Medial Parietal Lobe Research Articles

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.

The Temporal Lobe as a Symptomatogenic Zone in Medial Parietal Lobe Epilepsy.

Some surgical failures after temporal lobe epilepsy surgery may be due to the presence of an extratemporal epileptogenic zone. Of particular interest is the medial parietal lobe due to its robust connectivity with mesial temporal structures. Seizures in that area may be clinically silent before propagating to the symptomatogenic temporal lobe. In this paper, we present an overview of the anatomical connectivity, semiology, radiology, electroencephalography, neuropsychology, and outcomes in medial parietal lobe epilepsy. We also present two illustrative cases of seizures originating from the precuneus and the posterior cingulate cortex. We conclude that the medial parietal lobe should be strongly considered for sampling by intracranial electrodes in individuals with nonlesional temporal lobe epilepsy, especially if scrutinizing the presurgical data produces discordant findings.

MRI findings suggestive of Alzheimer's disease in patients with primary open angle glaucoma - a single sequence analysis using rapid 3D T1 spoiled gradient echo.

Primary open-angle glaucoma (POAG) is a degenerative optic neuropathy disease which has somewhat similar pathophysiology to Alzheimer's disease (AD). This study aims to determine the presence of medial temporal atrophy and parietal lobe atrophy in patients with POAG compared to normal controls using medial temporal atrophy (MTA) scoring and posterior cortical atrophy (PCA) scoring system on T1 magnetization-prepared rapid gradient-echo. 50 POAG patients and 50 normal subjects were recruited and an MRI brain with T1-magnetization-prepared rapid gradient-echo was performed. Medial temporal lobe and parietal lobe atrophy were by MTA and PCA/Koedam scoring. The score of the PCA and MTA were compared between the POAG group and the controls. There was a significant statistical difference between PCA score in POAG and the healthy control group (p-value = 0.026). There is no statistical difference between MTA score in POAG compared to the healthy control group (p-value = 0.58). This study suggests a correlation between POAG and PCA score. Potential application of this scoring method in clinical diagnosis and monitoring of POAG patients. The scoring method used in AD may also be applied in the diagnosis and monitoring of POAGMRI brain, specifically rapid volumetric T1 spoiled gradient echo sequence, may be applied in POAG assessment.

Influence of amyloid deposition on the interaction between tau and glucose metabolism

AbstractBackgroundPathological hallmarks of Alzheimer’s disease include the formation of extracellular Aβ plaques and intracellular neurofibrillary tau tangles, which with recent PET imaging advances can be assessed in vivo. Accumulation of tau has been closely linked to metabolic abnormalities in PET imaging studies, with inverse associations between tau deposition and glucose metabolism. This study aimed to assess whether the association between [18F]FDG and [18F]AV1451 in cognitively impaired patients is dependent on the presence of significant amyloid pathology.Method240 patients with mild cognitive impairment or Alzheimer’s disease (Mean age = 74.5 years, SD = 8.03) were evaluated from the Alzheimer’s Disease Neuroimaging Initiative (adni.loni.usc.edu). All participants completed a T1‐weighted MPRAGE MRI, amyloid ([18F]AV45 or [18F]florbetaben), [18F]AV1451 and [18F]FDG scans. Standard uptake ratio values were calculated in SPM12 to identify the glucose metabolic rate and tau deposition within cortical regions. Amyloid status (Aβ‐positive/Aβ‐negative) was determined from processed data using a whole brain cerebellar ratio with a cut‐off value of 1.11 ([18F]AV45) and 1.08 ([18F)florbetaben). Pearson’s correlation coefficients were calculated to assess the relationship between imaging modalities.ResultThere were significant negative associations between AV1451 and FDG tracer uptake in the medial temporal lobe (r = ‐0.389, p <0 .001), occipital lobe (r = ‐0.276, p = 0.001), parietal lobe (r = ‐0.209, p = 0.014), and posterior cingulate (r = ‐0.245, p = 0.004) in Aβ‐positive patients. Similarly, a strong negative relationship was observed between the imaging modalities in Aβ‐negative patients in the medial temporal lobe (r = ‐0.345, p < 0.001), however a significant positive association was also observed in the anterior cingulate cortex (r = 0.350, p < 0.001).ConclusionThis study demonstrated that [18]FDG and [18F]AV1451 tracers have strong regional signal associations in patients with cognitive impairment. The results indicate that tau has a detrimental effect on glucose metabolism in the medial temporal lobe, independent of significant amyloid plaque formation. In patients determined as amyloid‐negative, we may be observing some compensatory regional increase in glucose metabolism in the early stages of tau accumulation.

