Reduced lateralization of multiple functional brain networks in autistic males.

BACKGROUND: Autism spectrum disorder has been linked to a variety of organizational and developmental deviations in the brain. One such organizational difference involves hemispheric lateralization, which may be localized to language-relevant regions of the brain or distributed more broadly. METHODS: In the present study, we estimated brain hemispheric lateralization in autism based on each participant's unique functional neuroanatomy rather than relying on group-averaged data. Additionally, we explored potential relationships between the lateralization of the language network and behavioral phenotypes including verbal ability, language delay, and autism symptom severity. We hypothesized that differences in hemispheric asymmetries in autism would be limited to the language network, with the alternative hypothesis of pervasive differences in lateralization. We tested this and other hypotheses by employing a cross-sectional dataset of 118 individuals (48 autistic, 70 neurotypical). Using resting-state fMRI, we generated individual network parcellations and estimated network asymmetries using a surface area-based approach. A series of multiple regressions were then used to compare network asymmetries for eight significantly lateralized networks between groups. RESULTS: We found significant group differences in lateralization for the left-lateralized Language (d = -0.89), right-lateralized Salience/Ventral Attention-A (d = 0.55), and right-lateralized Control-B (d = 0.51) networks, with the direction of these group differences indicating less asymmetry in autistic males. These differences were robust across different datasets from the same participants. Furthermore, we found that language delay stratified language lateralization, with the greatest group differences in language lateralization occurring between autistic males with language delay and neurotypical individuals. CONCLUSIONS: These findings evidence a complex pattern of functional lateralization differences in autism, extending beyond the Language network to the Salience/Ventral Attention-A and Control-B networks, yet not encompassing all networks, indicating a selective divergence rather than a pervasive one. Moreover, we observed an association between Language network lateralization and language delay in autistic males.

Short-Term Practice Effects on Cognitive Tests Across the Late Life Cognitive Spectrum and How They Compare to Biomarkers of Alzheimer's Disease.

Background: Practice effects on cognitive testing in mild cognitive impairment (MCI) and Alzheimer's disease (AD) remain understudied, especially with how they compare to biomarkers of AD. Objective: The current study sought to add to this growing literature. Methods: Cognitively intact older adults (n = 68), those with amnestic MCI (n = 52), and those with mild AD (n = 45) completed a brief battery of cognitive tests at baseline and again after one week, and they also completed a baseline amyloid PET scan, a baseline MRI, and a baseline blood draw to obtain APOE ɛ4 status. Results: The intact participants showed significantly larger baseline cognitive scores and practice effects than the other two groups on overall composite measures. Those with MCI showed significantly larger baseline scores and practice effects than AD participants on the composite. For amyloid deposition, the intact participants had significantly less tracer uptake, whereas MCI and AD participants were comparable. For total hippocampal volumes, all three groups were significantly different in the expected direction (intact > MCI > AD). For APOE ɛ4, the intact had significantly fewer copies of ɛ4 than MCI and AD. The effect sizes of the baseline cognitive scores and practice effects were comparable, and they were significantly larger than effect sizes of biomarkers in 7 of the 9 comparisons. Conclusion: Baseline cognition and short-term practice effects appear to be sensitive markers in late life cognitive disorders, as they separated groups better than commonly-used biomarkers in AD. Further development of baseline cognition and short-term practice effects as tools for clinical diagnosis, prognostic indication, and enrichment of clinical trials seems warranted.

Tract- and gray matter- based spatial statistics show white matter and gray matter microstructural differences in autistic males.

