General Deficit Research Articles

Exhaustion Disorder in Primary Care: A Comparison With Major Depressive Disorder and Adjustment Disorder.

Exhaustion disorder (ED) was introduced to the Swedish version of the International Classification of Diseases, 10th edition (ICD-10) 2005. Primarily characterized by general fatigue and cognitive deficits, ED has become one of the most common mental health diagnoses in Sweden. Little is still known regarding the discriminative validity of the ED diagnosis and how it relates to other diagnostic constructs. The study aimed to investigate the discriminative validity of ED compared with two similar diagnoses, major depressive disorder (MDD) and adjustment disorder (AD). Using data from a sample of patients with a principal diagnosis of either ED (n = 352), MDD (n = 99), or AD (n = 302), we compared demographic and clinical variables and scores on self-report symptom scales. Results showed that ED patients were of a higher age and had a higher frequency of sickness absence than MDD and AD patients. There was a substantial overlap of symptoms between ED and MDD, only differing on two of nine self-report symptom scales, with ED patients rating lower work ability d = -0.37 and alcohol consumption d = -0.57. Compared with AD patients, ED patients reported more severe symptoms in every symptom domain. Given the prevalent use of ED diagnosis, its diagnostic validity and clinical usefulness merit further attention.

A 20-year tale on closing-in behavior in graphic copying tasks: Revisiting Della Sala's findings in new samples of patients with dementia and stroke

Closing-in behavior (CIB) is characterized by the placement of the graphic copy near (Near CIB) or even on the top of (Overlap CIB) the stimulus to be reproduced. Although CIB has received little attention in the literature, Sergio Della Sala and colleagues made important contributions to the understanding of the phenomenon. They noted that CIB is often observed in Alzheimer's Disease but is also present in other forms of dementia and mild cognitive impairment and stroke; they argued that CIB may reflect a deficit in executive function, rather than working memory, and that the phenomenon occurs more frequently in dual task conditions. Importantly, they demonstrated that CIB may not be specific to copying but may instead reflect a general deficit in decoupling movement location from the focus of attention. In the present study, we explored these observations in a mixed sample of 106 participants (AD n = 37, frontal stroke n = 25, other forms of dementia n = 24, and normal controls n = 20). First, we confirmed that CIB is equally common in AD, other forms of dementia and frontal stroke. Second, we confirmed the association between CIB and executive function deficits. Third, we showed that individuals with CIB are more likely to exhibit the phenomenon in dual task situations, in which line-drawing is associated with an unrelated secondary task (tapping, counting, or counting backward). The present work supports and extends the contributions of Della Sala and colleagues demonstrating that CIB is enhanced when the general attentional load of the task increases.

Current trends in vestibular schwannoma management at a referral center in Indonesia: A cross-sectional study with retrospective data collection

Background. Vestibular schwannoma (VS) is the most common benign brain tumor of the cerebellopontine angle. Due to its location, this pathology can create both focal and general deficits. The registry system for VS in Indonesia is developing, including in the author’s institution, which eventually shows a changing trend in managing VS. Methods. We retrospectively collected data from all patients diagnosed with vestibular schwannoma, based on histological or radiological results. Treatments included craniotomy and/or Gamma Knife Radiosurgery (GKRS) from 2018 to 2023. Results. Data from 88 patients were analyzed. The number of treated patients has increased annually. VS predominantly affects females (64%). The proportion between GKRS and craniotomy procedures also shifted throughout the year. Common symptoms included hearing loss (63.6%), disequilibrium (50%), and headaches (39.7%). The most common tumor size was medium (15-30 mm; n=37; 42%). Tumors that fell into the intrameatal and small (<15 mm) categories were all treated with GKRS, whereas the other groups were divided into GKRS and craniotomy. GKRS demonstrated high efficacy in tumor control and favorable hearing and facial nerve preservation, whereas craniotomy remained crucial for larger tumors. Conclusion. The number of VS diagnosed each year has increased in our center, accompanied by a noticeable shift in preference from GKRS to craniotomy, which is influenced by the integration of intraoperative monitoring. Treatment preference was further determined based on the clinical profile and tumor size. In the future, there is a need to develop a national registry to better reflect the true incidence of VS within the Indonesian population.