Comparison of linear combination modeling strategies for edited magnetic resonance spectroscopy at 3 T

J‐difference‐edited spectroscopy is a valuable approach for the in vivo detection of γ‐aminobutyric‐acid (GABA) with magnetic resonance spectroscopy (MRS). A recent expert consensus article recommends linear combination modeling (LCM) of edited MRS but does not give specific details regarding implementation. This study explores different modeling strategies to adapt LCM for GABA‐edited MRS. Sixty‐one medial parietal lobe GABA‐edited MEGA‐PRESS spectra from a recent 3‐T multisite study were modeled using 102 different strategies combining six different approaches to account for co‐edited macromolecules (MMs), three modeling ranges, three baseline knot spacings, and the use of basis sets with or without homocarnosine. The resulting GABA and GABA+ estimates (quantified relative to total creatine), the residuals at different ranges, standard deviations and coefficients of variation (CVs), and Akaike information criteria, were used to evaluate the models' performance. Significantly different GABA+ and GABA estimates were found when a well‐parameterized MM3cobasis function was included in the model. The mean GABA estimates were significantly lower when modeling MM3co, while the CVs were similar. A sparser spline knot spacing led to lower variation in the GABA and GABA+ estimates, and a narrower modeling range—only including the signals of interest—did not substantially improve or degrade modeling performance. Additionally, the results suggest that LCM can separate GABA and the underlying co‐edited MM3co. Incorporating homocarnosine into the modeling did not significantly improve variance in GABA+ estimates. In conclusion, GABA‐edited MRS is most appropriately quantified by LCM with a well‐parameterized co‐edited MM3cobasis function with a constraint to the nonoverlapped MM0.93, in combination with a sparse spline knot spacing (0.55 ppm) and a modeling range of 0.5–4 ppm.

Hippocampal Connectivity with Retrosplenial Cortex is Linked to Neocortical Tau Accumulation and Memory Function.

The mechanisms underlying accumulation of Alzheimer's disease (AD)-related tau pathology outside of the medial temporal lobe (MTL) in older adults are unknown but crucial to understanding cognitive decline. A growing body of evidence from human and animal studies strongly implicates neural connectivity in the propagation of tau in humans, but the pathways of neocortical tau spread and its consequences for cognitive function are not well understood. Using resting state functional magnetic resonance imaging (fMRI) and tau PET imaging from a sample of 97 male and female cognitively normal older adults, we examined MTL structures involved in medial parietal tau accumulation and associations with memory function. Functional connectivity between hippocampus (HC) and retrosplenial cortex (RsC), a key region of the medial parietal lobe, was associated with tau in medial parietal lobe. By contrast, connectivity between entorhinal cortex (EC) and RsC did not correlate with medial parietal lobe tau. Further, greater hippocampal-retrosplenial (HC-RsC) connectivity was associated with a stronger correlation between MTL and medial parietal lobe tau. Finally, an interaction between connectivity strength and medial parietal tau was associated with episodic memory performance, particularly in the visuospatial domain. This pattern of tau accumulation thus appears to reflect pathways of neural connectivity, and propagation of tau from EC to medial parietal lobe via the HC may represent a critical process in the evolution of cognitive dysfunction in aging and AD.SIGNIFICANCE STATEMENT The accumulation of tau pathology in the neocortex is a fundamental process underlying Alzheimer's disease (AD). Here, we use functional connectivity in cognitively normal older adults to track the accumulation of tau in the medial parietal lobe, a key region for memory processing that is affected early in the progression of AD. We show that the strength of connectivity between the hippocampus (HC) and retrosplenial cortex (RsC) is related to medial parietal tau burden, and that these tau and connectivity measures interact to associate with episodic memory performance. These findings establish the HC as the origin of medial parietal tau and implicate tau pathology in this region as a crucial marker of the beginnings of AD.

