Posterior Brain Research Articles

Eigenvector centrality dynamics are related to Alzheimer's disease pathological changes in non-demented individuals.

Amyloid-β accumulation starts in highly connected brain regions and is associated with functional connectivity alterations in the early stages of Alzheimer's disease. This regional vulnerability is related to the high neuronal activity and strong fluctuations typical of these regions. Recently, dynamic functional connectivity was introduced to investigate changes in functional network organization over time. High dynamic functional connectivity variations indicate increased regional flexibility to participate in multiple subnetworks, promoting functional integration. Currently, only a limited number of studies have explored the temporal dynamics of functional connectivity in the pre-dementia stages of Alzheimer's disease. We study the associations between abnormal cerebrospinal fluid amyloid and both static and dynamic properties of functional hubs, using eigenvector centrality, and their relationship with cognitive performance, in 701 non-demented participants from the European Prevention of Alzheimer's Dementia cohort. Voxel-wise eigenvector centrality was computed for the whole functional magnetic resonance imaging time series (static), and within a sliding window (dynamic). Differences in static eigenvector centrality between amyloid positive (A+) and negative (A-) participants and amyloid-tau groups were found in a general linear model. Dynamic eigenvector centrality standard deviation and range were compared between groups within clusters of significant static eigenvector centrality differences, and within 10 canonical resting-state networks. The effect of the interaction between amyloid status and cognitive performance on dynamic eigenvector centrality variability was also evaluated with linear models. Models were corrected for age, sex, and education level. Lower static centrality was found in A+ participants in posterior brain areas including a parietal and an occipital cluster; higher static centrality was found in a medio-frontal cluster. Lower eigenvector centrality variability (standard deviation) occurred in A+ participants in the frontal cluster. The default mode network and the dorsal visual networks of A+ participants had lower dynamic eigenvector centrality variability. Centrality variability in the default mode network and dorsal visual networks were associated with cognitive performance in the A- and A+ groups, with lower variability being observed in A+ participants with good cognitive scores. Our results support the role and timing of eigenvector centrality alterations in very early stages of Alzheimer's disease and show that centrality variability over time adds relevant information on the dynamic patterns that cause static eigenvector centrality alterations. We propose that dynamic eigenvector centrality is an early biomarker of the interplay between early Alzheimer's disease pathology and cognitive decline.

Investigating the Impact of Delivery Routes for Exon Skipping Therapies in the CNS of DMD Mouse Models

Nucleic acid-based therapies have demonstrated great potential for the treatment of monogenetic diseases, including neurologic disorders. To date, regulatory approval has been received for a dozen antisense oligonucleotides (ASOs); however, these chemistries cannot readily cross the blood-brain barrier when administered systemically. Therefore, an investigation of their potential effects within the central nervous system (CNS) requires local delivery. Here, we studied the brain distribution and exon-skipping efficacy of two ASO chemistries, PMO and tcDNA, when delivered to the cerebrospinal fluid (CSF) of mice carrying a deletion in exon 52 of the dystrophin gene, a model of Duchenne muscular dystrophy (DMD). Following intracerebroventricular (ICV) delivery (unilateral, bilateral, bolus vs. slow rate, repeated via cannula or very slow via osmotic pumps), ASO levels were quantified across brain regions and exon 51 skipping was evaluated, revealing that tcDNA treatment invariably generates comparable or more skipping relative to that with PMO, even when the PMO was administered at higher doses. We also performed intra-cisterna magna (ICM) delivery as an alternative route for CSF delivery and found a biased distribution of the ASOs towards posterior brain regions, including the cerebellum, hindbrain, and the cervical part of the spinal cord. Finally, we combined both ICV and ICM injection methods to assess the potential of an additive effect of this methodology in inducing efficient exon skipping across different brain regions. Our results provide useful insights into the local delivery and associated efficacy of ASOs in the CNS in mouse models of DMD. These findings pave the way for further ASO-based therapy application to the CNS for neurological disease.

Neurologic Consultations and Headache during Pregnancy and in Puerperium: A Retrospective Chart Review.

