Increase In Fractional Anisotropy Research Articles

Early Stage Alterations in White Matter and Decreased Functional Interhemispheric Hippocampal Connectivity in the 3xTg Mouse Model of Alzheimer's Disease.

Alzheimer’s disease (AD) is characterized in the late stages by amyloid-β (Aβ) plaques and neurofibrillary tangles. Nevertheless, recent evidence has indicated that early changes in cerebral connectivity could compromise cognitive functions even before the appearance of the classical neuropathological features. Diffusion tensor imaging (DTI), resting-state functional magnetic resonance imaging (rs-fMRI) and volumetry were performed in the triple transgenic mouse model of AD (3xTg-AD) at 2 months of age, prior to the development of intraneuronal plaque accumulation. We found the 3xTg-AD had significant fractional anisotropy (FA) increase and radial diffusivity (RD) decrease in the cortex compared with wild-type controls, while axial diffusivity (AD) and mean diffusivity (MD) were similar. Interhemispheric hippocampal connectivity was decreased in the 3xTg-AD while connectivity in the caudate putamen (CPu) was similar to controls. Most surprising, ventricular volume in the 3xTg-AD was four times larger than controls. The results obtained in this study characterize the early stage changes in interhemispheric hippocampal connectivity in the 3xTg-AD mouse that could represent a translational biomarker to human models in preclinical stages of the AD.

Effects of Acute Alcohol Consumption on the Human Brain: Diffusional Kurtosis Imaging and Arterial Spin-Labeling Study.

Brain function and microstructure are affected by alcohol consumption. Until recently, the effect of alcohol on neural mechanisms has not been fully elucidated. Our aim was to explore the acute effects of alcohol on healthy human brains by diffusional kurtosis imaging and 3D arterial spin-labeling and elucidate structural and functional changes in the brain on acute alcohol intake. Conventional MR imaging, diffusional kurtosis imaging, and 3D arterial spin-labeling were performed on 24 healthy volunteers before and 0.5 and 1 hour after drinking alcohol. Participants were divided into 2 groups according to the response to alcohol: blushing (n = 12) and unblushing (n = 12) groups. Twenty brain regions were analyzed. Diffusional kurtosis imaging revealed an increase in mean kurtosis and fractional anisotropy at 0.5 hour post-alcohol intake in most brain regions, whereas mean diffusion was decreased in several brain regions at 1 hour after drinking. 3D arterial spin-labeling showed increased cerebral blood flow in most brain regions, particularly in the frontal regions. However, perfusion in the anterior commissure decreased. Regional changes in the brain correlated with various behavioral performances with respect to blush response and sex. In general, blushing individuals and men are more sensitive to alcohol with acute effects. Physiologic and microstructural alterations in the brain on alcohol consumption were examined. Brain areas with blood flow alteration detected by 3D arterial spin-labeling were highly consistent with susceptible areas detected by diffusional kurtosis imaging. The current study provides new insight into the effects of alcohol on the brain and behavioral performance in different blush response and sex populations.

Developmental trajectories of white matter structure in children with and without reading impairments

Left temporal-parietal white matter structure is consistently associated with reading abilities in children. A small number of longitudinal studies show that development of this area over time is altered in children with impaired reading. However, it remains unclear how brain developmental patterns relate to specific reading skills such as fluency, which is a critical part of reading comprehension. Here, we examined white matter development trajectories in children with dysfluent reading (20 dysfluent and inaccurate readers, 36 dysfluent and accurate readers) compared to non-impaired readers (n = 14) over 18 months. We found typical age-related increases of fractional anisotropy (FA) in bilateral temporal-parietal areas in non-impaired readers, but a lack of similar changes in dysfluent readers. We also found steeper decreases of mean diffusivity (MD) in the right corona radiata and left uncinate fasciculus in dysfluent inaccurate readers compared to dysfluent accurate readers. Changes in diffusion parameters were correlated with changes in reading scores over time. These results suggest delayed white matter development in dysfluent readers, and show maturational differences between children with different types of reading impairment. Overall, these results highlight the importance of considering developmental trajectories, and demonstrate that the window of plasticity may be different for different children.

