesized that changes would relate to the side of hemisphere damage. Nine stroke patients with left, and 9 with right hemisphere damage (LHD and RHD) and 9 healthy subjects were included. Reaching movements to targets positioned close, far and high in three directions were recorded using an electromagnetic system. Initial and final postures of the scapula, GH and elbow joint were evaluated. Inter-joint rotations throughout the movements were analysed using principal component analysis (PCA). The main finding was that initial and final postures of the contralesional and ipsilesional shoulders differed depending on the side of brain lesion. On the contralesional side, there was less scapula protraction and GH lateral rotation for both groups. Scapula tilt was less anterior in LHD patients, and GH elevation was greater in RHD patients. On the ipsilesional side, GH lateral rotation was reduced in both groups, and scapula protraction was reduced only for LHD patients. PCA confirmed that postures of both shoulders of the LHD group were substantially different to the healthy subjects, while only the contralesional arm of the RHD subjects differed. These results add to existing knowledge of hemispheric specialization, suggesting that the left hemisphere plays a greater role in bilateral joint postures than the right hemisphere.

While a history of a single traumatic brain injury (TBI) is associated with the later development of syndromes of cognitive impairment such as Alzheimer's disease, the long-term pathology evolving after single TBI is poorly understood. However, a progressive tauopathy, chronic traumatic encephalopathy, is described in selected cohorts with a history of repetitive concussive/mild head injury. Here, post-mortem brains from long-term survivors of just a single TBI (1-47 years survival; n=39) vs. uninjured, age-matched controls (n=47) were examined for neurofibrillary tangles (NFTs) and amyloid-β (Aβ) plaques using immunohistochemistry and thioflavine-S staining. Detailed maps of findings permitted classification of pathology using semiquantitative scoring systems. NFTs were exceptionally rare in young, uninjured controls, yet were abundant and widely distributed in approximately one-third of TBI cases. In addition, Aβ-plaques were found in a greater density following TBI vs. controls. Moreover, thioflavine-S staining revealed that while all plaque-positive control cases displayed predominantly diffuse plaques, 64% of plaque-positive TBI cases displayed predominantly thioflavine-S-positive plaques or a mixed thioflavine-S-positive/diffuse pattern. These data demonstrate that widespread NFT and Aβ plaque pathologies are present in up to a third of patients following survival of a year or more from a single TBI. This suggests that a single TBI induces long-term neuropathological changes akin to those found in neurodegenerative disease., (© 2011 The Authors. Brain Pathology © 2011 International Society of Neuropathology.)

Recurrent respiratory problems are common in children with severe neurodisability, and respiratory deterioration is a leading cause of premature death in this group. Although the etiology is multifactorial, recurrent pulmonary aspiration is thought to play a significant role. Gastroesophageal reflux is known to be common, as is oral-motor discoordination. Differentiating direct aspiration of food and saliva and gastric reflux aspiration is difficult and presents a challenge in managing patients and assessing their suitability for surgical antireflux procedures. This is particularly the case when children present with predominantly respiratory symptoms, where there may be direct aspiration, reflux aspiration, neither, or both. A clinical biomarker to identify and quantify reflux aspiration would therefore be useful in surgical assessment and may also be applicable as an outcome measure for clinical trials of antireflux surgery. In this review, we discuss the evidence base behind existing and potentially novel biomarkers of aspiration in bronchoalveolar lavage fluid. We highlight the limitations of the lipid-laden macrophage index, particularly with regard to its specificity and interrater/intrarater reliability. We discuss the laboratory methods available to measure promising new biomarkers (pepsin and bile acids) and highlight their potential advantages and disadvantages. Finally, to understand how aspiration causes clinical signs and symptoms in our patients, we need to study the effect of aspirated substances on the lung, and here we review the available in vivo and in vitro literature., (Copyright © 2012 Elsevier Inc. All rights reserved.)

There is growing evidence that repeated brain concussion can result in cumulative and long-term behavioral symptoms, neuropathological changes, and neurodegeneration. Little is known about the factors and mechanisms that contribute to these effects. The current study addresses the need to investigate and better understand the effects of repeated concussion through the development of an animal model. Male Long-Evans rats received 1, 3, or 5 mild lateral fluid percussion injuries or sham injuries spaced 5 days apart. After the final injury, rats received either a short (24 h) or long (8 weeks) post-injury recovery period, followed by a detailed behavioral analysis consisting of tests for rodent anxiety-like behavior, cognition, social behavior, sensorimotor function, and depression-like behavior. Brains were examined immunohistochemically to assess neuroinflammation and cortical damage. Rats given 1, 3, or 5 mild percussion injuries displayed significant short-term cognitive impairments. Rats given repeated mild percussion injuries displayed significantly worse short- and long-term cognitive impairments. Rats given 5 mild percussion injuries also displayed increased anxiety- and depression-like behaviors. Neuropathological analysis revealed short-term neuroinflammation in 3-injury rats, and both short- and long-term neuroinflammation in 5-injury rats. There was also evidence that repeated injuries induced short- and long-term cortical damage. These cumulative and long-term changes are consistent with findings in human patients suffering repeated brain concussion, provide support for the use of repeated mild lateral fluid percussion injuries to study repeated concussion in the rat, and suggest that neuroinflammation may be important for understanding the cumulative and chronic effects of repeated concussion.

