Medial Parietal Lobe Research Articles

REPRODUCIBILITY OF BRAIN AGE SALIENCIES ACROSS DEEP NEURAL NETWORK ARCHITECTURES

Abstract The brain’s biological age (BA) reflects structural changes related to neuroanatomic senescence. BA is estimated from magnetic resonance images (MRIs) using convolutional neural networks (CNNs), which provide interpretability through saliency maps. By conveying the importance of brain regions to BA estimation, these maps reveal sex differences in brain-aging. We compared two CNN architectures to assess the reproducibility of such differences. Both regression CNNs had T1-weighted MRIs as inputs; outputs were estimated BAs. One CNN was trained on males and females separately, whereas the other was trained on both sexes. The dataset used consisted of T1-weighted MRIs from 5,851 cognitively normal individuals (3,142 females) aged 22 to 95 years, sampled from the Alzheimer’s Disease Neuroimaging Initiative (N = 510), Human Connectome Project Aging (N = 508) and Young Adult (N = 1,112), and UK Biobank (N = 3,721). For both models, compared to the average saliency for a null distribution, males’ BA estimation relied significantly (p < 0.05) more on the right lateral temporal lobe and superior frontal gyrus. Females’ BA estimation depended significantly (p <; 0.05) more on the right posterior and bilateral occipital regions, and medial parietal lobe. Simulated alterations in brain morphometry indicated saliencies correctly revealed regions with aging-related dynamics, which confirm prior findings on sex differences in brain-aging. Variations in CNN models’ saliencies did not affect overall anatomic patterns, suggesting that CNNs can capture brain-aging patterns robustly despite architecture differences. Novel statistical models for formal comparison of CNN saliencies should be developed to accommodate their nonlinear nature.

MUTUAL INFORMATION OF NEUROIMAGES AND GENETIC VARIANTS TO STUDY THE DETERMINANTS OF BRAIN AGING

Abstract Understanding the genetic determinants of brain aging is important because advanced biological age of the brain is a risk factor for Alzheimer’s disease (AD). Single-nucleotide polymorphisms (SNPs) are genetic variations with effects on brain aging; mapping their influence on brain structure can elucidate the genetic correlates of AD. We adopted an information theoretic approach to this by computing the mutual information (MI) between (A) 22 AD-risk SNPs and (B) the MRI intensities of the cortex in 6,000 UK Biobank participants (~50% females) aged 54 to 84 years. These cortex-wide calculations quantified how SNPs impact brain structure. As expected, the APOE-ε4 allele, the strongest genetic risk factor for AD, exhibited significantly (p < 0.025) higher MI with MRI intensity, when compared to the average MI expected for a null distribution model, in the medial parietal lobe, pars orbitalis, and left inferior occipital lobe, three brain structures responsible for memory recall, language processing, and visual perception. These findings reflect the memory loss, decreased speech, and reduced peripheral vision experienced by individuals with AD. The ABCA7 allele, a risk factor for late- onset AD, had significantly (p < 0.025) higher MI in the inferior temporal sulcus and angular gyrus. These structures are responsible for visual recognition and attention, two functions that are severely impaired by AD. Other findings reveal similar relationships between AD-risk SNPs and brain structure. Our findings illustrate how mapping the MI between MRI intensities and SNPs provides insight into genetic influences on brain structures linked to AD symptoms.

Association of focal epilepsy in Alzheimer’s disease with tau, amyloid, and neurodegeneration

AbstractBackgroundNetwork hyperexcitability has emerged as an important contributor to cognitive dysfunction and clinical progression in Alzheimer’s disease (AD), with work in animal AD models supporting a mechanistic, feed‐forward link between neuronal hyperexcitability and amyloid and tau pathology. Seizures are a quintessential manifestation of network hyperexcitability in AD. AD is associated with a 2‐3‐fold increased risk of developing epilepsy, and epilepsy in AD is most often a focal, unilateral temporal lobe epilepsy. We hypothesized that if network hyperexcitability is mechanistically linked to AD pathology, then focal unitemporal hyperexcitability in individuals with AD and epilepsy would be associated with increased deposition of tau and/or amyloid within the epileptogenic hemisphere.MethodWe studied eight individuals with early clinical stages of AD who developed focal epilepsy early in the course of AD. All individuals underwent overnight scalp EEG, 3T structural brain MRI, and PET imaging with 11C‐PiB and 18F‐MK‐6240. We performed region‐of‐interest based imaging analyses and calculated asymmetry indices (AI) as: 200 * (Ipsilateral ‐ Contralateral) / (Ipsilateral + Contralateral), where ipsilateral and contralateral are relative to the epileptogenic hemisphere.ResultTau deposition was asymmetrically increased within the epileptogenic hemisphere. Individuals with a higher global tau burden showed asymmetrically increased tau in the lateral temporal lobe, medial and lateral parietal lobes, and frontal lobes of the epileptogenic hemisphere, while those with a lower global tau burden demonstrated a highly focal, discrete tau accumulation within the lateral temporal lobe. Amyloid deposition was also increased within the epileptogenic hemisphere, particularly in the lateral temporal, medial and lateral parietal, and frontal regions, though the magnitude of amyloid AI was lower than that of tau AI. We also found increased cortical atrophy in the lateral temporal and lateral parietal regions of the epileptogenic hemisphere.ConclusionOur study reveals a spatial association between focal epilepsy and asymmetries in tau and amyloid deposition and cortical atrophy in early clinical stages of AD. While historically, individuals with AD and epilepsy have been excluded from most studies in AD, our findings demonstrate that studying these individuals can provide unique insights on mechanisms that underlie the clinical and pathologic heterogeneity of AD.

