Emerging differences between Huntington's disease-like 2 and Huntington's disease: A comparison using MRI brain volumetry.

Huntington's Disease-Like 2 (HDL2), caused by a CTG/CAG expansion in JPH3 on chromosome 16q24, is the most common Huntington's Disease (HD) phenocopy in populations with African ancestry. Qualitatively, brain MRIs of HDL2 patients have been indistinguishable from HD. To determine brain regions most affected in HDL2 a cross-sectional study using MRI brain volumetry was undertaken to compare the brains of nine HDL2, 11 HD and nine age matched control participants. Participants were ascertained from the region in South Africa with the world's highest HDL2 incidence. The HDL2 and HD patient groups showed no significant differences with respect to mean age at MRI, disease duration, abnormal triplet repeat length, or age at disease onset. Overall, intracerebral volumes were smaller in both affected groups compared to the control group. Comparing the HDL2 and HD groups across multiple covariates, cortical and subcortical volumes were similar with the exception that the HDL2 thalamic volumes were smaller. Consistent with other similarities between the two diseases, these results indicate a pattern of neurodegeneration in HDL2 that is remarkably similar to HD. However smaller thalamic volumes in HDL2 raises intriguing questions into the pathogenesis of both disorders, and how these volumetric differences relate to their respective phenotypes.

Hippocampal atrophy, asymmetry, and cognition in type 2 diabetes mellitus.

Introduction: Type 2 diabetes mellitus is associated with global and hippocampal atrophy and cognitive deficits, and some studies suggest that the right hippocampus may display greater vulnerability than the left. Methods: Hippocampal volumes, the hippocampal asymmetry index, and cognitive functioning were assessed in 120 nondemented adults with long duration type 2 diabetes. Results: The majority of the sample displayed left greater than right hippocampal asymmetry (which is the reverse of the expected direction seen with normal aging). After adjustment for age, sex, and IQ, right (but not left) hippocampal volumes were negatively associated with memory, executive function, and semantic fluency. These associations were stronger with the hippocampal asymmetry index and remained significant for memory and executive function after additional adjustment for global brain atrophy. Conclusions: We conclude that asymmetric hippocampal atrophy may occur in type 2 diabetes, with greater atrophy occurring in the right than the left hippocampus, and that this may contribute to cognitive impairment in this disorder. These cross-sectional associations require further verification but may provide clues into the pathogenesis of cognitive disorders in type 2 diabetes.

Preliminary Investigation of Cerebral Blood Flow and Amyloid Burden in Veterans With and Without Combat-Related Traumatic Brain Injury.

This study aimed to examine global and regional cerebral blood flow and amyloid burden in combat veterans with and without traumatic brain injury (TBI). Cerebral blood flow (in milliliters per minute per 100 mL) was measured by quantitative [(15)O]water, and amyloid burden was measured by [(11)C]PIB imaging. Mean global cerebral blood flow was significantly lower in veterans with TBI compared with non-TBI veterans. There were essentially no differences between groups for globally normalized regional cerebral blood flow. Amyloid burden did not differ between TBI and non-TBI veterans. Veterans who have suffered a TBI have significantly lower cerebral blood flow than non-TBI controls but did not manifest increased levels of amyloid, globally or regionally.

Assessing atrophy measurement techniques in dementia: Results from the MIRIAD atrophy challenge.

