Timing of conditioned eyeblink responses is impaired in children with attention-deficit/hyperactivity disorder

Structural changes of the cerebellum have been reported in several psychiatric diseases like schizophrenia, autism and attention-deficit/hyperactivity disorder (ADHD). Beside behavioral deficits children with ADHD often show slight motor abnormalities. Cerebellar malfunction may contribute. The cerebellum is a structure essential for motor coordination, various forms of motor learning and timing of motor responses. In the present study, eyeblink conditioning was applied to investigate learning and timing of motor responses both in children with ADHD and children with cerebellar lesions. Acquisition, timing and extinction of conditioned eyeblink responses were investigated in children with ADHD, children with chronic surgical cerebellar lesions and controls using a standard delay paradigm with two different interstimulus intervals. Timing of conditioned eyeblink responses was significantly impaired in children with ADHD in the long interstimulus interval condition. Also in children with cerebellar lesions conditioned responses (CR) tended to occur earlier than in controls. Incidences of CRs were significantly reduced in children with cerebellar lesions and tended to be less in children with ADHD than in controls. Extinction of the CRs was impaired in children with cerebellar lesions in both interstimulus interval conditions and in children with ADHD in the long interstimulus interval condition. Cerebellar malfunction may contribute to disordered eyeblink conditioning in ADHD. However, because CR abnormalities differed between ADHD and cerebellar subjects, dysfunction of non-cerebellar structures cannot be excluded.     

Set shifting in a rodent model of attention-deficit/hyperactivity disorder

Two experiments compared spontaneously hypertensive rats (SHRs; a rodent model of attention-deficit/hyperactivity disorder) and Wistar rats (a normoactive control strain), on the acquisition of a set-shifting strategy. In Experiment 1, SHRs and Wistar rats were equivalent in trials to criterion to learn a brightness or a texture discrimination but SHRs were faster than Wistar rats in shifting to the opposite discrimination when there was 1 or 2 days between the initial discrimination and the shift. In Experiment 2, SHRs and Wistar rats were equivalent in shifting when the shift between discriminations occurred immediately after a criterion had been met in the first discrimination. The results are discussed in terms of a failure of SHRs to store or retrieve an initial discrimination and/or latent inhibition over a delay, leading to faster acquisition of a set-shift. This failure in storage or retrieval may be the result of a hypoactive dopamine system in the prefrontal cortex and nucleus accumbens shell as well as abnormalities in entorhinal cortex in SHRs.     

Conditioned inhibition in a rodent model of attention-deficit/hyperactivity disorder

A deficit in inhibition may underlie some of the symptoms of attention-deficit/hyperactivity disorder (ADHD), particularly impulsivity. However, the data on inhibitory deficits in children with ADHD are mixed. Moreover, there has been little characterization of inhibitory processes in animal models of ADHD. Pavlov's conditioned inhibition procedure allows a direct assessment of the inhibitory status of a stimulus via summation and retardation tests. Therefore, in the current study, we examined conditioned inhibition in spontaneously hypertensive rats (SHRs), the most well-validated animal model of ADHD. SHRs and Wistar rats were trained in a simultaneous feature-negative discrimination in eyeblink conditioning. Each session consisted of a mixture of 2 trial types: a tone paired with a periocular stimulation (A+) or a tone and light presented simultaneously without a periocular stimulation (XA-). Both SHRs and Wistars were able to discriminate A+ from XA- trials. In subsequent summation (X presented simultaneously with a different conditioned excitor, B) and retardation (X paired with the periocular stimulation) tests, the presence of inhibition to X was confirmed in both SHRs and Wistars: X reduced responding to B, and X was slow to develop excitation when paired with periocular stimulation. These results are the first to demonstrate Pavlovian conditioned inhibition in SHRs and to use summation and retardation tests to confirm X as a conditioned inhibitor. The data indicate that conditioned inhibition is intact in SHRs; thus, inhibitory processes that do not require prefrontal cortex or cerebellum may be normal in this strain.     

