Subdural Hemorrhage in Asymptomatic Neonates: Neurodevelopmental Outcomes and MRI Findings at 2 Years.

Background Subdural hemorrhage (SDH) is thought to have a benign course in asymptomatic neonates. However, effects on neurodevelopmental outcomes have not been established. Purpose To evaluate neurodevelopmental outcomes, gray matter volumes, and MRI findings in asymptomatic neonates with SDH compared with control neonates. Materials and Methods This retrospective analysis was conducted between 2003 and 2016 and was based on data from the University of North Carolina Early Brain Development Study. Neurodevelopmental outcomes were evaluated at 2 years of age by using the Mullen Scales of Early Learning (MSEL). All infants were imaged with 3.0-T MRI machines and were evaluated for SDH at baseline (neonates) and at ages 1 and 2 years. Volumetric MRI for brain segmentation was performed at ages 1 and 2 years. A secondary analysis was performed in neonates matched 1:1 with control neonates. Differences in categorical variables were measured by using the Fisher exact test, and the t test was used for continuous variables. Results A total of 311 neonates (mean gestational age ± standard deviation, 39.3 weeks ± 1.5), including 57 with SDH (mean gestational age, 39.5 weeks ± 1.2), were evaluated. The subgroup included 55 neonates with SDH (mean gestational age, 39.6 weeks ± 1.2) and 55 matched control neonates (mean gestational age, 39.7 weeks ± 1.2). Fifty-five of 57 neonates with SDH (97%; 95% CI: 92, 100) were delivered vaginally compared with 157 of 254 control neonates (62%, 95% CI: 56, 68; P < .001). Otherwise, there were no differences in perinatal, maternal, or obstetric parameters. There were no differences in composite MSEL scores (115 ± 15 and 109 ± 16 at 2 years, respectively; P = .05) or gray matter volumes between the neonatal SDH group and control neonates (730 cm3 ± 85 and 742 cm3 ± 76 at 2 years, respectively; P = .70). There was no evidence of rebleeding at follow-up MRI. Conclusion Neurodevelopmental scores and gray matter volumes at age 2 years did not differ between asymptomatic neonates with subdural hemorrhage and control neonates. © RSNA, 2020 Online supplemental material is available for this article.

Radiation safety education and diagnostic imaging in pediatric patients with surgically treated hydrocephalus: the patient and family perspective.

PURPOSE: Surgically treated hydrocephalus patients are frequently imaged with head computed tomography (CT), and risk/benefit communication with families is inconsistent and unknown. We aimed to educate patients and caregivers about radiation safety in CT and explore their communication preferences. METHODS: We conducted a pediatric CT radiation safety and diagnostic imaging educational workshop for patients and caregivers at a national conference on hydrocephalus to characterize current practice and desired communication about CT imaging. Our workshop consisted of an interactive educational intervention with pre-/post-session surveys followed by feedback from participants. RESULTS: Our session included 34 participants (100% response rate for surveys) with 28 being parents of individuals with hydrocephalus. A total of 76% (n = 26) participants showed an increase in knowledge after the session (p < 0.01). All participants (N = 34) uniformly desired risk/benefit discussions before CT scans. However, 71% stated that they were not informed of risks/benefits of CT scans by a medical professional. Following the session, the number of participants indicating that informed consent should be obtained before CT scans increased from 30 to 33. Respondents also revealed that 14% of children and young adults had received > 100 CT scans for shunt evaluation with the median being 25 scans (IQR 20). CONCLUSIONS: Caregivers desire and deserve to be empowered through education and social support, and continuously engaged through sharing decisions and co-designing care plans. The neurosurgical community is in an ideal position to collaborate with radiologists, primary care providers, and parents in the development and testing of credible, high-quality online and social media resources.

The UNC/UMN Baby Connectome Project (BCP): An overview of the study design and protocol development.

