Prefrontal cortical α2A-adrenoceptors and a possible primate model of attention deficit and hyperactivity disorder.
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ABSTRACT:
SUBMITTER: Ma CL
PROVIDER: S-EPMC5563706 | biostudies-other | 2015 Apr
REPOSITORIES: biostudies-other
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Project description:Attention Deficit Hyperactivity Disorder (ADHD) is the most common neuropsychiatric disorder in childhood and is characterized by a delay of cortical maturation in frontal regions. In order to investigate interference control, which is a key function of frontal areas, a functional MRI study was conducted on 17 ADHD boys and 17 typically developing (TD) boys, while solving the multi source interference task (MSIT). This task consists of two conditions, a "congruent condition" and an "incongruent condition". The latter requires to inhibit information that interferes with task-relevant stimuli. Behavioral results showed that ADHD subjects committed more errors than TD children. In addition, TD children presented a larger MSIT effect -a greater difference in reaction times between the incongruent and the congruent conditions- than ADHD children. Associated to the MSIT effect, neuroimaging results showed a significant enhancement in the activation of the right lateral prefrontal cortex (rlPFC) in ADHD than in TD subjects. Finally, ADHD subjects presented greater functional connectivity between rlPFC and bilateral orbitofrontal cortex than the TD group. This difference in connectivity correlated with worse performance in both groups. Our results could reflect a compensatory strategy of ADHD children resulting from their effort to maintain an adequate performance during MSIT.
| S-EPMC5543103 | biostudies-literature
Project description:We sought to determine whether functional connectivity streams that link sensory, attentional, and higher-order cognitive circuits are atypical in attention-deficit/hyperactivity disorder (ADHD). We applied a graph-theory method to the resting-state functional magnetic resonance imaging data of 120 children with ADHD and 120 age-matched typically developing children (TDC). Starting in unimodal primary cortex-visual, auditory, and somatosensory-we used stepwise functional connectivity to calculate functional connectivity paths at discrete numbers of relay stations (or link-step distances). First, we characterized the functional connectivity streams that link sensory, attentional, and higher-order cognitive circuits in TDC and found that systems do not reach the level of integration achieved by adults. Second, we searched for stepwise functional connectivity differences between children with ADHD and TDC. We found that, at the initial steps of sensory functional connectivity streams, patients display significant enhancements of connectivity degree within neighboring areas of primary cortex, while connectivity to attention-regulatory areas is reduced. Third, at subsequent link-step distances from primary sensory cortex, children with ADHD show decreased connectivity to executive processing areas and increased degree of connections to default mode regions. Fourth, in examining medication histories in children with ADHD, we found that children medicated with psychostimulants present functional connectivity streams with higher degree of connectivity to regions subserving attentional and executive processes compared to medication-naïve children. We conclude that predominance of local sensory processing and lesser influx of information to attentional and executive regions may reduce the ability to organize and control the balance between external and internal sources of information in ADHD.
| S-EPMC4484811 | biostudies-literature
Project description:Attention-deficit hyperactivity disorder (ADHD), like other psychiatric disorders, represents an evolving construct that has been refined and developed over the past several decades in response to research into its clinical nature and structure. The clinical presentation and course of the disorder have been extensively characterised. Efficacious medication-based treatments are available and widely used, often alongside complementary psychosocial approaches. However, their effectiveness has been questioned because they might not address the broader clinical needs of many individuals with ADHD, especially over the longer term. Non-pharmacological approaches to treatment have proven less effective than previously thought, whereas scientific and clinical studies are starting to fundamentally challenge current conceptions of the causes of ADHD in ways that might have the potential to alter clinical approaches in the future. In view of this, we first provide an account of the diagnosis, epidemiology, and treatment of ADHD from the perspective of both the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders and the eleventh edition of the International Classification of Diseases. Second, we review the progress in our understanding of the causes and pathophysiology of ADHD on the basis of science over the past decade or so. Finally, using these discoveries, we explore some of the key challenges to both the current models and the treatment of ADHD, and the ways in which these findings can promote new perspectives.
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Project description:Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with a long-term impact on functioning, productivity and quality of life of patients. This impact is largely due to the symptoms of inattentiveness. However, despite its impairing role in the lives of ADHD patients, inattentiveness has been studied relatively less frequently than have symptoms of impulsivity/hyperactivity and problems with executive function. This review therefore seeks to integrate the neuropsychological theories and current findings in the research fields of neuropsychology, neurophysiology, and neuroimaging, in an attempt to gain a more complete understanding of the role that inattentiveness plays in ADHD, as well as to suggest directions for future studies. The need for a more comprehensive understanding of inattentiveness and ADHD, which integrates findings from each of the three disciplines mentioned above, is emphasized.
