Correction For Intracranial Volume Research Articles

Structural deviations of the posterior fossa and the cerebellum and their cognitive links in a neurodevelopmental deletion syndrome.

High-impact genetic variants associated with neurodevelopmental disorders provide biologically-defined entry points for mechanistic investigation. The 3q29 deletion (3q29Del) is one such variant, conferring a 40-100-fold increased risk for schizophrenia, as well as high risk for autism and intellectual disability. However, the mechanisms leading to neurodevelopmental disability remain largely unknown. Here, we report the first in vivo quantitative neuroimaging study in individuals with 3q29Del (N = 24) and neurotypical controls (N = 1608) using structural MRI. Given prior radiology reports of posterior fossa abnormalities in 3q29Del, we focused our investigation on the cerebellum and its tissue-types and lobules. Additionally, we compared the prevalence of cystic/cyst-like malformations of the posterior fossa between 3q29Del and controls and examined the association between neuroanatomical findings and quantitative traits to probe gene-brain-behavior relationships. 3q29Del participants had smaller cerebellar cortex volumes than controls, before and after correction for intracranial volume (ICV). An anterior-posterior gradient emerged in finer grained lobule-based and voxel-wise analyses. 3q29Del participants also had larger cerebellar white matter volumes than controls following ICV-correction and displayed elevated rates of posterior fossa arachnoid cysts and mega cisterna magna findings independent of cerebellar volume. Cerebellar white matter and subregional gray matter volumes were associated with visual-perception and visual-motor integration skills as well as IQ, while cystic/cyst-like malformations yielded no behavioral link. In summary, we find that abnormal development of cerebellar structures may represent neuroimaging-based biomarkers of cognitive and sensorimotor function in 3q29Del, adding to the growing evidence identifying cerebellar pathology as an intersection point between syndromic and idiopathic forms of neurodevelopmental disabilities.

Comparison of approaches to control for intracranial volume in research on the association of brain volumes with cognitive outcomes.

Most neuroimaging studies linking regional brain volumes with cognition correct for total intracranial volume (ICV), but methods used for this correction differ across studies. It is unknown whether different ICV correction methods yield consistent results. Using a brain-wide association approach in the MRI substudy of UK Biobank (N = 41,964; mean age = 64.5 years), we used regression models to estimate the associations of 58 regional brain volumetric measures with eight cognitive outcomes, comparing no correction and four ICV correction approaches. Approaches evaluated included: no correction; dividing regional volumes by ICV (proportional approach); including ICV as a covariate in the regression (adjustment approach); and regressing the regional volumes against ICV in different normative samples and using calculated residuals to determine associations (residual approach). We used Spearman-rank correlations and two consistency measures to quantify the extent to which associations were inconsistent across ICV correction approaches for each possible brain region and cognitive outcome pair across 2320 regression models. When the association between brain volume and cognitive performance was close to null, all approaches produced similar estimates close to the null. When associations between a regional volume and cognitive test were not null, the adjustment and residual approaches typically produced similar estimates, but these estimates were inconsistent with results from the crude and proportional approaches. For example, when using the crude approach, an increase of 0.114 (95% confidence interval [CI]: 0.103-0.125) in fluid intelligence was associated with each unit increase in hippocampal volume. However, when using the adjustment approach, the increase was 0.055 (95% CI: 0.043-0.068), while the proportional approach showed a decrease of -0.025 (95% CI: -0.035 to -0.014). Different commonly used methods to correct for ICV yielded inconsistent results. The proportional method diverges notably from other methods and results were sometimes biologically implausible. A simple regression adjustment for ICV produced biologically plausible associations.