Headache is a common symptom during pregnancy and in puerperium that requires careful consideration, as it may be caused by a life-threatening condition. Headaches in pregnant women and women in puerperium are classified as primary or secondary; acute, severe and newly diagnosed headaches should prompt further investigation. We aimed to further characterise the demographic features, symptoms, examination findings, and neuroimaging results of cases of headache during pregnancy and in puerperium. All pregnant women or women in postpartum conditions who attended neurological consultations at the emergency department of the clinic for Gynaecology, Obstetrics and Reproductive Medicine of Saarland University/Germany between 2001/2015 and 2012/2019 were enrolled in this retrospective chart review. Data collected from the charts included demographic/pregnancy characteristics, clinical features and imaging findings. Descriptive statistics as well as binary logistic regression were performed. More than 50% of 97 patients had abnormal findings in their neurological examination. Magnetic resonance imaging findings were pathological for almost 20% of patients-indicating conditions such as cerebral venous thrombosis, reversible posterior leukoencephalopathy, brain tumour and intracranial bleeding. The odds of abnormal neuroimaging results were 2.2-times greater among women with abnormal neurological examination findings than among those with normal examination results. In cases of headache during pregnancy and in puerperium, neuroimaging should be indicated early on. Further research is needed to determine which conditions indicate a need for immediate neuroimaging.

Diffusion tensor imaging reveals sex differences in pain sensitivity of rats.

Studies on differences in brain structure and function according to sex are reported to contribute to differences in behavior and cognition. However, few studies have investigated brain structures or used tractography to investigate gender differences in pain sensitivity. The identification of tracts involved in sex-based structural differences that show pain sensitivity has remained elusive to date. Here, we attempted to demonstrate the sex differences in pain sensitivity and to clarify its relationship with brain structural connectivity. In this study, pain behavior test and brain diffusion tensor imaging (DTI) were performed in male and female rats and tractography was performed on the whole brain using fiber tracking software. We selected eight brain regions related to pain and performed a tractography analysis of these regions. Fractional anisotropy (FA) measurements using automated tractography revealed sex differences in the anterior cingulate cortex (ACC)-, prefrontal cortex (PFC)-, and ventral posterior thalamus-related brain connections. In addition, the results of the correlation analysis of pain sensitivity and DTI tractography showed differences in mean, axial, and radial diffusivities, as well as FA. This study revealed the potential of DTI for exploring circuits involved in pain sensitivity. The behavioral and functional relevance's of measures derived from DTI tractography is demonstrated by their relationship with pain sensitivity.

Polysorbate 80-coated albumin nanoparticles to deliver paclitaxel into the brain to treat glioma.

Aim: To develop stable paclitaxel (PTX)-loaded bovine serum albumin (BSA) nanoparticles (BSA-NPs-PTX) as drug-delivery vehicles for delivering paclitaxel into the brain to treat glioma. Methods: This study used PTX-loadedBSA NPs coated with polysorbate 80 (Ps 80) to enhance PTX concentration in the brain. Results: The low IC50 indicated that the fabricated BSA-NPs-PTX and BSA-NPs-PTX-Ps 80 showed significantly enhanced cytotoxicity. The pharmacokinetic and biodistribution analysis of BSA-NPs-PTX and BSA-NPs-PTX 80 showed comparable pharmacokinetic profiles but were significantly different compared with free PTX. Conclusion: BSA-NPs-PTX-Ps 80 exhibited higher plasma concentration-time curves, as compared with BSA-NPs-PTX and PTX. BSA-NPs-PTX and BSA-NPs-PTX-Ps 80 showed significantly improved PTX distribution in the frontal cortex, posterior brain and cerebellum.

Systematic evaluation of high-level visual deficits and lesions in posterior cerebral artery stroke.

Knowledge about the consequences of stroke on high-level vision comes primarily from single case studies of patients selected based on their behavioural profiles, typically patients with specific stroke syndromes like pure alexia or prosopagnosia. There are, however, no systematic, detailed, large-scale evaluations of the more typical clinical behavioural and lesion profiles of impairments in high-level vision after posterior cerebral artery stroke. We present behavioural and lesion data from the Back of the Brain project, to date the largest (N = 64) and most detailed examination of patients with cortical posterior cerebral artery strokes selected based on lesion location. The aim of the current study was to relate behavioural performance with faces, objects and written words to lesion data through two complementary analyses: (i) a multivariate multiple regression analysis to establish the relationships between lesion volume, lesion laterality and the presence of a bilateral lesion with performance and (ii) a voxel-based correlational methodology analysis to establish whether there are distinct or separate regions within the posterior cerebral artery territory that underpin the visual processing of words, faces and objects. Behaviourally, most patients showed more general deficits in high-level vision (n = 22) or no deficits at all (n = 21). Category-selective deficits were rare (n = 6) and were only found for words. Overall, total lesion volume was most strongly related to performance across all three domains. While behavioural impairments in all domains were observed following unilateral left and right as well as bilateral lesions, the regions most strongly related to performance mainly confirmed the pattern reported in more selective cases. For words, these included a left hemisphere cluster extending from the occipital pole along the fusiform and lingual gyri; for objects, bilateral clusters which overlapped with the word cluster in the left occipital lobe. Face performance mainly correlated with a right hemisphere cluster within the white matter, partly overlapping with the object cluster. While the findings provide partial support for the relative laterality of posterior brain regions supporting reading and face processing, the results also suggest that both hemispheres are involved in the visual processing of faces, words and objects.