Abstract 160: Recurrent Multi‐territorial Ischemic Stroke as an Initial Presentation of Thrombotic Thrombocytopenic Purpura

Introduction Thrombotic thrombocytopenic purpura (TTP) is a rare hypercoagulable disorder characterized by acute hemolytic anemia, thrombocytopenia, neurologic deficits, and renal failure. Here, we describe a young patient with recurrent multi‐territory stroke, with the development of thrombocytopenia later in her course. Her prior diagnosis of etiologies for her ischemic stroke was confounded by the presence of grade 3 PFO and intrinsic arteriopathy attributed to accelerated atherosclerosis due to smoking tobacco with marijuana. Methods A 42‐year‐old woman, active tobacco and marijuana smoker, and recent cryptogenic ischemic and hemorrhagic stroke involving multiple vascular territories with hypercoagulable workup pending, presented with sudden left hemiplegia. Vessel imaging demonstrated irregularity and mild narrowing of the right posterior M2/M3 MCA branches without evidence of large vessel occlusion. MRI showed evidence of evolving left frontal encephalomalacia, prior ischemic stroke on the right inferior MCA and corpus callosum, and prior hemorrhagic stroke on the right parietal and left PCA. In addition, it showed T2 hyperintensities in bilateral anterior and posterior watershed areas. Work‐up was significant for grade 3 PFO/intrapulmonary shunt. Doppler ultrasound was negative for DVT. Basic labs showed LDL 56, A1c 4.8, and TSH 1.8. Hypercoagulable work‐up returned negative. Her platelet count during the admission was initially 169, and 208 on discharge to rehab on single agent antiplatelet (81mg aspirin) and high‐dose statin. After 11 days in rehab, she returned with sudden‐onset slurred speech and right‐sided hemiplegia. Vessel imaging was again negative for LVO and showed significant multi‐vessel arteriopathy. A repeat brain MRI showed a new stroke on the left precentral gyrus, left high frontal lobe, left medial parietal lobe, and left cerebellar hemisphere. The suspected mechanism of stroke was cardioembolic although the patient’s normal left atrial size was presumed to make this mechanism less likely. A few days into admission, her platelets began to decrease. With new‐onset thrombocytopenia (lowest platelet count was 38), ADAMTS screen was ordered and returned positive. The ADAMTS inhibitor Bethesda titer was notably high, 1.4 (nl <0.4). Uncharacteristically for TTP, the patient did not have a fever, anemia (Hb 12), or renal failure (good urine output and Cr 0.7). Nonetheless, given the absence of a clear alternative attributable stroke mechanism, thrombotic thrombocytopenia was suspected as the etiology of her ischemic strokes. For acute therapy, 3‐day 1 mg/kg methylprednisolone was started and hematology service was consulted for co‐management. The patient completed four rounds of plasmapheresis while receiving 90 mg of prednisone daily. She was then started on a regimen to complete four doses of weekly rituximab. The patient improved clinically during the course of her stay and with noted improvements in platelet count and ADAMTS as well. Results N/A Conclusion A low threshold to consider atypical presentations of cryptogenic stroke such as TTP in this case should be in mind when evaluating young adults with recurrent multi‐territory ischemic stroke. Thrombocytopenia may not be present until later in the disease course representing atypical presentations of TTP. As in our case, patients may present without fever, hemolytic anemia, and renal failure.

Magnetic Resonance Spectroscopy Spectral Registration Using Deep Learning.

