Hematocolpos due to lower vaginal agenesis in an adolescent girl.

Background: Hematocolpos due to imperforate hymen is an important differential diagnosis of abdominal pain in early adolescent stage. However, hematocolpos due to lower vaginal agenesis must be considered because the management differs. Case Presentation: A healthy 11-year-old girl presented with a 2-day left lower abdominal pain history. Her breast development had begun, but she had not reached menarche. Computed tomography showed high absorptive value liquid filling the upper vaginal to uterine cavity, a pale highly absorptive fluid component suggestive of hemorrhagic ascites in the abdominal cavity on both sides of the uterus, and normal bilateral ovaries. Magnetic resonance imaging diagnosed hematocolpos due to lower vaginal agenesis. The blood clot was aspirated with a transabdominal ultrasound-guided transvaginal puncture. Conclusion: History-taking, imaging tests, and appropriate collaboration with obstetrician/gynecologist with awareness of secondary sexual characteristics were crucial in this case.

Convenient Auditory-Based Language and Executive Function Test for Patients With Amyotrophic Lateral Sclerosis: A Pilot Study.

OBJECTIVE: About 30%-50% of patients with amyotrophic lateral sclerosis (ALS) show cognitive impairment ranging from mild dysexecutive syndrome to frontotemporal dementia. We aimed to develop a brief cognitive test, convenient auditory-based language and executive function test (CABLET), for rapid detection of cognitive impairment in ALS, with reduced load on motor function. METHOD: The CABLET comprises two tests using auditory verbal stimuli: Test 1, assessing word repetition and lexical judgment, and Test 2, evaluating verbal short-term memory and semantics knowledge. The administration time of Test 1 and Test 2 was 1 and 3-5 min, respectively. Overall, 61 patients with ALS and 46 age-, sex-, and education-matched healthy controls participated in this study. All participants underwent existing neuropsychological tests and the CABLET. We investigated the applicability of the CABLET to detect ALS with cognitive impairment (ALSci) from normal cognition. RESULTS: Receiver operating characteristic analyses showed that both the CABLET total and Test 2 had good diagnostic accuracy (area under the curve [AUC]: total = 0.894, Test 2 = 0.893). Test 2 had the highest sensitivity (100% sensitivity and 71.4% specificity). No significant difference existed in the AUC between the analyses with and without age, education, and disease severity as covariates. Correlations were observed between the CABLET and established neuropsychological tests, supporting its good convergent validity. CONCLUSIONS: Our findings indicated that the CABLET could be useful in identifying ALSci quickly without adjusting for confounding factors. Further validation is required to evaluate it in larger groups and compare with ALS-specific cognitive screen.

A New Quantitative Triage System for Hospitalized Neonates to Assist with Decisions of Hospital Evacuation Priorities.

INTRODUCTION: Hospitalized neonates are vulnerable to natural and man-made disasters because of their persistent requirement for medical resources and may need to be evacuated to safe locations when electricity and medical gas supply become unreliable. In Japan, a triage system for hospitalized neonates, or the Simple Triage and Rapid Treatment for Neonates, Revised (START-Neo-R), has been used to determine whether neonates are in suitable conditions for transportation. However, this scale is not useful to determine the evacuation order of neonates because a considerable number of evacuees are classified into the same categories. STUDY OBJECTIVE: To solve this problem, a novel triage system, Neonatal Extrication Triage (NEXT) was developed. This study tested the validity and reproducibility of both triages and compared them with a standardized prognostic scoring system for hospitalized neonates, the Neonatal Therapeutic Intervention Scoring System (NTISS). METHODS: In this retrospective observational study, physicians and nurses independently assessed each neonate hospitalized at a tertiary neonatal intensive care unit (NICU) twice weekly using NEXT and START-Neo-R. The NEXT system comprises six questionnaires regarding medical resources required during transition and transportation, providing composite scores on a 12-point scale. The START-Neo-R classified neonates into five levels based on the severity of disease and dependence on medical care. Inter-rater reliability of both systems was assessed using Cohen's kappa coefficient, whereas the criterion validity with NTISS was assessed using Spearman's correlation coefficient. RESULTS: Overall, 162 neonates were assessed for 49 days, resulting in triage data for 1,079 accumulated patients. Both NEXT scores and START-Neo-R ranks were well-dispersed across different levels without excessive accumulation in specific categories. Inter-rater reliability of NEXT (kappa coefficient, 0.973; 95% confidence interval, 0.969-0.976) and START-Neo-R (kappa coefficient, 0.952; 95% confidence interval, 0.946-0.957) between physicians and nurses was sufficiently high. The correlation coefficient of NEXT and START-Neo-R scores with NTISS scores were 0.889 (P <.001) and 0.850 (P <.001), respectively. CONCLUSIONS: Both START-Neo-R and NEXT had good reproducibility and correlation with the severity of neonates indicated by NTISS. With its well-dispersed scores across different levels, the NEXT system might be a powerful tool to determine the priority of evacuation objectively.