Response inhibition deficits in math-anxious individuals.

We examined whether math anxiety is related to a response inhibition deficit and, if so, whether it is a domain-specific inhibition deficit in numerical tasks or a general inhibition deficit. Behavioral performance and electroencephalogram activity were recorded while 28 highly math-anxious (HMA) and 28 low math-anxious (LMA) individuals performed both a numerical and a non-numerical Go/Nogo task. In the numerical task, single-digit numbers were presented, and participants were asked to press a button if the number was even. In the non-numerical task, letters were presented, and the button had to be pressed if the letter was a vowel. Nogo trials were answered less accurately and elicited larger Nogo-N2 and Nogo-P3 than Go trials in both tasks and both groups. Importantly, behavioral and brain response differences between tasks were only found in the HMA group. First, they were more error-prone in numerical Nogo than in non-numerical Nogo trials; and second, their Nogo-N2 and N2d (Nogo-Go difference) were smaller in the numerical task than in the non-numerical task. No differences were found in the LMA group. These results suggest that HMA individuals' response inhibition is impaired specifically when dealing with numbers, which could contribute to their low achievement in math tasks.

Acute nicotine exposure attenuates neurological deficits, ischemic injury and brain inflammatory responses and restores hippocampal long-term potentiation in ischemic stroke followed by lipopolysaccharide-induced sepsis-like state

Ischemic stroke is followed by an increased susceptibility to bacterial infections, which exacerbate histological stroke outcome, neurological deficits and memory impairment due to increased neuroinflammation and neurotransmitter dysfunction. Pharmacological activation of nicotinic acetylcholine receptors was suggested to mitigate brain inflammatory responses in ischemic stroke. The functional responses associated with nicotinic acetylcholine receptor activation were unknown. In this study, male NMRI mice subjected to transient intraluminal middle cerebral artery occlusion (MCAO) were intraperitoneally exposed to vehicle treatment or Escherichia coli lipopolysaccharide (LPS; 4 mg/kg)-induced sepsis-like state 24 h post-MCAO, followed by intraperitoneal administration of vehicle or nicotine (0.5 mg/kg) 30 min later. Over 96 h, rectal temperature, neurological deficits, spontaneous locomotor activity, working memory, ischemic injury, synaptic plasticity, and brain inflammatory responses were evaluated by temperature measurement, behavioral analysis, infarct volumetry, electrophysiological recordings, and polymerase-chain reaction analysis. LPS-induced sepsis induced hypothermia, increased general and focal neurological deficits, reduced spontaneous exploration behavior, reduced working memory, and increased infarct volume post-MCAO. Additional treatment with nicotine attenuated LPS-induced hypothermia, reduced neurological deficits, restored exploration behavior, restored working memory, and reduced infarct volume. Local field potential recordings revealed that LPS-induced sepsis decreased long-term potentiation (LTP) in the dentate gyrus post-MCAO, whereas concomitant nicotine exposure restored LTP in the contralateral dentate gyrus. LPS-induced sepsis increased microglial/ macrophage Iba-1 mRNA and astrocytic GFAP mRNA levels post-MCAO, whereas add-on nicotine treatment reduced astrocytic GFAP mRNA. Taken together, these findings indicate that acute nicotine exposure enhances functional stroke recovery. Future studies will have to evaluate the effects of (1) chronic nicotine exposure, a clinically relevant vascular risk factor, and (2) the cessation of nicotine exposure, which is widely recommended post-stroke, but might have detrimental effects in the early stroke recovery phase.

Examining Food-Specific and General Inhibitory Control and Working Memory as Moderators of Relations Between Emotion Regulation Difficulties and Eating Pathology in Adults With Overweight/Obesity: A Preregistered, Cross-Sectional Study.