A-62 Case of Gerstmann’s Syndrome Due to Brain Tumor of Unknown Etiology

Abstract Objective Gerstmann’s syndrome is a rare neurological condition that is characterized by agraphia, acalculia, finger agnosia, and right–left confusion. Gerstmann’s syndrome most commonly occurs due to stroke in parietal region of the brain. This case demonstrates the clinical presentation of Gerstmann’s syndrome in a patient due to a brain tumor in the parietal lobe. Method The patient is a 50-year-old, right-handed, Hispanic male with 16 years of education who reported memory changes over the last 10 months. His medical history is notable for two brain tumors of unknown etiology which have been present for 10 months. He has completed multiple biopsies and magnetic resonance imaging prior to his neuropsychological evaluation. Initial scans showed two tumors, one in the right medial occipital parietal lobe and one in the left parietal extending into the corpus callosum. The right medial occipital parietal lobe tumor has not been visualized for the past six months. Results His neurocognitive profile was characterized by impairments in verbal memory (both stories and word list), arithmetic, semantic fluency, and executive functioning. Across memory measures, he performed in the borderline to impaired range, and did not benefit from recognition items. Arithmetic performance was also in the borderline range and did not show improvement with additional time. Conclusions This case demonstrates the classical findings of Gerstmann’s syndrome with additional neurocognitive impairments in the areas of memory and executive functioning. This case is also unique in that the lesions of the parietal lobe are due to brain tumor with unknown etiology.

Changes in Default-Mode Network Associated With Childhood Trauma in Schizophrenia

BackgroundThere is considerable evidence of dysconnectivity within the default-mode network (DMN) in schizophrenia, as measured during resting-state functional MRI (rs-fMRI). History of childhood trauma (CT) is observed at a higher frequency in schizophrenia than in the general population, but its relationship to DMN functional connectivity has yet to be investigated.MethodsCT history and rs-fMRI data were collected in 65 individuals with schizophrenia and 132 healthy controls. Seed-based functional connectivity between each of 4 a priori defined seeds of the DMN (medial prefrontal cortex, right and left lateral parietal lobes, and the posterior cingulate cortex) and all other voxels of the brain were compared across groups. Effects of CT on functional connectivity were examined using multiple regression analyses. Where significant associations were observed, regression analyses were further used to determine whether variance in behavioral measures of Theory of Mind (ToM), previously associated with DMN recruitment, were explained by these associations.ResultsSeed-based analyses revealed evidence of widespread reductions in functional connectivity in patients vs controls, including between the left/right parietal lobe (LP) and multiple other regions, including the parietal operculum bilaterally. Across all subjects, increased CT scores were associated with reduced prefrontal-parietal connectivity and, in patients, with increased prefrontal-cerebellar connectivity also. These CT-associated differences in DMN connectivity also predicted variation in behavioral measures of ToM.ConclusionsThese findings suggest that CT history is associated with variation in DMN connectivity during rs-fMRI in patients with schizophrenia and healthy participants, which may partly mediate associations observed between early life adversity and cognitive performance.

Structural and Functional Brain Changes in Hemodialysis Patients with End-Stage Renal Disease: DTI Analysis Results and ALFF Analysis Results.

