Sex differences in autism: a resting-state fMRI investigation of functional brain connectivity in males and females

Alaerts, Kaat; Swinnen, Stephan P.; Wenderoth, Nicole

doi:10.1093/scan/nsw027

Cited by 151 publications

(179 citation statements)

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“…This might not only open new possibilities for experimental research but also lead to new therapeutic applications in diseases where resting-state connectivity is diminished as, for example, in autism or Alzheimer's disease (Greicius, 2008;Alaerts et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…This could open new opportunities for human fMRI research and new interventional approaches for modulating long-range connectivity of the human brain at rest. Potential therapeutic applications could be, for example, tACS-based modulation in patients with diminished resting-state connectivity within specific circuits, as for example in autism (Alaerts et al, 2014) and Alzheimer's disease (Greicius, 2008).…”

Section: Distribution Of the Electric Fieldmentioning

confidence: 99%

“…(Damoiseaux et al, 2006). Alterations in restingstate connectivity have been associated with several neuropathologies (Greicius, 2008;Bullmore and Sporns, 2009;Fornito and Bullmore, 2010;Alaerts et al, 2014Alaerts et al, , 2016 opening new opportunities for identifying disease-specific biomarkers and potential therapy targets at the brain circuit level (Alaerts et al, 2014;Woolley et al, 2015). However, which exact electrophysiological mechanisms cause RSNs to emerge is still debated, making it difficult to design new interventions that target activity at the cell population level with the aim of normalizing large-scale connectivity within specific circuits.…”

Section: Introductionmentioning

confidence: 99%

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Concurrent tACS-fMRI Reveals Causal Influence of Power Synchronized Neural Activity on Resting State fMRI Connectivity

et al. 2017

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Resting state fMRI (rs-fMRI) is commonly used to study the brain's intrinsic neural coupling, which reveals specific spatiotemporal patterns in the form of resting state networks (RSNs). It has been hypothesized that slow rs-fMRI oscillations (Ͻ0.1 Hz) are driven by underlying electrophysiological rhythms that typically occur at much faster timescales (Ͼ5 Hz); however, causal evidence for this relationship is currently lacking. Here we measured rs-fMRI in humans while applying transcranial alternating current stimulation (tACS) to entrain brain rhythms in left and right sensorimotor cortices. The two driving tACS signals were tailored to the individual's ␣ rhythm (8 -12 Hz) and fluctuated in amplitude according to a 1 Hz power envelope. We entrained the left versus right hemisphere in accordance to two different coupling modes where either ␣ oscillations were synchronized between hemispheres (phase-synchronized tACS) or the slower oscillating power envelopes (power-synchronized tACS). Power-synchronized tACS significantly increased rs-fMRI connectivity within the stimulated RSN compared with phase-synchronized or no tACS. This effect outlasted the stimulation period and tended to be more effective in individuals who exhibited a naturally weak interhemispheric coupling. Using this novel approach, our data provide causal evidence that synchronized power fluctuations contribute to the formation of fMRI-based RSNs. Moreover, our findings demonstrate that the brain's intrinsic coupling at rest can be selectively modulated by choosing appropriate tACS signals, which could lead to new interventions for patients with altered rs-fMRI connectivity.

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Section: Discussionmentioning

confidence: 99%

Section: Distribution Of the Electric Fieldmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Concurrent tACS-fMRI Reveals Causal Influence of Power Synchronized Neural Activity on Resting State fMRI Connectivity

et al. 2017

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“…[5][6][7] Moreover, gender has recently been shown to modulate the direction of connectivity differences in ASD. 8 In contrast, another study found default mode network (DMN) hypo-connectivity in both genders. 9 Finally, another source of bias that has been largely overlooked is the impact of age-related changes on functional connectivity.…”