Background: Autism spectrum disorder (ASD) is a neurodevelopmental condition commonly studied in the context of early childhood. As ASD is a life-long condition, understanding the characteristics of brain microstructure from adolescence into adulthood and associations to clinical features is critical for improving outcomes across the lifespan. In the current work, we utilized Tract Based Spatial Statistics (TBSS) and Gray Matter Based Spatial Statistics (GBSS) to examine the white matter (WM) and gray matter (GM) microstructure in neurotypical (NT) and autistic males. Methods: Multi-shell diffusion MRI was acquired from 78 autistic and 81 NT males (12-to-46-years) and fit to the DTI and NODDI diffusion models. TBSS and GBSS were performed to analyze WM and GM microstructure, respectively. General linear models were used to investigate group and age-related group differences. Within the ASD group, relationships between WM and GM microstructure and measures of autistic symptoms were investigated. Results: All dMRI measures were significantly associated with age across WM and GM. Significant group differences were observed across WM and GM. No significant age-by-group interactions were detected. Within the ASD group, positive relationships with WM microstructure were observed with ADOS-2 Calibrated Severity Scores. Conclusion: Using TBSS and GBSS our findings provide new insights into group differences of WM and GM microstructure in autistic males from adolescence into adulthood. Detection of microstructural differences across the lifespan as well as their relationship to the level of autistic symptoms will deepen to our understanding of brain-behavior relationships of ASD and may aid in the improvement of intervention options for autistic adults.

Delayed and More Variable Unimanual and Bimanual Finger Tapping in Alzheimer's Disease: Associations with Biomarkers and Applications for Classification.

BACKGROUND: Despite reports of gross motor problems in mild cognitive impairment (MCI) and Alzheimer's disease (AD), fine motor function has been relatively understudied. OBJECTIVE: We examined if finger tapping is affected in AD, related to AD biomarkers, and able to classify MCI or AD. METHODS: Forty-seven cognitively normal, 27 amnestic MCI, and 26 AD subjects completed unimanual and bimanual computerized tapping tests. We tested 1) group differences in tapping with permutation models; 2) associations between tapping and biomarkers (PET amyloid-ß, hippocampal volume, and APOEɛ4 alleles) with linear regression; and 3) the predictive value of tapping for group classification using machine learning. RESULTS: AD subjects had slower reaction time and larger speed variability than controls during all tapping conditions, except for dual tapping. MCI subjects performed worse than controls on reaction time and speed variability for dual and non-dominant hand tapping. Tapping speed and variability were related to hippocampal volume, but not to amyloid-ß deposition or APOEɛ4 alleles. Random forest classification (overall accuracy = 70%) discriminated control and AD subjects, but poorly discriminated MCI from controls or AD. CONCLUSIONS: MCI and AD are linked to more variable finger tapping with slower reaction time. Associations between finger tapping and hippocampal volume, but not amyloidosis, suggest that tapping deficits are related to neuropathology that presents later during the disease. Considering that tapping performance is able to differentiate between control and AD subjects, it can offer a cost-efficient tool for augmenting existing AD biomarkers.

Neurite outgrowth deficits caused by rare PLXNB1 mutation in pediatric bipolar disorder.

Pediatric bipolar disorder (PBD) is a severe mood dysregulation condition that affects 0.5-1% of children and teens in the United States. It is associated with recurrent episodes of mania and depression and an increased risk of suicidality. However, the genetics and neuropathology of PBD are largely unknown. Here, we used a combinatorial family-based approach to characterize cellular, molecular, genetic, and network-level deficits associated with PBD. We recruited a PBD patient and three unaffected family members from a family with a history of psychiatric illnesses. Using resting-state functional magnetic resonance imaging (rs-fMRI), we detected altered resting-state functional connectivity in the patient as compared to an unaffected sibling. Using transcriptomic profiling of patient and control induced pluripotent stem cell (iPSC)-derived telencephalic organoids, we found aberrant signaling in the molecular pathways related to neurite outgrowth. We corroborated the presence of neurite outgrowth deficits in patient iPSC-derived cortical neurons and identified a rare homozygous loss-of-function PLXNB1 variant (c.1360C>C; p.Ser454Arg) responsible for the deficits in the patient. Expression of wild-type PLXNB1, but not the variant, rescued neurite outgrowth in patient neurons, and expression of the variant caused the neurite outgrowth deficits in cortical neurons from PlxnB1 knockout mice. These results indicate that dysregulated PLXNB1 signaling may contribute to an increased risk of PBD and other mood dysregulation-related disorders by disrupting neurite outgrowth and functional brain connectivity. Overall, this study established and validated a novel family-based combinatorial approach for studying cellular and molecular deficits in psychiatric disorders and identified dysfunctional PLXNB1 signaling and neurite outgrowth as potential risk factors for PBD.

