Sex differences in the IQ-white matter microstructure relationship: A DTI study

Sex differences in the relationship between general intelligence and brain structure are a topic of increasing research interest. Early studies focused mainly on gray and white matter differences using voxel-based morphometry, while more recent studies investigated neural fiber tracts using diffusion tensor imaging (DTI) to analyze the white matter microstructure. In this study we used tract-based spatial statistics (TBSS) on DTI to test how intelligence is associated with brain diffusion indices and to see whether this relationship differs between men and women. 63 Men and women divided into groups of lower and higher intelligence were selected. Whole-brain DTI scans were analyzed using TBSS calculating maps of fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). The results reveal that the white matter microstructure differs between individuals as a function of intelligence and sex. In men, higher intelligence was related to higher FA and lower RD in the corpus callosum. In women, in contrast, intelligence was not related to the white matter microstructure. The higher values of FA and lower values of RD suggest that intelligence is associated with higher myelination and/or a higher number of axons particularly in men. This microstructural difference in the corpus callosum may increase cognitive functioning by reducing inter-hemispheric transfer time and thus account for more efficient brain functioning in men.     

Neuropsychological functioning in early hydrocephalus: review from a developmental perspective.

Children with hydrocephalus have deficits in several neuropsychological domains. The most notable are motor, visuoperceptual, and visuomotor function. These deficits are multiply determined and depend on the etiology and severity of the hydrocephalus to a large extent. Corpus callosum abnormalities resulting from stretching of callosal fibers and other cortical white matter tracts are implicated as contributory to these deficits. Enlarged ventricles and associated compression of posterior cortical areas also correlate with cognitive impairment. Distinguishing which cognitive domain negatively impacts on the child's functioning and which domains influence behavior in isolation or in combination has been the subject of numerous studies. Developmentally, we know little about the emergence of neuropsychological functioning in children with hydrocephalus. Study of the effects of hydrocephalus at different stages of development is useful to clinicians and researchers interested in the impact of diffuse neurophysiological damage on cognition in the developing brain. The medical and neuropsychological literature have begun to inform about these effects. The core deficits in hydrocephalus have yet to be explicated and a focus on investigations that answer these questions is required. This review summarizes the current knowledge about neurocognitive sequelae of hydrocephalus.     

Neuropsychological Functioning in Early Hydrocephalus: Review From a Developmental Perspective

Children with hydrocephalus have deficits in several neuropsychological domains. The most notable are motor, visuoperceptual, and visuomotor function. These deficits are multiply determined and depend on the etiology and severity of the hydrocephalus to a large extent. Corpus callosum abnormalities resulting from stretching of callosal fibers and other cortical white matter tracts are implicated as contributory to these deficits. Enlarged ventricles and associated compression of posterior cortical areas also correlate with cognitive impairment. Distinguishing which cognitive domain negatively impacts on the child’s functioning and which domains influence behavior in isolation or in combination has been the subject of numerous studies. Developmentally, we know little about the emergence of neuropsychological functioning in children with hydrocephalus. Study of the effects of hydrocephalus at different stages of development is useful to clinicians and researchers interested in the impact of diffuse neurophysiological damage on cognition in the developing brain. The medical and neuropsychological literature have begun to inform about these effects. The core deficits in hydrocephalus have yet to be explicated and a focus on investigations that answer these questions is required. This review summarizes the current knowledge about neurocognitive sequelae of hydrocephalus.     

Microstructural integrity of the corpus callosum linked with neuropsychological performance in adolescents

Background: Diffusion tensor imaging (DTI) has revealed microstructural aspects of adolescent brain development, the cognitive correlates of which remain relatively uncharacterized. Methods: DTI was used to assess white matter microstructure in 18 typically developing adolescents (ages 16–18). Fractional anisotropy (FA) and mean diffusion (MD) were evaluated within the splenium and body of the corpus callosum in relation to cognitive performance. Results: Visuospatial construction abilities were associated with white matter integrity in both the splenium and body of the corpus callosum, while only splenium integrity was associated with language and psychomotor function. Conclusion: Results suggest that, for typically developing adolescents, white matter coherence positively relates to visuospatial, psychomotor, and language skills. These findings may have implications for the cognitive functioning of clinical populations in which typical white matter development is altered.     