The human brain undergoes extensive and dynamic growth during the first years of life. The UNC/UMN Baby Connectome Project (BCP), one of the Lifespan Connectome Projects funded by NIH, is an ongoing study jointly conducted by investigators at the University of North Carolina at Chapel Hill and the University of Minnesota. The primary objective of the BCP is to characterize brain and behavioral development in typically developing infants across the first 5 years of life. The ultimate goals are to chart emerging patterns of structural and functional connectivity during this period, map brain-behavior associations, and establish a foundation from which to further explore trajectories of health and disease. To accomplish these goals, we are combining state of the art MRI acquisition and analysis techniques, including high-resolution structural MRI (T1-and T2-weighted images), diffusion imaging (dMRI), and resting state functional connectivity MRI (rfMRI). While the overall design of the BCP largely is built on the protocol developed by the Lifespan Human Connectome Project (HCP), given the unique age range of the BCP cohort, additional optimization of imaging parameters and consideration of an age appropriate battery of behavioral assessments were needed. Here we provide the overall study protocol, including approaches for subject recruitment, strategies for imaging typically developing children 0-5 years of age without sedation, imaging protocol and optimization, a description of the battery of behavioral assessments, and QA/QC procedures. Combining HCP inspired neuroimaging data with well-established behavioral assessments during this time period will yield an invaluable resource for the scientific community.

LCCC 1025: a phase II study of everolimus, trastuzumab, and vinorelbine to treat progressive HER2-positive breast cancer brain metastases.

PURPOSE: HER2 + breast cancer (BC) is an aggressive subtype with high rates of brain metastases (BCBM). Two-thirds of HER2 + BCBM demonstrate activation of the PI3K/mTOR pathway driving resistance to anti-HER2 therapy. This phase II study evaluated everolimus (E), a brain-permeable mTOR inhibitor, trastuzumab (T), and vinorelbine (V) in patients with HER2 + BCBM. PATIENTS AND METHODS: Eligible patients had progressive HER2 + BCBM. The primary endpoint was intracranial response rate (RR); secondary objectives were CNS clinical benefit rate (CBR), extracranial RR, time to progression (TTP), overall survival (OS), and targeted sequencing of tumors from enrolled patients. A two-stage design distinguished intracranial RR of 5% versus 20%. RESULTS: 32 patients were evaluable for toxicity, 26 for efficacy. Intracranial RR was 4% (1 PR). CNS CBR at 6 mos was 27%; at 3 mos 65%. Median intracranial TTP was 3.9 mos (95% CI 2.2-5). OS was 12.2 mos (95% CI 0.6-20.2). Grade 3-4 toxicities included neutropenia (41%), anemia (16%), and stomatitis (16%). Mutations in TP53 and PIK3CA were common in BCBM. Mutations in the PI3K/mTOR pathway were not associated with response. ERBB2 amplification was higher in BCBM compared to primary BC; ERBB2 amplification in the primary BC trended toward worse OS. CONCLUSION: While intracranial RR to ETV was low in HER2 + BCBM patients, one-third achieved CNS CBR; TTP/OS was similar to historical control. No new toxicity signals were observed. Further analysis of the genomic underpinnings of BCBM to identify tractable prognostic and/or predictive biomarkers is warranted. CLINICAL TRIAL: (NCT01305941).

Effects of Career Duration, Concussion History, and Playing Position on White Matter Microstructure and Functional Neural Recruitment in Former College and Professional Football Athletes.

Purpose To better understand the relationship between exposure to concussive and subconcussive head impacts, white matter integrity, and functional task-related neural activity in former U.S. football athletes. Materials and Methods Between 2011 and 2013, 61 cognitively unimpaired former collegiate and professional football players (age range, 52-65 years) provided informed consent to participate in this cross-sectional study. Participants were stratified across three crossed factors: career duration, concussion history, and primary playing position. Fractional anisotropy (FA) and blood oxygen level-dependent (BOLD) percent signal change (PSC) were measured with diffusion-weighted and task-related functional magnetic resonance imaging, respectively. Analyses of variance of FA and BOLD PSC were used to determine main or interaction effects of the three factors. Results A significant interaction between career duration and concussion history was observed; former college players with more than three concussions had lower FA in a broadly distributed area of white matter compared with those with zero to one concussion (t29 = 2.774; adjusted P = .037), and the opposite was observed for former professional players (t29 = 3.883; adjusted P = .001). A separate interaction between concussion history and position was observed: Nonspeed players with more than three concussions had lower FA in frontal white matter compared with those with zero to one concussion (t25 = 3.861; adjusted P = .002). Analysis of working memory-task BOLD PSC revealed a similar interaction between concussion history and position (all adjusted P < .004). Overall, former players with lower FA tended to have lower BOLD PSC across three levels of a working memory task. Conclusion Career duration and primary playing position seem to modify the effects of concussion history on white matter structure and neural recruitment. The differences in brain structure and function were observed in the absence of clinical impairment, which suggested that multimodal imaging may provide early markers of onset of traumatic neurodegenerative disease. © RSNA, 2017 Online supplemental material is available for this article.

