Neuroanatomical Findings Research Articles

Contribution of Magnetic Resonance Microscopy in the 12-Week Neurotoxicity Evaluation of Carbonyl Sulfide in Fischer 344 Rats

In this carbonyl sulfide (COS) study, magnetic resonance microscopy (MRM) and detailed light microscopic evaluation effectively functioned in parallel to assure that the distribution and degree of pathology in the brain was accurately represented. MRM is a powerful imaging modality that allows for excellent identification of neuroanatomical structures coupled with the ability to acquire 200 or more cross-sectional images of the brain, and the ability to display them in multiple planes. F344 rats were exposed to 200-600 ppm COS for up to 12 weeks. Prior to MRM, rats were anesthetized and cardiac perfused with McDowell Trump's fixative containing a gadolinium MR contrast medium. Fixed specimens were scanned at the Duke Center for In Vivo Microscopy on a 9.4 Tesla magnetic resonance system adapted explicitly for microscopic imaging. An advantage of MRM in this study was the ability to identify lesions in rats that appeared clinically normal prior to sacrifice and the opportunity to identify lesions in areas of the brain which would not be included in conventional studies. Other advantages include the ability to examine the brain in multiple planes (transverse, dorsal, sagittal) and obtain and save the MRM images in a digital format that allows for postexperimental data processing and manipulation. MRM images were correlated with neuroanatomical and neuropathological findings. All suspected MRM images were compared to corresponding H&E slides. An important aspect of this study was that MRM was critical in defining our strategy for sectioning the brain, and for designing mechanistic studies (cytochrome oxidase evaluations) and functional assessments (electrophysiology studies) on specifically targeted anatomical sites following COS exposure.

Anomia in patients with left inferior temporal lobe lesions

Background: Damage to left inferior temporal cortex has been associated with naming deficits resulting either from impaired access to phonological word forms (pure anomia) or from degraded semantic knowledge (semantic anomia). Neuropsychological evidence indicates that pure anomia may follow damage to posterior inferior temporal cortex (BA 37), whereas semantic anomia is associated with damage to more anterior temporal lobe regions (BA 20, 21, 38). By contrast, some investigators have suggested that it is the overall severity of anomia, rather than the nature of the underlying cognitive impairment, that is affected by the anterior extent of the lesion.Aims: To examine the naming performance of patients with left inferior temporal lobe damage and determine whether anterior extension of the lesion influences the nature and/or the severity of the naming impairment.Methods & Procedures: Eight participants with focal damage to left inferior temporal cortex completed a battery of language measures that included confrontation naming, semantic processing, and single‐word reading and spelling. Degree and type of anomia was examined relative to anterior lesion extension using both visual inspection and statistical analyses.Outcomes & Results: Naming performance ranged from unimpaired to severely defective, with only two participants demonstrating an additional mild impairment of semantic knowledge. The underlying mechanism of anomia seemed to be degraded access to phonological word forms in all participants, regardless of lesion configuration. The severity of the naming impairment was positively correlated with anterior extension of the lesion towards the temporal pole, although additional analyses suggested that these findings were significantly influenced by participant age. Naming was not correlated with performance on the nonverbal semantic task or any other demographic variable.Conclusions: The behavioural and neuroanatomical findings provide modest support for the hypothesis that a relationship exists between anterior lesion extension and the severity of concomitant anomia in patients with left inferior temporal lobe damage. The data suggest that such lesions may disconnect relatively preserved semantic knowledge from regions critical for access to phonological word forms. However, additional research is needed to discern to what extent age and individual variability temper these effects.

Clinical and Biological Interactions in Affective and Cognitive Geriatric Syndromes

