Manuscript #14/046 by Bosak and Martin
Reviewer Comments:
Reviewer #1: The goal of this manuscript is to present a study using fMRI to examine differential brain
response associated with body weight in midlife women performing a goal-directed task. Although the
findings are intriguing, the discussion is lacking in terms of explaining how the study fits into the literature.
Furthermore, the authors fail to document the behavioral findings, thus it is not known whether there are
performance differences due to BMI, or if performance differences might be responsible for the functional
differences reported.
1. Abstract: Although 30 women were recruited, only 19 were used in the final analyses. The abstract should
therefore state that 19 women participated in the study.
2. Methods: Were psychiatric disorders ruled out solely by self-report, or where assessments given? Given
the elevated risk for depression in women nearing menopause, it would seem prudent to assess this
carefully.
3. Methods: The neuroimaging processing path description seems incomplete. Were the data spatially
smoothed? To which template where the images aligned? Although the authors used AFNI (and hence the
Talairach is assumed here), it is possible the authors chose a different template space (e.g., MNI).
4. Methods: Please clarify whether the combined mask were bilateral or unilateral.
5. Methods: What was the cutoff for determining excessive motion?
6. Results: Within the final dataset, there are no details regarding their age, BMI range, education, etc.
7. Results: Other than stating in the methods that behavioral performance was used to exclude six
participants, there is no further discussion on behavior. Did all participants show equivalent learning? Was
there a difference due to BMI? How participants performed on the task has clear implications on interpreting
the functional results.
8. Results: Was BMI associated with age? If so, is it possible that age, rather than (or in addition to) BMI
might drive the effects reported?
9. Discussion: Although the introduction makes a point about using a task believed to support and dissociate
goal-directed and habit-based systems, there is very little about how the findings relate to these systems in
the discussion. Rather, the discussion seems to be focused upon the study's limitations rather than its
findings and how they relate to the literature. Are there other studies showing associations of cognitive
control with BMI in the literature? What information does this study add? What does this tell us clinically?
10. Figures: The authors should be sure to define any abbreviations within the figure caption. Also, Figure 4
had boxed question mark symbols on my copy; this might be due to the transformation from a word
processing document to PDF.
Reviewer #3: This is a well-written manuscript addressing a very important issue. Understanding the
neurobiology underlying behavior is as important area of science today.
I have two comments that will improve this manuscript.
First, the description of the Dual Framework on page 4 does not point out the importance of the ability to
use both emotional processing as well as task processing. Given your results, this aspect of the Dual
Framework should be added to your description of it on p.4.
Second, I suggest in your discussion section that you refer again to the Dual Framework, especially pointing
out the findings related to the emotion processing and its possible importance in activation for health
behavior.
Perhaps I missed it, but a couple of reads of the manuscript and I could not find a statement that the
protocol was IRB- approved.
Reviewer #4: NRES-D-14-00046
Review of Neuroimaging of Goal-directed Behavior in Midlife Women
This manuscript describes a function magnetic resonance imaging study that uses a goal-directed behavior
task to investigate the association of BMI with differences in brain BOLD response while participants perform
a specific goal-directed task. The authors restrict their investigations to specific brain regions hypothesized
to involve goal-directed behavior. The study uncovers clusters in several brain regions with activation
differences that are correlated with participant BMI. The authors infer that these findings show that over
weight middle aged women have different responses to tasks associated with goal driven behavior.
The global problem the , the need to improve the modest success rate of motivational intervention programs
in improving physical activity and overall health of middle aged women, is certainly relevant to nursing. The
objective of the study was to investigate whether there is a difference in the brain response between healthy
weight and overweight middle aged women to a particular goal-directed fMRI task. The hypothesis is that
activation differences would correlate in a linear way to participant BMI. The manuscript reports several such
regions with activation levels that correlate with BMI, some of which fall within hypothesized brain regions.
However, the link between the outcome measures (correlations of the differences in activation levels
between task states of this particular goal oriented task to BMI) to predicting the success a particular
subject would have in an interventional program is not as strongly made in this manuscript as would be
preferred.
The background section provides a good motivation of the importance of the global issue and the need to
understand how to motivate some middle aged to live healthier lifestyles. The theoretical framework and
description seem adequate to the problem.
The strengths of the research design include the MRI acquisition methods and the exclusion criteria. The
inclusion of only women of middle aged is a good choice given the limited sample size for the study. Several
problems were noted with the study methods, however:
1). The authors did not explicitly state that the study was performed under IRB approved methods.
2). There is no description of how the subjects were recruited and particularly given the small sample size it
is difficult to extrapolate the findings from this study to the general population of middle aged women. For
example, were the participants recruited from a cohort seeking to improve health?