The within-subject application of diffusion tensor MRI and CLARITY reveals brain structural changes in Nrxn2 deletion mice

BackgroundOf the many genetic mutations known to increase the risk of autism spectrum disorder, a large proportion cluster upon synaptic proteins. One such family of presynaptic proteins are the neurexins (NRXN), and recent genetic and mouse evidence has suggested a causative role for NRXN2 in generating altered social behaviours. Autism has been conceptualised as a disorder of atypical connectivity, yet how single-gene mutations affect such connectivity remains under-explored. To attempt to address this, we have developed a quantitative analysis of microstructure and structural connectivity leveraging diffusion tensor MRI (DTI) with high-resolution 3D imaging in optically cleared (CLARITY) brain tissue in the same mouse, applied here to the Nrxn2α knockout (KO) model.MethodsFixed brains of Nrxn2α KO mice underwent DTI using 9.4 T MRI, and diffusion properties of socially relevant brain regions were quantified. The same tissue was then subjected to CLARITY to immunolabel axons and cell bodies, which were also quantified.ResultsDTI revealed increases in fractional anisotropy in the amygdala (including the basolateral nuclei), the anterior cingulate cortex, the orbitofrontal cortex and the hippocampus. Axial diffusivity of the anterior cingulate cortex and orbitofrontal cortex was significantly increased in Nrxn2α KO mice, as were tracts between the amygdala and the orbitofrontal cortex. Using CLARITY, we find significantly altered axonal orientation in the amygdala, orbitofrontal cortex and the anterior cingulate cortex, which was unrelated to cell density.ConclusionsOur findings demonstrate that deleting a single neurexin gene (Nrxn2α) induces atypical structural connectivity within socially relevant brain regions. More generally, our combined within-subject DTI and CLARITY approach presents a new, more sensitive method of revealing hitherto undetectable differences in the autistic brain.

Diffusion Magnetic Resonance Imaging Unveils the Spatiotemporal Microstructural Gray Matter Changes following Injury in the Rodent Brain.

Traumatic brain injury (TBI) is associated with gray and white matter alterations in brain tissue. Gray matter alterations are not yet as well studied as those of the white matter counterpart. This work utilized T2-weighted structural imaging, diffusion tensor imaging (DTI), and diffusion kurtosis imaging to unveil the gray matter changes induced in a controlled cortical impact (CCI) mouse model of TBI at 5 h, 1 day, 3 days, 7 days, 14 days, and 30 days post-CCI. A cross-sectional histopathology approach was used to confer validity of the magnetic resonance imaging (MRI) data by performing cresyl violet staining and glial fibrillary acidic protein (GFAP) immunohistochemistry. The results demonstrated a significant increase in lesion volume up to 3 days post-injury followed by a significant decrease in the cavity volume for the period of 1 month. GFAP signals peaked on Day 7 and persisted until Day 30 in both ipsilateral and contralateral hippocampus, ipsilateral cortex, and thalamic areas. An increase in fractional anisotropy (FA) was seen at Day 7 in the pericontusional area but decreased FA in the contralateral cortex, hippocampus, and thalamus. Mean diffusivity (MD) was significantly lower in the pericontusional cortex. Increased MD and decreased mean kurtosis were limited to the injury site on Days 7 to 30 and to the contralateral hippocampus and thalamus on Days 3 and 7. This work is one of the few cross-sectional studies to demonstrate a link between MRI measures and histopathological readings to track gray matter changes in the progression of TBI.

Physical Activity Increases White Matter Microstructure in Children.

Children are becoming increasingly inactive, unfit, and overweight, yet there is relatively little causal evidence regarding the effects of physical activity on brain health during childhood. The present study examined the effects of an after-school physical activity program (FITKids2) on the microstructure of white matter tracts in 7- to 9-year-old children. We measured the microstructural properties of white matter via diffusion tensor imaging in 143 children before and after random assignment to either a 9-month after-school physical activity program (N = 76, mean age = 8.7 years) or a wait list control group (N = 67, mean age = 8.7 years). Our results demonstrate that children who participated in the physical activity program showed increased white matter microstructure in the genu of the corpus callosum, with no changes in white matter microstructure in the wait list control group which reflects typical development. Specifically, children in the physical activity program showed increases in fractional anisotropy (FA) and decreases in radial diffusivity (RD) in the genu from pre- to post-test, thereby suggesting more tightly bundled and structurally compact fibers (FA) and increased myelination (RD), with no changes in estimates of axonal fiber diameter (axial diffusivity, AD). The corpus callosum integrates cognitive, motor, and sensory information between the left and right hemispheres of the brain, and the white matter tract plays a role in cognition and behavior. Our findings reinforce the importance of physical activity for brain health during child development.