Clinical and biological complexity is the rule rather than the exception in geriatric psychiatric syndromes. Typically, geriatric psychopathology develops in the context of medical and neurological disorders. Under these circumstances, ascertainment of symptoms and signs is difficult. Moreover, behavioral abnormalities, cognitive deficits, and physical symptoms and signs are often contributed by more than one psychiatric, neurological, or medical condition. Finally, symptoms change over time as various coexisting disease processes progress or subside, further complicating clinical assessment and diagnosis. Complexity has been viewed as an obstacle to medical research, which by necessity depends on reduction. Biological and psychosocial hypotheses are nothing but logical reductions, designed to permit understanding of a small part of a larger problem. Experimental design is an operational reduction intended at giving the best chance for hypothesis testing. Such reduction processes become complicated by the clinical intricacies of geriatric psychiatry syndromes. Despite the logical and experimental challenges posed by geriatric syndromes, their complexity has begun to provide meaningful clinical and biological information. Studying depression in Alzheimer’s disease patients exemplifies how comorbid geriatric syndromes can help address clinical and biological questions. In the study by Zubenko et al. in this issue [May 2003], the high prevalence of depression in patients with probable Alzheimer’s disease was confirmed. The study also observed that the depressive syndrome of Alzheimer’s patients is of mild severity and characterized by indecisiveness and diminished ability to concentrate but with limited depressive ideation and sleep disturbances. This symptom profile is difficult to distinguish from an uncomplicated dementia syndrome, thereby contributing to the underrecognition of depression. The increased frequency of psychotic symptoms in depressed Alzheimer’s disease patients further complicates ascertainment of depression. The difficulty in diagnosing depression is evidenced by the wide differences in depression prevalence estimates among patients with Alzheimer’s disease. Improving the methods of ascertainment (1) and treatment of depression in Alzheimer’s patients is critical, since depression contributes to excess disability, personal suffering, family disruption, and premature institutionalization. In addition to highlighting an important clinical problem, the comorbidity of depression and dementia has served as the stimulus for answering both clinical and biological questions. The early concept of “pseudodementia” was based on the assumption that the biological abnormalities of depression were the unitary cause of reversible Clinical and Biological Interactions in Affective and Cognitive Geriatric Syndromes George S. Alexopoulos, M.D.

Avoidance response in goldfish: emotional and temporal involvement of medial and lateral telencephalic pallium.

The hippocampus and the amygdala are involved in avoidance learning in mammals. The medial and lateral pallia of actinopterygian fish have been proposed as homologous to the mammalian pallial amygdala and hippocampus, respectively, on the basis of neuroanatomical findings. This work was aimed at studying the effects of ablation of the medial telencephalic pallia (MP) and lateral telencephalic pallia (LP) in goldfish on the retention of a conditioned avoidance response previously acquired in two experimental conditions. In the first experiment, fish were trained in nontrace avoidance conditioning. In the second experiment, fish were trained in trace avoidance conditioning in which temporal cues were crucial for the learning process. An MP lesion affected the retention of the avoidance response in both procedures; in contrast, an LP lesion impaired the retention only in the trace-conditioning procedure. These data support the presence of two different systems of memory in fish, based on discrete telencephalic areas: the MP, involved in an emotional memory system; and the LP, involved in a spatial, relational, or temporal memory system. Moreover, these differential effects were similar to those produced by amygdalar and hippocampal lesions in mammals. We conclude that these specialized systems of memory could have appeared early during phylogenesis and could have been conserved throughout vertebrate evolution.

Rapid processing and unsupervised learning in a model of the cortical macrocolumn.

We study a model of the cortical macrocolumn consisting of a collection of inhibitorily coupled minicolumns. The proposed system overcomes several severe deficits of systems based on single neurons as cerebral functional units, notably limited robustness to damage and unrealistically large computation time. Motivated by neuroanatomical and neurophysiological findings, the utilized dynamics is based on a simple model of a spiking neuron with refractory period, fixed random excitatory interconnection within minicolumns, and instantaneous inhibition within one macrocolumn. A stability analysis of the system's dynamical equations shows that minicolumns can act as monolithic functional units for purposes of critical, fast decisions and learning. Oscillating inhibition (in the gamma frequency range) leads to a phase-coupled population rate code and high sensitivity to small imbalances in minicolumn inputs. Minicolumns are shown to be able to organize their collective inputs without supervision by Hebbian plasticity into selective receptive field shapes, thereby becoming classifiers for input patterns. Using the bars test, we critically compare our system's performance with that of others and demonstrate its ability for distributed neural coding.