Structural MRI is widely used for investigating brain atrophy in many neurodegenerative disorders, with several research groups developing and publishing techniques to provide quantitative assessments of this longitudinal change. Often techniques are compared through computation of required sample size estimates for future clinical trials. However interpretation of such comparisons is rendered complex because, despite using the same publicly available cohorts, the various techniques have been assessed with different data exclusions and different statistical analysis models. We created the MIRIAD atrophy challenge in order to test various capabilities of atrophy measurement techniques. The data consisted of 69 subjects (46 Alzheimer's disease, 23 control) who were scanned multiple (up to twelve) times at nine visits over a follow-up period of one to two years, resulting in 708 total image sets. Nine participating groups from 6 countries completed the challenge by providing volumetric measurements of key structures (whole brain, lateral ventricle, left and right hippocampi) for each dataset and atrophy measurements of these structures for each time point pair (both forward and backward) of a given subject. From these results, we formally compared techniques using exactly the same dataset. First, we assessed the repeatability of each technique using rates obtained from short intervals where no measurable atrophy is expected. For those measures that provided direct measures of atrophy between pairs of images, we also assessed symmetry and transitivity. Then, we performed a statistical analysis in a consistent manner using linear mixed effect models. The models, one for repeated measures of volume made at multiple time-points and a second for repeated "direct" measures of change in brain volume, appropriately allowed for the correlation between measures made on the same subject and were shown to fit the data well. From these models, we obtained estimates of the distribution of atrophy rates in the Alzheimer's disease (AD) and control groups and of required sample sizes to detect a 25% treatment effect, in relation to healthy ageing, with 95% significance and 80% power over follow-up periods of 6, 12, and 24months. Uncertainty in these estimates, and head-to-head comparisons between techniques, were carried out using the bootstrap. The lateral ventricles provided the most stable measurements, followed by the brain. The hippocampi had much more variability across participants, likely because of differences in segmentation protocol and less distinct boundaries. Most methods showed no indication of bias based on the short-term interval results, and direct measures provided good consistency in terms of symmetry and transitivity. The resulting annualized rates of change derived from the model ranged from, for whole brain: -1.4% to -2.2% (AD) and -0.35% to -0.67% (control), for ventricles: 4.6% to 10.2% (AD) and 1.2% to 3.4% (control), and for hippocampi: -1.5% to -7.0% (AD) and -0.4% to -1.4% (control). There were large and statistically significant differences in the sample size requirements between many of the techniques. The lowest sample sizes for each of these structures, for a trial with a 12month follow-up period, were 242 (95% CI: 154 to 422) for whole brain, 168 (95% CI: 112 to 282) for ventricles, 190 (95% CI: 146 to 268) for left hippocampi, and 158 (95% CI: 116 to 228) for right hippocampi. This analysis represents one of the most extensive statistical comparisons of a large number of different atrophy measurement techniques from around the globe. The challenge data will remain online and publicly available so that other groups can assess their methods.

Individual differences in transcranial electrical stimulation current density.

Transcranial electrical stimulation (TCES) is effective in treating many conditions, but it has not been possible to accurately forecast current density within the complex anatomy of a given subject's head. We sought to predict and verify TCES current densities and determine the variability of these current distributions in patient-specific models based on magnetic resonance imaging (MRI) data. Two experiments were performed. The first experiment estimated conductivity from MRIs and compared the current density results against actual measurements from the scalp surface of 3 subjects. In the second experiment, virtual electrodes were placed on the scalps of 18 subjects to model simulated current densities with 2 mA of virtually applied stimulation. This procedure was repeated for 4 electrode locations. Current densities were then calculated for 75 brain regions. Comparison of modeled and measured external current in experiment 1 yielded a correlation of r = .93. In experiment 2, modeled individual differences were greatest near the electrodes (ten-fold differences were common), but simulated current was found in all regions of the brain. Sites that were distant from the electrodes (e.g. hypothalamus) typically showed two-fold individual differences. MRI-based modeling can effectively predict current densities in individual brains. Significant variation occurs between subjects with the same applied electrode configuration. Individualized MRI-based modeling should be considered in place of the 10-20 system when accurate TCES is needed.

White matter abnormalities in veterans with mild traumatic brain injury.