Fetal Alcohol Spectrum Disorders: Neuropsychological and Behavioral Features

Heavy prenatal alcohol exposure can cause alterations to the developing brain. The resulting neurobehavioral deficits seen following this exposure are wide-ranging and potentially devastating and, therefore, are of significant concern to individuals, families, communities, and society. These effects occur on a continuum, and qualitatively similar neuropsychological and behavioral features are seen across the spectrum of effect. The term fetal alcohol spectrum disorders (FASD) has been used to emphasize the continuous nature of the outcomes of prenatal alcohol exposure, with fetal alcohol syndrome (FAS) representing one point on the spectrum. This paper will provide a comprehensive review of the neuropsychological and behavioral effects of heavy prenatal alcohol exposure, including a discussion of the emerging neurobehavioral profile. Supporting studies of lower levels of exposure, brain-behavior associations, and animal model systems will be included when appropriate.     

Brain abnormalities observed in childhood-onset schizophrenia: a review of the structural magnetic resonance imaging literature

Childhood-onset schizophrenia (COS) is a rare, severe form of schizophrenia in which there are structural brain abnormalities that may be related to the psychotic symptomatology and neurocognitive deficits found in these patients. While there are numerous structural imaging studies of the adult-onset variant of schizophrenia (with many conflicting findings), relatively few brain imaging studies of COS have been conducted. This paper summarizes the extant literature of magnetic resonance imaging (MRI) studies of structural brain abnormalities in COS, and compares findings to similar studies of adult-onset patients. Volumetric MRI studies of COS patients have consistently shown evidence for increased ventricular volume, reduced cerebral gray matter, and increased caudate volume, consistent with findings from adult-onset studies. Other volumetric brain abnormalities are observed in COS patients, such as reduced total brain volume, but not consistently across all studies. Voxel-based morphometric analyses have revealed abnormalities in the shape and spatial location of structures in COS such as the corpus callosum, caudate, and thalamus that could not be observed in the more traditional volumetric assessments. Similar findings also are observed in adult-onset patients. Progressive degenerative changes, such as ventricular enlargement, appear to occur in COS only until young adulthood where there is an apparent asymptote with no further degenerative changes. This is consistent with the lack of progressive changes noted in most longitudinal studies of adult-onset schizophrenia.     

What Does Diffusion Tensor Imaging Reveal About the Brain and Cognition in Fetal Alcohol Spectrum Disorders?

Over the past 5 years, Diffusion Tensor Imaging (DTI) has begun to provide new evidence about the effects of prenatal alcohol exposure on white matter development. DTI, which examines microstructural tissue integrity, is sensitive to more subtle white matter abnormalities than traditional volumetric MRI methods. Thus far, the available DTI data suggest that white matter microstructural abnormalities fall on a continuum of severity in Fetal Alcohol Spectrum Disorder (FASD). Abnormalities are prominent in the corpus callosum, but also evident in major anterior-posterior fiber bundles, corticospinal tracts, and cerebellum. These subtle abnormalities are correlated with neurocognitive deficits, especially in processing speed, non-verbal ability, and executive functioning. Future studies using larger samples, increasingly sophisticated DTI methods, and additional functional MRI connectivity measures will better characterize the full range of abnormalities in FASD. Ultimately, these measures may serve as indices of change in future longitudinal studies and in studies of interventions for FASD.     

Imaging the Impact of Prenatal Alcohol Exposure on the Structure of the Developing Human Brain

Prenatal alcohol exposure has numerous effects on the developing brain, including damage to selective brain structure. We review structural magnetic resonance imaging (MRI) studies of brain abnormalities in subjects prenatally exposed to alcohol. The most common findings include reduced brain volume and malformations of the corpus callosum. Advanced methods have been able to detect shape, thickness and displacement changes throughout multiple brain regions. The teratogenic effects of alcohol appear to be widespread, affecting almost the entire brain. The only region that appears to be relatively spared is the occipital lobe. More recent studies have linked cognition to the underlying brain structure in alcohol-exposed subjects, and several report patterns in the severity of brain damage as it relates to facial dysmorphology or to extent of alcohol exposure. Future studies exploring relationships between brain structure, cognitive measures, dysmorphology, age, and other variables will be valuable for further comprehending the vast effects of prenatal alcohol exposure and for evaluating possible interventions.     

