Structural Brain Abnormalities Research Articles

Biological Underpinnings of Criminal Behavior: A Comprehensive Review

Background: Traditional criminological theories often emphasize social and environmental factors in criminal behavior. However, early biological research, which was initially reductionist and focused on physical traits, has evolved significantly with advancements in genetics and neuroimaging techniques. This evolution has led to a more nuanced understanding of the role of biological factors in criminal behavior. Objective: This review aims to critically examine how genetic, neurobiological, and psychophysiological factors contribute to criminal behavior, and to explore the interplay between these biological predispositions and environmental influences. Methods: We systematically analyzed empirical studies that investigate the impact of abnormalities in brain structures, neurotransmitter systems, and genetic predispositions on antisocial behaviors, integrating these findings with socio-environmental conditions. Results: Findings from recent studies indicate significant contributions of abnormalities in brain areas such as the prefrontal cortex and amygdala, and dysregulation in neurotransmitter systems to antisocial behaviors. These biological factors, when combined with environmental influences, enhance our understanding of criminal tendencies. Conclusion: The integration of biological perspectives into criminological theories marks a significant shift towards a more holistic approach in the study of criminal behavior. This review advocates for the development of targeted intervention strategies and ethical policy formulations, emphasizing the potential of biological research to improve the efficacy and humanity of the criminal justice system. Ongoing interdisciplinary research and collaboration are essential to continue advancing our understanding and management of criminal behavior.

Structural and functional brain alterations in subthreshold depression: A multimodal coordinate-based meta-analysis.

Imaging studies of subthreshold depression (StD) have reported structural and functional abnormalities in a variety of spatially diverse brain regions. However, there is no consensus among different studies. In the present study, we applied a multimodal meta-analytic approach, the Activation Likelihood Estimation (ALE), to test the hypothesis that StD exhibits spatially convergent structural and functional brain abnormalities compared to healthy controls. A total of 31 articles with 25 experiments were included, collectively representing 1001 subjects with StD. We found consistent differences between StD and healthy controls mainly in the left insula across studies with various neuroimaging methods. Further exploratory analyses found structural atrophy and decreased functional activities in the right pallidum and thalamus in StD, and abnormal spontaneous activity converged to the middle frontal gyrus. Coordinate-based meta-analysis found spatially convergent structural and functional impairments in StD. These findings provide novel insights for understanding the neural underpinnings of subthreshold depression and enlighten the potential targets for its early screening and therapeutic interventions in the future.

Epilepsia partialis continua: A review.

Epilepsia partialis continua (EPC) is a rare type of focal motor seizure characterized by continuous, involuntary muscle contractions in a specific part of the body. These contractions usually involve rhythmic, twitching movements and can last for several hours to days. The seizures are usually limited to one part of the body and can be clonic or dystonic. EPC can affect people of all ages but is more common in children and adolescents. The pathophysiology of EPC is complex and depends on the cause. There are several possible causes of EPC including structural brain abnormalities, infections, metabolic and genetic disorders, inflammatory conditions, traumatic brain injury, and vascular causes. The work-up of EPC includes electroencephalography (EEG), magnetic resonance imaging (MRI) of the brain, position emission tomography (PET) scan of the brain, autoimmune antibodies, infection work-up, and metabolic and genetic work-up. The management of EPC can be challenging. Antiseizure medications (ASDs) including benzodiazepines are an integral part of the management of EPC. Immunotherapy trials are recommended in resistant cases. Epilepsy surgery is one of the effective modalities in some surgically amenable cases. This article reviews the topic of EPC and summarizes diagnostic and .treatment recommendations.

Associations between accelerometer-measured circadian rest-activity rhythm, brain structural and genetic mechanisms, and dementia.