Comparison of two corticosteroid regimens on brain volumetrics in patients with Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a neuromuscular disorder in which many patients also have neurobehavioral problems. Corticosteroids, the primary pharmacological treatment for DMD, have been shown to affect brain morphology in other conditions, but data in DMD are lacking. This study aimed to investigate the impact of two corticosteroid regimens on brain volumetrics in DMD using magnetic resonance imaging (MRI). In a cross-sectional, two-center study, T1-weighted MRI scans were obtained from three age-matched groups (9-18 years): DMD patients treated daily with deflazacort (DMDd, n = 20, scan site: Leuven), DMD patients treated intermittently with prednisone (DMDi, n = 20, scan site: Leiden), and healthy controls (n = 40, both scan sites). FSL was used to perform voxel-based morphometry analyses and to calculate intracranial, total brain, gray matter, white matter, and cerebrospinal fluid volumes. A MANCOVA was employed to compare global volumetrics between groups, with site as covariate. Both patient groups displayed regional differences in gray matter volumes compared to the control group. The DMDd group showed a wider extent of brain regions affected and a greater difference overall. This was substantiated by the global volume quantification: the DMDd group, but not the DMDi group, showed significant differences in gray matter, white matter, and cerebrospinal fluid volumes compared to the control group, after correction for intracranial volume. Volumetric differences in the brain are considered part of the DMD phenotype. This study suggests an additional impact of corticosteroid treatment showing a contrast between pronounced alterations seen in patients receiving daily corticosteroid treatment and more subtle differences in those treated intermittently.

Mammillary body and hypothalamic volumes in mood disorders

We have previously reported an in vivo enlargement of the left hypothalamus in mood disorders using 7 T magnetic resonance imaging. The aim of this follow-up study was to find out whether the hypothalamic volume difference may be located in the mammillary bodies (MB) rather than being widespread across the hypothalamus.We developed and evaluated a detailed segmentation algorithm that allowed a reliable segmentation of the MBs, and applied it to 20 unmedicated (MDDu) and 20 medicated patients with major depressive disorder, 21 medicated patients with bipolar disorder, and 23 controls. 20 out of 23 healthy controls were matched to the MDDu. We tested for group differences in MB and hypothalamus without MB (HTh) volumes using analyses of covariance. Associations between both volumes of interest were analysed using bivariate and partial correlations.In contrast to postmortem findings, we found no statistically significant differences of the MB volumes between the study groups. Left HTh volumes differed significantly across the study groups after correction for intracranial volume (ICV) and for ICV and sex. Our result of an HTh enlargement in mood disorders was confirmed by a paired t-test between the matched pairs of MDDu and healthy controls using the native MB and HTh volumes. In the whole sample, MB volumes correlated significantly with the ipsilateral HTh volumes.Our results indicate a structural relationship between both volumes, and that our previous in vivo finding of a hypothalamus enlargement does not extend to the MB, but is limited to the HTh. The enlargement is more likely related to the dysregulation of the HPA axis than to cognitive dysfunctions accompanying mood disorders.

Proportional intracranial volume correction differentially biases behavioral predictions across neuroanatomical features, sexes, and development

Individual differences in brain anatomy can be used to predict variations in cognitive ability. Most studies to date have focused on broad population-level trends, but the extent to which the observed predictive features are shared across sexes and age groups remains to be established. While it is standard practice to account for intracranial volume (ICV) using proportion correction in both regional and whole-brain morphometric analyses, in the context of brain-behavior predictions the possible differential impact of ICV correction on anatomical features and subgroups within the population has yet to be systematically investigated. In this work, we evaluate the effect of proportional ICV correction on sex-independent and sex-specific predictive models of individual cognitive abilities across multiple anatomical properties (surface area, gray matter volume, and cortical thickness) in healthy young adults (Human Connectome Project; n = 1013, 548 females) and typically developing children (Adolescent Brain Cognitive Development study; n = 1823, 979 females). We demonstrate that ICV correction generally reduces predictive accuracies derived from surface area and gray matter volume, while increasing predictive accuracies based on cortical thickness in both adults and children. Furthermore, the extent to which predictive models generalize across sexes and age groups depends on ICV correction: models based on surface area and gray matter volume are more generalizable without ICV correction, while models based on cortical thickness are more generalizable with ICV correction. Finally, the observed neuroanatomical features predictive of cognitive abilities are unique across age groups regardless of ICV correction, but whether they are shared or unique across sexes (within age groups) depends on ICV correction. These findings highlight the importance of considering individual differences in ICV, and show that proportional ICV correction does not remove the effects of cranial volume from anatomical measurements and can introduce ICV bias where previously there was none. ICV correction choices affect not just the strength of the relationships captured, but also the conclusions drawn regarding the neuroanatomical features that underlie those relationships.

Changes in structural brain development after selective fetal growth restriction in monochorionic twins.