Brain structure and neurological and behavioural functioning in infants born preterm.

To examine: (1) relationships between brain structure, and concurrently assessed neurological and behavioural functioning, in infants born preterm at term-equivalent age (TEA; approximately 38-44wks); and (2) whether brain structure-function relationships differ between infants born very (24-29wks) and moderate-late (32-36wks) preterm. A total of 257 infants (91 very preterm, 166 moderate-late preterm; 120 males, 137 females) had structural magnetic resonance imaging (MRI) and neurological and behavioural assessments (Prechtl's general movements assessment, Neonatal Intensive Care Unit Network Neurobehavioral Scale [NNNS] and Hammersmith Neonatal Neurological Examination [HNNE]). Two hundred and sixty-three infants (90 very preterm, 173 moderate-late preterm; 131 males, 132 females) had diffusion MRI and assessments. Associations were investigated between assessment scores and global brain volumes using linear regressions, regional brain volumes using Voxel-Based Morphometry, and white matter microstructure using Tract-Based Spatial Statistics. Suboptimal scores on some assessments were associated with lower fractional anisotropy and/or higher axial, radial, and mean diffusivities in some tracts: NNNS attention and reflexes, and HNNE total score and tone, were associated with the corpus callosum and optic radiation; NNNS quality of movement with the corona radiata; HNNE abnormal signs with several major tracts. Brain structure-function associations generally did not differ between the very and moderate-late preterm groups. White matter microstructural alterations may be associated with suboptimal neurological and behavioural performance in some domains at TEA in infants born preterm. Brain structure-function relationships are similar for infants born very preterm and moderate-late preterm. Brain volume is not related to neurological/behavioural function in infants born preterm at term. White matter microstructure is related to some neurological/behavioural domains at term. Brain-behaviour relationships are generally similar for infants born very preterm and moderate-late preterm.

The plasticity of the corticospinal tract in children with obstetric brachial plexus palsy after Botulinum Toxin A treatment

Botulinum neurotoxin A (BTX-A) intervention has long-term benefits for children with obstetric brachial plexus palsy (OBPP). Although cortical plasticity has been widely studied, plasticity in white matter has not received as much attention. Here, six children with OBPP underwent functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) before and 6 months after BTX-A treatment. Surface electromyography (EMG) was recorded. The aim was to investigate changes in the corticospinal tract (CST) as an example longitudinal observation of white matter plasticity. Deterministic fiber tracking with a Fiber Assignment by Continuous Tracking algorithm was used to reconstruct the CST. Fiber tracts passing through a region of interest (ROI) in the posterior limb of the internal capsule and a target ROI in the upper-limb representation of M1 (defined by task-related fMRI) were selected as the CST. Motor performances were improved while EMG showed no significant difference 6 months after the treatment. We observed a significant increase in mean fractional anisotropy and a significant decrease in fiber number after treatment. We analyzed the correlations between DTI metrics and clinical motor assessments. Although the correlation results were not statistically significant, they support the notion that BTX-A treatment causes white matter plasticity and has a positive long-term outcome. Peripheral deafferentation may lead to altered information flow, resulting in the positive adaptation of white matter. This study provides novel insight into cerebral plasticity following peripheral nerve regeneration and indicates that a combination of relatively non-invasive therapies can accelerate plasticity of sensorimotor circuits and promote functional recovery in OBPP.

