Callosum Genu Research Articles

Tela-choroidea-to-anterior-cerebral-artery distance (TACAD): novel marker on color Doppler to identify fetuses with complete or partial agenesis of corpus callosum.

To assess objectively the course of the anterior cerebral artery (ACA) by measuring its distance to the tela choroidea in the midsagittal view, and to compare this distance in normal fetuses with that in those with agenesis of the corpus callosum (ACC), a condition known to be associated with an abnormal course of the ACA. The tela-choroidea-to-anterior-cerebral-artery distance (TACAD) was measured in the midsagittal view of the brain on color Doppler, between the anterior border of the tela choroidea and the ACA at the level of the callosal genu. Reference ranges in relation to gestational age were established in a prospective, cross-sectional study of 253 normal healthy fetuses between 19 and 36 weeks of gestation. The study group included fetuses with complete ACC (n = 28) or partial ACC (n = 18). TACAD of normal fetuses showed an increase during the second half of pregnancy, with a mean value of 10.1 mm and 14.2 mm at 22 and 30 weeks of gestation, respectively. All (28/28) fetuses with complete ACC and 83% (15/18) of those with partial ACC had significantly shorter TACAD, with mean values of 3.9 mm and 6.6 mm, respectively. TACAD is a measurement that is simple to obtain during fetal color Doppler neurosonography, which enables quantification of the course of the ACA and pericallosal artery. TACAD is shorter in fetuses with complete or partial ACC than in normal fetuses and provides an objective, quantifiable value, rather than merely descriptive information. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Corpus Callosal Microstructure Predicts Bimanual Motor Performance in Chronic Stroke Survivors: a Preliminary Cross-Sectional Study

ABSTRACT Background Microstructural changes in the corpus callosum (CC) are associated with more severe motor impairment in the paretic hand, poor recovery, and general disability. The purpose of this study was to determine if CC microstructure predicts bimanual motor performance in chronic stroke survivors. Methods We examined the relationship between the fractional anisotropy (FA) across the CC, in both the sensorimotor and non-sensorimotor regions, and movement times for two self-initiated and self-paced bimanual tasks in 41 chronic stroke survivors. Using publicly available control datasets (n = 52), matched closely for imaging acquisition parameters, we also explored the effect of stroke and age on callosal microstructure. Results In mild-to-moderate chronic stroke survivors with relatively localized lesions to the motor areas, lower callosal FA values, suggestive of a more disorganized microstructure, were associated with slower bimanual performance. Associations were strongest for the primary motor fibers (b = −2.19 ± 1.03, p = .035), followed closely by premotor/supplementary motor (b = −2.07 ± 1.07, p = .041) and prefrontal (b = −1.92 ± 0.97, p = .05) fibers of the callosum. Secondary analysis revealed that compared to neurologically age-similar adults, chronic stroke survivors exhibited significantly lower mean FA in all regions of the CC, except the splenium. Conclusion Remote widespread changes in the callosal genu and body are associated with slower performance on cooperative bimanual tasks that require precise and interdependent coordination of the hands. Measures of callosal microstructure may prove to be a useful predictor of real-world bimanual performance in chronic stroke survivors.

Older age, male sex, and cerebral microbleeds predict white matter loss after traumatic brain injury.