ObjectivesFetal growth restriction (FGR) may alter brain development permanently, resulting in lifelong structural and functional changes. However, in studies addressing this research question, FGR singletons have been compared primarily to matched appropriately grown singletons, a design which is inherently biased by differences in genetic and maternal factors. To overcome these limitations, we conducted a within‐pair comparison of neonatal structural cerebral ultrasound measurements in monochorionic twin pairs with selective FGR (sFGR).MethodsStructural cerebral measurements on neonatal cerebral ultrasound were compared between the smaller and larger twins of monochorionic twin pairs with sFGR, defined as a birth‐weight discordance (BWD) ≥ 20%, born in our center between 2010 and 2020. Measurements from each twin pair were also compared with those of an appropriately grown singleton, matched according to sex and gestational age at birth.ResultsIncluded were 58 twin pairs with sFGR, with a median gestational age at birth of 31.7 (interquartile range, 29.9–33.8) weeks and a median birth weight of 1155 g for the smaller twin and 1725 g for the larger twin (median BWD, 32%). Compared with both the larger twin and the singleton, the smaller twin had significantly smaller cerebral structures (corpus callosum, vermis, cerebellum), less white/deep gray matter and smaller intracranial surface area and volume. Intracranial‐volume discordance and BWD correlated significantly (R 2 = 0.228, P < 0.0001). The median intracranial‐volume discordance was smaller than the median BWD (19% vs 32%, P < 0.0001). After correction for intracranial volume, only one of the observed differences (biparietal diameter) remained significant for the smaller twin vs both the larger twin and the singleton.ConclusionsIn monochorionic twins with sFGR, neonatal cerebral ultrasound reveals an overall, proportional restriction in brain growth, with smaller cerebral structures, less white/deep gray matter and smaller overall brain‐size parameters in the smaller twin. There was a positive linear relationship between BWD and intracranial‐volume discordance, with intracranial‐volume discordance being smaller than BWD. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

P685. Intracranial Volume Correction Differentially Biases Behavioral Predictions across Neuroanatomical Features and Populations

Individual differences in neuroanatomy can predict variability in cognitive functioning. However, most studies focus on broad population-level trends, and the extent to which observed predictive features are shared across sexes and age groups remains largely unknown. Furthermore, while it is standard practice to account for intracranial volume (ICV) in morphometric analyses, the possible differential impact of ICV correction on anatomical features and subgroups within the population in the context of brain-behavior predictions has yet to be investigated.

Neurodevelopment in adolescents and adults with fetal alcohol spectrum disorders (FASD): A magnetic resonance region of interest analysis

The neurodevelopmental trajectory in individuals with fetal alcohol spectrum disorders (FASD) has not been well characterized. We examined age-related differences in the volume of the corpus callosum, basal ganglia, and cerebellum across adolescence and young adulthood, due to the sensitivity of these regions to prenatal alcohol exposure. T1-weighted anatomical magnetic resonance images (MRI) were acquired from a cross-sectional sample of subjects 13–30 years old who had received an alcohol-related diagnosis (FASD, n = 107) and typically developing controls (CON, n = 56). FreeSurfer v5.3 was used to obtain volumetric data for the corpus callosum, caudate, putamen, pallidum, and cerebellum. Analysis of variance (ANOVA) was used to examine the effects of group (FASD, CON), sex, and age on region volume. Data were analyzed with and without correction for intracranial volume (ICV). All subregions were significantly smaller in the FASD group compared to controls, and these findings persisted even after ICV correction. Furthermore, the FASD and control groups differed in their relationship between age and total volume of the corpus callosum, caudate, and cerebellum. Specifically, older FASD individuals had smaller total volume in these regions; this relationship was not seen in the control group. Control males demonstrated larger volumes than control females in all regions prior to ICV correction; however, sex differences were attenuated in the FASD group in both the pallidum and cerebellum. Sex differences remained after ICV correction in the pallidum and cerebellum. These cross-sectional findings suggest that at least some brain regions may become smaller at an earlier than expected age in individuals with FASD, and that sex is an important factor to consider when examining neural structures in FASD. Further evaluation is necessary using longitudinal methods and including older ages.

Brain structure, IQ, and psychopathology in young offspring of patients with schizophrenia or bipolar disorder.

