The neuroanatomy of developmental language disorder: a systematic review and meta-analysis.

Developmental language disorder (DLD) is a common neurodevelopmental disorder with adverse impacts that continue into adulthood. However, its neural bases remain unclear. Here we address this gap by systematically identifying and quantitatively synthesizing neuroanatomical studies of DLD using co-localization likelihood estimation, a recently developed neuroanatomical meta-analytic technique. Analyses of structural brain data (22 peer-reviewed papers, 577 participants) revealed highly consistent anomalies only in the basal ganglia (100% of participant groups in which this structure was examined, weighted by group sample sizes; 99.8% permutation-based likelihood the anomaly clustering was not due to chance). These anomalies were localized specifically to the anterior neostriatum (again 100% weighted proportion and 99.8% likelihood). As expected given the task dependence of activation, functional neuroimaging data (11 peer-reviewed papers, 414 participants) yielded less consistency, though anomalies again occurred primarily in the basal ganglia (79.0% and 95.1%). Multiple sensitivity analyses indicated that the patterns were robust. The meta-analyses elucidate the neuroanatomical signature of DLD, and implicate the basal ganglia in particular. The findings support the procedural circuit deficit hypothesis of DLD, have basic research and translational implications for the disorder, and advance our understanding of the neuroanatomy of language.

Early-life education may help bolster declarative memory in old age, especially for women.

Although declarative memory declines with age, sex and education might moderate these weaknesses. We investigated effects of sex and education on nonverbal declarative (recognition) memory in 704 older adults (aged 58-98, 0-17 years of education). Items were drawings of real and made-up objects. Age negatively impacted declarative memory, though this age effect was moderated by sex and object-type: it was steeper for males than females, but only for real objects. Education was positively associated with memory, but also interacted with sex and object-type: education benefited women more than men (countering the age effects, especially for women), and remembering real more than made-up objects. The findings suggest that nonverbal memory in older adults is associated negatively with age but positively with education; both effects are modulated by sex, and by whether learning relates to preexisting or new information. The study suggests downstream benefits from education, especially for girls.

Brain and blood biomarkers of tauopathy and neuronal injury in humans and rats with neurobehavioral syndromes following blast exposure.

Traumatic brain injury (TBI) is a risk factor for the later development of neurodegenerative diseases that may have various underlying pathologies. Chronic traumatic encephalopathy (CTE) in particular is associated with repetitive mild TBI (mTBI) and is characterized pathologically by aggregation of hyperphosphorylated tau into neurofibrillary tangles (NFTs). CTE may be suspected when behavior, cognition, and/or memory deteriorate following repetitive mTBI. Exposure to blast overpressure from improvised explosive devices (IEDs) has been implicated as a potential antecedent for CTE amongst Iraq and Afghanistan Warfighters. In this study, we identified biomarker signatures in rats exposed to repetitive low-level blast that develop chronic anxiety-related traits and in human veterans exposed to IED blasts in theater with behavioral, cognitive, and/or memory complaints. Rats exposed to repetitive low-level blasts accumulated abnormal hyperphosphorylated tau in neuronal perikarya and perivascular astroglial processes. Using positron emission tomography (PET) and the [18F]AV1451 (flortaucipir) tau ligand, we found that five of 10 veterans exhibited excessive retention of [18F]AV1451 at the white/gray matter junction in frontal, parietal, and temporal brain regions, a typical localization of CTE tauopathy. We also observed elevated levels of neurofilament light (NfL) chain protein in the plasma of veterans displaying excess [18F]AV1451 retention. These findings suggest an association linking blast injury, tauopathy, and neuronal injury. Further study is required to determine whether clinical, neuroimaging, and/or fluid biomarker signatures can improve the diagnosis of long-term neuropsychiatric sequelae of mTBI.

Working memory in older adults declines with age, but is modulated by sex and education.

Working memory (WM), which underlies the temporary storage and manipulation of information, is critical for multiple aspects of cognition and everyday life. Nevertheless, research examining WM specifically in older adults remains limited, despite the global rapid increase in human life expectancy. We examined WM in a large sample ( N = 754) of healthy older adults (aged 58-89) in a non-Western population (Chinese speakers) in Taiwan, on a digit n-back task. We tested not only the influence of age itself and of load (1-back vs. 2-back) but also the effects of both sex and education, which have been shown to modulate WM abilities. Mixed-effects regression revealed that, within older adulthood, age negatively impacted WM abilities (with linear, not nonlinear, effects), as did load (worse performance at 2-back). In contrast, education level was positively associated with WM. Moreover, both age and education interacted with sex. With increasing age, males showed a steeper WM decline than females; with increasing education, females showed greater WM gains than males. Together with other findings, the evidence suggests that age, sex, and education all impact WM in older adults, but interact in particular ways. The results have both basic research and translational implications and are consistent with particular benefits from increased education for women.

A compensatory role for declarative memory in neurodevelopmental disorders.

Most research on neurodevelopmental disorders has focused on their abnormalities. However, what remains intact may also be important. Increasing evidence suggests that declarative memory, a critical learning and memory system in the brain, remains largely functional in a number of neurodevelopmental disorders. Because declarative memory remains functional in these disorders, and because it can learn and retain numerous types of information, functions, and tasks, this system should be able to play compensatory roles for multiple types of impairments across the disorders. Here, we examine this hypothesis for specific language impairment, dyslexia, autism spectrum disorder, Tourette syndrome, and obsessive-compulsive disorder. We lay out specific predictions for the hypothesis and review existing behavioral, electrophysiological, and neuroimaging evidence. Overall, the evidence suggests that declarative memory indeed plays compensatory roles for a range of impairments across all five disorders. Finally, we discuss diagnostic, therapeutic and other implications.