Francesca Benassi

Auditory sensory processing in autism: a magnetoencephalographic study

BACKGROUND Patients with autism show clinical features suggestive of abnormal processing of auditory and other sensory information. We hypothesized that low-functioning autistic subjects present abnormalities in discriminating simple auditory stimuli at sensory system preconscious stages of cortical processing. METHODS To verify our hypothesis, we used magnetoencephalographic measurements of mismatch field (MMF), which reflects the detection of a change in the physical characteristics of a repetitive sound. Fourteen patients (aged 8-32 years) who met DSM-IV diagnostic criteria for autistic disorder participated in an auditory oddball experiment. Ten healthy participants matched for age and gender acted as control subjects. RESULTS Significant differences in cerebral responses between patients and control subjects were recorded. Whereas control subjects showed a clearly identifiable MMF, with distinct generators in the M100 brain wave with regard to latency, position, and strength, no identifiable MMF was present in the autistic group. CONCLUSIONS Our findings suggest that low-functioning autistic subjects present a dysfunction at preconscious stages of cortical auditory discrimination, playing a role in the abnormal processing of auditory sensory afferences. The attention independence of the MMF allows for exclusion of an effect related to impaired attention or task-related responses.

White matter reduced streamline coherence in young men with autism and mental retardation

Background and purpose:  It has been proposed that white matter alterations might play a role in autistic disorders; however, published data are mainly limited to high‐functioning autism. The goal of this study was to apply diffusion tensor imaging (DTI) and fiber tractography (FT) to study white matter in low‐functioning autism and the relationship between white matter and cognitive impairment.

Long-term cognitive and behavioral therapies, combined with augmentative communication, are related to uncinate fasciculus integrity in autism.

Recent evidence points to white-matter abnormalities as a key factor in autism physiopathology. Using Diffusion Tensor Imaging, we studied white-matter structural properties in a convenience sample of twenty-two subjects with low-functioning autism exposed to long-term augmentative and alternative communication, combined with sessions of cognitive and behavioral therapy. Uncinate fasciculus structural properties correlated significantly with therapy length and early onset, as well as to clinical outcome, independently from IQ, age or symptoms severity at therapy onset. Moreover, adherence to therapy was linked with better clinical outcome and uncinate fasciculus structural integrity. The results point to the capability of a long-term rehabilitation of subjects with low-functioning autism to produce white-matter structural modifications, which could thus play a role in the rehabilitative outcome.

Isolated theory of mind deficits and risk for frontotemporal dementia: a longitudinal pilot study

Objective Recent data suggest that theory of mind (ToM) deficits represent an early symptom of the behavioural variant of frontotemporal dementia (bvFTD). However, longitudinal data on the natural history of subjects presenting with isolated ToM deficits are lacking. The aim of the study was to verify if isolated ToM deficits represent an at-risk state for prefrontal dysfunction and bvFTD. Methods A population of healthy subjects (n=4150, age range: 50–60 years) completed a clinical and neuropsychological evaluation including the Reading the Mind in the Eyes Test (RMET), a widely used ToM task. From this group, we recruited a low-RMET group (n=83) including subjects with RMET scores lower than 2 SDs but an otherwise normal neuropsychological evaluation and a control group. All subjects underwent evaluation at baseline and after 2 years. Results Subjects in the low-RMET group showed decline in prefrontal functions at follow-up. Moreover, at follow-up 12 subjects in the low-RMET group presented with findings suggestive of bvFTD. Neuropsychological performance was stable in the control group. Conclusions Our data suggest that isolated ToM deficits could represent an at-risk situation for the development of future prefrontal dysfunction and bvFTD. ToM evaluation should be included in neuropsychological protocols aimed to evaluate the early phases of dementia.

Are caesarean sections, induced labor and oxytocin regulation linked to Autism Spectrum Disorders?

