Altered White Matter Structure of the Dentatorubrothalamic Pathway in Children with Autistic Spectrum Disorders

Neuropathological studies have demonstrated decreased Purkinje cells in cerebellar cortex and changes in the dentate nucleus of the cerebellum, the projection target for the Purkinje cells, in autistic spectrum disorders (ASD). The dentatorubrothalamic tract is formed by efferents from the dentate nucleus projecting toward the red nucleus with axon collaterals to this nucleus and continuing to innervate the ventral lateral and ventral anterior nuclei of the thalamus. In the current study, we assessed whether the dentatorubrothalamic tract is altered in ASD using Q-ball imaging (QBI). The QBI tractography was performed in 13 children with high functioning ASD (HFA), 11 children with low functioning ASD (LFA), and 14 typically developing children (TD). Regions of interest in dentate nucleus and red nucleus in both hemispheres were objectively placed to sort bilateral dorsal?Crostral (DR), dorsal?Ccaudal (DC), ventral?Crostral (VR), and ventral?Ccaudal (VC) portions of the dentatorubrothalamic pathway. Group differences in fractional anisotropy (FA), axial diffusivity, radial diffusivity, and fiber volume of individual pathways were analyzed. Significantly reduced FA was found in children with LFA and HFA, compared to the TD group in tracts originating in all four subdivisions of the right dentate nucleus. Tract-based morphometry (TBM) analysis demonstrated significant reductions of FA in caudal midbrain (p?<?0.0001), dorsal?Ccaudal dentate (p?=?0.0013), and ventral?Ccaudal dentate (p?=?0.0061) on the right in the LFA group. The FA values in TBM segments of right VR and VC pathways were significantly correlated with communication skills in the combined HFA/LFA group, while there was a significant correlation found between TBM segments of right DR pathway and daily living skills (r?=?0.76; p?=?0.004). Decreased white matter integrity in dorsal portions of the dentatorubrothalamic tract may be related to motor features in ASD, while changes in the ventral portions are related more to communication behavior.     

Medicaid Expenditures for Children with Autistic Spectrum Disorders: 1994 to 1999

This study used data from 1994 to 1999 from one large county in Pennsylvania to estimate the Medicaid expenditures of children diagnosed with autism spectrum disorders (ASD) and to compare these expenditures with those of other Medicaid-eligible children. On average, children diagnosed with ASD had expenditures 10 times those of other children. Differences in expenditures were driven in large part by inpatient psychiatric care. Further research is required to determine whether hospitalized children could be served in less restrictive and less expensive settings. Lack of differences in ambulatory care expenditures suggests that children with ASD are not receiving additional primary care services that would be indicative of appropriately coordinated services as suggested by the medical home model.     

Glutamate Dysfunction Associated with Developmental Cerebellar Damage: Relevance to Autism Spectrum Disorders

Neural abnormalities commonly associated with autism spectrum disorders include prefrontal cortex (PFC) dysfunction and cerebellar pathology in the form of Purkinje cell loss and cerebellar hypoplasia. It has been reported that loss of cerebellar Purkinje cells results in aberrant dopamine neurotransmission in the PFC which occurs via dysregulation of multisynaptic efferents from the cerebellum to the PFC. Using a mouse model, we investigated the possibility that developmental cerebellar Purkinje cell loss could disrupt glutamatergic cerebellar projections to the PFC that ultimately modulate DA release. We measured glutamate release evoked by local electrical stimulation using fixed-potential amperometry in combination with glutamate selective enzyme-based recording probes in urethane-anesthetized Lurcher mutant and wildtype mice. Target sites included the mediodorsal and ventrolateral thalamic nuclei, reticulotegmental nuclei, pedunculopontine nuclei, and ventral tegmental area. With the exception of the ventral tegmental area, the results indicated that in comparison to wildtype mice, evoked glutamate release was reduced in Lurcher mutants by between 9 and 72 % at all stimulated sites. These results are consistent with the notion that developmental loss of cerebellar Purkinje cells drives reductions in evoked glutamate release in cerebellar efferent pathways that ultimately influence PFC dopamine release. Possible mechanisms whereby reductions in glutamate release could occur are discussed.     

Locomotor Adaptation Is Associated with Microstructural Properties of the Inferior Cerebellar Peduncle

The Cerebellum - In sensorimotor adaptation paradigms, participants learn to adjust their behavior in response to an external perturbation. Locomotor adaptation and reaching adaptation depend on...     