OBJECTIVE: It has been estimated that 10%-20% of U.S. veterans of the wars in Iraq and Afghanistan experienced mild traumatic brain injury (TBI), mostly secondary to blast exposure. Diffusion tensor imaging (DTI) may detect subtle white matter changes in both the acute and chronic stages of mild TBI and thus has the potential to detect white matter damage in patients with TBI. The authors used DTI to examine white matter integrity in a relatively large group of veterans with a history of mild TBI. METHOD: DTI images from 72 veterans of the wars in Iraq and Afghanistan who had mild TBI were compared with DTI images from 21 veterans with no exposure to TBI during deployment. Conventional voxel-based analysis as well as a method of identifying spatially heterogeneous areas of decreased fractional anisotropy ("potholes") were used. Veterans also underwent psychiatric and neuropsychological assessments. RESULTS: Voxel-based analysis did not reveal differences in DTI parameters between the veterans with mild TBI and those with no TBI. However, the veterans with mild TBI had a significantly higher number of potholes than those without TBI. The difference in the number of potholes was not influenced by age, time since trauma, a history of mild TBI unrelated to deployment, or coexisting psychopathology. The number of potholes was correlated with the severity of TBI and with performance in executive functioning tasks. CONCLUSIONS: Veterans who had blast-related mild TBI showed evidence of multifocal white matter abnormalities that were associated with severity of the injury and with relevant functional measures. Overall, white matter potholes may constitute a sensitive biomarker of axonal injury that can be identified in mild TBI at acute and chronic stages of its clinical course.

Striatal volume contributes to the prediction of onset of Huntington disease in incident cases.

BACKGROUND: Previous neuroimaging research indicates that brain atrophy in Huntington disease (HD) begins many years before movement abnormalities become severe enough to warrant diagnosis. Most clinical trials being planned for individuals in the prediagnostic stage of HD propose to use delay of disease onset as the primary outcome measure. Although formulas have been developed based on age and CAG repeat length, to predict when HD motor onset will occur, it would be useful to have additional measures that can improve the accuracy of prediction of disease onset. METHODS: The current study examined magnetic resonance imaging (MRI) measures of striatum and white matter volume in 85 individuals prospectively followed from pre-HD stage through diagnosable motor onset (incident cases) and 85 individuals individually matched with incident cases on CAG repeat length, sex, and age, who were not diagnosed with HD during the course of the study. RESULTS: Volumes of striatum and white matter were significantly smaller in individuals who would be diagnosed 1 to 4 years following the initial MRI scan, compared with those who would remain in the pre-HD stage. Putamen volume was the measure that best distinguished between the two groups. CONCLUSIONS: Results suggest that MRI volumetric measures may be helpful in selecting individuals for future clinical trials in pre-HD where HD motor onset is the primary outcome measure. In planning for multisite clinical trials in pre-HD, investigators may also want to consider using more objective measures, such as MRI volumes, in addition to onset of diagnosable movement disorder, as major outcome measures.

Beyond alcoholism: Wernicke-Korsakoff syndrome in patients with psychiatric disorders.

OBJECTIVE: Wernicke encephalopathy and Korsakoff syndrome (the combined disorder is named Wernicke-Korsakoff syndrome [WKS]) are preventable, life-threatening neuropsychiatric syndromes resulting from thiamine deficiency. WKS has historically been associated with alcoholism; more recently, it has been recognized in patients who have anorexia nervosa or have undergone bariatric surgery for obesity. However, patients with nutritional deficiencies of any origin are at risk for WKS. We present clinical histories and neuroimaging data on 2 young adults with underlying psychiatric disorders who became malnourished and developed WKS. METHODS: A young woman with bipolar disorder and somatization disorder was hospitalized for intractable vomiting. A young man with chronic paranoid schizophrenia developed delusions that food and water were harmful, and was hospitalized after subsisting for 4 months on soda pop. RESULTS: Acute, life-threatening Wernicke encephalopathy was confirmed in both patients by brain magnetic resonance imaging showing classic thalamic injury. The patients were left with persistent cognitive and physical disabilities that were consistent with Korsakoff syndrome. CONCLUSIONS: Failure to suspect a vitamin deficiency led to permanent cognitive and physical disabilities that may necessitate lifelong care for these patients. The neuropsychiatric consequences could have been prevented by prompt recognition of their thiamine deficiency.

Progressive brain change in schizophrenia: a prospective longitudinal study of first-episode schizophrenia.