Knowledge of how circadian rhythm influences brain health remains limited. We aimed to investigate the associations of accelerometer-measured circadian rest-activity rhythm (CRAR) with incident dementia, cognitive dysfunction, and structural brain abnormalities in the general population and underlying biological mechanisms. Fifty-seven thousand five hundred and two participants aged over 60 years with accelerometer data were included to investigate the association of CRAR with incidental dementia. Non-parametric CRAR parameters were utilized, including activity level during active periods of the day (M10), activity level during rest periods of the day (L5), and the relative difference between the M10 and L5 (relative amplitude, RA). Associations of CRAR with cognitive dysfunction and brain structure were studied in a subset of participants. Neuroimaging-transcriptomics analysis was utilized to identify the underlying molecular mechanisms. Over 6.86 (4.94-8.78) years of follow-up, 494 participants developed dementia. The risk of incident dementia was associated with decreasing M10 (hazard ratio [HR] 1.45; 95% conference interval [CI], 1.28-1.64) and RA (HR 1.37; 95% CI, 1.28-1.64), increasing L5 (HR 1.14, 95% CI 1.07-1.21) and advanced L5 onset time (HR 1.12; 95% CI, 1.02-1.23). The detrimental associations were exacerbated by APOE ε4 status and age (>65 years). Decreased RA was associated with lower processing speed (Beta -0.04; SE 0.011), predominantly mediated by abnormalities in subcortical regions and white matter microstructure. The genes underlying CRAR-related brain regional structure variation were enriched for synaptic function. Our study underscores the potential of intervention targeting at maintaining a healthy CRAR pattern to prevent dementia risk.

Congenital brain malformations

Malformations of the central nervous system belong to the most common developmental disorders in humans. The clinical presentation of brain malformations is nonspecific including developmental delay, hypotonia, and/or epilepsy. The great heterogeneity concerning etiology, mechanisms of development and morphology is challenging for diagnosis and classification of brain malformations. Thereby recognizing specific malformations is essential for optimal patient management and prognostic evaluation. The aim of this article is to give an overview of several clinically relevant brain malformations occurring from different disrupted developmental processes in brain formation. Several brain malformations are already diagnosed during routine ultrasound in pregnancy. However pre- and postnatal magnetic resonance imaging remains the gold standard in detecting the partially subtle changes and to classify the malformations. Advances in pre- and postnatal neuroimaging techniques and increasing investigation of genetic mechanisms underlying brain formation and its abnormalities have led to abetter understanding of embryologic development and pathogeneses of brain malformations. Besides patient's history and clinical phenotype, neuroimaging plays akey role in diagnosis. Not always aspecific diagnosis can be made, but neuroimaging patterns often enable afocused genetic testing and therefore are revolutionary for etiologic and prognostic assignment. Basic knowledge of brain development facilitates understanding and classifying of structural brain abnormalities.

Abnormal longitudinal changes of structural covariance networks of cortical thickness in mild traumatic brain injury with posttraumatic headache

BackgroundIt is widely acknowledged that mild traumatic brain injury (MTBI) leads to either functionally or anatomically abnormal brain regions. Structural covariance networks (SCNs) that depict coordinated regional maturation patterns are commonly employed for investigating brain structural abnormalities. However, the dynamic nature of SCNs in individuals with MTBI who suffer from posttraumatic headache (PTH) and their potential as biomarkers have hitherto not been investigated. MethodsThis study included 36 MTBI patients with PTH and 34 well-matched healthy controls (HCs). All participants underwent magnetic resonance imaging scans and were assessed with clinical measures during the acute and subacute phases. Structural covariance matrices of cortical thickness were generated for each group, and global as well as nodal network measures of SCNs were computed. ResultsMTBI patients with PTH demonstrated reduced headache impact and improved cognitive function from the acute to subacute phase. In terms of global network metrics, MTBI patients exhibited an abnormal normalized clustering coefficient compared to HCs during the acute phase, although no significant difference in the normalized clustering coefficient was observed between the groups during the subacute phase. Regarding nodal network metrics, MTBI patients displayed alterations in various brain regions from the acute to subacute phase, primarily concentrated in the prefrontal cortex (PFC). ConclusionsThese findings indicate that the cortical thickness topography in the PFC determines the typical structural-covariance topology of the brain and may serve as an important biomarker for MTBI patients with PTH.

Uremic toxins and the brain in chronic kidney disease.

Chronic kidney disease (CKD) patients have an increased risk for cognitive impairment compared to the general population. The risk is much higher in CKD patients who progress to end-stage kidney disease (ESKD) and require hemodialysis or peritoneal dialysis. Multiple factors maycontribute to cognitive impairment in CKD patients and in patients on chronic dialysis. However, the observation that, after kidney transplantation, there is an improvement in several cognitive performance markers and that some structural and functional brain abnormalities mayimprove suggests that cognitive deficits in patients on dialysis may be at least partially reversible. Recent evidence supports the hypothesis that uremic toxins may disrupt the blood brain barrier and damage the brain cells. Such brain toxicity should prompt efforts to lower the burden of uremic toxins through dialytic and non-dialytic strategies.

