# Testing the Bottom-Up vs Top-Down Imbalance Hypothesis of ASD

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $796,501

## Abstract

ABSTRACT / PROJECT SUMMARY
 Functional connectivity in the brains of individuals with autism spectrum disorders (ASD) has emerged
as an important marker of neural abnormalities associated with the disorder. However, despite hundreds of
studies on the topic, the specific nature of functional connectivity abnormalities that characterize the disorder
remains unresolved and no unifying framework has emerged to describe it. Constructing a consistent model of
the functional connectivity abnormalities that underlie ASD is absolutely essential for advancing our
understanding of the neural etiology of the disorder. While the commonly accepted model is one where long-
range functional connectivity is decreased in ASD while local functional connectivity is increased, many studies
have shown increased or normal long-range functional connectivity in ASD and the evidence supporting the
hypothesis that local functional connectivity is increased remains scant and indirect.
 To date, the vast majority of studies of functional connectivity in ASD have been carried out using fMRI,
a technique that relies on the hemodynamic response and thus has a temporal resolution of <1Hz. It is well
known, however, that functional connectivity is usually mediated by much faster frequency bands, commonly
divided into five fundamental frequency bands: delta (1-2 Hz), theta (3-7 Hz), alpha (8-12 Hz), beta (13-30 Hz),
and gamma (31-80 Hz). There is also recent evidence that these frequency bands mediate functional
connectivity with preferred directionality. Based on our own preliminary data and current studies, we propose to
test the hypothesis that ASD is characterized by increased long-range bottom-up (feedforward)
functional connectivity, alongside decreased long-range top-down (feedback ) functional connectivity,
and that the gamma and beta frequency bands, respectively, mediate these functional connectivity
abnormalities.
 Here, we propose to test our hypothesis by obtaining MEG (magnetoencephalography) data from two
spatial attention paradigms, visual and auditory, optimized for assessing bottom-up versus top-down functional
connectivity, in 50 TD and 60 ASD individuals, ages 14-17. Specifically, we propose the following aims: (1)
Test the hypothesis that bottom-up functional connectivity is abnormally increased in ASD in the auditory and
visual domains, and this is manifested primarily in the gamma frequency band. (2) Test the hypothesis that top-
down functional connectivity is abnormally reduced in ASD in the auditory and visual domains, and this is
manifested primarily in the beta frequency band. (3) Test the hypothesis that neurophysiological functional
connectivity measures derived using MEG will be predictive of ASD severity, diagnosis, and behavioral
features, using robust correlations, canonical correlations, and machine learning techniques. We expect that
the results of this study will lead to a substantially more detailed, comprehensive, and mechanistically
motivate...

## Key facts

- **NIH application ID:** 9960583
- **Project number:** 5R01MH117998-03
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Tal Kenet
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $796,501
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9960583

## Citation

> US National Institutes of Health, RePORTER application 9960583, Testing the Bottom-Up vs Top-Down Imbalance Hypothesis of ASD (5R01MH117998-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9960583. Licensed CC0.

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