Executive function emerges late in development and displays different developmental trends in males and females. Sex differences in executive function in youth have been linked to vulnerability to psychopathology as well as to behaviors that impinge on health. Yet, the neurobiological basis of these differences is not well understood. Here we test the hypothesis that sex differences in executive function in youth stem from sex differences in the controllability of structural brain networks as they rewire over development. Combining methods from network neuroscience and network control theory, we characterize the network control properties of structural brain networks estimated from diffusion imaging data acquired in males and females in a sample of 882 youth aged 8-22 years. We summarize the control properties of these networks by estimating average and modal controllability, two statistics that probe the ease with which brain areas can drive the network towards easy- versus difficult-to-reach states. We find that females have higher modal controllability in frontal, parietal, and subcortical regions while males have higher average controllability in frontal and subcortical regions. Furthermore, average controllability values in the medial frontal cortex and subcortex, both higher in males, are negatively related to executive function. Finally, we find that average controllability predicts sex-dependent individual differences in activation during an n-back working memory task. Taken together, our findings support the notion that sex differences in the controllability of structural brain networks can partially explain sex differences in executive function. Controllability of structural brain networks also predicts features of task-relevant activation, suggesting the potential for controllability to represent context-specific constraints on network state more generally.
The functions of the human brain are metabolically expensive and reliant on coupling between cerebral blood flow (CBF) and neural activity, yet how this coupling evolves over development remains unexplored. Here, we examine the relationship between CBF, measured by arterial spin labeling, and the amplitude of low-frequency fluctuations (ALFF) from resting-state magnetic resonance imaging across a sample of 831 children (478 females, aged 8-22 years) from the Philadelphia Neurodevelopmental Cohort. We first use locally weighted regressions on the cortical surface to quantify CBF-ALFF coupling. We relate coupling to age, sex, and executive functioning with generalized additive models and assess network enrichment via spin testing. We demonstrate regionally specific changes in coupling over age and show that variations in coupling are related to biological sex and executive function. Our results highlight the importance of CBF-ALFF coupling throughout development; we discuss its potential as a future target for the study of neuropsychiatric diseases.
Outline effects of functional neuroimaging on neuropsychology over the past 25 years.Functional neuroimaging methods and studies will be described that provide a historical context, offer examples of the utility of neuroimaging in specific domains, and discuss the limitations and future directions of neuroimaging in neuropsychology.Tracking the history of publications on functional neuroimaging related to neuropsychology indicates early involvement of neuropsychologists in the development of these methodologies. Initial progress in neuropsychological application of functional neuroimaging has been hampered by costs and the exposure to ionizing radiation. With rapid evolution of functional methods-in particular functional MRI (fMRI)-neuroimaging has profoundly transformed our knowledge of the brain. Its current applications span the spectrum of normative development to clinical applications. The field is moving toward applying sophisticated statistical approaches that will help elucidate distinct neural activation networks associated with specific behavioral domains. The impact of functional neuroimaging on clinical neuropsychology is more circumscribed, but the prospects remain enticing.The theoretical insights and empirical findings of functional neuroimaging have been led by many neuropsychologists and have transformed the field of behavioral neuroscience. Thus far they have had limited effects on the clinical practices of neuropsychologists. Perhaps it is time to add training in functional neuroimaging to the clinical neuropsychologist's toolkit and from there to the clinic or bedside. (PsycINFO Database Record
Brain iron is vital to multiple aspects of brain function, including oxidative metabolism, myelination, and neurotransmitter synthesis. Atypical iron concentration in the basal ganglia is associated with neurodegenerative disorders in aging and cognitive deficits. However, the normative development of brain iron concentration in adolescence and its relationship to cognition are less well understood. Here, we address this gap in a longitudinal sample of 922 humans aged 8–26 years at the first visit (M = 15.1, SD = 3.72; 336 males, 486 females) with up to four multiecho T2* scans each. Using this sample of 1236 imaging sessions, we assessed the longitudinal developmental trajectories of tissue iron in the basal ganglia. We quantified tissue iron concentration using R2* relaxometry within four basal ganglia regions, including the caudate, putamen, nucleus accumbens, and globus pallidus. The longitudinal development of R2* was modeled using generalized additive mixed models (GAMMs) with splines to capture linear and nonlinear developmental processes. We observed significant increases in R2* across all regions, with the greatest and most prolonged increases occurring in the globus pallidus and putamen. Further, we found that the developmental trajectory of R2* in the putamen is significantly related to individual differences in cognitive ability, such that greater cognitive ability is increasingly associated with greater iron concentration through late adolescence and young-adulthood. Together, our results suggest a prolonged period of basal ganglia iron enrichment that extends into the mid-twenties, with diminished iron concentration associated with poorer cognitive ability during late adolescence. SIGNIFICANCE STATEMENT Brain tissue iron is essential to healthy brain function. Atypical basal ganglia tissue iron levels have been linked to impaired cognition in iron deficient children and adults with neurodegenerative disorders. However, the normative developmental trajectory of basal ganglia iron concentration during adolescence and its association with cognition are less well understood. In the largest study of tissue iron development yet reported, we characterize the developmental trajectory of tissue iron concentration across the basal ganglia during adolescence and provide evidence that diminished iron content is associated with poorer cognitive performance even in healthy youth. These results highlight the transition from adolescence to adulthood as a period of dynamic maturation of tissue iron concentration in the basal ganglia.