Deep learning-based methods have been successfully applied to MRI image registration. However, there is a lack of deep learning-based registration methods for magnetic resonance spectroscopy (MRS) spectral registration (SR). To investigate a convolutional neural network-based SR (CNN-SR) approach for simultaneous frequency-and-phase correction (FPC) of single-voxel Meshcher-Garwood point-resolved spectroscopy (MEGA-PRESS) MRS data. Retrospective. Forty thousand simulated MEGA-PRESS datasets generated from FID Appliance (FID-A) were used and split into the following: 32,000/4000/4000 for training/validation/testing. A 101 MEGA-PRESS medial parietal lobe data retrieved from the Big GABA were used as the in vivo datasets. 3T, MEGA-PRESS. Evaluation of frequency and phase offsets mean absolute errors were performed for the simulation dataset. Evaluation of the choline interval variance was performed for the in vivo dataset. The magnitudes of the offsets introduced were -20 to 20 Hz and -90° to 90° and were uniformly distributed for the simulation dataset at different signal-to-noise ratio (SNR) levels. For the in vivo dataset, different additional magnitudes of offsets were introduced: small offsets (0-5 Hz; 0-20°), medium offsets (5-10 Hz; 20-45°), and large offsets (10-20 Hz; 45-90°). Two-tailed paired t-tests for model performances in the simulation and in vivo datasets were used and a P-value <0.05 was considered statistically significant. CNN-SR model was capable of correcting frequency offsets (0.014 ± 0.010 Hz at SNR 20 and 0.058 ± 0.050 Hz at SNR 2.5 with line broadening) and phase offsets (0.104 ± 0.076° at SNR 20 and 0.416 ± 0.317° at SNR 2.5 with line broadening). Using in vivo datasets, CNN-SR achieved the best performance without (0.000055 ± 0.000054) and with different magnitudes of additional frequency and phase offsets (i.e., 0.000062 ± 0.000068 at small, -0.000033 ± 0.000023 at medium, 0.000067 ± 0.000102 at large) applied. The proposed CNN-SR method is an efficient and accurate approach for simultaneous FPC of single-voxel MEGA-PRESS MRS data. 4 TECHNICAL EFFICACY: Stage 2.

Differential effects of expectancy on memory formation in young and older adults.

Novelty can promote subsequent long-term memory via the mesolimbic system, including the medial temporal lobe and midbrain structures. Importantly, these and other brain regions typically degenerate during healthy aging, which suggests a reduced impact of novelty on learning. However, evidence in favor of such a hypothesis is scarce. Thus, we used functional MRI in combination with an established paradigm in healthy young (19-32 years, n = 30) and older (51-81 years, n = 32) humans. During encoding, colored cues predicted the subsequent presentation of either a novel or previously familiarized image (75% cue validity), and approximately 24 h later, recognition memory for novel images was tested. Behaviorally, expected novel images, as compared to unexpected novel images, were better recognized in young and, to a lesser degree, older subjects. At the neural level, familiar cues activated memory related areas, especially the medial temporal lobe, whereas novelty cues activated the angular gyrus and inferior parietal lobe, which may reflect enhanced attentional processing. During outcome processing, expected novel images activated the medial temporal lobe, angular gyrus and inferior parietal lobe. Importantly, a similar activation pattern was observed for subsequently recognized novel items, which helps to explain the behavioral effect of novelty on long-term memory. Finally, age-effects were pronounced for successfully recognized novel images with relatively stronger activations in attention-related brain regions in older adults; younger adults, on the other hand, showed stronger hippocampal activation. Together, expectancy promotes memory formation for novel items via neural activity in medial temporal lobe structures and this effect appears to be reduced with age.

Clinical Images: Symmetrical Gyriform Restricted Diffusion in Severe Reversible Cerebral Vasoconstriction Syndrome

A 45-year-old woman with chronic depression and currently receiving dual serotonergic therapy was transferred to our department with sudden dysbasia; she also reported an antecedent thunderclap headache. Magnetic resonance imaging (MRI) revealed a symmetrical bilateral acute infarction in the medial parietal lobe and severe vasoconstriction in the cerebral arteries. We diagnosed reversible cerebral vasoconstriction syndrome (RCVS) and stopped the serotonergic drug regimen. Her symptoms improved after receiving a calcium blocker and magnesium sulfate, and she was discharged after 20days. Cerebral infarctions developed in 30%-40% of reversible cerebral vasoconstriction syndrome (RCVS) cases, mostly within watershed regions; however, these atypical infarctions were bilateral and symmetrical, potentially because of hypoperfusion caused by long-lasting severe vasoconstriction in the anterior cerebral arteries. Rare bilateral neurologic deficits can be mistaken for hypochondriac delusions, particularly in patients with depression. Since serotonergic drugs are the main cause of RCVS, primary care psychiatrists must be aware of drug-induced RCVS.