Original Research: Clinical Significance of a Unique Pediatric EEG Configuration: Bi-Frontal Spikes With Simultaneous Bi-Occipital Positivity.

Introduction: Frontal-predominant epileptiform discharges (EDs) include generalized spike-wave (GSW) and frontal spikes (FS). However, negative bi-frontal ED with simultaneous occipital positivity (BFOD) are rare, leading to questions regarding physiological generators. Methods: To determine the clinical significance of BFOD, electroclinical features of children with BFOD (n = 40) were compared to control patients with GSW (n = 102) and FS (n = 100). Results: Results are presented in the following order: BFOD, GSW, and FS. Epilepsy was prevalent among the groups: 95.0%, 90.2%, and 77.0%, respectively. The median age of seizure-onset did not significantly differ between groups: 3.00, 4.00, and 2.25 years, respectively. Regarding EEG background features, the BFOD group had more disorganized sleep architecture than other groups, P < .005. There was a significant difference in the proportion of developmental delay (DD) between the groups (P < .005). BFOD had much higher odds of DD compared to GSW and FS groups: odds ratio (OR) (confidence interval [CI]) 19.44 [5.64, 64.05] and 3.98 [1.16, 13.34]. Furthermore, BFOD had much higher odds of severe DD compared to GSW and FS groups: 9.60 [2.75, 33.45] and 2.73 [1.03, 7.27]. A Gross Motor Function Classification System (GMFCS) score of ≥ 4 was more prevalent in BFOD (22.5%), than GSW (0%) and FS groups (9%). On neuroimaging, BFOD had more structural (P < .005) and multilobar structural (P < .05) abnormalities than control groups. Conclusion: Children with BFOD had particularly severe significant DD, considerable motor deficit (GMFCS ≥ 4), and brain structural abnormalities, often multilobar. This suggests BFOD is a marker of severe underlying brain dysfunction and not benign when encountered on routine EEG review.

Causal interactions in brain networks predict pain levels in trigeminal neuralgia

Trigeminal neuralgia (TN) is a highly debilitating facial pain condition. Magnetic resonance imaging (MRI) is the main method for generating insights into the central mechanisms of TN pain in humans. Studies have found both structural and functional abnormalities in various brain structures in TN patients as compared with healthy controls. Whereas studies have also examined aberrations in brain networks in TN, no studies have to date investigated causal interactions in these brain networks and related these causal interactions to the levels of TN pain. We recorded fMRI data from 39 TN patients who either rested comfortably in the scanner during the resting state session or tracked their pain levels during the pain tracking session. Applying Granger causality to analyze the data and requiring consistent findings across the two scanning sessions, we found 5 causal interactions, including: (1) Thalamus → dACC, (2) Caudate → Inferior temporal gyrus, (3) Precentral gyrus → Inferior temporal gyrus, (4) Supramarginal gyrus → Inferior temporal gyrus, and (5) Bankssts → Inferior temporal gyrus, that were consistently associated with the levels of pain experienced by the patients. Utilizing these 5 causal interactions as predictor variables and the pain score as the predicted variable in a linear multiple regression model, we found that in both pain tracking and resting state sessions, the model was able to explain ∼36 % of the variance in pain levels, and importantly, the model trained on the 5 causal interaction values from one session was able to predict pain levels using the 5 causal interaction values from the other session, thereby cross-validating the models. These results, obtained by applying novel analytical methods to neuroimaging data, provide important insights into the pathophysiology of TN and could inform future studies aimed at developing innovative therapies for treating TN.

Limb-Clasping Response in NMDA Receptor Palmitoylation-Deficient Mice.