Temporal Cognition in Children with Autistic Spectrum Disorders: Tests of Diachronic Thinking

Impaired diachronic thinking-(the propensity and capacity to think about events spreading across time)-was demonstrated in a 2-Phase study in which children with autism were compared with age and ability matched controls. Identical tests of diachronic thinking were administered in both phases of the study, but to different participant groups, with the same results. The marked impairments shown are therefore robust. Various non-temporal explanations of the findings were eliminated by the results of control tasks in Phase 2. Diachronic thinking did not correlate with verbal or non-verbal ability, age, or mentalising ability, consistent with other evidence of the specificity of diachronic thinking ability. Possible causes of impaired diachronic thinking in autism are discussed.     

Private Speech and Executive Functioning among High-Functioning Children with Autistic Spectrum Disorders

Private speech used by high-functioning children with autistic spectrum disorders (ASD) (n = 33) during two executive functioning tasks was compared to that of typically developing children (n = 28), and children with ADHD (n = 21). Children with ASD were as likely as others to talk to themselves and their speech was similarly relevant and likely to appear in moments of task difficulty. Unlike others, children with ASD were more likely to get items correct when they were talking than when they were silent. Group differences in performance were observed when children were silent but not when children were talking. Findings suggest that autistic children talk to themselves in relevant ways during problem-solving and that such speech is helpful in normalizing their executive performance relative to controls.     

Characteristics of Children with Autistic Spectrum Disorders Served in Comprehensive Community-based Mental Health Settings

This study describes the characteristics of children with autistic spectrum disorders (ASD) receiving treatment in community mental health settings. Data from a national community mental health initiative was used to identify children who had received a primary diagnosis of ASD. These children were compared with children with other diagnoses on socio-demographic and psychosocial characteristics, presenting problems and service histories. Regardless of diagnosis, children were most often referred to service because of disruptive behaviors. Children with ASD were less likely to be referred for drug use, truancy or running away, but were more likely to be referred for social interaction difficulties and strange behavior. Many children had family histories of mental illness, substance abuse and domestic violence. Implications of these findings are discussed in detail.     

Abnormalities in Myelination of the Superior Cerebellar Peduncle in Patients with Schizophrenia and Deficits in Movement Sequencing

Deficits in the execution of a sequence of movements are common in schizophrenia. Previous studies reported reduced functional activity in the motor cortex and cerebellum in schizophrenic patients with deficits in movement sequencing. The corticospinal tract (CST) and superior cerebellar peduncle (SCP) are fiber tracts that are involved in movement sequencing. However, the integrity of these tracts has not been evaluated in schizophrenic patients with respect to the performance of movement sequencing yet. Diffusion tensor magnetic resonance images (DT-MRI) were acquired from 24 patients with schizophrenia and 23 matched control subjects. Tractography was applied to reconstruct the CST and SCP and DT-MRI-specific parameters such as fractional anisotropy (FA) and radial diffusivity (RD) were reported. The patient group was further subdivided based on the score of sequencing of complex motor acts subscale of the Neurological Evaluation Scale into those with deficits in sequencing motor acts, the SQ^abn group (n?=?7), and those with normal performance, the SQ^norm group (n?=?17). Schizophrenia patients of the SQ^norm subgroup had significantly reduced FA and increased RD values in the right CST in comparison to the control group; the SQ^abn subgroup did not differ from the controls. However, the SQ^abn subgroup showed impaired integrity of the left SCP, whereas the SQ^norm subgroup did not. Abnormalities in the right CST in the SQ^norm and in the left SCP in SQ^abn groups suggest that the patients with SQ^abn represent subgroups with distinct deficits. Moreover, these results demonstrate the involvement of the SCP in the pathogenesis of movement sequencing in schizophrenia.     

Extinction of Over-selected Stimuli Causes Emergence of Under-selected Cues in Higher-functioning Children with Autistic Spectrum Disorders

Two experiments examined whether over-selectivity is the product of a post-acquisition performance deficit, rather than an attention problem. In both experiments, children with Autistic Spectrum Disorder were presented with a trial-and-error discrimination task using two, two-element stimuli and over-selected in both studies. After behavioral control by the previously over-selected stimulus was extinguished, behavioral control by the previously under-selected cue emerged without direct training. However, this effect was only found in higher-functioning children, and not with more severely impaired children. These findings suggest that over-selectivity is not simply due to a failure to attend to all of the stimuli presented. They also suggest that extinction of over-selected stimuli may be a fruitful line of intervention for clinical intervention for some individuals.     