BACKGROUND: Schizophrenia has a characteristic onset during adolescence or young adulthood but also tends to persist throughout life. Structural magnetic resonance studies indicate that brain abnormalities are present at onset, but longitudinal studies to assess neuroprogression have been limited by small samples and short or infrequent follow-up intervals. METHODS: The Iowa Longitudinal Study is a prospective study of 542 first-episode patients who have been followed up to 18 years. In this report, we focus on those patients (n = 202) and control subjects (n = 125) for whom we have adequate structural magnetic resonance data (n = 952 scans) to provide a relatively definitive determination of whether progressive brain change occurs over a time interval of up to 15 years after intake. RESULTS: A repeated-measures analysis showed significant age-by-group interaction main effects that represent a significant decrease in multiple gray matter regions (total cerebral, frontal, thalamus), multiple white matter regions (total cerebral, frontal, temporal, parietal), and a corresponding increase in cerebrospinal fluid (lateral ventricles and frontal, temporal, and parietal sulci). These changes were most severe during the early years after onset. They occur at severe levels only in a subset of patients. They are correlated with cognitive impairment but only weakly with other clinical measures. CONCLUSIONS: Progressive brain change occurs in schizophrenia, affects both gray matter and white matter, is most severe during the early stages of the illness, and occurs only in a subset of patients. Measuring severity of progressive brain change offers a promising new avenue for phenotype definition in genetic studies of schizophrenia.

Association between Age and Striatal Volume Stratified by CAG Repeat Length in Prodromal Huntington Disease.

BACKGROUND: Longer CAG repeat length is associated with faster clinical progression in Huntington disease, although the effect of higher repeat length on brain atrophy is not well documented. METHOD: Striatal volumes were obtained from MRI scans of 720 individuals with prodromal Huntington disease. Striatal volume was plotted against age separately for groups with CAG repeat lengths of 38-39, 40, 41, 42, 43, 44, 45, 46, and 47-54. RESULTS: Slopes representing the association between age and striatal volume were significantly steeper as CAG repeat length increased. DISCUSSION: Although cross-sectional, these data suggest that striatal atrophy, like clinical progression, may occur faster with higher CAG repeat lengths.

Long-term antipsychotic treatment and brain volumes: a longitudinal study of first-episode schizophrenia.

CONTEXT: Progressive brain volume changes in schizophrenia are thought to be due principally to the disease. However, recent animal studies indicate that antipsychotics, the mainstay of treatment for schizophrenia patients, may also contribute to brain tissue volume decrement. Because antipsychotics are prescribed for long periods for schizophrenia patients and have increasingly widespread use in other psychiatric disorders, it is imperative to determine their long-term effects on the human brain. OBJECTIVE: To evaluate relative contributions of 4 potential predictors (illness duration, antipsychotic treatment, illness severity, and substance abuse) of brain volume change. DESIGN: Predictors of brain volume changes were assessed prospectively based on multiple informants. SETTING: Data from the Iowa Longitudinal Study. PATIENTS: Two hundred eleven patients with schizophrenia who underwent repeated neuroimaging beginning soon after illness onset, yielding a total of 674 high-resolution magnetic resonance scans. On average, each patient had 3 scans (≥2 and as many as 5) over 7.2 years (up to 14 years). MAIN OUTCOME MEASURE: Brain volumes. RESULTS: During longitudinal follow-up, antipsychotic treatment reflected national prescribing practices in 1991 through 2009. Longer follow-up correlated with smaller brain tissue volumes and larger cerebrospinal fluid volumes. Greater intensity of antipsychotic treatment was associated with indicators of generalized and specific brain tissue reduction after controlling for effects of the other 3 predictors. More antipsychotic treatment was associated with smaller gray matter volumes. Progressive decrement in white matter volume was most evident among patients who received more antipsychotic treatment. Illness severity had relatively modest correlations with tissue volume reduction, and alcohol/illicit drug misuse had no significant associations when effects of the other variables were adjusted. CONCLUSIONS: Viewed together with data from animal studies, our study suggests that antipsychotics have a subtle but measurable influence on brain tissue loss over time, suggesting the importance of careful risk-benefit review of dosage and duration of treatment as well as their off-label use.

