From early markers to neuro-developmental mechanisms of autism

A fast growing field, the study of infants at risk because of having an older sibling with autism (i.e. infant sibs) aims to identify the earliest signs of this disorder, which would allow for earlier diagnosis and intervention. More importantly, we argue, these studies offer the opportunity to validate existing neuro-developmental models of autism against experimental evidence. Although autism is mainly seen as a disorder of social interaction and communication, emerging early markers do not exclusively reflect impairments of the “social brain”. Evidence for atypical development of sensory and attentional systems highlight the need to move away from localized deficits to models suggesting brain-wide involvement in autism pathology. We discuss the implications infant sibs findings have for future work into the biology of autism and the development of interventions.     

Cerebellar ataxia: quantitative assessment and cybernetic interpretation

To assess neuromotor disorders clinicians often rely on rating scales. Unfortunately, these scales lack the sensitivity and accuracy needed to detect the small changes in motor coordination that reflect the clinical progression of the disease on the basis of which treatment programmes can be adjusted. As a contribution to this topic, the present paper proposes a straightforward kinematic and kinetic analysis of reaching movements of patients with cerebellar ataxia in conjunction with a cybernetic interpretation of the data. The aim of the approach is to capture key deficits in the underlying motor control processes. We suggest that cerebellar ataxia may be characterized by defective feedforward control.     

Intellectual similarities within families of both adopted and biological children

The effects of genetic and environmental differences on intellectual differences among children were examined in a study of families with both biological and adopted children. IQ scores of all family members and education of natural parents were used to estimate intellectual similarities among related and unrelated persons, living together and apart. Comparisons of correlations between related and unrelated siblings produced negligible heritability values, whereas the parent-child data suggested moderate heritability for the children's IQ differences. The high mean values of the adopted children's IQ scores and the high degree of similarity among unrelated sibs suggest that IQ scores are more maleable than previously thought.     

Impairments in tactile search following superior parietal damage

The superior parietal cortex is critical for the control of visually guided actions. Research suggests that visual stimuli relevant to actions are preferentially processed when they are in peripersonal space. One recent study demonstrated that visually guided movements towards the body were more impaired in a patient with damage to superior parietal cortex. Whereas past studies have explored disordered movement in optic ataxic patients, there has been less exploration of space perception in terms of search capacity in this population. In addition, there is some debate concerning the relationship between deficits of visuomotor control and impaired attention/perception in optic ataxia. Given that the dorsal stream has been implicated in the spatial processing of stimuli in peripersonal space, and damage to this region is known to cause optic ataxia, we felt that further investigation was warranted. We examined tactile search behavior in the fronto-parallel and radial planes in a patient with right superior parietal damage and optic ataxia. We used a pegboard with removable cylindrical pegs that allowed for the reorganization of targets between trials. To better characterize three-dimensional search behavior, we included both horizontal and vertical search conditions. Results showed that the patient spent more time searching, was more accurate and revisited more targets in right versus left space. Interestingly, the patient spent the majority of her time specifically searching the lower right quadrant of the stimulus array. Further analysis revealed lower target detection rates along the outer borders of the pegboard on all sides. The search pattern observed here is unusual considering that all targets were within arm's reach. The present experiment demonstrates that damage to superior parietal cortex impairs tactile search and biases exploration towards lower right peripersonal space.     

The training & support programme for parents of children with ataxia: a pilot study

The aim of the study was to evaluate the impact of the Training and Support Programme among parents of children with ataxia. A total of 39 parents expressed an interest in the TSP, 27 (mean age 41; range 25-58) returned baseline questionnaires and completed the study. Twenty-four children (mean age 12.5 years, SD=12.4) received the TSP. Data were collected by self-administered questionnaires mailed to parents immediately before attending the TSP and at 4-month follow-up. Interviews were conducted with 10 parents immediately following TSP completion. Comparisons over time revealed significant decreases in parental anxious mood (p=.011), depressed mood (p=.046) and perceived stress (p=.020) and significant improvements in generalized self-efficacy (p=.010), satisfaction with life (p=.045) and parental health status (p=.020). Parents reported improvements in children's mobility, "jumping legs", sleep patterns, energy and activity levels, relaxation, and happiness (e.g., more smiles). Parents felt closer to their children and one parent had become "more accepting" of their child's ataxia. Results indicate that the TSP may enhance the psychosocial well-being of parents of children with ataxia although a randomized controlled trial would be necessary to determine whether the changes reported here are in fact due to attending the TSP.     