Little is known on how mild traumatic brain injury affects white matter based on age at injury, sex, cerebral microbleeds, and time since injury. Here, we study the fractional anisotropy of white matter to study these effects in 109 participants aged 18-77 (46 females, age μ ± σ = 40 ± 17years) imaged within [Formula: see text] 1week and [Formula: see text] 6months post-injury. Age is found to be linearly associated with white matter degradation, likely due not only to injury but also to cumulative effects of other pathologies and to their interactions with injury. Age is associated with mean anisotropy decreases in the corpus callosum, middle longitudinal fasciculi, inferior longitudinal and occipitofrontal fasciculi, and superficial frontal and temporal fasciculi. Over [Formula: see text] 6months, the mean anisotropies of the corpus callosum, left superficial frontal fasciculi, and left corticospinal tract decrease significantly. Independently of other predictors, age and cerebral microbleeds contribute to anisotropy decrease in the callosal genu. Chronically, the white matter of commissural tracts, left superficial frontal fasciculi, and left corticospinal tract degrade appreciably, independently of other predictors. Our findings suggest that large commissural and intra-hemispheric structures are at high risk for post-traumatic degradation. This study identifies detailed neuroanatomic substrates consistent with brain injury patients' age-dependent deficits in information processing speed, interhemispheric communication, motor coordination, visual acuity, sensory integration, reading speed/comprehension, executive function, personality, and memory. We also identify neuroanatomic features underlying white matter degradation whose severity is associated with the male sex. Future studies should compare our findings to functional measures and other neurodegenerative processes.

Mapping the principal gradient onto the corpus callosum

Gradients capture some of the variance of the resting-state functional magnetic resonance imaging (rsfMRI) signal. Amongst these, the principal gradient depicts a functional processing hierarchy that spans from sensory-motor cortices to regions of the default-mode network. While the cortex has been well characterised in terms of gradients little is known about its underlying white matter. For instance, comprehensive mapping of the principal gradient on the largest white matter tract, the corpus callosum, is still missing. Here, we mapped the principal gradient onto the midsection of the corpus callosum using the 7T human connectome project dataset. We further explored how quantitative measures and variability in callosal midsection connectivity relate to the principal gradient values. In so doing, we demonstrated that the extreme values of the principal gradient are located within the callosal genu and the posterior body, have lower connectivity variability but a larger spatial extent along the midsection of the corpus callosum than mid-range values. Our results shed light on the relationship between the brain's functional hierarchy and the corpus callosum. We further speculate about how these results may bridge the gap between functional hierarchy, brain asymmetries, and evolution.

Long-term clinically relevant rodent model of methotrexate-induced cognitive impairment.

With the enhanced use of chemotherapy and the advent of increased patient survival rates, there are an increasing number of cancer survivors living with chemotherapy-induced cognitive impairment. A growing number of clinical studies have brought to light the association of agents like methotrexate in generating these neurological sequelae, although mechanisms remain unclear. Here, we use a clinically relevant regimen of several cycles of methotrexate and leucovorin rescue to develop a model of chemotherapy-induced cognitive impairment, and investigate the in vivo long-term (16 mo) impact of high-dose systemic methotrexate on white matter cellular dynamics as assessed by stereology, animal behavior, and diffusion tensor imaging. Our results indicate that at 6 and 16 months post-chemotherapy, methotrexate-treated rats exhibit a significant and permanent decrease in the number of oligodendrocytes and their progenitors in the white matter, in corpus callosum volumes, and myelin basic protein. These findings are associated with mostly delayed deficits in performance on Morris Water Maze and Novel Object Recognition tasks. Diffusion tensor imaging demonstrates significantly decreased fractional anisotropy values in the callosum genu, body, and splenium, as well as previously unassessed areas like the fimbria. Interestingly, these white matter changes are preceded by an earlier, transient decrement in white matter microglia at 3 months, and hippocampal neural progenitors at 3 and 6 months. These results demonstrate a significant negative impact of methotrexate on the oligodendrocyte compartment and white matter, associated with cognitive impairment. The data also support the use of diffusion tensor imaging in monitoring white matter integrity in this context.