The nature and extent of cerebellar atrophy in chronic temporal lobe epilepsy.

PURPOSE: Research indicates that patients with chronic temporal lobe epilepsy (TLE) exhibit cerebellar atrophy compared to healthy controls, but the degree to which specific regions of the cerebellum are affected remains unclear. The purpose of this study was to characterize the extent and lateralization of atrophy in individual cerebellar lobes and subregions in unilateral TLE using advanced quantitative magnetic resonance imaging (MRI) techniques. METHODS: Study participants were 46 persons with TLE and 31 age- and gender- matched healthy controls. All participants underwent high-resolution MRI with manual tracing of the cerebellum yielding gray and white matter volumes of the right and left anterior lobes, superior posterior lobes, inferior posterior lobes, and corpus medullare. The degree to which asymmetric versus generalized abnormalities was evident in unilateral chronic TLE was determined and related to selected clinical seizure features (age of onset, duration of disorder). KEY FINDINGS: There were no lateralized abnormalities in cerebellar gray matter or white matter in patients with right or left TLE (all p's > 0.2). Compared with controls, unilateral TLE was associated with significant bilateral reductions in the superior (p = 0.032) and inferior (p = 0.023) posterior lobes, whereas volume was significantly increased in the anterior lobes (p = 0.002), especially in patients with early onset TLE, and not significantly different in the corpus medullare (p = 0.71). Total superior cerebellar tissue volumes were reduced in association with increasing duration of epilepsy. SIGNIFICANCE: Patients with unilateral TLE exhibit a pattern of bilateral cerebellar pathology characterized by atrophy of the superior and inferior posterior lobes, hypertrophy of the anterior lobe, and no effect on the corpus medullare. Cross-sectional analyses show that specific aspects of cerebellar pathology are associated with neurodevelopmental (anterior lobe) or chronicity-related (superior posterior lobe) features of the disorder.

Smaller intracranial volume in prodromal Huntington's disease: evidence for abnormal neurodevelopment.

Huntington's disease is an autosomal dominant brain disease. Although conceptualized as a neurodegenerative disease of the striatum, a growing number of studies challenge this classic concept of Huntington's disease aetiology. Intracranial volume is the tissue and fluid within the calvarium and is a representation of the maximal brain growth obtained during development. The current study reports intracranial volume obtained from an magnetic resonance imaging brain scan in a sample of subjects (n = 707) who have undergone presymptomatic gene testing. Participants who are gene-expanded but not yet manifesting the disease (prodromal Huntington's disease) are compared with subjects who are non-gene expanded. The prodromal males had significantly smaller intracranial volume measures with a mean volume that was 4% lower compared with controls. Although the prodromal females had smaller intracranial volume measures compared with their controls, this was not significant. The current findings suggest that mutant huntingtin can cause abnormal development, which may contribute to the pathogenesis of Huntington's disease.

Longitudinal change in regional brain volumes in prodromal Huntington disease.

OBJECTIVE: As therapeutics are being developed to target the underlying neuropathology of Huntington disease, interest is increasing in methodologies for conducting clinical trials in the prodromal phase. This study was designed to examine the potential utility of structural MRI measures as outcome measures for such trials. METHODS: Data are presented from 211 prodromal individuals and 60 controls, scanned both at baseline and at the 2-year follow-up. Prodromal participants were divided into groups based on proximity to estimated onset of diagnosable clinical disease: far (>15 years from estimated onset), mid (9-15 years) and near (<9 years). Volumetric measurements of caudate, putamen, total striatum, globus pallidus, thalamus, total grey and white matter and cerebrospinal fluid were performed. RESULTS: All prodromal groups showed a faster rate of atrophy than controls in striatum, total brain and cerebral white matter (especially in the frontal lobe). Neither prodromal participants nor controls showed any significant longitudinal change in cortex (either total cortical grey or within individual lobes). When normal age-related atrophy (ie, change observed in the control group) was taken into account, there was more statistically significant disease-related atrophy in white matter than in striatum. CONCLUSION: Measures of volume change in striatum and white-matter volume, particularly in the frontal lobe, may serve as excellent outcome measures for future clinical trials in prodromal Huntington disease. Clinical trials using white matter or striatal volume change as an outcome measure will be most efficient if the sample is restricted to individuals who are within 15 years of estimated onset of diagnosable disease.