Regional cerebral atrophy correlates with amyloid accumulation in preclinical Alzheimer’s disease

AbstractBackgroundThis study was aimed to evaluate the regional hierarchical brain atrophy among the preclinical to mild cognitive impairment (MCI) stages of Alzheimer’s disease associated with amyloid deposition using [18F]flutemetamol positron emission tomography and volumetric magnetic resonance imaging.MethodThis was a prospective, single‐cohort study of volunteers who were living independently in Itabashi‐ku (Tokyo, Japan). One hundred thirty‐six participants (female/male = 96/40, mean age/standard deviation = 79.2/4.0 years) were recruited. Two subjects, one with meningeal thickening and another with sequelae in the brain, and 17 visually amyloid‐negative MCI subjects who possibly had neurodegenerative disease other than Alzheimer’s disease were excluded from the further analysis. We applied voxel‐based regression slope analysis between composite voxel of interest values calculated with Cortex ID Suite (GE Healthcare) on [18F]flutemetamol positron emission tomography and volumetric magnetic resonance images in three groups: 70 amyloid‐negative cognitively normal (CN) participants, 29 amyloid‐positive cognitively normal (PreC) participants, and 18 amyloid‐positive MCI (MCI+) participants. Statistical Parametric Mapping 12 software was used for analysis.ResultEven in the cognitively normal stage, the PreC group showed a larger slope of atrophy in the basal forebrain and middle frontal gyri than the CN group. In the MCI+ group, the slopes were larger in the lateral and medial parietal lobes, uncus, and right lateral temporal areas.ConclusionThe speed of amyloid‐related atrophy in the basal forebrain and middle frontal gyri was quick even in the preclinical stage of Alzheimer’s disease. As no significant slope changes were observed among the three groups in the medial temporal area, except for the uncus, the well‐known medial temporal atrophy in early Alzheimer’s disease might not be related to the accumulation of amyloid.

Emotional Dysregulation in Mild Behavioral Impairment Is Associated with Reduced Cortical Thickness in the Right Supramarginal Gyrus.

Mild behavioral impairment (MBI) has attracted attention as a possible precursor symptom of dementia, but its neural basis has not been fully investigated. We aimed to investigate the relationship between MBI and surface area, cortical thickness, and volume in the temporal and parietal lobes, which are strongly associated with dementia and emotional disorders. This retrospective study evaluated 123 participants: 90 with mild cognitive impairment (MCI), 13 with subjective cognitive decline (SCD), and 20 cognitively healthy (CH). Using analysis of covariance (ANCOVA) with sex, age, and MMSE score as covariates, cortical thickness, surface area, and volume in 10 regions were compared between groups with and without MBI. Groups with MBI emotional dysregulation were also compared with groups without MBI. ANCOVA revealed significantly smaller cortical thickness in the MBI group's right parahippocampal (p = 0.01) and supramarginal gyri (p = 0.002). After multiple comparison correction, only the right supramarginal gyrus was significantly smaller (p = 0.02). When considering only MBI emotional dysregulation, the right parahippocampal and supramarginal gyrus' cortical thicknesses were significantly smaller in this MBI group (p = 0.03, 0.01). However, multiple comparison correction identified no significant differences (p = 0.14, 0.11). Overall MBI and the emotional dysregulation domains were associated with reduced cortical thickness in the right parahippocampal and supramarginal gyri. Since neurodegeneration in the medial temporal and parietal lobe precedes early Alzheimer's disease (AD), MBI, particularly emotion dysregulation, may predict early AD below the diagnostic threshold.

Mixed emotions to social situations: An fMRI investigation

BackgroundNeuroscience research has generally studied emotions each taken in isolation. However, mixed emotional states (e.g., the co-occurrence of amusement and disgust, or sadness and pleasure) are common in everyday life. Psychophysiological and behavioral evidence suggests that mixed emotions may have response profiles that are distinguishable from their constituent emotions. Yet, the brain bases of mixed emotions remain unresolved. MethodsWe recruited 38 healthy adults who viewed short, validated film clips, eliciting either positive (amusing), negative (disgusting), neutral, or mixed (a mix of amusement and disgust) emotional states, while brain activity was assessed by functional magnetic resonance imaging (fMRI). We assessed mixed emotions in two ways: first by comparing neural reactivity to ambiguous (mixed) with that to unambiguous (positive and negative) film clips and second by conducting parametric analyses to measure neural reactivity with respect to individual emotional states. We thus obtained self-reports of amusement and disgust after each clip and computed a minimum feeling score (shared minimum of amusement and disgust) to quantify mixed emotional feelings. ResultsBoth analyses revealed a network of the posterior cingulate (PCC), medial superior parietal lobe (SPL)/precuneus, and parieto-occipital sulcus to be involved in ambiguous contexts eliciting mixed emotions. ConclusionOur results are the first to shed light on the dedicated neural processes involved in dynamic social ambiguity processing. They suggest both higher-order (SPL) and lower-order (PCC) processes may be needed to process emotionally complex social scenes.

