Dafna Sussman

The autism puzzle: Diffuse but not pervasive neuroanatomical abnormalities in children with ASD

Autism Spectrum Disorder (ASD) is a clinically diagnosed, heterogeneous, neurodevelopmental condition, whose underlying causes have yet to be fully determined. A variety of studies have investigated either cortical, subcortical, or cerebellar anatomy in ASD, but none have conducted a complete examination of all neuroanatomical parameters on a single, large cohort. The current study provides a comprehensive examination of brain development of children with ASD between the ages of 4 and 18 years who are carefully matched for age and sex with typically developing controls at a ratio of one-to-two. Two hundred and ten magnetic resonance images were examined from 138 Control (116 males and 22 females) and 72 participants with ASD (61 males and 11 females). Cortical segmentation into 78 brain-regions and 81,924 vertices was conducted with CIVET which facilitated a region-of-interest- (ROI-) and vertex-based analysis, respectively. Volumes for the cerebellum, hippocampus, striatum, pallidum, and thalamus and many associated subregions were derived using the MAGeT Brain algorithm. The study reveals cortical, subcortical and cerebellar differences between ASD and Control group participants. Diagnosis, diagnosis-by-age, and diagnosis-by-sex interaction effects were found to significantly impact total brain volume but not total surface area or mean cortical thickness of the ASD participants. Localized (vertex-based) analysis of cortical thickness revealed no significant group differences, even when age, age-range, and sex were used as covariates. Nonetheless, the region-based cortical thickness analysis did reveal regional changes in the left orbitofrontal cortex and left posterior cingulate gyrus, both of which showed reduced age-related cortical thinning in ASD. Our finding of region-based differences without significant vertex-based results likely indicates non-focal effects spanning the entirety of these regions. The hippocampi, thalamus, and globus pallidus, were smaller in volume relative to total cerebrum in the ASD participants. Various sub-structures showed an interaction of diagnosis-by-age, diagnosis-by-sex, and diagnosis-by-age-range, in the case where age was divided into childhood (age < 12) and adolescence (12 < age < 18). This is the most comprehensive imaging-based neuro-anatomical pediatric and adolescent ASD study to date. These data highlight the neurodevelopmental differences between typically developing children and those with ASD, and support aspects of the hypothesis of abnormal neuro-developmental trajectory of the brain in ASD.

The developing human brain: age‐related changes in cortical, subcortical, and cerebellar anatomy

This study is the first to characterize normal development and sex differences across neuroanatomical structures in cortical, subcortical, and cerebellar brain regions in a single large cohort.

Gestational ketogenic diet programs brain structure and susceptibility to depression & anxiety in the adult mouse offspring.

The ketogenic diet (KD) has seen an increase in popularity for clinical and non‐clinical purposes, leading to rise in concern about the diets impact on following generations. The KD is known to have a neurological effect, suggesting that exposure to it during prenatal brain development may alter neuro‐anatomy. Studies have also indicated that the KD has an anti‐depressant effect on the consumer. However, it is unclear whether any neuro‐anatomical and/or behavioral changes would occur in the offspring and persist into adulthood.

A gestational ketogenic diet alters maternal metabolic status as well as offspring physiological growth and brain structure in the neonatal mouse

BackgroundThe use of the ketogenic diet (KD) among women of child-bearing age has been increasing, leading to increased interest in identifying the diet’s suitability during gestation. To date, no studies have thoroughly investigated the effect of a gestational KD on offspring growth. Since ketones have been reported to play a role in cerebral lipid and myelin synthesis, it is particularly important to investigate the diet’s impact on brain anatomy of the offspring.MethodsTo fill this knowledge gap we imaged CD-1 mouse neonates whose mothers were fed either a standard diet (SD) or a KD prior to and during gestation. Images were collected at postnatal (P) 11.5 and 21.5 using Magnetic Resonance Imaging (MRI). Maternal metabolic status was also tracked during lactation, by following their body weight, blood glucose, ketone, cholesterol, and triglyceride concentrations.ResultsThe KD dams exhibit a significant reduction in maternal fertility and litter size, as well as a high risk of developing fatal ketoacidosis by mid-lactation. To increase survival of the KD dams and offspring, fostering of P2.5 pups (from both KD and SD litters) by SD-foster dams was carried out. This resulted in stabilization of blood ketones of the KD dams, and aversion of the fatal ketoacidosis. We also note a slower and smaller weight loss for the KD compared with the SD dams. The average fostered KD pup exhibits retarded growth by P21.5 compared with the average fostered SD pup. An anatomical comparison of their brains further revealed significant structural differences at P11.5, and particularly at P21.5. The KD brain shows a relative bilateral decrease in the cortex, fimbria, hippocampus, corpus callosum and lateral ventricle, but a relative volumetric enlargement of the hypothalamus and medulla.ConclusionA gestational ketogenic diet deleteriously affects maternal fertility and increases susceptibility to fatal ketoacidosis during lactation. Prenatal and early postnatal exposure to a ketogenic diet also results in significant alterations to neonatal brain structure, and results in retarded physiological growth. These alterations could be accompanied by functional and behavioural changes in later postnatal life.