IntroductionThe current study aimed to depict intrinsic structural changes and the spontaneous brain activity patterns in voxel level in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD) by using diffusion-tensor imaging and resting-state functional magnetic resonance (MR) imaging with an amplitude of low-frequency fluctuations (ALFF) algorithm and their clinical relevance.Materials and MethodsIn the study, the diffusion-tensor imaging and resting-state functional MR imaging were performed in forty-two hemodialysis patients with ESRD and 42 healthy control subjects. Neuropsychological and laboratory tests were performed in all subjects. ALFF, fraction anisotropy (FA), and mean diffusivity (MD) values were compared between the two groups. Correlations between ALFF, FA or MD values, and clinical markers were analyzed.ResultsWe found that ESRD patients exhibited significantly lower ALFF values in multiple areas, including medial frontal gyrus, limbic lobe, superior frontal gyrus, bilateral lingual gyri, occipital lobe, parahippocampal gyrus, precuneus, while increased ALFF values in medial frontal gyrus than healthy controls. FA values were decreased in medial frontal gyrus, parietal lobe, and left precuneus regions in the ESRD group compared with controls. Importantly, FA for the frontal and parietal lobes was negatively associated with the dialysis duration of ESRD patients, ALFF z-scores for the medial prefrontal cortex (MPFC) were positively correlated with the dialysis duration of ESRD patients and Serum calcium of ESRD patients negatively correlated with FA values in the frontal and parietal lobes (p<0.05).ConclusionOur study revealed that both impaired brain structure and function in ESRD patients with routine hemodialysis distributed mainly in the parietal, temporal, and frontal lobes. ESRD patients have cognitive impairment and declined memory ability. Serum calcium and dialysis duration might be associated with the impairment of brain structure and function in patients with ESRD.

Altered Inferior Parietal Functional Connectivity is Correlated with Praxis and Social Skill Performance in Children with Autism Spectrum Disorder.

Children with autism spectrum disorder (ASD) have difficulties perceiving and producing skilled gestures, or praxis. The inferior parietal lobule (IPL) is crucial to praxis acquisition and expression, yet how IPL connectivity contributes to autism-associated impairments in praxis as well as social-communicative skill remains unclear. Using resting-state functional magnetic resonance imaging, we applied independent component analysis to test how IPL connectivity relates to praxis and social-communicative skills in children with and without ASD. Across all children (with/without ASD), praxis positively correlated with connectivity of left posterior-IPL with the left dorsal premotor cortex and with the bilateral posterior/medial parietal cortex. Praxis also correlated with connectivity of right central-IPL connectivity with the left intraparietal sulcus and medial parietal lobe. Further, in children with ASD, poorer praxis and social-communicative skills both correlated with weaker right central-IPL connectivity with the left cerebellum, posterior cingulate, and right dorsal premotor cortex. Our findings suggest that IPL connectivity is linked to praxis development, that contributions arise bilaterally, and that right IPL connectivity is associated with impaired praxis and social-communicative skills in autism. The findings underscore the potential impact of IPL connectivity and impaired skill acquisition on the development of a range of social-communicative and motor functions during childhood, including autism-associated impairments.

QOL-53. GENOME ASSOCIATIONS WITH NEUROCOGNITIVE OUTCOMES, CEREBRAL MICROBLEEDS (CMBS), AND BRAIN VOLUME AND WHITE MATTER (WM) CHANGES IN PEDIATRIC BRAIN TUMOR SURVIVORS

OBJECTIVETo identify genetic predictors of neurocognition, CMBs, brain volume, and WM changes in pediatric brain tumor survivors.METHODSPatients were selected from an existing cohort (RadART) if they had: 1) at least one neurocognitive evaluation using computer-based CogState; 2) available DNA; 3) standard imaging. Candidate gene or genome-wide genotyping was performed on all patients. CMBs were identified using a semi-automated algorithm developed in MATLAB. Volume of T2/FLAIR WM signal abnormality was measured using a semi-automated method based on a convolutional neural network. Brain volume and cortical thickness were measured using FreeSurfer volumetric analysis. Logistic and linear regression were done to compare phenotypes with candidate genotypes. Genome-wide efficient mixed-model analysis was done to compare neurocognition and CMBs. Gene set analysis was done using https://fuma.ctglab.nl/.RESULTSAPOE4 was a candidate variant associated with non-lobar, larger volume CMBs (p<0.05). At the GWAS-level (n=225), specific genes trended with visual memory, psychomotor function, and CMB count (p<5x10-8). Using gene set analyses, there were gene set trends seen with CMB count and psychomotor function. Small sample size and low mutant allele frequency limited reliability of these findings. Preliminary volumetric analysis show reduced volume within the right parietal, medial occipital and inferior temporal lobes with increased cortical thickness in the left occipital and medial parietal lobe in patients carrying the ApoE4 allele. WM signal assessments are ongoing.CONCLUSIONGenetic markers may be associated with neurocognition, CMBs, brain volume and WM changes in pediatric brain tumor survivors; however, larger cohorts are needed to confirm specific gene relevance.