3). Task performance and brain activity during task performance might be influenced by uncontrolled
variables, such as participant IQ or educational achievement. The authors should report such information if
this available.
5). Over all task accuracy was not reported nor was accuracy reported on a per condition basis. Brain
activation level will change if a subject stops performing the task, even when the subject knew how to
perform the task.
6). It is not clear why "earning points" was actually motivating to some or all of the participants in the
study. Was there any tangible result provided based on points scored? Differences in participant
motivational level could drive the differences in brain activation.
The data analysis methods used in this manuscript are adequate and for the most part adequately
described. Restricting the parts of the brain in which the analysis was performed to specific regions of
hypothesis is a reasonable way to help control for multiple comparisons. Including a figure which shows
these regions, a figure similar to supplement figure 1 from de Wit et al 2009, would help the reader better
visualize which brain regions were under investigation. The exclusion of participants that failed to learn at
least 50% of the correct responses is reasonable, although this should be (and is) noted as a limitation in
the discussion. The authors are justified in excluding the subject with "excessive" motion however the
authors should state what motion threshold was used as the criteria for rejection. Also, because motion
during fMRI can impact measured activation levels in fMRI analysis the authors should consider computing a
motion metric, for example mean RMS motion during task, for each subject. It would be helpful for the
authors to confirm motion RMS does not correlate to BMI, as motion effects are known to lead to artifactual
correlations in fMRI.
Only 2 participants with BMI above 30 were included in the analysis. This limits the interpretation of the
results from this study for seriously overweight women and should be mentioned as a limitation. Of the 30
participants originally enrolled in the study, 11 participants were not included in the analysis for various
reasons. If these 11 participants had higher BMI on average than the 19 included the authors should state
this in the manuscript. Increased exclusion rates for higher BMI participants might bias the same. Also,
future studies may use this finding to recruit higher rates of overweight participants to achieve a more
balanced weight distribution in their final analysis.
The results from the analysis are described adequately. Tables 1 and two are helpful, although they would
be more helpful if the reader knew whether the coordinates were for the centroid of the cluster or were for
the voxel within the cluster with maximum activation. Figures 3 and 4 are helpful in visualizing the brain
locations of the various finds.
Several minor issues with the organization and style of manuscript are noted:
1). The abstract can be improved. The last sentence of the results of the abstract belongs in the discussion
while the discussion part of the abstract describes brain regions associated with emotional processing, et al
without references which regions the authors are referring to.
2). In the fMRI data acquisition section (page 8 line 12-13) the authors report that the data were "?warped
to standard space?" This statement belongs in the data analysis discussion.
3). In the fMRI data acquisition section (page 8 line 17-20) the authors report that the subjects were
"...positioned in Talairach space?" It is unclear what this statement means. Did the authors position the
participants in the head coil such that they had a specific range in the tilt of the AC-PC plane relative to the
scanner coordinates?
4). It would be helpful to the reader if the authors would use both the abbreviations and full names when
describing the regions of correlations in tables 1 and 2, i.e. superior frontal gyrus (dlPFC) or just refer to the
regions as superior frontal gyrus or dlPFC.
5). The first sentence of the discussions section states: "?healthy weight to overweight women with no
routine exercise program." This is helpful information regarding the study population however this
information should be included in the methods section rather than introduced for the first time in the
discussion section.
6). Hare, et al. is referenced in the discussion section only. Literature citations should not be introduced in
the discussions section.
The strengths of this manuscript include the global problem of the study and how it relates to nursing. The
fMRI methods and analysis methods are reasonable and the task has been successfully used in previous
studies. The weakness includes a relatively small sample size with few participants with BMI >30. A second
weakness is that it is unclear how relevant this task is to the global questions of better understanding how
to better design motivational interventions for this population.
ADDITIONAL COMMENTS FROM THE EDITOR:
SAMPLE
In the abstract, include both the number recruited, the number disqualified from further participation, and
number analyzed.
IRB
In the paper, include information about approval of the protocol by the IRB.
COPYRIGHT TRANSFER AGREEMENTS
A completely filled out, signed copyright transfer agreement is needed from Author 2.
---------------------------------------------------------------------CHECKLIST FOR STYLE
TITLE PAGE ---Supply professional working title for each author.
--Supply running head of less than 50 characters (no abbreviations).
--Include a Conflict of Interest statement here.
TEXT ---When your revision has been completed, run a final spell check. Also, proof to be sure that spelling errors
not picked up by the spell check have been corrected.
REFERENCES ---Do not include issue number if the journal is consecutively paginated.
FIGURES ---In Figure 3, please correct the label for Part a to "% Signal Change"