Attention-deficit disorder (attention-deficit/ hyperactivity disorder without hyperactivity): a neurobiologically and behaviorally distinct disorder from attention-deficit/hyperactivity disorder (with hyperactivity)

Most studies of attention-deficit/hyperactivity disorder (ADHD) have focused on the combined type and emphasized a core problem in response inhibition. It is proposed here that the core problem in the truly inattentive type of ADHD (not simply the subthreshold combined type) is in working memory. It is further proposed that laboratory measures, such as complex-span and dual-task dichotic listening tasks, can detect this. Children with the truly inattentive type of ADHD, rather than being distractible, may instead be easily bored, their problem being more in motivation (underarousal) than in inhibitory control. Much converging evidence points to a primary disturbance in the striatum (a frontal-striatal loop) in the combined type of ADHD. It is proposed here that the primary disturbance in truly inattentive-type ADHD (ADD) is in the cortex (a frontal-parietal loop). Finally, it is posited that these are not two different types of ADHD, but two different disorders with different cognitive and behavioral profiles, different patterns of comorbidities, different responses to medication, and different underlying neurobiologies.     

Cerebellar neuronal activity expresses the complex topography of conditioned eyeblink responses

Pavlovian eyeblink conditioning is a useful model system for studying how the temporal relationship between a conditioned stimulus and an unconditioned stimulus is represented in the brain. As an example, the response topography formed under a complex conditioning paradigm, involving 2 randomly alternating interstimulus intervals (ISIs), manifests a conditioned response (CR) with 2 distinctive peaks that correspond to the 2 ISIs. The authors present the first full report of neuronal activities in the cerebellar interpositus nucleus of rabbits performing bimodal responses. All CR-related activities exhibited firing patterns that highly correlated with and preceded eyeblink responses. The striking similarity between the time course of bimodal CRs and neuronal responses indicates that neuronal activities in the cerebellum are causally related to the production of behavioral CRs.     

The neurophysiology of attention-deficit/hyperactivity disorder.

Recent reviews of the neurobiology of Attention-Deficit/Hyperactivity Disorder (AD/HD) have concluded that there is no single pathophysiological profile underlying this disorder. Certainly, dysfunctions in the frontal/subcortical pathways that control attention and motor behavior are implicated. However, no diagnostic criteria or behavioral/neuroimaging techniques allow a clear discrimination among subtypes within this disorder, especially when problems with learning are also considered. Two major Quantitative EEG (QEEG) subtypes have been found to characterize AD/HD. Here we review the major findings in the neurophysiology of AD/HD, focusing on QEEG, and briefly present our previous findings using a source localization technique called Variable Resolution Electromagnetic Tomography (VARETA). These two techniques represent a possible objective method to identify specific patterns corresponding to EEG-defined subtypes of AD/HD. We then propose a model representing the distribution of the neural generators in these two major AD/HD subtypes, localized within basal ganglia and right anterior cortical regions, and hippocampal, para-hippocampal and temporal cortical regions, respectively. A comprehensive review of neurochemical, genetic, neuroimaging, pharmacological and neuropsychological evidence in support of this model is then presented. These results indicate the value of the neurophysiological model of AD/HD and support the involvement of different neuroanatomical systems, particularly the dopaminergic pathways.     

Planning ability in adults with attention-deficit/hyperactivity disorder

Planning ability was investigated in 26 patients diagnosed with attention-deficit/hyperactivity disorder in adulthood and in 27 control participants, with groups matched for age, predicted IQ, and social class. They were tested using the 3-dimensional computerized Tower of London Test (Morris, Ahmed, Syed, & Toone, 1993; Morris, Rushe, Woodruffe, & Murray, 1995), which measures planning latencies as well as accuracy, with problems increasing in graded difficulty. For the control group, planning latencies increased systematically with task difficulty, with the participants slowing their initial responses to ensure accuracy. For those with attention-deficit/hyperactivity disorder, there was no increase in planning time and a corresponding diminution in accuracy on the most difficult problems. This pattern of impairment is interpreted as resulting from failure to inhibit responses when confronted with problem solving, leading to reduced planning activity.     