Intraoperative Neurophysiological Mo-nitoring (IONM) identifies eloquent areas or nerves fibers during neurosurgical interventions and monitors their function. For several interventions IONM has become mandatory in neurosurgery. IONM increases patient safety during surgery as the risk of neurological deficits is reduced. Safer surgery reduces the time needed for the intervention and thereby reduces risk. IONM contributes to complete resection of tumors, which in turn prolongs patients' survival. Complicated surgical interventions associated with an elevated risk of neurological deficits have only become possible due to IONM. IONM comprises a variety of procedures that are selected for a particular intervention. With appropriate selection of the procedures IONM has been shown to improve neurological and functional outcome after neurosurgical interventions.

Studies of patients with major depressive disorder (MDD) and schizophrenia (SCH) have revealed reduced hippocampal volumes, but findings have been inconsistent due to sample and measurement differences. The current study sought to measure this structure in a large sample of MDD, SCH, and healthy subjects, using a strict measurement protocol, to elucidate morphological-specific volumetric differences. Patients with treatment-resistant MDD (N = 182) and treatment-resistant SCH with auditory-verbal hallucinations (N = 52), and healthy controls (N = 76) underwent psychiatric assessments and brain MRI. The findings indicate that (1) MDD and SCH patients have reduced total hippocampal volume which was marked in the tails (more so in patients with MDD), (2) region of interest estimation protocols and sample characteristics may help explain volumetric differences between previous SCH studies., (Copyright © 2010 Wiley Periodicals, Inc., Inc.)

Diminished emotional recognition, expression, and responsivity are frequent legacies of traumatic brain injury (TBI) that can have an adverse impact on relationships and psychosocial recovery. However, assessment of emotion responsivity is often difficult because many patients lack insight into their altered personality. To overcome this obstacle, we used a physiological measure of emotion responsivity, the startle reflex, to examine how this can vary according to the affective valence of stimuli by comparing a TBI group with a matched control group. The study also examined whether weaknesses of attention and speed of information processing could account for differences in startle modulation across groups. Sixty-four TBI patients and controls completed the startle reflex procedure. Participants were presented with pictures that differed in affective valence, and measures were taken of eyeblink startle responses to an acoustic probe. Subjective ratings of affect and arousal for each picture were obtained, and TBI patients completed measures of attention and information processing. Results revealed that the TBI group did not show the pattern of startle modulation observed in the control group. Whilst pleasant pictures produced the usual attenuation of the startle response, startle responses to unpleasant pictures were significantly lower in the TBI group than in controls. No significant correlations emerged between startle responses and performance on neuropsychological measures in the TBI group. The TBI group also rated unpleasant pictures as significantly less arousing than did controls. The results provide partial support for a growing body of evidence that has proposed impaired emotion responsivity following TBI.

Background: Preterm infants with progressive post-hemorrhagic ventricular dilatation (PHVD) in the absence of associated parenchymal lesions may have a normal neurodevelopmental outcome., Objectives: To evaluate neurodevelopmental and cognitive outcomes among preterm infants with severe intraventricular hemorrhage (IVH) and PHVD requiring neurosurgical intervention., Methods: 32 preterm infants were admitted to a neonatal intensive care unit with PHVD requiring neurosurgical intervention, and were seen in the follow-up clinic for standardized cognitive, behavioral and neurological assessments between 5 and 8 years of age. Only preterm infants with a gestational age (GA) of <30 weeks, as well as preterm and full-term infants with PHVD and full-term infants with perinatal asphyxia are seen in our follow-up clinic at this age. There were 23 infants with a GA of <30 weeks in this study population. For these 23, matched controls were available and compared with the IVH group., Results: The majority (59.4%) had no impairments. None of the children with grade III and 8 of the 15 children (53%) with grade IV hemorrhage developed cerebral palsy. More subtle motor problems assessed with the Movement-ABC score were seen in 39% (n = 9); the mean IQ of all children was 93.4, and 29% of the children had an IQ of <85 (-1 SD). Timing of intervention did not have a beneficial effect on outcome. With respect to cognition, no significant differences were found between the IVH and the control group., Conclusion: The majority of the children in our population had no impairments. Cerebral palsy was not seen in any of the infants with a grade III hemorrhage., (Copyright © 2011 S. Karger AG, Basel.)

Aim: The current study aimed to test the intensity of spontaneous emotional expressions and the accuracy of posed emotional expressions in patients with severe traumatic brain injury (TBI)., Method: Twenty-three participants with TBI and 27 matched control participants were asked to relate personal angry, happy, and sad events (spontaneous expressivity) and to pose angry, happy, and sad expressions in response to a photo or word cue (posed expressivity). Their emotional facial expressions were coded via judges' ratings., Results: Participants with TBI had less intense sad expressions when relating a sad event than did control participants. No group difference emerged in the happy and angry events, the latter possibly due to differentially low interrater reliability for anger ratings. Participants with TBI were impaired in their ability to pose sad emotions., Conclusions: These preliminary findings suggest that patients with TBI are impaired at expressing sad expressions either spontaneously or deliberately. This may reflect difficulties in the initiation or suppression of facial expression as well as an impaired semantic knowledge of the facial configuration of sad expression.