Neural networks engaged in short-term memory rehearsal are disrupted by irrelevant speech in human subjects

Rehearsal mechanisms in human short-term memory are increasingly understood in the light of both behavioural and neuroanatomical findings. However, little is known about the cooperation of participating brain structures and how such cooperations are affected when memory performance is disrupted. In this paper we use EEG coherence as a measure of synchronization to investigate rehearsal processes and their disruption by irrelevant speech in a delayed serial recall paradigm. Fronto-central and fronto-parietal theta (4–7.5 Hz), beta (13–20 Hz), and gamma (35–47 Hz) synchronizations are shown to be involved in our short-term memory task. Moreover, the impairment in serial recall due to irrelevant speech was preceded by a reduction of gamma band coherence. Results suggest that the irrelevant speech effect has its neural basis in the disruption of left-lateralized fronto-central networks. This stresses the importance of gamma band activity for short-term memory operations.

Assessment of cortical gyrus and sulcus formation using MR images in normal fetuses.

The purpose of this study was to estimate the development of the gyrus and sulcus formation in normal fetuses on the basis of the neuroanatomical findings using MR images in relation to gestational age. The MR images were obtained from 109 normal fetuses from 18 to 39 weeks of gestation with no neurological problems. The MR images were classified into 8 stages of development for the gyrus and sulcus formation in the frontal and temporal lobes on the basis of the neuroanatomical findings reported by Chi et al. (1977) and Dorovini-Zis and Dolman (1977). We examined retrospectively the relationship between our classification and gestational age in comparison with the five-stage classification proposed by McArdle et al. (1987). There were significant differences in the gestational age among the 8 groups (P < 0.001). Multiple comparison of individual groups revealed significant differences in the gestational age among the groups (P < 0.05). Images from 28 to 34 weeks of gestation were classified into 4 stages in our classification, while being covered by one stage in McArdle's classification. Our classification is useful for the assessment of fetal cerebral maturation during the third trimester of pregnancy and may contribute to the prenatal diagnosis of developmental delay of the gyrus and sulcus formation.

The cadherin hypothesis of schizophrenia

Disturbance of prenatal brain development and/or postnatal brain maturation in the context of the etiology and pathophysiology of schizophrenic psychoses is increasingly recognized as the developmental hypothesis of schizophrenia. This hypothesis is based on findings in neuroimaging and neuroanatomical findings in schizophrenic disorders. Cell adhesion molecules, such as the cadherins, are of critical importance for morphogenesis in the CNS during embryonic development. Recent investigations of the genomic organization and chromosomal localization of cadherins show a remarkable association with linkage results in affected multiplex pedigrees. Taken together, these findings should lead to an investigation of the role of cadherins in complex psychiatric disorders.

Olfactory-hypoglossal connections.

Natural olfactory stimulation with amyl acetate significantly modulates the electrical activity of hypoglossal neurons and the electromyographic responses of the tongue musculature. The aim of the present study was to identify and characterize, using neuroanatomical and neurophysiological approaches, the pathways involved in the transmission of the olfactory information to the hypoglossal nucleus (XIIn). The neuroanatomical findings provided the initial demonstration that olfactory information is conveyed from the olfactory bulb to the hypoglossal nucleus via the interpeduncular nucleus (IPn) by both fast disynaptic and different polysynaptic pathways. The latter, in particular, involve many of the brain structures that process olfactory information. The electrophysiological studies demonstrated that the IPn neurons respond with a variety of patterns to natural stimulation of the olfactory receptors, thus supporting the hypothesis that the IPn is a crucial relay station for the elaboration and transmission of olfactory stimuli to XIIn.

The neurobiological context of autism.

Autistic disorder (AD) is a complex neuropsychiatric disorder of neurodevelopmental origin, where multiple genetic and environmental factors may interact, resulting in a clinical continuum. The genetic component is best described by a multilocus model that takes into account epistatic interactions between several susceptibility genes. In the past ten years enormous progress has been made in identifying chromosomal regions in linkage with AD, but moving from chromosomal regions to candidate genes has proven to be tremendously difficult. Neuroanatomical findings point to early dysgenetic events taking place in the cerebral cortex, cerebellum, and brainstem. At the cellular level, disease mechanisms may include altered cell migration, increased cell proliferation, decreased cell death, or altered synapse elimination. Neurochemical findings in AD point to involvement of multiple neurotransmitter systems. The serotoninergic system has been intensively investigated in AD, but other neurotransmitter systems (e.g., the GABAergic and the cholinergic system) are also coming under closer scrutiny. The role of environmental factors is still poorly characterized. It is not clear yet whether environmental factors act merely as precipitating agents, always requiring an underlying genetic liability, or whether they represent an essential component of a pathogenetic process where genetic liability alone does not lead to the full-blown autism phenotype. A third potential player in the pathogenesis of autism, in addition to genetic and environmental factors, is developmental variability due to "random" factors, e.g. small fluctuations of gene expression and complex, non-deterministic interactions between genes during brain development. These considerations suggest that a non-deterministic conceptual framework is highly appropriate for autism research.