Volumetric regional MRI and neuropsychological predictors of motor task variability in cognitively unimpaired, Mild Cognitive Impairment, and probable Alzheimer's disease older adults.

INTRODUCTION: The mechanisms linking motor function to Alzheimer's disease (AD) progression have not been well studied, despite evidence of AD pathology within motor brain regions. Thus, there is a need for new motor measure that is sensitive and specific to AD. METHODS: In a sample of 121 older adults (54 cognitive unimpaired [CU], 35 amnestic Mild Cognitive Impairment [aMCI], and 32 probable mild AD), intrasubject standard deviation (ISD) across six trials of a novel upper-extremity motor task was predicted with volumetric regional gray matter and neuropsychological scores using classification and regression tree (CART) analyses. RESULTS: Both gray matter and neuropsychological CART models indicated that motor task ISD (our measure of motor learning) was related to cortical regions and cognitive test scores associated with memory, executive function, and visuospatial skills. CART models also accurately distinguished motor task ISD of MCI and probable mild AD from CU. DISCUSSION: Variability in motor task performance across practice trials may be valuable for understanding preclinical and early-stage AD.

Repeatable battery for the assessment of neuropsychological status and its relationship to biomarkers of Alzheimer's disease.

The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) has been associated with commonly used biomarkers of Alzheimer's disease (AD). However, prior studies have typically utilized small and poorly characterized samples, and they have not analyzed the subtests of the RBANS. The current study sought to expand on prior work by examining the relationship between the Indexes and subtest scores of the RBANS and three AD biomarkers: amyloid deposition via positron emission tomography, hippocampal volume via magnetic resonance imaging, and APOE ε4 status.One-hundred twenty-one older adults across the AD continuum (intact, amnestic Mild Cognitive Impairment, mild AD), who were mostly Caucasian and well-educated, underwent assessment with the RBANS and collection of the three biomarkers.Greater amyloid deposition was significantly related to lower scores on all five Indexes and the Total Scale score of the RBANS, as well as 11 of 12 subtests. For bilateral hippocampal volume, significant correlations were observed for 4 of the 5 Indexes, Total Scale score, and 9 of 12 subtests, with smaller hippocampi being related to lower RBANS scores. Participants with at least one APOE ε4 allele had significantly lower scores on 3 of the 5 Indexes, Total Scale score, and 8 of the 12 subtests.In this sample of participants across the dementia spectrum, most RBANS Indexes and subtests showed relationships with the amyloid deposition, hippocampal volumes, and APOE status, with poorer performance on the RBANS being associated with biomarker positivity. Although memory scores on the RBANS have traditionally been linked to biomarkers in AD, other Index and subtest scores also hold promise as indicators of AD. Replication in a more diverse sample is needed.

Recall and recognition subtests of the repeatable battery for the assessment of neuropsychological status and their relationship to biomarkers of Alzheimer's disease.

Recently, two new recognition subtests for the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were developed and initially validated in a cohort of older adults who were cognitively intact or classified as amnestic Mild Cognitive Impairment (MCI) or mild Alzheimer's disease (AD). The current paper extends that validation by comparing the recall and recognition subtests of the RBANS, including the existing and recently developed scores, to three commonly used biomarkers in AD in an expanded sample from the initial validation. One hundred fifty-four older adults (65 intact, 46 MCI, 43 AD) were administered the RBANS, which included the recently developed subtests for Story Recognition and Figure Recognition (hits, false positives, total correct), as part of a study on memory and biomarkers. Participants also completed magnetic resonance imaging to obtain hippocampal volumes, positron emission tomography to obtain amyloid plaque deposition, and a blood draw to obtain APOE ε4 status. Whereas correlations between recall scores and biomarkers tended to be moderate (average r = ±0.48), these correlations were comparable across the three recognition total scores (average r = ±0.42), but tended to be lower for recognition hits (average r = ±0.28) and false positives (average r = ±0.38). These results further validate the existing and recently developed recognition scores on the RBANS as providing useful information about brain and genetic pathology in older adults with intact and impaired cognitive functioning.

Reduced Lateralization of Multiple Functional Brain Networks in Autistic Males.