Axonal myelin decrease in the splenium in major depressive disorder

The corpus callosum has become a key area of interest for researchers in severe mental illness. Disruptions in fractional anisotropy in the callosum have been reported in schizophrenia and major depressive disorder. No change has been reported in oligodendrocyte density and overall size of the callosum in either illness, suggesting that gross morphology is unchanged, but subtler organisational disruption may exist within this structure. Using high-resolution oil immersion microscopy, we examined the cross-sectional area of the nerve fibre and the axonal myelin sheath; and using standard high-resolution light microscopy, we measured the density of myelinated axons. These measurements were made in the splenium of the corpus callosum. Measures were taken in the sagittal plane in the callosal splenium to contrast with the previous similar examination of the callosal genu. Cases of major depressive disorder had significantly decreased mean myelin cross-sectional area (p = 0.014) per axon in the splenium than in controls or schizophrenia groups. There was no significant change in the density of myelinated axons. The results suggest a clear decrease of myelin in the axons of the callosal splenium in MDD, although this type of neuropathological study is unable to clarify whether this is caused by changes during life or has a developmental origin. In contrast with increased myelin in the callosal genu, this result suggests a longitudinal change in callosal myelination in major depressive disorder not present in normal or schizophrenic brains.

S138. White Matter Integrity Predicts Anti-Depressant Response in Late-Life Depression

White matter integrity in fronto-limbic-striatal circuits are frequently reduced in depression. We investigated the effect of local tract integrity on antidepressant outcome in geriatric depression. Regions of interest (ROIs) comprised the callosal genu (GCC), anterior and posterior internal capsule (ALIC, PLIC), cingulum (CGC), inferior and superior fronto-occipital and superior longitudinal fasciculi (IFO, SFO, SLF).

Generalized epilepsy syndromes and callosal thickness: Differential effects between patients with juvenile myoclonic epilepsy and those with generalized tonic-clonic seizures alone

PurposeThe definition of two well-studied genetic generalized epilepsy syndromes (GGE) − juvenile myoclonic epilepsy (JME) and epilepsy with generalized tonic-clonic seizures alone (GTCS) − suggests the absence of structural cerebral abnormalities. Nevertheless, there are various reports of such abnormalities (especially in JME), where effects mainly occur within thalamus and mesial prefrontal regions. This raises the question of whether JME is particularly linked to midline structure abnormalities, which may also involve the corpus callosum. MethodWe studied callosal morphology in a well-matched sample of 22 JME patients, 15 GTCS patients, and 42 controls (CTL) for all of whom we obtained T1-weighted data on a 3T MRI scanner. More specifically, we measured callosal thickness at 100 equidistant points across the callosal surface, and subsequently compared the three groups (JME, GTCS, and CTL) against each other. ResultsSignificant differences between JME patients and controls were observed within the callosal genu, anterior midbody, and isthmus, with thinner regions in JME patients. There were no significant differences between GTCS patients and controls, and also not between JME patients and GTCS patients. ConclusionThe present outcomes point to callosal abnormalities in JME patients suggesting an impairment of interhemisperic communication between prefrontal, motor, parietal and temporal cortices. These findings further support the notion that structural aberrations are present and differentiated across GGE syndromes, with significant callosal deviations from normality in JME.

DTI-based response-driven modeling of mTLE laterality.

PurposeTo develop lateralization models for distinguishing between unilateral and bilateral mesial temporal lobe epilepsy (mTLE) and determining laterality in cases of unilateral mTLE.BackgroundmTLE is the most common form of medically refractory focal epilepsy. Many mTLE patients fail to demonstrate an unambiguous unilateral ictal onset. Intracranial EEG (icEEG) monitoring can be performed to establish whether the ictal origin is unilateral or truly bilateral with independent bitemporal ictal origin. However, because of the expense and risk of intracranial electrode placement, much research has been done to determine if the need for icEEG can be obviated with noninvasive neuroimaging methods, such as diffusion tensor imaging (DTI).MethodsFractional anisotropy (FA) was used to quantify microstructural changes reflected in the diffusivity properties of the corpus callosum, cingulum, and fornix, in a retrospective cohort of 31 patients confirmed to have unilateral (n = 24) or bilateral (n = 7) mTLE. All unilateral mTLE patients underwent resection with an Engel class I outcome. Eleven were reported to have hippocampal sclerosis on pathological analysis; nine had undergone prior icEEG. The bilateral mTLE patients had undergone icEEG demonstrating independent epileptiform activity in both right and left hemispheres. Twenty-three nonepileptic subjects were included as controls.ResultsIn cases of right mTLE, FA showed significant differences from control in all callosal subregions, in both left and right superior cingulate subregions, and in forniceal crura. Comparison of right and left mTLE cases showed significant differences in FA of callosal genu, rostral body, and splenium and the right posteroinferior and superior cingulate subregions. In cases of left mTLE, FA showed significant differences from control only in the callosal isthmus. Significant differences in FA were identified when cases of right mTLE were compared with bilateral mTLE cases in the rostral and midbody callosal subregions and isthmus. Based on 11 FA measurements in the cingulate, callosal and forniceal subregions, a response-driven lateralization model successfully differentiated all cases (n = 54) into groups of unilateral right (n = 12), unilateral left (n = 12), and bilateral mTLE (n = 7), and nonepileptic control (23).ConclusionThe proposed response-driven DTI biomarker is intended to lessen diagnostic ambiguity of laterality in cases of mTLE and help optimize selection of surgical candidates. Application of this model shows promise in reducing the need for invasive icEEG in prospective cases.

