Increase In Brain Volume Research Articles

A Dual Parameter Synchronous Monitoring System of Brain Edema Based on the Reflection and Transmission Characteristics of Two-Port Test Network

As a common secondary disease, edema after traumatic brain injury (TBI) can increase brain volume, resulting in elevated intracranial pressure (ICP), brain shift, and cerebral hernia, and can eventually lead to death. The real-time continuous monitoring of edema may significantly reduce mortality and disability. In this paper, a dual-parameter synchronous monitoring system of edema based on the reflection and transmission characteristics of the two-port test network was established; 15 rabbits were chosen to perform 24-h reflection phase shift (RPS) and transmission phase shift (TPS) simultaneously monitoring the experiments of brain edema. With the development of brain edema, the variation law of the RPS and TPS was investigated. Combined with the power amplitude spectrum and the principle of the two-port test network, the influence of frequency on the detection sensitivity of RPS and TPS was analyzed in detail, and the optimal detection frequency point was found. After that, the classification of three different degrees of edema is performed by the BP algorithm. In the animal experiment, the RPS showed a continuous increasing trend within time, and it presented the variation of (9.35910° ± 1.65702°), (12.60117° ± 2.30218°), and (16.33423° ± 2.11118°) after 6, 12, and 24 h, respectively. Meanwhile, the TPS showed a continuous downward trend with the variation of (-12.62555° ± 0.99441°), (-19.23976° ± 1.27488°), and (-27.26285° ± 2.62291°) after 6, 12, and 24 h, respectively. The RPS was negatively correlated with the TPS. The RPS and the TPS together as a recognition feature can achieve 100% accurate classification of three different brain edema severities. Based on these results, it can be concluded that the system established in this paper can monitor gradual increases in brain edema severity. Furthermore, neither the RPS nor the TPS can be set as the recognition feature alone to achieve the completely accurate classification, which shows the necessity of presenting two parameters in the monitoring process.

Neural signatures of the risk for bipolar disorder: A meta-analysis of structural and functional neuroimaging studies.

Widespread functional and structural alterations in the brain have been extensively reported in unaffected relatives (RELs) of patients with bipolar disorder (BD) who are at genetic risk for BD. A sufficiently powered meta-analysis of structural (sMRI) and functional magnetic resonance imaging (fMRI) alterations in RELs is still lacking. Functional and structural magnetic resonance imaging studies investigating RELs and healthy controls (HCs) published by July 2017 were included in the meta-analyses. Study procedures were conducted in accordance with the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. Random-effects coordinate-based meta-analyses were performed across all the studies per imaging modality using Seed-based d Mapping (SDM). For fMRI studies, meta-analyses were calculated for each task type. For sMRI studies, regional volumetric changes-analyses were estimated using R. Finally, multimodal meta-analyses of structural and functional abnormalities were performed. Sixty-nine imaging studies (2195 RELs and 3169 HCs) were included in the meta-analyses. RELs showed hyperactivation in the fronto-striatal regions as well as parietal hypoactivation during cognition. Also, activation was increased in the amygdala during emotional processing and in the orbitofrontal cortex during reward, respectively. Frontal and superior temporal cortex were hypertrophic in RELs. The right inferior frontal gyrus (rIFG) showed both increased activation during cognitive tasks and greater volume in RELs. Our findings demonstrate that increased brain volume and activation are present in RELs and may represent intermediate phenotypes for the disorder. Furthermore, some neural changes including increased rIFG volume may be associated with the resilience to BD.

Heterozygosity for Nuclear Factor One X in mice models features of Malan syndrome.