Studying offspring of schizophrenia (SZo) and bipolar disorder patients (BDo) provides important information on the putative neurodevelopmental trajectories underlying development toward severe mental illnesses. We compared intracranial volume (ICV), as a marker for neurodevelopment, and global and local brain measures between SZo or BDo and control offspring (Co) in relation to IQ and psychopathology. T1-weighted magnetic resonance imaging (MRI) brain scans were obtained from 146 participants (8-19 years; 40 SZo, 66 BDo, 40 Co). Linear mixed models were applied to compare ICV, global, and local brain measures between groups. To investigate the effect of ICV, IQ (four subtests Wechsler Intelligence Scale for Children/Wechsler Adult Intelligence Scale-III) or presence of psychopathology these variables were each added to the model. SZo and BDo had significantly lower IQ and more often met criteria for a lifetime psychiatric disorder than Co. ICV was significantly smaller in SZo than in BDo (d = -0.56) and Co (d = -0.59), which was largely independent of IQ (respectively, d = -0.54 and d = -0.35). After ICV correction, the cortex was significantly thinner in SZo than in BDo (d = -0.42) and Co (d = -0.75) and lateral ventricles were larger in BDo than in Co (d = 0.55). Correction for IQ or lifetime psychiatric diagnosis did not change these findings. Despite sharing a lower IQ and a higher prevalence of psychiatric disorders, brain abnormalities in BDo appear less pronounced (but are not absent) than in SZo. Lower ICV in SZo implies that familial risk for schizophrenia has a stronger association with stunted early brain development than familial risk for bipolar disorder.

The Association Between Familial Risk and Brain Abnormalities Is Disease Specific: An ENIGMA-Relatives Study of Schizophrenia and Bipolar Disorder

BackgroundSchizophrenia and bipolar disorder share genetic liability, and some structural brain abnormalities are common to both conditions. First-degree relatives of patients with schizophrenia (FDRs-SZ) show similar brain abnormalities to patients, albeit with smaller effect sizes. Imaging findings in first-degree relatives of patients with bipolar disorder (FDRs-BD) have been inconsistent in the past, but recent studies report regionally greater volumes compared with control subjects. MethodsWe performed a meta-analysis of global and subcortical brain measures of 6008 individuals (1228 FDRs-SZ, 852 FDRs-BD, 2246 control subjects, 1016 patients with schizophrenia, 666 patients with bipolar disorder) from 34 schizophrenia and/or bipolar disorder family cohorts with standardized methods. Analyses were repeated with a correction for intracranial volume (ICV) and for the presence of any psychopathology in the relatives and control subjects. ResultsFDRs-BD had significantly larger ICV (d = +0.16, q < .05 corrected), whereas FDRs-SZ showed smaller thalamic volumes than control subjects (d = −0.12, q < .05 corrected). ICV explained the enlargements in the brain measures in FDRs-BD. In FDRs-SZ, after correction for ICV, total brain, cortical gray matter, cerebral white matter, cerebellar gray and white matter, and thalamus volumes were significantly smaller; the cortex was thinner (d < −0.09, q < .05 corrected); and third ventricle was larger (d = +0.15, q < .05 corrected). The findings were not explained by psychopathology in the relatives or control subjects. ConclusionsDespite shared genetic liability, FDRs-SZ and FDRs-BD show a differential pattern of structural brain abnormalities, specifically a divergent effect in ICV. This may imply that the neurodevelopmental trajectories leading to brain anomalies in schizophrenia or bipolar disorder are distinct.

F17. DIFFERENCES IN INTRACRANIAL VOLUME, IQ AND PSYCHOPATHOLOGY IN YOUNG OFFSPRING OF PATIENTS AFFECTED WITH SCHIZOPHRENIA OR BIPOLAR DISORDER