Effects of the nonagouti pelage-color allele on the behavior of captive wild Norway rats (Rattus norvegicus)

The objective of the present study was to determine the extent to which the nonagouti pelage-color allele influences selected behaviors (including docility) of the wild Norway rat. Agouti and nonagouti (black) littermates were compared in tests for handling, open-field behavior, platform jumping, and response to a novel food item, all of which clearly differentiate wild and domestic rats. Nonagouti rats were significantly easier to approach, capture, and handle than their agouti sibs. However, differences between agouti and nonagouti rats for the other variables studied were not significant. Although the presence of the nonagouti allele cannot fully account for the behavioral differences between wild and domestic Norway rats, it may have facilitated the domestication of this species by improving ease of handling.     

Fragile X-associated tremor/ataxia syndrome (FXTAS)

Carriers of fragile X mental retardation 1 (FMR1) premutation alleles (55 to 200 CGG repeats) are generally spared the more serious neurodevelopmental problems associated with the full-mutation carriers (>200 repeats) of fragile X syndrome. However, some adult male premutation carriers (55-200 repeats) develop a neurological syndrome involving intention tremor, ataxia, dementia, parkinsonism, and autonomic dysfunction. In excess of one-third of male premutation carriers over 50 years of age develop the fragile X-associated tremor/ataxia syndrome (FXTAS). FXTAS also represents a new form of inclusion disease, with eosinophilic intranuclear inclusions found throughout the brain in both neurons and astrocytes. Because FXTAS appears to be relatively specific to male premutation carriers, who are known to possess elevated levels of FMR1 mRNA, the neuropathology may arise as a consequence of a toxic gain-of-function of the mRNA itself, although this proposal requires additional direct testing. One of the critical needs at present is a better estimate for the prevalence of this disorder, because FXTAS is likely to be underdiagnosed in the adult movement disorders clinics.     

Depressive symptoms in Friedreich ataxiaSíntomas depresivos en la ataxia de Friedreich

Background/Objective: Almost no attention has been paid to depression in Friedreich ataxia (FRDA), a highly disabling cerebellar degenerative disease. Our aim was to study the presence and the profile of depressive symptoms in FRDA and their relationship with demographic-disease variables and cognitive processing speed. Method: The study groups consisted of 57 patients with a diagnosis of FRDA. The Beck Depression Inventory-II was used to assess symptoms of depression. Speed of information processing was measured with a Choice Reaction time task. Results: The mean BDI score for patients was significantly higher than the mean score in the general population. Twenty one percent of participants scored in the moderate/severe range. A Cognitive-Affective score and a Somatic-Motivational score was calculated for each patient. Patients’ scores in both dimensions were significantly higher than the scores in the general population. Demographic and disease variables were not related with symptoms of depression, except for severity of ataxia. Depressive symptoms predict cognitive reaction times. The greater proportion of variance was explained by the Cognitive-Affective dimension. Conclusions: Our data show that both somatic-motivational and cognitive affective symptoms of depression are frequent in individuals with FRDA. In addition, depressive symptoms may influence cognition, especially, the cognitive and affective symptoms.     

Biotinidase deficiency--a progressive metabolic disease in children with seizures and ataxia

Biotinidase deficiency is the primary biochemical defect in late-onset multiple carboxylase deficiency and an autosomal recessive disorder and characterized by seizures, ataxia, alopecia and skin rash. We describe a colorimetric semiquantitative method for screening for biotinidase activity from dried samples of whole blood spotted on filter papers. The administration of biotin to affected children can be a lifesaving procedure and can prevent irreversible neurologic damage.     

Line-bisectioning and obstacle avoidance: Evidence for separate strategies

Previous studies have frequently applied a combination of line-bisection tasks (in which participants indicate the middle of a line) and obstacle avoidance tasks (in which participants move their hand between two obstacles) with the aim of revealing perception–action dissociations in certain neurological disorders, such as visual form agnosia and optic ataxia. However, valid conclusions about the underlying processing pathways can only be drawn if participants apply the same strategy in both tasks (i.e. finding the middle between the obstacles). Yet, this assumption has never been tested directly. In this experiment, we investigated whether participants perform obstacle avoidance and line-bisectioning using similar strategies by manipulating the position of the obstacles and the start position of the hand relative to the obstacles. Our results indicate that the lateral hand position during obstacle avoidance does not only vary as a function of obstacle location but also strongly depends on the start position. Moreover, participants showed increased sensitivity to obstacle shifts occurring closer to the hand's start position. In contrast, during line-bisectioning the sensitivity to obstacles shifts was unaffected by the hand's start position. The findings suggest that during obstacle-avoidance the need to keep a safe distance from the obstacles is balanced with the requirement to minimise energetic demands. In contrast, the main intention during line-bisectioning is to move to the perceived midpoint as accurately as possible. The fact that very different constraints underlie trajectory planning in both tasks implies that caution has to be taken when interpreting differences in performance levels.     