Zonally Magnified Oblique Multislice and Non-Zonally Magnified Oblique Multislice DWI of the Cervical Spinal Cord

The zonally magnified oblique multislice EPI (ZOOM-EPI) diffusion-weighted sequence has been visually shown to provide superior MR diffusion image quality compared with the full-FOV single-shot EPI sequence (non-ZOOM-EPI) in the adult cervical spinal cord. The purpose of this study was to examine the diffusion tensor imaging indices in the normal human cervical spinal cord between ZOOMED and non-ZOOMED DTI acquisitions and determine whether DTI values are comparable between direct and indirect age-matched groups. Fifty-four subjects 23-58 years of age (9 direct age-matched and 45 indirect age-matched) were scanned using a 1.5T scanner. Diffusion tensor indices including fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity were generated from the DTI dataset. These DTI values were calculated for both ZOOM and non-ZOOM acquisitions and compared at each intervertebral disc level. The variability of the DTI values for ZOOM and non-ZOOM sequences was measured using a coefficient of variation within direct and indirect age-matched controls. The mean diffusivity, axial diffusivity, and radial diffusivity values obtained along the cervical spinal cord in the age-matched controls showed a significant decrease using the ZOOM sequence (P = .05, P = .002, and P < .001). Mean fractional anisotropy showed a significant increase (P = .04) using the ZOOM sequence. The indirect age-matched controls showed a statistically significant increase in fractional anisotropy (P = .03) and a decrease in mean diffusivity (P = .002), axial diffusivity (P < .001), and radial diffusivity (P = .002) using the ZOOM sequence. Less variability has been shown in DTI using the ZOOM sequence compared with the non-ZOOM sequence in both direct and indirect age groups. The ZOOM sequence exhibited higher SNR (SNRZOOM = 22.84 ± 7.59) compared with the non-ZOOM sequence (SNRnon-ZOOM = 19.7 ± 7.05). However, when we used a 2-tailed t test assuming unequal variances, the ZOOM sequence did not demonstrate a statistically significant increase. ZOOM DTI acquisition methods provide superior image quality and precision over non-ZOOM techniques and are recommended over conventional full-FOV single-shot EPI DTI for clinical applications in cervical spinal cord imaging.

Impact of transcranial direct current stimulation on structural plasticity of the somatosensory system.

While there is a growing body of evidence regarding the behavioral and neurofunctional changes in response to the longitudinal delivery of transcranial direct current stimulation (tDCS), there is limited evidence regarding its structural effects. Therefore, the present study was intended to investigate the effect of repeatedly applied anodal tDCS over the primary somatosensory cortex on the gray matter (GM) and white matter (WM) compartment of the brain. Structural tDCS effects were, moreover, related to effects evidenced by functional imaging and behavioral assessment. tDCS was applied over the course of 5 days in 25 subjects with concomitant assessment of tactile acuity of the right and left index finger as well as imaging at baseline, after the last delivery of tDCS and at follow-up 4 weeks thereafter. Irrespective of the stimulation condition (anodal vs. sham), voxel-based morphometry revealed a behaviorally relevant decrease of GM in the precuneus co-localized with a functional change of its activity. Moreover, there was a decrease in GM of the bilateral lingual gyrus and the right cerebellum. Diffusion tensor imaging analysis showed an increase of fractional anisotropy exclusively in the tDCSanodal condition in the left frontal cortex affecting the final stretch of a somatosensory decision making network comprising the middle and superior frontal gyrus as well as regions adjacent to the genu of the corpus callosum. Thus, this is the first study in humans to identify structural plasticity in the GM compartment and tDCS-specific changes in the WM compartment in response to somatosensory learning.

Postnatal Microstructural Developmental Trajectory of Corpus Callosum Subregions and Relationship to Clinical Factors in Very Preterm Infants

Our objectives were to define the microstructural developmental trajectory of six corpus callosum subregions and identify perinatal clinical factors that influence early development of these subregions in very preterm infants. We performed a longitudinal cohort study of very preterm infants (32 weeks gestational age or younger) (N = 36) who underwent structural MRI and diffusion tensor imaging serially at four time points - before 32, 32, 38, and 52 weeks postmenstrual age. We divided the corpus callosum into six subregions, performed probabilistic tractography, and used linear mixed effects models to evaluate the influence of antecedent clinical factors on its microstructural growth trajectory. The genu and splenium demonstrated the most rapid developmental maturation, exhibited by a steep increase in fractional anisotropy. We identified several factors that favored greater corpus callosum microstructural development, including advancing postmenstrual age, higher birth weight, and college level or higher maternal education. Bronchopulmonary dysplasia, low 5-minute Apgar scores, caffeine therapy/apnea of prematurity and male sex were associated with reduced corpus callosum microstructural integrity/development over the first six months after very preterm birth. We identified a unique postnatal microstructural growth trajectory and associated clinical factor profile for each of the six corpus callosum subregions that is consistent with the heterogeneous functional role of these white matter subregions.

