HBM 2001 Poster

1
Three-Way Multidimensional Scaling of Functional
MRI Data Shows Increased Heterogeneity of
Inter-regional Connectivity in Patients with
Schizophrenia
D. E. Welchew, G. Honey, T. Sharma, T. W.
Robbins, E. T. Bullmore
University of Cambridge and Institute of
Psychiatry, UK
E-mail dew22_at_cam.ac.uk
INTRODUCTION
RESULTS

• Functional MRI data can be used to examine the
  functional connectivity between specified
  cortical areas, by the generation of
  inter-regional correlation matrices from time
  series extracted from individual images1.
• Three-way multidimensional scaling (MDS)2 can be
  used to explore the configuration of regions of
  the brain, whilst also providing a measure of the
  extent to which individual subjects differ from
  their generic configuration.
• Various measurements have been proposed to
  quantify the relative atypicalness of individual
  subjects within a group. One such metric is
  weirdness, a measure of deviation from the
  average configuration standardised to the range
  0,1.
• Here, we present an application of the MDS
  technique to a linguistic processing task to
  compare weirdness in schizophrenic patients and
  normal volunteers.

Derived Stimulus Configuration

• The eleven areas separate on the first derived
  dimension according to anatomical location
  (frontotemporal vs occipitoparietal regions), and
  according to hypothesised function (analysis of
  input vs. subvocal output) on the second
  dimension

METHODS
Summary of Weirdness Statistic
Imaging and Subjects

• Gradient echo echo-planar imaging at 1.5 Tesla
  was used to study nineteen right-handed
  schizophrenic patients receiving anti-psychotic
  therapy, and twenty volunteers matched for age
  and sex.
• We used a periodic AB design
• A (30 sec) subjects were visually presented
  with a series of nouns (ISI1.5 sec), asked to
  decide whether each referred to a living or
  non-living object, and subvocalise their
  decision.
• B (30 sec) subjects viewed an isoluminant
  screen.
• This cycle was repeated five times over the
  course of each five-minute experiment.
• Generic brain activation mapping 3 was used to
  identify one left unilateral and five bilateral
  foci of activation ventral extrastriate cortex,
  superior temporal gyrus, supplementary motor
  area, inferior parietal lobule and prefrontal
  cortex bilaterally, and left inferior frontal
  gyrus unilaterally.

Relative Importance of Dimensions
CONCLUSIONS

• The configuration map obtained from all subjects
  follows previous results showing a separation of
  functionally active cortical regions according to
  their anatomical location and hypothesised rôle
  in the task.
• We have demonstrated a previously unreported
  difference in individual subject heterogeneity
  between control subjects and schizophrenic
  patients.
• This finding indicates that there may be greater
  heterogeneity of inter-regional covariance
  structures in patients with schizophrenia than in
  normal comparison subjects.

Statistics

• Eleven time series were extracted from the means
  of index voxels and their eight nearest
  neighbours in each cluster for all subjects. A
  configuration map of the regions was generated
  from all the subjects using weighted individual
  differences scaling on the ALSCAL program in
  SPSS, and the weirdness of each subject was
  derived from the individual subject correlation
  matrices.
• Weirdness is an index of how similar the
  weighting on each dimension of a given subject is
  to the group weighting, and ranges from zero (the
  subject has weights proportional to the average
  weight) to one (the subject has only a single
  non-zero weight). Weirdness was compared
  between groups using Students t-test for unequal
  variances.

REFERENCES

• Bullmore, E.T., Rabe-Hesketh, S. et al.
  NeuroImage 1996, 416-33
• Everitt, B.S. and Rabe-Hesketh, S. The Analysis
  of Proximity Data. Arnold, 1997
• Brammer, M.J. et al. 1997, Magnetic Resonance
  Imaging, 15 763-770