Characterization of spastic paraplegia in a family with a novel PSEN1 mutation.

Spastic paraparesis has been described to occur in 13.7% of PSEN1 mutations and can be the presenting feature in 7.5%. In this paper, we describe a family with a particularly young onset of spastic paraparesis due to a novel mutation in PSEN1 (F388S). Three affected brothers underwent comprehensive imaging protocols, two underwent ophthalmological evaluations and one underwent neuropathological examination after his death at age 29. Age of onset was consistently at age 23 with spastic paraparesis, dysarthria and bradyphrenia. Pseudobulbar affect followed with progressive gait problems leading to loss of ambulation in the late 20s. Cerebrospinal fluid levels of amyloid-β, tau and phosphorylated tau and florbetaben PET were consistent with Alzheimer's disease. Flortaucipir PET showed an uptake pattern atypical for Alzheimer's disease, with disproportionate signal in posterior brain areas. Diffusion tensor imaging showed decreased mean diffusivity in widespread areas of white matter but particularly in areas underlying the peri-Rolandic cortex and in the corticospinal tracts. These changes were more severe than those found in carriers of another PSEN1 mutation, which can cause spastic paraparesis at a later age (A431E), which were in turn more severe than among persons carrying autosomal dominant Alzheimer's disease mutations not causing spastic paraparesis. Neuropathological examination confirmed the presence of cotton wool plaques previously described in association with spastic parapresis and pallor and microgliosis in the corticospinal tract with severe amyloid-β pathology in motor cortex but without unequivocal disproportionate neuronal loss or tau pathology. In vitro modelling of the effects of the mutation demonstrated increased production of longer length amyloid-β peptides relative to shorter that predicted the young age of onset. In this paper, we provide imaging and neuropathological characterization of an extreme form of spastic paraparesis occurring in association with autosomal dominant Alzheimer's disease, demonstrating robust diffusion and pathological abnormalities in white matter. That the amyloid-β profiles produced predicted the young age of onset suggests an amyloid-driven aetiology though the link between this and the white matter pathology remains undefined.

Reproductive phase-dependent and sexually dimorphic expression of leptin and its receptor in different parts of brain of spotted snakehead Channa punctata.

The reproductive phase-wise leptin (lep) and its receptor (lepr) expression in different parts of the brain of adult male and female spotted snakehead Channa punctata reveals sexual dimorphism in the brain leptin system. In anterior, middle and posterior parts of the brain of males, a maximum lep was observed in resting, spawning and postspawning reproductive phases, respectively. In females, a high level of lep was seen during the preparatory phase in the anterior brain, preparatory and postspawning phases in the middle brain and resting and postspawning phases in the posterior brain. Nonetheless, the transcript level of lepr was recorded highest during the spawning phase, irrespective of sex and region of the brain. Regardless of the reproductive state of fishes, lep and lepr were seen considerably high in middle and posterior parts of male brain than that of female, implying the involvement of factors other than sex steroids for sex-related variation in the leptin system in these regions of the brain. Nonetheless, no sex difference was evidenced in the expression of either ligand or its receptor in the anterior brain. In summary, the presence of lep and lepr in different regions of the brain and variation in their expression depending on sex and reproductive phases raise the possibility of pivotal actions of leptin in influencing neuronal circuitry and thereby reproductive functions.

Posterior white matter integrity and self-reported posterior cortical symptoms using the Colorado Posterior Cortical Questionnaire.