BackgroundNuclear Factor One X (NFIX) haploinsufficiency in humans results in Malan syndrome, a disorder characterized by overgrowth, macrocephaly and intellectual disability. Although clinical assessments have determined the underlying symptomology of Malan syndrome, the fundamental mechanisms contributing to the enlarged head circumference and intellectual disability in these patients remains undefined.MethodsHere, we used Nfix heterozygous mice as a model to investigate these aspects of Malan syndrome. Volumetric magnetic resonance imaging (MRI) was used to calculate the volumes of 20 brain sub regions. Diffusion tensor MRI was used to perform tractography-based analyses of the corpus callosum, hippocampal commissure, and anterior commissure, as well as structural connectome mapping of the whole brain. Immunohistochemistry examined the neocortical cellular populations. Two behavioral assays were performed, including the active place avoidance task to assess spatial navigation and learning and memory function, and the 3-chambered sociability task to examine social behaviour.FindingsAdult Nfix+/− mice exhibit significantly increased brain volume (megalencephaly) compared to wildtypes, with the cerebral cortex showing the highest increase. Moreover, all three forebrain commissures, in particular the anterior commissure, revealed significantly reduced fractional anisotropy, axial and radial diffusivity, and tract density intensity. Structural connectome analyses revealed aberrant connectivity between many crucial brain regions. Finally, Nfix+/− mice exhibit behavioral deficits that model intellectual disability.InterpretationCollectively, these data provide a significant conceptual advance in our understanding of Malan syndrome by suggesting that megalencephaly underlies the enlarged head size of these patients, and that disrupted cortical connectivity may contribute to the intellectual disability these patients exhibit.FundAustralian Research Council (ARC) Discovery Project Grants, ARC Fellowship, NYSTEM and Australian Postgraduate Fellowships.

Functional recovery after the systemic administration of mesenchymal stem cells in a rat model of neonatal hypoxia-ischemia.

The authors intravenously infused mesenchymal stem cells (MSCs) into a rat model of neonatal hypoxia-ischemia and found improvements in functional outcome, increased brain volume, and enhanced synaptogenesis. The results of this animal study suggest that the intravenous administration of MSCs should be further explored as a potential treatment for patients suffering from cerebral palsy after hypoxic-ischemic encephalopathy.

Targeting phosphocreatine metabolism in relapsing-remitting multiple sclerosis: evaluation with brain MRI, 1H and 31P MRS, and clinical and cognitive testing.

Fluoxetine and prucalopride might change phosphocreatine (PCr) levels via the cAMP-PKA pathway, an interesting target in the neurodegenerative mechanisms of MS. We conducted a two-center double-blind, placebo-controlled, randomized trial including 48 relapsing-remitting MS patients. Patients were randomized to receive placebo (n = 13), fluoxetine (n = 15), or prucalopride (n = 14) for 6 weeks. Proton (1H) and phosphorus (31P) magnetic resonance spectroscopy (MRS) as well as volumetric and perfusion MR imaging were performed at weeks 0, 2, and 6. Clinical and cognitive testing were evaluated at weeks 0 and 6. No significant changes were observed for both 31P and 1H MRS indices. We found a significant effect on white matter volume and a trend towards an increase in grey matter and whole brain volume in the fluoxetine group at week 2; however, these effects were not sustained at week 6 for white matter and whole brain volume. Fluoxetine and prucalopride showed a positive effect on 9-HPT, depression, and fatigue scores. Both fluoxetine and prucalopride had a symptomatic effect on upper limb function, fatigue, and depression, but this should be interpreted with caution. No effect of treatment was found on 31P and 1H MRS parameters, suggesting that these molecules do not influence the PCr metabolism.

Ischemic Brain Injury Leads to Brain Edema via Hyperthermia-Induced TRPV4 Activation.