More than one-half of the variance in in vivo proton MR spectroscopy metabolite estimates is common to all metabolites.

The present study characterized associations among brain metabolite levels, applying bivariate and multivariate (i.e., factor analysis) statistical methods to total creatine (tCr)-referenced estimates of the major Point RESolved Spectroscopy (PRESS) proton MR spectroscopy (1 H-MRS) metabolites (i.e., total NAA/tCr, total choline/tCr, myo-inositol/tCr, glutamate + glutamine/tCr) acquired at 3 T from medial parietal lobe in a large (n = 299), well-characterized international cohort of healthy volunteers. Results supported the hypothesis that 1 H-MRS-measured metabolite estimates are moderately intercorrelated (Mr = 0.42, SDr = 0.11, ps < 0.001), with more than one-half (i.e., 57%) of the total variability in metabolite estimates explained by a single common factor. Older age was significantly associated with lower levels of the identified common metabolite variance (CMV) factor (β = -0.09, p = 0.048), despite not being associated with levels of any individual metabolite. Holding CMV factor levels constant, females had significantly lower levels of total choline (i.e., unique metabolite variance; β = -0.19, p < 0.001), mirroring significant bivariate correlations between sex and total choline reported previously. Supplementary analysis of water-referenced metabolite estimates (i.e., including tCr/water) demonstrated lower, although still substantial, intercorrelations among metabolites, with 37% of total metabolite variance explained by a single common factor. If replicated, these results would suggest that applied 1 H-MRS researchers shift their analytical framework from examining bivariate associations between individual metabolites and specialty-dependent (e.g., clinical, research) variables of interest (e.g., using t-tests) to examining multivariable (i.e., covariate) associations between multiple metabolites and specialty-dependent variables of interest (e.g., using multiple regression).

Interhemispheric Transcingulate Sulcus Approach to Deep-Seated Medial Frontal and Parietal Lesions-Fiber Dissection Study With Illustrative Cases.

Surgery for lesions located in the medial frontal and parietal lobes can be quite challenging for neurosurgeons because of morbidities that may arise from damage to critical midline structures or intact neural tissue that need to be crossed to reach the lesion. In our anatomic studies, the cingulate sulcus was observed as an alternative access route for lesions located in medial frontal and parietal lobes. To explain the microsurgical anatomy of the medial hemisphere and cingulate sulcus and to demonstrate the interhemispheric transcingulate sulcus approach (ITCSA) with 3 clinical cases. Five formalin-fixed brain specimens, which were frozen at -18 °C for at least 2 weeks and then thawed under tap water, were gradually dissected from medial to lateral. Diffusion fiber tracking performed using DSI Studio software in data was provided by the Human Connectome Project. Clinical data of 3 patients who underwent ITCSA were reviewed. Cingulate sulcus is an effortlessly identifiable continuous sulcus on the medial surface of the brain. Our anatomic dissection study revealed that the lesions located in the deep medial frontal and parietal lobes can be reached through the cingulate sulcus with minor injury only to the cingulum and callosal fibers. Three patients were treated with ITCSA without any neurological morbidity. Deep-seated lesions in the medial frontal lobe and parietal lobe medial to the corona radiata can be approached by using microsurgical techniques based on anatomic information. ITCSA offers an alternative route to these lesions besides the known lateral transcortical/transsulcal and interhemispheric transcingulate gyrus approaches.

Two progression patterns in Alzheimer's disease identified from structural MRI in a memory clinic‐based cohort

AbstractBackgroundAlzheimer’s disease (AD) is known to be heterogeneous in pathobiology and clinical manifestation. Most previous studies demarcating AD subtypes rely on data‐driven clustering methods that are likely confounded by interindividual differences in disease progression within samples. Addressing this problem, we aim to identify and characterize distinct AD atrophy progression patterns in a memory clinic‐based cohort.Method N = 914 subjects (296 cognitively unimpaired, 366 with subjective cognitive impairment, 153 with mild cognitive impairment, and 99 with AD dementia) from the multicenter observational DZNE Longitudinal Cognitive Impairment and Dementia Study (DELCODE) were included. The Subtype and Stage Inference algorithm (Young et al., 2018, Nat. Commun.) was applied to ROI‐based cortical thickness and gray matter volume data obtained from T1w and T2w 3T‐MRI using FreeSurfer. Subtypes were characterized in demographics, ApoE genotype, various fluid biomarkers, and cognition.ResultTwo atrophy subtypes were identified. A limbic‐predominant subtype exhibited initial volume loss in the amygdala and hippocampus, followed by cortical thinning in the medial temporal, temporal, frontal, parietal, and occipital lobes. Contrary, in a hippocampal‐sparing subtype, cortical thinning first occured in the frontal, parietal, and occipital lobes before the temporal and medial temporal lobes, hippocampus, and amygdala were affected. Compared to the hippocampal‐sparing subtype, the limbic‐predominant subtype included subjects who were older, reported fewer years of education, and tended to have more ApoE e4 alleles, higher risk of vascular pathology, and higher plasma neurofilament light levels. The subtypes differed in their CSF biomarker profiles indicating higher β‐amyloid and tau burden in the limbic‐predominant subtype. In the limbic‐predominant subtype, cognitive impairment was accentuated in the learning and memory as well as language domains. Belonging to the hippocampal‐sparing subtype was associated with an impairment in executive functions and processing speed, visuospatial functions, and working memory.ConclusionWe provide evidence on atrophy heterogeneity that is largely in line with previous theoretical and empirical contributions while overcoming key limitations that are commonly faced in earlier studies. Heterogeneity may have substantial impact even in cohort studies designed to primarily include “typical” amnestic AD which highlights the need for optimized and subtype‐specific measures of early detection and disease progression.