The topography of aggressive behavior of an attacking rat is determined by the behavior of the victim

Untreated rats were observed to either bite or box with Pentobarbital-treated opponents in a shockelicited aggression situation. Specific behaviors such as ataxia movements and submissive postures immediately preceded biting attacks, but rarely boxing whereas behaviors such as moving around the chamber and upright threat postures immediately preceded boxing attacks, but rarely biting. These data suggest that the topography of aggressive behavior of an attacking rat is determined by the behavior of the victim.     

Effects of NMDA receptor channel blockade on aggression in isolated male mice

N‐Methyl‐D ‐aspartate (NMDA) receptor antagonists are perspective candidates for medication development for a number of diseases/states that are associated with increased aggressiveness (e.g., opioid withdrawal). The prototypic NMDA receptor antagonist phencyclidine (PCP) itself is a widely abused substance and is known to elevate levels of aggression in drug users. The present study was aimed at testing several drugs that share with PCP the ability to block NMDA receptor–associated channel. The resident‐intruder procedure was used to assess drug effects on aggressive behavior in isolated male mice. Resident aggressive mice were administered NMDA channel blockers (PCP; 0.3–10 mg/kg), dizocilpine (MK‐801; 0.01–0.3 mg/kg), memantine (1–30 mg/kg), and MRZ 2/579 (0.1–5.6 mg/kg). The competitive NMDA receptor antagonist D CPPene (0.1–5.6 mg/kg) was also tested as a compound representing an alternative approach to reduce activity of NMDA receptor complex. PCP, dizocilpine, and memantine inhibited expression of aggressive behaviors only at doses that produced ataxia. The novel channel blocker MRZ 2/579 also produced ataxia at the highest dose level but failed to affect aggressiveness. Reduction in aggression with a corresponding increase in sociability was observed after administration of D ‐CPPene. Overall, the present results suggest that NMDA receptor channel blockers do not exert selective effects on aggressive behavior. Aggr. Behav. 25:381–396, 1999. © 1999 Wiley‐Liss, Inc.     

Clinical and cisternographic differential diagnosis between presenile dementia and Hakim syndrome

The authors compared with regard clinical and the radionuclide cisternography examination 27 patients with Hakim-Syndrome and 11 with Alzheimer-Disease. In all cases, dementia was a stable symptom. Patients with Hakim-Syndrome have an early gait disturbance, ataxia and epileptic seizures. Only in case of patients with Alzheimer-Disease we found aphasia, apraxia and psychotic disorders. 24 hours after the injection radionuclide cisternography showed ventricular retention and absence of parasagital accumulation only in patients with Hakim-Syndrome. Lighter changes (mixed cisternographic pattern) were found in patients with Alzheimer-Disease as well.     

Response specific temporal expectancy: Evidence from a variable foreperiod paradigm

When a stimulus-response event is frequently paired with a specific foreperiod, response performance for this event is improved after this foreperiod. This phenomenon is referred to as specific temporal expectancy. In four experiments, we investigated whether stimulus- or response-related processing benefits from specific temporal expectancy. In a speeded choice reaction task, different features of the imperative stimuli were frequently paired with foreperiods in such a way that only in some experiments were the responses also frequently paired with foreperiods. Participants revealed evidence for specific temporal expectancy when responses were frequently paired with foreperiods, but not when only the stimuli were frequently paired with foreperiods. We concluded that specific temporal expectancy affects response-related processing.     

Temperament and its Relationship to Autistic Symptoms in a High-Risk Infant Sib Cohort

The present study prospectively investigated early temperamental profiles and their associations with autistic symptoms in high-risk infants (N = 138) with an older sibling with autistic spectrum disorder (ASD) and low-risk infants (N = 73) with no family history of ASD. Children who were diagnosed with ASD at 36 months were distinguished from non-ASD sibs and controls by a temperament profile marked by lower positive affect, higher negative affect and difficulty controlling attention and behavior, which we labeled Effortful Emotion Regulation. This profile also distinguished the non-ASD sib group from the control group. Children with ASD were distinguished from both of the other two groups by a temperament profile of low Behavioral Approach (lower sensitivity to “social” reward cues). Low levels of Behavioral Approach were associated with a higher number of ASD symptoms, even after taking into account IQ, sex and group membership. Finally, a cluster analysis revealed two ASD subgroups distinguished by number of ASD symptoms, IQ, age of diagnosis and scores on the Behavioral Approach profile. These findings suggest that temperament may be a useful framework for understanding the emergence of ASD early in life.     

