Changes in brain blood flow associated with deltamethrin-induced choreoathetosis in the rat

Summary Deltamethrin is a pyrethroid insecticide which produces reversible motor symptoms in mammals involving facial movements, progressive incoordination, and choreoathetosis. These symptoms were found to be preceded and accompanied by increases in blood flow in the caudate nucleus and cerebral cortex of conscious rats. Blood flow, measured by the hydrogen polarography method, showed a 2.8–3.8 fold increase in the caudate nucleus and a 1.9–2.6 increase in the cortex after intraperitoneal deltamethrin. The increase in caudate blood flow provided an early and sensitive indicator of the development of motor symptoms, and preceded development of EEG spike discharges.A different pattern of motor symptoms consisting largely of tremor with no choreoathetosis was produced for comparison using another pyrethroid, cismethrin. This, whilst producing a similar increase in cortical flow, did not produce the disproportionate increase in caudate flow characteristic of deltamethrin.Although the actions of deltamethrin were shown not to be restricted to the extrapyramidal system, the selectivity of the blood flow increases, and the nature of the symptoms produced show deltamethrin to be a useful tool for the production of experimental extrapyramidal motor hyperactivity.     

Marfan syndrome: neuropsychological aspects

We evaluated the neurodevelopmental status and cognitive ability of 30 school-age children with Marfan syndrome. We found average intellectual (mean full scale IQ = 109.3) and gross motor development. Fifty percent had one or more neuropsychologic deficits: learning disability (LD) (13%), attention deficit disorder with or without hyperactivity (ADD +/- H) (17%), neuromaturational immaturity (NMI) (10%), and a performance IQ score different from their verbal score by more than 20 points (30%). Patients with a large verbal-performance discrepancy, with one exception, scored lower on tests of performance, and particularly low on two subtests, object assembly and coding, compared with the rest of the patients (P less than 0.01). The factor most highly correlated with verbal-performance discrepancy was the severity of joint hypermobility (P = 0.02), which suggests that the depressed performance score was due, in part, to motor incoordination. Children with Marfan syndrome may be prone to neuropsychologic problems; the role of routine screening remains to be tested. Those with hand-wrist hypermobility seem at particular risk for difficulties with tasks that involve writing and should receive careful evaluation in the classroom. Due to the high risk of aortic dilatation in these patients, if stimulant medications are considered for treatment of ADD +/- H, the risk of adverse sympathomimetic effect should be weighed against the potential benefit.     

Behavioral Physical Therapy and Spina Bifida: A Case Study

Behavioral physical therapy is a relatively new subspecialityfield involving the concurrent use of physical therapy and behavioraltechnology/assessment practices. The present study examinedthe relative efficacy of combining behavioral technology andtraditional physical therapy to facilitate an 8-year-old spinabifida child's fine and gross motor incoordination. A multiplebaseline across outcome measures design was used to evaluatetreatment efficacy over a 1-year period. The child's fine andgross motor incoordination improved the most under the combinedtreatment protocol and remained or showed further gains duringa 6-month follow-up period. Results were discussed with an emphasison factors contributing to the program's success and the desirabilityof assessing effects using single-subject methodology.     

Cognitive performance of medicated schizophrenics with tardive dyskinesia

Twenty schizophrenic patients with tardive dyskinesia and an equal number of matched controls were tested on a novel cognitive task. The task had two components: cued response and spatial memory. Relative to controls, the dyskinetic subjects showed a superior cued response performance but an equal spatial memory ability. We speculate that this selective facilitation may reflect dopaminergic hyperactivity in the dyskinetic group.     

Hyperactive and antisocial behaviors: comorbid or two points in the same process?

We hypothesized that hyperactivity defines the first stage and that antisocial problems define a second stage in a progression that leads eventually to early-onset delinquency. As expected, a structural equation model (SEM) showed that a latent construct for hyperactivity was significantly related to a latent construct for antisocial problems. We hypothesized that this path reflected a shared mechanism, disrupted parental discipline. A second SEM showed that the relation between hyperactivity and antisocial behavior really reflected a shared disruption in parental discipline. A third SEM showed that having antisocial parents was uniquely correlated with antisocial children but not with hyperactivity. A fourth SEM showed that early-onset delinquency was predicted by a latent construct for antisocial child; but when this was partialed out, the contribution for hyperactivity was nonsignificant.     