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Project description:Genetic Investigations of Attention-Deficit/Hyperactivity Disorder
| PRJNA1114309 | ENA
Project description:Genetic Investigations of Attention-Deficit/Hyperactivity Disorder
| PRJNA1114310 | ENA
Project description:The occurrence of attention deficit-hyperactivity disorder (ADHD) symptoms in patients with cystic fibrosis (CF) is substantially higher than in the general population, and the cystic fibrosis transmembrane conductance regulator (CFTR) is the pathogenic gene of cystic fibrosis, suggesting the potentially critical role of CFTR in ADHD. Here, we identified three heterozygous missense mutations (p.E217G, p.F316L and p.T1220I) in CFTR, segregating with ADHD in two consanguineous families with 6 affected individuals. Using the zebrafish model, we found that the cftr knockout line displays hyperactive, impulsive-like, and attention deficit-like behaviors, reminiscent of human ADHD patients. Single-cell RNA-seq of 7 dpf larvae identified clusters of neuron cells that were sensitive to cftr, especially, the number of dopaminergic neuron cells decreased in the cftr mutant fish. Bulk RNA-seq and proteomic analysis at the early gastrulation period showed that the expression of nerve system genes was abnormal. Notably, we tried to use CFTR activitors Lumacaftor (VX-809) and Ivacaftor (VX-770) to treat the ADHD zebrafish model (established by per1b mutant), and found enhanced CFTR activity could rescue the ADHD-like behaviors. In brief, we uncover the role of CFTR in ADHD pathogenesis and explore novel diagnoses and therapy for ADHD by targeting CFTR.
2024-12-16 | GSE284214 | GEO
Project description:Deficient operant extinction has been hypothesized to be constitutive of ADHD dysfunction. In order to elucidate the behavioral mechanisms underlying this deficit, the performance of an animal model of ADHD, the spontaneously hypertensive rat (SHR), was compared against the performance of a control strain, the Wistar-Kyoto rat (WKY) during extinction.Following extensive training of lever pressing under variable interval schedules of food reinforcement (reported previously), SHR and WKY rats were exposed to two sessions of extinction training. Extinction data was analyzed using the Dynamic Bi-Exponential Refractory Model (DBERM) of operant performance. DBERM assumes that operant responses are organized in bouts separated by pauses; during extinction, bouts may decline across multiple dimensions, including frequency and length. DBERM parameters were estimated using hierarchical Bayesian modeling.SHR responded more than WKY during the first extinction session. DBERM parameter estimates revealed that, at the onset of extinction, SHR produced more response bouts than WKY. Over the course of extinction, response bouts progressively shortened for WKY but not for SHR.Based on prior findings on the sensitivity of DBERM parameters to motivational and schedule manipulations, present data suggests that (1) more frequent response bouts in SHR are likely related to greater incentive motivation, and (2) the persistent length of bouts in SHR are likely related to a slower updating of the response-outcome association. Overall, these findings suggest specific motivational and learning deficits that may explain ADHD-related impairments in operant performance.
| S-EPMC3542014 | biostudies-literature
Project description:There is controversy over the nature of the disturbance in brain development that underpins attention-deficit/hyperactivity disorder (ADHD). In particular, it is unclear whether the disorder results from a delay in brain maturation or whether it represents a complete deviation from the template of typical development. Using computational neuroanatomic techniques, we estimated cortical thickness at >40,000 cerebral points from 824 magnetic resonance scans acquired prospectively on 223 children with ADHD and 223 typically developing controls. With this sample size, we could define the growth trajectory of each cortical point, delineating a phase of childhood increase followed by adolescent decrease in cortical thickness (a quadratic growth model). From these trajectories, the age of attaining peak cortical thickness was derived and used as an index of cortical maturation. We found maturation to progress in a similar manner regionally in both children with and without ADHD, with primary sensory areas attaining peak cortical thickness before polymodal, high-order association areas. However, there was a marked delay in ADHD in attaining peak thickness throughout most of the cerebrum: the median age by which 50% of the cortical points attained peak thickness for this group was 10.5 years (SE 0.01), which was significantly later than the median age of 7.5 years (SE 0.02) for typically developing controls (log rank test chi(1)(2) = 5,609, P < 1.0 x 10(-20)). The delay was most prominent in prefrontal regions important for control of cognitive processes including attention and motor planning. Neuroanatomic documentation of a delay in regional cortical maturation in ADHD has not been previously reported.
| S-EPMC2148343 | biostudies-literature
Project description:ObjectiveThe neurobiological basis of inattentiveness, a core feature of attention-deficit/hyperactivity disorder (ADHD), is not yet well understood. Structural abnormalities in thalamus, especially the pulvinar nuclei, have recently been reported in ADHD. Pulvinar nuclei maintain reciprocal connections with cortical/subcortical areas, and play a central coordinating role during visual attention processing. The objective of this study was to test the hypothesis that children and young adolescents with ADHD would show atypical pulvinar-cortical functional pathways during sustained attention performance, and that these functional abnormalities would be associated with the inattentive symptoms of the disorder.MethodVisual attention task-based functional magnetic resonance imaging (fMRI) data from 22 children and young adolescents with ADHD and 22 demographically matched, normal control subjects were analyzed. Cortical activation maps and temporal correlations of activity patterns between pulvinar nuclei and the remainder of brain were constructed for each participant. Correlations between activation magnitude of pulvinar and diagnostic measures were calculated in subjects with ADHD.ResultsCompared to controls, subjects with ADHD showed significantly reduced pulvinar activations bilaterally, significantly decreased functional connectivity between bilateral pulvinar and right prefrontal regions, and significantly increased connectivity between the right pulvinar and bilateral occipital regions. In addition, the activation magnitude in the left pulvinar was negatively correlated with the DSM-IV inattentive index in ADHD group.ConclusionsAllied with previous evidence of structural abnormalities in pulvinar, the current data suggest that inappropriate development of pulvinar may lead to disrupted functional circuits for visual attention processing, and that these disruptions contribute significantly to the pathophysiological mechanisms of the inattentiveness symptoms in ADHD.
| S-EPMC3734849 | biostudies-literature