The Colorado Posterior Cortical Questionnaire (CPC-Q) is a self-report, 15-item screening questionnaire for posterior cortical symptoms, including visuospatial and visuoperceptual difficulties. Changes in white matter connectivity may precede obvious gray matter atrophy in neurodegenerative conditions, especially posterior cortical atrophy. Integration of CPC-Q scores and measures of white matter integrity could contribute to earlier detection of posterior cortical syndromes. We investigated the relationships between posterior cortical symptoms as captured by the CPC-Q and diffusion tensor imaging fractional anisotropy (DTI FA) of white matter regions of interest localized to posterior brain regions (posterior thalamic radiations, splenium of corpus callosum, tapetum). Comparisons were also made by diagnostic group [healthy older adult (n = 31), amnestic Alzheimer's disease (AD, n = 18), and posterior cortical atrophy (PCA, n = 9)] and by SENAS battery visuospatial composite score quartile. Exploratory comparisons of all available individual white matter region DTI FA to CPC-Q, as well as comparisons of DTI FA between diagnostic groups and visuospatial quartiles, were also made. CPC-Q score was correlated with the average DTI FA for the averaged posterior white matter regions of interest (r = -0.31, p = 0.02). Posterior thalamic radiation DTI FA was most strongly associated with CPC-Q (r = -0.34, p = 0.01) and visuospatial composite (r = 0.58, p < 0.01) scores and differed between the PCA and AD groups and the lower and higher visuospatial quartiles. The DTI FA of body and splenium of the corpus callosum also demonstrated this pattern but not the DTI FA of the tapetum. The integrity of posterior white matter tracts is associated with scores on the CPC-Q, adding to the validation evidence for this new questionnaire. White matter regions that may be related to posterior cortical symptoms detected by the CPC-Q, and distinct from those affected in amnestic syndromes, include the posterior thalamic radiations and body and splenium of the corpus callosum. These findings are in line with previous neuroimaging studies of PCA and support continued research on white matter in posterior cortical dysfunction.

Oscillatory brain responses to emotional stimuli are effects related to events rather than states.

Emotional cues draw attention, thereby enabling enhanced processing. Electrophysiological brain research in humans suggests that increased gamma band activity and decreased alpha band activity over posterior brain areas is associated with the allocation of attention. However, emotional events can alternate quickly, like rapidly changing news items and it remains unknown whether the modulation of brain oscillations happens in a stimulus induced manner, changing with each individual stimulus, or whether the events lead to prolonged, state-like changes. To investigate this, we measured the electroencephalogram (EEG) during a passive viewing task (N = 32) while emotional pictures International Affective Picture System (IAPS) were presented in blocks containing either pleasant and neutral or unpleasant and neutral pictures. As predicted, we found decreased alpha and increased gamma power over posterior areas in response to unpleasant compared to pleasant pictures (and also compared to neutral pictures for gamma power). When testing the neutral pictures of the unpleasant and pleasant block against each other, we found no significant difference, which speaks to a stimulus induced effect of alpha and gamma power rather than a state effect. In addition, the inter-trial interval (ITI) between the pictures did not differ between the unpleasant and pleasant block either, corroborating this conclusion. Since emotional pictures can at the same time elicit a freezing-like response and we were interested in whether this freezing-like response co-occurs with enhanced attention, we also collected postural sway data. However, within this EEG-setup, postural analyses indicated no stimulus-related effects nor a correlation with EEG-data. We interpret the alpha and gamma band results as reflecting event-related attention toward unpleasant compared to pleasant (and neutral) pictures and discuss this finding in light of previous EEG research and in combination with behavioral research on threat-induced reductions in body sway (freezing-like response).

First Trimester Ultrasound Detection of Fetal Central Nervous System Anomalies.

To evaluate the potential of the first-trimester ultrasound (US) features for the detection of central nervous system (CNS) anomalies. Methods/Methodology: This is a prospective one-center three-year study. Unselected singleton pregnant women were examined using an extended first-trimester anomaly scan (FTAS) that included the CNS assessment: the calvaria shape, the septum (falx cerebri), the aspect of the lateral ventricles, the presence of the third ventricle and aqueduct of Sylvius (AS) and the posterior brain morphometry: the fourth ventricle, namely intracranial translucency (IT), brain stem/brain stem-occipital bone ratio (BS/BSOB) and cisterna magna (CM). The spine and underlying skin were also evaluated. The cases were also followed during the second and third trimesters of pregnancy and at delivery. FTAS efficiency to detect major CNS abnormalities was calculated. We detected 17 cases with CNS major abnormalities in a population of 1943 first-trimester (FT) fetuses, including spina bifida with myelomeningocele, exencephaly-anencephaly, holoprosencephaly, hydrocephaly, cephalocele and Dandy-Walker malformation. The CNS features in the abnormal group are presented. In the second trimester (ST), we further diagnosed cases of corpus callosum agenesis, cerebellar hypoplasia, vein of Galen aneurysm and fetal infection features (ventriculomegaly, intraventricular bands, intraventricular cyst and hyperechoic foci), all declared normal at the FTAS. During the third trimester (TT) scan we identified a massive fetal cerebral haemorrhage absent at previous investigations. We report a detection rate of 72.7% of fetal brain anomalies in the FT using the proposed CNS parameters. The sensitivity of the examination protocol was 72.7%, and the specificity was 100%. A detailed FT CNS scan is feasible and efficient. The majority of cases of major CNS abnormalities can be detected early in pregnancy. The visualization rates of the CNS parameters in the FT are great with short, if any, additional investigation time. FT cerebral disorders such as haemorrhage or infections were missed in the FT even when an extended evaluation protocol was used.

Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes with an MT-TL1 m.3243A>G point mutation: Neuroradiological features and their implications for underlying pathogenesis.

Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) is one of the most common inherited mitochondrial disorders. Due to the high clinical and genetic heterogeneity of MELAS, it is still a major challenge for clinicians to accurately diagnose the disease at an early stage. Herein, we evaluated the neuroimaging findings of MELAS with an m.3243A>G mutation in MT-TL1 and analyzed the possible underlying pathogenesis of stroke-like episodes. Fifty-nine imaging studies in 24 patients who had a confirmed genetic diagnosis of m.3243A>G (MT-TL1; tRNA Leu) associated with MELAS were reviewed in our case series. The anatomic location, morphological features, signal/intensity characteristics and temporal evolution of lesions were analyzed on magnetic resonance imaging (MRI), and computed tomography (CT) images. The supplying vessels and metabolite content of the lesions were also evaluated by using MR angiography (MRA)/CT angiography (CTA), and MR spectroscopy (MRS), respectively. The lesions were most commonly located in the posterior brain, with 37 (37/59, 63%) in the occipital lobe, 32 (32/59, 54%) in the parietal lobe, and 30 (30/59, 51%) in the temporal lobe. The signal characteristics of the lesions varied and evolved over time. Bilateral basal ganglia calcifications were found in 6 of 9 (67%) patients who underwent CT. Cerebral and cerebellar atrophy were found in 38/59 (64%) and 40/59 (68%) patients, respectively. Lesion polymorphism was found in 37/59 (63%) studies. MRS showed elevated lactate doublet peaks in 9/10 (90%) cases. MRA or CTA revealed that the lesion-related arteries were slightly dilated compared with those of the contralateral side in 4 of 6 (67%) cases. The imaging features of MELAS vary depending on the disease stage. Polymorphic lesions in a single imaging examination should be considered a diagnostic clue for MELAS. Stroke-like episodes may be involved in a complex pathogenetic process, including mitochondrial angiopathy, mitochondrial cytopathy, and neuronal excitotoxicity.

Sex and age variations in the impact of puberty on cortical thickness and associations with internalizing symptoms and suicidal ideation in early adolescence

PurposeThe childhood-to-adolescence transition is a notable period of change including pubertal development, neurodevelopment, and psychopathology onset, that occurs in divergent patterns between sexes. This study examined the effects of sex and puberty on cortical thickness (CT) in children and explored whether CT changes over time related to emergence of psychopathology in early adolescence. MethodsWe used longitudinal data (baseline ages 9–10 and Year 2 [Y2] ages 11–12) from the ABCD Study (n = 9985). Linear and penalized function-on-function regressions modeled the impact of puberty, as it interacts with sex, on CT. Focusing on regions that showed sex differences, linear and logistic regressions modeled associations between change in CT and internalizing problems and suicide ideation. ResultsWe identified significant sex differences in the inverse relation between puberty and CT in fifteen primarily posterior brain regions. Nonlinear pubertal effects across age were identified in the fusiform, isthmus cingulate, paracentral, and precuneus. All effects were stronger for females relative to males during this developmental window. We did not identify associations between CT change and early adolescent clinical outcomes. ConclusionDuring this age range, puberty is most strongly associated with regional changes in CT in females, which may have implications for the later emergence of psychopathology.

Fetal behavior during MRI changes with age and relates to network dynamics.