Effectiveness of a novel semi-closed barrier device with a personalized exhaust in cough aerosol simulation according to particle counts and visualization of particles.

Oxygen therapy is an essential treatment for patients with coronavirus disease 2019, although there is a risk of aerosolization of additional viral droplets occurring during this treatment that poses a danger to healthcare professionals. High-flow oxygen through nasal cannula (HFNC) is a vital treatment bridging low-flow oxygen therapy with tracheal intubation. Although many barrier devices (including devices without negative pressure in the barrier) have been reported in the literature, few barrier devices are suitable for HFNC and aerosol infection control procedures during HFNC have not yet been established. Hence, we built a single cough simulator model to examine the effectiveness of three protective measures (a semi-closed barrier device, a personalized exhaust, and surgical masks) administered in isolation as well as in combination using particle counter measurements and laser sheet visualization. We found that the addition of a personalized exhaust to a semi-closed barrier device reduced aerosol leakage during HFNC without negative pressure. This novel combination may thus reduce aerosol exposure during oxygen therapy, enhance the protection of healthcare workers, and likely reduce nosocomial infection risk.

Reserve and Maintenance in the Aging Brain: A Longitudinal Study of Healthy Older Adults.

The aging brain undergoes structural changes even in very healthy individuals. Quantifying these changes could help disentangle pathologic changes from those associated with the normal human aging process. Using longitudinal magnetic resonance imaging (MRI) data from 227 carefully selected healthy human cohort with age ranging from 50 to 80 years old at baseline scan, we quantified age-related volumetric changes in the brain of healthy human older adults. Longitudinally, the rates of tissue loss in total gray matter (GM) and white matter (WM) were 2497.5 and 2579.8 mm3 per year, respectively. Across the whole brain, the rates of GM decline varied with regions in the frontal and parietal lobes having faster rates of decline, whereas some regions in the occipital and temporal lobes appeared relatively preserved. In contrast, cross-sectional changes were mainly observed in the temporal-occipital regions. Similar longitudinal atrophic changes were also observed in subcortical regions including thalamus, hippocampus, putamen, and caudate, whereas the pallidum showed an increasing volume with age. Overall, regions maturing late in development (frontal, parietal) are more vulnerable to longitudinal decline, whereas those that fully mature in the early stage (temporal, occipital) are mainly affected by cross-sectional changes in healthy older cohort. This may suggest that, for a successful healthy aging, the former needs to be maximally developed at an earlier age to compensate for the longitudinal decline later in life and the latter to remain relatively preserved even in old age, consistent with both concepts of reserve and brain maintenance.

Fiber-specific white matter analysis reflects upper motor neuron impairment in amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: To clarify the relationship between fiber-specific white matter changes in amyotrophic lateral sclerosis (ALS) and clinical signs of upper motor neuron (UMN) involvement, we performed a fixel-based analysis (FBA), a novel framework for diffusion-weighted imaging analysis. METHODS: We enrolled 96 participants, including 48 nonfamilial ALS patients and 48 age- and sex-matched healthy controls (HCs), in this study and conducted whole-brain FBA and voxel-based morphometry analysis. We compared the fiber density (FD), fiber morphology (fiber cross-section [FC]), and a combined index of FD and FC (FDC) between the ALS and HC groups. We performed a tract-of-interest analysis to extract FD values across the significant regions in the whole-brain analysis. Then, we evaluated the associations between FD values and clinical variables. RESULTS: The bilateral corticospinal tracts (CSTs) and the corpus callosum (CC) showed reduced FD and FDC in ALS patients compared with HCs (p < 0.05, familywise error-corrected), and the comparison of FCs revealed no region that was significantly different from another. Voxel-based morphometry showed cortical volume reduction in the regions, including the primary motor area. Clinical scores showed correlations with FD values in the CSTs (UMN score: rho = -0.530, p < 0.001; central motor conduction time [CMCT] in the upper limb: rho = -0.474, p = 0.008; disease duration: rho = -0.383, p = 0.007; ALS Functional Rating Scale-Revised: rho = 0.340, p = 0.018). In addition, patients whose CMCT was not calculated due to unevoked waves also showed FD reduction in the CSTs. CONCLUSIONS: Our findings suggest that FD values in the CST estimated via FBA can be potentially used in evaluating UMN impairments.