Proper regulation of N-methyl-D-aspartate-type glutamate receptor (NMDA receptor) expression is responsible for excitatory synaptic functions in the mammalian brain. NMDA receptor dysfunction can cause various neuropsychiatric disorders and neurodegenerative diseases. Posttranslational protein S-palmitoylation, the covalent attachment of palmitic acid to intracellular cysteine residues via thioester bonds, occurs in the carboxyl terminus of GluN2B, which is the major regulatory NMDA receptor subunit. Mutations of three palmitoylatable cysteine residues in the membrane-proximal cluster of GluN2B to non-palmitoylatable serine (3CS) lead to the dephosphorylation of GluN2B Tyr1472 in the hippocampus and cerebral cortex, inducing a reduction in the surface expression of GluN2B-containig NMDA receptors. Furthermore, adult GluN2B 3CS homozygous mice demonstrated a definite clasping response without abnormalities in the gross brain structure, other neurological reflexes, or expression levels of synaptic proteins in the cerebrum. This behavioral disorder, observed in the GluN2B 3CS knock-in mice, indicated that complex higher brain functions are coordinated through the palmitoylation-dependent regulation of NMDA receptors in excitatory synapses.

Machine learning based on the EEG and structural MRI can predict different stages of vascular cognitive impairment.

Vascular cognitive impairment (VCI) is a major cause of cognitive impairment in the elderly and a co-factor in the development and progression of most neurodegenerative diseases. With the continuing development of neuroimaging, multiple markers can be combined to provide richer biological information, but little is known about their diagnostic value in VCI. A total of 83 subjects participated in our study, including 32 patients with vascular cognitive impairment with no dementia (VCIND), 21 patients with vascular dementia (VD), and 30 normal controls (NC). We utilized resting-state quantitative electroencephalography (qEEG) power spectra, structural magnetic resonance imaging (sMRI) for feature screening, and combined them with support vector machines to predict VCI patients at different disease stages. The classification performance of sMRI outperformed qEEG when distinguishing VD from NC (AUC of 0.90 vs. 0,82), and sMRI also outperformed qEEG when distinguishing VD from VCIND (AUC of 0.8 vs. 0,0.64), but both underperformed when distinguishing VCIND from NC (AUC of 0.58 vs. 0.56). In contrast, the joint model based on qEEG and sMRI features showed relatively good classification accuracy (AUC of 0.72) to discriminate VCIND from NC, higher than that of either qEEG or sMRI alone. Patients at varying stages of VCI exhibit diverse levels of brain structure and neurophysiological abnormalities. EEG serves as an affordable and convenient diagnostic means to differentiate between different VCI stages. A machine learning model that utilizes EEG and sMRI as composite markers is highly valuable in distinguishing diverse VCI stages and in individually tailoring the diagnosis.

De novo variants in GABRA4 are associated with a neurological phenotype including developmental delay, behavioral abnormalities and epilepsy.

Nine out of 19 genes encoding GABAA receptor subunits have been linked to monogenic syndromes characterized by seizures and developmental disorders. Previously, we reported the de novo variant p.(Thr300Ile) in GABRA4 in a patient with epilepsy and neurodevelopmental abnormalities. However, no new cases have been reported since then. Through an international collaboration, we collected molecular and phenotype data of individuals carrying de novo variants in GABRA4. Patients and their parents were investigated either by exome or genome sequencing, followed by targeted Sanger sequencing in some cases. All variants within the transmembrane domain, including the previously reported p.(Thr300Ile) variant, were characterized in silico and analyzed by molecular dynamics (MD) simulation studies. We identified three novel de novo missense variants in GABRA4 (NM_000809.4): c.797 C > T, p.(Pro266Leu), c.899 C > A, p.(Thr300Asn), and c.634 G > A, p.(Val212Ile). The p.(Thr300Asn) variant impacts the same codon as the previously reported variant p.(Thr300Ile) and likely arose post-zygotically as evidenced by sequencing oral mucosal cells. Overlapping phenotypes among affected individuals included developmental delay (4/4), epileptiform EEG abnormalities (3/4), attention deficits (3/4), seizures (2/4), autistic features (2/4) and structural brain abnormalities (2/4). MD simulations of the three variants within the transmembrane domain of the receptor indicate that sub-microsecond scale dynamics differ between wild-type and mutated subunits. Taken together, our findings further corroborate an association between GABRA4 and a neurological phenotype including variable neurodevelopmental, behavioral and epileptic abnormalities.

Cognitive outcome and its neural correlates after cardiorespiratory arrest in childhood.