Section: Introductionmentioning

confidence: 94%

Alterations in resting state connectivity along the autism trait continuum: a twin study

et al. 2017

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Autism spectrum disorder (ASD) has been found to be associated with alterations in resting state (RS) functional connectivity, including areas forming the default mode network (DMN) and salience network (SN). However, insufficient control for confounding genetic and environmental influences and other methodological issues limit the generalizability of previous findings. Moreover, it has been hypothesized that ASD might be marked by early hyper-connectivity followed by later hypo-connectivity. To date, only a few studies have explicitly tested age-related influences on RS connectivity alterations in ASD. Using a within-twin pair design (N = 150 twins; 8-23 years), we examined altered RS connectivity between core regions of the DMN and SN in relation to autistic trait severity and age in a sample of monozygotic (MZ) and dizygotic (DZ) twins showing typical development, ASD or other neurodevelopmental conditions. Connectivity between core regions of the SN was stronger in twins with higher autistic traits compared to their co-twins. This effect was significant both in the total sample and in MZ twins alone, highlighting the effect of non-shared environmental factors on the link between SN-connectivity and autistic traits. While this link was strongest in children, we did not identify differences between age groups for the SN. In contrast, connectivity between core hubs of the DMN was negatively correlated with autistic traits in adolescents and showed a similar trend in adults but not in children. The results support hypotheses of age-dependent altered RS connectivity in ASD, making altered SN and DMN connectivity promising candidate biomarkers for ASD.Molecular Psychiatry advance online publication, 1 August 2017; doi:10.1038/mp.2017.160 INTRODUCTION Altered patterns of brain connectivity have been suggested as a key neurobiological correlate of the behavioral characteristics of autism spectrum disorder (ASD). However, as findings are inconsistent, the precise brain connectivity characteristics of ASD remain unclear. A large number of resting-state (RS) functional magnetic resonance imaging (MRI) brain connectivity studies have shown a complex pattern of both hypo-and hyper-connectivity in ASD.1-3 Notably, a large multi-site classification study including ASD and typically developing individuals (N = 252, 6-36 years) showed that of the top 100 biomarkers of brain connectivity achieving together 90.8% accuracy, 45% were related to hyperconnectivity and the remaining 55% to hypo-connectivity. 4 It is likely that the observed inconsistencies in classical brain connectivity investigations are limited by methodological issues, such as insufficient control for head motion or the inclusion of global signal regression which can modulate or even invert the direction of functional connectivity differences. [5][6][7] Moreover, gender has recently been shown to modulate the direction of connectivity differences in ASD. 8 In contrast, another study found default mode network (DMN) hypo-connectivity in both genders.

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“…By contrast, Di & Biswal12 found solely sex-independent, large-scale neuroanatomical alterations in children with ASD, which were deemed to be consistent with the predictions of EMB theory. On the other hand, Alaerts et al 13. identified highly-consistent patterns of functional hypo-connectivity in ASD males compared to TD males, and hyper-connectivity in females with ASD compared to TD females.…”

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The connectomes of males and females with autism spectrum disorder have significantly different white matter connectivity densities

Irimia

Torgerson

Jacokes

et al. 2017

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Autism spectrum disorder (ASD) encompasses a set of neurodevelopmental conditions whose striking sex-related disparity (with an estimated male-to-female ratio of 4:1) remains unknown. Here we use magnetic resonance imaging (MRI) and diffusion weighted imaging (DWI) to identify the brain structure correlates of the sex-by-ASD diagnosis interaction in a carefully selected cohort of 110 ASD patients (55 females) and 83 typically-developing (TD) subjects (40 females). The interaction was found to be predicated primarily upon white matter connectivity density innervating, bilaterally, the lateral aspect of the temporal lobe, the temporo-parieto-occipital junction and the medial parietal lobe. By contrast, regional gray matter (GM) thickness and volume are not found to modulate this interaction significantly. When interpreted in the context of previous studies, our findings add considerable weight to three long-standing hypotheses according to which the sex disparity of ASD incidence is (A) due to WM connectivity rather than to GM differences, (B) modulated to a large extent by temporoparietal connectivity, and (C) accompanied by brain function differences driven by these effects. Our results contribute substantially to the task of unraveling the biological mechanisms giving rise to the sex disparity in ASD incidence, whose clinical implications are significant.

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Sex differences in autism: a resting-state fMRI investigation of functional brain connectivity in males and females

Cited by 151 publications

References 63 publications

Concurrent tACS-fMRI Reveals Causal Influence of Power Synchronized Neural Activity on Resting State fMRI Connectivity

Concurrent tACS-fMRI Reveals Causal Influence of Power Synchronized Neural Activity on Resting State fMRI Connectivity

Alterations in resting state connectivity along the autism trait continuum: a twin study

The connectomes of males and females with autism spectrum disorder have significantly different white matter connectivity densities

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