Rapidly progressive acute necrotizing encephalopathy associated with influenza A in an elderly adult.

BACKGROUND: Among the influenza-associated encephalopathies, acute necrotizing encephalopathy (ANE) has a particularly poor prognosis. While it usually progresses within 48 h, we encountered a rapidly evolving case with the patient falling into coma from lucidity within 10 min. CASE PRESENTATION: A 71-year-old man was found unconscious after taking a 10-min bath and brought to the emergency room. The head computed tomography (HCT) was normal, and he was diagnosed with heatstroke as a complication of influenza A. Despite effective therapy to correct his temperature, his consciousness did not improve, and within 24 h he progressed to multiple organ injury. Repeat HCT and subsequent magnetic resonance imaging revealed irreparably progressed ANE. CONCLUSION: To effectively treat ANE, early recognition and diagnosis are critical. Our case suggests that ANE should be considered and added to the differential diagnosis for adult patients with rapid cognitive deterioration.

Aging Impacts the Overall Connectivity Strength of Regions Critical for Information Transfer Among Brain Networks.

Recent studies have demonstrated that connector hubs, regions considered critical for the flow of information across neural systems, are mostly involved in neurodegenerative dementia. Considering that aging can significantly affect the brain's intrinsic connectivity, identifying aging's impact on these regions' overall connection strength is important to differentiate changes associated with healthy aging from neurodegenerative disorders. Using resting state functional magnetic resonance imaging data from a carefully selected cohort of 175 healthy volunteers aging from 21 to 86 years old, we computed an intrinsic connectivity contrast (ICC) metric, which quantifies a region's overall connectivity strength, for whole brain, short-range, and long-range connections and examined age-related changes of this metric over the adult lifespan. We have identified a limited number of hub regions with ICC values that showed significant negative relationship with age. These include the medial precentral/midcingulate gyri and insula with both their short-range and long-range (and thus whole-brain) ICC values negatively associated with age, and the angular, middle frontal, and posterior cingulate gyri with their long-range ICC values mainly involved. Seed-based connectivity analyses further confirmed that these regions are connector hubs with connectivity profile that strongly overlapped with multiple large-scale brain networks. General cognitive performance was not associated with these hubs' ICC values. These findings suggest that even healthy aging could negatively impact the efficiency of regions critical for facilitating information transfer among different functional brain networks. The extent of the regions involved, however, was limited.

CHARACTERISTICS and considerations in the medical treatment of COVID-19 in children.

It is rare for children to be in serious condition or die from coronavirus disease 2019 (COVID-19) caused by the 2019 novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) except for those with underlying diseases such as chronic lung disease (including asthma), cardiovascular disease, and immunosuppressive disease. Recently, patients with hyperinflammatory shock have been identified among children who are confirmed to have or are suspected of having SARS-CoV-2 infection. The presenting signs and symptoms are characterized by prolonged fever, abdominal pain, and cardiac involvement without any signs of pneumonia on chest computed tomography. However, it is uncertain at this time whether SARS-CoV-2 infection affects this syndrome. Compared with adults, quite a few children are asymptomatic even when infected with SARS-CoV-2, which could make these children serious sources of infection at home or in medical institutions. Considering these characteristics, it is important to take appropriate precautions during medical examinations and perform infection control in emergency departments to save the lives of both the children and adult patients. Most healthy children are suffering from huge stress due to restrictions against going outside and school closures as social means to control infection. It is possible that children are socially isolated when they come to the emergency department, and they might require mental or social support even if they are only complaining about their physical condition. Health-care providers are required to examine the children's circumstances carefully and cooperate with workers in other professions appropriately.