Hypoxia-ischaemia (HI) can result in structural brain abnormalities, which in turn can lead to behavioural deficits in various cognitive and motor domains, in both adult and paediatric populations. Cardiorespiratory arrest (CA) is a major cause of hypoxia-ischaemia in adults, but it is relatively rare in infants and children. While the effects of adult CA on brain and cognition have been widely studied, to date, there are no studies examining the neurodevelopmental outcome of children who suffered CA early in life. Here, we studied the long-term outcome of 28 children who suffered early CA (i.e., before age 16). They were compared to a group of control participants (n=28) matched for age, sex and socio-economic status. The patient group had impairments in the domains of memory, language and academic attainment (measured using standardised tests). Individual scores within the impaired range were most commonly found within the memory domain (79%), followed by academic attainment (50%), and language (36%). The patient group also had reduced whole brain grey matter volume, and reduced volume and fractional anisotropy of the white matter. In addition, lower performance on memory tests was correlated with bilaterally reduced volume of the hippocampi, thalami, and striatum, while lower attainment scores were correlated with bilateral reduction of fractional anisotropy in the superior cerebellar peduncle, the main output tract of the cerebellum. We conclude that patients who suffered early CA are at risk of developing specific cognitive deficits associated with structural brain abnormalities. RESEARCH HIGHLIGHTS: Our data shed light on the long-term outcome and associated neural mechanisms after paediatric hypoxia-ischaemia as a result of cardiorespiratory arrest. Patients had impaired scores on memory, language and academic attainment. Memory impairments were associated with smaller hippocampi, thalami, and striatum. Lower academic attainment correlated with reduced fractional anisotropy of the superior cerebellar peduncle.

Is Cranial Imaging Necessary in Children with First-Time Focal Seizures?

Objective: Seizures in children represent a common cause of admission to the emergency department. This study aimed to determine clinically significant intracranial abnormalities in children presenting to the pediatric emergency department with first-time focal seizures.&#x0D; Methods: Patients aged 1 month-18 years, who presented to the pediatric emergency department with first-time focal seizures between 2009 and 2019, were retrospectively screened. Patients with a history of trauma, cases in which focal neurological signs could not be assessed, and patients with pre-existing structural brain or neurological abnormalities, and metabolic disorders were excluded from the study. Cranial computed tomography findings were re-evaluated by a pediatric radiologist. The fourth and fifth-level according to the classification of the International League Against Epilepsy were interpreted as urgent intracranial pathologies requiring medical or surgical intervention. The univariate analysis was performed using the chi-square test for categorical data and the Mann-Whitney U test for continuous data.&#x0D; Results: The mean age of the 121 patients was 46.8±44.4 months, and 52.9% were male. Clinically significant emergency intracranial pathologies were detected in the neuroimaging of eight patients. Intracranial masses, bleeding, and hematomas were the most common pathologies. The presence of focal neurologic findings and an age below six months were clinically determined as predictors of an urgent intracranial pathology.&#x0D; Conclusion: We found the rate of urgent cranial pathologies to be 6.6% in patients presenting to the emergency department following the first focal seizure. Children younger than six months with focal neurological signs should be evaluated for emergency neuroimaging.

Gestational diabetes mellitus as a risk factor for neuropsychiatric pathology in offspring

This review article summarizes current ideas about gestational diabetes mellitus as an independent risk factor for long-term neuropsychiatric morbidity in offspring. Herein, we describe the genetic programming patterns of morphofunctional brain development during intrauterine life, which provide the basis for short- and long-term functions of the central nervous system. The results of experimental and clinical studies are presented that explain the pathophysiological mechanisms of the harmful effects on the fetal brain of hyperglycemia, hyperinsulinemia, hyperlepthyremia, oxidative stress, and systemic inflammation in the mother with pregnancy complicated by diabetes mellitus. We also discuss structural brain abnormalities and neuropsychiatric consequences. The article substantiates the need for the prevention of neuropsychiatric diseases in the offspring of women with obesity and other concomitant pathology at the stage of family planning, and at the onset of pregnancy, the expediency of early screening, treatment of gestational diabetes mellitus and neuroprotection in the perinatal period of the child’s life.