No objectively measured sleep disturbances in children with attention‐deficit/hyperactivity disorder

The main goal of this study was to gain more insight into sleep disturbances in children with attention‐deficit/hyperactivity disorder, using objective measures of sleep quality and quantity. The evidence for sleep problems in children with attention‐deficit/hyperactivity disorder thus far is inconsistent, which might be explained by confounding influences of comorbid internalizing and externalizing problems and low socio‐economic status. We therefore investigated the mediating and moderating role of these factors in the association between attention‐deficit/hyperactivity disorder and sleep problems. To control for the effects of stimulant medication use, all participants were tested free of medication. Sixty‐three children with attention‐deficit/hyperactivity disorder and 61 typically developing children, aged 6–13 years, participated. Sleep was monitored for one to three school nights using actigraphy. Parent and teacher questionnaires assessed symptoms of attention‐deficit/hyperactivity disorder, internalizing behaviour, oppositional defiant disorder and conduct disorder. Results showed no differences between the attention‐deficit/hyperactivity disorder and typically developing group in any sleep parameter. Within the attention‐deficit/hyperactivity disorder group, severity of attention‐deficit/hyperactivity disorder symptoms was not related to sleep quality or quantity. Moderation analyses in the attention‐deficit/hyperactivity disorder group showed an interaction effect between attention‐deficit/hyperactivity disorder symptoms and internalizing and externalizing behaviour on total sleep time, time in bed and average sleep bout duration. The results of our study suggest that having attention‐deficit/hyperactivity disorder is not a risk factor for sleep problems. Internalizing and externalizing behaviour moderate the association between attention‐deficit/hyperactivity disorder and sleep, indicating a complex interplay between psychiatric symptoms and sleep.     

Leptin's effect on hyperactivity: potential downstream effector mechanisms

Up to 80% of patients with Anorexia Nervosa (AN) demonstrate hyperactivity. Hyperactivity counteracts weight gain during treatment and is associated with poor outcome of the disease. We hypothesized that hyperactivity in AN patients has a neurobiological basis and used an animal model-based translational approach to gain insight in mechanisms underlying this hyperactivity. Previously we and others showed that leptin treatment attenuates hyperactivity in the rat activity-based anorexia (ABA) model. The mechanisms involved in this process are, however, unknown. Here we describe potential downstream effector mechanisms involved in the attenuation of hyperactivity by leptin treatment in ABA rats.     

Spontaneous class switching and B cell hyperactivity increase autoimmunity against intracellular self antigen in Lyn-deficient mice

IgG autoantibodies cause pathology due to their ability to bind self antigens. However, the extent to which the initial B cell activation and isotype switching is antigen-driven is unclear and it has been widely proposed that intrinsic B cell hyperactivity may be a contributing factor. To explore this issue we generated mice with B cell hyperactivity secondary to deficiency in the src kinase Lyn that also expressed a gene-targeted anti-hen egg lysozyme Ig construct (VDJkappa) capable of class switching to all isotypes. The B cell hyperactivity caused spontaneous hypersecretion of antibodies and class switching to IgM, IgA, IgG1 and IgG3 isotypes in the absence of self antigen, and this persisted as an autoimmune phenomenon in the presence of intracellularly expressed hen egg lysozyme. Exaggerated class switching was also unaffected by antigen in vitro. These findings show that systemic high-avidity intracellular self antigens do not induce self tolerance in the face of B cell hyperactivity. Under these circumstances, spontaneous activation of hyperactive B cells leads to isotype switching and the development of high titres of IgG autoantibodies against intracellular proteins.     