Smaller splenium in children with nonverbal learning disability compared to controls,high-functioning autism and ADHD

The current study investigated morphological differences in the corpus callosum in children ages 8 to 18 years old with nonverbal learning disability (NLD; n = 19), high-functioning autism (HFA; n = 23), predominantly inattentive ADHD (ADHD:PI; n = 23), and combined type ADHD (ADHD:C; n = 25), as well as those demonstrating typical development (n = 57). Midsagittal area of the corpus callosum and five midsagittal anterior-to-posterior corpus callosum segments were examined using magnetic resonance imaging. Controlling for midsagittal brain area and age, no group differences were found for total corpus callosum area. This finding indicates that higher functioning children on the autistic spectrum do not have smaller corpus callosi as has been found in previous research with heterogeneous samples. Following segmentation of the corpus callosum, the NLD group was observed to have significantly smaller splenia compared to all other groups. Smaller splenia in the NLD group was associated with lower WASI PIQ scores but not WASI VIQ scores. Children with HFA were observed to have larger midbody areas than children with NLD and neurotypically developing children. Children with HFA and NLD demonstrated behavioral symptoms of inattention and hyperactivity similar to the ADHD groups indicating that corpus callosum differences seen in the NLD and HFA groups are not related to these behaviors.     

Cognitive impairment and whole brain diffusion in patients with neuromyelitis optica after acute relapse

The objective of this study investigated cognitive impairments and their correlations with fractional anisotropy (FA) and mean diffusivity (MD) in patients with neuromyelitis optica (NMO) without visible lesions on conventional brain MRI during acute relapse. Twenty one patients with NMO and 21 normal control subjects received several cognitive tests to assess cognitive function. Head diffusion tensor imaging (DTI) of all patients with NMO were collected with a 3-T MR system. Correlations of cognitive test scores and whole brain FA and MD were examined by voxel-based analysis. Region-of-interest analysis was applied to the significantly correlated regions which the most frequently appeared. We found that NMO patients without visible brain lesions had significantly impaired learning and memory, decreased information processing speed, and damaged attention compared with normal control subjects. These impaired cognitive domains were significantly correlated with FA and MD in local regions of corpus callosum, anterior cingulate and medial frontal cortex. In corpus callosum of NMO patients, mean FA was significantly lower and mean MD higher than normal control subjects. Our findings suggest that cognitive impairments in learning and memory, information processing speed and attention occur in NMO patients without visible brain lesions during acute relapse. The impairments in immediate and short-term memory in NMO patients may be due to information encoding deficits in the process of information acquisition. The corpus callosum of such patients may have local microscopic damages that play a role in cognitive impairments during acute relapse.     

Neuropsychological correlates of impaired emotion recognition following traumatic brain injury

Previous research has shown that individuals with traumatic brain injury (TBI) are significantly impaired on emotion recognition tasks. In this study, the relationship between neuropsychological functioning and emotion recognition was examined in 11 individuals with moderate to severe TBI and a control group of 13 individuals matched for age,sex, and education. Emotion recognition stimuli were from Ekman and Friesen's pictures of facial affect. The group with TBI showed neuropsychological deficits consistent with those commonly found following moderate to severe TBI. The group with TBI also identified significantly fewer emotion recognition stimuli than the control group.The number of correctly identified emotion recognition stimuli was significantly correlated with measures of verbal cognitive processing in the group with TBI. These findings suggest that the role of left hemisphere brain mechanisms in the recognition of facial (nonverbal)emotion may be more important than previously recognized.     

