Frontal Gray Matter Research Articles

Fronto-Parietal Gray Matter Volume Loss Is Associated with Decreased Working Memory Performance in Adolescents with a First Episode of Psychosis.

Cognitive maturation during adolescence is modulated by brain maturation. However, it is unknown how these processes intertwine in early onset psychosis (EOP). Studies examining longitudinal brain changes and cognitive performance in psychosis lend support for an altered development of high-order cognitive functions, which parallels progressive gray matter (GM) loss over time, particularly in fronto-parietal brain regions. We aimed to assess this relationship in a subsample of 33 adolescents with first-episode EOP and 47 matched controls over 2 years. Backwards stepwise regression analyses were conducted to determine the association and predictive value of longitudinal brain changes over cognitive performance within each group. Fronto-parietal GM volume loss was positively associated with decreased working memory in adolescents with psychosis (frontal left (B = 0.096, p = 0.008); right (B = 0.089, p = 0.015); parietal left (B = 0.119, p = 0.007), right (B = 0.125, p = 0.015)) as a function of age. A particular decrease in frontal left GM volume best predicted a significant amount (22.28%) of the variance of decreased working memory performance over time, accounting for variance in age (14.9%). No such association was found in controls. Our results suggest that during adolescence, EOP individuals seem to follow an abnormal neurodevelopmental trajectory, in which fronto-parietal GM volume reduction is associated with the differential age-related working memory dysfunction in this group.

3Tesla post-mortem MRI quantification of anatomical brain structures

Quantitative post-mortem magnetic resonance imaging (PMMR) allows for measurement of T1 and T2 relaxation times and proton density (PD) of brain tissue. Quantitative PMMR values may be used for advanced post-mortem neuro-imaging diagnostics such as computer aided diagnosis. So far, the quantitative T1, T2 and PD post-mortem values of regular anatomical brain structures were unknown for a 3 Tesla PMMR application. The goal of this basic research study was to evaluate the quantitative values of post-mortem brain structures for a 3 T post-mortem magnetic resonance application with regard to various corpse temperatures. In 50 forensic cases, a quantitative PMMR brain sequence was applied prior to autopsy. Measurements of T1 (in ms), T2 (in ms), and PD (in %) values of cerebrum (Group 1: frontal grey matter, frontal white matter, thalamus, caudate nucleus, globus pallidus, putamen, internal capsule) brainstem and cerebellum (Group 2: cerebral peduncle, substantia nigra, red nucleus, pons, middle cerebellar peduncle, cerebellar hemisphere, medulla oblongata) were conducted in synthetically calculated axial PMMR brain images. Assessed quantitative values were corrected for corpse temperature. Temperature dependence was observed mainly for T1 values. ANOVA testing resulted in significant differences of quantitative values between the investigated anatomical brain structures in both groups. It can be concluded that temperature corrected 3 Tesla PMMR T1, T2 and PD values are feasible for characterization and discrimination of regular anatomical brain structures. This may provide a base for future advanced diagnostics of forensically relevant brain lesions and pathology.

Shared and specific patterns of structural and functional thalamo-frontal disturbances in manic and euthymic pediatric bipolar disorder

Bipolar disorder (BD) is clinically defined by alternating depressive and manic episodes with a separated period of euthymia. Thalamo-frontal loop plays vital role in psychotic symptoms, altered motor control and executive difficulties in BD. It remains unclear that structural and functional alterations of thalamo-frontal loop among the different mood states in BD, especially in pediatric BD(PBD).Twenty manic PBD (mPBD), 20 euthymic PBD (ePBD) and 19 healthy controls (HCs) were included in the study. By analyzing the T1 images and fMRI signals, thalamus volume and frontal grey matter cortical thickness were tested, and functional connectivity (FC) between bilateral thalamus and frontal cortex was calculated. Relationship between clinical indices and thalamo-frontal FC was also evaluated in mPBD and ePBD adolescents.Compared to HCs, the cortical thickness of left middle frontal gyrus (MFG), bilateral superior frontal gyrus (SFG) was significantly decreased in both mPBD and ePBD patients, and volume of left thalamus and cortical thickness of right MFG significantly decreased in mPBD patients. Compared to that of the HCs and ePBD subjects, thalamo-frontal hyperconnectivity with MFG was found in mPBD, and compared with that of HCs, thalamo-frontal hypoconnectivity with precentral gyrus/SFG was found in ePBD. In ePBD patients, episode times positively correlated with FC values between thalamus and precentral gyrus.The findings of the present study demonstrate detailed knowledge regarding shared and specific structural and functional disruption in thalamo-frontal loop in mPBD and ePBD subjects. Thalamo-frontal abnormalities reported in adult BD subjects were also observed in adolescent BD patients, and thalamo-frontal dysfunction may be a crucial treatment target in BD.