Brain Lesions Associated with Communication-Related Quality of Life Following Surgical Removal of Primary Left-Hemisphere Tumours

ABSTRACT Background Long-term health-related quality of life (HRQoL) is an important consideration in planning treatment for individuals with brain tumours. Aim The current study examined relationships between HRQoL and anatomical location of the lesion in patients 6-24 months post-surgery. Methods Following left-hemisphere tumour resection, 37 individuals underwent behavioural testing and MRI. A principal component analysis across 10 HRQoL measures identified two components explaining ~62% of the variance: a communication-related and a mood-related component. Three lesion maps were generated per participant capturing (1) the primary resection, (2) the resection plus residual tumour, oedema, and peri-resection treatment effect (resection+), and (3) residual tumour, oedema, and peri-resection treatment effect alone (residual). Relationships between HRQoL components and lesion maps were examined using voxel-wise lesion symptom-mapping as well as general linear models predicting tract- and voxel-wise disconnection severities. Results Communication-related quality of life was significantly associated with lesions comprising both the resection+ and residual tumour in the left medial inferior parietal lobe. Voxel-wise analyses of white matter disconnection severities revealed significant associations between communication-related quality of life and thalamostriatal fibres for the residual tumour lesions. None of the analyses involving mood-related quality of life or the primary resection lesion maps were significant. Conclusions The findings highlight the role of the residual tumour, oedema, and peri-resection treatment effects and associated white matter disconnection in communication-related quality of life following treatment.

Feasibility and implications of using subject-specific macromolecular spectra to model short echo time magnetic resonance spectroscopy data.

Expert consensus recommends linear-combination modeling (LCM) of 1 H MR spectra with sequence-specific simulated metabolite basis function and experimentally derived macromolecular (MM) basis functions. Measured MM basis functions are usually derived from metabolite-nulled spectra averaged across a small cohort. The use of subject-specific instead of cohort-averaged measured MM basis functions has not been studied widely. Furthermore, measured MM basis functions are not widely available to non-expert users, who commonly rely on parameterized MM signals internally simulated by LCM software. To investigate the impact of the choice of MM modeling, this study, therefore, compares metabolite level estimates between different MM modeling strategies (cohort-mean measured; subject-specific measured; parameterized) in a lifespan cohort and characterizes its impact on metabolite-age associations. 100 conventional (TE = 30 ms) and metabolite-nulled (TI = 650 ms) PRESS datasets, acquired from the medial parietal lobe in a lifespan cohort (20-70 years of age), were analyzed in Osprey. Short-TE spectra were modeled in Osprey using six different strategies to consider the MM baseline. Fully tissue- and relaxation-corrected metabolite levels were compared between MM strategies. Model performance was evaluated by model residuals, the Akaike information criterion (AIC), and the impact on metabolite-age associations. The choice of MM strategy had a significant impact on the mean metabolite level estimates and no major impact on variance. Correlation analysis revealed moderate-to-strong agreement between different MM strategies (r > 0.6). The lowest relative model residuals and AIC values were found for the cohort-mean measured MM. Metabolite-age associations were consistently found for two major singlet signals (total creatine (tCr])and total choline (tCho)) for all MM strategies; however, findings for metabolites that are less distinguishable from the background signals associations depended on the MM strategy. A variance partition analysis indicated that up to 44% of the total variance was related to the choice of MM strategy. Additionally, the variance partition analysis reproduced the metabolite-age association for tCr and tCho found in the simpler correlation analysis. In summary, the inclusion of a single high signal-to-noise ratio MM basis function (cohort-mean) in the short-TE LCM leads to more lower model residuals and AIC values compared with MM strategies with more degrees of freedom (Gaussian parametrization) or subject-specific MM information. Integration of multiple LCM analyses into a single statistical model potentially allows to identify the robustness in the detection of underlying effects (e.g., metabolite vs. age), reduces algorithm-based bias, and estimates algorithm-related variance.

