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"Brain damage Imaging."
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Semantic representation in the white matter pathway
Object conceptual processing has been localized to distributed cortical regions that represent specific attributes. A challenging question is how object semantic space is formed. We tested a novel framework of representing semantic space in the pattern of white matter (WM) connections by extending the representational similarity analysis (RSA) to structural lesion pattern and behavioral data in 80 brain-damaged patients. For each WM connection, a neural representational dissimilarity matrix (RDM) was computed by first building machine-learning models with the voxel-wise WM lesion patterns as features to predict naming performance of a particular item and then computing the correlation between the predicted naming score and the actual naming score of another item in the testing patients. This correlation was used to build the neural RDM based on the assumption that if the connection pattern contains certain aspects of information shared by the naming processes of these two items, models trained with one item should also predict naming accuracy of the other. Correlating the neural RDM with various cognitive RDMs revealed that neural patterns in several WM connections that connect left occipital/middle temporal regions and anterior temporal regions associated with the object semantic space. Such associations were not attributable to modality-specific attributes (shape, manipulation, color, and motion), to peripheral picture-naming processes (picture visual similarity, phonological similarity), to broad semantic categories, or to the properties of the cortical regions that they connected, which tended to represent multiple modality-specific attributes. That is, the semantic space could be represented through WM connection patterns across cortical regions representing modality-specific attributes.
Journal Article
Preconditioning Exercise in Rats Attenuates Early Brain Injury Resulting from Subarachnoid Hemorrhage by Reducing Oxidative Stress, Inflammation, and Neuronal Apoptosis
Subarachnoid hemorrhage (SAH) is a catastrophic form of stroke responsible for significant morbidity and mortality. Oxidative stress, inflammation, and neuronal apoptosis are important in the pathogenesis of early brain injury (EBI) following SAH. Preconditioning exercise confers neuroprotective effects, mitigating EBI; however, the basis for such protection is unknown. We investigated the effects of preconditioning exercise on brain damage and sensorimotor function after SAH. Male rats were assigned to either a sham-operated (Sham) group, exercise (Ex) group, or no-exercise (No-Ex) group. After a 3-week exercise program, they underwent SAH by endovascular perforation. Consciousness level, neurological score, and sensorimotor function were studied. The expression of nuclear factor erythroid 2 p45-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), 4-hydroxynonenal (4HNE), nitrotyrosine (NT), ionized calcium-binding adaptor molecule 1 (Iba1), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin 1β (IL-1β), 14–3-3γ,
p
-β-catenin Ser37, Bax, and caspase-3 were evaluated by immunohistochemistry or western blotting. The terminal deoxynucleotidyl transferase-mediated biotinylated dUTP nick end labeling (TUNEL) assay was also performed. After SAH, the Ex group had significantly reduced neurological deficits, sensorimotor dysfunction, and consciousness disorder compared with the No-Ex group. Nrf2, HO-1, and 14–3-3γ were significantly higher in the Ex group, while 4HNE, NT, Iba1, TNF-α, IL-6, IL-1β, Bax, caspase-3, and TUNEL-positive cells were significantly lower. Our findings suggest that preconditioning exercise ameliorates EBI after SAH. The expression of 4HNE and NT was reduced by Nrf2/HO-1 pathway activation; additionally, both oxidative stress and inflammation were reduced. Furthermore, preconditioning exercise reduced apoptosis, likely via the 14–3-3γ/
p
-β-catenin Ser37/Bax/caspase-3 pathway.
Journal Article
Preterm infants with isolated cerebellar hemorrhage show bilateral cortical alterations at term equivalent age
The cerebellum is connected to numerous regions of the contralateral side of the cerebrum. Motor and cognitive deficits following neonatal cerebellar hemorrhages (CbH) in extremely preterm neonates may be related to remote cortical alterations, following disrupted cerebello-cerebral connectivity as was previously shown within six CbH infants. In this retrospective case series study, we used MRI and advanced surface-based analyses to reconstruct gray matter (GM) changes in cortical thickness and cortical surface area in extremely preterm neonates (median age = 26; range: 24.9–26.7 gestational weeks) with large
isolated
unilateral CbH (
N
= 5 patients). Each CbH infant was matched with their own preterm infant cohort (range: 20–36 infants) based on sex and gestational age at birth. On a macro level, our data revealed that the contralateral cerebral hemisphere of CbH neonates did not show less cortical thickness or cortical surface area than their ipsilateral cerebral hemisphere at term. None of the cases differed from their matched cohort groups in average cortical thickness or average cortical surface area in the ipsilateral or contralateral cerebral hemisphere. On a micro (i.e. vertex) level, we established high variability in significant local cortical GM alteration patterns across case-cohort groups, in which the cases showed thicker or bigger volume in some regions, among which the caudal middle frontal gyrus, insula and parahippocampal gyrus, and thinner or less volume in other regions, among which the cuneus, precuneus and supratentorial gyrus. This study highlights that cerebellar injury during postnatal stages may have widespread bilateral influence on the early maturation of cerebral cortical regions, which implicate complex cerebello-cerebral interactions to be present at term birth.