Hydrogen-rich water and caffeine for alertness and brain metabolism in sleep-deprived habitual coffee drinkers.

The main aim of this randomized‐controlled cross‐over interventional trial was to assess the acute effects of taking a single dose of hydrogen‐rich water (HRW), and compare it with caffeine, HRW plus caffeine, and control water, for alertness, brain metabolism, brain and oxygen saturation, and self‐reported adverse events in healthy men and women who were habitual coffee drinkers and were sleep‐deprived for 24 hr. Sixteen apparently healthy young adults (8 men and 8 women; age 24.0 ± 3.5 years) were allocated in a cross‐over design to receive a single‐dose drink of HRW (8 ppm), caffeine (50 mg), HRW plus caffeine, or control drink (tap water) in the morning after 24‐hr sleep deprivation and 12‐hr fasting. The primary and secondary outcomes were assessed at baseline (pre‐intervention) and 15‐min follow‐up. Significantly less time was needed to complete trail‐making test after both HRW and HRW plus caffeine compared with the control drink (p < .05). The number of errors in the symbol digit modalities test was significantly lower after drinking HRW or caffeine than control drink (p < .05). Both HRW and caffeine significantly increased the choline‐to‐creatine ratio in several brain regions (frontal white and gray matter), while HRW and the combination intervention also affected brain metabolism in the paracentral brain. No participants reported any side effects from any intervention. The attention enhancement driven by HRW appears along with changes in brain metabolism. Being generally recognized as a safe intervention, hydrogen could be thus recommended as a novel intervention that upholds attention in stressed conditions, with its metabolic footprint likely different from caffeine.

DIAGNOSTIC ACCURACY OF 1H-MRS IN PROGNOSTICATION OF PERINATAL ASPHYXIA, KEEPING CLINICAL NEUROMOTOR SCORING SYSTEM IN COMPARISON

Objective: To determine the diagnostic accuracy of 1H- magnetic resonance spectroscopy imaging findings in predicting neurodevelopmental abnorma-lities in term neonates having respiratory distress, using clinical neurological examination as reference standard.&#x0D; Study Design: Cross sectional validation study.&#x0D; Place and Duration of Study: Armed Forces Institute of Radiology and Imaging (AFIRI), Pak Emirates Military Hospital, Rawalpindi, from Oct 2017 to Apr 2018.&#x0D; Methodology: A total of 86 patients were included in study. All term neonates suspected of hypoxic ischemic encephalopathy (HIE) referred for magnetic resonance spectroscopy (MRS) meeting our inclusion criteria were enrolled for study acquisition after taking informed consent from attendants.&#x0D; Results: Approximately 47 out of 86 patients suspected to have perinatal asphyxia showed raised lactate peaks (resonating at 1.3 ppm) in both watershed and ganglionic regions and at 6 months neurological evaluation showed significantly delayed neurological development and delayed milestones. Seven (8.1%) patients clinically suspected to have birth asphyxia showed no specific detectable spectral spikes at 1.31 ppm. Twenty six (30.2%) patients presenting with delayed cry but no laboratory evidence of birth asphyxia showed no definite evidence of visualization of lactate peaks. Six (6.97%) patients showed normal magnetic resonance spectroscopy who had clinical, biochemical suspicion of systemic ischemic insult and later on showed retarded neurodevelopment at 6 months of age.&#x0D; Conclusion: Magnetic resonance spectroscopy (magnetic resonance spectroscopy) spectra in patients having high documented clinical and biochemical suspicion of transitory birth asphyxia from any cause, acquired at frontal watershed territory and deep grey matter showed a characteristic spectral resonance of...............