BackgroundOffspring of patients with schizophrenia and bipolar disorder are at increased risk to develop psychopathology. It has been suggested that the development of these disorders may be a result of early neurodevelopmental abnormalities. The intracranial volume (ICV) is a direct marker for neurodevelopment in the early years, as ICV reaches 90% of its full size around the age of five. Interestingly, a smaller ICV is more consistently found in SZ patients, compared to controls, than in bipolar disorder patients. The offspring of these two patients group may provide important information on the putative neurodevelopmental trajectory underlying the development of these disorders. We compared ICV between offspring of at least one parent with SZ (SZo) or BD (BDo) and control offspring (Co) in relation to IQ and the presence of psychopathology.MethodsA large sample of children and adolescents (8–18 years old; 54 SZo, 90 BDo, and 46 Co) was included. T1-weighted (3-Tesla) MRI brain scans were available for 146 participants. Group differences in ICV, global and local brain measures, psychopathology (K-SADS-PL, CBCL/6–18), IQ (WISC-III/WAIS-III), and their interactions were analyzed. FreeSurfer-5.3.0 was used for subcortical and cortical volume, cortical thickness, and cortical surface area estimations. Groups were compared using linear mixed effects modeling, corrected for family dependencies. FDR-correction was applied.ResultsOur main finding was that ICV was significantly smaller in SZo, compared to BDo and Co. IQ was significantly lower in both SZo and BDo, relative to Co, but could not explain the smaller ICV in SZo. ICV was also not explained by psychopathology, even though there was no significant difference in ‘any psychopathology’ between SZo and BDo. There was however some illness specificity as BDo had a higher prevalence of ‘any mood disorder’ as compared with Co, and SZo had a higher prevalence of major depressive disorder and autism spectrum disorders as compared with BDo and Co. After correcting for ICV, the cortex was significantly thinner in SZo compared to BDo and Co, and BDo had larger lateral ventricles than Co. Without correction for ICV, volumes of the total brain and gray matter were significantly smaller in SZo than in BDo and Co. Cortical white matter volume was significantly smaller in SZo as compared with Co.DiscussionIrrespective of a lower IQ and increased presence of psychopathology in both high-risk offspring groups, abnormal early brain development, expressed as smaller ICV, differentiates offspring of patients with schizophrenia from offspring of patients with bipolar disorder and offspring of healthy parents. This suggest that the risk for schizophrenia is, in contrast to that in bipolar disorder, characterized by stunted brain development.

The power-proportion method for intracranial volume correction in volumetric imaging analysis.

In volumetric brain imaging analysis, volumes of brain structures are typically assumed to be proportional or linearly related to intracranial volume (ICV). However, evidence abounds that many brain structures have power law relationships with ICV. To take this relationship into account in volumetric imaging analysis, we propose a power law based method—the power-proportion method—for ICV correction. The performance of the new method is demonstrated using data from the PREDICT-HD study.

Hippocampal degeneration in patients with amyotrophic lateral sclerosis

There is increasing appreciation of non-motor system involvement in amyotrophic lateral sclerosis (ALS), although its full extent and clinical significance remains to be established. This study tested the hypothesis that memory impairment in patients with ALS is related to hippocampal degeneration. Consecutive patients with ALS (58) and 29 matched controls participated in standardized neuropsychological assessment and magnetic resonance imaging. Patients with ALS performed worse in global cognitive functioning and executive and verbal memory tests (p < 0.05). The hippocampus was manually segmented in each hemisphere, and volumes were calculated with correction for intracranial volume. Analysis of covariance, controlled for the effect of age and education years, showed significantly smaller hippocampal volume on the right (p = 0.004) in patients with ALS. Verbal memory test performance correlated with the left hippocampal volume in patients with ALS (p < 0.05), although there was no significant correlation with tests of executive function and clinical variables underscoring the specificity of the present findings. Hippocampal volume loss and its correlation with the severity of verbal memory impairment highlight significant hippocampal involvement which can occur as a non-motor deficit in patients with ALS.

Evaluation of hippocampal volume based on MR imaging in patients with bipolar affective disorder applying manual and automatic segmentation techniques

To compare the hippocampal volumes in patients with bipolar disorder (BD) and healthy controls, obtained by applying different segmentation methods (manual, Freesurfer [FS], and FSL). The study included 27 patients with BD and 40 healthy controls. T1-weighted images in the sagittal plane were acquired on a 3 Tesla (T) MR scanner. Hippocampal volumetry was performed using one manual and two automated methods (FS and FSL). One-way repeated analysis of variance was applied to test the differences in hippocampal volumes using the three segmentation methods. To evaluate the agreement among the three tested volumetric segmentation methods the intraclass correlation coefficients (ICCs) were calculated. Hippocampal volumes obtained from all methods were significantly different (P < 0.05) in BD patients after intracranial volume correction, indicating a reduction in volume, unless from the manual method of the left hippocampal volume. The ICCs of the hippocampal volume between the manual method and FS were 0.846 (right) and 0.859 (left), and between the manual method and FSL were 0.746 (right) and 0.654 (left). Both manual and automatic segmentation methods detected reductions in the hippocampal volumes in BD patients. Automated segmentation methods are a robust and reproducible option for assessing hippocampal volume.