Controlled visuomotor preparation deficits in attention-deficit/hyperactivity disorder

To the best of the authors' knowledge, there are no published reports on visuomotor preparation in attention-deficit/hyperactivity disorder (ADHD). This is unfortunate, because research suggests that ADHD is an output-related deficit, and suboptimal execution of tasks may be the result of incomplete visuomotor preparation. The authors compared 19 children with ADHD with 124 healthy and 120 pathological controls in terms of their performance (speed, speed variability, and accuracy) on the finger precuing test, a test measuring (automatic and controlled) visuomotor preparation. The data implied that children with ADHD have an impaired ability to engage in effortful, controlled visuomotor preparation activities. Fast, automatic response preparation was not affected by ADHD. In addition, children with ADHD showed more variability in overall test performance than other children. No group differences were found in response accuracy.     

Stimulants and growth in children with attention-deficit/hyperactivity disorder

Initial suggestions that suppression of growth may be an intrinsic characteristic of attention-deficit/hyperactivity disorder (ADHD) have now largely been disproven. Although controversy persists regarding the possible negative effect of adrenergic stimulants on growth in children with ADHD, the consensus that appears to be reached in the scientific literature is that stimulant usage may cause a manageable attenuation of growth in these children. Since it is known that stimulants increase the amount of dopamine and noradrenaline in the synapse, this writing suggests that these increases in dopamine and noradrenaline are responsible for the growth attenuation in these children. It appears that increased amounts of dopamine and noradrenaline have the ability to inhibit the secretion of growth hormone and growth-related hormones such as prolactin, thyroid hormones, sex hormones and insulin. Therefore, it would be reasonable to suggest that the increases in dopamine and noradrenaline caused by stimulant usage can disrupt the homeostasis of both growth hormone and growth-related hormones, generating the potential for the suppression of growth.     

Stimulus context and motor preparation in attention-deficit/hyperactivity disorder

AIM: To investigate (1) whether and how local stimulus context variation may modify behavioural and preparatory motor processes in children, and (2) if these effects differ between healthy children and children with attention-deficit/hyperactivity disorder (ADHD) aged 9-12 years. METHODS: Behavioural parameters and contingent negative variation (CNV) at cortical motor electrodes were recorded during a cued continuous performance task (AX-CPT) in three stimulus context conditions (Go, NoGo, neutral). Stimulus context was varied on the basis of stimulus types preceding the cue letter A. RESULTS: In all children, responses were slowed in both the NoGo- and Go-conditions relative to the neutral condition. Stimulus context affected preparatory motor processes in both groups but differentially. ADHD children showed smaller CNV potentials and a functionally irrelevant over-activation of the ipsilateral motor area. CONCLUSIONS: Local stimulus context may modify behavioural and preparatory motor processes in children. In ADHD, local context variations may disrupt behaviour due to inefficient regulation of supervisory higher control systems.     

Stroop interference and attention-deficit/hyperactivity disorder: a review and meta-analysis

Previous reviews and meta-analyses that addressed abnormal Stroop interference in attention-deficit/hyperactivity disorder (ADHD) yielded mixed results. The authors of the present study argue that the inconsistencies may reflect the problematic nature of 2 frequently used methods to quantify Stroop interference-the difference score and Golden's method (C. J. Golden, 1978). Golden's method correction for base-word reading is inadequate, and the difference score is sensitive to the nature of the outcome variable. The latter can be remedied with a ratio score. Contrasting previous meta-analyses, this meta-analysis covers all age groups and all Stroop test variants, and it excludes studies using the Golden quantification method. Mean effect sizes for interference in ADHD as quantified by difference scores relative to control scores were 0.24 across all studies but 1.11 for time-per-item studies; outcome variable was a significant moderator variable, reflecting the sensitivity of the difference score to this variable. Consistency analysis of ratio scores across 19 studies reveals more interference for the ADHD groups relative to the control groups. It is concluded that interference control is consistently compromised in individuals with ADHD.     