White matter pathways for prosodic structure building: A case study

The relevance of left dorsal and ventral fiber pathways for syntactic and semantic comprehension is well established, while pathways for prosody are little explored. The present study examined linguistic prosodic structure building in a patient whose right arcuate/superior longitudinal fascicles and posterior corpus callosum were transiently compromised by a vasogenic peritumoral edema. Compared to ten matched healthy controls, the patient’s ability to detect irregular prosodic structure significantly improved between pre- and post-surgical assessment. This recovery was accompanied by an increase in average fractional anisotropy (FA) in right dorsal and posterior transcallosal fiber tracts. Neither general cognitive abilities nor (non-prosodic) syntactic comprehension nor FA in right ventral and left dorsal fiber tracts showed a similar pre-post increase. Together, these findings suggest a contribution of right dorsal and inter-hemispheric pathways to prosody perception, including the right-dorsal tracking and structuring of prosodic pitch contours that is transcallosally informed by concurrent syntactic information.

Physical activity is associated with left corticospinal tract microstructure in bipolar depression.

Psychomotor retardation and reduced daily activities are core features of the depressive syndrome including bipolar disorder (BD). It was the aim of this study to investigate white matter microstructure of the motor system in BD during depression and its association with motor activity. We hypothesized reduced physical activity, microstructural alterations of motor tracts and different associations between activity levels and motor tract microstructure in BD. Nineteen bipolar patients with a current depressive episode (BD) and 19 healthy controls (HC) underwent diffusion weighted magnetic resonance imaging (DW-MRI)-scans. Quantitative motor activity was assessed with 24 h actigraphy recordings. Bilateral corticospinal tracts (CST), interhemispheric connections between the primary motor cortices (M1) and between the pre-supplementary motor areas (pre-SMA) were reconstructed individually based on anatomical landmarks using Diffusion Tensor Imaging (DTI) based tractography. Mean fractional anisotropy (FA) was sampled along the tracts. To enhance specificity of putative findings a segment of the optic radiation was reconstructed as comparison tract. Analyses were complemented with Tract Based Spatial Statistics (TBSS) analyses. BD had lower activity levels (AL). There was a sole increase of fractional anisotropy (FA) in BD in the left CST. Further, there was a significant group x AL interaction for FA of the left CST pointing to a selective positive association between FA and AL in BD. The comparison tract and TBSS analyses did not detect significant group differences. Our results point to white matter microstructure alterations of the left CST in BD. The positive association between motor activity and white matter microstructure suggests a compensatory role of the left CST for psychomotor retardation in BD.

Reduced brain glutamine in female varsity rugby athletes after concussion and in non-concussed athletes after a season of play.

The purpose of this study was to use non-invasive proton magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) to monitor changes in prefrontal white matter metabolite levels and tissue microstructure in female rugby players with and without concussion (ages 18-23, n = 64). Evaluations including clinical tests and 3 T MRI were performed at the beginning of a season (in-season) and followed up at the end of the season (off-season). Concussed athletes were additionally evaluated 24-72 hr (n = 14), three months (n = 11), and six months (n = 8) post-concussion. Reduced glutamine at 24-72 hr and three months post-concussion, and reduced glutamine/creatine at three months post-concussion were observed. In non-concussed athletes (n = 46) both glutamine and glutamine/creatine were lower in the off-season compared to in-season. Within the MRS voxel, an increase in fractional anisotropy (FA) and decrease in radial diffusivity (RD) were also observed in the non-concussed athletes, and correlated with changes in glutamine and glutamine/creatine. Decreases in glutamine and glutamine/creatine suggest reduced oxidative metabolism. Changes in FA and RD may indicate neuroinflammation or re-myelination. The observed changes did not correlate with clinical test scores suggesting these imaging metrics may be more sensitive to brain injury and could aid in assessing recovery of brain injury from concussion.

White Matter Microstructural Changes Following Quadrato Motor Training: A Longitudinal Study.