Empirical research and theory support the interaction of executive functions (e.g., inhibitory control, working memory) and emotion regulation in guiding goal-oriented behavior; however, applications to eating pathology (e.g., binge eating) are limited. Such research is scant with adults with overweight/obesity (AwO/O), a population reporting high levels of binge eating, emotion regulation difficulties, and deficits in inhibitory control and working memory. We tested interactions between emotion regulation and executive functioning in relation to eating pathology in AwO/O while considering stimuli-specific deficits (e.g., food-specific deficits) in behavioral task performance. AwO/O (N = 204; MBMI = 32.11; Mage = 38.30 [SD = 12.16]) completed a preregistered, online study assessing demographics and emotion regulation difficulties (Difficulties in Emotional Regulation Scale), inhibitory control (go/no-go task, food and general stimuli), working memory (N-Back Task, food and general stimuli), binge eating (Binge Eating Scale), and disordered eating (Eating Disorder Examination-Questionnaire). There was limited evidence of moderation in models examining food-specific and general inhibitory control and working memory, emotion regulation difficulties, and binge eating. Preliminary support was found for emotion regulation difficulties to be more strongly associated with more disordered eating in AwO/O reporting more food-specific and general working memory deficits. Consistent, positive associations between emotion regulation difficulties and eating pathology were observed. Among adults with AwO/O, emotion regulation difficulties are closely related to eating pathology, regardless of performance on working memory and inhibitory control tasks. Clinicians and researchers working with AwO/O may consider how emotion regulation difficulties and working memory deficits work together to influence disordered eating.

The Impact of Customs Revenues on The General Budget Deficit in A Middle East Country

This research aims to identify the concept of customs revenues and their impact on the state’s general budget deficit. The problem of the study stems from the following question: What is the impact of customs revenues on the general budget deficit in Iraq? To answer this question, this research uses the deductive approach and the estimation approach by analyzing and measuring the impact of customs revenues in supporting the state’s general budget. Among the most important results of the study are: There are many reasons that led to the emergence of a deficit in the state’s general budget throughout the study period, the most important of which is the decrease in Customs revenues as a result of the weak role of tax revenues It recommended the need to address the imbalance in the structure of public revenues by activating the role of taxes and fees and reducing dependence on the oil resource.

Targeting heterozygous dominant negative variant of KCNA2 using Gapmer ASO for the treatment of drug-resistant epilepsy

A missense mutation c.1220C>G of KCN2A gene was recently identified in an infant with epilepsy. KCNA2 encodes Kv1.2 subunits that form voltage-gated potassium channels (VGKC) via tetrameric assembly. The mutation results in amino acid change P407R at the highly conserved PVP motif. Functional characterization revealed that mutant Kv1.2_P407R subunits formed loss-of-function channels and suppressed both Kv1.2 and Kv1.1 channel activities. Hetero-tetrameric assembly of the Kv1.2_P407R subunits with other neuronal voltage-gated potassium channels of Shaker subfamily could lead to general deficit of repolarising potassium current and potentially underlie the enhanced seizure susceptibility. Indeed, expression of human Kv1.2_P407R in early postnatal rat cortical neurons or genetically engineered hESC-derived neurons disclosed broadening of action potential duration and early afterdepolarization (EAD), associating with reduced potassium current. We hypothesize that Gapmer antisense oligonucleotides (ASO) targeted to c.1220C>G mutation will selectively degrade the mutant mRNA while allowing the remaining WT subunits to form functional channels. As a proof of principle, delivery of Gapmer packaged in lipid nanoparticle into cortical neurons selectively suppressed Kv1.2_P407R over the WT protein expression, reversing the broadening of action potential duration, abrogating the EAD and leading to overall increase in potassium current.

Subjective visual vertical/horizontal and video head impulse test in dyslexic children.