Brain edema is characterized by an increase in net brain water content, which results in an increase in brain volume. Although brain edema is associated with a high fatality rate, the cellular and molecular processes of edema remain largely unclear. Here, we developed an in vitro model of ischemic stroke-induced edema in which male mouse brain slices were treated with oxygen-glucose deprivation (OGD) to mimic ischemia. We continuously measured the cross-sectional area of the brain slice for 150 min under macroscopic microscopy, finding that OGD induces swelling of brain slices. OGD-induced swelling was prevented by pharmacologically blocking or genetically knocking out the transient receptor potential vanilloid 4 (TRPV4), a member of the thermosensitive TRP channel family. Because TRPV4 is activated at around body temperature and its activation is enhanced by heating, we next elevated the temperature of the perfusate in the recording chamber, finding that hyperthermia induces swelling via TRPV4 activation. Furthermore, using the temperature-dependent fluorescence lifetime of a fluorescent-thermosensitive probe, we confirmed that OGD treatment increases the temperature of brain slices through the activation of glutamate receptors. Finally, we found that brain edema following traumatic brain injury was suppressed in TRPV4-deficient male mice in vivo Thus, our study proposes a novel mechanism: hyperthermia activates TRPV4 and induces brain edema after ischemia.SIGNIFICANCE STATEMENT Brain edema is characterized by an increase in net brain water content, which results in an increase in brain volume. Although brain edema is associated with a high fatality rate, the cellular and molecular processes of edema remain unclear. Here, we developed an in vitro model of ischemic stroke-induced edema in which mouse brain slices were treated with oxygen-glucose deprivation. Using this system, we showed that the increase in brain temperature and the following activation of the thermosensitive cation channel TRPV4 (transient receptor potential vanilloid 4) are involved in the pathology of edema. Finally, we confirmed that TRPV4 is involved in brain edema in vivo using TRPV4-deficient mice, concluding that hyperthermia activates TRPV4 and induces brain edema after ischemia.

Utility of Transcranial Doppler in the Coordination of Transplants: 10 Years of Experience

Transcranial Doppler (TCD) integrated to multimodal neuromonitoring of neurocritical patients is a useful tool in the clinical follow-up. A retrospective and descriptive study of 194 patients who were admitted into the intensive care unit (ICU) was carried out from December 2007 to February 2017. We analyzed the distribution of study frequencies with respect to the pathologies that motivated them, the characteristics of patients who evolved to brain death (BD), and most frequent patterns of cerebral circulatory arrest. Ninety-four of the patients that evolved to BD required 126 studies during their follow-up. The insonation of the 2 middle cerebral arteries and the basilar artery was the most frequent combination (30%). Most frequent reasons of request for a TCD included apnea test intolerance and reduction of waiting time and sedation analgesia. These 10 years of experience have enabled a deeper understanding of the cerebral hemodynamics and the identification of common patterns of high resistance to different pathologies (subarachnoid hemorrhage, severe skull trauma, anoxic ischemia, ammonia encephalopathy) that explain the severity of the acute brain injury, related to the increase of brain volume and its deleterious consequence: the elevation of intracranial pressure (ICP). In the same way, because invasive ICP monitoring is not available in all cases, with a tomographic scan of the skull we have been able to observe a correlation of some imaging signs suggestive of intracranial hypertension with patterns of high resistance obtained by the TCD in the pathologies mentioned. We recommend that each ICU that assists neurocritical patients should have TCD equipment and the skilled personnel to carry out the technique.

Osmotic Shifts, Cerebral Edema, and Neurologic Deterioration in Severe Hepatic Encephalopathy.

We sought to determine the effect of acute electrolyte and osmolar shifts on brain volume and neurologic function in patients with liver failure and severe hepatic encephalopathy. Retrospective analysis of brain CT scans and clinical data. Tertiary care hospital ICUs. Patients with acute or acute-on-chronic liver failure and severe hepatic encephalopathy. Clinically indicated CT scans and serum laboratory studies. Change in intracranial cerebrospinal fluid volume between sequential CT scans was measured as a biomarker of acute brain volume change. Corresponding changes in serum osmolality, chemistry measurements, and Glasgow Coma Scale were determined. Associations with cerebrospinal fluid volume change and Glasgow Coma Scale change for initial volume change assessments were identified by Spearman's correlations (rs) and regression models. Consistency of associations with repeated assessments was evaluated using generalized estimating equations. Forty patients were included. Median baseline osmolality was elevated (310 mOsm/Kg [296-321 mOsm/Kg]) whereas sodium was normal (137 mEq/L [134-142 mEq/L]). Median initial osmolality change was 9 mOsm/kg (5-17 mOsm/kg). Neuroimaging consistent with increased brain volume occurred in 27 initial assessments (68%). Cerebrospinal fluid volume change was more strongly correlated with osmolality (r = 0.70; p = 4 × 10) than sodium (r = 0.28; p = 0.08) change. Osmolality change was independently associated with Glasgow Coma Scale change (p = 1 × 10) and cerebrospinal fluid volume change (p = 2.7 × 10) in initial assessments and in generalized estimating equations using all 103 available assessments. Acute decline in osmolality was associated with brain swelling and neurologic deterioration in severe hepatic encephalopathy. Minimizing osmolality decline may avoid neurologic deterioration.