The latent structure of attention-deficit/hyperactivity disorder in a clinic-referred sample

The question of whether attention-deficit/hyperactivity disorder (ADHD) represents a continuum of attentional and executive dysfunction or a natural category has yet to be extensively investigated. Subjective report and neuropsychological data from 437 individuals referred for neuropsychological evaluation were analyzed using latent class and taxometric analyses (mean above minus below a cut [MAMBAC], maximum eigenvalue [MAXEIG], and latent mode [LMODE]). Results indicated no significant evidence for a taxonic representation of ADHD across multiple procedures and indicator sets. Similarly, there was no evidence that ADHD subtypes represent a qualitative distinction. These findings may suggest that current diagnostic conceptualizations are inadequate for accurately identifying and characterizing individuals with problems related to attention and executive dysfunction. Alternatively, the null findings may have resulted from inadequate indicator selection. A dimensional model may better facilitate accurate identification of individuals at risk for functional impairment.     

Electroencephalogram differences in two subtypes of attention-deficit/hyperactivity disorder

This study investigated EEG differences between children with two subtypes of Attention-Deficit/Hyperactivity Disorder (ADHD) and normal control subjects. EEG was recorded during an eyes-closed resting condition and Fourier transformed to provide absolute and relative power estimates for the delta, theta, alpha, and beta bands, and the mean frequency for each band was calculated. Ratio coefficients were also calculated between frequency bands. Mean group differences were found in the theta, alpha, and beta bands between all three groups. Similarly, differences were found between all three groups for the theta/alpha and theta/beta ratios and for the mean frequency of the total EEG. These results support a model of ADHD resulting from a developmental deviation rather than a maturational lag in the central nervous system. Differences between the clinical groups in frontal activity suggest that different neuroanatomical systems are involved in the different subtypes of ADHD.     

Effects of ipsilateral cerebellum ablation on acquisition and retention of classically conditioned eyeblink responses in rats

The ipsilateral cerebellum to the trained eye has been reported to be essential for acquisition and retention of the conditioned response (CR) in rabbit eyeblink conditioning. Although pharmacological studies have suggested its important roles in other species too, to what degree does eyeblink conditioning in rats depend on the ipsilateral cerebellum is not clear. In this work, we ablated the ipsilateral cerebellum in rats before or after conditioning to examine its roles in acquisition and retention of the CR. In the first experiment, rats received ablation of the ipsilateral cerebellum and recovered for more than 3 weeks. They then underwent eyeblink conditioning for 7 days with a tone and a periorbital electrical shock. Consistent with other previous reports, hemicerebellectomized rats showed significant impairment compared to sham-lesioned rats. However, the hemicerebellectomized rats acquired CRs to some degree, and the acquired CR showed adaptive timing. In the second experiment, rats received the hemicerebellectomy after acquiring CR by 7 days of conditioning in a delay paradigm. After more than 3 weeks of recovery, they were again conditioned in a delay paradigm. Rats with ipsilateral cerebellar lesions showed severe impairment in retention of the pre-acquired CR; however, they reacquired CR to some degree during the subsequent reconditioning sessions. These results suggest that the ipsilateral cerebellum plays an important role in rat eyeblink conditioning as well but that other brain regions can partially compensate for its removal.     

注意缺陷多动障碍儿童的时间知觉特征

目的:探讨注意缺陷多动障碍(ADHD)儿童的时间知觉特征及其可能相关的原因。方法:选取符合美国精神障碍诊断与统计手册第4版(DSM-IV)中ADHD的诊断标准,Conners父母症状问卷和Conners教师评定量表中的多动指数Z≥1.5的儿童55例及正常对照儿童55例,以中国修订韦氏儿童智力量表手册(C-WISC)评定总体智商,以时间辨别任务测试(TDTT)、Coirs积木测验(CBT)、儿童持续注意反应测试(C-SART)分别评定100 ms和1000 ms的时间知觉差别阈限值、视觉工作记忆广度、持续性注意的遗漏性错误次数和执行错误次数。结果:ADHD儿童总体智商得分低于正常组儿童[(97.4±11.2)vs.(110.3±12.1),P<0.01)],C-SART中的遗漏性错误次数高于正常儿童[(25.5±2.4)vs.(14.6±2.1),P<0.01]。100 ms条件下,ADHD儿童与正常儿童的时间知觉差别阈限值差异无统计学意义(P>0.05)。1000 ms条件下,注意缺陷多动障碍儿童时间知觉差别阈限值高于正常儿童(P<0.01)。在控制总体智商之后,注意缺陷多动障碍儿童加工1000 ms时的差别阈限值与其CBT得分呈负相关(r=-0.54 P<0.01),与其C-SART中的遗漏错误和执行错误次数呈正相关(r=0.47、0.44,均P<0.01)。结论:注意缺陷多动障碍儿童相比正常儿童存在时间知觉缺陷,这一缺陷可能与其持续性注意和工作记忆的受损有关。     

