Olfactory dysfunction is recognized in neurodevelopmental disorders and may serve as an early indicator of global dysfunction. The present meta-analysis measures olfaction effect sizes in ...attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASDs), and obsessive–compulsive disorder (OCD). Meta-analysis included 320 ADHD, 346 ASD, and 208 OCD individuals as compared to 910 controls. Olfactory performance deficits were small-to-moderate and heterogeneous (d = − 0.42, 95% CI = − 0.59 < δ < − 0.25). Meta-analytic results indicate that olfactory dysfunction is evident in individuals with ASD and OCD, with small-to-negligible effects in ADHD. These findings imply olfactory dysfunction is related to clinical phenotype in ASD and OCD, but not ADHD, and warrant inclusion in clinical assessment and evaluation of certain neurodevelopmental disorders.
There are known relationships between psychopathology, personality, and executive function (EF), though the association between personality and EF, independent of psychopathology, remains ...understudied. The present study investigated relationships between Five Factor Model personality traits and indices of response inhibition, sustained attention, and response variability on a continuous performance test (CPT) among 50 healthy adults (male = 27, female = 23; Mage = 19.9 years, range 18–24 years) of primarily Caucasian descent (58.0%). Participants performed an open-source CPT, the Psychology Experiment Building Language Battery Test of Attentional Vigilance (TOAV), and completed self-ratings of conscientiousness, extraversion, and neuroticism on an inventory developed from the public-domain International Personality Item Pool. After controlling for the influences of age, gender, and other personality traits, neuroticism was significantly associated with faster error reaction time and a higher frequency of multiple responses. Neuroticism was also nominally predictive of more frequent commission errors and faster correct and mean reaction time. The present findings indicate that neuroticism is associated with error-prone behavioral performance on a CPT, suggesting that a propensity to experience negative emotions may manifest as impulsivity and hyperactivity on performance-based measures of EF.
Low reward responsiveness (RR) is associated with poor psychological well-being, psychiatric disorder risk, and psychotropic treatment resistance. Functional MRI studies have reported decreased ...activity within the brain's reward network in individuals with RR deficits, however the neurochemistry underlying network hypofunction in those with low RR remains unclear. This study employed ultra-high field glutamate chemical exchange saturation transfer (GluCEST) imaging to investigate the hypothesis that glutamatergic deficits within the reward network contribute to low RR. GluCEST images were acquired at 7.0 T from 45 participants (ages 15-29, 30 females) including 15 healthy individuals, 11 with depression, and 19 with psychosis spectrum symptoms. The GluCEST contrast, a measure sensitive to local glutamate concentration, was quantified in a meta-analytically defined reward network comprised of cortical, subcortical, and brainstem regions. Associations between brain GluCEST contrast and Behavioral Activation System Scale RR scores were assessed using multiple linear regressions. Analyses revealed that reward network GluCEST contrast was positively and selectively associated with RR, but not other clinical features. Follow-up investigations identified that this association was driven by the subcortical reward network and network areas that encode the salience of valenced stimuli. We observed no association between RR and the GluCEST contrast within non-reward cortex. This study thus provides new evidence that reward network glutamate levels contribute to individual differences in RR. Decreased reward network excitatory neurotransmission or metabolism may be mechanisms driving reward network hypofunction and RR deficits. These findings provide a framework for understanding the efficacy of glutamate-modulating psychotropics such as ketamine for treating anhedonia.
Task‐based functional magnetic resonance imaging (tfMRI) has developed as a common alternative in epilepsy surgery to the intracarotid amobarbital procedure, also known as the Wada procedure. Prior ...studies have implicated tfMRI as a comparable predictor of postsurgical cognitive outcomes. However, the predictive validity of tfMRI has not been established. This preregistered systematic review and meta‐analysis (CRD42020183563) synthesizes the literature predicting postsurgical cognitive outcomes in temporal lobe epilepsy (TLE) using tfMRI. The PubMed and PsycINFO literature databases were queried for English‐language articles published between January 1, 2009 and December 31, 2020 associating tfMRI laterality indices or symmetry of task activation with outcomes in TLE. Their references were reviewed for additional relevant literature, and unpublished data from our center were incorporated. Nineteen studies were included in the meta‐analysis. tfMRI studies predicted postsurgical cognitive outcomes in left TLE (ρ̂ = −.27, 95% confidence interval CI = −.32 to −.23) but not right TLE (ρ̂ = −.02, 95% CI = −.08 to .03). Among studies of left TLE, language tfMRI studies were more robustly predictive of postsurgical cognitive outcomes (ρ̂ = −.27, 95% CI = −.33 to −.20) than memory tfMRI studies (ρ̂ = −.27, 95% CI = −.43 to −.11). Further moderation by cognitive outcome domain indicated language tfMRI predicted confrontation naming (ρ̂ = −.32, 95% CI = −.41 to −.22) and verbal memory (ρ̂ = −.26, 95% CI = −.35 to −.17) outcomes, whereas memory tfMRI forecasted only verbal memory outcomes (ρ̂ = −.37, 95% CI = −.57 to −.18). Surgery type, birth sex, level of education, age at onset, disease duration, and hemispheric language dominance moderated study outcomes. Sensitivity analyses suggested the interval of postsurgical follow‐up, and reporting and methodological practices influenced study outcomes as well. These findings intimate tfMRI is a modest predictor of outcomes in left TLE that should be considered in the context of a larger surgical workup.