Abstract 52: Global Cerebral Edema in Patients With Primary Intracerebral Hemorrhage: Results From Brain Edema at Cerebral Hemorrhage (BEACH) Study

Background: Recent data supports presence of neuronal injury and blood brain barrier breakdown in brain regions distant to hematoma in patients with intracerebral hemorrhage (ICH). We determined the prevalence of global cerebral edema and its impact on clinical outcome in patients with ICH recruited in a multicenter clinical trial. Methods: BEACH was a pre-planned prospective observational study (N=278) nested in the Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH)-2 clinical trial which randomized ICH patients with SBP ≥ 180 mmHg who presented within 4.5 hours of symptom onset. The aim of the ATACH-2 was to ascertain whether SBP reduction to < 140 mmHg would yield reduction in death and disability (defined as modified Rankin Scale 4-6) at 90 days compared to the current guideline. Total brain volume, parenchymal hematoma volume, and peri-hematoma edema volume were measured on CT scans acquired on admission and at 24 (±8) hours (and later intervals when available) post-randomization using computerized image analysis software(Analyze. Inc). Global cerebral edema was defined as 5% or greater increase in the brain volume (excluding parenchymal hematoma and peri-hematoma edema volumes) on follow up CT scan compared with baseline scan. Results: A total of 48 (17%) of 278 patients had global cerebral edema by 24 hours CT scan. The median increase in total brain volume was 9 cm3 (range 5 - 20 cm3). Additional occurrence of global cerebral edema was seen in 3% and 1% of patients by 48 hours and 72 hours, respectively. Baseline characteristics were similar, but median NIHSS was higher and median GCS score was lower in patients with global cerebral edema. The prevalence of global cerebral edema was significantly lower in intensive SBP reduction group compared to standard SBP reduction group (12% vs 23%, p-value: 0.02). While not statistically significant, higher rates of death or disability at 90 days were observed among subjects with global cerebral edema within 24 hours (48% vs 36%, p-value: 0.12) Conclusion: Global cerebral edema at 24 hours occurred in 17% of the BEACH subgroup of ATACH 2 subjects. Global cerebral edema was associated with higher level of clinical severity of disease and its prevalence was significantly lower among intensive SBP reduction group.

Effect of electroconvulsive therapy on hippocampal and amygdala volumes: systematic review and meta-analysis.

Electroconvulsive therapy (ECT) is one of the most effective treatments for depression, although the underlying mechanisms remain unclear. Animal studies have shown that electroconvulsive shock induced neuroplastic changes in the hippocampus. Aims To summarise volumetric magnetic resonance imaging studies investigating the effects of ECT on limbic brain structures. A systematic review and meta-analysis was conducted to assess volumetric changes of each side of the hippocampus and amygdala before and after ECT. Standardised mean difference (SMD) was calculated. A total of 8 studies (n = 193) were selected for our analyses. Both right and left hippocampal and amygdala volumes increased after ECT. Meta-regression analyses revealed that age, percentage of those responding and percentage of those in remission were negatively associated with volume increases in the left hippocampus. ECT increased brain volume in the limbic structures. The clinical relevance of volume increase needs further investigation. Declaration of interest None.