Inhibitory processes in adults with persistent childhood onset ADHD

The theory that attention-deficit/hyperactivity disorder (ADHD) stems from a deficit in an executive behavioral inhibition process has been little studied in adults, where the validity of ADHD is in debate. This study examined, in high-functioning young adults with persistent ADHD and a control group, 2 leading measures of inhibitory control: the antisaccad task and the negative priming task. ADHD adults showed weakened ability to effortfully stop a refle ve or anticipated oculomotor response but had normal ability to automatically suppress irrelevant information. Results suggest that an inhibitory deficit in ADHD is confined to effortful inhibition of motor response, that antisaccade and negative priming tasks index distinct inhibition systems, and that persistence of ADHD symptoms into adulthood is associated with persistence of executive motor inhibition deficits.     

BOOK REVIEW: Clinical Handbook of Child Abuse and Neglect

Investigated the relation among response inhibition, hyperactivity, and conduct problems in a nonclinical sample of 115 preschool children, using 2 different types of go/no-go tasks as well as a Stroop-like task. In line with the assumption that hyperactivity is related to disinhibition, the results showed that it was the measures of response inhibition, and not other performance measures, that were related to teacher ratings of hyperactivity. There was also a significant relation between response inhibition and conduct problems. Interestingly, the correlation between response inhibition and conduct problems was not significant when partialling out the effect of hyperactivity, whereas the correlation between inhibition and hyperactivity did remain significant when controlling for conduct problems. Although the association between inhibition, hyperactivity, and conduct problems appeared to be partly different for boys and girls, these differences were not statistically significant.     

The potential synergism by combining external counterpulsation with intermittent theta burst stimulation in post-stroke motor function recovery

Upper limb weakness and incoordination is a common disability following ischemic stroke. Previous studies have showed that the single application of external counterpulsation (ECP) and intermittent theta burst stimulation (iTBS) can effectively enhance the cortical motor excitability and facilitate recovery. However, it remains uncertain if sequential application of these therapies would further augment the recovery. We hypothesize a synergistic effect of ECP followed by iTBS to upper limb function may happen through improvements in both cerebral perfusion and neuron excitability.     

Persistent neonatal Borna disease virus (BDV) infection of the brain causes chronic emotional abnormalities in adult rats.

Neonatal Borna disease virus (BDV) brain infection results in selective developmental damage to the hippocampal dentate gyrus and the cerebellum. When mature, neonatally BDV-infected rats show extreme locomotor hyperactivity and reduced freezing behavior in novel environments. Traditional interpretation of both of these behavioral abnormalities would suggest decreased anxiety in infected rats compared to normal animals. However, it also possible that the locomotor hyperactivity in infected rats reflects higher rather than reduced anxiety, and is the result of increased escape responses to aversive stimuli. The present experiments were undertaken to test a hypothesis about elevated anxiety in neonatally BDV-infected adult Lewis rats by studying their species-specific fear-related responses. Compared to normal subjects, BDV-infected rats exhibited locomotor hyperactivity and elevated defecation in a highly aversive, brightly lit open field. As expected, in a less aversive, dimly lit open field, uninfected controls increased ambulation, whereas infected rats significantly decreased locomotor activity and defecation. Unlike uninfected rats, BDV-infected rats exhibited an attenuated freezing response immediately after loud auditory stimuli. On the contrary, immediate freezing responses following footshock were comparable in the two groups of animals indicating an intact ability to freeze in BDV-infected rats. Despite a decreased baseline startle responsiveness, BDV-infected rats demonstrated increased sensitization of the startle response by preceding footshocks, suggesting a tendency toward elevated escape responses. Compared to normal subjects, BDV-infected rats showed decreased conditional freezing and elevated conditional defecation response in the context previously paired with aversive stimulation indicating sparing of an autonomic component of fear conditioning. The findings indicate that neonatally BDV-infected adult rats are hyperreactive to aversive stimuli, possibly as a result of chronic emotional abnormalities.     