Background: Autism spectrum disorder has been linked to a variety of organizational and developmental deviations in the brain. One such organizational difference involves hemispheric lateralization, which may be localized to language-relevant regions of the brain or distributed more broadly. Methods: In the present study, we estimated brain hemispheric lateralization in autism based on each participant's unique functional neuroanatomy rather than relying on group-averaged data. Additionally, we explored potential relationships between the lateralization of the language network and behavioral phenotypes including verbal ability, language delay, and autism symptom severity. We hypothesized that differences in hemispheric asymmetries in autism would be limited to the language network, with the alternative hypothesis of pervasive differences in lateralization. We tested this and other hypotheses by employing a cross-sectional dataset of 118 individuals (48 autistic, 70 neurotypical). Using resting-state fMRI, we generated individual network parcellations and estimated network asymmetries using a surface area-based approach. A series of multiple regressions were then used to compare network asymmetries for eight significantly lateralized networks between groups. Results: We found significant group differences in lateralization for the left-lateralized Language (d = -0.89), right-lateralized Salience/Ventral Attention-A (d = 0.55), and right-lateralized Control-B (d = 0.51) networks, with the direction of these group differences indicating less asymmetry in autistic individuals. These differences were robust across different datasets from the same participants. Furthermore, we found that language delay stratified language lateralization, with the greatest group differences in language lateralization occurring between autistic individuals with language delay and neurotypical individuals. Limitations: The generalizability of our findings is restricted due to the male-only sample and greater representation of individuals with high verbal and cognitive performance. Conclusions: These findings evidence a complex pattern of functional lateralization differences in autism, extending beyond the Language network to the Salience/Ventral Attention-A and Control-B networks, yet not encompassing all networks, indicating a selective divergence rather than a pervasive one. Furthermore, a differential relationship was identified between Language network lateralization and specific symptom profiles (namely, language delay) of autism.

Test-retest reliability of FreeSurfer-derived volume, area and cortical thickness from MPRAGE and MP2RAGE brain MRI images.

Background and purpose: Large MRI studies often pool data gathered from widely varying imaging sequences. Pooled data creates a potential source of variation in structural analyses which may cause misinterpretation of findings. The purpose of this study is to determine if data acquired using different scan sequences, head coils and scanners offers consistent structural measurements. Materials and methods: Participants (163 right-handed males: 82 typically developing controls, 81 participants with autism spectrum disorder) were scanned on the same day using an MPRAGE sequence with a 12-channel headcoil on a Siemens 3T Trio scanner and an MP2RAGE sequence with a 64-channel headcoil on a Siemens 3T Prisma scanner. Segmentation was performed using FreeSurfer to identify regions exhibiting variation between sequences on measures of volume, surface area, and cortical thickness. Intraclass correlation coefficient (ICC) and mean percent difference (MPD) were used as test-retest reproducibility measures. Results: ICC for total brain segmented volume yielded a 0.99 intraclass correlation, demonstrating high overall volumetric reproducibility. Comparison of individual regions of interest resulted in greater variation. Volumetric variability, although low overall, was greatest in the entorhinal cortex (ICC = 0.71), frontal (ICC = 0.60) and temporal (ICC = 0.60) poles. Surface area variability was greatest in the insula (ICC = 0.65), temporal (ICC = 0.64) and frontal (ICC = 0.68) poles. Cortical thickness was most variable in the frontal (ICC = 0.41) and temporal (ICC = 0.35) poles. Conclusion: Data collected on different scanners and head coils using MPRAGE and MP2RAGE are generally consistent for surface area and volume estimates. However, regional variability may constrain accuracy in some regions and cortical thickness measurements exhibit higher generalized variability.

The Quick Dementia Rating System and Its Relationship to Biomarkers of Alzheimer's Disease and Neuropsychological Performance.