Journal Article
Meta-Cognitive Ability and Brain Damage in Autoimmune Encephalitis: A Case Report
Autoimmune encephalitis is an important contributor to rapidly progressive cognitive and behavioral decline. The purpose of this work was to evaluate the effects of cognitive rehabilitation in a patient with autoimmune encephalitis. We also wanted to evaluate the effectiveness of rehabilitative treatment by monitoring the cognitive and metacognitive outcomes over a time interval. We reported a case of 22 year-old female patient with autoimmune encephalitis, cognitive behavioral impairments, and severe reduction in metarepresentational capacity. We performed an assessment of personality, neuropsychological, and meta-cognitive functions at the beginning of the rehabilitative training. The last evaluation was performed six months after the discharge from the rehabilitation unit. We applied a combination of remediation, psycho-educational treatment, and psychotherapy to improve the knowledge and the empathy of the patient, to promote the selfcontrol strategies, and to prompt better behavioral management. Our findings revealed an improvement in the performance of the individual tests after rehabilitative training.
Journal Article
Which CT features help predict outcome after head injury?
Background: Information collected at baseline can be useful in predicting patient outcome after head injury. The appearance of the CT brain scan may add useful baseline information. The aim of this study was to evaluate which features on the admission CT scan might add significantly to other baseline clinical information for predicting survival in patients with head injury. Methods: Baseline CT scans were reviewed for patients with all grades of traumatic head injury in a head injury registry, in which baseline demographic and injury status and outcome at 1 year were recorded. Details from the CT scan on haemorrhage, brain swelling, and focal or diffuse damage were noted blind to clinical or outcome information and the scans classified according to the simple seven point grading (normal, mild, moderate, or severe focal injury, mild, moderate, or severe diffuse injury). An existing CT scoring system, the trauma coma databank (TCDB) classification, was also used. Logistic regression modelling was used to test the value of the CT appearance, in addition to the other baseline clinical characteristics, in predicting survival at 1 year. Results: 425 CT scans were read from patients with all severities of injury. Significant independent outcome predictors were age, Glasgow coma score (GCS), pupil reaction, presence of subarachnoid blood, and the simple grading of the overall appearance of the scan (all p<0.001). The TCDB classification was not a significant predictor of outcome. Conclusion: Age, GCS, and pupil reaction were all previously shown to be significant predictors of patient survival after head injury. A further two, easy to identify, CT scan variables are independent prognostic variables, and might help to identify patients at high risk of death at the time of admission.
Journal Article
Showing No Spot Sign Is a Strong Predictor of Independent Living after Intracerebral Haemorrhage
Background: A spot sign on computed tomography angiography (CTA) is a potentially strong predictor of poor outcome on ultra-early radiological imaging. The aim of this study was to assess the spot sign as a predictor of functional outcome at 3 months as well as long-term mortality, with a focus on the ability to identify patients with a spontaneous, acceptable outcome. Methods: In a prospective, consecutive single-centre registry of acute stroke patients, we investigated patients with spontaneous intracerebral haemorrhage (ICH) admitted within 4.5 h after symptom onset from April 2009 to January 2013. The standard work-up in our centre included CTA for spot sign status, unless a contraindication was present. Modified Rankin Scale (mRS) scores were assessed at 3 months in the outpatient clinic or by telephone interviews. Long-term mortality was assessed by electronic chart follow-up for up to 1,500 days. Results: Of the 128 patients, 37 (28.9%) had a spot sign on admission CTA. The presence of a spot sign was associated with larger median admission haematoma volume [38.0 ml (IQR 18.0-78.0) vs. 12.0 ml (5.0-24.0); p < 0.0001] and higher median National Institutes of Health Stroke Scale score [19 (IQR 12-23) vs. 12 (6-16); p < 0.0001]. Three months after stroke, the median functional outcome was considerably better in patients without spot sign [mRS score 3 (IQR 2-4) vs. 6 (4-6); p < 0.0001]. The absence of a spot sign showed a sensitivity and specificity for good outcome (mRS scores 0-2) of 0.91 and 0.36, respectively. The presence of a spot sign was, in multivariate models, an independent inverse predictor of good 3-month outcome (OR 0.17; 95% CI: 0.03-0.88) as well as a prominent independent predictor of poor 3-month outcome (mRS scores 5-6; OR 3.40; 95% CI: 1.10-10.5) and death during follow-up (HR 3.04; 95% CI: 1.45-6.34). Patients with a spot sign surviving the acute phase had long-term survival comparable to patients with no spot sign. Conclusion: The absence or presence of a spot sign is a reliable ultra-early predictor of long-term mortality and functional outcome in patients with spontaneous ICH.