Dynamic Responses of Selective Brain White Matter Fiber Tracts to Binge Alcohol and Recovery in the Rat

To determine the dynamics of white matter vulnerability to excessive alcohol consumption, diffusion tensor imaging (DTI) was used in an animal model of alcohol exposure. Quantitative, in vivo fiber tracking results are presented from rats with DTI conducted at 3 time points: baseline; after 4 days of intragastric alcohol to blood alcohol levels of ~250mg/dL; and after one week of recovery. Binge alcohol followed by a week of sobriety resulted in rapidly reversible decreases in fractional anisotropy (FA), a measure of the coherence of fiber tracts, in callosal genu and fimbria-fornix but not splenium; and increases in mean diffusivity (MD), an index of freely diffusing water in tissue, selective to the fimbria-fornix. These effects were confirmed with tract-based spatial statistics (TBSS). The directionality of changes in DTI metrics reproduce those observed in human alcoholism. That a single exposure to binge alcohol can cause substantial transient changes detectable in DTI metrics demonstrates the potential for rapid neuroplasticity.

Functionally relevant white matter degradation in multiple sclerosis: a tract-based spatial meta-analysis.

To identify statistical consensus between published studies for distribution and functional relevance of tract white matter (WM) degradation in multiple sclerosis (MS). By systematically searching online databases, tract-based spatial statistics studies were identified that compared fractional anisotropy (FA; a marker for WM integrity) in MS patients to healthy control subjects, correlated FA in MS patients with physical disability, or correlated FA in MS patients with cognitive performance. Voxelwise meta-analysis was performed by using the Signed Differential Mapping method for each comparison. Moderating effects of mean age, mean physical disability score, imager magnet strength, lesion load, and number of diffusion directions were assessed by means of meta-regression. Meta-analysis was performed on data from 495 patients and 253 control subjects across 12 studies. MS diagnosis was significantly associated with widespread lower tract FA (nine studies; largest cluster, 4379 voxels; z = 7.1; P < .001). Greater physical disability was significantly associated with lower FA in the right posterior cingulum, left callosal splenium, right inferior fronto-occipital fasciculus, and left fornix crus (six studies; 323 voxels; z = 1.7; P = .001). Impaired cognition was significantly associated with lower FA in the callosal genu, thalamus, right posterior cingulum, and fornix crus (seven studies; largest cluster, 980 voxels; z = 2.5; P < .001). WM damage is widespread in MS with differential and only minimally overlapping distributions of low FA that relates to physical disability and cognitive impairment. The higher number of clusters of lower FA in relation to cognition and their higher z scores suggest that cerebral WM damage may have a greater relevance to cognitive dysfunction than physical disability in MS, and that low anterior callosal and thalamic FA have specific importance to cognitive status.