Fetal motor behavior is an important clinical indicator of healthy development. However, our understanding of associations between fetal behavior and fetal brain development is limited. To fill this gap, this study introduced an approach to automatically and objectively classify long durations of fetal movement from a continuous four-dimensional functional magnetic resonance imaging (fMRI) data set, and paired behavior features with brain activity indicated by the fMRI time series. Twelve-minute fMRI scans were conducted in 120 normal fetuses. Postnatal motor function was evaluated at 7 and 36 months age. Fetal motor behavior was quantified by calculating the frame-wise displacement (FD) of fetal brains extracted by a deep-learning model along the whole time series. Analyzing only low motion data, we characterized the recurring coactivation patterns (CAPs) of the supplementary motor area (SMA). Results showed reduced motor activity with advancing gestational age (GA), likely due in part to loss of space (r=-.51, p < .001). Evaluation of individual variation in motor movement revealed a negative association between movement and the occurrence of coactivations within the left parietotemporal network, controlling for age and sex (p=.003). Further, we found that the occurrence of coactivations between the SMA to posterior brain regions, including visual cortex, was prospectively associated with postnatal motor function at 7months (r=.43, p=.03). This is the first study to pair fetal movement and fMRI, highlighting potential for comparisons of fetal behavior and neural network development to enhance our understanding of fetal brain organization.

Genetic and environmental influence on resting state networks in young male and female adults: a cartographer mapping study.

We propose a unique, minimal assumption, approach based on variance analyses (compared with standard approaches) to investigate genetic influence on individual differences on the functional connectivity of the brain using 65 monozygotic and 65 dizygotic healthy young adult twin pairs' low-frequency oscillation resting state functional Magnetic Resonance Imaging (fMRI) data from the Human Connectome Project. Overall, we found high number of genetically-influenced functional (GIF) connections involving posterior to posterior brain regions (occipital/temporal/parietal) implicated in low-level processes such as vision, perception, motion, categorization, dorsal/ventral stream visuospatial, and long-term memory processes, as well as high number across midline brain regions (cingulate) implicated in attentional processes, and emotional responses to pain. We found low number of GIF connections involving anterior to anterior/posterior brain regions (frontofrontal > frontoparietal, frontotemporal, frontooccipital) implicated in high-level processes such as working memory, reasoning, emotional judgment, language, and action planning. We found very low number of GIF connections involving subcortical/noncortical networks such as basal ganglia, thalamus, brainstem, and cerebellum. In terms of sex-specific individual differences, individual differences in males were more genetically influenced while individual differences in females were more environmentally influenced in terms of the interplay of interactions of Task positive networks (brain regions involved in various task-oriented processes and attending to and interacting with environment), extended Default Mode Network (a central brain hub for various processes such as internal monitoring, rumination, and evaluation of self and others), primary sensorimotor systems (vision, audition, somatosensory, and motor systems), and subcortical/noncortical networks. There were >8.5-19.1 times more GIF connections in males than females. These preliminary (young adult cohort-specific) findings suggest that individual differences in the resting state brain may be more genetically influenced in males and more environmentally influenced in females; furthermore, standard approaches may suggest that it is more substantially nonadditive genetics, rather than additive genetics, which contribute to the differences in sex-specific individual differences based on this young adult (male and female) specific cohort. Finally, considering the preliminary cohort-specific results, based on standard approaches, environmental influences on individual differences may be substantially greater than that of genetics, for either sex, frontally and brain-wide. [Correction added on 10 May 2023, after first online publication: added: functional Magnetic Resonance Imaging. Added: individual differences in, twice. Added statement between furthermore … based on standard approaches.].

Prognostic value of pretreatment diffusion-weighted imaging score for acute basilar artery occlusion with successful endovascular recanalization.

The aim of this study is to test the prognostic value of a diffusion-weighted imaging (DWI) score in acute basilar artery occlusion (ABAO) with successful recanalization. The DWI-based pons-midbrain and thalamus (PMT) score was developed to assess posterior circulation infarcts. We test its prognostic value and compare it with other two established scales, the DWI-based posterior circulation acute stroke prognosis Early CT score (PC-ASPECTS) and brain stem score (BSS). A retrospective cohort of consecutive ABAO patients with pretreatment magnetic resonance imaging and successful recanalization (defined as modified Thrombolysis in Cerebral Infarction 2b-3) were analyzed. A favorable outcome was defined as a 90-day modified Rankin Scale (mRS) score of 2 or less. The prognostic performance of three scales was estimated by receiver operating characteristic (ROC) curve analyses. One hundred and sixteen eligible patients (mean age, 59.1 ± 11.7 [standard deviation]; 96 [82.8%] man) were included and evaluated. Between favorable (mRS ≤ 2) and unfavorable groups, the baseline PMT score (median [interquartile range], 3 [1-4] versus 6 [5-8]; P < 0.001) differs significantly. ROC curve analyses showed the PMT score had the best prognostic value for favorable outcome (area under the curve, PMT versus BSS versus PC-ASPECTS = 0.80 versus 0.72 versus 0.68, P = 0.010). Multivariate logistic regression analyses showed baseline National Institute of Health stroke scale (OR, 0.90 [95%CI, 0.86-0.95], P = 0.004) and PMT score < 5 (OR, 17.83 [95%CI, 3.91-81.19], P < 0.001) were independent prognostic factors of favorable outcome. The PMT score seems to predict clinical outcome of ABAO patients with successful recanalization.