Olfactory dysfunction in epilepsy is well-documented in several olfactory domains. However, the clinical specificity of these deficits remains unknown. The aim of this systematic meta-analysis was to ...determine which domains of olfactory ability were most impaired in individuals with epilepsy, and to assess moderating factors affecting olfactory ability. Extant peer-reviewed literature on olfaction in epilepsy were identified via a computerized literature search using PubMed, MEDLINE, PsycInfo, and Google Scholar databases. Twenty-one articles met inclusion criteria. These studies included a total of 912 patients with epilepsy and 794 healthy comparison subjects. Included studies measured olfaction using tests of odor identification, discrimination, memory, and detection threshold in patients with different types of epilepsy, including temporal lobe epilepsy (TLE), mixed frontal epilepsy (M-F), and mixed epilepsy (MIX). Olfactory deficits were robust in patients with epilepsy when compared to healthy individuals, with effect sizes in the moderate to large range for several olfactory domains, including odor identification (d = −1.59), memory (d = −1.10), discrimination (d = −1.04), and detection threshold (d = −0.58). Olfactory deficits were most prominent in patients with TLE and M-F epilepsy. Amongst patients with epilepsy, sex, age, smoking status, education, handedness, and age of illness onset were significantly related to olfactory performance. Overall, these meta-analytic findings indicate that the olfactory system is compromised in epilepsy and suggest that detailed neurobiological investigations of the olfactory system may provide further insight into this disorder.
Neurofibromatosis Type 1 (NF1) is a common genetic disorder frequently associated with cognitive deficits. Despite cognitive deficits being a key feature of NF1, the profile of such impairments in ...NF1 has been shown to be heterogeneous. Thus, we sought to quantitatively synthesize the extant literature on cognitive functioning in NF1. A random-effects meta-analysis of cross-sectional studies was carried out comparing cognitive functioning of patients with NF1 to typically developing or unaffected sibling comparison subjects of all ages. Analyses included 50 articles (Total N
= 1,522; M
= 15.70 years, range = 0.52-69.60), yielding 460 effect sizes. Overall moderate deficits were observed g = -0.64, 95% CI = (-0.69, -0.60) wherein impairments differed at the level of cognitive domain. Deficits ranged from large general intelligence: g = -0.95, 95% CI = (-1.12, -0.79) to small emotion: g = -0.37, 95% CI = (-0.63, -0.11). Moderation analyses revealed nonsignificant contributions of age, sex, educational attainment, and parental level of education to outcomes. These results illustrate that cognitive impairments are diffuse and salient across the lifespan in NF1. Taken together, these results further demonstrate efforts should be made to evaluate and address cognitive morbidity in patients with NF1 in conjunction with existing best practices.
Abstract Background Minor physical anomalies (MPAs) are congenital morphological abnormalities linked to disruptions of fetal development. MPAs are common in 22q11.2 deletion syndrome (22q11DS) and ...psychosis spectrum disorders (PS) and likely represent a disruption of early embryologic development that may help identify overlapping mechanisms linked to psychosis in these disorders. Methods Here, 2D digital photographs were collected from 22q11DS ( n = 150), PS ( n = 55), and typically developing (TD; n = 93) individuals. Photographs were analyzed using two computer-vision techniques: (1) DeepGestalt algorithm (Face2Gene (F2G)) technology to identify the presence of genetically mediated facial disorders, and (2) Emotrics—a semi-automated machine learning technique that localizes and measures facial features. Results F2G reliably identified patients with 22q11DS; faces of PS patients were matched to several genetic conditions including FragileX and 22q11DS. PCA-derived factor loadings of all F2G scores indicated unique and overlapping facial patterns that were related to both 22q11DS and PS. Regional facial measurements of the eyes and nose were smaller in 22q11DS as compared to TD, while PS showed intermediate measurements. Conclusions The extent to which craniofacial dysmorphology 22q11DS and PS overlapping and evident before the impairment or distress of sub-psychotic symptoms may allow us to identify at-risk youths more reliably and at an earlier stage of development.
Primary microcephaly (MIM
251200) is an autosomal recessive neurodevelopmental condition in which there is a global reduction in cerebral cortex volume, to a size comparable with that of early ...hominids. We previously mapped the MCPH1 locus, for primary microcephaly, to chromosome 8p23, and here we report that a gene within this interval, encoding a BRCA1 C-terminal domain–containing protein, is mutated in MCPH1 families sharing an ancestral 8p23 haplotype. This gene,
microcephalin, is expressed in the developing cerebral cortex of the fetal brain. Further study of this and related genes may provide important new insights into neocortical development and evolution.
The primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals
. Here, using high-throughput transcriptomic and epigenomic profiling of more ...than 450,000 single nuclei in humans, marmoset monkeys and mice, we demonstrate a broadly conserved cellular makeup of this region, with similarities that mirror evolutionary distance and are consistent between the transcriptome and epigenome. The core conserved molecular identities of neuronal and non-neuronal cell types allow us to generate a cross-species consensus classification of cell types, and to infer conserved properties of cell types across species. Despite the overall conservation, however, many species-dependent specializations are apparent, including differences in cell-type proportions, gene expression, DNA methylation and chromatin state. Few cell-type marker genes are conserved across species, revealing a short list of candidate genes and regulatory mechanisms that are responsible for conserved features of homologous cell types, such as the GABAergic chandelier cells. This consensus transcriptomic classification allows us to use patch-seq (a combination of whole-cell patch-clamp recordings, RNA sequencing and morphological characterization) to identify corticospinal Betz cells from layer 5 in non-human primates and humans, and to characterize their highly specialized physiology and anatomy. These findings highlight the robust molecular underpinnings of cell-type diversity in M1 across mammals, and point to the genes and regulatory pathways responsible for the functional identity of cell types and their species-specific adaptations.
PDF