Diffusion tensor imaging (DTI) is an important way to characterize white matter (WM) microstructural changes. While several cross-sectional DTI studies investigated possible links between mindfulness practices and WM, only few longitudinal investigations focused on the effects of these practices on WM architecture, behavioral change, and the relationship between them. To this aim, in the current study, we chose to conduct an unbiased tract-based spatial statistics (TBSS) analysis (n = 35 healthy participants) to identify longitudinal changes in WM diffusion parameters following 6 and 12 weeks of daily Quadrato Motor Training (QMT), a whole-body mindful movement practice aimed at improving well-being by enhancing attention, coordination, and creativity. We also investigated the possible relationship between training-induced WM changes and concomitant changes in creativity, self-efficacy, and motivation. Our results indicate that following 6 weeks of daily QMT, there was a bilateral increase of fractional anisotropy (FA) in tracts related to sensorimotor and cognitive functions, including the corticospinal tracts, anterior thalamic radiations, and uncinate fasciculi, as well as in the left inferior fronto-occipital, superior and inferior longitudinal fasciculi. Interestingly, significant FA increments were still present after 12 weeks of QMT in most of the above WM tracts, but only in the left hemisphere. FA increase was accompanied by a significant decrease of radial diffusivity (RD), supporting the leading role of myelination processes in training-related FA changes. Finally, significant correlations were found between training-induced diffusion changes and increased self-efficacy as well as creativity. Together, these findings suggest that QMT can improve WM integrity and support the existence of possible relationships between training-related WM microstructural changes and behavioral change.

Comprehensive analysis of early fractional anisotropy changes in acute ischemic stroke.

Background and purposeCerebral ischemia leads to a rapid decrease of the apparent diffusion coefficient. For fractional anisotropy both increase and decrease have been reported in acute ischemic stroke. Aim of this study was to characterize early water diffusion changes in a homogenous group of acute stroke patients and to clarify the issue of early fractional anisotropy changes and their relation to time from symptom onset.MethodsMRI data of patients with acute ischemic stroke examined by diffusion tensor imaging within 8h after symptom were analyzed. We calculated fractional anisotropy, eigenvalues and the isotropic and anisotropic components of the diffusion tensor. The values were calculated as ratios between the ischemic lesion and a mirror region in the unaffected side and correlated with clinical parameters.ResultsWe included 63 patients: 49% female, mean age 69 ± 14 years, median NIHSS on admission 9 (IQR 4–14). For the whole sample, mean fractional anisotropy was increased (ratio: 1.083 ± 0.168), while all other diffusion parameters were decreased. Both the isotropic and anisotropic component of the diffusion tensor were decreased with a more pronounced decrease of the isotropic component (ratios: isotropic = 0.730 ± 0.106, anisotropic = 0.788 ± 0.127; p<0.001). There was no correlation of fractional anisotropy with time from symptom onset. Looking at individual patients, fractional anisotropy was increased in 70%. There were no differences in clinical characteristics between patients with increased and decreased fractional anisotropy.ConclusionFractional anisotropy increase in acute stroke results from a more pronounced decrease of the isotropic diffusion component and is not related to time from symptom onset. Thus, fractional anisotropy is not helpful as a surrogate marker of lesion age in the very first hours of stroke.

Diffusion tensor imaging marks dopaminergic and serotonergic lesions in the Parkinsonian monkey.

Diffusion tensor imaging has received major interest to highlight markers of neurodegeneration in Parkinson's disease. Whether the alteration of diffusion parameters mostly depicts dopaminergic lesions or can also reveal serotonergic denervation remains a question. The aim of this study was to determine the best diffusion tensor imaging markers of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 3,4-methylene-dioxy-methamphetamine (MDMA; also known as ecstasy) lesions in the nonhuman primate. We acquired measures of mean diffusivity and fractional anisotropy longitudinally (before and after MPTP and MDMA) and correlated them with severity of parkinsonism, PET imaging, and postmortem fiber quantification. MPTP-induced lesions were associated with increases of mean diffusivity within both the caudate nucleus and the anterior cingulate cortex, whereas MDMA-induced lesions caused an increase of fractional anisotropy within the caudate nucleus. These variations of diffusion tensor imaging correlated with the motor score. Taken together, these results demonstrate that diffusion measures within specific brain regions can mark severity of dopaminergic and serotonergic induced lesions in a neurotoxic nonhuman primate model of Parkinson's disease. © 2017 International Parkinson and Movement Disorder Society.