Criminal arrests associated with reduced regional brain volumes in an adult population with documented childhood lead exposure

Childhood lead exposure interferes with brain maturation, which adversely impacts cognitive and behavioral development. Lower intelligence scores, impairments in decision making, and increased rates of delinquent and criminal behavior are adverse outcomes linked to childhood lead absorption. The present study examined the relationships between childhood blood lead concentrations, structural brain volume, and measures of adult criminality. We hypothesized that increased rates of criminal arrests in adulthood would be inversely correlated with regional gray and white matter volumes, especially prefrontal areas responsible for decision making and self-control. We obtained childhood blood lead histories and anatomical magnetic resonance imaging from a subset of the longitudinally followed birth cohort known as the Cincinnati Lead Study. Criminality data for cohort participants were extracted from public databases. Voxel based morphometry was used to examine spatial differences in regional gray and white matter volumes associated with childhood blood lead concentrations and measures of adult criminality, respectively. Conjunction analyses allowed for the exploratory evaluation of common regions of volume change. Childhood blood lead concentrations were inversely associated with gray and white matter volume in the frontal, parietal and temporal lobes. Gray matter volumes were also inversely associated with criminal arrests with key regions within the cingulate, precuneus, several frontal gyri and the supplementary motor area. Conjunction analyses identified regions in the anterior cingulate, frontal gray matter and supplementary motor area associated with childhood lead absorption and criminality. The results from this study suggest that reduced brain volumes in regions responsible for cognition and emotional regulation are associated with childhood lead exposure and criminal arrests.

Childhood trauma is associated with reduced frontal gray matter volume: a large transdiagnostic structural MRI study.

Childhood trauma increases risk for psychopathology and cognitive impairment. Prior research mainly focused on the hippocampus and amygdala in single diagnostic categories. However, other brain regions may be impacted by trauma as well, and effects may be independent of diagnosis. This cross-sectional study investigated cortical and subcortical gray matter volume in relation to childhood trauma severity. We included 554 participants: 250 bipolar-I patients, 84 schizophrenia-spectrum patients and 220 healthy individuals without a psychiatric history. Participants filled in the Childhood Trauma Questionnaire. Anatomical T1 MRI scans were acquired at 3T, regional brain morphology was assessed using Freesurfer. In the total sample, trauma-related gray matter reductions were found in the frontal lobe (β = -0.049, p = 0.008; q = 0.048), this effect was driven by the right medial orbitofrontal, paracentral, superior frontal regions and the left precentral region. No trauma-related volume reductions were observed in any other (sub)cortical lobes nor the hippocampus or amygdala, trauma-by-group (i.e. both patient groups and healthy subjects) interaction effects were absent. A categorical approach confirmed a pattern of more pronounced frontal gray matter reductions in individuals reporting multiple forms of trauma and across quartiles of cumulative trauma scores. Similar dose-response patterns were revealed within the bipolar and healthy subgroups, but did not reach significance in schizophrenia-spectrum patients. Findings show that childhood trauma is linked to frontal gray matter reductions, independent of psychiatric morbidity. Our results indicate that childhood trauma importantly contributes to the neurobiological changes commonly observed across psychiatric disorders. Frontal volume alterations may underpin affective and cognitive disturbances observed in trauma-exposed individuals.

Spectral analysis of physiological brain pulsations affecting the BOLD signal.

Physiological pulsations have been shown to affect the global blood oxygen level dependent (BOLD) signal in human brain. While these pulsations have previously been regarded as noise, recent studies show their potential as biomarkers of brain pathology. We used the extended 5 Hz spectral range of magnetic resonance encephalography (MREG) data to investigate spatial and frequency distributions of physiological BOLD signal sources. Amplitude spectra of the global image signals revealed cardiorespiratory envelope modulation (CREM) peaks, in addition to the previously known very low frequency (VLF) and cardiorespiratory pulsations. We then proceeded to extend the amplitude of low frequency fluctuations (ALFF) method to each of these pulsations. The respiratory pulsations were spatially dominating over most brain structures. The VLF pulsations overcame the respiratory pulsations in frontal and parietal gray matter, whereas cardiac and CREM pulsations had this effect in central cerebrospinal fluid (CSF) spaces and major blood vessels. A quasi‐periodic pattern (QPP) analysis showed that the CREM pulsations propagated as waves, with a spatiotemporal pattern differing from that of respiratory pulsations, indicating them to be distinct intracranial physiological phenomenon. In conclusion, the respiration has a dominant effect on the global BOLD signal and directly modulates cardiovascular brain pulsations.

