Brain Connectivity in Autism: The Significance of Null Findings

Kennedy, Daniel P.; Paul, Lynn K.; Adolphs, Ralph

doi:10.1016/j.biopsych.2015.05.002

Cited by 8 publications

(8 citation statements)

References 10 publications

(7 reference statements)

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“…Despite intense research efforts, the malconnectivity model has not been successfully replicated (Ecker et al 2015;Kennedy et al 2015;Khan et al 2015;Lefebvre et al 2015), and neither has any of the myriad other unitary ASD brain impairment models. Moreover, none of these models has accounted for the variation in ASD global and regional brain structures, or the variation in ASD electrophysiology findings (Billeci et al 2013), or the variation in neurochemistry findings (Zürcher et al 2015).…”

Section: Does Asd Have Neurobiological Validity?mentioning

confidence: 99%

“…Another problem for standardizing the overgrowthmalconnectivity model is that there are so many different versions of this model (Fishman et al 2014;Kennedy et al 2015;Khan et al 2015;Kitzbichler et al 2015;Venkataraman et al 2015). As noted by Kennedy et al (2015), Bthe connectivity hypothesis has been vague ever since its inception… slowly morphing from a theory about underconnectivity in ASD, to one about distal underconnectivity paired with local overconnectivity, to one about atypical connectivity in either direction (or both)^(p. 81).…”

Section: Does Asd Have Neurobiological Validity?mentioning

confidence: 99%

“…As noted by Kennedy et al (2015), Bthe connectivity hypothesis has been vague ever since its inception… slowly morphing from a theory about underconnectivity in ASD, to one about distal underconnectivity paired with local overconnectivity, to one about atypical connectivity in either direction (or both)^(p. 81).…”

Section: Does Asd Have Neurobiological Validity?mentioning

confidence: 99%

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ASD Validity

Waterhouse

London

Gillberg

2016

Rev J Autism Dev Disord

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ASD research is at an important crossroads. The ASD diagnosis is important for assigning a child to early behavioral intervention and explaining a child's condition. But ASD research has not provided a diagnosis-specific medical treatment, or a consistent early predictor, or a unified life course. If the ASD diagnosis also lacks biological and construct validity, a shift away from studying ASD-defined samples would be warranted. Consequently, this paper reviews recent findings for the neurobiological validity of ASD, the construct validity of ASD diagnostic criteria, and the construct validity of ASD spectrum features. The findings reviewed indicate that the ASD diagnosis lacks biological and construct validity. The paper concludes with proposals for research going forward.Keywords DSM-5 . ASD . Autism . Diagnosis . Validity . Comorbidity . HeterogeneityThe goal of the DSM-3 nosology (American Psychiatric Association 1980) was to create reliable and standard categorical psychiatric diagnoses (Robins and Guze 1970). However, in the past 30 years, clinical, genetics, and neuroscience findings have revealed that the DSM diagnoses are not biologically valid. The National Institutes of Mental Health (NIMH) responded by proposing the Research Domain Criteria (RDoC) framework for a brain-based transdiagnostic psychiatric symptom nosology (Cuthbert and Insel 2013;Insel et al. 2010;Lilienfeld and Treadway 2016). Peterson (2015) and Weinberger et al. (2015) argued that the RDoC could not replace the DSM-5 psychiatric nosology (American Psychiatric Association 2013) or the parallel International Classification of Diseases (ICD) psychiatric nosology (World Health Organization 2012). But BFor the foreseeable future, RDoC is not envisioned as a system of psychiatric classification in its own right. Instead, in the near term, RDoC and DSM-ICD are expected to coexist. Nevertheless, RDoC is intended to provide scaffolding for a large-scale research program that will ultimately yield an alternative to DSM-ICD^ (Lilienfeld and Treadway 2016, p. 445).RDoC advocates accept that DSM-5/ICD psychiatric categories remain necessary in clinical practice, but argue that researchers should shift to RDoC study designs immediately. They assert that studying psychiatric categories lacking biological validity blocks the discovery of brain bases for psychopathology and thus cannot lead to effective medical treatments for specific psychiatric symptoms (Cuthbert and Insel 2013;Insel et al. 2010;Lilienfeld and Treadway 2016;Yee et al. 2015). Against this RDoC imperative for biological validity, Weinberger et al. (2015) countered that current DSM-5 psychiatric behavioral diagnoses were valid when they yielded effective medical treatment, clear prognosis, and a life course specific to a diagnosis.Autism spectrum disorder (ASD) research has been productive (Dawson 2016;de la Torre-Ubieta et al. 2016;Szatmari et al. 2016), but no ASD research findings have met the validity criteria of Weinberger et al. (2015). DSM-5 ASD research has found no s...

