Disruptions to brain development associated with shortened gestation place individuals at risk for the development of behavioral and psychological dysfunction throughout the lifespan. The purpose of the present study was to determine if the benefit for brain development conferred by increased gestational length exists on a continuum across the gestational age spectrum among healthy children with a stable neonatal course. Neurodevelopment was evaluated with structural magnetic resonance imaging in 100 healthy right-handed 6- to 10-year-old children born between 28 and 41 gestational weeks with a stable neonatal course. Data indicate that a longer gestational period confers an advantage for neurodevelopment. Longer duration of gestation was associated with region-specific increases in gray matter density. Further, the benefit of longer gestation for brain development was present even when only children born full term were considered. These findings demonstrate that even modest decreases in the duration of gestation can exert profound and lasting effects on neurodevelopment for both term and preterm infants and may contribute to long-term risk for health and disease.

The concept of auditory-motor interaction pervades speech science research, yet the cortical systems supporting this interface have not been elucidated. Drawing on experimental designs used in recent work in sensory-motor integration in the cortical visual system, we used fMRI in an effort to identify human auditory regions with both sensory and motor response properties, analogous to single-unit responses in known visuomotor integration areas. The sensory phase of the task involved listening to speech (nonsense sentences) or music (novel piano melodies); the "motor" phase of the task involved covert rehearsal/humming of the auditory stimuli. A small set of areas in the superior temporal and temporal-parietal cortex responded both during the listening phase and the rehearsal/humming phase. A left lateralized region in the posterior Sylvian fissure at the parietal-temporal boundary, area Spt, showed particularly robust responses to both phases of the task. Frontal areas also showed combined auditory + rehearsal responsivity consistent with the claim that the posterior activations are part of a larger auditory-motor integration circuit. We hypothesize that this circuit plays an important role in speech development as part of the network that enables acoustic-phonetic input to guide the acquisition of language-specific articulatory-phonetic gestures; this circuit may play a role in analogous musical abilities. In the adult, this system continues to support aspects of speech production, and, we suggest, supports verbal working memory.

Producing and maintaining distinct (orthogonal) neural representations for similar events is critical to avoiding interference in long-term memory. Recently, our laboratory provided the first evidence for separation-like signals in the human CA3/dentate. Here, we extended this by parametrically varying the change in input (similarity) while monitoring CA1 and CA3/dentate for separation and completion-like signals using high-resolution fMRI. In the CA1, activity varied in a graded fashion in response to increases in the change in input. In contrast, the CA3/dentate showed a stepwise transfer function that was highly sensitive to small changes in input.

Summary Because the brain undergoes dramatic changes during fetal development it is vulnerable to environmental insults. There is evidence that maternal stress and anxiety during pregnancy influences birth outcome but there are no studies that have evaluated the influence of stress during human pregnancy on brain morphology. In the current prospective longitudinal study we included 35 women for whom serial data on pregnancy anxiety was available at 19 (±0.83), 25 (±0.9) and 31 (±0.9) weeks gestation. When the offspring from the target pregnancy were between six to nine years of age, their neurodevelopmental stage was assessed by a structural MRI scan. With the application of voxel based morphometry, we found regional reductions in gray matter density in association with pregnancy anxiety after controlling for total gray matter volume, age, gestational age at birth, handedness and postpartum perceived stress. Specifically, independent of postnatal stress, pregnancy anxiety at 19 weeks gestation was associated with gray matter volume reductions in the prefrontal cortex, the premotor cortex, the medial temporal lobe, the lateral temporal cortex, the postcentral gyrus as well as the cerebellum extending to the middle occipital gyrus and the fusiform gyrus. High pregnancy anxiety at 25 and 31 weeks gestation was not significantly associated with local reductions in gray matter volume. This is the first prospective study to show that a specific temporal pattern of pregnancy anxiety is related to specific changes in brain morphology. Altered gray matter volume in brain regions affected by prenatal maternal anxiety may render the developing individual more vulnerable to neurodevelopmental and psychiatric disorders as well as cognitive and intellectual impairment.