INTRODUCTION: The Quick Dementia Rating System (QDRS) is a brief, patient-reported dementia staging tool that has approximated scores on the Clinical Dementia Rating Scale in patients with Alzheimer's disease (AD). However, no studies have examined its relationship with AD-related biomarkers. METHODS: One-hundred twenty-one older adults (intact, amnestic mild cognitive impairment, mild AD) completed the QDRS, and three biomarkers (amyloid deposition via positron emission tomography, hippocampal volume via magnetic resonance imaging, and apolipoprotein [APOE] ε4 status). RESULTS: The Total score on the QDRS was statistically significantly related to all three biomarkers (after controlling for age, education, sex, and race), with greater levels of dementia severity being associated with greater amyloid deposition, smaller hippocampi, and having copies of APOE ε4 allele. DISCUSSION: In participants across the cognitive spectrum, the QDRS showed modest relationships with amyloid deposition, hippocampal volumes, and APOE status. Therefore, the QDRS may offer a cost-effective screening method for clinical trials in AD.

Longitudinal Stability of Intellectual Functioning in Autism Spectrum Disorder: From Age 3 Through Mid-adulthood.

Intelligence (IQ) scores are used in educational and vocational planning for individuals with autism spectrum disorder (ASD) yet little is known about the stability of IQ throughout development. We examined longitudinal age-related IQ stability in 119 individuals with ASD (3-36 years of age at first visit) and 128 typically developing controls. Intelligence measures were collected over a 20-year period. In ASD, Full Scale (FSIQ) and Verbal (VIQ) Intelligence started lower in childhood and increased at a greater rate with age relative to the control group. By early adulthood, VIQ and working memory stabilized, whereas nonverbal and perceptual scores continued to change. Our results suggest that in individuals with ASD, IQ estimates may be dynamic in childhood and young adulthood.

Relationship between a novel learning slope metric and Alzheimer's disease biomarkers.

The Learning Ratio (LR) is a novel learning score examining the proportion of information learned over successive learning trials relative to information available to be learned. Validation is warranted to understand LR's sensitivity to Alzheimer's disease (AD) pathology. One-hundred twenty-three participants across the AD continuum underwent memory assessment, quantitative brain imaging, and genetic analysis. LR scores were calculated from the HVLT-R, BVMT-R, RBANS List Learning, and RBANS Story Memory, and compared to total hippocampal volumes,18F-Flutemetamol composite SUVR uptake, and APOE ε4 status. Lower LR scores were consistently associated with smaller total hippocampal volumes, greater cerebral ß-amyloid deposition, and APOE ε4 positivity. This LR score outperformed a traditional learning slope calculation in all analyses. LR is sensitive to AD pathology along the AD continuum - more so than a traditional raw learning score - and reducing the competition between the first trial and subsequent trials can better depict learning capacity.

Association Between Motor Task Performance and Hippocampal Atrophy Across Cognitively Unimpaired, Amnestic Mild Cognitive Impairment, and Alzheimer's Disease Individuals.

Hippocampal atrophy is a widely used biomarker for Alzheimer's disease (AD), but the cost, time, and contraindications associated with magnetic resonance imaging (MRI) limit its use. Recent work has shown that a low-cost upper extremity motor task has potential in identifying AD risk. Fifty-four older adults (15 cognitively unimpaired, 24 amnestic mild cognitive impairment, and 15 AD) completed six motor task trials and a structural MRI. Several measures of motor task performance significantly predicted bilateral hippocampal volume, controlling for age, sex, education, and memory. Thus, this motor task may be an affordable, non-invasive screen for AD risk and progression.

Evidence for normal extra-axial cerebrospinal fluid volume in autistic males from middle childhood to adulthood.

Autism spectrum disorder has long been associated with a variety of organizational and developmental abnormalities in the brain. An increase in extra-axial cerebrospinal fluid volume in autistic individuals between the ages of 6 months and 4 years has been reported in recent studies. Increased extra-axial cerebrospinal fluid volume was predictive of the diagnosis and severity of the autistic symptoms in all of them, irrespective of genetic risk for developing the disorder. In the present study, we explored the trajectory of extra-axial cerebrospinal fluid volume from childhood to adulthood in both autism and typical development. We hypothesized that an elevated extra-axial cerebrospinal fluid volume would be found in autism persisting throughout the age range studied. We tested the hypothesis by employing an accelerated, multi-cohort longitudinal data set of 189 individuals (97 autistic, 92 typically developing). Each individual had been scanned between 1 and 5 times, with scanning sessions separated by 2-3 years, for a total of 439 T1-weighted MRI scans. A linear mixed-effects model was used to compare developmental, age-related changes in extra-axial cerebrospinal fluid volume between groups. Inconsistent with our hypothesis, we found no group differences in extra-axial cerebrospinal fluid volume in this cohort of individuals 3 to 42 years of age. Our results suggest that extra-axial cerebrospinal fluid volume in autistic individuals is not increased compared with controls beyond four years of age.