Hierarchical versus parallel processing in tactile object recognition: a behavioural-neuroanatomical study of aperceptive tactile agnosia.

The organization of the normal perceptual processing subserving tactile object recognition is poorly understood. While perceptual deficits associated with cases of tactile agnosia may pinpoint sites of critical interference with normal tactile information processing, the precise character of such deficits remains unclear. The aim of the present study was to explore the behavioural and neuroanatomical correlates of perceptual disturbances in two cases of unilateral aperceptive tactile agnosia. Perception of microgeometrical and macrogeometrical features was tested using an alternative forced choice paradigm. While both patients were impaired in the assessment of microgeometrical properties of objects (i.e. detecting subtle differences in grating profiles), one patient showed an additional deficit in the perception of macrogeometrical properties of objects (i.e. detecting differences in length of cuboids). The pattern of perceptual deficits for both patients suggested a severely compromised (if not totally lost) ability to recognize everyday objects. Perceptual performance improved when the patients had complementary tactile information (i.e. for intramodal comparison), despite a persistent inability to explicitly name the objects. That is, the patients were able to recognize objects, but only implicitly. Improved perceptual performance was also observed when complementary visual information was available (i.e. transmodal information transfer). In this case, the perceptual improvement was accompanied by a corresponding improvement in explicit object recognition. High resolution MRIs identified lesions in the postcentral gyrus in both patients, and additionally in the secondary somatosensory area (SII) and the posterior parietal cortex in the more severely affected patient. The results demonstrate that the underlying failure in tactile agnosia is mainly impaired perception of microgeometrical properties of objects due to a lesion of primary sensory cortex. The related neuroanatomical findings suggest a degradation of serial information processing within postcentral gyrus. In one case tactile agnosia was almost complete due to additionally impaired perception of macrogeometrical properties of objects, which correlated with the extension of lesion to the posterior parietal cortex. Importantly, the findings indicate traces of two distributed networks for tactile information processing and the associated parallel processing of complementary micro- and macrogeometrical information within postcentral gyrus and posterior parietal lobe.

The development of exogenous orienting: mechanisms of control

The present study examined exogenous orienting in children ages 6 years ( n=14), 10 years ( n=13), 14 years ( n=14), and adults ( n=13). The main purpose was to identify which of the attentional operations underlying exogenous orienting (disengaging, shifting, and/or engaging) improves with age. A simple detection task was used in which single targets were correctly (80%) or incorrectly (20%) cued. The main finding was that disengaging attention alone distinguished the performance of younger children from that of older children and adults, regardless of whether attention alone (covert attention) or attention and associated sensory and motor systems (overt attention) were involved. In addition, our data, in contrast to those reported previously, raise the possibility that even the youngest children tested were able to use the predictability of the cue to enhance their performance. These and related neuroanatomical findings are taken as evidence for the development with age of more flexible control in orienting visual attention.

Endophenotypes in bipolar disorder.

The search for genes in bipolar disorder has provided numerous genetic loci that have been linked to susceptibility to developing the disorder. However, because of the genetic heterogeneity inherent in bipolar disorder, additional strategies may need to be employed to fully dissect the genetic underpinnings. One such strategy involves reducing complex behaviors into their component parts (endophenotypes). Abnormal neurophysiological, biochemical, endocrinological, neuroanatomical, cognitive, and neuropsychological findings are characteristics that often accompany psychiatric illness. It is possible that some of these may eventually be useful in subdefining complex genetic disorders, allowing for improvements in diagnostic assessment, genetic linkage studies, and development of animal models. Findings in patients with bipolar disorder that may eventually be useful as endophenotypes include abnormal regulation of circadian rhythms (the sleep/wake cycle, hormonal rhythms, etc.), response to sleep deprivation, P300 event-related potentials, behavioral responses to psychostimulants and other medications, response to cholinergics, increase in white matter hyperintensities (WHIs), and biochemical observations in peripheral mononuclear cells. Targeting circadian rhythm abnormalities may be a particularly useful strategy because circadian cycles appear to be an inherent evolutionarily conserved function in all organisms and have been implicated in the pathophysiology of bipolar disorder. Furthermore, lithium has been shown to regulate circadian cycles in diverse species, including humans, possibly through inhibition of glycogen synthase kinase 3-beta (GSK-3beta), a known target of lithium.