The etiology of Autism Spectrum Disorders (ASDs) continues to be elusive. While ASDs have been shown to be heritable, several environmental co-factors, such as, e.g. pre- or perinatal adverse events, could play a role in the pathogenesis of the disorder as well. Prevalence of ASDs appears to have increased in the last three decades, but the causes of this surge are not fully understood. As perinatal adverse events have increased as well, they have been regarded as logical contributors to the risen prevalence of ASDs. Over the last three decades there has been also a considerable increase in the rates of induced labor and caesarean sections (CS). However, even if a causal association between CS and ASDs increase has been suggested, it has not yet been proven. Nevertheless, we hypothesize here that such an association is actual and that it might help to explain a part of the increase in ASD diagnoses. Our assumption is based on the wider epidemiological picture of ASDs and CS, as well as on the possible biological plausibility of this correlation, by postulating potential epigenetic and neurobiological mechanisms underpinning this relationship. Today, several observations point toward the existence of epigenetic dysregulation in ASDs and this raises the issue of the role of environmental factors in bringing about epigenetic modifications. Epigenetic dysregulations in some brain neuropeptide systems could play a role in the behavioral dysfunctions of ASDs. Particularly, some evidence suggests a dysregulation of the oxytocinergic system in autistic brains. Perinatal alterations of oxytocin (OT) can also have life-long lasting effects on the development of social behaviors. Within the perinatal period, various processes, like pitocin infusion or CS, can alter the OT balance in the newborn; OT dysregulation could then interact with genetic factors, leading ultimately to the development of ASDs. Large long-term prospective studies are needed to identify causal pathways for ASDs and examine whether and how (epi-)genetic susceptibility interacts with obstetric risk factors in the development of ASDs. A better understanding of such a potential interplay could become paradigmatic for a wide range of genetic-environmental interactions in ASDs.

Effectiveness of community-based treatment on clinical outcome in children with autism spectrum disorders: An Italian prospective study

Abstract Objective: Little is known about outcomes of Autism Spectrum Disorders (ASDs) interventions in real-life settings. The main aim of this naturalistic study was to collect real-life data on the actual ASDs treatment practices in Italy. Methods: A cohort of 48 children undergoing community-based interventions was observed in terms of personal and environmental characteristics, treatment typology and outcomes. Results: An earlier start of treatment was associated with an improvement of autistic symptoms, independently from symptoms severity (p < 0.05), but not with improvements in terms of intelligence quotient (p = 0.8). Children belonging to lower socioeconomic status families began treatment later (48.0 months) than those belonging to middle (39.8 months) or upper (39.2 months) classes (p < 0.05), and received less hours of treatment. Conclusion: The study showed that ASDs interventions should be observed not only in experimental settings, but also in naturalistic environments, so to appraise the actual effectiveness of integrating different treatment methods in community settings.

Agomelatine but not melatonin improves fatigue perception: A longitudinal proof-of-concept study

Chronic Fatigue Syndrome (CFS) represents a disabling condition characterized by persistent mental and physical fatigue, bodily discomfort and cognitive difficulties. To date the neural bases of CFS are poorly understood; however, mono-aminergic abnormalities, sleep-wake cycle changes and prefrontal dysfunctions are all thought to play a role in the development and maintenance of this condition. Here we explored in a group of 62 CFS subjects the impact on fatigue levels of agomelatine, an antidepressant with agonist activity at melatonin receptors (MT1 and MT2) and antagonist activity at serotoninergic 2C receptors (5HT2C). To tease out the relative effects of MT-agonism and 5HT2C antagonism on fatigue, we compared agomelatine 50mg u.i.d. with sustained release melatonin 10mg u.i.d. in the first 12-week-long phase of the study, and then switched all melatonin-treated subjects to agomelatine in the second 12-week-long phase of the study. Agomelatine treatment, but not melatonin, was associated with a significant reduction of perceived fatigue and an increase in perceived quality of life. Moreover the switch from melatonin to agomelatine was associated with a reduction of fatigue levels. Agomelatine was well tolerated by all enrolled subjects. Our data, albeit preliminary, suggest that agomelatine treatment could represent a novel useful approach to the clinical care of subjects with CFS.