Different studies have tried to establish a relationship between dyslexia and the vestibular system function. Subjective Visual Vertical/Horizontal (SVV and SVH) and Video Head Impulse Test (VHIT) are useful for studying the vestibular system and can be easily performed in children. Our aim was to evaluate the vestibular function in dyslexic children by SVV/SVH and VHIT. We enrolled 18 dyslexic children (10M/8F; mean age 10.7 ± 2.3 years; range 7-14 years) and 18 age-matched children with typical development of learning abilities. All children performed VHIT, SVV and SVH. We found normal gain and symmetry of vestibulo-ocular-reflex both in dyslexic and typically developing children. Fifteen out of 18 dyslexic children (83.3%) showed a difference of at least one amongst SVV or SVH. The mean value of SVV was 2.3° and the mean value of SVH was 2.6°. Statistical analysis showed a significant difference between typically developing and dyslexic children for both SVV and SVH. We confirm a relationship between dyslexia and the alteration of SVV and SVH. Our results could be related to the pathogenetic hypothesis of a visual processing impairment related to a dysfunction of the magnocellular pathway or to a general deficit related to a multimodal cortical network.

Not a Deficit, Just Different: Prepulse Inhibition Disruptions in Autism Depend on Startle Stimulus Intensities.

Sensory processing disruptions are a core symptom of autism spectrum disorder (ASD) and other neurological disorders. The acoustic startle response and prepulse inhibition (PPI) are common metrics used to assess disruptions in sensory processing and sensorimotor gating in clinical studies and animal models. However, often there are inconsistent findings on ASD-related PPI deficits across different studies. Here, we used a novel method for assessing changes in startle and PPI in rodents, using the Cntnap2 knock-out (KO) rat model for neurodevelopmental disorder/ASD that has consistently shown PPI disruptions in past studies. We discovered that not only sex and prepulse intensity but also the intensity of the startle stimulus profoundly impacts whether PPI deficits are evident in the Cntnap2 KO rat or not. We show that rats do not universally exhibit a PPI deficit; instead, impaired PPI is contingent on specific testing conditions. Notably, at lower startle stimulus intensities, Cntnap2 KO rats not only demonstrated intact PPI but also exhibited evidence of enhanced PPI compared with their wild-type counterparts. This finding emphasizes the importance of considering specific testing conditions when evaluating startle and PPI in the context of ASD and other neuropsychiatric conditions and might explain some of the inconsistencies between different studies.

Evidence for different visual processing strategy for non-face stimuli in developmental prosopagnosia

ABSTRACT We assembled a test battery to investigate developmental prosopagnosia (DP), a neurodevelopmental syndrome resulting in severe face recognition difficulties. To screen for general cognitive deficits that could explain poor face test performance, participants completed a fluid reasoning task using abstract shapes. This initial screening showed that DPs (n = 21) were more accurate than neurotypical controls (n = 90) but significantly slower, suggesting speed-accuracy trade-off. To address this, we calculated the Balanced Integration Score and found no group differences, highlighting that DPs clearly adopted a different strategy from controls. DPs’ longer response times (RT) on face tasks vs controls are commonly interpreted as evidence of impairment and of lengthy, atypical featural face processing. Our data suggest this interpretation may be unreliable since clear RT differences were also observed in two non-face tasks where DPs showed no accuracy impairment. Instead, slower RTs appear to reflect a strategy shift in DPs.

Predictors Associated with the Need for Open Reduction of Pediatric Supracondylar Humerus Fractures: A Meta-analysis of the Recent Literature.

Supracondylar humerus (SCH) fractures are some of the most common fractures in pediatric patients with surgery typically consisting of either open or closed reduction with internal fixation. The aim of this meta-analysis was to identify patient, injury, and administrative factors that are associated with treating pediatric SCH fractures with open techniques. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, PubMed and CINAHL database searches were conducted for studies from 2010 to 2023 that made direct comparisons between open reduction and internal fixation (ORIF) and closed reduction and percutaneous pinning (CRPP) for treating SCH fractures in the pediatric population. The search terms used were "pediatric" AND "SCH fracture" OR "distal humerus fracture." Screening, quality assessment, and data extraction were performed by 4 reviewers. After testing for heterogeneity between studies, data were aggregated using random-effects model analysis. Forty-nine clinical studies were included in the meta-analysis. Summated, there were 94,415 patients: 11,329 treated with ORIF and 83,086 treated with CRPP. Factors that were significantly associated with greater rates of ORIF included obesity (p = 0.001), Gartland type IV fractures (p < 0.001), general neurological deficits (p = 0.019), and ulnar nerve deficits (p = 0.003). Gartland type II (p = 0.033) and medially displaced fractures (p = 0.011) were significantly associated with lower rates of ORIF. Secondary analysis showed cross-pinning constructs (p = 0.033) and longer hospital stays (p = 0.005) are more likely to be observed in patients undergoing ORIF compared with CRPP. This meta-analysis demonstrates that factors such as obesity, fracture displacement, and concomitant nerve deficits are more likely to require ORIF as opposed to CRPP. Therapeutic Level III.