Functional Network Development During the First Year: Relative Sequence and Socioeconomic Correlations.

The first postnatal year is characterized by the most dramatic functional network development of the human lifespan. Yet, the relative sequence of the maturation of different networks and the impact of socioeconomic status (SES) on their development during this critical period remains poorly characterized. Leveraging a large, normally developing infant sample with multiple longitudinal resting-state functional magnetic resonance imaging scans during the first year (N = 65, scanned every 3 months), we aimed to delineate the relative maturation sequence of 9 key brain functional networks and examine their SES correlations. Our results revealed a maturation sequence from primary sensorimotor/auditory to visual to attention/default-mode, and finally to executive control networks. Network-specific critical growth periods were also identified. Finally, marginally significant positive SES-brain correlations were observed at 6 months of age for both the sensorimotor and default-mode networks, indicating interesting SES effects on functional brain maturation. To the best of our knowledge, this is the first study delineating detailed longitudinal growth trajectories of all major functional networks during the first year of life and their SES correlations. Insights from this study not only improve our understanding of early brain development, but may also inform the critical periods for SES expression during infancy.

Intersubject variability of and genetic effects on the brain's functional connectivity during infancy.

Infancy is a period featuring a high level of intersubject variability but the brain basis for such variability and the potential genetic/environmental contributions remain largely unexplored. The assessment of the brain's functional connectivity during infancy by the resting state functional magnetic resonance imaging (rsfMRI) technique (Biswal et al., 1995) provides a unique means to probe the brain basis of intersubject variability during infancy. In this study, an unusually large typically developing human infant sample including 58 singletons, 132 dizygotic twins, and 98 monozygotic twins with rsfMRI scans during the first 2 years of life was recruited to delineate the spatial and temporal developmental patterns of both the intersubject variability of and genetic effects on the brain's functional connectivity. Through systematic voxelwise functional connectivity analyses, our results revealed that the intersubject variability at birth features lower variability in primary functional areas but higher values in association areas. Although the relative pattern remains largely consistent, the magnitude of intersubject variability undergoes an interesting U-shaped growth during the first 2 years of life. Overall, the intersubject variability patterns during infancy show both adult-like and infant-specific characteristics (Mueller et al., 2013). On the other hand, age-dependent genetic effects were observed showing significant but bidirectional relationships with intersubject variability. The temporal and spatial patterns of the intersubject variability of and genetic contributions to the brain's functional connectivity documented in this study shed light on the largely uncharted functional development of the brain during infancy.

Development of thalamocortical connectivity during infancy and its cognitive correlations.

Although commonly viewed as a sensory information relay center, the thalamus has been increasingly recognized as an essential node in various higher-order cognitive circuits, and the underlying thalamocortical interaction mechanism has attracted increasing scientific interest. However, the development of thalamocortical connections and how such development relates to cognitive processes during the earliest stages of life remain largely unknown. Leveraging a large human pediatric sample (N = 143) with longitudinal resting-state fMRI scans and cognitive data collected during the first 2 years of life, we aimed to characterize the age-dependent development of thalamocortical connectivity patterns by examining the functional relationship between the thalamus and nine cortical functional networks and determine the correlation between thalamocortical connectivity and cognitive performance at ages 1 and 2 years. Our results revealed that the thalamus-sensorimotor and thalamus-salience connectivity networks were already present in neonates, whereas the thalamus-medial visual and thalamus-default mode network connectivity emerged later, at 1 year of age. More importantly, brain-behavior analyses based on the Mullen Early Learning Composite Score and visual-spatial working memory performance measured at 1 and 2 years of age highlighted significant correlations with the thalamus-salience network connectivity. These results provide new insights into the understudied early functional brain development process and shed light on the behavioral importance of the emerging thalamocortical connectivity during infancy.

TBCRC 018: phase II study of iniparib in combination with irinotecan to treat progressive triple negative breast cancer brain metastases.