Regional white matter volume differences in nondemented aging and Alzheimer's disease

Accumulating evidence suggests that altered cerebral white matter (WM) influences normal aging, and further that WM degeneration may modulate the clinical expression of Alzheimer's disease (AD). Here we conducted a study of differences in WM volume across the adult age span and in AD employing a newly developed, automated method for regional parcellation of the subcortical WM that uses curvature landmarks and gray matter (GM)/WM surface boundary information. This procedure measures the volume of gyral WM, utilizing a distance constraint to limit the measurements from extending into the centrum semiovale. Regional estimates were first established to be reliable across two scan sessions in 20 young healthy individuals. Next, the method was applied to a large clinically-characterized sample of 299 individuals including 73 normal older adults and 91 age-matched participants with very mild to mild AD. The majority of measured regions showed a decline in volume with increasing age, with strong effects found in bilateral fusiform, lateral orbitofrontal, superior frontal, medial orbital frontal, inferior temporal, and middle temporal WM. The association between WM volume and age was quadratic in many regions suggesting that WM volume loss accelerates in advanced aging. A number of WM regions were further reduced in AD with parahippocampal, entorhinal, inferior parietal and rostral middle frontal WM showing the strongest AD-associated reductions. There were minimal sex effects after correction for intracranial volume, and there were associations between ventricular volume and regional WM volumes in the older adults and AD that were not apparent in the younger adults. Certain results, such as the loss of WM in the fusiform region with aging, were unexpected and provide novel insight into patterns of age associated neural and cognitive decline. Overall, these results demonstrate the utility of automated regional WM measures in revealing the distinct patterns of age and AD associated volume loss that may contribute to cognitive decline.

Aging, gender, and the elderly adult brain: An examination of analytical strategies

We sought to examine the relations between age, gender and brain volumes in an elderly population; we also sought to examine ways of measuring these relations. Three sets of analyses were used: correlational analyses, in which correlations between independent variables and brain volumes were calculated without correction for intracranial volume (ICV); covariational analyses, in which ICV was used as a covariate in regression equations; and ratio analyses, in which the dependent variable was the ratio of brain volume to ICV. These analyses yielded similar results, except that (as expected) adjusting for ICV altered estimates of gender differences. Analyses of age showed decreases in left caudate, putamen, and right hippocampus and an increase in CSF, a result generally in accord with previous findings. However, we also found a significant decrease of white-matter volumes and no significant decrease in total gray-matter volumes. Correlational analyses showed that men did not always have larger volumes despite their larger head size; women generally had larger volumes after adjusting for ICV. We found no age–gender interactions.

Correction for intracranial volume in analysis of whole brain atrophy in multiple sclerosis: the proportion vs. residual method

Two techniques that correct (normalize) regional and whole brain volumes according to head size—the proportion method (tissue-to-intracranial volume ratio) and the residual method (regression-based predicted brain tissue volumes)—are used pervasively in neuroimaging research, but have received little critical evaluation or direct comparison. Using a quantitatively derived MRI data set of patients with multiple sclerosis ( n = 18) and age-/sex-matched normal controls ( n = 18), we introduced various types of error into estimates of intracranial volume (ICV) and absolute parenchymal volume (APV) to observe how this error affected the final outcome of normalized brain measures and their ability to detect group differences, as computed by a proportion (brain parenchymal fraction [BPF]) and residual method (predicted parenchymal volume [PPV]). The results indicated that systemic error in ICV and APV values considerably affected BPF means based on the proportion method, except with dependent-related systematic APV error, but essentially did not change statistical power associated with group differences in BPF. Random error altered BPF means to a much smaller extent, but was associated with moderate reductions in statistical power. On the other hand, PPV estimates based on the residual method were unaffected by these same ICV and APV errors, except with dependent-related systematic APV error, and were not associated with reductions in statistical power. Our findings suggest that head size correction of brain regions with the residual method generally may provide advantages over the proportion method.

Parkinson's disease is associated with hippocampal atrophy.