White matter microstructural recovery with abstinence and decline with relapse in alcohol dependence interacts with normal ageing: a controlled longitudinal DTI study

Alcohol dependence exacts a toll on brain white matter microstructure, which has the potential of repair with prolonged sobriety. Diffusion tensor imaging (DTI) enables in-vivo quantification of tissue constituents and localisation of tracts potentially affected in alcohol dependence and its recovery. We did an extended longitudinal study of alcoholism's trajectory of effect on selective fibre bundles with sustained sobriety or decline with relapse. Participants were drawn from a longitudinal, 1·5T DTI database of 841 scans of individuals with various medical or neuropsychiatric conditions and normal ageing. Participants diagnosed with alcohol dependence had to meet the criteria from DSM-IV for alcohol dependence. Controls were screened and free of any DSM-IV axis I diagnosis, including being without history of alcohol or drug abuse or dependence. Tract-based spatial statistics (TBSS) quantified white matter integrity throughout the brain in 47 alcohol-dependent individuals and 56 controls examined 2-5 times over 1-8 year intervals. We identified regions showing group differences with a white matter atlas. For macrostructural comparison, we measured corpus callosum and centrum semiovale volumes on MRI. This study took place in the USA, between June 23, 2000, and Sept 6, 2011. TBSS identified a large cluster (threshold p<0·001), where controls showed significant fractional anisotropy (FA) decrease with ageing and alcohol-dependent individuals had significantly lower FA than controls regardless of age. Over the examination interval, 27 (57%) alcohol-dependent individuals abstained, ten (21%) relapsed into light drinking, and ten (21%) relapsed into heavy drinking (>5 kg of alcohol/year). Despite abnormally low FA, age trajectories of the abstainers were positive and progressing toward normality, whereas those of the relapsers and controls were negative. Axial diffusivity (lower values indexing myelin integrity) was abnormally high in the total alcohol-dependent group; however, the abstainers' slopes paralleled those of controls, whereas the heavy-drinking relapsers' slopes showed accelerated ageing. Callosal genu and body microstructure but not macrostructure showed untoward alcohol-related effects. Affected projection and association tracts had an anterior and superior neuroanatomical distribution. Return to heavy drinking resulted in accelerating microstructural white matter damage. Despite evidence for damage, alcohol-dependent individuals maintaining sobriety over extended periods showed improvement in brain fibre tract integrity reflective of fibre reorganisation and myelin restoration, indicative of a neural mechanism explaining recovery. US National Institute on Alcohol Abuse and Alcoholism (AA012388, AA017168, AA005965, AA013521-INIA).

Preserved white matter integrity is a marker of familial longevity

Brain tissue integrity is highly heritable, and its decline is a common phenomenon of ageing. This study aimed to determine whether the phenotype of familial longevity is marked by a relative preservation of brain tissue microstructure. Participants were enrolled in the Leiden Longevity Study. In total, 185 middle-aged to elderly offspring of nonagenarian siblings, who were enriched for familial factors of longevity, were contrasted with 171 environment- and age-matched controls. All subjects underwent 3T whole brain magnetic resonance diffusion tensor imaging. Voxel-wise analysis revealed widespread age-related decrease of white matter fractional anisotropy and increases of axial, radial, and mean diffusivity (all p < 0.003). Offspring showed higher mean white matter fractional anisotropy (mean [standard error]: offspring, 0.3232 [0.0009]; controls, 0.3212 [0.0009]; p = 0.04) compared to control subjects independent of cardiovascular risk factors. When differences in white matter diffusion parameters between offspring and control subjects were assessed voxel-wise, offspring showed higher white matter fractional anisotropy and lower white matter radial diffusivity predominantly in the callosal genu and body (both p < 0.003). With the effect of chronological age on white matter microstructure taken into account, offspring can be considered 4.5 years "biologically younger" compared to control subjects with regard to white matter integrity. Both middle-aged to elderly offspring of nonagenarian siblings and control subjects show common age-related decline of white matter integrity, but it is less marked in the callosal genu and body in the offspring. This corresponds to a biological age benefit of 4.5 years of the offspring as compared to the control subjects.