Stress-induced failure of embodied cognition: A general model

We derive the classic, ubiquitous, but enigmatic Yerkes–Dodson effect of applied stress on real-world performance in a highly natural manner from fundamental assumptions on cognition and its dynamics, as constrained by the asymptotic limit theorems of information and control theories. We greatly extend the basic approach by showing how differences in an underlying probability model can affect the dynamics of decision across a broad range of cognitive enterprise. Most particularly, however, this development may help inform our understanding of the different expressions of human psychopathology. A ‘thin tailed’ underlying distribution appears to characterize expression of ‘ordinary’ situational depression/anxiety symptoms of conditions like burnout induced by toxic stress. A ‘fat tailed’ underlying distribution appears to be associated with brain structure and function abnormalities leading to serious mental illness and poor decision making where symptoms are not only emerging in the setting of severe stress but may also appear in a highly punctuated manner at relatively lower levels of stress. A simple hierarchical optimization shows how environmental ‘shadow price’ constraints can buffer or aggravate the effects of stress and arousal. Extension of the underlying theory to other patterns of pathology, like immune disorders and premature aging, seems apt. Applications to the punctuated dynamics of institutional cognition under stress also appear possible. Ultimately, the probability models studied here can be converted to new statistical tools for the analysis of observational and experimental data.

Application of machine learning techniques in the diagnostic approach of PTSD using MRI neuroimaging data: A systematic review

BackgroundAt present, the diagnosis of post-traumatic stress disorder（PTSD） mainly relies on clinical symptoms and psychological scales, and finding objective indicators that are helpful for diagnosis has always been a challenge in clinical practice and academic research. Neuroimaging is a useful and powerful tool for discovering the biomarkers of PTSD,especially functional MRI (fMRI), structural MRI (sMRI) and Diffusion Weighted Imaging（DTI）are the most commonly used technologies, which can provide multiple perspectives on brain function, structure and its connectivity. Machine learning (ML) is an emerging and potentially powerful method, which has aroused people's interest because it is used together with neuroimaging data to define brain structural and functional abnormalities related to diseases, and identify phenotypes, such as helping physicians make early diagnosis. ObjectivesAccording to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) declaration, a systematic review was conducted to assess its accuracy in distinguishing between PTSD patients, TEHC(Trauma-Exposed Healthy Controls), and HC(healthy controls). MethodsWe searched PubMed, Embase, and Web of Science using common words for ML methods and PTSD until June 2023, with no language or time limits. This review includes 13 studies, with sensitivity, specificity, and accuracy taken from each publication or acquired directly from the authors. ResultsAll ML techniques have an diagnostic accuracy rate above 70%，and support vector machine（SVM） are the most commonly used techniques. This series of studies has revealed significant neurobiological differences in key brain regions among individuals with PTSD, TEHC, and HC. The connectivity patterns of regions such as the Insula and Amygdala hold particular significance in distinguishing these groups. TEHC exhibits more normal connectivity patterns compared to PTSD, providing valuable insights for the application of machine learning in PTSD diagnosis. ConclusionIn contrast to any currently available assessment and clinical diagnosis, ML techniques can be used as an effective and non-invasive support for early identification and detection of patients as well as for early screening of high-risk populations.

Structural brain abnormalities in Pallister-Killian syndrome: a neuroimaging study of 31 children

BackgroundPallister-Killian syndrome (PKS) is a rare genetic disorder caused by mosaic tetrasomy of 12p with wide neurological involvement. Intellectual disability, developmental delay, behavioral problems, epilepsy, sleep disturbances, and brain malformations have been described in most individuals, with a broad phenotypic spectrum. This observational study, conducted through brain MRI scan analysis on a cohort of patients with genetically confirmed PKS, aims to systematically investigate the neuroradiological features of this syndrome and identify the possible existence of a typical pattern. Moreover, a literature review differentiating the different types of neuroimaging data was conducted for comparison with our population.ResultsThirty-one individuals were enrolled (17 females/14 males; age range 0.1–17.5 years old at first MRI). An experienced pediatric neuroradiologist reviewed brain MRIs, blindly to clinical data. Brain abnormalities were observed in all but one individual (compared to the 34% frequency found in the literature review). Corpus callosum abnormalities were found in 20/30 (67%) patients: 6 had callosal hypoplasia; 8 had global hypoplasia with hypoplastic splenium; 4 had only hypoplastic splenium; and 2 had a thin corpus callosum. Cerebral hypoplasia/atrophy was found in 23/31 (74%) and ventriculomegaly in 20/31 (65%). Other frequent features were the enlargement of the cisterna magna in 15/30 (50%) and polymicrogyria in 14/29 (48%). Conversely, the frequency of the latter was found to be 4% from the literature review. Notably, in our population, polymicrogyria was in the perisylvian area in all 14 cases, and it was bilateral in 10/14.ConclusionsBrain abnormalities are very common in PKS and occur much more frequently than previously reported. Bilateral perisylvian polymicrogyria was a main aspect of our population. Our findings provide an additional tool for early diagnosis.Further studies to investigate the possible correlations with both genotype and phenotype may help to define the etiopathogenesis of the neurologic phenotype of this syndrome.