The neural network basis of altered decision-making in patients with amyotrophic lateral sclerosis.

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a multisystem disorder associated with motor impairment and behavioral/cognitive involvement. We examined decision-making features and changes in the neural hub network in patients with ALS using a probabilistic reversal learning task and resting-state network analysis, respectively. METHODS: Ninety ALS patients and 127 cognitively normal participants performed this task. Data from 62 ALS patients and 63 control participants were fitted to a Q-learning model. RESULTS: ALS patients had anomalous decision-making features with little shift in choice until they thought the value of the two alternatives had become equal. The quantified parameters (Pαß) calculated by logistic regression analysis with learning rate and inverse temperature well represented the unique choice pattern of ALS patients. Resting-state network analysis demonstrated a strong correlation between Pαß and decreased degree centrality in the anterior cingulate gyrus and frontal pole. INTERPRETATION: Altered decision-making in ALS patients may be related to the decreased hub function of medial prefrontal areas.

Changes in white matter fiber density and morphology across the adult lifespan: A cross-sectional fixel-based analysis.

White matter (WM) fiber bundles change dynamically with age. These changes could be driven by alterations in axonal diameter, axonal density, and myelin content. In this study, we applied a novel fixel-based analysis (FBA) framework to examine these changes throughout the adult lifespan. Using diffusion-weighted images from a cohort of 293 healthy volunteers (89 males/204 females) from ages 21 to 86 years old, we performed FBA to analyze age-related changes in microscopic fiber density (FD) and macroscopic fiber morphology (fiber cross section [FC]). Our results showed significant and widespread age-related alterations in FD and FC across the whole brain. Interestingly, some fiber bundles such as the anterior thalamic radiation, corpus callosum, and superior longitudinal fasciculus only showed significant negative relationship with age in FD values, but not in FC. On the other hand, some segments of the cerebello-thalamo-cortical pathway only showed significant negative relationship with age in FC, but not in FD. Analysis at the tract-level also showed that major fiber tract groups predominantly distributed in the frontal lobe (cingulum, forceps minor) exhibited greater vulnerability to the aging process than the others. Differences in FC and the combined measure of FD and cross section values observed between sexes were mostly driven by differences in brain sizes although male participants tended to exhibit steeper negative linear relationship with age in FD as compared to female participants. Overall, these findings provide further insights into the structural changes the brain's WM undergoes due to the aging process.

Semantic deficits in ALS related to right lingual/fusiform gyrus network involvement.

BACKGROUND: The clinicopathological continuity between amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) is well known. Although ALS demonstrates language symptoms similar to FTLD, including semantic dementia, word reading impairments in ALS have not been well studied. "Jukujikun" are Kanji-written words with irregular pronunciation comparable to "exception words" and useful for detecting semantic deficits in Japan. We conducted a cross-sectional study to investigate Jukujikun reading impairments and related network changes in ALS. METHODS: We enrolled 71 ALS patients and 69 healthy controls (HCs). Age-, sex-, and education matched HCs were recruited from another cohort study concurrently with patient registration. We examined neuropsychological factors including low frequency Jukujikun reading. We performed resting-state functional magnetic resonance imaging with voxel-based graph analysis on a subset of participants who agreed. FINDINGS: Low frequency Jukujikun score was decreased in ALS (15·0[11·0-19·0](median[25-75 percentile])) compared with HCs (19·0[17·3-20·0]) (p < 0·001, effect size = 0·43). Fifty-two percent of ALS (N = 37) with low frequency Jukujikun score ≤ 5th percentile of HCs was classified as ALS with positive Jukujikun deficit (ALS-JD+). Compared with HCs, ALS-JD+ showed decreased degree centrality in the right lingual/fusiform gyrus, where connectivities with regions associated with word perception, semantic processing, or speech production were decreased. They also showed increased degree centrality in the left inferior/middle temporal gyrus, associated with increased connectivities involving semantic processing. INTERPRETATION: Dysfunction of the "hub" in the right lingual/fusiform gyrus can affect semantic deficit in ALS. Considering neuropsychological symptoms as network impairments is vital for understanding various diseases. FUND: MHLW and MEXT, Japan.