Hippocampal‐retrosplenial connectivity is associated with tau pathology and memory in cognitively normal older adults

AbstractBackgroundTau pathology is thought to spread transneuronally from medial temporal lobe (MTL) to medial parietal lobe (MPL) in cognitively normal older adults, but it is not known precisely which structures and processes are involved. We hypothesize that functional connectivity influences tau spread from hippocampus to the MPL, with consequences for cognition.MethodNinety‐seven cognitively normal older adults from the Berkeley Aging Cohort Study (76.4±6.1 years) received tau‐PET with 18F‐Flortaucipir, Aβ‐PET with 11C‐PiB, and resting state fMRI. We assessed unilateral resting state functional connectivity (FC) between retrosplenial cortex (RsC), an area of known connectivity with the MTL, and hippocampus (HC), anterolateral entorhinal cortex (alEC), and posteromedial entorhinal cortex (pmEC). We then used linear models to examine the association of FC strength (β‐weight) between RsC and the proportion of suprathreshold voxels for tau accumulation (SUVR&gt;1.4) in MPL. Finally, we examined interactions between FC strength and tau to predict downstream tau accumulation and memory.ResultSemipartial region‐region correlations revealed RsC FC with HC in both hemispheres [Left: β=0.33, p&lt;0.001, Right: β=0.40, p&lt;0.001], but not with alEC or pmEC in either hemisphere (Figure 1). Adjusting for age, sex, and amyloid status, proportion of suprathreshold voxels in MPL was associated with RsC‐HC connectivity strength bilaterally [Left: β=0.153, p=0.004; Right: β=0.186, p=0.002], but not RsC‐alEC or RsC‐pmEC connectivity strength (Figure 2). In addition, proportion of suprathreshold voxels in MPL was associated with the interaction between RsC‐HC connectivity strength and hippocampal tau (pvc‐SUVR) [Left: β=0.586, p=0.008; Right: β=0.613, p=0.022] (Figure 3a). Adjusting for age, years of education, and practice effects, the interaction between RsC‐HC connectivity strength and MPL tau (left hemisphere only) was associated with spatial memory performance [β=‐12.773, p=0.002] (Figure 3b).ConclusionIn cognitively normal older adults, RsC exhibits FC with hippocampus but not alEC or pmEC, and the strength of this RsC‐HC connectivity predicts tau accumulation in the MPL, suggesting that tau pathology spreads to MPL through the hippocampus. Further, RsC‐HC connectivity modulated the relationship between MTL and MPL tau as well as between MPL tau and spatial memory, indicating that MTL‐MPL FC may influence the spread of tau and cognitive function.

NCOG-71. GENOME ASSOCIATIONS WITH NEUROCOGNITIVE OUTCOMES, CEREBRAL MICROBLEEDS (CMBS), AND BRAIN VOLUME AND WHITE MATTER (WM) CHANGES IN PEDIATRIC BRAIN TUMOR SURVIVORS