Noninvasive measures of brain edema predict outcome in pediatric cerebral malaria.

Background:Increased brain volume (BV) and subsequent herniation are strongly associated with death in pediatric cerebral malaria (PCM), a leading killer of children in developing countries. Accurate noninvasive measures of BV are needed for optimal clinical trial design. Our objectives were to examine the performance of six different magnetic resonance imaging (MRI) BV quantification measures for predicting mortality in PCM and to review the advantages and disadvantages of each method.Methods:Receiver operator characteristics were generated from BV measures of MRIs of children admitted to an ongoing research project with PCM between 2009 and 2014. Fatal cases were matched to the next available survivor. A total of 78 MRIs of children aged 5 months to 13 years (mean 4.0 years), of which 45% were males, were included.Results:Areas under the curve (AUC) with 95% confidence interval on measures from the initial MRIs were: Radiologist-derived score = 0.69 (0.58–0.79; P = 0.0037); prepontine cistern anteroposterior (AP) dimension = 0.70 (0.56–0.78; P = 0.0133); SamKam ratio [Rt. parietal lobe height/(prepontine AP dimension + fourth ventricle AP dimension)] = 0.74 (0.63–0.83; P = 0.0002); and global cerebrospinal fluid (CSF) space ascertained by ClearCanvas = 0.67 (0.55–0.77; P = 0.0137). For patients with serial MRIs (n = 37), the day 2 global CSF space AUC was 0.87 (0.71–0.96; P < 0.001) and the recovery factor (CSF volume day 2/CSF volume day 1) was 0.91 (0.76–0.98; P < 0.0001). Poor prognosis is associated with radiologist score of ≥7; prepontine cistern dimension ≤3 mm; cisternal CSF volume ≤7.5 ml; SamKam ratio ≥6.5; and recovery factor ≤0.75.Conclusion:All noninvasive measures of BV performed well in predicting death and providing a proxy measure for brain volume. Initial MRI assessment may inform future clinical trials for subject selection, risk adjustment, or stratification. Measures of temporal change may be used to stage PCM.

The choice of the hypnotic drug (volatile or propofol) for maintenance of anesthesia does not influence surgical conditions during cranioplasty.

Background and Aims:In contrast to propofol, volatile agents are often considered harmful to maintain anesthesia due to increasing brain volume and potential deleterious effects. Patients for cranioplasty, including patients with large bone defects, could be susceptible for intraoperative complications but have not properly been investigated so far. The aim of the present study was to evaluate brain swelling, intraoperative conditions, surgical course, and postoperative complication rates of propofol-based vs. volatile-based anesthesia.Material and Methods:In this monocentric, retrospective, and observational study, we collected demographic, clinical, and outcome data of patients undergoing cranioplasty between December 2010 and September 2014. According to the hypnotic drug used, patients were assigned to either a propofol or a volatile group. The primary outcome parameter was brain swelling. For comparison of the groups, univariate analysis was performed using Chi-square and Mann–Whitney-U test.Results:One hundred and one patients were identified in the period. Twenty-three patients were excluded due to cerebrospinal fluid diversion. Baseline characteristics and preoperative conditions did not vary between the groups except a higher body mass index and positive end-expiratory pressure (PEEP) in the propofol group. The choice of anesthesia (volatile or intravenous) influence neither the intraoperative local conditions nor postoperative complication rate. No significant risk factor for impaired bone flap placement was identified.Conclusions:In a well-defined cohort, the choice of the anesthetic agent does not influence the degree of intraoperative brain swelling, bone flap fit, and postoperative course.