Expression of Oligodendrocyte and Oligoprogenitor Cell Proteins in Frontal Cortical White and Gray Matter: Impact of Adolescent Development and Ethanol Exposure.

Adolescent development of prefrontal cortex (PFC) parallels maturation of executive functions as well as increasing white matter and myelination. Studies using MRI and other methods find that PFC white matter increases across adolescence into adulthood in both humans and rodents. Adolescent binge drinking is common and has been found to alter adult behaviors and PFC functions. This study examines development of oligoprogenitor (OPC) and oligodendrocytes (OLs) in Wistar rats from adolescence to adulthood within PFC white matter, corpus callosum forceps minor (fmi), PFC gray matter, and the neurogenic subventricular zone (SVZ) using immunohistochemistry for marker proteins. In addition, the effects of adolescent intermittent ethanol exposure [AIE; 5.0 g/kg/day, intragastric, 2 days on/2 days off on postnatal day (P)25–54], which is a weekend binge drinking model, were determined. OPC markers NG2+, PDGFRα+ and Olig2+IHC were differentially impacted by both age and PFC region. In both fmi and SVZ, NG2+IHC cells declined from adolescence to adulthood with AIE increasing adult NG2+IHC cells and their association with microglial marker Iba1. PFC gray matter decline in NG2+IHC in adulthood was not altered by AIE. Both adult maturation and AIE impacted OL expression of PLP+, MBP+, MAG+, MOG+, CNPase+, Olig1+, and Olig2+IHC in all three PFC regions, but in region- and marker-specific patterns. These findings are consistent with PFC region-specific changes in OPC and OL markers from adolescence to adulthood as well as following AIE that could contribute to lasting changes in PFC function.

Combination of apparent diffusion coefficient and amplitude-integrated electroencephalogram to predict the outcome of comatose patients with severe traumatic brain injury

To examine whether the combination of quantitative regional apparent diffusion coefficient (ADC) and amplitude-integrated electroencephalogram (aEEG) can predict the outcome of comatose patients with severe traumatic brain injury (sTBI). A prospective study was conducted. The patients with coma caused by sTBI [Glasgow coma scale (GCS) < 8] admitted to Suqian First Hospital from January 2016 to June 2019 were enrolled. All patients underwent aEEG examination and magnetic resonance imaging (MRI) scan within 1 week after emergency treatment. The ADC values of 9 regions of interest (frontal gray matter and white matter, parietal gray matter and white matter, temporal gray matter and white matter, caudate nucleus of basal ganglia, lenticular nucleus and thalamus) were measured by head MRI, and the mean ADC values of frontal lobe, parietal lobe, temporal lobe and basal ganglia were calculated respectively. According to the follow-up results after 12 months, the differences of each index between patients with poor prognosis [Glasgow outcome score (GOS) 1-2] and patients with good prognosis (GOS 3-5) were compared; the receiver operating characteristic curve (ROC curve) was drawn to evaluate the predictive ability of aEEG and ADC for the good prognosis of patients with sTBI, and the predictive value of the combination of aEEG and ADC. A total of 52 patients with sTBI were enrolled, with mean age of (36.7±13.9) years old, 35 of whom were male. Within 12 months follow-up, 29 patients had achieved favorable outcomes and 23 patients had unfavorable outcome. There were 21, 17 and 14 patients with aEEG, and grade, respectively, and 19, 10 and 0 patients had good prognosis respectively. ADC values of 9 regions of interest in patients with good prognosis were significantly higher than those in patients with poor prognosis (×10-6 mm2/s: 924±107 vs. 531±87 in frontal gray matter, 804±95 vs. 481±74 in frontal white matter, 831±93 vs. 683±72 in temporal gray matter, 726±87 vs. 654±63 in temporal white matter, 767±79 vs. 690±75 in parietal gray matter, 716±84 vs. 642±62 in parietal white matter, 689±70 vs. 465±68 in caudate nucleus, 723±84 vs. 587±71 in lenticular nucleus, 807±79 vs. 497±67 in thalamus, all P < 0.01). ROC curve analysis showed that the area under ROC curve (AUC) of aEEG for predicting good prognosis of sTBI patients was 0.826, when the cut-off value of aEEG was < 1.5, the sensitivity was 94.7% and the specificity was 72.8%. Among the ADC value prediction abilities in the interested areas, the prediction of ADC value in frontal lobe and basal ganglia area were better than that in sTBI patients. AUC was 0.817 and 0.903 respectively. The best cut-off values were > 726×10-6 mm2/s and > 624×10-6 mm2/s respectively, the sensitivity of predicting prognosis were both 100%, and the specificity was 63.4% and 61.8%. A model combining frontal ADC and basal ganglia ADC with aEEG was 91.0% sensitive and 93.7% specific for favorable outcome of sTBI patients. Combination of the quantitative measurement of regional ADC and aEEG may be useful for predicting the outcome of the patients with sTBI.

