Feb 24

Structural Abnormalities in the Brains of Human Subjects Who Use Methamphetamine

We visualize, for the first time, the profile of structural deficits in the human brain associated with chronic methamphetamine (MA) abuse. Studies of human subjects who have used MA chronically have revealed deficits in dopaminergic and serotonergic systems and cerebral metabolic abnormalities. Using magnetic resonance imaging (MRI) and new computational brain-mapping techniques, we determined the pattern of structural brain alterations associated with chronic MA abuse in human subjects and related these deficits to cognitive impairment. We used high-resolution MRI and surface-based computational image analyses to map regional abnormalities in the cortex, hippocampus, white matter, and ventricles in 22 human subjects who usedMAand 21 age-matched, healthy controls. Cortical maps revealed severe gray-matter deficits in the cingulate, limbic, and paralimbic cortices ofMAabusers (averaging 11.3% below control;p-0.05). On average,MAabusers had 7.8% smaller hippocampal volumes than control subjects ( p-0.01; left, p-0.01; right, p-0.05) and significant white-matter hypertrophy (7.0%; p - 0.01). Hippocampal deficits were mapped and correlated with memory performance on a word-recall test ( p- 0.05). MRI-based maps suggest that chronic methamphetamine abuse causes a selective pattern of cerebral deterioration that contributes to impaired memory performance. MA may selectively damage the medial temporal lobe and, consistent with metabolic studies, the cingulate–limbic cortex, inducing neuroadaptation, neuropil reduction, or cell death. Prominent white-matter hypertrophy may result from altered myelination and adaptive glial changes, including gliosis secondary to neuronal damage. These brain substrates may help account for the symptoms of MA abuse, providing therapeutic targets for drug-induced brain injury.
Key words: methamphetamine; brain imaging; drug abuse; MRI; cortex; hippocampus; limbic system; memory introduction Methamphetamine (MA) abuse is a growing epidemic worldwide. Read the rest of this entry »

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Feb 20

We report the dynamic anatomical sequence of human cortical gray matter development between the age of 4–21 years using quantitative four-dimensional maps and time-lapse sequences. Thirteen healthy children for whom anatomic brain MRI scans were obtained every 2 years, for 8–10 years, were studied. By using models of the cortical surface and sulcal landmarks and a statistical model for gray matter density, human cortical development could be visualized across the age range in a spatiotemporally detailed time-lapse sequence. The resulting time-lapse ‘‘movies’’ reveal that (i) higher-order association cortices mature only after lower-order somatosensory and visual cortices, the functions of which they integrate, are developed, and (ii) phylogenetically older brain areas mature earlier than newer ones. Direct comparison with normal cortical development may help understanding of some neurodevelopmental disorders such as childhood-onset schizophrenia or autism.


Human brain development is structurally and functionally a nonlinear process, and understanding normal brain maturation is essential for understanding neurodevelopmental disorders. The heteromodal nature of cognitive brain
development is evident from studies of neurocognitive performance, functional imaging (functional MRI or positronemission tomography) , and electroencephalogram coherence studies. Prior imaging studies show regional nonlinear changes in gray matter (GM) density during childhood and adolescence with prepubertal increase followed by postpubertal loss. The GM density on MRI is an indirect measure of a complex architecture of glia, vasculature, and neurons with dendritic and synaptic processes. Studies of GM maturation show a loss in corticalGMdensity over time, which temporally correlates with postmortem findings of increased synaptic pruning during adolescence and early adulthood. Here we present a study of cortical GM development in children and adolescents by using a brain-mapping technique and a prospectively studied sample of 13 healthy children (4–21 years old), who were scanned with MRI every 2 years for 8–10 years. Because the scans were obtained repeatedly on the same subjects over time, statistical extrapolation of points in between scans enabled construction of an animated time-lapse sequence (‘‘movie’’) of pediatric brain development. We hypothesized that GM development in childhood through early adulthood would be nonlinear as described before and would progress in a localized, region-specific manner coinciding with the functional maturation. We also predicted that the regions associated with more primary functions (e.g., primary motor cortex) would develop earlier compared with the regions that are involved with more complex and integrative tasks (e.g., temporal lobe).
The result is a dynamic map of GM maturation in the pre- and postpubertal period. Our results, while highlighting the remarkable heterogeneity, show that the cortical GM development appears to follow the functional maturation sequence, with the primary sensorimotor cortices along with frontal and occipital poles maturing first, and the remainder of the cortex developing in a parietal-to-frontal (back-to-front) direction. The superior temporal cortex, which contains association areas that integrate information from several sensory modalities, matured last. Furthermore, the maturation of the cortex also appeared to follow the evolutionary sequence in which these regions were created. Read the rest of this entry »

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