A physical multifield model predicts the development of volume and structure in the human brain

The prenatal development of the human brain is characterized by a rapid increase in brain volume and a development of a highly folded cortex. At the cellular level, these events are enabled by symmetric and asymmetric cell division in the ventricular regions of the brain followed by an outwards cell migration towards the peripheral regions. The role of mechanics during brain development has been suggested and acknowledged in past decades, but remains insufficiently understood. Here we propose a mechanistic model that couples cell division, cell migration, and brain volume growth to accurately model the developing brain between weeks 10 and 29 of gestation. Our model accurately predicts a 160-fold volume increase from 1.5 cm3 at week 10 to 235 cm3 at week 29 of gestation. In agreement with human brain development, the cortex begins to form around week 22 and accounts for about 30% of the total brain volume at week 29. Our results show that cell division and coupling between cell density and volume growth are essential to accurately model brain volume development, whereas cell migration and diffusion contribute mainly to the development of the cortex. We demonstrate that complex folding patterns, including sinusoidal folds and creases, emerge naturally as the cortex develops, even for low stiffness contrasts between the cortex and subcortex.

Improved Precision of Automatic Brain Volume Measurements in Patients with Clinically Isolated Syndrome and Multiple Sclerosis Using Edema Correction.

The presence of edema will result in increased brain volume, which may obscure progressing brain atrophy. Similarly, treatment-induced edema reduction may appear as accelerated brain tissue loss (pseudoatrophy). The purpose of this study was to correlate brain tissue properties to brain volume, to investigate the possibilities for edema correction and the resulting improvement of the precision of automated brain volume measurements. A group of 38 patients with clinically isolated syndrome or newly diagnosed MS were imaged at inclusion and after 1, 2, and 4 years using an MR quantification sequence. Brain volume, relaxation rates (R1 and R2), and proton density were measured by automated software. The reduction of normalized brain volume with time after inclusion was 0.273%/year. The mean SDs were 0.508%, 0.526%, 0.454%, and 0.687% at baseline and 1, 2, and 4 years. Linear regression of the relative change of normalized brain volume and the relative change of R1, R2, and proton density showed slopes of -0.198 (P < .001), 0.156 (P = .04), and 0.488 (P < .001), respectively. After we applied the measured proton density as a correction factor, the mean SDs decreased to 24.2%, 4.8%, 33.3%, and 17.4%, respectively. The observed atrophy rate reduced from 0.273%/year to 0.238%/year. Correlations between volume and R1, R2, and proton density were observed in the brain, suggesting that a change of brain tissue properties can affect brain volume. Correction using these parameters decreased the variation of brain volume measurements and may have reduced the effect of pseudoatrophy.

Increased Brain Glucose Uptake After 12 Weeks of Aerobic High-Intensity Interval Training in Young and Older Adults

Aerobic exercise training can increase brain volume and blood flow, but the impact on brain metabolism is less known. We determined whether high-intensity interval training (HIIT) increases brain metabolism by measuring brain glucose uptake in younger and older adults. Brain glucose uptake was measured before and after HIIT or a sedentary (SED) control period within a larger exercise study. Study procedures were performed at the Mayo Clinic in Rochester, MN. Participants were younger (18 to 30 years) or older (65 to 80 years) SED adults who were free of major medical conditions. Group sizes were 15 for HIIT (nine younger and six older) and 12 for SED (six younger and six older). Participants completed 12 weeks of HIIT or SED. HIIT was 3 days per week of 4 × 4 minute intervals at over 90% of peak aerobic capacity (VO2peak) with 2 days per week of treadmill walking at 70% VO2peak. Resting brain glucose uptake was measured using 18F-fluorodeoxyglucose positron emission tomography scans at baseline and at week 12. Scans were performed at 96 hours after exercise. VO2peak was measured by indirect calorimetry. Glucose uptake increased significantly in the parietal-temporal and caudate regions after HIIT compared with SED. The gains with HIIT were not observed in all brain regions. VO2peak was increased for all participants after HIIT and did not change with SED. We demonstrate that brain glucose metabolism increased after 12 weeks of HIIT in adults in regions where it is reduced in Alzheimer's disease.