Nearly half of patients with advanced triple negative breast cancer (TNBC) develop brain metastases (BM) and most will also have uncontrolled extracranial disease. This study evaluated the safety and efficacy of iniparib, a small molecule anti-cancer agent that alters reactive oxygen species tumor metabolism and penetrates the blood brain barrier, with the topoisomerase I inhibitor irinotecan in patients with TNBC-BM. Eligible patients had TNBC with new or progressive BM and received irinotecan and iniparib every 3 weeks. Time to progression (TTP) was the primary end point; secondary endpoints were response rate (RR), clinical benefit rate (CBR), overall survival (OS), toxicity, and health-related quality of life. Correlative endpoints included molecular subtyping and gene expression studies on pre-treatment archival tissues, and determination of germline BRCA1/2 status. Thirty-seven patients began treatment; 34 were evaluable for efficacy. Five of 24 patients were known to carry a BRCA germline mutation (4 BRCA1, 1 BRCA2). Median TTP was 2.14 months and median OS was 7.8 months. Intracranial RR was 12 %, while intracranial CBR was 27 %. Treatment was well-tolerated; the most common grade 3/4 adverse events were neutropenia and fatigue. Grade 3/4 diarrhea was rare (3 %). Intrinsic subtyping revealed 19 of 21 tumors (79 %) were basal-like, and intracranial response was associated with high expression of proliferation-related genes. This study suggests a modest benefit of irinotecan plus iniparib in progressive TNBC-BM. More importantly, this trial design is feasible and lays the foundation for additional studies for this treatment-refractory disease.

The health risks of ionizing radiation from computed tomography.

Concerns have increased about the potential health risks of ionizing radiation from computed tomography (CT) scans. This paper discusses the biological effects of radiation, describes research findings related to CT use, cites strategies for radiation dose reduction, and emphasizes the need to be judicious in ordering CT scans for children.

Evidence on the emergence of the brain's default network from 2-week-old to 2-year-old healthy pediatric subjects.

Several lines of evidence have implicated the existence of the brain's default network during passive or undirected mental states. Nevertheless, results on the emergence of the default network in very young pediatric subjects are lacking. Using resting functional magnetic resonance imaging in healthy pediatric subjects between 2 weeks and 2 years of age, we describe the temporal evolution of the default network in a critical, previously unstudied, period of early human brain development. Our results demonstrate that a primitive and incomplete default network is present in 2-week-olds, followed by a marked increase in the number of brain regions exhibiting connectivity, and the percent of connection at 1 year of age. By 2 years of age, the default network becomes similar to that observed in adults, including medial prefrontal cortex (MPFC), posterior cingulate cortex/retrosplenial (PCC/Rsp), inferior parietal lobule, lateral temporal cortex, and hippocampus regions. While the anatomical representations of the default network highly depend on age, the PCC/Rsp is consistently observed at in both age groups and is central to the most and strongest connections of the default network, suggesting that PCC/Rsp may serve as the main "hub" of the default network as this region does in adults. In addition, although not as remarkable as the PCC/Rsp, the MPFC also emerges as a potential secondary hub starting from 1 year of age. These findings reveal the temporal development of the default network in the critical period of early brain development and offer new insights into the emergence of brain default network.

Twin-singleton differences in neonatal brain structure.

Twin studies suggest that global and regional brain volumes are highly heritable. However, estimates of heritability vary across development. Given that all twin studies are open to the potential criticism of non-generalizability due to differences in intrauterine environment between twins and singletons, these age effects may reflect the influence of perinatal environmental factors, which are unique to twins and which may be especially evident early in life. To address this question, we compared brain volumes and the relationship of brain volumes to gestational age in 136 singletons (67 male, 69 female) and 154 twins (75 male, 79 female; 82 DZ, 72 MZ) who had received high resolution MRI scans of the brain in the first month of life. Intracranial volume, total white matter, and ventricle volumes did not differ between twins and singletons. However, cerebrospinal fluid and frontal white matter volume was greater in twins compared to singletons. While gray matter volumes at MRI did not differ between groups, the slope of the relationship between total and cortical gray matter and gestational age at the MRI scan was steeper in MZ twins compared to DZ twins. Post-hoc analyses suggested that gray matter development is delayed in MZ twins in utero and that they experience 'catch-up' growth in the first month of life. These differences should be taken into account when interpreting and designing studies in the early postnatal period.

ABCnet: Adversarial bias correction network for infant brain MR images.