Functional Hyperconnectivity and Task-Based Activity Changes Associated With Neuropathic Pain After Spinal Cord Injury: A Pilot Study.

Neuropathic pain (NP) is a devastating chronic pain condition affecting roughly 80% of the spinal cord injury (SCI) patient population. Current treatment options are largely ineffective and neurophysiological mechanisms of NP are not well-understood. Recent studies in neuroimaging have suggested that NP patients have differential patterns of functional activity that are dependent upon the neurological condition causing NP. We conducted an exploratory pilot study to examine functional activation and connectivity in SCI patients with chronic NP compared to SCI patients without NP. We developed a novel somatosensory attention task to identify short term fluctuations in neural activity related to NP vs. non-painful somatosensation using functional magnetic resonance imaging (fMRI). We also collected high-resolution resting state fMRI to identify connectivity-based correlations over time between the two groups. We observed increased activation during focus on NP in brain regions associated with somatosensory integration and representational knowledge in pain subjects when compared with controls. Similarly, NP subjects showed increased connectivity at rest in many of the same areas of the brain, with positive correlations between somatomotor networks, the dorsal attention network, and regions associated with pain and specific areas of painful and non-painful sensation within our cohort. Although this pilot analysis did not identify statistically significant differences between groups after correction for multiple comparisons, the observed correlations between NP and functional activation and connectivity align with a priori hypotheses regarding pain, and provide a well-controlled preliminary basis for future research in this severely understudied patient population. Altogether, this study presents a novel task, identifies regions of increased task-based activation associated with NP after SCI in the insula, prefrontal, and medial inferior parietal cortices, and identifies similar regions of increased functional connectivity associated with NP after SCI in sensorimotor, cingulate, prefrontal, and inferior medial parietal cortices. This, along with our complementary results from a structurally based analysis, provide multi-modal evidence for regions of the brain specific to the SCI cohort as novel areas for further study and potential therapeutic targeting to improve outcomes for NP patients.

A 16-year study of longitudinal volumetric brain development in males with autism.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with unknown brain etiology. Our knowledge to date about structural brain development across the lifespan in ASD comes mainly from cross-sectional studies, thereby limiting our understanding of true age effects within individuals with the disorder that can only be gained through longitudinal research. The present study describes FreeSurfer-derived volumetric findings from a longitudinal dataset consisting of 607 T1-weighted magnetic resonance imaging (MRI) scans collected from 105 male individuals with ASD (349 MRIs) and 125 typically developing male controls (258 MRIs). Participants were six to forty-five years of age at their first scan, and were scanned up to 5 times over a period of 16 years (average inter-scan interval of 3.7 years). Atypical age-related volumetric trajectories in ASD included enlarged gray matter volume in early childhood that approached levels of the control group by late childhood, an age-related increase in ventricle volume resulting in enlarged ventricles by early adulthood and reduced corpus callosum age-related volumetric increase resulting in smaller corpus callosum volume in adulthood. Larger corpus callosum volume was related to a lower (better) ADOS score at the most recent study visit for the participants with ASD. These longitudinal findings expand our knowledge of volumetric brain-based abnormalities in males with ASD, and highlight the need to continue to examine brain structure across the lifespan and well into adulthood.

Predicting biomarkers in intact older adults and those with amnestic Mild Cognitive Impairment, and mild Alzheimer's Disease using the Repeatable Battery for the Assessment of Neuropsychological Status.