A Training Study of Theory of Mind and Executive Function in Children with Autistic Spectrum Disorders

This study investigated the relationship between theory of mind and executive functioning in children with autistic spectrum disorders through a training study. Ten children were trained on theory of mind, whilst ten were trained in executive function. Seven children were assigned to a control group, receiving no intervention. Training programmes were administered individually, lasting for 25 minutes per day for 5–10 days. Children were tested before training, after training and at a two-month follow-up. Significant improvements were seen in performance on theory of mind tasks in both trained groups, whilst the control group showed no improvement. No improvement on the executive function tasks was seen in any of the groups. The implications of these findings are discussed.     

Brief Report: Pilot Investigation of Service Receipt by Young Children with Autistic Spectrum Disorders

Whether children with autistic spectrum disorders (ASD) and their families are receiving recommended assessments and services is poorly known. This pilot study examined service receipt as reported by parents of young children with ASD (n = 64) from four specialty centers in Canada. While almost all children had a speech and language assessment (94%), less than half had psychological (42%), or genetic (31%) testing. Speech and language (88%) and occupational (78%) therapies were the most frequently received treatments. Overall, certain findings did not correspond to recent recommended practice guidelines. Future studies should obtain more detailed information on assessments and treatments received from larger and more representative samples to better determine the quality of care received by families with children with ASD.     

Typical Emotion Processing for Cartoon but not for Real Faces in Children with Autistic Spectrum Disorders

This study evaluated whether atypical face processing in autism extends from human to cartoon faces for which they show a greater interest. Twenty children with autistic spectrum disorders (ASD) were compared to two groups of typically developing children, matched on chronological and mental age. They processed the emotional expressions of real faces, human cartoon and nonhuman cartoon faces. Children with ASD were as capable as controls in processing emotional expressions, but strategies differed according to the type of face. Controls relied on a configural strategy with all faces. By contrast, ASD children exploited this typical configural strategy with cartoons but used a local strategy with real faces. This atypical visual processing style is discussed in the context of face expertise.     

Evaluation of Planning Dysfunction in Attention Deficit Hyperactivity Disorder and Autistic Spectrum Disorders Using the Zoo Map Task

Attention-Deficit-Hyperactivity-Disorders (ADHD) and Autistic-Spectrum-Disorders (ASD) share overlapping clinical and cognitive features that may confuse the diagnosis. Evaluation of executive problems and planning dysfunction may aid the clinical diagnostic process and help disentangle the neurobiological process underlying these conditions. This study evaluates the planning function problems in 80 male children and adolescents diagnosed with ADHD and 23 male children and adolescents with ASD using the Zoo Map Task; both groups were comparable in terms of age and IQ. The relationship between planning function and other executive functions is also assessed. In comparison to the ADHD groups, ASD children presented more errors in the open-ended tasks; these planning function problems seem to be mediated by processing speed and motor coordination, however it does not seem to be mediated by other executive function problems, including attention, working memory or response inhibition. In the time for planning, an interaction between the specific subgroups and working memory components was observed. ADHD and ASD present with different patterns of planning function, even when other components of executive function are taken into account; clinical and educational implications are discussed.     

Cerebrospinal Fluid Biomarkers of Synaptic Dysfunction are Altered in Parkinson's Disease and Related Disorders

Background

Synaptic dysfunction and degeneration are central contributors to the pathogenesis and progression of parkinsonian disorders. Therefore, identification and validation of biomarkers reflecting pathological synaptic alterations are greatly needed and could be used in prognostic assessment and to monitor treatment effects.

Objective

To explore candidate biomarkers of synaptic dysfunction in Parkinson's disease (PD) and related disorders.

Methods

Mass spectrometry was used to quantify 15 synaptic proteins in two clinical cerebrospinal fluid (CSF) cohorts, including PD (n₁ = 51, n₂ = 101), corticobasal degeneration (CBD) (n₁ = 11, n₂ = 3), progressive supranuclear palsy (PSP) (n₁ = 22, n₂ = 21), multiple system atrophy (MSA) (n₁ = 31, n₂ = 26), and healthy control (HC) (n₁ = 48, n₂ = 30) participants, as well as Alzheimer's disease (AD) (n₂ = 23) patients in the second cohort.

Results

Across both cohorts, lower levels of the neuronal pentraxins (NPTX; 1, 2, and receptor) were found in PD, MSA, and PSP, compared with HC. In MSA and PSP, lower neurogranin, AP2B1, and complexin-2 levels compared with HC were observed. In AD, levels of 14-3-3 zeta/delta, beta- and gamma-synuclein were higher compared with the parkinsonian disorders. Lower pentraxin levels in PD correlated with Mini-Mental State Exam scores and specific cognitive deficits (NPTX2; rho = 0.25–0.32, P < 0.05) and reduced dopaminergic pre-synaptic integrity as measured by DaTSCAN (NPTX2; rho = 0.29, P = 0.023). Additionally, lower levels were associated with the progression of postural imbalance and gait difficulty symptoms (All NPTX; β-estimate = −0.025 to −0.038, P < 0.05) and cognitive decline (NPTX2; β-estimate = 0.32, P = 0.021).

