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Subject:

localizing inferences

From:

David Wack <[log in to unmask]>

Reply-To:

[log in to unmask]

Date:

Wed, 1 Dec 2004 12:48:52 -0500

Content-Type:

text/plain

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Parts/Attachments

text/plain (62 lines)

Re: Can one make localizing inferences when
a cluster reaches significance but no voxels reach voxel-level
significance?


We have seen a number of PET publications (the imaging modality we use)
that attribute regional significance to data defined at a cluster-level.
However, having read what we think are the relevant publications, we
still have some uncertainty and doubt about the ability to associate a
specific location on the basis of a cluster when the significance of the
cluster is less than 0.05 (corrected) and when there are no voxels within
the cluster that reach statistically significant level.  The SPM99
manual seems fairly clear, stating that the cluster level significance
means that the size of the cluster exceeds that expected by chance.
Nothing is said about the cluster location.  In Human Brain
Function, page 91, it says that within a cluster, nothing can be said at
the voxel level [yet] the interpretation of results will clearly be
different depending on threshold.  This seems to be a clear
reference to the ROC curves discussed in that chapter and in NeuroImage
1996;4:223.  A high threshold increases the chance that the voxels
within a cluster are a part of an underlying signal, without making any
claim as to where that signal might occur, from an anatomical
perspective.  However, in NeuroImage 1996;4:223, nearly the last
sentence says this example highlights the potential benefit of set-level
inferences; in that the entire activation profile can be described
anatomically and characterized as significant, therein providing a
complete and comprehensive picture of activations ...
(emphasis added). This implies that one can make anatomical inferences
based on set-level statistics.  If one can do this at the set level,
then why not at the cluster level as this is a stronger test?


In the SPM output, the cluster data are shown as the cluster size at the
specified analytical threshold.  No anatomical data are provided,
although one can find the cluster on the glass-brain projections.
Any statement about a specific anatomical location would seem to take the
analysis further toward the voxel level.  Thus, if a cluster
achieves significant size and appears on the glass-brain images in a
location that indicates a specific region of the brain, say the occipital
lobe, can one say that the contrast utilized yields a significant
difference in the occipital lobe?  I would think not.  If one
wanted to make an anatomical inference, then one of two strategies or
conditions should be employed: 1) there should be significance at a voxel
level, or, 2) there should be an a priori regional hypothesis, in
which case the investigator would create a mask to define the region,
thus enabling the investigator to use small volume correction option to
seek significance in the region.  It would not seem to be
appropriate to create the mask using post hoc information based on
the appearance of the glass-brain projections.


We would appreciate a clarification on this issue.


As always, we are very appreciative of your help.

Alan Lockwood
[log in to unmask]
voice:  (716) 862-8788
voice mail (716) 862-8788
fax:     (716) 862-8766

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