This study analyzed resting-state fMRI scans from over 1100 individuals with and without autism spectrum disorder (ASD) to investigate abnormalities in thalamocortical functional connectivity in ASD. The thalamus plays a key role in sensory processing and cortical activity. The researchers found that in individuals with ASD, connectivity was abnormally increased between the thalamus and prefrontal, motor, temporal, and parietal cortical regions. However, increased thalamocortical connectivity did not correlate with ASD symptom severity. The study helps clarify mixed previous findings on thalamocortical connectivity in ASD.
The «System 3 + 3» in a Problem of Searching of a New Paradigm in Psychiatry_...
MonicaGiraldoChica_Atlanta2016_ABIDE_v4
1. Introduction
Autism spectrum disorders (ASD) are defined by deficits in social
interaction and communication, rigid or stereotypical behaviors, and
abnormal sensory processing. The thalamus plays a key role in
gating sensory information to the cortex, modulating efferent motor
signals, and regulating overall cortical activity by virtue of the
sensory input it receives and dense connections with virtually all
regions of the cortex. Consequently, the neuropathology of ASD may
involve dysfunction of the thalamus and its connections with the
cortex.
Using data from the Autism Brain Imaging Data Exchange (ABIDE),
a large, publically-available repository of resting-state fMRI scans
collected on over 1100 individuals, the goal of this study is to clarify
mixed findings on thalamocortical functional connectivity in ASD.
Thalamocortical Dysconnectivity in Autism Spectrum Disorder: An Analysis of
the Autism Brain Imaging Data Exchange (ABIDE)
Monica Giraldo-Chica, Carissa J. Cascio, Neil D. Woodward
Vanderbilt University School of Medicine, Department of Psychiatry
Conclusions
• Thalamocortical networks are abnormal in ASD.
• The abnormalities are characterized by marked prefrontal,
sensorimotor, and temporal hyper-connectivity with the
thalamus.
• More research is needed to determine the functional
consequences of thalamic hyper-connectivity and determine the
trajectory of the changes in ASD.
Acknowledgements
Methods
Table 1. Demographic Characteristics
Variable ASD Controls
N 228 228
Gender (male:female) 119:29 119:29
Mean SD Mean SD t p
Age 16.6 6.1 16.6 6.0 0.65 .948
Full-Scale IQ 101.9 22.0 111.3 13.4 5.45 <.001
RS-fMRI Data Quality Metrics
Percent Scrubbed Volumes 5.34 5.19 4.91 5.00 0.91 .362
Pre-scrubbing RMS FD 0.22 0.13 0.21 0.12 0.47 .641
Post-scrubbing RMS FD 0.16 0.05 0.15 0.04 0.93 .351
Pre-scrubbing DVARS 2.95 1.03 2.97 1.02 0.23 .816
Post-scrubbing DVARS 2.25 0.74 2.25 0.73 0.05 .960
Imaging analysis steps:
1) The cortex was divided into 6 non-overlapping cortical ROIs:
2) Within Thalamus Connectivity:
• Cortical ROIs were used as seeds in a functional connectivity analysis
restricted to the thalamus;
• Cortical-to-thalamic connectivity maps compared between ASD and TD
3) Whole Brain Connectivity of Thalamic Sub-regions:
• Using all 456 subjects, the thalamus was segmented into functional sub-
divisions using the ‘winner take all’ approach in which each voxel in the
thalamus is assigned to the cortical ROI it is most strongly connected to;
• Thalamic sub-divisions then used as seeds in a whole-brain functional
connectivity analysis;
• Thalamic sub-region connectivity maps compared between ASD and TD
Temporal Cortex (TMP) Prefrontal Cortex (PFC)
Motor Cortex (MT)
Somatosensory Cortex (SS)Parietal Cortex (PAR)
Occipital Cortex (OCC)
Results
PFC MT SS
TMP PAR OCC
Whole Brain Connectivity of Thalamic
Functional Sub-Divisions
Prefrontal, motor, temporal, and posterior parietal cortex thalamic
sub-divisions demonstrated increased connectivity in ASD.
Association between thalamocortical
connectivity abnormalities and ASD symptoms
The association between clinical symptoms and abnormal
functional connectivity was examined. Mean functional
connectivity was extracted from the clusters identified in the
between groups comparisons and correlated with the following
variables: ADOS social, communication, stereotypical behaviors
scores and social responsiveness.
None of the correlations reached significance.
This research was supported by:
- NIMH (5 R21 MH101321 awarded to CJC and NDW)
- Jack Martin Professorship in Psychopharmacology
(held by NDW).
Within Thalamus Connectivity
All results thresholded at cluster-level Family-wise error corrected p(FWE)=.05 for voxel-wise p(uncorrected)=.001.
Whole Brain Connectivity of Thalamic Functional
Sub-Divisions
‘Winner Take All’ Functional Segmentation of the Thalamus (n=456)
Thalamic Functional Sub-divisions Exhibit Distinct Cortical
Connectivity Profiles (n=456)
Within group results thresholded at whole-brain voxel-level Family-wise error corrected p(FWE)=.001.
Between group results thresholded at whole-brain cluster-level Family-wise error corrected p(FWE)=.05 for voxel-wise
p(uncorrected)=.001.