Journal Article
Serial Transcranial Doppler Measurements in Traumatic Brain Injury with Special Focus on the Early Posttraumatic Period
Cerebral ischemia is considered a key factor in the development of secondary damage after Traumatic Brain Injury (TBI). Studies on Cerebral Blood Flow (CBF) have documented decreased flow in over 50% of patients with TBI, studied in the acute phase. Transcranial Doppler (TCD) sonography is a non-invasive technique, permitting frequent or continuous measurements of blood flow velocity in the basal cerebral arteries.
To investigate the potential of TCD to detect decreased blood flow velocity in the early phase after TBI;To investigate whether flow velocity differs between hemispheres in patients with focal lesions versus those with more diffuse injuries;To investigate if decreased blood flow velocity is indicative of cerebral ischemia, as evidenced by measurements of brain tissue pO(2).
TCD examinations were performed in 57 patients with severe TBI (GCS
Journal Article
Modification of glucose metabolism in radiation-induced brain injury areas using cervical spinal cord stimulation
Purpose
Radiation-induced brain injury (RBI) is an insidious side-effect of radiotherapy mediated by vascular alterations, inflammation and ischaemia. In previous studies we had shown potential increases in loco-regional blood flow and glucose metabolism in brain tumours by using electrical cervical spinal cord stimulation (SCS). In this preliminary report we demonstrate the effect of cervical SCS on RBI-tissue metabolism, as assessed using [
18
F]fluorodeoxyglucose-positron emission tomography (FDG-PET).
Methods
SCS devices were inserted in eight patients with diagnosis of potential RBI in previously irradiated areas. While the SCS device was deactivated, each patient underwent an initial FDG-PET study to evaluate the clinical status. A second FDG-PET study was performed later the same day while the SCS device was activated in order to evaluate the effect of cervical SCS on glucose metabolism.
Results
Basal glucose metabolism in RBI areas was 31% lower than peri-RBI areas (
p
= 0.009) and 32% lower than healthy contra-lateral areas (
p
= 0.020). There was a significant increase in glucose uptake during SCS in both the RBI (
p
= 0.005) and the peri-RBI (
p
= 0.004) areas, with measured increases of 38 and 42%, respectively. The estimated potential maximal residual activity of the first FDG dose’s contribution to the activity on the second scan was ≤14.3 ± 4.6%.
Conclusions
In this study using PET, SCS increased glucose metabolism in RBI and peri-RBI areas. These results warrant further clinical investigation to elucidate more fully the clinical usefulness of SCS in these patients.
Journal Article
Increase of interstitial glycerol reflects the degree of ischaemic brain damage: a PET and microdialysis study in a middle cerebral artery occlusion-reperfusion primate model
OBJECTIVE To evaluate interstitial glycerol as a marker of ischaemia by studying the changes in glycerol in direct relation to changes in regional cerebral metabolic rate of oxygen (CMRO2), the lactate/pyruvate ratio (LP ratio), and glutamate. METHODS Transorbital 2 hour middle cerebral artery occlusion (MCAO) was performed in eight monkeys, which were studied with continuous microdialysis for 24 hours. Interstitial fluids were collected by microdialysis and analysed for glycerol, lactate, pyruvate, and glutamate with an enzymatic assay and high performance liquid chromatography. Sequential PET studies of cerebral blood flow (CBF), CMRO2, oxygen extraction ratio (OER), and cerebral blood volume (CBV) were performed. The microdialysis probe regions were classified as severe ischaemia or penumbra, depending on whether the mean CMRO2 side to side ratio was below or above 60%, respectively. RESULTS A nine-fold, sustained increase in glycerol was registered after MCAO in severe ischaemia regions. In penumbra regions, the increase in glycerol was five-fold, but the glycerol concentration returned to baseline within 8 hours of clip removal. The difference between severe ischaemia and penumbra glycerol values was statistically significant. As expected from previous studies, the interstitial LP ratio and glutamate increased markedly in severe ischaemia, with a less pronounced change in penumbra regions. There was a time lag between the biochemical changes in severe ischaemia regions, with the LP ratio preceding glutamate, followed by glycerol. CONCLUSIONS A marked, sustained increase in interstitial glycerol is indicative of severe ischaemia in this stroke model. A transient, diminutive increase in interstitial glycerol may reflect a penumbra situation. Interstitial glycerol in combination with other biochemical markers such as the LP ratio and glutamate may be useful for clinical monitoring of the ischaemic brain, reflecting a sequence of secondary pathophysiological events.
Journal Article