Conclusions

These novel findings show different alterations of synaptic proteins in parkinsonian disorders compared with AD and HC. The neuronal pentraxins may serve as prognostic CSF biomarkers for both cognitive and motor symptom progression in PD. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

Posttraumatic Stress Disorder in individuals with diagnosis of Autistic Spectrum Disorders

Although children and adolescents with developmental disabilities are said to have higher risks of abuse than those without, trauma and Posttraumatic Stress Disorder (PTSD) are little examined in those diagnosed with Autistic Spectrum Disorders (ASDs). Our study aims to assess trauma types, prevalence, risk factors and symptoms; and PTSD in individuals with diagnosis of ASD. Participants were 69 children and adolescents (53 males, 16 females) who were consecutively followed-up at our clinic and met DSM-IV criteria for ASD. Assessment was done using semi-structured interview forms. 18 had trauma history and 12 were diagnosed with PTSD. Witnessing or being a victim of accidents/disasters/violence was the most common type of trauma. Interestingly, the rate of sexual and/or physical abuse was less than in the general population. Trauma history and PTSD rates were higher in girls than boys. Deterioration in social and communicative abilities, increase in stereotypes, aggression, distractibility, sleep disorders, agitation, hyperactivity, self-injury, and loss of self-care skills were the most common symptoms detected following trauma. These results underscore the importance of detailed assessment of behavioral and emotional problems in this group by ruling out any trauma history at periods which might otherwise be misdiagnosed as an exacerbation of symptoms of ASD.     

Short Breaks Services for Children with Autistic Spectrum Disorders: Factors Associated with Service Use and Non-use

Short break services in a UK county were studied using a postal survey of 256 families with a child with an autistic spectrum disorder (ASD). Results confirmed high degrees of stress and low levels of informal support for all families, but no significant difference in the informal support available to non-users as compared to users of short break services. Robinson & Stalker's (1990) 10-point dependency scale showed a significant difference in dependence and more difficult behaviors between children of users and non-users. However, a large number of non-users had children with high dependence (scoring > 7 points). Access was denied by the age of the child (under 11) diagnosis (Asperger syndrome), educational placement (mainstream) and lack of social worker referral.     

Connectivity Theory of Autism: Use of Connectivity Measures in Assessing and Treating Autistic Disorders

Background. Autism is a disorder characterized by deficits in communication, social interaction, a limited range of interests, and repetitive stereotypical behavior. Although it is believed that changes in the brain leading to Autism occur early on in prenatal and early postnatal development, there is no definitive test for a diagnosis of Autism. The diagnosis is made on the basis of behavioral signs and symptoms alone and is usually not made until age 2 or later. There have been numerous neuroanatomical abnormalities noted in Autism, some of which can be linked to neuropsychological dysfunction. Recently a new theory has become prominent which suggests the disorder may be due to aberrant neural connectivity patterns. Evidence in support of this theory has come from anatomical studies of white matter as well as functional neuroimaging studies.

Methods. Most studies have employed functional magnetic resonance imaging to investigate connectivity, or electroencephalography (EEG) coherence studies. The high temporal resolution of EEG lends itself well to the investigation of cerebral connectivity. Research suggests there may be patterns of both hyper- and hypoconnectivity between various brain regions. Seven different patterns of abnormal connectivity which can be analyzed with EEG are proposed.

Results. Patterns of hyperconnectivity may be found in frontotemporal and left hemispheric regions, whereas patterns of hypoconnectivity are often seen in frontal (orbitofrontal), right posterior (occipital/parietal-temporal), frontal-posterior, and left hemispheric regions. In addition to these patterns of hypo- and hyperconnectivity, a mu rhythm complex has been identified. Treatment goals may be based on coherence anomalies identified by quantitative EEG analysis. Increased coherence between brain regions may be downtrained, whereas decreased coherence between brain regions may be uptrained. Clinical examples of each pattern and a discussion of their neurofeedback treatment are provided.

Conclusion. A theory of autistic disorders is presented that has at its' core neural connectivity disturbances. Multivariate EEG connectivity indices are utilized to formulate a typology of connectivity anomalies or patterns that have been observed over a series of autistic patients. These represent phenotypic expressions of the underlying pathology that leads to autistic symptoms. Examples demonstrate how these connectivity metrics can be used to understand autistic disturbances and formulate neurofeedback strategies for remedying these difficulties.