Abstract OBJECTIVE To identify genetic predictors of neurocognition, CMBs, brain volume, and WM changes in pediatric brain tumor survivors. METHODS Patients were selected from an existing cohort (RadART) if they had: 1) at least one neurocognitive evaluation using computer-based CogState; 2) available DNA; 3) standard imaging. Candidate gene or genome-wide genotyping was performed on all patients. CMBs were identified using a semi-automated algorithm developed in MATLAB. Volume of T2/FLAIR WM signal abnormality was measured using a semi-automated method based on a convolutional neural network. Brain volume and cortical thickness were measured using FreeSurfer volumetric analysis. Logistic and linear regression were done to compare phenotypes with candidate genotypes. Genome-wide efficient mixed-model analysis was done to compare neurocognition and CMBs. Gene set analysis was done using https://fuma.ctglab.nl/. RESULTS APOE4 was a candidate variant associated with non-lobar, larger volume CMBs (p&amp;lt; 0.05). At the GWAS-level (n=225), specific genes trended with visual memory, psychomotor function, and CMB count (p&amp;lt; 5x10-8). Using gene set analyses, there were gene set trends seen with CMB count and psychomotor function. Small sample size and low mutant allele frequency limited reliability of these findings. Preliminary volumetric analysis show reduced volume within the right parietal, medial occipital and inferior temporal lobes with increased cortical thickness in the left occipital and medial parietal lobe in patients carrying the ApoE4 allele. WM signal assessments are ongoing. CONCLUSION Genetic markers may be associated with neurocognition, CMBs, brain volume and WM changes in pediatric brain tumor survivors; however, larger cohorts are needed to confirm specific gene relevance.

Regional Hypoperfusion Predicts Decline in Everyday Functioning at Three-Year Follow-Up in Older Adults without Dementia

Increasing evidence indicates that cerebrovascular dysfunction may precede cognitive decline in aging and Alzheimer's disease (AD). Reduced cerebral blood flow (CBF) is associated with cognitive impairment in older adults. However, less is known regarding the association between CBF and functional decline, and whether CBF predicts functional decline beyond cerebrovascular and metabolic risk factors. To examine the association between regional CBF and functional decline in nondemented older adults. One hundred sixty-six (N = 166) participants without dementia from the Alzheimer's Disease Neuroimaging Initiative underwent neuropsychological testing and neuroimaging. Pulsed arterial spin labeling magnetic resonance imaging was acquired to quantify resting CBF. Everyday functioning was measured using the Functional Assessment Questionnaire at baseline and annual follow-up visit across three years. Adjusting for age, education, sex, cognitive status, depression, white matter hyperintensity volume, cerebral metabolism, and reference (precentral) CBF, linear mixed effects models showed that lower resting CBF at baseline in the medial temporal, inferior temporal, and inferior parietal lobe was significantly associated with accelerated decline in everyday functioning. Results were similar after adjusting for conventional AD biomarkers, including cerebrospinal fluid (CSF) amyloid-β (Aβ) and hyperphosphorylated tau (p-tau) and apolipoprotein E (APOE) ɛ4 positivity. Individuals who later converted to dementia had lower resting CBF in the inferior temporal and parietal regions compared to those who did not. Lower resting CBF in AD vulnerable regions including medial temporal, inferior temporal, and inferior parietal lobes predicted faster rates of decline in everyday functioning. CBF has utility as a biomarker in predicting functional declines in everyday life and conversion to dementia.

Assessment of visually guided reaching in prodromal Alzheimer’s disease: a cross-sectional study protocol

IntroductionRecent evidence has implicated the precuneus of the medial parietal lobe as one of the first brain areas to show pathological changes in Alzheimer’s disease (AD). Damage to the precuneus...

