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ABSTRACT: 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.
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.
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.
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.
Biological psychiatry 07/2011; 70(7):672-9. · 8.93 Impact Factor
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ABSTRACT: 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.
To evaluate relative contributions of 4 potential predictors (illness duration, antipsychotic treatment, illness severity, and substance abuse) of brain volume change.
Predictors of brain volume changes were assessed prospectively based on multiple informants.
Data from the Iowa Longitudinal Study.
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).
Brain volumes.
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.
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.
Archives of general psychiatry 02/2011; 68(2):128-37. · 12.26 Impact Factor
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ABSTRACT: 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.
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).
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.
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.
Epilepsia 01/2011; 52(4):698-706. · 3.96 Impact Factor
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ABSTRACT: 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.
NeuroImage 01/2011; 54(1):328-36. · 5.89 Impact Factor
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ABSTRACT: 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.
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.
Slopes representing the association between age and striatal volume were significantly steeper as CAG repeat length increased.
Although cross-sectional, these data suggest that striatal atrophy, like clinical progression, may occur faster with higher CAG repeat lengths.
PLoS currents. 01/2011; 3:RRN1235.
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ABSTRACT: 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.
NeuroImage 09/2009; 49(1):63-70. · 5.89 Impact Factor
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ABSTRACT: For many years the cerebellum has been considered to serve as a coordinator of motor function. Likewise, for many years schizophrenia has been considered to be a disease that primarily affects the cerebrum. This review summarizes recent evidence that both these views must be revised in the light of emerging evidence about cerebellar function and the mechanisms of schizophrenia. Evidence indicating that the cerebellum plays a role in higher cortical functions is summarized. Evidence indicating that cerebellar abnormalities occur in schizophrenia is also reviewed. These suggest interesting directions for future research.
Biological psychiatry 08/2008; 64(2):81-8. · 8.93 Impact Factor
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ABSTRACT: The large amount of imaging data collected in several ongoing multi-center studies requires automated methods to delineate brain structures of interest. We have previously reported on using artificial neural networks (ANN) to define subcortical brain structures. Here we present several automated segmentation methods using multidimensional registration. A direct comparison between template, probability, artificial neural network (ANN) and support vector machine (SVM)-based automated segmentation methods is presented. Three metrics for each segmentation method are reported in the delineation of subcortical and cerebellar brain regions. Results show that the machine learning methods outperform the template and probability-based methods. Utilization of these automated segmentation methods may be as reliable as manual raters and require no rater intervention.
NeuroImage 02/2008; 39(1):238-47. · 5.89 Impact Factor
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ABSTRACT: While the role of the cerebellum in motor coordination is widely accepted, the notion that it is involved in emotion has only recently gained popularity. To date, functional neuroimaging has not been used in combination with lesion studies to elucidate the role of the cerebellum in the processing of emotional material. We examined six participants with cerebellar stroke and nine age and education matched healthy volunteers. In addition to a complete neuropsychological, neurologic, and psychiatric examination, participants underwent [15O]water positron emission tomography (PET) while responding to emotion-evoking visual stimuli. Cerebellar lesions were associated with reduced pleasant experience in response to happiness-evoking stimuli. Stroke patients reported an unpleasant experience to frightening stimuli similar to healthy controls, yet showed significantly lower activity in the right ventral lateral and left dorsolateral prefrontal cortex, amygdala, thalamus, and retrosplenial cingulate gyrus. Frightening stimuli led to increased activity in the ventral medial prefrontal, anterior cingulate, pulvinar, and insular cortex. This suggests that alternate neural circuitry became responsible for maintaining the evolutionarily critical fear response after cerebellar damage.
Neuropsychologia 04/2007; 45(6):1331-41. · 3.64 Impact Factor
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ABSTRACT: Previous structural and functional imaging studies suggest that the corticocerebellar-thalamic-cortical circuit is dysfunctional in schizophrenia. Accurate identification and volumetric measurement of cerebellar subregions are essential to the assessment of the cerebellum's role in healthy and disease states. Manual parcellation of the cerebellum on MR images was performed with the use of guide traces. Guide traces identified relevant fissures and borders in several planes, and their intersections with the primary tracing plane were used to maintain consistency and accuracy during the parcellation. The cerebellum was parcellated into right and left anterior lobes, superior posterior lobes, inferior posterior lobes, and corpus medullare. A systematic review of the final traces ensured their accuracy. An artificial neural network was trained using a novel landmark-warped method to help account for wide variability in structure size and location. Overlaps of the manually traced lobes (intersection/union) ranged from 0.78 to 0.85 and intraclass correlations (r2) ranged from 0.82 to 0.94. In a comparison of the semiautomated method with the manual method overlaps ranged from 0.83 to 0.88 and intraclass correlations ranged from 0.92 to 0.97. For two raters using the semiautomated method overlaps ranged from 0.83 to 0.88 and intraclass correlations ranged from 0.97 to 0.99. The semiautomated method was built on the groundwork of the manual method to produce more reliable results in a fraction of the time, making valid measurements possible on a large number of subjects.
NeuroImage 10/2002; 17(1):61-76. · 5.89 Impact Factor
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ABSTRACT: Cerebellar structures were measured in 30 chronic schizophrenic men and 18 healthy men using high resolution MRI. The volume of the posterior superior vermis was found to be significantly smaller in the schizophrenic men, but there was no difference in other cerebellar regions or the intracranial volume. The findings support the view that within the cerebellum the posterior superior vermis may be selectively reduced in men with chronic schizophrenia.
Schizophrenia Research 06/2002; 55(1-2):61-7. · 4.75 Impact Factor
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ABSTRACT: A common procedure performed by many groups in the analysis of neuroimaging data is separating the brain from other tissues. This procedure is often utilized both by volumetric studies as well as functional imaging studies. Regardless of the intent, an accurate, robust method of identifying the brain or cranial vault is imperative. While this is a common requirement, there are relatively few tools to perform this task. Most of these tools require a T1 weighted image and are therefore not able to accurately define a region that includes surface CSF. In this paper, we have developed a novel brain extraction technique termed Maximize Uniformity by Summation Heuristic (MUSH) optimization. The algorithm was designed for extraction of the brain and surface CSF from a multi-modal magnetic resonance (MR) imaging study. The method forms a linear combination of multi-modal MR imaging data to make the signal intensity within the brain as uniform as possible. The resulting image is thresholded and simple morphological operators are utilized to generate the resulting representation of the brain. The resulting method was applied to a sample of 20 MR brain scans and compared to the results generated by 3dSkullStrip, 3dIntracranial, BET, and BET2. The average Jaccard metrics for the twenty subjects was 0.66 (BET), 0.61 (BET2), 0.88 (3dIntracranial), 0.91 (3dSkullStrip), and 0.94 (MUSH).
Proceedings of SPIE. 7259:72593N-72593N-7.