Human Brain Lipidomics: Utilities of Chloride Adducts in Flow Injection Analysis.

Ceramides have been implicated in a number of disease processes. However, current means of evaluation with flow infusion analysis (FIA) have been limited primarily due to poor sensitivity within our high-resolution mass spectrometry lipidomics analytical platform. To circumvent this deficiency, we investigated the potential of chloride adducts as an alternative method to improve sensitivity with electrospray ionization. Chloride adducts of ceramides and ceramide subfamilies provided 2- to 50-fold increases in sensitivity both with analytical standards and biological samples. Chloride adducts of a number of other lipids with reactive hydroxy groups were also enhanced. For example, monogalactosyl diacylglycerols (MGDGs), extracted from frontal lobe cortical gray and subcortical white matter of cognitively intact subjects, were not detected as ammonium adducts but were readily detected as chloride adducts. Hydroxy lipids demonstrate a high level of specificity in that phosphoglycerols and phosphoinositols do not form chloride adducts. In the case of choline glycerophospholipids, the fatty acid substituents of these lipids could be monitored by MS2 of the chloride adducts. Monitoring the chloride adducts of a number of key lipids offers enhanced sensitivity and specificity with FIA. In the case of glycerophosphocholines, the chloride adducts also allow determination of fatty acid substituents. The chloride adducts of lipids possessing electrophilic hydrogens of hydroxyl groups provide significant increases in sensitivity. In the case of glycerophosphocholines, chloride attachment to the quaternary ammonium group generates a dominant anion, which provides the identities of the fatty acid substituents under MS2 conditions.

Absence of negative associations of insular and medial frontal gray matter volume with dissociative symptoms in schizophrenia

BackgroundDissociative symptoms have been constantly found in schizophrenia (SCZ). Traumatic experience seems to relate to dissociative symptoms and brain volume alterations in SCZ. The current study aimed to clarify the inter-relations of dissociative symptoms, traumatic experience, and brain volume in SCZ. MethodsWe employed voxel-based morphometry to compare the distributions of gray matter volumes (GMV) in 37 SCZ patients and 26 healthy volunteers (HV). All participants underwent T1-weighted images on a 1.5 T MRI system. Traumatic experience was examined by the Brief Betrayal Trauma Survey. Pathological and non-pathological dissociation were measured by the Dissociative Symptoms Scale and the Dissociative Experiences Scale, respectively. ResultsA GMV reduction was found in SCZ patients in the right thalamus. Importantly, a significant group by pathological dissociation interaction was observed in the medial frontal cortex (MFC), bilateral anterior insular area, and precuneus. A negative correlation between MFC/insular GMV and pathological dissociation was observed in HV; higher non-pathological dissociation and smaller volume in MFC/insula were associated with pathological dissociation. In contrast, higher traumatic experience, higher non-pathological dissociation, and larger volume in MFC/insula were associated with pathological dissociation in SCZ. ConclusionThe negative association between MFC/insula GMV and pathological dissociation in HV was not observed in SCZ patients. The absent negative association in SCZ suggests a unique neural underpinning in SCZ with dissociative pathology, in which medial frontal and temporal regions play crucial roles.