Clock drawing performance and brain morphology in mild cognitive impairment and Alzheimer's disease

The Clock Drawing Test (CDT) is a widely used instrument in the neuropsychological assessment of Alzheimer's disease (AD). As CDT performance necessitates several cognitive functions (e.g., visuospatial and constructional abilities, executive functioning), an interaction of multiple brain regions is likely. Fifty-one subjects with mild cognitive impairment, 23 with AD and 15 healthy controls underwent high-resolution magnetic resonance imaging. Optimized voxel-based morphometry (VBM) was performed to investigate the putative association between CDT performance and gray matter (GM) density throughout the entire brain. In the first step of analysis (p<.001, uncorrected), VBM revealed a reduced GM density in numerous cortical (temporal lobe, frontal lobe, parietal lobe, cerebellum) and subcortical (thalamus, basal ganglia) brain regions to be associated with poorer CDT performance. When corrected for multiple comparisons (p<.01), the associations remained significant predominantly in the left temporal and--less pronounced--the right temporal lobe. VBM demonstrated CDT performance to depend on the integrity of widely distributed cortical and subcortical areas in both brain hemispheres with accentuation in the left-sided temporal lobe region.     

Memory and brain volume in adults prenatally exposed to alcohol

The impact of prenatal alcohol exposure on memory and brain development was investigated in 92 African-American, young adults who were first identified in the prenatal period. Three groups (Control, n=26; Alcohol-related Neurodevelopmental Disorder, n=36; and Dysmorphic, n=30) were imaged using structural MRI with brain volume calculated for multiple regions of interest. Memory was measured using the Verbal Selective Reminding Memory Test and its nonverbal counterpart, the Nonverbal Selective Reminding Memory Test, which each yielding measures of learning and recall. For both Verbal and Nonverbal Recall and Slope, linear trends were observed demonstrating a spectrum of deficits associated with prenatal alcohol exposure. Dysmorphic individuals performed significantly poorer than unexposed controls on 5 of 6 memory outcomes. Alcohol-exposed individuals demonstrated significantly lower total brain volume than controls, as well as lower volume in a number of specific regions including hippocampus. Mediation analyses indicated that memory performance associated with effects of prenatal alcohol exposure was mediated from dysmorphic severity through hippocampal volume, particularly right hippocampus. These results indicate that the association between the physical effects of prenatal alcohol exposure and deficits in memory are mediated by volumetric reduction in specific brain regions.     

MR Diffusion Tensor Imaging: A Window into White Matter Integrity of the Working Brain

As Norman Geschwind asserted in 1965, syndromes resulting from white matter lesions could produce deficits in higher-order functions and “disconnexion” or the interruption of connection between gray matter regions could be as disruptive as trauma to those regions per se. The advent of in vivo diffusion tensor imaging, which allows quantitative characterization of white matter fiber integrity in health and disease, has served to strengthen Geschwind’s proposal. Here we present an overview of the principles of diffusion tensor imaging (DTI) and its contribution to progress in our current understanding of normal and pathological brain function.     

The neural basis of syntactic deficits in primary progressive aphasia

Patients with primary progressive aphasia (PPA) vary considerably in terms of which brain regions are impacted, as well as in the extent to which syntactic processing is impaired. Here we review the literature on the neural basis of syntactic deficits in PPA. Structural and functional imaging studies have most consistently associated syntactic deficits with damage to left inferior frontal cortex. Posterior perisylvian regions have been implicated in some studies. Damage to the superior longitudinal fasciculus, including its arcuate component, has been linked with syntactic deficits, even after gray matter atrophy is taken into account. These findings suggest that syntactic processing depends on left frontal and posterior perisylvian regions, as well as intact connectivity between them. In contrast, anterior temporal regions, and the ventral tracts that link frontal and temporal language regions, appear to be less important for syntax, since they are damaged in many PPA patients with spared syntactic processing.     

Communicative deficits in agenesis of the corpus callosum: nonliteral language and affective prosody