Characteristics of diffusion-tensor imaging for healthy adult rhesus monkey brains.

Diffusion-tensor imaging can be used to observe the microstructure of brain tissue. Fractional sotropy reflects the integrity of white matter fibers. Fractional anisotropy of a young adult brain is low in gray matter, high in white matter, and highest in the splenium of the corpus callosum. Thus, we selected the anterior and posterior limbs of the internal capsule, head of the caudate nucleus, semioval center, thalamus, and corpus callosum (splenium and genu) as regions of interest when using diffusion-tensor imaging to observe fractional anisotropy of major white matter fiber tracts and the deep gray matter of healthy rhesus monkeys aged 4–8 years. Results showed no laterality ferences in fractional anisotropy values. Fractional anisotropy values were low in the head of date nucleus and thalamus in gray matter. Fractional anisotropy values were highest in the splenium of corpus callosum in the white matter, followed by genu of the corpus callosum and the posterior limb of the internal capsule. Fractional anisotropy values were lowest in the semioval center and posterior limb of internal capsule. These results suggest that fractional anisotropy values in major white matter fibers and the deep gray matter of 4–8-year-old rhesus monkeys are similar to those of healthy young people.

Ultrasound measurement of the corpus callosum and neural development of premature infants.

Length and thickness of 152 corpus callosa were measured in neonates within 24 hours of birth. Using ultrasonic diagnostic equipment with a neonatal brain-specific probe, corpus callosum length and thickness of the genu, body, and splenium were measured on the standard mid-sagittal plane, and the anteroposterior diameter of the genu was measured in the coronal plane. Results showed that corpus callosum length as well as thickness of the genu and splenium increased with tional age and birth weight, while other measures did not. These three factors on the standard mid-sagittal plane are therefore likely to be suitable for real-time evaluation of corpus callosum velopment in premature infants using cranial ultrasound. Further analysis revealed that thickness of the body and splenium and the anteroposterior diameter of the genu were greater in male infants than in female infants, suggesting that there are sex differences in corpus callosum size during the neonatal period. A second set of measurements were taken from 40 premature infants whose gestational age was 34 weeks or less. Corpus callosum measurements were corrected to a gestational age of 40 weeks, and infants were grouped for analysis depending on the outcome of a neonatal behavioral neurological assessment. Compared with infants with a normal neurological assessment, corpus callosum length and genu and splenium thicknesses were less in those with abnormalities, indicating that corpus callosum growth in premature infants is associated with neurobehavioral development during the early extrauterine stage.

Effects of different field strengths, gradient directions, and acquisitions on fractional anisotropy in diffusion tensor imaging: A tract-based spatial statistics study

The effects of increasing acquisitions and gradient directions on fractional anisotropy (FA) at 1.5T versus 3T were investigated using an operator-independent methodology (tract-based spatial statistics) by minimizing technical differences in image acquisition between the two magnetic resonance imaging platforms and also FA values at roughly equivalent signal-to-noise ratio and data acquisition time were compared. Five healthy subjects underwent this experiment. Diffusion tensor imaging (DTI) was performed at 1.5T and 3T. Gradient schemes were 6, 30, and 96 directions. The numbers of acquisitions were 5, 10, and 15 for 6-direction; 1, 2, and 3 acquisitions for 30-direction; and 1 acquisition for 96-direction scheme. FA values in the callosal genu (CG), callosal splenium (CS), posterior limb of the internal capsule (PLIC), and the superior longitudinal fasciculus (SLF) bilaterally were assessed. For 6-direction scheme at 5 acquisitions, FA values were higher at 1.5T than at 3T. FA values derived using 30-direction scheme were higher at 3T than 1.5T in the left SLF and PLIC bilaterally. In the CG and CS, FA values at equivalent signal-to-noise ratio derived from different acquisitions and gradient directions differed by 11% at 1.5T. DTI data acquired at 3T are not always comparable to that at 1.5T. The center of the brain does not appear to be affected but the peripheral white matter appears to be affected by field strengths, number of acquisitions, and gradient directions. © 2013 Wiley Periodicals, Inc. Concepts Magn Reson Part B (Magn Reson Engineering) 43B:41–48, 2013