Severity related neuroanatomical alteration across symptom dimensions in obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) is a symptomatically heterogeneous disease. Symptoms of OCD can be grouped into a six-factor structure including washing, checking, neutralizing, obsessing, ordering and hoarding. These different symptom profiles might be one of the critical factors contributing to the inconsistent neuroanatomical findings in OCD according to the literature. In this study, whole-brain voxel-based morphometry was used to examine neuroanatomical alterations in gray matter (GM) for OCD compared to healthy controls, and the variations associated with differing symptoms of OCD. The high-quality structural imaging data from 39 OCD individuals and 42 age-matched healthy controls were recruited. First, we found increased cortical GM volume in the left postcentral gyrus in OCD participants compared to healthy controls. Next, six independent regression analyses were conducted to examine the correlation between OCD symptom dimensions and inter-individual variation in neuroanatomy. After a rigorous multiple comparison correction, greater hoarding symptom was robustly found associated with greater GM volumes at various frontotemporal regions (including orbitofrontal, middle frontal and superior temporal GMs). Additionally, greater washing symptoms were associated with increased GM volume at the superior temporal cortex. The symptom-specific GM alterations observed here support the notion that OCD is an etiologically heterogeneous disorder, with both overlapping and distinct neuroanatomical structure across symptom dimensions.

Adult-onset neuronal intranuclear inclusion disease, with both stroke-like onset and encephalitic attacks: a case report

BackgroundNeuronal intranuclear inclusion disease (NIID) is a neurodegenerative disease, the clinical manifestations of which are complex and easily misdiagnosed. NIID clinical characteristics are varied, affecting the central and peripheral nervous systems and autonomic nerves. In this study, we present an NIID case with both stroke-like onset and encephalitic attacks, which is a rare case report.Case presentationA 68-year-old Chinese female presented with sudden aphasia and limb hemiplegia as the first symptoms, as well as fever, cognitive impairment and mental irritability from encephalitic attacks. During hospitalization, a brain magnetic resonance imaging (MRI) examination detected high signal intensity from diffusion-weighted imaging (DWI) of the bilateral frontal grey matter-white matter junction. Electrophysiological tests revealed the main site of injury was at the myelin sheath in the motor nerves. A skin biopsy revealed eosinophilic spherical inclusion bodies in the nuclei of small sweat gland cells, fibroblasts and fat cells, whilst immunohistochemistry revealed that p62 and ubiquitin antibodies were positive. From genetic analyses, the patient was not a carrier of the fragile X mental retardation 1 (FMR1) permutation, but repeated GGC sequences in the NOTCH2NLC gene confirmed an NIID diagnosis. Through antipsychotic and nutritional support therapy, the patient’s symptoms were completely relieved within 3 weeks.ConclusionsThis report of an NIID case with both stroke-like onset and encephalitic attacks provides new information for NIID diagnoses, and a comprehensive classification of clinical characteristics.

Brain Structure, Cardiorespiratory Fitness, and Executive Control Changes after a 9-Week Exercise Intervention in Young Adults: A Randomized Controlled Trial.

Cardiorespiratory fitness (CRF) is assumed to exert beneficial effects on brain structure and executive control (EC) performance. However, empirical evidence of exercise-induced cognitive enhancement is not conclusive, and the role of CRF in younger adults is not fully understood. Here, we conducted a study in which healthy young adults took part in a moderate aerobic exercise intervention program for 9 weeks (exercise group; n = 48), or control condition of non-aerobic exercise intervention (waitlist control group; n = 72). Before and after the intervention period maximal oxygen uptake (VO2max) as an indicator of CRF, the Flanker task as a measure of EC performance and grey matter volume (GMV), as well as cortical thickness via structural magnetic resonance imaging (MRI), were assessed. Compared to the control group, the CRF (heart rate, p < 0.001; VO2max, p < 0.001) and EC performance (congruent and incongruent reaction time, p = 0.011, p < 0.001) of the exercise group were significantly improved after the 9-week aerobic exercise intervention. Furthermore, GMV changes in the left medial frontal gyrus increased in the exercise group, whereas they were significantly reduced in the control group. Likewise, analysis of cortical morphology revealed that the left lateral occipital cortex (LOC.L) and the left precuneus (PCUN.L) thickness were considerably increased in the exercise group, which was not observed in the control group. The exploration analysis confirmed that CRF improvements are linked to EC improvement and frontal grey matter changes. In summary, our results support the idea that regular endurance exercises are an important determinant for brain health and cognitive performance even in a cohort of younger adults.