Diffusion MRI is the dominant non-invasive imaging method used to characterize white matter organization in health and disease. Increasingly, fiber-specific properties within a voxel are analyzed using fixels. While tools for conducting statistical analyses of fixel-wise data exist, currently available tools support only a limited number of statistical models. Here we introduce ModelArray, an R package for mass-univariate statistical analysis of fixel-wise data. At present, ModelArray supports linear models as well as generalized additive models (GAMs), which are particularly useful for studying nonlinear effects in lifespan data. In addition, ModelArray also aims for scalable analysis. With only several lines of code, even large fixel-wise datasets can be analyzed using a standard personal computer. Detailed memory profiling revealed that ModelArray required only limited memory even for large datasets. As an example, we applied ModelArray to fixel-wise data derived from diffusion images acquired as part of the Philadelphia Neurodevelopmental Cohort (n = 938). ModelArray revealed anticipated nonlinear developmental effects in white matter. Moving forward, ModelArray is supported by an open-source software development model that can incorporate additional statistical models and other imaging data types. Taken together, ModelArray provides a flexible and efficient platform for statistical analysis of fixel-wise data.
Precisely how the anatomical structure of the brain supports a wide range of complex functions remains a question of marked importance in both basic and clinical neuroscience. Progress has been hampered by the lack of theoretical frameworks explaining how a structural network of relatively rigid interareal connections can produce a diverse repertoire of functional neural dynamics. Here, we address this gap by positing that the brain's structural network architecture determines the set of accessible functional connectivity patterns according to predictions of network control theory. In a large developmental cohort of 823 youths aged 8 to 23 years, we found that the flexibility of a brain region's functional connectivity was positively correlated with the proportion of its structural links extending to different cognitive systems. Notably, this relationship was mediated by nodes' boundary controllability, suggesting that a region's strategic location on the boundaries of modules may underpin the capacity to integrate information across different cognitive processes. Broadly, our study provides a mechanistic framework that illustrates how temporal flexibility observed in functional networks may be mediated by the controllability of the underlying structural connectivity.
Patients with schizophrenia exhibit olfactory deficits, but it is unclear whether these represent a specific abnormality. The link between olfactory impairments and regional brain abnormalities has yet to be established.
Objectives
To determine whether patients with schizophrenia exhibit volumetric deficits in the anterior ventromedial temporal lobe, the target for neuronal inputs from the olfactory bulb, and whether these are related to olfactory performance deficits.
Design
A cohort study of patients and healthy control subjects who underwent both 1-mm spoiled-gradient echo magnetic resonance imaging and behavioral tests of olfaction and memory.
Setting
Schizophrenia Research Center at the University of Pennsylvania, Philadelphia.
Participants
Fifty-two patients with aDSM-IVdiagnosis of schizophrenia and 38 healthy control subjects. Individuals were excluded for history of head trauma, significant substance abuse, and medical conditions affecting brain function or olfactory capacity.
Main Outcome Measures
Gray matter volumes of the left and right temporal poles and the perirhinal and entorhinal cortexes; olfactory threshold detection sensitivity and identification test scores; composite indexes of verbal and spatial memory ability.
Results
Patients had reduced volumes, relative to cranial size, in left (P= .003) and right (P= .01) perirhinal and left (P= .002) and right (P= .002) entorhinal cortexes, but not in the temporal pole. Perirhinal, but not entorhinal, cortical volume decrement was associated with decreased olfactory threshold sensitivity. Neither region was associated with impaired memory performance.
Conclusions
Patients with schizophrenia have reduced cortical volumes in brain regions that receive afferents directly from the olfactory bulb. Behavioral olfactory deficits are related to structural brain abnormalities in these regions.
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