Small nuclei identification with a hemispherical brain PET

BackgroundTo confirm the performance of the first hemispherical positron emission tomography (PET) for the brain (Vrain) that we developed to visualise the small nuclei in the deep brain area, we compared 18F-fluorodeoxyglucose (FDG) brain images with whole-body PET images.MethodsTen healthy male volunteers (aged 22–45 years) underwent a representative clinical whole-body PET, followed by Vrain each for 10 min. These two scans were initiated 30 min and 45 min after FDG injection (4.1 ± 0.5 MBq/kg), respectively. First, we visually identified the small nuclei and then compared their standardised uptake values (SUVs) with the participants’ age. Next, the SUVs of each brain region, which were determined by applying a volume-of-interest template for anatomically normalised PET images, were compared between the brain images with the Vrain and those with the whole-body PET images.ResultsSmall nuclei, such as the inferior colliculus, red nucleus, and substantia nigra, were more clearly visualised in Vrain than in whole-body PET. The anterior nucleus and dorsomedial nucleus in the thalamus and raphe nucleus in the brainstem were identified in Vrain but not in whole-body PET. The SUVs of the inferior colliculus and dentate gyrus in the cerebellum positively correlated with age (Spearman’s correlation coefficient r = 0.811, p = 0.004; r = 0.738, p = 0.015, respectively). The SUVs of Vrain were slightly higher in the mesial temporal and medial parietal lobes than those in whole-body PET.ConclusionsThis was the first time that the raphe nuclei, anterior nuclei, and dorsomedial nuclei were successfully visualised using the first hemispherical brain PET.Trial registration Japan Registry of Clinical Trials, jRCTs032210086, Registered 13 May 2021, https://jrct.niph.go.jp/latest-detail/jRCTs032210086.

High Fall Risk Associated With Memory Deficit and Brain Lobes Atrophy Among Elderly With Amnestic Mild Cognitive Impairment and Mild Alzheimer's Disease.

ObjectivesThis study aimed to primarily examine the association between memory deficit and increased fall risk, second, explore the underlying neuroanatomical linkage of this association in the elderly with aMCI and mild AD.MethodsIn this cross-sectional study, a total of 103 older adults were included (55 cognitively normal, CN; 48 cognitive impairment, CI, elderly with aMCI, and mild AD). Memory was assessed by the Auditory Verbal Learning Test (AVLT). Fall risk was evaluated by the Timed Up and Go (TUG) Test, heel strike angles, and stride speed, which were collected by an inertial-sensor-based wearable instrument (the JiBuEn™ gait analysis system). Brain volumes were full-automatic segmented and quantified using AccuBrain® v1.2 from three-dimensional T1-weighted (3D T1W) MR images. Multivariable regression analysis was used to examine the extent of the association between memory deficit and fall risk, the association of brain volumes with memory, and fall risk. Age, sex, education, BMI, and HAMD scores were adjusted. Sensitivity analysis was conducted.ResultsCompared to CN, participants with aMCI and mild AD had poorer cognitive performance (p < 0.001), longer TUG time (p = 0.018), and smaller hippocampus and medial temporal volumes (p = 0.037 and 0.029). In the CI group, compared to good short delayed memory (SDM) performance (AVLT > 5), the elderly with bad SDM performance (AVLT ≤ 3) had longer TUG time, smaller heel strike angles, and slower stride speed. Multivariable regression analysis showed that elderly with poor memory had higher fall risk than relative good memory performance among cognitive impairment elderly. The TUG time increased by 2.1 s, 95% CI, 0.54∼3.67; left heel strike angle reduced by 3.22°, 95% CI, −6.05 to −0.39; and stride speed reduced by 0.09 m/s, 95% CI, −0.19 to −0.00 for the poor memory elderly among the CI group, but not found the association in CN group. In addition, serious medial temporal atrophy (MTA), small volumes of the frontal lobe and occipital lobe were associated with long TUG time and small heel strike angles; small volumes of the temporal lobe, frontal lobe, and parietal lobe were associated with slow stride speed.ConclusionOur findings suggested that memory deficit was associated with increased fall risk in the elderly with aMCI and mild AD. The association might be mediated by the atrophy of medial temporal, frontal, and parietal lobes. Additionally, increased fall risk, tested by TUG time, heel stride angles, and stride speed, might be objective and convenient kinematics markers for dynamic monitoring of both memory function and fall risk.

Medial Temporal Atrophy Contributes to Cognitive Impairment in Cerebral Small Vessel Disease.