Reduction in Retinal Nerve Fiber Layer Thickness in Young Adults with Autism Spectrum Disorders.

Recent years have seen an increase in the use of retinal nerve fiber layer (RNFL) evaluation as an easy-to-use, reproducible, proxy-measure of brain structural abnormalities. Here, we evaluated RNFL thickness in a group of subjects with high functioning autism (HFA) or with Asperger Syndrome (AS) to its potential as a tool to study autism pathophysiology. All subjects underwent high-resolution spectral domain optical coherence tomography to evaluate RNFL thickness. HFA subjects presented with reduced global RNFL thickness compared both to AS subjects and controls. AS subjects showed a reduced nasal quadrant RNFL thickness compared to controls. Verbal-IQ/performance-IQ discrepancy correlated with RNFL thickness. Our data suggest that RNFL evaluation could help in the development of biological markers of autism pathophysiology.

Reduction in retinal nerve fiber layer thickness in tuberous sclerosis complex

PurposeThe aim of our study was to non-invasively investigate central nervous system axonal integrity in patients with tuberous sclerosis complex (TSC). Diffuse microstructural white matter abnormalities reflecting axonal disorganization, reduced/altered myelination, or gliosis have been described in individuals with TSC. Optical coherence tomography (OCT) is a fast, easy-to-perform, non-invasive, and cost-efficient method to assess retinal morphology in vivo and to measure the thickness of the retinal nerve fiber layer (RNFL).MethodsIn order to assess central nervous system axonal integrity, eight subjects with TSC have been investigated by OCT to evaluate RNFL and they have been compared with matched healthy controls.ResultsWhen comparing mean overall RNFL thicknesses of the TSC group with those of the control group, the TSC group presented with significantly lower RNFL values, compared to the control group, in the temporal quadrant (62.5 ± 6.9 vs. 76.9 ± 5.4; t = 14.438; p < 0.0001).ConclusionsSince a reduced RNFL thickness might be seen as an indicator of chronic axonal degeneration or lack of appropriate neuronal development, our results support the presence of axonal alterations in TSC and also that white matter disorganization could be much more diffuse than originally thought. Since axonal alterations directly derive from mammalian target of rapamycin (mTOR) overactivation, which occurs early during fetus development, the RNFL thinning we observed could represent one of the facets of such early neurodevelopmental abnormalities.

OPTICAL COHERENCE TOMOGRAPHY AND INFRARED IMAGES OF ASTROCYTIC HAMARTOMAS NOT REVEALED BY FUNDUSCOPY IN TUBEROUS SCLEROSIS COMPLEX.

Purpose: To detect, describe, and classify the morphologic characteristics of astrocytic hamartomas in tuberous sclerosis complex, using both spectral-domain optical coherence tomography (OCT) and infrared images. Methods: Ten subjects (20 eyes) with tuberous sclerosis complex underwent a complete ophthalmologic examination and multimodality imaging with spectral-domain OCT and infrared images. The imaging protocol included a 30°scan angle of the posterior pole and of the four quadrants. Line scans, detail, raster, and posterior pole patterns were used. The identified astrocytic hamartomas were described and characterized qualitatively and quantitatively. Results: Forty-four hamartomas were detected in 8 patients. In five cases, lesions were bilateral. Thirty of these hamartomas had not been revealed by previous ophthalmoscopy. Through multimodality imaging, it was possible to define multiple lesions with characteristic optical reflective qualities. All the 44 hamartomas were measured and morphologically characterized in terms of the type of tumor, retinal and/or vitreous involvement, calcifications, and posterior optical shadowing. Conclusion: The combined imaging with spectral-domain OCT and infrared images improves the detection of hamartomas if compared with the spectral-domain OCT technique alone. Moreover, a new subtype of hamartoma is proposed to complete a previous classification based on OCT.