S162. MULTI-MODAL ANALYSIS OF THE EFFECTS OF URBAN UPBRINGING ON BRAIN STRUCTURE: THE FOR2107 COHORT

BackgroundUrbanicity has been identified as a major environmental risk factor for schizophrenia as well as other major mental disorders. While initial structural brain imaging studies have pointed to medial and lateral prefrontal cortices being associated with urbanicity during childhood and adolescence, most of these studies have been limited to smaller samples and single analysis methods. The present study used the large ongoing FOR2107 multi-centre study cohort (Kircher et al., 2018) to analyse associations of urban upbringing.MethodsWe analysed a data set of n=625 healthy subjects without a current or previous psychiatric disorder (ascertained through SCID-I interviews), who underwent 3 Tesla MRI scanning, obtaining a high-resolution T1-weighted MPRAGE and a DTI scan. We subsequently also analysed a pilot samples of 42 patients with DSM-IV schizophrenia. We obtained data on urban upbringing (Lederbogen score; Lederbogen et al., 2014) for the first 15 years of life, as well as number of moves. T1 data were pre-processed using CAT12 software, using surface-based morphometric analysis of cortical thickness (CT) with 15 mm smoothing. DTI data were analysed using the TBSS approach in FSL software. We used general linear models to calculate multiple regression analyses using both linear and quadratic (non-linear) associations with urbanicity scores, followed up by analyses of correlations with number of relocations (as unspecific stress factors). Analyses of CT and DTI were each corrected for multiple comparisons using FWE.ResultsIn the healthy subject cohort we identified a significant negative linear correlation (p=0.042 FWE cluster-level; p=0.014 peak-level) between urban upbringing scores and cortical thickness (CT) in a right precuneus / posterior cingulate cluster (x/y/z=35;-88;-15), while non-linear analysis identified an additional trend in the left occipital cortex (p=0.073 FWE cluster-level; -17;-100;15). We did not find significant effects for number of relocations/moves. DTI analysis of fractional anisotropy (FA) showed a significant association (all p<0.05 FWE-corrected) for the uncinate fasciculus and inferior fronto-occipital fasciculus. CT analysis in the schizophrenia pilot cohort showed similar effects, but in a more dorsal precuneus cluster (6;-56;45) only at uncorrected levels.DiscussionOur study identified structural variation in cortical thickness in the precuneus / posterior cingulate cortex of healthy subjects, regions linked to abnormal DMN activity and stress. While the trend-level finding in schizophrenia patients was located in an adjacent cluster, our findings can be interpreted as these medial parietal lobe structure mediating this particular risk factor. Our findings argue against a more wide-spread non-specific effect, as seen in some earlier smaller studies, but points to distinct neuronal network as mediators of this particular risk. The identified brain regions are linked to stress. Unlike previous prefrontal findings, they suggest a new link to the precuneus, a central hub of the default mode network. Given that these effects were observed in clinically healthy subjects, our findings also carry implications for a better understanding of the macro-environment in adolescence.

Subjective well-being is associated with the functional connectivity network of the dorsal anterior insula

The feeling of happiness is beneficial for both mental and physical health. Based on the findings of previous studies that reported that the insular cortex is a crucial region for subjective feelings, including happiness, in this study, we further identified the subregion of the insula and its functional connectivity associated with subjective well-being (SWB). Using an iterative seed-target-seed approach, we labelled the posterior, dorsal, and ventral anterior insular regions of interest (ROIs) and evaluated the association between functional connectivity of each of these insular ROIs and the self-reported SWB in a group of 75 healthy elderly adults. We demonstrated that the functional connectivity of the dorsal anterior insula (dAI) was significantly correlated with SWB. This relationship was negative and unique for the functional connectivity of left dAI with specific regions from the default-mode network, including the anterior medial prefrontal cortex and inferior parietal lobe. Our result suggested a functional connectivity network of the left dAI with specific DMN brain regions, suggesting the neural basis of SWB.

Functional MRI and Structural Connectome Analysis of Language Networks in Japanese-English Bilinguals

We aimed to clarify the mechanisms of neural plasticity involved in language. We hypothesized that alterations which occur in bilinguals could reflect the mechanisms of acquisition of a second language and simulate neural plasticity related to language. We compared spatial characteristics of story listening-related hemodynamic modulations and subcortical fiber networks between monolinguals and bilinguals. Participants were Japanese monolinguals and Japanese–English bilinguals whose first language was Japanese. We divided bilinguals into early and late bilinguals depending on whether the age of acquisition was before after 7 years of age. We applied intergroup analysis to investigate the following: (1) blood oxygen level-dependent response (BOLD) responses during story listening by block-based fMRI; (2) number of fibers (NOFs) between specific edges by DTI. Both bilingual samples showed larger BOLD responses (BRs) in the right putamen and bilateral superior temporal gyri compared to the Japanese monolinguals in fMRI. Late bilinguals demonstrated bigger BRs in the right anterior temporal lobe and left medial parietal lobe than early bilinguals. Early bilinguals showed a higher NOFs between the right putamen and precentral gyrus than monolinguals and late bilinguals in DTI. Late bilinguals showed a lower NOFs between the left superior temporal gyrus and supramarginal gyrus than monolinguals and early bilinguals. Early bilinguals reinforce the subcortical fiber network between the right putamen and precentral gyrus, and activate the right putamen to gain alternative language function. We conclude that these key cerebral regions and subcortical fiber networks could contribute to the neural plasticity of language.