The perforant path (PP) undergoes synaptic changes in the course of aging and dementia. Previous studies attempting to assess the integrity of the PP in humans using diffusion tensor imaging (DTI) were limited by low resolution and the inability to identify PP fibers specifically. Here we present an application of DTI at ultrahigh submillimeter resolution that has allowed us to successfully identify diffusion signals unique to the PP and compare the intensity of these signals in a sample of young adults and older adults. We report direct evidence of age-related PP degradation in humans in vivo. We find no evidence of such loss in a control pathway, the alveus, suggesting that these findings are not evidence for a global decline. We also find no evidence for specific entorhinal gray matter atrophy. The extent of PP degradation correlated with performance on a word-list learning task sensitive to hippocampal deficits. We also show evidence for gray matter diffusion signals consistent with pyramidal dendrite orientation in the hippocampus and cerebral cortex. Ultrahigh-resolution microstructural DTI is a unique biomarker that can be used in combination with traditional structural and functional neuroimaging methods to enhance detection of Alzheimer disease in its earliest stages, test the effectiveness of new therapies, and monitor disease progression.T here is converging evidence that one of the earliest locations in the brain to undergo age-related change is the medial temporal lobe (MTL) region (1, 2), which plays an important role in learning new facts and remembering events (3, 4). Selective structural and functional changes in the MTL are evident with aging and specifically target white matter connectivity and cellular function (1). One MTL pathway that is particularly vulnerable to age-related changes is the perforant path (PP) (5-7). This pathway perforates the subiculum carrying input from the entorhinal cortex to the hippocampal formation ( Fig. 1 A and B). The integrity of this pathway is essential for normal hippocampal function (8). Studies in rodents have shown that the PP input to the hippocampus is reduced by approximately one third in aged rats compared with young rats (9, 10) and that stimulation of the PP in aged rats results in less excitation than in young rats (1). Histological studies have observed reduced myelin staining in the PP in Alzheimer disease (AD) (8), and more recently, synaptic loss in this region in individuals with mild cognitive impairment (11). Thus, numerous studies have suggested that the PP undergoes changes with aging and in the course of dementia. However, observing evidence of this degradation in humans in vivo, a key requirement of any viable biomarker, has remained elusive.Diffusion tensor imaging (DTI) is used to investigate the microstructural features of white matter (12), and has recently been applied to the study of aging and dementia (13). DTI is based on the principle that water will diffuse more readily along the principal axis of an axon than perpendicular to ...

This functional magnetic resonance imaging study investigated the relationship between the neural correlates of associative memory encoding, callosal integrity, and memory performance in older adults. Thirty-six older and 18 young subjects were scanned while making relational judgments on word pairs. Neural correlates of successful encoding (subsequent memory effects) were identified by contrasting the activity elicited by study pairs that were correctly identified as having been studied together with the activity elicited by pairs wrongly judged to have come from different study trials. Subsequent memory effects common to the 2 age groups were identified in several regions, including left inferior frontal gyrus and bilateral hippocampus. Negative effects (greater activity for forgotten than for remembered items) in default network regions in young subjects were reversed in the older group, and the amount of reversal correlated negatively with memory performance. Additionally, older subjects' subsequent memory effects in right frontal cortex correlated positively with anterior callosal integrity and negatively with memory performance. It is suggested that recruitment of right frontal cortex during verbal memory encoding may reflect the engagement of processes that compensate only partially for age-related neural degradation.

No abstract

Morphometry of brain structures based on magnetic resonance imaging (MRI) data has become an important tool in neurobiology. Recent multicenter studies in neurodegenerative diseases raised the issue of the precision of volumetric measures, and their dependence on the scanner properties and imaging protocol. A large dataset consisting of 1073 MRI examinations in 843 subjects, acquired on 90 scanners at 58 sites, is analyzed here. A comprehensive set of image quality and content measures is used to describe the influence of the scanner hardware and imaging protocol on the variability of morphometric measures. Scanners equipped with array coils show a remarkable advantage over conventional coils in terms of image quality measures. The signal-and contrast-to-noise ratio in similar systems is equal or slightly better at 1.5 T than 3.0 T, while the white/grey matter tissue contrast is generally better on high-field systems. Repeated MRI investigations on the same scanner were available in 41 subjects, on different scanners in 172 subjects. The retest reliability of repeated volumetric measures under the same conditions was found as sufficient to track changes in longitudinal examinations in individual subjects. Using different acquisition conditions in the same subject, however, the variance of volumetric measures was up to 10 times greater. Two likely factors explaining this finding are scanner-dependent geometrical inaccuracies and differences in the white/ grey matter tissue contrast.