Distinct signatures of loss of consciousness in focal impaired awareness versus tonic-clonic seizures.

Loss of consciousness is a hallmark of many epileptic seizures and carries risks of serious injury and sudden death. While cortical sleep-like activities accompany loss of consciousness during focal impaired awareness seizures, the mechanisms of loss of consciousness during focal to bilateral tonic-clonic seizures remain unclear. Quantifying differences in markers of cortical activation and ictal recruitment between focal impaired awareness and focal to bilateral tonic-clonic seizures may also help us to understand their different consequences for clinical outcomes and to optimize neuromodulation therapies. We quantified clinical signs of loss of consciousness and intracranial EEG activity during 129 focal impaired awareness and 50 focal to bilateral tonic-clonic from 41 patients. We characterized intracranial EEG changes both in the seizure onset zone and in areas remote from the seizure onset zone with a total of 3386 electrodes distributed across brain areas. First, we compared the dynamics of intracranial EEG sleep-like activities: slow-wave activity (1-4 Hz) and beta/delta ratio (a validated marker of cortical activation) during focal impaired awareness versus focal to bilateral tonic-clonic. Second, we quantified differences between focal to bilateral tonic-clonic and focal impaired awareness for a marker validated to detect ictal cross-frequency coupling: phase-locked high gamma (high-gamma phased-locked to low frequencies) and a marker of ictal recruitment: the epileptogenicity index. Third, we assessed changes in intracranial EEG activity preceding and accompanying behavioural generalization onset and their correlation with electromyogram channels. In addition, we analysed human cortical multi-unit activity recorded with Utah arrays during three focal to bilateral tonic-clonic seizures. Compared to focal impaired awareness, focal to bilateral tonic-clonic seizures were characterized by deeper loss of consciousness, even before generalization occurred. Unlike during focal impaired awareness, early loss of consciousness before generalization was accompanied by paradoxical decreases in slow-wave activity and by increases in high-gamma activity in parieto-occipital and temporal cortex. After generalization, when all patients displayed loss of consciousness, stronger increases in slow-wave activity were observed in parieto-occipital cortex, while more widespread increases in cortical activation (beta/delta ratio), ictal cross-frequency coupling (phase-locked high gamma) and ictal recruitment (epileptogenicity index). Behavioural generalization coincided with a whole-brain increase in high-gamma activity, which was especially synchronous in deep sources and could not be explained by EMG. Similarly, multi-unit activity analysis of focal to bilateral tonic-clonic revealed sustained increases in cortical firing rates during and after generalization onset in areas remote from the seizure onset zone. Overall, these results indicate that unlike during focal impaired awareness, the neural signatures of loss of consciousness during focal to bilateral tonic-clonic consist of paradoxical increases in cortical activation and neuronal firing found most consistently in posterior brain regions. These findings suggest differences in the mechanisms of ictal loss of consciousness between focal impaired awareness and focal to bilateral tonic-clonic and may account for the more negative prognostic consequences of focal to bilateral tonic-clonic.

NCOG-45. DIFFERENTIAL AND DOSE-DEPENDENT EFFECTS OF CRANIAL IRRADIATION ON BRAIN STRUCTURES AND NEUROPSYCHOLOGICAL OUTCOMES IN CHILDREN WITH POSTERIOR FOSSA BRAIN TUMORS TREATED WITH DIFFERENT MODALITIES