Brain structure changes over time in normal and mildly impaired aged persons.

Structural brain changes in aging are known to occur even in the absence of dementia, but the magnitudes and regions involved vary between studies. To further characterize these changes, we analyzed paired MRI images acquired with identical protocols and scanner over a median 5.8-year interval. The normal study group comprised 78 elders (25M 53F, baseline age range 70–78 years) who underwent an annual standardized expert assessment of cognition and health and who maintained normal cognition for the duration of the study. We found a longitudinal grey matter (GM) loss rate of 2.56 ± 0.07 ml/year (0.20 ± 0.04%/year) and a cerebrospinal fluid (CSF) expansion rate of 2.97 ± 0.07 ml/year (0.22 ± 0.04%/year). Hippocampal volume loss rate was higher than the GM and CSF global rates, 0.0114 ± 0.0004 ml/year (0.49 ± 0.04%/year). Regions of greatest GM loss were posterior inferior frontal lobe, medial parietal lobe and dorsal cerebellum. Rates of GM loss and CSF expansion were on the low end of the range of other published values, perhaps due to the relatively good health of the elder volunteers in this study. An additional smaller group of 6 subjects diagnosed with MCI at baseline were followed as well, and comparisons were made with the normal group in terms of both global and regional GM loss and CSF expansion rates. An increased rate of GM loss was found in the hippocampus bilaterally for the MCI group.

Tau PET and relative cerebral blood flow in dementia with Lewy bodies: A PET study

PurposeAlpha-synuclein often co-occurs with Alzheimer’s disease (AD) pathology in Dementia with Lewy Bodies (DLB). From a dynamic [18F]flortaucipir PET scan we derived measures of both tau binding and relative cerebral blood flow (rCBF). We tested whether regional tau binding or rCBF differed between DLB patients and AD patients and controls and examined their association with clinical characteristics of DLB. MethodsEighteen patients with probable DLB, 65 AD patients and 50 controls underwent a dynamic 130-minute [18F]flortaucipir PET scan. DLB patients with positive biomarkers for AD based on cerebrospinal fluid or amyloid PET were considered as DLB with AD pathology (DLB-AD+). Receptor parametric mapping (cerebellar gray matter reference region) was used to extract regional binding potential (BPND) and R1, reflecting (AD-specific) tau pathology and rCBF, respectively. First, we performed regional comparisons of [18F]flortaucipir BPND and R1 between diagnostic groups. In DLB patients only, we performed regression analyses between regional [18F]flortaucipir BPND, R1 and performance on ten neuropsychological tests. ResultsRegional [18F]flortaucipir BPND in DLB was comparable with tau binding in controls (p > 0.05). Subtle higher tau binding was observed in DLB-AD+ compared to DLB-AD- in the medial temporal and parietal lobe (both p < 0.05). Occipital and lateral parietal R1 was lower in DLB compared to AD and controls (all p < 0.01). Lower frontal R1 was associated with impaired performance on digit span forward (standardized beta, stβ = 0.72) and category fluency (stβ = 0.69) tests. Lower parietal R1 was related to lower delayed (stβ = 0.50) and immediate (stβ = 0.48) recall, VOSP number location (stβ = 0.70) and fragmented letters (stβ = 0.59) scores. Lower occipital R1 was associated to worse performance on VOSP fragmented letters (stβ = 0.61), all p < 0.05. ConclusionThe amount of tau binding in DLB was minimal and did not differ from controls. However, there were DLB-specific occipital and lateral parietal relative cerebral blood flow reductions compared to both controls and AD patients. Regional rCBF, but not tau binding, was related to cognitive impairment. This indicates that assessment of rCBF may give more insight into disease mechanisms in DLB than tau PET.