Schizophrenia: brain morphology and treatment aspects

Since the first findings of enlarged ventricles in computer tomography studies and with the development of MRIbased segmentation, brain morphology findings in schizophrenia point to abnormal structural findings in several brain regions involved in neuronal circuits [1]. One of the often cited environmental risk factors in schizophrenia is cannabis abuse. In an invited review, Malchow et al. [2], however, found inconclusive results with respect to alterations in brain morphology. They assume that chronic cannabis abuse may induce structural changes, whereas in first-episode and high-risk patients, studies need replication. In subjects at high risk and patients with schizophrenia, the gyrification index as a measure of cortico-cortical connection differed from healthy controls in the frontal and parietal cortex [3]. This may be based on the neurodevelopmental abnormalities, since the gyrification pattern is determined during the perinatal period. Accordingly, in a recent postmortem study, a reduced gyrification index has been observed in the parietal cortex in schizophrenia [4] showing no differences between monozygotic twins compared to dizygotic twin pairs which points to the influence of different intrauterine and postnatal factors [5]. Postmortem studies with a resolution on the cellular and even molecular level with, for example, focus on synaptic structural elements [6] may contribute to elucidate the pathophysiology of schizophrenia. Williams et al. [7] investigated neuronal cell density and found decreased pyramidal layer thickness resulting in decreased frontal lobe thickness in schizophrenia patients. They additionally report decreased astrocyte density in the subgenual cingulated cortex and callosal genu for their sample [8], which extends neurobiological hypotheses on the dysfunction of astrocytes in maintaining synaptic stability. Investigations in healthy subjects are indispensable to elucidate risk factors influencing brain volumes and for exclusion of confounding factors such as other diseaserelated and treatment effects. Beside environmental factors, schizophrenia risk genes may contribute to altered brain structures. Trost et al. [9] found a dysbindin-1 gene variant to be associated with hippocampal and prefrontal gray matter volumes. On the molecular level, another risk gene such as brain-derived neurotrophic factor (BDNF) val66met polymorphism has been shown to affect the glutamate system [10]. Moreover, D-amino acid oxidase activator gene (DAOA) variation has been found to affect homovanillic acid levels in cerebrospinal fluid [11]. Unraveling neurobiological effects of such risk factors may contribute to develop a more personalized medicine in psychiatry [12]. Even effects of traditional neuroleptic treatment strategies may be influenced by genetic factors. Giegling et al. [13] found that three haplotype blocks, one among ankyrin repeat and kinase domain containing 1 (ANKK1) and two among dopamine receptor D2 (DRD2) genes, were associated with better clinical improvement in schizophrenia patients. These often are heavy smokers attempting to treat negative and cognitive symptoms themselves. In a clinical trial investigating effects of transdermal nicotine patch, Chen et al. [14], however, found no correlation with replacement doses and only a low smoking cessation rate. They recommend more effective smoking cessation programs for this group of hospitalized patients. Due to restricted therapeutic effects of current treatment strategies in severe psychiatric disorders, the editorial A. Schmitt (&) P. Falkai Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University Munich, Nusbaumstr. 7, 80336 Munich, Germany e-mail: Andrea.Schmitt@med.uni-muenchen.de

Diffusion tensor imaging metrics in neonates—a comparison of manual region-of-interest analysis vs. tract-based spatial statistics