Abstract BACKGROUND Studies investigating dose-dependent effects of cranial irradiation (CRT) in children with posterior fossa brain tumors are limited by examining combined effects of surgery, chemotherapy, and radiation. We aimed to determine alterations in brain volume and microstructure, and neuropsychological outcomes in children with posterior fossa tumors treated with surgery alone, surgery and chemotherapy, and surgery, chemotherapy, and CRT combined. We explored the relationship of radiation dose to the thalamus, putamen, and hippocampus to outcomes of intelligence, processing speed, executive functions, memory, and social/emotional functioning. METHODS Forty-seven children with treated posterior fossa tumors (17 with surgery; 11 with surgery and chemotherapy; 19 with surgery, chemotherapy, and CRT) underwent neuroimaging and neuropsychological assessment a mean of 4.8 years after treatment, along with 17 healthy sibling controls (n=64). The putamen, thalamus and hippocampus were manually segmented on MRI, and structural mean radiation doses were calculated. Differences in demographics and medical history were evaluated using χ2 and t-tests. Linear regression examined differences in neuropsychological performance, structural volumes, and diffusion indices. Pearson correlation explored relationships of structural radiation doses to diffusion indices and neuropsychological outcomes. RESULTS All patients scored lower on Block Design than controls (p=0.01), and the surgery and chemotherapy group scored the lowest. There was no significant difference in mean fractional anisotropy (FA) values in the thalamus, hippocampus and putamen between the three patient groups and controls. Hippocampal volume and mean radiation dose approached significant correlation (r= -0.49; p=0.07). Right putamen FA correlated with mean radiation dose (r=0.56; p=0.02). When controlling for age, thalamic volume was lowest in the irradiated group (p=0.02). CONCLUSIONS Treatment of pediatric posterior fossa brain tumors with surgery, chemotherapy, and CRT impacts thalamic volume and may have a dose-dependent effect on the microstructure of the putamen compared to treatment with surgery/chemotherapy.

RADT-12. PRE- AND POST-OPERATIVE RADIATION TREATMENT PLANNING FOR PATIENTS RECEIVING STEREOTACTIC RADIOSURGERY FOR BRAIN METASTASES: A VOLUMETRIC ANALYSIS

Abstract BACKGROUND Pre-operative stereotactic radiosurgery (SRS) has emerged as a recent treatment option to treat large or symptomatic brain metastases. Compared to post-operative SRS, pre-operative treatment may reduce rates of radiation necrosis (RN) and meningeal disease through treating a smaller treatment volume and by preventing post-operative tumor seeding. We hypothesize that pre-operative radiation volumes will be smaller than post-operative volumes, which in turn may lead to a decreased treatment morbidity. METHODS A retrospective analysis was conducted and patients who had surgical resection and post-operative SRS or fractionated stereotactic radiosurgery (FSRT) for a posterior fossa brain metastasis were eligible for inclusion. Both pre-operative and post-operative MRIs were required to allow for accurate radiation target delineation. A pre-operative tumor volume was added for each patient, and the post-operative clinical treatment volume (CTV) used for radiation treatment was included. Pre-operative tumor and post-operative cavity volumes were compared using Wilcoxon signed rank test. RESULTS 28 patients who received post-operative SRS or FSRT from 1/1/2016-12/31/2020 were included in this analysis. The mean pre-operative tumor volume was 14.9 ccs, and the mean post-operative CTV was 21.0 ccs (p &amp;lt; 0.01). 75% of patients had a smaller initial tumor size compared to the post-operative CTV used for radiation treatment planning. For patients with at least 4 follow up MRIs (n = 8), the size of the post-operative cavity progressively decreased with a mean initial cavity volume of 18.9 ccs and mean follow up volumes of 8.1, 7.1, 6.9, and 6.2 ccs. CONCLUSIONS In this study evaluating patients who received post-operative SRS, the pre-operative tumor volume was lower than the post-operative CTV for most patients. Previous studies including PROPS-BM have shown how pre-operative treatment may reduce the risk of RN because smaller radiation volumes are used. Pre-operative radiosurgery for patients with brain metastases requires prospective validation.

A Headrest Made of Extruded Polystyrene Reduces the Influence of Attenuation Correction on Human Brain SPECT Images.

Previous reports suggest that a headrest made of carbon significantly influences cerebral blood flow in the anterior and posterior regions by image reconstruction and attenuation correction (AC). The present study aimed to develop a headrest that reduces the influence of the AC process on human brain SPECT. Methods: To validate the performance of a headrest made of extruded polystyrene (XPS), 10 healthy controls and 43 patients with cerebrovascular disease underwent 99mTc-ethyl cysteinate dimer SPECT using a carbon headrest and an XPS headrest. We evaluated the anterior-to-posterior and middle-to-posterior ratio of the brain regions in filtered backprojection (FBP) Chang AC, ordered-subset expectation maximization (OSEM) Chang AC, and OSEM CT-based AC. Results: The anterior-to-posterior ratio was significantly higher with the carbon headrest than with the XPS headrest in FBP Chang AC and OSEM Chang AC (P < 0.001). There was no significant difference between the materials in OSEM CT-based AC. The middle-to-posterior ratio did not differ to a statistically significant extent in any correction process. Conclusion: Acquisition of brain SPECT images with an XPS headrest and processing by the FBP or OSEM Chang AC method enables the influence of the headrest to be reduced, especially in anterior and posterior brain regions.