Effects of a ketogenic diet during pregnancy on embryonic growth in the mouse

BackgroundThe increasing use of the ketogenic diet (KD), particularly by women of child-bearing age, raises a question about its suitability during gestation. To date, no studies have thoroughly investigated the direct implications of a gestational ketogenic diet on embryonic development.MethodsTo fill this knowledge gap we imaged CD-1 mouse embryos whose mothers were fed either a Standard Diet (SD) or a KD 30 days prior to, as well as during gestation. Images were collected at embryonic days (E) 13.5 using Optical Projection Tomography (OPT) and at E17.5 using Magnetic Resonance Imaging (MRI).ResultsAn anatomical comparison of the SD and KD embryos revealed that at E13.5 the average KD embryo was volumetrically larger, possessed a relatively larger heart but smaller brain, and had a smaller pharynx, cervical spinal cord, hypothalamus, midbrain, and pons, compared with the average SD embryo. At E17.5 the KD embryo was found to be volumetrically smaller with a relatively smaller heart and thymus, but with enlarged cervical spine, thalamus, midbrain and pons.ConclusionA ketogenic diet during gestation results in alterations in embryonic organ growth. Such alterations may be associated with organ dysfunction and potentially behavioral changes in postnatal life.

Concussion induces focal and widespread neuromorphological changes

Concussion induces transient, and oftentimes chronic, lingering impairment to mental functioning, which must be driven by some underlying neurobiological perturbation - however, the physical changes related to sequelae are difficult to detect. Previous imaging studies on concussion have focused on alterations to cortical anatomy, but few have examined the cerebrum, subcortex, and cerebellum. Here, we present an analysis of these structures in a single cohort (all males, 21 patients, 22 controls) using MRI and diagnosed with a single-concussive episode in the acute and sub-acute stages of injury. Structural images were segmented into 78 cortical brain regions and 81,924 vertices using the CIVET algorithm. Subcortical volumetric analyses of the cerebellum, thalamus, globus pallidus, caudate and putamen were conducted following segmentation. Participants with concussion were found to have reduced white and grey matter volume, total cortical volume, as well as cortical thinning, primarily in left frontal areas. No differences were observed in the cerebellum or subcortical structures. In conclusion, just a single concussive episode induces measurable changes in brain structure manifesting as diffuse and local patterns of altered neuromorphometry.

Impact of maternal physical activity on fetal breathing and body movement—A review

Fetal movements, which include body and breathing movement, are important indicators of fetal well-being and nervous system development. These have been shown to be affected by intrauterine conditions. While maternal physical activity does induce a change in intrauterine conditions and physiology, its impact on fetal movements is still unclear. This paper will provide a brief review of the literature and outline the current knowledge with regards to the effects of maternal exercise on fetal body and breathing movements.

Eye model for the ground squirrel

This paper presents an anatomically-correct eye model for the ground squirrel, a diurnal, highly-developed mammal with high visual acuity. This model can assist in understanding the relationship between ocular structural development and its corresponding function. The eye model is constructed based on anatomical measurements of thicknesses and indices of refraction of the various ocular media. The model then derives the gradient index distribution of the crystalline lens using a ray tracing method with a Monte Carlo optimization. Results indicate a diffraction-limited ocular behaviour, implying the visual acuity of the ground squirrel is more likely to be limited by photoreceptor density and diffraction effects, than by ocular geometry.

The science calibration system for the TMT NFIRAOS and client instruments: requirements and design studies

We present the results of the design studies of the science calibration system for the adaptive optics and infrared instruments of the Thirty Meter Telescope. The two major requirements of the science calibration system are to provide pupil-simulated telescope beams to the adaptive optics system for calibration of the telescope pupil and to provide flatfielding and wavelength-calibration illuminations to client instruments of the adaptive optics system. Our current system is composed an integrating sphere with calibration light sources, a retractable pupil-mask system, a lens assembly consisting of a pair of achromatic triplets, and fold mirrors. This system appears to be capable of producing highlyuniform of f/15 beams at the telescope focal plane and pupil simulation at a pupil location within the adaptive optics system. We describe the present design and development of the calibration system along with relevant analyses.

Introductory editorial: Effects of maternal physical activity on the fetus.

Regular physical activity during an uncomplicated pregnancy has been shown to improve health-related pregnancy outcomes while being harmless for the fetus. The benefits of regular exercise led the American Association of Obstetricians and Gynaecologists (ACOG) to recommend that a minimum of 30 min of moderate exercise a day occurs on most days of the week. Many studies have been published on the health benefits of exercise during pregnancy. These benefits include managing weight gain to lower the risk of hypertension, preeclampsia, and gestational diabetes. Despite these findings and the recommendations by the ACOG, many women still decrease their physical activity level during pregnancy due to reasons such as low motivation, per