A double-blind, parallel, multicenter comparison of L-acetylcarnitine with placebo on the attention deficit hyperactivity disorder in fragile X syndrome boys

Attention deficit hyperactivity disorder (ADHD) is a frequent behavioral problem in young boys with fragile X syndrome (FXS), and its treatment is critical for improving social ability. The short-term efficacy of stimulant medications like methylphenidate (MPH) is well established in children with ADHD. FXS boys treated with MPH have improved attention span and socialization skills; however their mood becomes unstable at higher doses. Therefore, alternative pharmacological treatment of ADHD symptoms is desirable. A recent study showed that carnitine has a beneficial effect on the hyperactive-impulsive behavior in boys with ADHD without side effects. Our previous placebo-controlled trial indicated that L-acetylcarnitine (LAC) reduces hyperactivity in FXS boys. The objective of this study was to determine the efficacy of LAC in a larger sample of FXS boys with ADHD. The study design was randomized, double blind placebo controlled, parallel, and multicenter (with eight centers involved in Italy, France, and Spain). Sixty-three FXS males with ADHD (aged 6-13 years) were enrolled; 7 patients dropped out, 56 completed the one-year treatment, and 51 were included in the statistical analysis. Both groups improved their behavior, showing that psychosocial intervention has a significant therapeutic effect. However, we observed a stronger reduction of hyperactivity and improvement of social behavior in patients treated with LAC, compared with the placebo group, as determined by the Conners' Global Index Parents and the Vineland Adaptive Behavior Scale. Our results show that LAC (20-50 mg/kg/day) represents a safe alternative to the use of stimulant drugs for the treatment of ADHD in FXS children.     

感觉统合训练对多动症儿童的行为及智力的疗效研究

目的探讨感觉统合训练对ADHD儿童的行为与智力的疗效。方法将30例ADHD儿童作为实验组给予感觉统合训练,将30名正常儿童志愿者为对照组不予任何干预。在干预前后主要采用Conners父母评定量表(Conners Parents SymPtomQuestionnaire,PSQ)和瑞文智力测验联合型(Combined Raven’s Test,CRT)评定。结果实验组训练后PSQ各项指标得分均低于训练前(t=10.49,10.7,5.14,7.05,5.9,8.7;P<0.001)。实验组训练后在PSQ的学习问题、冲动一多动和多动指数3项因子上得分低于对照组(t=2.12,2.35,2.75;P<0.05)。实验组训练后在CRT的IQ值及知觉辨别力、比较推理能力、系列关系能力上得分均高于训练前(t=-6.6,-2.72,-3.81,P<0.01);但与对照组比较无显著差异(P>0.05)。结论感觉统合训练能有效提高ADHD儿童注意力,改善其多动、冲动行为,对儿童的智商及空间知觉和比较推理能力有一定程度的提高。     

Motor perseveration in geriatric medical patients.

Perseveration has long been considered as a pathognomonic sign of neurological disease, yet, surprisingly, little research exists regarding the accuracy of this assumption. This study matched 56 geriatric medical inpatients with 56 inpatients with recent cerebrovascular accidents. Participants were given one of two measures of general cognition and four Lurian tasks of motor coordination. The results suggest that both motor incoordination and across-tasks perseveration were associated with decreased cognitive status. After controlling for cognitive status, individuals with a neurological history evidenced greater dyscoordination and increased perseveration when compared to age-equivalent general medical patients. Perseveration in participants with recent strokes appeared more related to the amount of neural system disruption as opposed to specific lesion sites. Overall, the results suggest that motor incoordination and "stuck-in-set" perseveration are more indicative of global than localizable brain dysfunction. Possible nonneurologic factors associated with this behavior are also proposed as benchmarks for future research.     

Neonatal Tolerance to Alloantigens is Induced by Enriched Antigen-Presenting Cells

Spleen and bone marrow cells from normal or Rag-1-deficient donors are equally competent in their ability to induce neonatal transplantation tolerance in semi-allogeneic hosts, and the latter are also capable of tolerizing fully allogeneic recipients. Both types of donor cells resulted in comparable levels of haemopoietic chimerism in tolerant animals. Lymphoid hyperactivity, however, was absent in animals tolerized with Rag-1-deficient cells. The authors conclude that neonatal tolerance induced with haemopoietic cells requires no donor lymphocytes, and is thus not the result of deficient antigen presentation. Furthermore, the state of tolerance can be dissociated from the lymphoid hyperactivity that requires donor lymphocytes and is regularly scored in conventionally tolerized animals.     