Reorganization of brain networks and its association with general cognitive performance over the adult lifespan.

Healthy aging is associated with structural and functional changes in the brain even in individuals who are free of neurodegenerative diseases. Using resting state functional magnetic resonance imaging data from a carefully selected cohort of participants, we examined cross sectional changes in the functional organization of several large-scale brain networks over the adult lifespan and its potential association with general cognitive performance. Converging results from multiple analyses at the voxel, node, and network levels showed widespread reorganization of functional brain networks with increasing age. Specifically, the primary processing (visual and sensorimotor) and visuospatial (dorsal attention) networks showed diminished network integrity, while the so-called core neurocognitive (executive control, salience, and default mode) and basal ganglia networks exhibited relatively preserved between-network connections. The visuospatial and precuneus networks also showed significantly more widespread increased connectivity with other networks. Graph analysis suggested that this reorganization progressed towards a more integrated network topology. General cognitive performance, assessed by Addenbrooke's Cognitive Examination-Revised total score, was positively correlated with between-network connectivity among the core neurocognitive and basal ganglia networks and the integrity of the primary processing and visuospatial networks. Mediation analyses further indicated that the observed association between aging and relative decline in cognitive performance could be mediated by changes in relevant functional connectivity measures. Overall, these findings provided further evidence supporting widespread age-related brain network reorganization and its potential association with general cognitive performance during healthy aging.

Age-related impairment in Addenbrooke's cognitive examination revised scores in patients with amyotrophic lateral sclerosis.

OBJECTIVE: Older age is thought to be a risk factor for cognitive impairment in amyotrophic lateral sclerosis (ALS). However, very few clinical studies have investigated this relationship using sufficient numbers of healthy controls that correspond to each generation. The purpose of this study was to determine the age-related changes of Addenbrooke's Cognitive Examination-Revised (ACE-R) score in ALS patients by comparing healthy controls of various ages. METHODS: 131 ALS patients (86 males, 45 females; mean age: 64.8 ± 10.2; mean education: 12.5 ± 2.7) and 151 age-, gender-, and education-matched healthy controls were enrolled. We applied ACE-R, which could evaluate not only global cognition but five cognitive subdomains that included orientation/attention, memory, verbal fluency, language, and visuospatial ability. RESULTS: ALS patients had significantly lower total and subdomain scores of ACE-R than healthy controls. Multiple regression analysis suggested that age at examination and age at onset had significant influence on ACE-R scores. When we divided ALS patients and healthy controls into 4 groups according to age at examination for ALS, total and each subdomain scores were significantly lower with age, particularly in the older-middle and the oldest group (66.31 years or more) of ALS compared with healthy controls. Locally weighted scatterplot smoothing analysis supported that these reductions of ACE-R total and subdomain scores in ALS patients were more accelerated by approximately 60 years as compared with healthy controls. CONCLUSION: ALS patients showed accelerated age-related ACE-R score reduction beyond normal ageing processes.

Involvement of the Precuneus/Posterior Cingulate Cortex Is Significant for the Development of Alzheimer's Disease: A PET (THK5351, PiB) and Resting fMRI Study.

Background: Imaging studies in Alzheimer's disease (AD) have yet to answer the underlying questions concerning the relationship among tau retention, neuroinflammation, network disruption and cognitive decline. We compared the spatial retention patterns of 18F-THK5351 and resting state network (RSN) disruption in patients with early AD and healthy controls. Methods: We enrolled 23 11C-Pittsburgh compound B (PiB)-positive patients with early AD and 24 11C-PiB-negative participants as healthy controls. All participants underwent resting state functional MRI and 18F-THK5351 PET scans. We used scaled subprofile modeling/principal component analysis (SSM/PCA) to reduce the complexity of multivariate data and to identify patterns that exhibited the largest statistical effects (variances) in THK5351 concentration in AD and healthy controls. Findings: SSM/PCA identified a significant spatial THK5351 pattern composed by mainly three clusters including precuneus/posterior cingulate cortex (PCC), right and left dorsolateral prefrontal cortex (DLPFC) which accounted for 23.6% of the total subject voxel variance of the data and had 82.6% sensitivity and 79.1% specificity in discriminating AD from healthy controls. There was a significant relationship between the intensity of the 18F-THK5351 covariation pattern and cognitive scores in AD. The spatial patterns of 18F-THK5351 uptake showed significant similarity with intrinsic functional connectivity, especially in the PCC network. Seed-based connectivity analysis from the PCC showed significant decrease in connectivity over widespread brain regions in AD patients. An evaluation of an autopsied AD patient with Braak V showed that 18F-THK5351 retention corresponded to tau deposition, monoamine oxidase-B (MAO-B) and astrogliosis in the precuneus/PCC. Interpretation: We identified an AD-specific spatial pattern of 18F-THK5351 retention in the precuneus/PCC, an important connectivity hub region in the brain. Disruption of the functional connections of this important network hub may play an important role in developing dementia in AD.