Age- and sex-related effects in children with mild traumatic brain injury on diffusion magnetic resonance imaging properties: A comparison of voxelwise and tractography methods.

Although there are several techniques to analyze diffusion-weighted imaging, any technique must be sufficiently sensitive to detect clinical abnormalities. This is especially critical in disorders like mild traumatic brain injury (mTBI), where pathology is likely to be subtle. mTBI represents a major public health concern, especially for youth under 15 years of age. However, the developmental period from birth to 18 years is also a time of tremendous brain changes. Therefore, it is important to establish the degree of age- and sex-related differences. Participants were children aged 8-15 years with mTBI or mild orthopedic injuries. Imaging was obtained within 10 days of injury. We performed tract-based spatial statistics (TBSS), deterministic tractography using Automated Fiber Quantification (AFQ), and probabilistic tractography using TRACULA (TRActs Constrained by UnderLying Anatomy) to evaluate whether any method provided improved sensitivity at identifying group, developmental, and/or sex-related differences. Although there were no group differences from any of the three analyses, many of the tracts, but not all, revealed increases of fractional anisotropy and decreases of axial, radial, and mean diffusivity with age. TBSS analyses resulted in age-related changes across all white matter tracts. AFQ and TRACULA revealed age-related changes within the corpus callosum, cingulum cingulate, corticospinal tract, inferior and superior longitudinal fasciculus, and uncinate fasciculus. The results are in many ways consistent across all three methods. However, results from the tractography methods provided improved sensitivity and better tract-specific results for identifying developmental and sex-related differences within the brain.

Ventricular myocardium development and the role of connexins in the human fetal heart

The developmental timeline of the human heart remains elusive. The heart takes on its characteristic four chambered appearance by ~56 days gestational age (DGA). However, owing to the complexities (both technical and logistical) of exploring development in utero, we understand little of how the ventricular walls develop. To address this, we employed diffusion tensor magnetic resonance imaging to explore the architecture and tissue organization of the developing heart aged 95–143 DGA. We show that fractional anisotropy increases (from ~0.1 to ~0.5), diffusion coefficients decrease (from ~1 × 10−3mm2/sec to ~0.4 × 10−3mm2/sec), and fiber paths, extracted by tractography, increase linearly with gestation, indicative of the increasing organization of the ventricular myocytes. By 143 DGA, the developing heart has the classical helical organization observed in mature mammalian tissue. This was accompanied by an increase in connexin 43 and connexin 40 expression levels, suggesting their role in the development of the ventricular conduction system and that electrical propagation across the heart is facilitated in later gestation. Our findings highlight a key developmental window for the structural organization of the fetal heart.

Increase in gray matter volume and white matter fractional anisotropy in the motor pathways of patients with secondarily generalized neocortical seizures

PurposeConvulsive motor activity is a clinical manifestation of secondarily generalized seizures evolving from different focal regions. The way in which the motor seizures present themselves is not very different from most of the generalized seizures in and between epilepsy patients. This might point towards the involvement of motor-related cortices and corticospinal pathway for wide spread propagation of epileptic activity. Our aim was to identify changes in the cerebral structures and to correlate clinical variables with structural changes particularly in the motor-related cortices and pathway of patients with generalized convulsions from different seizure foci. MethodsSixteen patients with focal onset and secondarily generalized seizures were included, along with sixteen healthy volunteers. Structural differences were analysed by measuring grey matter (GM) volume and thickness via T1-weighted MRI, and white matter (WM) fractional anisotropy (FA) via diffusion tensor imaging. GM and WM microstructural properties were compared between patients and controls by voxel- and surface- based analyses. Next, morphometric findings were correlated with seizure severity and disease duration to identify the pathologic process. Key findingsIn addition to widely reduced GM and WM properties, increased GM volume in the bilateral precentral gyri and paracentral lobules, and elevated regional FA in the bilateral corticospinal tracts adjacent to these motor -related GM were observed in patients and with higher statistical difference in the sub-patient group with drug-resistance. SignificanceThe increment of GM volume and WM FA in the motor pathway positively correlated with severity and duration of epilepsy. The demonstrated microstructural changes of motor pathways imply a plastic process of motor networks in the patients with frequent generalization of focal seizures.