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Background: Huntington disease (HD) is characterized by striatal atrophy that begins long before the onset of motor symptoms. Objective: To determine when striatal atrophy begins, the extent and rate of atrophy before diagnosis of motor symptoms, and whether striatal atrophy can predict when symptom onset will occur. Methods: Caudate and putamen volumes were measured on MRI scans of 19 preclinical subjects with the HD gene expansion who were very far (9 to 20 years) from estimated onset, and on serial scans from 17 preclinical subjects, six of whom were diagnosed with HD within 5 years after the initial scan. Results: Striatal volumes were significantly smaller for the subjects who were very far from estimated onset than for age-matched control subjects. Statistical models fit to the longitudinal data suggest that rate of caudate atrophy becomes significant when subjects are approximately 11 years from estimated onset and rate of putamen atrophy becomes significant approximately 9 years prior to onset. In the six incident cases, caudate and putamen were approximately one-third to one-half of normal volume at diagnosis, and caudate volume alone was able to predict with 100% accuracy those subjects who would be diagnosed within 2 years of imaging. Conclusions: Striatal atrophy begins many years prior to diagnosable HD, and assessment of atrophy on MRI may be very useful in both predicting HD onset and in tracking progression in future therapeutic trials in preclinical subjects.

Objective: To assess the effects of reading instruction on fMRI brain activation in children with dyslexia. Background: fMRI differences between dyslexic and control subjects have most often involved phonologic processing tasks. However, a growing body of research documents the role of morphologic awareness in reading and reading disability. Methods: The authors developed tasks to probe brain activation during phoneme mapping (assigning sounds to letters) and morpheme mapping (understanding the relationship of suffixed words to their roots). Ten children with dyslexia and 11 normal readers performed these tasks during fMRI scanning. Children with dyslexia then completed 28 hours of comprehensive reading instruction. Scans were repeated on both dyslexic and control subjects using the same tasks. Results: Before treatment, children with dyslexia showed less activation than controls in left middle and inferior frontal gyri, right superior frontal gyrus, left middle and inferior temporal gyri, and bilateral superior parietal regions for phoneme mapping. Activation was significantly reduced for children with dyslexia on the initial morpheme mapping scan in left middle frontal gyrus, right superior parietal, and fusiform/occipital region. Treatment was associated with improved reading scores and increased brain activation during both tasks, such that quantity and pattern of activation for children with dyslexia after treatment closely resembled that of controls. The elimination of group differences at follow-up was due to both increased activation for the children with dyslexia and decreased activation for controls, presumably reflecting practice effects. Conclusion: These results suggest that behavioral gains from comprehensive reading instruction are associated with changes in brain function during performance of language tasks. Furthermore, these brain changes are specific to different language processes and closely resemble patterns of neural processing characteristic of normal readers.

Objective: To explore the specific gross neuroanatomic substrates of this brain developmental disorder, the authors examine brain morphometric features in a large sample of carefully diagnosed 3- to 4-year-old children with autism spectrum disorder (ASD) compared with age-matched control groups of typically developing (TD) children and developmentally delayed (DD) children.Methods: Volumes of the cerebrum, cerebellum, amygdala, and hippocampus were measured from three-dimensional coronal MR images acquired from 45 children with ASD, 26 TD children, and 14 DD children. The volumes were analyzed with respect to age, sex, volume of the cerebrum, and clinical status.Results: Children with ASD were found to have significantly increased cerebral volumes compared with TD and DD children. Cerebellar volume for the ASD group was increased in comparison with the TD group, but this increase was proportional to overall increases in cerebral volume. The DD group had smaller cerebellar volumes compared with both of the other groups. Measurements of amygdalae and hippocampi in this group of young children with ASD revealed enlargement bilaterally that was proportional to overall increases in total cerebral volume. There were similar findings of cerebral enlargement for both girls and boys with ASD. For subregion analyses, structural abnormalities were observed primarily in boys, although this may reflect low statistical power issues because of the small sample (seven girls with ASD) studied. Among the ASD group, structural findings were independent of nonverbal IQ. In a subgroup of children with ASD with strictly defined autism, amygdalar enlargement was in excess of increased cerebral volume.Conclusions: These structural findings suggest abnormal brain developmental processes early in the clinical course of autism. Research currently is underway to better elucidate mechanisms underlying these structural abnormalities and their longitudinal progression.

Objective: To determine whether volumes of hippocampus and amygdala are abnormal in people with autism. Background: Neuropathologic studies of the limbic system in autism have found decreased neuronal size, increased neuronal packing density, and decreased complexity of dendritic arbors in hippocampus, amygdala, and other limbic structures. These findings are suggestive of a developmental curtailment in the maturation of the neurons and neuropil. Methods: Measurement of hippocampus, amygdala, and total brain volumes from 1.5-mm coronal, spoiled gradient-recalled echo MRI scans in 14 non–mentally retarded autistic male adolescents and young adults and 14 individually matched, healthy community volunteers. Results: Amygdala volume was significantly smaller in the autistic subjects, both with ( p = 0.006) and without ( p = 0.01) correcting for total brain volume. Total brain volume and absolute hippocampal volume did not differ significantly between groups, but hippocampal volume, when corrected for total brain volume, was significantly reduced ( p = 0.04) in the autistic subjects. Conclusions: There is a reduction in the volume of amygdala and hippocampus in people with autism, particularly in relation to total brain volume. The histopathology of autism suggests that these volume reductions are related to a reduction in dendritic tree and neuropil development, and likely reflect the underdevelopment of the neural connections of limbic structures with other parts of the brain, particularly cerebral cortex.

Brain Imaging in Psychiatry by Shon Lewis and Nicholas Higgins , 326 pp., ill., Oxford, Blackwell Science Ltd, 1996, $99.95 Chapters in this book are devoted to two major topics: explanation of various neuroimaging methods and reviews of neuroimaging research in psychiatric disorders. In addition, there are chapters on the history of brain imaging and on normal brain anatomy. The book is intended for "clinical and academic psychiatrists at all levels, including those who have no detailed knowledge of brain imaging." In general, the chapters explaining neuroimaging methods (including CT, MRI, fMRI, PET, SPET, MRS, EEG, and MEG) will serve as excellent references for investigators who want to more fully understand these methodologies. Some chapters, however, contain detail that will be difficult to understand for those without a fairly sophisticated background in …