Corpus callosal involvement is correlated with cognitive impairment in multiple system atrophy.

OBJECTIVE: We examined the anatomical involvement related to cognitive impairment in patients with multiple system atrophy (MSA). METHODS: We examined 30 patients with probable MSA and 15 healthy controls. All MSA patients were assessed by the Unified MSA-Rating scale and Addenbrooke's Cognitive Examination-Revised (ACE-R). We classified 15 MSA patients with ACE-R scores > 88 as having normal cognition (MSA-NC) and 15 with scores ≤ 88 as having cognitive impairment (MSA-CI). All subjects underwent 3 T MRI scanning and were investigated using voxel-based morphometry and diffusion tensor imaging. RESULTS: Both the MSA-NC and MSA-CI patients exhibited cerebellar but not cerebral atrophy in voxel-based morphometry compared to controls. In contrast, tract-based spatial statistics revealed widespread and significantly decreased fractional anisotropy (FA) values, as well as increased mean diffusivity, radial diffusivity, and axial diffusivity in both the cerebrum and cerebellum in MSA-CI patients compared to controls. MSA-NC patients also exhibited similar involvement of the cerebellum but less extensive involvement of the cerebrum compared with the MSA-CI patients. In particular, FA values in MSA-CI patients were significantly decreased in the anterior part of the left corpus callosum compared with those in MSA-NC patients. The mean FA values in the left anterior part of the corpus callosum were significantly correlated with total ACE-R scores and subscores (memory, fluency, and language) in MSA patients. CONCLUSIONS: Decreased FA values in the anterior corpus callosum showed a significant correlation with cognitive impairment in MSA.

Distinct manifestation of cognitive deficits associate with different resting-state network disruptions in non-demented patients with Parkinson's disease.

Cognitive deficits in Parkinson's disease (PD) are heterogeneous entities, but a relationship between the heterogeneity of cognitive deficits and resting-state network (RSN) changes remains elusive. In this study, we examined five sub-domain scores according to Addenbrooke's Cognitive Examination-Revised (ACE-R) for the cognitive evaluation and classification of 72 non-demented patients with PD. Twenty-eight patients were classified as PD with normal cognition (PD-NC). The remaining 44 were subdivided into the following 2 groups using a hierarchical cluster analysis: 20 with a predominant decrease in memory (PD with amnestic cognitive deficits: PD-A) and 24 with good memory who exhibited a decrease in other sub-domains (PD with non-amnestic cognitive deficits: PD-NA). We used an independent component analysis of RS-fMRI data to investigate the inter-group differences of RSN. Compared to the controls, the PD-A showed lower FC within the ventral default mode network (vDMN) and the visuospatial network. On the other hand, the PD-NA showed lower FC within the visual networks and the cerebellum-brainstem network. Significant differences in the FC within the vDMN and cerebellum-brainstem network were observed between the PD-A and PD-NA, which provided a good discrimination between PD-A and PD-NA using a support vector machine. Distinct patterns of cognitive deficits correspond to different RSN changes.

Severe hyposmia and aberrant functional connectivity in cognitively normal Parkinson's disease.