PAK3 activation promotes the tangential to radial migration switch of cortical interneurons by increasing leading process dynamics and disrupting cell polarity.

Mutations of PAK3, a p21-activated kinase, are associated in humans with cognitive deficits suggestive of defective cortical circuits and with frequent brain structural abnormalities. Most human variants no longer exhibit kinase activity. Since GABAergic interneurons express PAK3 as they migrate within the cortex, we here examined the role of PAK3 kinase activity in the regulation of cortical interneuron migration. During the embryonic development, cortical interneurons migrate a long distance tangentially and then re-orient radially to settle in the cortical plate, where they contribute to cortical circuits. We showed that interneurons expressing a constitutively kinase active PAK3 variant (PAK3-ca) extended shorter leading processes and exhibited unstable polarity. In the upper cortical layers, they entered the cortical plate and extended radially oriented processes. In the deep cortical layers, they exhibited erratic non-processive migration movements and accumulated in the deep pathway. Pharmacological inhibition of PAK3 kinase inhibited the radial migration switch of interneurons to the cortical plate and reduced their accumulation in the deep cortical layers. Interneurons expressing a kinase dead PAK3 variant (PAK3-kd) developed branched leading processes, maintained the same polarity during migration and exhibited processive and tangentially oriented movements in the cortex. These results reveal that PAK3 kinase activity, by promoting leading process shortening and cell polarity changes, inhibits the tangential processive migration of interneurons and favors their radial re- orientation and targeting to the cortical plate. They suggest that patients expressing PAK3 variants with impaired kinase activity likely present alterations in the cortical targeting of their GABAergic interneurons.

Children’s early signs and developmental trajectories of psychotic-like experiences

IntroductionChildren who experience persistent psychotic-like experiences (PLEs) are at a higher risk of developing psychotic disorder later in life. The developmental trajectories of PLEs are influenced by various factors. Therefore, it is important to identify early characteristics that can distinguish and predict between different developmental trajectories of PLEs. MethodsUsing PLEs scores from the Adolescent Brain Cognitive Development (ABCD) data across three waves, we categorized participants into five distinct PLEs trajectories groups: persistent group (n = 47), remitting group (n = 185), increasing group (n = 117), remittent group (n = 21), and no PLEs group (n = 4,476). We utilized linear mixed-effect models and generalized linear mixed-effect models to examine the differences in baseline characteristics, including psychological and behavioral problems, suicidality, trauma experiences, developmental milestones, cognitive function, physical health, family income, family history of mental illness, and brain structureamong these PLEs trajectory groups. ResultsWe found that psychological and behavioral problems (such as DSM-oriented scales/externalizing/ADHD/social/attention/thought problems) assessed by the Child Behavior Checklist (CBCL) were associated with all PLEs groups. The persistent PLEs group had greater ADHD/social/thought problems and suicidal behavior compared to the remitting PLEs group. Comparing with the no PLEs group, poor cognitive function, abnormal brain structure (such as temporal lobe and supramarginal gyrus), more trauma experiences, and lower family income were found in only one of the PLEs groups, but not all PLEs groups. ConclusionThe development of PLEs is accompanied by changes in many domains, implying a dynamic and complex developmental process. Given that psychological and behavioral problems can predict the emergence of PLEs at any time and can be regarded as risk factors for persistent PLEs, thereby enabling early precisely interventions, it is important to place greater emphasis on assessing psychological and behavioral problems.