Effect of prenatal androgen receptor antagonist or aromatase inhibitor on sexual behavior, partner preference and neuronal Fos responses to estrous female odors in the rat accessory olfactory system

Many socially relevant odors are detected in rodent species by the vomeronasal organ and subsequently processed by the accessory olfactory system (AOS). We previously found that gonadectomized male and female rats treated in adulthood with testosterone propionate (TP) showed equivalent Fos responses in the AOS to odors derived from estrous females. Likewise, in contrast with numerous other mammalian species, gonadectomized female rats show surprisingly high levels of male-typical mounting behavior in response to adult TP. We tested the hypothesis that prenatal testosterone (T) exposure, acting via androgen receptors (ARs) or via estrogen receptors, masculinizes the AOS in rats of both sexes. Pregnant dams were treated with either the AR blocker, Flutamide, the aromatase inhibitor, 1,4,6-androstatriene-3,17-dione (ATD), or nothing (control) to assess the role of prenatal androgen and estradiol receptor activation, respectively, in this masculinization. Beginning at birth, male and female offspring were injected subcutaneously (sc) every other day with either ATD (pre- and neonatal ATD group) or oil vehicle (Flutamide and control groups) until postnatal Day 12. Subjects were gonadectomized as adults, hormonally treated and tested for different behaviors before having their AOS Fos responses to estrous female odors assessed. Prenatal treatment with Flutamide (but not ATD) significantly decreased anogenital distance and severely impaired intromissive and ejaculatory behaviors in males tested after TP replacement without disrupting mounting capacity in either sex. Pre- and neonatal treatment with ATD (but not Flutamide) enhanced lordosis responsiveness in males tested after sc injections of estradiol and progesterone, whereas these perinatal treatments had no effect on any aspect of masculine coital performance in either sex. After TP treatment, male and female control subjects preferred to approach a tethered stimulus female as opposed to a male, and prenatal Flutamide or perinatal ATD treatments did not modify this pattern of partner preference. Neuronal Fos responses to estrous odors were (as in previous studies) identical in the AOS of gonadectomized TP-treated control males and females. Prenatal Flutamide or perinatal ATD treatments failed to disrupt consistently this profile of Fos responses to estrous odors in the AOS of rats of either sex. These behavioral and neuroanatomical findings raise the possibility that the similar level of male-typical responsiveness to social odors that occurs in male and female rats after adult TP treatment results from nonsteroid-hormone-dependent, species-specific factors that act perinatally in the brains of rats of both sexes.

Williams Syndrome: Neuropsychological Findings and Implications for Practice

Williams syndrome (WS) is a genetic disorder resulting from a deletion on Chromosome 7. Individuals with WS exhibit distinct physical features such as facial abnormalities, hypercalcemia, and congenital heart disease. Psychosocial characteristics include an outgoing, friendly personality, excellent conservational skills, and mild to moderate mental retardation. Neuroanatomical findings related to WS indicate that the overall size of the cerebrum is reduced although there is proportionately no lateralized volume reduction. Additionally, individuals with WS have a smaller corpus callosum and an enlarged neocerebellum. Observed neuropsychological characteristics form a distinct profile of strengths and weaknesses. In general, strengths are demonstrated in linguistic skills and facial processing, despite overall cognitive impairment and visuo–spatial processing deficiencies. Further research is needed on the relationship between brain structure and function of individuals with WS in order to elucidate the brain systems that contribute to the observed neuropsychological sequelae. Implications for the provision of school psychological services and educational planning of children with WS are provided.

Interference with the GABAergic system in the dorsolateral telencephalon and modulation of the electric organ discharge frequency in the weakly electric fish Gymnotus carapo.