BackgroundThe role of brain atrophy in cognitive decline related to cerebral small vessel disease (CSVD) remains unclear. This study used AccuBrain™ to identify major CSVD-related brain changes and verified the relationship between brain atrophy and different cognition domains in CSVD patients.MethodsAll enrolled 242 CSVD patients and 76 healthy participants underwent magnetic resonance imaging examinations and detailed neuropsychological scale assessments were collected at the same time. The AccuBrain™ technology was applied to fully automated image segmentation, measurement, and calculation of the acquired imaging results to obtain the volumes of different brain partitions and the volume of WMH for quantitative analysis. Correlation analyses were used to estimate the relationship between MRI features and different cognitive domains. Multifactor linear regression models were performed to analyze independent predictors of MTA and cognitive decline.ResultsCSVD patients exhibited multiple gray matter nucleus volume decreases in the basal ganglia regions and brain lobes, including the temporal lobe (P = 0.019), especially in the medial temporal lobe (p < 0.001), parietal lobe (p = 0.013), and cingulate lobe (p = 0.036) compare to HC. The volume of PWMH was an independent predictor of MTA for CSVD patients. Both medial temporal atrophy (MTA) and PWMH were associated with cognition impairment in CSVD-CI patients. MTA mediated the effect of PWMH on executive function in CSVD-CI patients.ConclusionsOur results showed that MTA was related to cognition impairment in CSVD patients, which might become a potential imaging marker for CSVD-CI.

Cognitive, academic, executive and psychological functioning in children with spastic motor type cerebral palsy: Influence of extent, location, and laterality of brain lesions.

To investigate, in spastic motor-type cerebral palsy, the association between 1) the location and extent of brain lesions and numerous psychological outcomes; 2) the laterality of brain lesions and performance of verbal-related cognitive functions. The semi-quantitative scale for MRI (sqMRI) was scored for 101 children with cerebral palsy. Non-verbal and verbal proxy intelligence quotients (IQ), word reading, spelling, numerical operations skills, executive functioning, and psychological adjustment were assessed. Relationships between global and regional sqMRI scores and clinical scores were examined. The best multivariable linear regression model for each outcome was identified using the Bayesian Information Criteria. Regional sqMRI scores, gross motor functioning, manual ability, and epilepsy status were considered for inclusion as covariables. Where sqMRI scores made statistically significant contributions to models of verbal-related functioning, data were reanalysed including these sqMRI scores' laterality index. Verbal-related outcomes were compared between participants with left-sided versus bilateral brain lesions. Medial dorsal thalamus and parietal lobe lesions significantly accounted for poorer verbal proxy-IQ. Left-hemisphere lateralization of temporal lobe lesions was associated with poorer verbal proxy-IQ. Participants with bilateral lesions performed significantly better than those with unilateral left-sided lesions in verbal cognitive functions. Controlling for epilepsy diagnosis, participants with ventral posterior lateral thalamus lesions presented with better Behaviour Rating Inventory of Executive Function scores, although within the normal range. sqMRI scores were not significantly associated with some psychological outcomes or these only bordered on significance after accounting for relevant control variables. The laterality of early-life lesions influences the development of verbal-related cognitive functions.

The neuroprotective effects of oxygen therapy in Alzheimer’s disease: a narrative review

Alzheimer’s disease (AD) is a degenerative neurological disease that primarily affects the elderly. Drug therapy is the main strategy for AD treatment, but current treatments suffer from poor efficacy and a number of side effects. Non-drug therapy is attracting more attention and may be a better strategy for treatment of AD. Hypoxia is one of the important factors that contribute to the pathogenesis of AD. Multiple cellular processes synergistically promote hypoxia, including aging, hypertension, diabetes, hypoxia/obstructive sleep apnea, obesity, and traumatic brain injury. Increasing evidence has shown that hypoxia may affect multiple pathological aspects of AD, such as amyloid-beta metabolism, tau phosphorylation, autophagy, neuroinflammation, oxidative stress, endoplasmic reticulum stress, and mitochondrial and synaptic dysfunction. Treatments targeting hypoxia may delay or mitigate the progression of AD. Numerous studies have shown that oxygen therapy could improve the risk factors and clinical symptoms of AD. Increasing evidence also suggests that oxygen therapy may improve many pathological aspects of AD including amyloid-beta metabolism, tau phosphorylation, neuroinflammation, neuronal apoptosis, oxidative stress, neurotrophic factors, mitochondrial function, cerebral blood volume, and protein synthesis. In this review, we summarized the effects of oxygen therapy on AD pathogenesis and the mechanisms underlying these alterations. We expect that this review can benefit future clinical applications and therapy strategies on oxygen therapy for AD.