胃肠道手术术后并发韦尼克脑病临床分析

探讨胃肠道手术术后并发韦尼克（Wernicke）脑病的临床特点、患病机制及诊断和治疗方法。回顾性分析我院2006年~2010年胃肠道手术术后并发Wernieke脑病的临床资料。结果5例经补充维生素B1症状迅速消失,1例因获得诊断较迟,共济失调改善效果差,1例死亡。因此,Wernicke脑病临床表现极不典型,对于禁食时间...     

Auditory neglect after right frontal lobe and right pulvinar thalamic lesions

Auditory unilateral neglect or extinction to simultaneous stimulation is reported in a right-handed male with a lesion in the right frontal lobe and in the right thalamic pulvinar area. The patient was submitted to stereotactic thalamotomy for a post-traumatic intentional ataxia in the left extremities. He was subjected to repeated tests with dichotic listening to consonant-vowel syllables under three different attentional instructions. He was also tested monaurally with the same stimulus materials as used in the dichotic test. The results showed almost complete extinction of the left ear input during dichotic presentations, despite normal hearing when tested with audiometer screening. The left ear extinction effect was independent of instructions to attend to the left or right ear input. However, during monaural presentation, correct left ear reports increased to about 85%. The results are interpreted as showing an auditory attentional neglect caused by the right frontal and pulvinar lesions.     

Spatial neglect, Balint-Homes' and Gerstmann's syndrome, and other spatial disorders

Brain-damaged patients with lesion or dysfunction involving the parietal cortex may show a variety of neuropsychological impairments involving spatial cognition. The more frequent and disabling deficit is the syndrome of unilateral spatial neglect that, in a nutshell, consists in a bias of spatial representation and attention ipsilateral to of extrapersonal, personal (ie, the body) space, or both, toward the side of the hemispheric lesion. The deficit is more frequent and severe after damage to the right hemisphere, involving particularly the posterior-inferior parietal cortex at the temporo-parietal junction. Damage to these posterior parietal regions may also impair visuospatial short-term memory, which may be associated with and worsen spatial neglect. The neural network supporting spatial representation, attention and short-term memory is, however, more extensive, including the right premotor cortex. Also disorders of drawing and building objects (traditionally termed constructional apraxia) are a frequent indicator of posterior parietal damage in the left and in the right hemispheres. Other less frequent deficits, which, however, have a relevant localizing value, include optic ataxia (namely, the defective reaching of visual objects, in the absence of elementary visuo-motor impairments), which is typically brought about by damage to the superior parietal lobule. Optic ataxia, together with deficits of visual attention, of estimating distances and depth, and with apraxia of gaze, constitutes the severely disabling Balint-Holmes' syndrome, which is typically associated with bilateral posterior parietal and occipital damage. Finally, lesions of the posterior parietal lobule (angular gyrus) in the left hemisphere may bring about a tetrad of symptoms (left-right disorientation, acalculia, finger agnosia, and agraphia) termed Gerstmann's syndrome, that also exists in a developmental form.     

Simulating a lesion in a basis function model of spatial representations: comparison with hemineglect

The basis function theory of spatial representations explains how neurons in the parietal cortex can perform nonlinear transformations from sensory to motor coordinates. The authors present computer simulations showing that unilateral parietal lesions leading to a neuronal gradient in basis function maps can account for the behavior of patients with hemineglect, including (a) neglect in line cancellation and line bisection experiments; (b) neglect in multiple frames of reference simultaneously; (c) relative neglect, a form of what is sometime called object-centered neglect; and (d) neglect without optic ataxia. Contralateral neglect arises in the model because the lesion produces an imbalance in the salience of stimuli that is modulated by the orientation of the body in space. These results strongly support the basis function theory for spatial representations in humans and provide a computational model of hemineglect at the single-cell level.     

Locomotor analysis of the taiep rat

Locomotor activity (tremor, ataxia, immobility, epilepsy, and paralysis) in the taiep rat, which suffers from a myelin deficient disorder, has not been previously documented. This study used walking track analysis of footprints to analyze locomotor activity in the taiep rat in comparison to normal, age-matched controls. The results confirmed differences between normal and taiep rats in terms of stride length, step length, and stride width. In addition, we found significant interactions between age and condition for stride and step length. The results suggest that locomotor analysis is a sensitive indicator of myelin deficiency. The results are discussed in terms of the underlying myelin deficiency and possible treatment regimens.