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Section: Does Asd Have Neurobiological Validity?mentioning

confidence: 99%

Section: Does Asd Have Neurobiological Validity?mentioning

confidence: 99%

Section: Does Asd Have Neurobiological Validity?mentioning

confidence: 99%

See 1 more Smart Citation

ASD Validity

Waterhouse

London

Gillberg

2016

Rev J Autism Dev Disord

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“…Although these studies have attempted to localize regional brain alterations in ASD, theories of brain mechanisms underlying ASD usually focused on brain connectivity (Just et al 2012;Kennedy et al 2015). The underconnectivity theory attributes ASD to lower anatomical and functional connectivity between the frontal and parietal cortex.…”

Section: Introductionmentioning

confidence: 99%

Sex-dependent and sex-independent brain resting-state functional connectivity in children with autism spectrum disorder

2016

Preprint

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Background: Males are more likely to suffer from autism spectrum disorder (ASD) than females.As to whether females with ASD have similar brain alterations remain an open question. The current study aimed to examine sex-dependent as well as sex-independent alterations in restingstate functional connectivity in individuals with ASD compared with typically developing (TD) individuals. Method:Resting-state functional MRI data were acquired from the Autism Brain Imaging Data Exchange (ABIDE). Subjects between 6 to 20 years of age were included for analysis. After matching the intelligence quotient between groups for each dataset, and removing subjects due to excessive head motion, the resulting effective sample contained 28 females with ASD, 49 TD females, 129 males with ASD, and 141 TD males, with a two (diagnosis) by two (sex) design.Functional connectivity among 153 regions of interest (ROIs) comprising the whole brain was computed. Two by two analysis of variance was used to identify connectivity that showed diagnosis by sex interaction or main effects of diagnosis. Results:The main effects of diagnosis were found mainly between visual cortex and other brain regions, indicating sex-independent connectivity alterations. We also observed two connections whose connectivity showed diagnosis by sex interaction between the precuneus and medial cerebellum as well as the precunes and dorsal frontal cortex. While males with ASD showed higher connectivity in these connections compared with TD males, females with ASD had lower connectivity than their counterparts.Conclusions: Both sex-dependent and sex-independent functional connectivity alterations are present in ASD.

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“…A recent commentary highlights a disconnection between autism spectrum disorder as a clinical entity and the logical pathway that leads there from genetics and neuroanatomical findings (Kennedy, Paul, and Adolphs 2015). It refers to the meta-analysis of null findings for callosal size in ASD in the same issue (Lefebvre et al 2015).…”

Section: Pathophysiologymentioning

confidence: 99%

A theory inspired proposal for a novel medical treatment in autism. The cerebellar model of autism and the hypothesis of dorsal stream dysfunction: evidence from idiopathic and syndromic cases.

Vakalopoulos¹

2017

Preprint

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The cerebellum figures prominently in the pathophysiology of idiopathic autism. Many syndromic comorbid cases and animal studies also highlight cerebellar involvement. The role of the cerebellum is implicated in cognitive and affective disorders. However, there remains a profound gap in understanding the route from genes, the effect of mutations on Purkinje cells and ultimately the behavioural phenotype. Given that conditions like autism are disorders of consciousness it is likely that progress will be made beyond the data generating enterprise, by improved theoretical models of the mind-body gap. A way forward is the proposal of consciousness as embodiment of a process of world discovery through motor efference copy. The cerebellum and basal ganglia are essential to a component theory of motor efference copy, providing a heuristic for understanding the structure of cortical dorsal and ventral stream pathways of a sensory modality. This then, further suggests that autism results from a selective dorsal stream dysfunction with all the attendant and hierarchical features that follow such a model and lead to both high level social and attentional deficits as well as lower level motor and restrictive interests. The paper aims to present evidence for dorsal stream dysfunction and how it may relate to a primary cerebellar pathology. The involvement of the cerebellum in most if not all syndromic cases of comorbid ASD is then presented. Finally, it is shown how such insights can be used to propose a general medical intervention based on the use of cerebellar rTMS across the disorder spectrum.

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Brain Connectivity in Autism: The Significance of Null Findings

Cited by 8 publications

References 10 publications

ASD Validity

ASD Validity

Sex-dependent and sex-independent brain resting-state functional connectivity in children with autism spectrum disorder

A theory inspired proposal for a novel medical treatment in autism. The cerebellar model of autism and the hypothesis of dorsal stream dysfunction: evidence from idiopathic and syndromic cases.

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