Fully automated analysis using BRAINS: AutoWorkup.

The BRAINS (Brain Research: Analysis of Images, Networks, and Systems) image analysis software has been in use, and in constant development, for over 20 years. The original neuroimage analysis pipeline using BRAINS was designed as a semiautomated procedure to measure volumes of the cerebral lobes and subcortical structures, requiring manual intervention at several stages in the process. Through use of advanced image processing algorithms the need for manual intervention at stages of image realignment, tissue sampling, and mask editing have been eliminated. In addition, inhomogeneity correction, intensity normalization, and mask cleaning routines have been added to improve the accuracy and consistency of the results. The fully automated method, AutoWorkup, is shown in this study to be more reliable (ICC ≥ 0.96, Jaccard index ≥ 0.80, and Dice index ≥ 0.89 for all tissues in all regions) than the average of 18 manual raters. On a set of 1130 good quality scans, the failure rate for correct realignment was 1.1%, and manual editing of the brain mask was required on 4% of the scans. In other tests, AutoWorkup is shown to produce measures that are reliable for data acquired across scanners, scanner vendors, and across sequences. Application of AutoWorkup for the analysis of data from the 32-site, multivendor PREDICT-HD study yield estimates of reliability to be greater than or equal to 0.90 for all tissues and regions.

Cerebral cortex structure in prodromal Huntington disease.

Neuroimaging studies of subjects who are gene-expanded for Huntington Disease, but not yet diagnosed (termed prodromal HD), report that the cortex is "spared," despite the decrement in striatal and cerebral white-matter volume. Measurement of whole-cortex volume can mask more subtle, but potentially clinically relevant regional changes in volume, thinning, or surface area. The current study addressed this limitation by evaluating cortical morphology of 523 prodromal HD subjects. Participants included 693 individuals enrolled in the PREDICT-HD protocol. Of these participants, 523 carried the HD gene mutation (prodromal HD group); the remaining 170 were non gene-expanded and served as the comparison group. Based on age and CAG repeat length, gene-expanded subjects were categorized as "Far from onset," "Midway to onset," "Near onset," and "already diagnosed." MRI scans were processed using FreeSurfer. Cortical volume, thickness, and surface area were not significantly different between the Far from onset group and controls. However, beginning in the Midway to onset group, the cortex showed significant volume decrement, affecting most the posterior and superior cerebral regions. This pattern progressed when evaluating the groups further into the disease process. Areas that remained mostly unaffected included ventral and medial regions of the frontal and temporal cortex. Morphologic changes were mostly in thinning as surface area did not substantially change in most regions. Early in the course of HD, the cortex shows changes that are manifest as cortical thinning and are most robust in the posterior and superior regions of the cerebrum.

Striatal and white matter predictors of estimated diagnosis for Huntington disease.

Previous MRI studies with participants prior to manifest Huntington disease have been conducted in small single-site samples. The current study reports data from a systematic multi-national study during the prodromal period of Huntington disease and examines whether various brain structures make unique predictions about the proximity to manifest disease. MRI scans were acquired from 657 participants enrolled at 1 of 32 PREDICT-HD research sites. Only prodromal Huntington disease participants (those not meeting motor criteria for diagnosis) were included and subgrouped by estimated diagnosis proximity (Near, Mid, and Far) based upon a formula incorporating age and CAG-repeat length. Results show volumes of all three subgroups differed significantly from Controls for total brain tissue, cerebral spinal fluid, white matter, cortical gray matter, thalamus, caudate, and putamen. Total striatal volume demonstrated the largest differences between Controls and all three prodromal subgroups. Cerebral white matter offered additional independent power in the prediction of estimated proximity to diagnosis. In conclusion, this large cross-sectional study shows that changes in brain volume are detectable years to decades prior to estimated motor diagnosis of Huntington disease. This suggests that a clinical trial of a putative neuroprotective agent could begin as much as 15 years prior to estimated motor diagnosis in a cohort of persons at risk for but not meeting clinical motor diagnostic criteria for Huntington disease, and that neuroimaging (striatal and white matter volumes) may be among the best predictors of diagnosis proximity.