The impact of vascular risk factors on brain volume and lesion load in patients with early multiple sclerosis

Background: Vascular risk factors (VRF) in multiple sclerosis (MS) patients have been associated with lower brain volumes. It is currently unknown if this association already exists in early MS and how it develops over time. Methods: We identified 82 patients with clinically isolated syndrome (CIS) (n = 61) or with early relapsing-remitting MS (n = 21) and assessed their VRF including arterial hypertension, hyperlipidaemia, diabetes mellitus and smoking. We analysed T2-lesion load, normalized brain volume (NBV), cortical grey (cGMV) and white matter volumes (WMV), thalamic and basal ganglia volumes at baseline and follow-up magnetic resonance imaging (MRI) and assessed the percentage of brain volume change (PBVC) using SIENA. Results: Patient mean age was 32.4 (±8.7) years and 54 (65%) were women. Median follow-up period was 42 (29–54) months. In total, 26 patients (31.7%) had one or more VRF (VRF+). At baseline, VRF+ patients had a lower NBV (1530.9 cm3 vs 1591.2 cm3, p = 0.001), a lower cGMV (628.5 cm3 vs 668.6 cm3, p = 0.002) and WMV (752.2 cm3 vs 783.9 cm3, p = 0.009) than VRF-negative patients. Similar results were obtained at follow-up. PBVC was comparable between patients with and without VRF. Conclusion: VRF are associated with lower brain volume already in early MS but do not lead to increased brain volume loss during 3.5 years of follow-up.

Mapping orbitofrontal-limbic maturation in non-human primates: A longitudinal magnetic resonance imaging study

Brain development involves spatiotemporally complex microstructural changes. A number of neuropsychiatric disorders are linked to the neural processes of development and aging. Thus, it is important to understanding the typical developmental patterns of various brain structures, which will help to define critical periods of vulnerability for neural maturation, as well as anatomical mechanisms of brain structure-related neuropathology. In this study, we used magnetic resonance imaging to assess development of the orbitofrontal cortex, cingulate cortex, amygdala, and hippocampus in a non-human primate species, the common marmoset (Callithrix jacchus). We collected a total of 114 T2-weighted and 91 diffusion-weighted scans from 23 animals from infancy to early adulthood. Quantitative and qualitative evaluation of age-related brain growth patterns showed non-linear structural developmental changes in all measured brain regions, consistent with reported human data. Overall, robust volumetric growth was observed from 1 to 3 months of age (from infancy to the early juvenile period). This rapid brain growth was associated with the largest decrease in mean, axial, and radial diffusivities of diffusion tensor imaging in all brain regions, suggesting an increase in the number and size of cells, dendrites, and spines during this period. After this developmental period, the volume of various brain regions steadily increased until adolescence (7–13 months of age, depending on the region). Further, structural connectivity derived from tractography data in various brain regions continuously changed from infancy to adolescence, suggesting that the increase in brain volume was related to continued axonal myelination during adolescence. Thereafter, the volume of the cortical regions decreased considerably, while there was no change in subcortical regions. Familial factors, rather than sex, contributed the development of the front-limbic brain regions. Overall, this study provides further data on the factors and timing important for normal brain development, and suggest that the common marmoset is a useful animal model for human neural development.

Coevolution of cultural intelligence, extended life history, sociality, and brain size in primates

Explanations for primate brain expansion and the evolution of human cognition and culture remain contentious despite extensive research. While multiple comparative analyses have investigated variation in brain size across primate species, very few have addressed why primates vary in how much they use social learning. Here, we evaluate the hypothesis that the enhanced reliance on socially transmitted behavior observed in some primates has coevolved with enlarged brains, complex sociality, and extended lifespans. Using recently developed phylogenetic comparative methods we show that, across primate species, a measure of social learning proclivity increases with absolute and relative brain volume, longevity (specifically reproductive lifespan), and social group size, correcting for research effort. We also confirm relationships of absolute and relative brain volume with longevity (both juvenile period and reproductive lifespan) and social group size, although longevity is generally the stronger predictor. Relationships between social learning, brain volume, and longevity remain when controlling for maternal investment and are therefore not simply explained as a by-product of the generally slower life history expected for larger brained species. Our findings suggest that both brain expansion and high reliance on culturally transmitted behavior coevolved with sociality and extended lifespan in primates. This coevolution is consistent with the hypothesis that the evolution of large brains, sociality, and long lifespans has promoted reliance on culture, with reliance on culture in turn driving further increases in brain volume, cognitive abilities, and lifespans in some primate lineages.