Apolipoprotein E ε4 Allele-Based Differences in Brain Volumes Are Largely Uniform Across Late Middle Aged and Older Hispanic/Latino- and Non-Hispanic/Latino Whites Without Dementia.

Hispanics/Latinos are at an equal or a greater risk for Alzheimer's disease (AD), yet risk factors remain more poorly characterized as compared to non-Hispanic/Latino Whites. Among non-Hispanic/Latino White cohorts, the apolipoprotein E (APOE) ε4 allele is one of the strongest risk factors for AD with subtle declines in episodic memory and brain volumes detectable in the preclinical stages. We examined whether the APOE ε4 status had a differential impact on cognition and brain volumes among cognitively healthy and mild cognitively impaired Hispanics/Latinos (n = 86; ε4 n = 23) compared to a well-matched group of non-Hispanic/Latino Whites (n = 92; ε4 n = 29). Neither the APOE ε4 status nor the interaction between the ε4 status and ethnicity was associated with cognitive performance. The APOE ε4 status was associated with white matter and not with gray matter volumes. APOE ε4 carriers had a significantly smaller total brain white matter volumes, as well as smaller right middle temporal and left superior temporal volumes. The Hispanics/Latinos had significantly smaller left middle frontal gray matter volumes, yet marginally larger overall white matter volumes, than the non-Hispanic/Latino Whites. Exploratory analysis within the Hispanic/Latino sample found that those people whose primary language was Spanish had larger total brain white matter volumes compared primarily to the English speakers. Importantly, primary language differences only held for Hispanic/Latino ε4 carriers and did not differentiate Hispanic/Latino non-carriers, underscoring the need for further investigation into the impacts of language and acculturation on cognitive aging among the fastest growing ethnic minority group in the United States.

Upregulation of Cortical A2A Adenosine Receptors Is Reflected in Platelets of Patients with Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative pathology covering about 70%of all cases of dementia. Adenosine, a ubiquitous nucleoside, plays a key role in neurodegeneration, through interaction with four receptor subtypes. The A2A receptor is upregulated in peripheral blood cells of patients affected by Parkinson's and Huntington's diseases, reflecting the same alteration found in brain tissues. However, whether these changes are also present in AD pathology has not been determined. In this study we verified any significant difference between AD cases and controls in both brain and platelets and we evaluated whether peripheral A2A receptors may reflect the status of neuronal A2A receptors. We evaluated the expression of A2A receptors in frontal white matter, frontal gray matter, and hippocampus/entorhinal cortex, in postmortem AD patients and control subjects, through [3H]ZM 241385 binding experiments. The same analysis was performed in peripheral platelets from AD patients versus controls. The expression of A2A receptors in frontal white matter, frontal gray matter, and hippocampus/entorhinal cortex, revealed a density (Bmax) of 174±29, 219±33, and 358±84 fmol/mg of proteins, respectively, in postmortem AD patients in comparison to 104±16, 103±19, and 121±20 fmol/mg of proteins in controls (p < 0.01). The same trend was observed in peripheral platelets from AD patients versus controls (Bmax of 214±17 versus 95±4 fmol/mg of proteins, respectively, p < 0.01). AD subjects show significantly higher A2A receptor density than controls. Values on platelets seem to correlate with those in the brain supporting a role for A2A receptor as a possible marker of AD pathology and drug target for novel therapies able to modify the progression of dementia.

Response assessment during chemoradiation using a hypercellular/hyperperfused imaging phenotype predicts survival in patients with newly diagnosed glioblastoma.