Diffusion tensor data can be analyzed using region-of-interest (ROI) analysis and tract-based spatial statistics (TBSS). There is essentially no literature validating or comparing these techniques in the neonate. The purpose of this study was to perform a direct comparison of fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD) derived using manual ROI analysis and TBSS modified for use in neonates. This study was IRB-approved. Thirty-nine infants, 32-49weeks post-conception age, underwent MRI at 3T. FA, AD and RD of the callosal genu (CG) and splenium (CS) and posterior limbs of both internal capsules (PLIC) were determined using both techniques. Pearson correlation (r) was used to estimate the concordance of tensor metrics derived from these techniques. The r value for FA in the CG, CS and left and right PLIC was 0.88, 0.75, 0.78 and 0.35, respectively. The r value for axial/radial diffusivity in the CG, CS and left and right PLIC was 0.62/0.72, 0.76/0.64, 0.68/0.9 and 0.3/0.72, respectively. The variable concordance results from problems with spatial correspondence of ROI masks between the native space and the FA skeleton. Direct comparison between these methodologies shows tensor metrics varied with location and by degree, suggesting the two techniques do not provide consistently comparable results.

Minimum SNR and acquisition for bias-free estimation of fractional anisotropy in diffusion tensor imaging — a comparison of two analytical techniques and field strengths

Although it is known that low signal-to-noise ratio (SNR) can affect tensor metrics, few studies reporting disease or treatment effects on fractional anisotropy (FA) report SNR; the implicit assumption is that SNR is adequate. However, the level at which low SNR causes bias in FA may vary with tissue FA, field strength and analytical methodology. We determined the SNR thresholds at 1.5 T vs. 3 T in regions of white matter (WM) with different FA and compared FA derived using manual region-of-interest (ROI) analysis to tract-based spatial statistics (TBSS), an operator-independent whole-brain analysis tool. Using ROI analysis, SNR thresholds on our hardware–software magnetic resonance platforms were 25 at 1.5 T and 20 at 3 T in the callosal genu (CG), 40 at 1.5 and 3 T in the anterior corona radiata (ACR), and 50 at 1.5 T and 70 at 3 T in the putamen (PUT). Using TBSS, SNR thresholds were 20 at 1.5 T and 3 T in the CG, and 35 at 1.5 T and 40 at 3 T in the ACR. Below these thresholds, the mean FA increased logarithmically, and the standard deviations widened. Achieving bias-free SNR in the PUT required at least nine acquisitions at 1.5 T and six acquisitions at 3 T. In the CG and ACR, bias-free SNR was achieved with at least three acquisitions at 1.5 T and one acquisition at 3 T. Using diffusion tensor imaging (DTI) to study regions of low FA, e.g., basal ganglia, cerebral cortex, and WM in the abnormal brain, SNR should be documented. SNR thresholds below which FA is biased varied with the analytical technique, inherent tissue FA and field strength. Studies using DTI to study WM injury should document that bias-free SNR has been achieved in the region of the brain being studied as part of quality control.

Gene Network Effects on Brain Microstructure and Intellectual Performance Identified in 472 Twins

A major challenge in neuroscience is finding which genes affect brain integrity, connectivity, and intellectual function. Discovering influential genes holds vast promise for neuroscience, but typical genome-wide searches assess approximately one million genetic variants one-by-one, leading to intractable false positive rates, even with vast samples of subjects. Even more intractable is the question of which genes interact and how they work together to affect brain connectivity. Here, we report a novel approach that discovers which genes contribute to brain wiring and fiber integrity at all pairs of points in a brain scan. We studied genetic correlations between thousands of points in human brain images from 472 twins and their nontwin siblings (mean age: 23.7 ± 2.1 SD years; 193 male/279 female). We combined clustering with genome-wide scanning to find brain systems with common genetic determination. We then filtered the image in a new way to boost power to find causal genes. Using network analysis, we found a network of genes that affect brain wiring in healthy young adults. Our new strategy makes it computationally more tractable to discover genes that affect brain integrity. The gene network showed small-world and scale-free topologies, suggesting efficiency in genetic interactions and resilience to network disruption. Genetic variants at hubs of the network influence intellectual performance by modulating associations between performance intelligence quotient and the integrity of major white matter tracts, such as the callosal genu and splenium, cingulum, optic radiations, and the superior longitudinal fasciculus.