Automatic correction of intensity nonuniformity (also termed as the bias correction) is an essential step in brain MR image analysis. Existing methods are typically developed for adult brain MR images based on the assumption that the image intensities within the same brain tissue are relatively uniform. However, this assumption is not valid in infant brain MR images, due to the dynamic and regionally-heterogeneous image contrast and appearance changes, which are caused by the underlying spatiotemporally-nonuniform myelination process. Therefore, it is not appropriate to directly use existing methods to correct the infant brain MR images. In this paper, we propose an end-to-end 3D adversarial bias correction network (ABCnet), tailored for direct prediction of bias fields from the input infant brain MR images for bias correction. The "ground-truth" bias fields for training our network are carefully defined by an improved N4 method, which integrates manually-corrected tissue segmentation maps as anatomical prior knowledge. The whole network is trained alternatively by minimizing generative and adversarial losses. To handle the heterogeneous intensity changes, our generative loss includes a tissue-aware local intensity uniformity term to reduce the local intensity variation in the corrected image. Besides, it also integrates two additional terms to enhance the smoothness of the estimated bias field and to improve the robustness of the proposed method, respectively. Comprehensive experiments with different sizes of training datasets have been carried out on a total of 1492 T1w and T2w MR images from neonates, infants, and adults, respectively. Both qualitative and quantitative evaluations on simulated and real datasets consistently demonstrate the superior performance of our ABCnet in both accuracy and efficiency, compared with popularly available methods.

Radiology Resident Journal Club: Enhancements Add Educational Value.

RATIONALE AND OBJECTIVES: Resident journal clubs are essential to develop skills to critically appraise existing literature. However, most reports of journal clubs focus on logistics of the activity and less on established roles of those involved. Our objective is to report on an innovative journal club from the perspective of key participants. MATERIALS AND METHODS: Journal club schedule, assignments, evaluations, and analysis are proffered from our institution. The journal club goals were formulated as: (1) improving resident understanding of research (biostatistical and epidemiologic) methods and statistical concepts, (2) teaching critical appraisal skills, and (3) promoting the use of evidence-based medicine. Each session's format is interactive, consisting of a 10 minute lecture with radiology examples of a research or statistical concept, followed by a journal club style discussion. Crucial to the success of this curriculum has been input and engagement of multiple parties: radiology residents, epidemiologist directors, and subspecialist clinician educator faculty members. CONCLUSION: A well-thought out and well-run resident journal club offers numerous solutions to radiology residencies. To residency program leadership and to each individual resident annually, resident journal club offers cutting edge medical knowledge, interactive conferences in the formal didactic curriculum, resident training in critical thinking skills and research design, resident training in interpersonal and communication skills, opportunity for residents to be teachers, and expanded resident interprofessional education. It meets Accreditation Council for Graduate Medical Education common program, Residency Review Committee diagnostic radiology program, and American Board of Radiology Milestones requirements.

Disentangled-Multimodal Adversarial Autoencoder: Application to Infant Age Prediction With Incomplete Multimodal Neuroimages.

Effective fusion of structural magnetic resonance imaging (sMRI) and functional magnetic resonance imaging (fMRI) data has the potential to boost the accuracy of infant age prediction thanks to the complementary information provided by different imaging modalities. However, functional connectivity measured by fMRI during infancy is largely immature and noisy compared to the morphological features from sMRI, thus making the sMRI and fMRI fusion for infant brain analysis extremely challenging. With the conventional multimodal fusion strategies, adding fMRI data for age prediction has a high risk of introducing more noises than useful features, which would lead to reduced accuracy than that merely using sMRI data. To address this issue, we develop a novel model termed as disentangled-multimodal adversarial autoencoder (DMM-AAE) for infant age prediction based on multimodal brain MRI. Specifically, we disentangle the latent variables of autoencoder into common and specific codes to represent the shared and complementary information among modalities, respectively. Then, cross-reconstruction requirement and common-specific distance ratio loss are designed as regularizations to ensure the effectiveness and thoroughness of the disentanglement. By arranging relatively independent autoencoders to separate the modalities and employing disentanglement under cross-reconstruction requirement to integrate them, our DMM-AAE method effectively restrains the possible interference cross modalities, while realizing effective information fusion. Taking advantage of the latent variable disentanglement, a new strategy is further proposed and embedded into DMM-AAE to address the issue of incompleteness of the multimodal neuroimages, which can also be used as an independent algorithm for missing modality imputation. By taking six types of cortical morphometric features from sMRI and brain functional connectivity from fMRI as predictors, the superiority of the proposed DMM-AAE is validated on infant age (35 to 848 days after birth) prediction using incomplete multimodal neuroimages. The mean absolute error of the prediction based on DMM-AAE reaches 37.6 days, outperforming state-of-the-art methods. Generally, our proposed DMM-AAE can serve as a promising model for prediction with multimodal data.