While some individuals with agenesis of the corpus callosum can perform normally on standardized intelligence tests, clinical observations suggest that they nevertheless have deficits in the domains of fluid and social intelligence. Particularly important for social competence is adequate understanding and use of paralinguistic information. This study examined the impact of callosal absence on the processing of pragmatic and paralinguistic information. Young adult males with agenesis of the corpus callosum (ACC) were evaluated in the areas of nonliteral language comprehension, proverb recognition and interpretation, and perception of affective prosody. Ten ACC individuals with normal Wechsler IQ were compared to 14 sex, age, and IQ matched normal controls. The Formulaic and Novel Language Comprehension Test (FANL-C), Gorham Proverbs Test, and LA Prosody Test were administered. ACC subjects exhibited significant impairment on the nonliteral items of the FANL-C, but no significant difference from controls in comprehension of literal items. ACC subjects also exhibited significant deficits in both self-generated interpretation and recognition of proverb meaning, and in recognition of affective prosody. These results demonstrate that normally intelligent individuals with ACC are impaired in the understanding of nonliteral language and emotional-prosodic cues that are important in social communication. In all three tests, the performance of individuals with ACC was similar to patients with right hemisphere brain damage. Thus, persons with ACC appear to lack interhemispheric integration of critical aspects of language processed by the right hemisphere.     

Functional Neuroimaging in the Examination of Effects of Prenatal Alcohol Exposure

Functional neuroimaging offers the opportunity to understand the effect of prenatal alcohol exposure on the activities of the brain as well as providing a window into the relationship between neural activation and the behavioral outcomes that have been described in affected individuals. Several different methodologies have been used to examine the neurophysiological signal changes associated with different brain functions in prenatally exposed individuals and those diagnosed with fetal alcohol syndrome (FAS) or other fetal alcohol spectrum disorders (FASD). These include electroencephalography (EEG), positron emission tomography (PET), single-photon emission computed tomography (SPECT), and functional magnetic resonance imaging (fMRI). These studies demonstrate that it is feasible to use these technologies with this clinical population and that the damage to the central nervous system associated with prenatal alcohol exposure has widespread functional implications; however, currently, the literature in these areas is limited and unsystematic. Functional MRI with this clinical population has just begun to explore the implications of prenatal alcohol exposure with the first paper published in 2005. Other methodologies are similarly limited in scope. Nonetheless, these functional neuroimaging studies suggest that prenatal alcohol exposure, or a diagnosis of FAS, may lead to restrictions in neural efficiency or a global decrement in processing resources.     

Neuroimaging of Wernicke’s Encephalopathy and Korsakoff’s Syndrome

There is considerable evidence that neuroimaging findings can improve the early diagnosis of Wernicke's encephalopathy (WE) in clinical settings. The most distinctive neuroimaging finding of acute WE are cytotoxic edema and vasogenic edema, which are represented by bilateral symmetric hyperintensity alterations on T2-weighted MR images in the periphery of the third ventricle, periaqueductal area, mammillary bodies and midbrain tectal plate. An initial bout of WE can result in Korsakoff's syndrome (KS), but repeated bouts in conjunction with its typical comorbidity, chronic alcoholism, can result in signs of tissue degeneration in vulnerable brain regions. Chronic abnormalities identified with neuroimaging enable examination of brain damage in living patients with KS and have expanded the understanding of the neuropsychological deficits resulting from thiamine deficiency, alcohol neurotoxicity, and their comorbidity. Brain structure and functional studies indicate that the interactions involving the thalamus, mammillary bodies, hippocampus, frontal lobes, and cerebellum are crucial for memory formation and executive functions, and the interruption of these circuits by WE and chronic alcoholism can contribute substantially to the neuropsychological deficits in KS.     

Relationship of temporal lobe volumes to neuropsychological test performance in healthy children

Ecological validity of neuropsychological assessment includes the ability of tests to predict real-world functioning and/or covary with brain structures. Studies have examined the relationship between adaptive skills and test performance, with less focus on the association between regional brain volumes and neurobehavioral function in healthy children. The present study examined the relationship between temporal lobe gray matter volumes and performance on two neuropsychological tests hypothesized to measure temporal lobe functioning (visual perception-VP; peabody picture vocabulary test, third edition-PPVT-III) in 48 healthy children ages 5-18 years. After controlling for age and gender, left and right temporal and left occipital volumes were significant predictors of VP. Left and right frontal and temporal volumes were significant predictors of PPVT-III. Temporal volume emerged as the strongest lobar correlate with both tests. These results provide convergent and discriminant validity supporting VP as a measure of the "what" system; but suggest the PPVT-III as a complex measure of receptive vocabulary, potentially involving executive function demands.