EEG coherence in adults with attention-deficit/hyperactivity disorder.

Attention-Deficit/Hyperactivity Disorder (AD/HD) is the most common psychiatric disorder of childhood, but it is becoming increasingly more apparent that more than half the childhood sufferers will continue to manifest symptoms of the disorder as adults. While EEG coherence in children with AD/HD has been examined extensively, no studies have investigated coherence in adults with the disorder. This study investigated EEG coherence in adults with AD/HD. EEG was recorded from 18 adult males with AD/HD, and an age- and gender-matched control group, during an eyes-closed resting condition. Waveshape coherence was calculated for 8 intrahemispheric electrode pairs (4 in each hemisphere), and 8 interhemispheric electrode pairs, within each of the delta, theta, alpha and beta bands. A laterality effect was found for intrahemispheric coherence at long inter-electrode distances, with the AD/HD group showing reduced hemispheric differences in the delta band compared to the control group. In the alpha band, at short-medium inter-electrode distances, the AD/HD group also had lower coherences than the control group. The results suggest that theta coherence differences reported in children with AD/HD may be associated with hyperactivity, which is reduced in adults with AD/HD, while reduced alpha coherence could be associated with inattention, which remains in adult with AD/HD. Reduced delta coherence also appears to be an aspect of the disorder which may develop from later childhood into adolescence and adulthood.     

Allergic rhinitis in children with attention-deficit/hyperactivity disorder.

BACKGROUND: Both allergic rhinitis and attention-deficit/hyperactivity disorder (ADHD) are common pediatric conditions associated with learning difficulties and sleep disturbances. There are conflicting research data regarding the association between ADHD and atopic disorders. OBJECTIVE: To determine the prevalence of allergic rhinitis in patients with physician-diagnosed ADHD. METHODS: Patients 5 to 18 years of age who presented with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of ADHD to an outpatient pediatric psychiatry clinic were screened for allergic rhinitis with focused history, physical examination, and skin prick testing to common aeroallergens. RESULTS: Thirty patients were interviewed, with 23 of these undergoing physical examination and skin prick testing. Eighty percent reported allergic rhinitis symptoms, whereas 61% had at least 1 positive prick skin test result. Forty-three percent showed typical physical signs of allergic rhinitis, 100% had a positive atopic family history, and 53% had other associated atopic disorders. CONCLUSIONS: Most children with ADHD displayed symptoms and skin prick test results consistent with allergic rhinitis. Nasal obstruction and other symptoms of allergic rhinitis could explain some of the cognitive patterns observed in ADHD, which might result from sleep disturbance known to occur with allergic rhinitis. Therefore, evaluation and treatment of allergic rhinitis could benefit patients with ADHD.     

Neuropsychology of adults with attention-deficit/hyperactivity disorder: a meta-analytic review

A comprehensive, empirically based review of the published studies addressing neuropsychological performance in adults diagnosed with attention-deficit/hyperactivity disorder (ADHD) was conducted to identify patterns of performance deficits. Findings from 33 published studies were submitted to a meta-analytic procedure producing sample-size-weighted mean effect sizes across test measures. Results suggest that neuropsychological deficits are expressed in adults with ADHD across multiple domains of functioning, with notable impairments in attention, behavioral inhibition, and memory, whereas normal performance is noted in simple reaction time. Theoretical and developmental considerations are discussed, including the role of behavioral inhibition and working memory impairment. Future directions for research based on these findings are highlighted, including further exploration of specific impairments and an emphasis on particular tests and testing conditions.