Adversely prognostic hypercellular and hyperperfused regions of glioblastoma (GBM) predict progression-free survival, and are a novel target for dose-intensified chemoradiation (chemoRT) recently implemented in a phase II clinical trial. As a secondary aim, we hypothesized that dose-intensified chemoRT would induce greater mid-treatment response of hypercellular/hyperperfused tumor regions vs standard chemoradiation, and that early response would improve overall survival (OS). Forty-nine patients with newly diagnosed GBM underwent prospective, multiparametric high b value diffusion-weighted MRI (DW-MRI) and perfusion dynamic contrast-enhanced MRI (DCE-MRI) pre-RT and 3-4 weeks into RT. The hypercellular tumor volume (TVHCV, mean contralateral normal brain + 2SD) and hyperperfused tumor volume (TVCBV, contralateral normal frontal gray matter + 1SD) were generated using automated thresholding. Twenty-six patients were enrolled on a dose-escalation trial targeting TVHCV/TVCBV with 75 Gy in 30 fractions, and 23 non-trial patients comprised the control group. OS was estimated using the Kaplan-Meier method and compared using the log-rank test. The effect of TVHCV/TVCBV and Gd-enhanced tumor volume on OS was assessed using multivariable Cox proportional-hazard regression. Most patients had gross total (47%) or subtotal resection (37%), 25% were MGMT-methylated. Patients treated on the dose-escalation trial had significantly greater reduction in TVHCV/TVCBV (41% reduction, IQR 17%-75%) vs non-trial patients (6% reduction, IQR 6%-22%, P = .002). An increase in TVHCV/TVCBV during chemoRT was associated with worse OS (adjusted hazard ratio [aHR] 1.2, 95%CI 1.0-1.4, P = .02), while pre-treatment tumor volumes (P > .5) and changes in Gd-enhanced volume (P = .9) were not. Multiparametric MRI permits identification of therapeutic resistance during chemoRT and supports adaptive strategies in future trials.

The clinical relevance of gray matter atrophy and microstructural brain changes across the psychosis continuum

Patients with psychotic spectrum disorders (PSD) exhibit similar patterns of atrophy and microstructural changes that may be associated with common symptomatology (e.g., symptom burden and/or cognitive impairment). Gray matter concentration values (proxy for atrophy), fractional anisotropy (FA), mean diffusivity (MD), intracellular neurite density (Vic) and isotropic diffusion volume (Viso) measures were therefore compared in 150 PSD (schizophrenia, schizoaffective disorder, and bipolar disorder Type I) and 63 healthy controls (HC). Additional analyses evaluated whether regions showing atrophy and/or microstructure abnormalities were better explained by DSM diagnoses, symptom burden or cognitive dysfunction. PSD exhibited increased atrophy within bilateral medial temporal lobes and subcortical structures. Gray matter along the left lateral sulcus showed evidence of increased atrophy and MD. Increased MD was also observed in homotopic fronto-temporal regions, suggesting it may serve as a precursor to atrophic changes. Global cognitive dysfunction, rather than DSM diagnoses or psychotic symptom burden, was the best predictor of increased gray matter MD. Regions of decreased FA (i.e., left frontal gray and white matter) and Vic (i.e., frontal and temporal regions and along central sulcus) were also observed for PSD, but were neither spatially concurrent with atrophic regions nor associated with clinical symptoms. Evidence of expanding microstructural spaces in gray matter demonstrated the greatest spatial overlap with current and potentially future regions of atrophy, and was associated with cognitive deficits. These results suggest that this particular structural abnormality could potentially underlie global cognitive impairment that spans traditional diagnostic categories.

Brain structure and neural activity related to reading in boys with isolated oral clefts

ABSTRACT Background: The purpose of this study was to evaluate brain structure and function in participants with iCL/P and unaffected controls. Effects of cleft presence and reading status (average vs impaired) were evaluated. Methods: Males, ages 8–11 years old, including 26 with iCL/P and 57 unaffected peers were recruited and coded for reading status (average vs impaired). All participants underwent a volumetric and task-based functional MRI. Volumes and significant regions of activation during the decoding task were obtained. Main effects of cleft and reading status, and their interaction were evaluated. Results: Participants with iCL/P had significantly increased frontal gray matter volume (associated with average reading) and occipital gray and white matter volume (associated with impaired reading). Impaired readers with iCL/P had a distinctive activation pattern in visual association and motor regions relative to other groups. Conclusions: Findings suggest that increases in frontal gray matter volume may be associated with effective compensation during reading, while posterior increases in occipital volume may be associated with ineffective compensation for participants with iCL/P. These patterns were different from idiopathic dyslexia. Further work in a larger sample is needed to determine if these differences are associated with cleft type and with sex. Abbreviations: iCL/P (isolated cleft lip and/or palate); iCL (isolated cleft lip only); iCLP (isolated cleft lip and palate); iCP (isolated cleft palate only); uAR (unaffected average reader); uIR (unaffected impaired reader); cAR (average reader with iCL/P); cIR (impaired reader with iCL/P).