The functional role of the dorsal portions of dorsolateral telencephalon in modulating the stable electric organ discharge was determined by microinjection of an agonist or antagonist GABAergic drug in the awake weak electric fish, Gymnotus carapo. The dorsolateral telencephalon, which is interconnected with the preglomerular complex and the dorsocentral telencephalic area was microinjected through a guide cannula previously implanted, with different doses of bicuculline, muscimol and saline. Microinjection of bicuculline into the dorsolateral telencephalon induced a complex response consisting of increase, decrease and abrupt interruptions in the frequency of electric organ discharges and an increase in motor activity. Motor activity and modulations in the electric organ discharge are dose dependent. The somatic, but not the electric, effect is abolished under anesthesia by urethane, suggesting that the two responses are parallel but unrelated in terms of occurrence. These data, together with former neuroanatomical findings by this laboratory, suggest two parallel pathways by which the blockage of GABAA receptors in the dorsolateral telencephalon causes modulations in the firing of the medullary pacemaker nucleus. A possible route for the motor effect through reticular projection from the torus semicircularis dorsalis is discussed.

Behavioral, Biological, Genetic and Neuroanatomical Findings: Revealing Multidisciplinary Perspectives on Complex Disorders

History, theories, methods and findings are characteristic of all disciplines. Also characteristic is the tendency to keep within a discipline much of what is known from discovery by scholars in other fields. While unintentional for the most part, the scant knowledge sharing across disciplines arises from deficits or uncertainties in understanding the definitions of terms, references to key constructs and features, variations in methodologies, and in interpretations of findings. Yet, as the chapters of this book reveal, much is known across several disciplines that converge on many of the same developmental disorders that are (and have been for decades) the focus of considerable research activity. The extensive interest in the study of developmental disorders exists both to understand their natures and causes as well as to reveal differences and similarities in development across normal and abnormal populations.

Neuroarchitecture of the auditory cortex in the rufous horseshoe bat (Rhinolophus rouxi).

This study describes the location and anatomical subdivisions of the auditory cortex of the horseshoe bat, Rhinolophus rouxi. The basic cyto- and myeloarchitectural features and cytochrome oxidase reactivity patterns are evaluated in brains where auditory fields have been previously established neurophysiologically (Radtke-Schuller and Schuller 1995). Thus, the neuroanatomical findings from these brains and additional analyzed material are related to neurophysiological characteristics. The neocortex of Rhinolophus shows a typical mammalian six-layered organization. It is poorly laminated, has a low density of granular elements, a wide layer I, and a phylogenetically old pyramidal cell type in a sharply accentuated layer II. These features are generally considered 'primitive' or conservative. Frontal, parietal, temporal and occipital regions can be distinguished. In the temporal cortex, layers III and IV are found to be markedly thicker than layer V, in contrast to the parietal region, where a prominent layer V, containing a high concentration of large pyramidal cells is the most outstanding feature. The entire temporal region, most of the parietal and parts of the occipital region are responsive to auditory stimuli. The primary auditory field corresponds to most of the temporal region. The fields of the parietal region almost completely coincide with the dorsal fields of the auditory cortex. Border zones between the temporal, parietal, and occipital regions correspond to the posterior auditory field. The non-primary fields of the auditory cortex occupy a larger area of the bat's neocortex than the primary field. The accentuated neuroarchitectural features, like cortical thickness and staining intensity, are shown to coincide with the physiological representation of biologically significant parameters.

Neuropsychiatric Significance of Subcortical Hyperintensity

Neuropsychiatric Significance of Subcortical Hyperintensity

Corpus callosum morphology of Williams syndrome: relation to genetics and behavior

As the largest interhemispheric commissure in the brain, the corpus callosum is of particular interest in disorders that may preferentially affect white matter development such as Williams syndrome (WS). Individuals with WS possess a remarkable array of neurobehavioral peaks and valleys, including deficits in visuospatial ability, mathematics, and attention, but with relative preservation of language and affect. Our study measured the corpus callosum and its primary subdivisions using high-resolution MRI in 20 individuals with WS (13 females and seven males; mean age 28.5, SD 8.3 years; range 19 to 44 years) and 20 age- and sex-matched control participants (mean age 28.5, SD 8.2 years; range 19 to 48 years). Total midsagittal corpus callosum area was reduced (F=4.5, p=0.04, df=36) in the WS population. The area of the splenium (F=12.4, p=0.001, df=36) and isthmus (F=9.4, p=0.004, df=36) were disproportionately reduced in WS beyond the absolute reduction of the entire corpus callosum. These reductions are in concordance with other neuroanatomical findings of decreased parietooccipital volumes as well as the observed visuospatial problems associated with WS.