INTRODUCTION: The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) has been associated, to varying degrees, with commonly used biomarkers of Alzheimer's disease (AD). Given the ease of RBANS administration as a screening tool for clinical trials and other applications, a better understanding of how RBANS performance is associated with presence of APOE ε4 allele[s], cerebral amyloid burden, and hippocampal volume is warranted. METHOD: One hundred twenty-one older adults who were classified as intact, amnestic Mild Cognitive Impairment, or mild AD underwent cognitive assessment with the RBANS, genetic analysis, and quantitative brain imaging. APOE ε4 carrier status, 18F-Flutemetamol composite standardized uptake value ratio (SUVR), and hippocampal volume were each regressed on demographic variables and RBANS Total Scale score, Index scores, and subtest scores. RESULTS: Lower RBANS Total Scale score or Delayed Memory Index (DMI) predicted the presence of APOE ε4 allele[s], higher cerebral amyloid burden, and lower hippocampal volumes. DMI was a slightly better predictor than Total Scale score for most AD biomarkers. No demographic variables consistently contributed to these models. CONCLUSIONS: The RBANS - DMI in particular - is sensitive to AD pathology. As such, it could be used as a predictive tool, particularly in clinical drug trials to enrich samples prior to less accessible AD biomarker investigation.

Left Ear Hearing Predicts Functional Activity in the Brains of Patients with Alzheimer's Disease Dementia.

OBJECTIVES: To determine whether central speech processing ability, as measured by hearing in noise, differs between right and left ears in adults with Alzheimer's disease related dementia (AD) as well as whether differences in central speech processing ability correlate with an fMRI-based measurement of global functional brain connectivity. METHODS: This prospective study was carried out at a tertiary referral center. Patients with an AD diagnosis and pure tone averages 40 dB HL or better were included. They were examined using resting-state fMRI and underwent central audiometric testing using the Dichotic Sentence Identification Test (DSI), the Dichotic Digits Test (DD), and the Synthetic Sentence Identification Test (SS), which test hearing in noise. DSI scores were correlated with resting-state fMRI connectivity between 361 distinct gray matter brain regions of interest (ROIs). Average global connectivity was calculated as mean functional connectivity between an ROI and the other 360 regions, a quantitative marker representing overall functional connectivity in the brain. RESULTS: Sixteen subjects had adequate fMRI and hearing data. The average age was 71.5 years old (±6.0). The average DSI score for the left ear was 40% (±34%) compared to 90% (±10%) in the right ear (P < .001). No difference between ears was noted on the DD. SS does not differentiate between ears, but worsening scores were noted with increasing background noise. Of the fMRI ROIs, 269 of the 361 had multiple comparison corrected significant correlations between global connectivity and DSI of the left ear (P = .004, r = .673), and all 269 showed higher functional connectivity for individuals with higher left DSI score. No correlations between DSI of the right ear and functional connectivity were found. CONCLUSIONS: Correlation was noted between left sided DSI and functional connectivity in patients with AD. Auditory input from the left ear was more susceptible to impairment, suggesting that side-specific auditory input may influence central auditory processing.

Understanding heterosexual women's erotic flexibility: the role of attention in sexual evaluations and neural responses to sexual stimuli.

Many women experience desires, arousal and behavior that run counter to their sexual orientation (orientation inconsistent, 'OI'). Are such OI sexual experiences cognitively and neurobiologically distinct from those that are consistent with one's sexual orientation (orientation consistent, 'OC')? To address this question, we employed a mindful attention intervention-aimed at reducing judgment and enhancing somatosensory attention-to examine the underlying attentional and neurobiological processes of OC and OI sexual stimuli among predominantly heterosexual women. Women exhibited greater neural activity in response to OC, compared to OI, sexual stimuli in regions associated with implicit visual processing, volitional appraisal and attention. In contrast, women exhibited greater neural activity to OI, relative to OC, sexual stimuli in regions associated with complex visual processing and attentional shifting. Mindfully attending to OC sexual stimuli reduced distraction, amplified women's evaluations of OC stimuli as sexually arousing and deactivated the superior cerebellum. In contrast, mindfully attending to OI sexual stimuli amplified distraction, decreased women's evaluations of OI stimuli as sexually arousing and augmented parietal and temporo-occipital activity. Results of the current study constrain hypotheses of female erotic flexibility, suggesting that sexual orientation may be maintained by differences in attentional processing that cannot be voluntarily altered.