Estimation and analysis of the economic effects of the Corona Virus on Food Security in Iraq

The coronavirus pandemic is one of the types of communicable and infectious diseases that have caused very significant impacts in many economic variables, especially the food gap for wheat and rice crops in Iraq and in the majority of the world. The problem of research lies in the nature of the challenges and constraints to the production of these two crops, which has made the effects of the pandemic add additional burden to it. Iraq has thus lost its ability to achieve food security, while food prices have risen significantly, reflecting the high rate of deficits in the State's general budget, as Iraq is a net importer of most types of agricultural products, particularly the strategy. The research aims to study the reality of food security from wheat and rice crops during the period of the pandemic and its repercussions in the Iraqi economy. A number of findings have been reached in the practical aspect of the study, including the emergence of the inverse relationship between the quantities produced by wheat and its food gap. The relationship between the quantities produced and imported from rice and its food gap has been expulsive. The State's general budget deficit relationship with the food gap in both crops was expulsive. We recommend diversifying the production of the Iraqi economy, reducing dependence on the oil sector's foreign exchange revenues, adopting a policy of protection for domestic products from foreign competition and developing agricultural infrastructure to the extent that it is capable of achieving food security from both crops at all times.

Higher Number of Children Is Associated With Increased Risk of Generalization Deficits in Older African American Women.

The objectives of this project were to: (1) examine the relationship between the number of biological children and hippocampal-dependent cognitive performance among older African American women and (2) determine the influence of socioeconomic status (i.e., age, education, marital status, median household income), if any, on this relationship. A total of 146 cognitively unimpaired African American women aged 60 and older were recruited from the greater Newark area and reported their number of biological children, marital status, educational level, and age. We retrieved median household income from census tract data based on the participants' addresses. Participants' cognitive performance was assessed using the Rey Auditory Verbal Learning Test (RAVLT) long delay recall and a Rutgers generalization task (Concurrent Discrimination and Transfer Task). As the number of biological children a woman has had increases, the number of generalization errors also increased, indicating poorer hippocampal-dependent cognitive performance when controlling for age, education, marital status, and median household income. There was no significant relationship between the number of children and performance on a standardized neuropsychological measure of episodic memory (RAVLT), although education was a significant covariate. Generalization tasks may better capture early changes in cognitive performance in older African American women who have had children than standardized neuropsychological assessments. This finding may be explained by the fluctuations in estrogen associated with having children. Future studies should explore how these findings can be applied to protecting cognitive function and preventing Alzheimer's disease in older African American women who have had children.