Dietary Iodine Exposure and Brain Structures and Cognition in Older People. Exploratory Analysis in the Lothian Birth Cohort 1936.

Iodine deficiency is one of the three key micronutrient deficiencies highlighted as major public health issues by the World Health Organisation. Iodine deficiency is known to cause brain structural alterations likely to affect cognition. However, it is not known whether or how different (lifelong) levels of exposure to dietary iodine influences brain health and cognitive functions. From 1091 participants initially enrolled in The Lothian Birth Cohort Study 1936, we obtained whole diet data from 882. Three years later, from 866 participants (mean age 72 yrs, SD±0.8), we obtained cognitive information and ventricular, hippocampal and normal and abnormal tissue volumes from brain structural magnetic resonance imaging scans (n=700). We studied the brain structure and cognitive abilities of iodine-rich food avoiders/low consumers versus those with a high intake in iodine-rich foods (namely dairy and fish). We identified individuals (n=189) with contrasting diets, i) belonging to the lowest quintiles for dairy and fish consumption, ii) milk avoiders, iii) belonging to the middle quintiles for dairy and fish consumption, and iv) belonging to the middle quintiles for dairy and fish consumption. Iodine intake was secured mostly though the diet (n=10 supplement users) and was sufficient for most (75.1%, median 193 µg/day). In individuals from these groups, brain lateral ventricular volume was positively associated with fat, energy and protein intake. The associations between iodine intake and brain ventricular volume and between consumption of fish products (including fish cakes and fish-containing pasties) and white matter hyperintensities (p=0.03) the latest being compounded by sodium, proteins and saturated fats, disappeared after type 1 error correction. In this large Scottish older cohort, the proportion of individuals reporting extreme (low vs. high)/medium iodine consumption is small. In these individuals, low iodine-rich food intake was associated with increased brain volume shrinkage, raising an important hypothesis worth being explored for designing appropriate guidelines.

Using magnetic resonance imaging to elucidate the mechanism of experimental cerebral malaria rescue by 6-diazo-5-oxo-norleucine

Abstract We have previously demonstrated the efficacy of 6-diazo-5-oxo-L-norleucine (DON), a glutamine analog, as a possible adjunctive therapy to mitigate the clinical severity of human cerebral malaria (HCM) (Gordon et al. PNAS 2016). The pathology of HCM is heterogeneous, but generally includes the accumulation of infected red blood cells in the brain vascular endothelium, cerebral microhemorrhages, compromised blood-brain barrier and brain swelling. These changes manifest in severe neurologic symptoms including headache, fever, ataxia, seizures, retinopathy, and coma. The mouse model of CM, experimental cerebral malaria (ECM), approximates the main characteristics of HCM when susceptible C57BL/6 mice are infected with Plasmodium berghei ANKA (PbA) parasites. Studies in these mice found that treatment with DON, even in late stage ECM, rescued animals and increased survival while mitigating and reversing blood-brain barrier dysfunction and brain swelling. Recently, Seydel et al. (NEJM 2015) used magnetic resonance imaging (MRI) to characterize HCM pathology and correlate it to disease severity in children in Malawi. They observed increased brain volume in children that died from HCM that was uncommon in children that survived HCM. Herein, we perform MRI studies in the mouse model to determine if the disease course effectively recapitulates that of HCM, based on morphological changes in MRI. These studies may help elucidate the mechanisms underlying CM pathology, aiding the development of effective treatments. Furthermore, we utilize MRI to probe the mechanisms of action of recovery with DON treatment in order to evaluate the drug for possible clinical trials in HCM.