Behavioral and pharmacological assessment of a potential new mouse model for mania

Bipolar disorder (BPD) is a devastating long-term disease for which a significant symptom is mania. Rodent models for mania include psychostimulant-induced hyperactivity and single gene alterations, such as in the Clock or DAT genes, but there is still a pressing need for additional models. Recently, our lab isolated a line of mice, termed Madison (MSN), that exhibit behavioral characteristics that may be analogous to symptoms of mania. In this study we quantified possible traits for mania and tested the response to common anti-BPD drugs in altering the behavioral profiles observed in this strain. Relative to other mouse lines, MSN mice showed significant elevations of in-cage hyperactivity levels, significant decreases in daytime sleep, and significant increases in time swimming in the forced swim test. In terms of sexual behavior, the MSN mice showed significantly higher number of mounts and a trend toward higher time mounting. In separate studies, olanzapine and lithium (or respective controls) were administered to MSN mice for at least 2weeks and response to treatments was evaluated. Olanzapine (1mg/kg/day) significantly decreased in-cage hyperactivity and significantly increased time sleeping. Lithium (0.2-0.4% in food) significantly decreased in-cage hyperactivity. Given the behavioral phenotypes and the response to anti-BPD treatments, we propose that MSN mice may provide a possible new model for understanding the neural and genetic basis of phenotypes related to mania and for developing pharmaceutical treatments.     

Experimental studies of pathogenesis of chronic fluoride intoxication

The article presents the results of studies of occupational fluorosis pathogenesis on experimental model of chronic fluoride intoxication (CFI). In early fluoride intoxication, fluoride and calcium in the body are in compensatory relations. Later, they are disturbed. High reaction ability of fluoride in CFI is associated with hypocalciemia which triggers parathyroid hyperactivity. This results in hyperproduction of PHH which is unrelated with development of secondary hyperparathyrosis. CFI is accompanied also with elevated calcitonin having a hypocalciemic and hypophosphatemic action. The experiments showed double content of collagen fragments of bone tissue in urine of animals with fluoride intoxication which reflects resorption of bone tissue. Serum osteocalcin rose three-fold as it was unable to include in the bone tissue. There was also activation of lipid peroxidation in subnormal activity of respiratory enzymes.     

Methylphenidate and attributions in boys with attention-deficit hyperactivity disorder.

In Experiment 1, 28 attention-deficit hyperactivity disorder (ADHD) boys underwent a double-blind, placebo-controlled medication assessment in a summer day-treatment program. Daily, boys were asked questions to assess their attributions for and evaluations of their behavior. Objective measures showed improved behavior with methylphenidate; however, boys tended to attribute their performance to effort rather than to medication, particularly when medicated. Experiment 2 involved 38 ADHD boys the following summer and replicated the procedures in Experiment 1, with the addition of a no-pill condition and a comparison of attributions for success and failure outcomes. Simply taking a pill (no-pill vs. placebo comparison) did not show significant effects, whereas the results of Experiment 1 were replicated with placebo-methylphenidate comparisons. Across drug conditions a self-enhancing attributional pattern was obtained; the majority of attributions for success were to ability or effort, whereas attributions for failure were to the pill or to counselors.     

Increases in diversive exploration in rats during hippocampal microinfusions of isoproterenol but not methoxamine

To test the hypothesis that the increase in locomotor activity and the diversification of stimulus sampling observed during intrahippocampal microinfusions of norepinephrine are mediated by beta adrenergic receptors, rats were infused with either the beta agonist isoproterenol or the alpha-1 agonist methoxamine while being tested in a Behavioral Pattern Monitor. The behavioral profile induced by isoproterenol was qualitatively similar to that observed previously with norepinephrine. Methoxamine had no significant effects. The ability of isoproterenol to mimic the norepinephrine-induced blockade of the hyperactivity associated with intrahippocampal microinfusions of the cholinergic agonist carbachol was also tested. Carbachol produced hyperactivity which was attenuated by the coinfusion of isoproterenol. These results are consistent with the hypothesis that increases in diversive exploration and stimulus sampling induced by intrahippocampal norepinephrine are due to the activation of beta adrenergic receptors within the dentate gyrus.