Facial emotion recognition in children of parents with a mental illness

ObjectiveFacial emotion recognition (FER) is a fundamental social skill essential for adaptive social behaviors, emotional development, and overall well-being. FER impairments have been linked to various mental disorders, making it a critical transdiagnostic mechanism influencing the development and trajectory of mental disorders. FER has also been found to play a role in the transgenerational transmission of mental disorders, with the majority of research suggesting FER impairments in children of parents with a mental illness (COPMI). Previous research primarily concentrated on COPMI of parents with internalizing disorders, which does not cover the full spectrum of outpatient mental health service populations. Furthermore, research focuses on varying components of FER by using different assessment paradigms, making it challenging to compare study results. To address these gaps, we comprehensively investigated FER abilities in COPMI using multiple tasks varying in task characteristics.MethodsWe included 189 children, 77 COPMI and 112 children of parents without a diagnosed mental illness (COPWMI), aged 6 to 16 years. We assessed FER using three tasks with varying task demands: an emotional Go/NoGo task, a morphing task, and a task presenting short video sequences depicting different emotions. We fitted separate two-level hierarchical Bayesian models (to account for sibling pairs in our sample) for reaction times and accuracy rates for each task. Good model fit was assured by comparing models using varying priors.ResultsContrary to our expectations, our results revealed no general FER deficit in COPMI compared to COPWMI. The Bayesian models fitted for accuracy in the morphing task and Go/NoGo task yielded small yet significant effects. However, Bayes factors fitted for the models suggested that these effects could be due to random variations or noise in the data.ConclusionsOur study does not support FER impairments as a general feature of COPMI. Instead, individual factors, such as the type of parental disorder and the timing of its onset, may play a crucial role in influencing FER development. Future research should consider these factors, taking into account the diverse landscape of parental mental disorders.

Political Economy of Tax and Digital Transformations in Pakistan (Special Invited Lecture)

1. THE NEED FOR A COORDINATED TAX AND SUSTAINABLE GROWTH STRATEGY I The 1985 National Tax Reform Commission (NTC) recommended a coordinated set of policies on tax policy, administration, and digital transformation to take the tax/GDP ratio from around 14 percent as it was then, to 20 percent by 1990, to underpin a sustainable growth path. The interim report of the NTC called the CBR “the most corrupt of Pakistani institutions.” The final report paid a great deal of attention to the interrelationships between tax evasion, smuggling and corruption. 1 The report emphasised a coordinated approach to reforming all taxes and administration, and that a tax-by-tax approach with tax administration determined separately would not do. Unfortunately, the report was shelved as Pakistan extracted geographic rents from the war against the Soviets in Afghanistan. While the NTC could not have imagined that the tax/GDP ratio would decline after three decades of interactions and support from the IFIs, that the country would find itself on the brink of default consequently, or the depths to which rent-seeking and corruption might plumb. A coordinated approach to multilevel tax policy and administration should also address key political economy challenges if Pakistan is to overcome the current economic crisis and move towards resilient and sustainable growth in the medium term. This is especially critical given the unprecedented “perfect storm” of the pandemic, climate shocks and once in a century floods, and ongoing disruptions in global value chains. The contrast with India is striking. With a general government tax/GDP ratio well above “the tipping point” of around 15 percent, India has been able to run a greater general deficit and much higher overall debt level than Pakistan (see Table 1 and Chart 1), without running into a potential debt crisis. It is important to stress that India by a Constitutional Amendment to harmonise the VAT across subnational jurisdictions has begun to address faults inherited from the pernicious 1935 Government of India Act, that still influences revenue assignments in Pakistan. The increasing geo-political importance of India, and the country’s greater resilience and attractiveness for FDI provide important contrasts and lessons for policy makers in Pakistan.

Dorsal pulvinar inactivation leads to spatial selection bias without perceptual deficit

The dorsal pulvinar has been implicated in visuospatial attentional and perceptual confidence processing. Pulvinar lesions in humans and monkeys lead to spatial neglect symptoms, including an overt spatial saccade bias during free choices. However, it remains unclear whether disrupting the dorsal pulvinar during target selection that relies on a perceptual decision leads to a perceptual impairment or a more general spatial orienting and choice deficit. To address this question, we reversibly inactivated the unilateral dorsal pulvinar by injecting GABA-A agonist THIP while two macaque monkeys performed a color discrimination saccade task with varying perceptual difficulty. We used Signal Detection Theory and simulations to dissociate perceptual sensitivity (d-prime) and spatial selection bias (response criterion) effects. We expected a decrease in d-prime if dorsal pulvinar affects perceptual discrimination and a shift in response criterion if dorsal pulvinar is mainly involved in spatial orienting. After the inactivation, we observed response criterion shifts away from contralesional stimuli, especially when two competing stimuli in opposite hemifields were present. Notably, the d-prime and overall accuracy remained largely unaffected. Our results underline the critical contribution of the dorsal pulvinar to spatial orienting and action selection while showing it to be less important for visual perceptual discrimination.