A structural MRI study of human brain development from birth to 2 years.

Brain development in the first 2 years after birth is extremely dynamic and likely plays an important role in neurodevelopmental disorders, including autism and schizophrenia. Knowledge regarding this period is currently quite limited. We studied structural brain development in healthy subjects from birth to 2. Ninety-eight children received structural MRI scans on a Siemens head-only 3T scanner with magnetization prepared rapid gradient echo T1-weighted, and turbo spin echo, dual-echo (proton density and T2 weighted) sequences: 84 children at 2-4 weeks, 35 at 1 year and 26 at 2 years of age. Tissue segmentation was accomplished using a novel automated approach. Lateral ventricle, caudate, and hippocampal volumes were also determined. Total brain volume increased 101% in the first year, with a 15% increase in the second. The majority of hemispheric growth was accounted for by gray matter, which increased 149% in the first year; hemispheric white matter volume increased by only 11%. Cerebellum volume increased 240% in the first year. Lateral ventricle volume increased 280% in the first year, with a small decrease in the second. The caudate increased 19% and the hippocampus 13% from age 1 to age 2. There was robust growth of the human brain in the first two years of life, driven mainly by gray matter growth. In contrast, white matter growth was much slower. Cerebellum volume also increased substantially in the first year of life. These results suggest the structural underpinnings of cognitive and motor development in early childhood, as well as the potential pathogenesis of neurodevelopmental disorders.

White matter abnormalities revealed by diffusion tensor imaging in non-demented and demented HIV+ patients.

HIV associated dementia (HAD) is the most advanced stage of central nervous system disease caused by HIV infection. Previous studies have demonstrated that patients with HAD exhibit greater cerebral and basal ganglia atrophy than non-demented HIV+ (HND) patients. However, the extent to which white matter is affected in HAD patients compared to HND patients remains elusive. This study is designed to address the potential white matter abnormalities through the utilization of diffusion tensor imaging (DTI) in both HND and HAD patients. DTI and T1-weighted images were acquired from 18 healthy controls, 21 HND and 8 HAD patients. T1 image-based registration was performed to 1) parcellate the whole brain white matter into major white matter regions, including frontal, parietal, temporal and occipital white matter, corpus callosum and internal capsule for statistical comparisons of the mean DTI values, and 2) warp all DTI parametric images towards the common template space for voxel-based analysis. The statistical comparisons were performed with four DTI parameters including fractional anisotropy (FA), mean (MD), axial (AD), and radial (RD) diffusivities. With Whitney U tests on the mean DTI values, both HND and HAD demonstrated significant differences from the healthy control in multiple white matter regions. In addition, HAD patients exhibited significantly elevated MD and RD in the parietal white matter when compared to HND patients. In the voxel-based analysis, widespread abnormal regions were identified for both HND and HAD patients, although a much larger abnormal volume was observed in HAD patients for all four DTI parameters. Furthermore, both region of interest (ROI) based and voxel-based analyses revealed that RD was affected to a much greater extent than AD by HIV infection, which may suggest that demyelination is the prominent disease progression in white matter.

Exercise and the aging mind: buffing the baby boomer's body and brain.

Among the fears of aging are loss of memory, cognitive decline, and loss of independence. Baby boomers have entered the "aged" cohort and are actively seeking ways to maintain strong bodies and strong minds. Bench to clinical research suggests that keeping physically active and engaged in moderate to vigorous exercise may be vital to brain health. Because exercise promotes neurogenesis, increased brain volume, and improved cognitive function, it can help the aging brain to retain plasticity. However the precise mechanisms by which exercise accomplishes these changes in the brain are not clearly understood. This study argues that "what is good for the heart is good for the brain," although more research is needed to determine the optimal exercise prescription for brain health and successful cognitive aging.