OBJECTIVE: Severe hyposmia is a risk factor of dementia in Parkinson's disease (PD), while the underlying functional connectivity (FC) and brain volume alterations in PD patients with severe hyposmia (PD-SH) are unclear. METHODS: We examined voxel-based morphometric and resting state functional magnetic resonance imaging findings in 15 cognitively normal PD-SH, 15 cognitively normal patients with PD with no/mild hyposmia (PD-N/MH), and 15 healthy controls (HCs). RESULTS: Decreased gray matter volume (GMV) was observed in the bilateral cuneus, right associative visual area, precuneus, and some areas in anterior temporal lobes in PD-SH group compared to HCs. Both the PD-SH and PD-N/MH groups showed increased GMV in the bilateral posterior insula and its surrounding regions. A widespread significant decrease in amygdala FC beyond the decreased GMV areas and olfactory cortices were found in the PD-SH group compared with the HCs. Above all, decreased amygdala FC with the inferior parietal lobule, lingual gyrus, and fusiform gyrus was significantly correlated with both reduction of Addenbrooke's Cognitive Examination-Revised scores and severity of hyposmia in all participants. Canonical resting state networks exhibited decreased FC in the precuneus and left executive control networks but increased FC in the primary and high visual networks of patients with PD compared with HCs. Canonical network FC to other brain regions was enhanced in the executive control, salience, primary visual, and visuospatial networks of the PD-SH. CONCLUSION: PD-SH showed extensive decreased amygdala FC. Particularly, decreased FC between the amygdala and inferior parietal lobule, lingual gyrus, and fusiform gyrus were associated with the severity of hyposmia and cognitive performance. In contrast, relatively preserved canonical networks in combination with increased FC to brain regions outside of canonical networks may be related to compensatory mechanisms, and preservation of brain function.

An unbiased data-driven age-related structural brain parcellation for the identification of intrinsic brain volume changes over the adult lifespan.

This study aims to elucidate age-related intrinsic brain volume changes over the adult lifespan using an unbiased data-driven structural brain parcellation. Anatomical brain images from a cohort of 293 healthy volunteers ranging in age from 21 to 86 years were analyzed using independent component analysis (ICA). ICA-based parcellation identified 192 component images, of which 174 (90.6%) showed a significant negative correlation with age and with some components being more vulnerable to aging effects than others. Seven components demonstrated a convex slope with aging; 3 components had an inverted U-shaped trajectory, and 4 had a U-shaped trajectory. Linear combination of 86 components provided reliable prediction of chronological age with a mean absolute prediction error of approximately 7.2 years. Structural co-variation analysis showed strong interhemispheric, short-distance positive correlations and long-distance, inter-lobar negative correlations. Estimated network measures either exhibited a U- or an inverted U-shaped relationship with age, with the vertex occurring at approximately 45-50 years. Overall, these findings could contribute to our knowledge about healthy brain aging and could help provide a framework to distinguish the normal aging processes from that associated with age-related neurodegenerative diseases.

Structural MRI correlates of amyotrophic lateral sclerosis progression.

PURPOSE: Amyotrophic lateral sclerosis (ALS) presents with varying degrees of brain degeneration that can extend beyond the corticospinal tract (CST). Furthermore, the clinical course and progression of ALS varies widely. Brain degeneration detected using structural MRI could reflect disease progression. SUBJECTS AND METHODS: On study registration, 3-Tesla volumetric MRI and diffusion tensor imaging scans were obtained at baseline in 38 healthy controls and 67 patients with sporadic ALS. Patients had Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) scores of ≥36 and did not have the chromosome 9, open reading frame 72 repeat expansion. Six months later, changes in ALSFRS-R (ΔALSFRS-R) scores were calculated and patients were grouped into three categories, namely, patients with slow progression with ΔALSFRS-R scores ≤3 (n=19), intermediate progression with ΔALSFRS-R scores =4, 5 and 6 (n=36) and rapid progression with ΔALSFRS-R scores ≥7 (n=12). We analysed voxel-based morphometry and tract-based spatial statistics among these subgroups and controls. RESULTS: In comparison with controls, patients with ALS showed grey matter atrophy and decreased fractional anisotropy beyond the motor cortex and CST, especially in the frontotemporal lobes and basal ganglia. Moreover, the degree of change was highly proportional to ΔALSFRS-R at the 6-month assessment. CONCLUSION: A more rapid disease progression and poorer functional decline were associated with greater involvement of the extra-motor cortex and basal ganglia, suggesting that the spatial extent of brain involvement can be an indicator of the progression in ALS.