Does the procedural deficit hypothesis of dyslexia account for the lack of automatization and the comorbidity among developmental disorders?

ABSTRACT We critically examine the procedural deficit hypothesis (PDH) that proposes that a deficit in procedural (as opposed to declarative) learning underlies dyslexia and other developmental disorders. We first note that the existence of dissociated learning disorders (and multiple forms for each disorder) appears incompatible with a general deficit account. Moreover, the PDH formulation appears generally underspecified in terms of predictions to be tested. A particular focus is on the conceptualization of automatization. However, there are alternative views of automaticity, and comparing these different views helps frame the body of findings on the PDH. The insufficient PDH specification led to tasks touching on different skills and selecting target groups based on general diagnostic categories. Accordingly, several recent reviews and meta-analyses reported mixed patterns of findings and reached contradictory conclusions on the PDH. We propose avenues for future research to effectively examine the role of PDH in learning and other developmental disorders.

Accelerated decline in motor suppression in patients with cerebrovascular disorders: A kinetic analysis using the square-tracing task.

Patients with cerebrovascular disorders (CVDs) tend to exhibit impulsive behaviour without controlling their movements, leading to difficulty in performing activities of daily living and an increased risk of accidents. This hastiness, termed 'pacing impairment', has been studied but is not fully understood. To experimentally examine the kinetic features of pacing impairment by focusing on changes in speed and investigating neuropsychological substrates. We instructed 53 inpatients with CVDs, 20 orthopaedic inpatients, and 20 healthy participants to trace a 200 mm-sided square as slowly as possible for 120 seconds. We measured the tracing length and mean acceleration and examined the relationship between these measurements, neuropsychological symptoms, and lesion sites. Gradual acceleration in drawing, i.e., decline in motor suppression, was observed more frequently in the CVD group than in the control groups. Excessive acceleration was associated with unilateral spatial neglect, frontal lobe signs, and attention disorders but not with motor impersistence. Additionally, the incidence of excessive acceleration did not differ between left and right hemisphere lesion subgroups and was not associated with any specific lesion site. Pacing impairment can manifest as general or holistic deficits in attentional function widely distributed throughout the cerebral hemispheres.

Systemic histone deacetylase inhibition ameliorates the aberrant responses to acute stress in socially isolated male mice.

Adverse experiences in early life can induce maladaptive responses to acute stress in later life. Chronic social isolation during adolescence is an early life adversity that can precipitate stress-related psychiatric disorders. We found that male mice after 8weeks of adolescent social isolation (SI) have markedly increased aggression after being exposed to 2h of restraint stress (RS), which was accompanied by a significant increase of AMPA receptor- and NMDA receptor-mediated synaptic transmission in prefrontal cortex (PFC) pyramidal neurons of SIRS males. Compared to group-housed counterparts, SIRS males exhibited a significantly decreased level of histone H3 acetylation in PFC. Systemic administration of class I histone deacetylase inhibitors, romidepsin or MS-275, ameliorated the aggressive behaviour, as well as general social interaction deficits, of SIRS males. Electrophysiological recordings also found normalization of PFC glutamatergic currents by romidepsin treatment of SIRS male mice. These results revealed an epigenetic mechanism and intervention avenue for aggression induced by chronic social isolation. KEY POINTS: Adolescent chronic social isolation can precipitate stress-related psychiatric disorders. A significant increase of glutamatergic transmission is found in the prefrontal cortex (PFC) of socially isolated male mice exposed to an acute stress (SIRS). Treatment with class I histone deacetylase (HDAC) inhibitors ameliorates the aggressive behaviour and social interaction deficits of SIRS males, and normalizes glutamatergic currents in PFC neurons. It provides an epigenetic mechanism and intervention avenue for aberrant stress responses induced by chronic social isolation.