Patients with Parkinson's disease (PD) may have hippocampal atrophy compared with controls. We compared hippocampal, and extra-hippocampal volumes between PD, PDD (patients with PD who have mild cognitive impairment or dementia), Alzheimer's disease (AD) and controls using volumetric magnetic resonance imaging (MRI). Participants (10 patients with PD, 10 with PDD, 11 with AD, and 12 control subjects) had an informant interview, neurological examination, and psychometric testing. Established, reliable methods were used to measure the hippocampus, parahippocampal gyrus, temporal, frontal, and parieto-occipital lobes. Correction for intracranial volume was carried out before comparison. There was no age difference between groups (mean age, 74 years). On the Clinical Dementia Rating scale (CDR) cognitive impairment was mild (CDR = 0.5) in the majority of PDD and AD patients. Hippocampal (P < 0.0004) volumes were smaller in the patient groups. Effect sizes compared with the control group were: PD, 0.66; PDD, 1.22; and AD, 1.81. The other volumes did not differ significantly. Among PD and PDD patients, recognition memory (r = 0.54, P = 0.015) and Mini-Mental State Examination scores (r = 0.56, P = 0.01) correlated with left, but not right hippocampal volume. In conclusion, hippocampal volume showed a pattern (Control > PD > PDD > AD) suggesting progressive hippocampal volume loss in PD. Volumetric MRI imaging might provide an early marker for dementia in PD.

Temporal horn enlargement is present in schizophrenia and bipolar disorder

Background: Ventricular enlargement and temporal lobe volume deficits have been demonstrated in patients with affective disorder as well as those with schizophrenia. This study compares quantitative measures of temporal lobe, hemispheric, and ventricular volumes in a group of patients with chronic schizophrenia and bipolar disorder and seeks to determine if the groups can be differentiated on the basis of measured brain abnormalities. Methods: A series of coronal magnetic resonance imaging sections were acquired and analyzed for each of 22 patients with chronic schizophrenia, 14 patients with bipolar disorder, and 15 community volunteers. Eleven regions of interest for each brain were defined, which included temporal lobe, superior temporal gyrus, hemisphere, lateral ventricle, third ventricle, and temporal horn measures. Tissue measures were obtained by tracing, and cerebrospinal fluid measures were obtained by fluid–tissue thresholding using specialized computer software. Results: Both patient groups had significantly larger temporal horn volumes in comparison with the control group both before and after correction for intracranial volume. The two patient groups did not differ from each other or controls on any other tissue or fluid measure. Conclusions: This study confirms the finding of increased temporal horn volume in patients with schizophrenia and suggests that this structural abnormality does not differentiate the structural neuropathology of schizophrenia from that of bipolar disorder.

Intérêt d'une seconde cure d'interféron a chez des patients atteints d'hépatite virale C

Schizophrenia and bipolar disorder share genetic liability, and some structural brain abnormalities are common to both conditions. First-degree relatives of patients with schizophrenia (FDRs-SZ) show similar brain abnormalities to patients, albeit with smaller effect sizes. Imaging findings in first-degree relatives of patients with bipolar disorder (FDRs-BD) have been inconsistent in the past, but recent studies report regionally greater volumes compared with control subjects.We performed a meta-analysis of global and subcortical brain measures of 6008 individuals (1228 FDRs-SZ, 852 FDRs-BD, 2246 control subjects, 1016 patients with schizophrenia, 666 patients with bipolar disorder) from 34 schizophrenia and/or bipolar disorder family cohorts with standardized methods. Analyses were repeated with a correction for intracranial volume (ICV) and for the presence of any psychopathology in the relatives and control subjects.FDRs-BD had significantly larger ICV (d = +0.16, q < .05 corrected), whereas FDRs-SZ showed smaller thalamic volumes than control subjects (d = −0.12, q < .05 corrected). ICV explained the enlargements in the brain measures in FDRs-BD. In FDRs-SZ, after correction for ICV, total brain, cortical gray matter, cerebral white matter, cerebellar gray and white matter, and thalamus volumes were significantly smaller; the cortex was thinner (d < −0.09, q < .05 corrected); and third ventricle was larger (d = +0.15, q < .05 corrected). The findings were not explained by psychopathology in the relatives or control subjects.Despite shared genetic liability, FDRs-SZ and FDRs-BD show a differential pattern of structural brain abnormalities, specifically a divergent effect in ICV. This may imply that the neurodevelopmental trajectories leading to brain anomalies in schizophrenia or bipolar disorder are distinct.