Cerebellum development during childhood and adolescence: a longitudinal morphometric MRI study.

In addition to its well-established role in balance, coordination, and other motor skills, the cerebellum is increasingly recognized as a prominent contributor to a wide array of cognitive and emotional functions. Many of these capacities undergo dramatic changes during childhood and adolescence. However, accurate characterization of co-occurring anatomical changes has been hindered by lack of longitudinal data and methodologic challenges in quantifying subdivisions of the cerebellum. In this study we apply an innovative image analysis technique to quantify total cerebellar volume and 11 subdivisions (i.e. anterior, superior posterior, and inferior posterior lobes, corpus medullare, and three vermal regions) from anatomic brain MRI scans from 25 healthy females and 25 healthy males aged 5-24 years, each of whom was scanned at least three times at approximately 2-year intervals. Total cerebellum volume followed an inverted U shaped developmental trajectory peaking at age 11.8 years in females and 15.6 years in males. Cerebellar volume was 10% to 13% larger in males depending on the age of comparison and the sexual dimorphism remained significant after covarying for total brain volume. Subdivisions of the cerebellum had distinctive developmental trajectories with more phylogenetically recent regions maturing particularly late. The cerebellum's unique protracted developmental trajectories, sexual dimorphism, preferential vulnerability to environmental influences, and frequent implication in childhood onset disorders such as autism and ADHD make it a prime target for pediatric neuroimaging investigations.

Cerebellar volume and cognitive functioning in children who experienced early deprivation.

BACKGROUND: The cerebellum is a brain region recognized primarily in the coordination of movement and related accessory motor functions. In addition, emerging evidence implicates the cerebellum in cognitive processes and suggests that this brain region might be subject to experience-dependent changes in structure. Therefore, the aim of this study was to evaluate the role of early environmental deprivation in the maturation of the cerebellum and aspects of cognitive development. METHODS: Structural magnetic resonance imaging volumes of 12 cerebellar sub-regions from 31 previously neglected and 30 typically developing children were compared with subjects' corresponding neuropsychological test scores. RESULTS: Neglected children had smaller volume of the superior-posterior cerebellar lobes. Moreover, superior-posterior lobe volume was found to mediate neuropsychological test performance differences between groups, with larger volumes yielding better outcomes on tests of memory and planning. CONCLUSIONS: These data support the importance of experience-dependent changes in cerebellar structure and highlight the role of the cerebellum in higher cognitive functions.

A method to fuse fMRI tasks through spatial correlations: applied to schizophrenia.

Single task analysis methods of functional MRI brain data, though useful, are not able to evaluate the joint information between tasks. Data fusion of multiple tasks that probe different cognitive processes provides knowledge of the joint information and may be important in order to better understand complex disorders such as schizophrenia. In this article, we introduce a simple but effective technique to fuse two tasks by computing the histogram of correlations for all possible combinations of whole brain voxels. The approach was applied to data derived from healthy controls and patients with schizophrenia from four different tasks, auditory oddball (target), auditory oddball (novel), Sternberg working memory, and sensorimotor. It was found that in four out of six task combinations patients' intertask correlations were more positively correlated than controls', in one combination the controls showed more positive correlations and in another there was no significant difference. The robustness of this result was checked with several testing techniques. The four task combinations for which patients had more positive correlation occurred at different scanning sessions and the task combination that showed the opposite result occurred within the same scanning session. Brain regions that showed high intertask correlations were found for both groups and regions that correlated differently between the two groups were identified. The approach introduced finds interesting results and new differential features that cannot be achieved through traditional methods.