Going Beyond Finding the “Lesion”: A Path for Maturation of Neuroimaging
Publication: American Journal of Psychiatry
To the Editor: In their Review and Overview Article, published in the January 2016 issue of the Journal, Weinberger and Radulescu (1) highlight a number of conceptual and methodological issues that have challenged the field of neuroimaging as a whole, as well as its application to the neurobiology of psychiatric disorders. We generally agree with the authors that “conventional MRI does not allow us to make firm inferences about the primary biology of mental disorders,” but we see the convergence of insights being made through clinical neuroimaging as opportunities despite their limitations. We outline below our view of the critical directions to transform neuroimaging from the gold-rush mentality that has pervaded it to a mature field that provides a diagnostic, prognostic, or treatment-development basis for psychiatry. Critically, we argue for directly addressing methodological limitations, rather than lamenting or ignoring them, in order to overcome them:
1.
Measurements should not be considered in isolation: interpretation of structural imaging changes should be examined side by side with functional imaging, behavioral, treatment, genetic, or other measurements on the same individuals. Interpretation of any one measure is thus strengthened by comparison with other measures.
2.
Surpassing limited sample sizes: the emerging trend toward larger and more broadly representative sample sizes should be fostered and accelerated. This trend will help overcome frequently limited power for observing true effects and will also minimize the effects of spurious findings when assessing hundreds of thousands of voxels. This includes data sharing and pooled analyses, which come with the benefit (not cost) of capturing additional heterogeneity in the represented population (2).
3.
Standards in reporting: despite multiple appeals to the contrary, clinical neuroimaging studies still often fail to fully report their methods, thereby impeding evaluation of potential technical confounders and undermining the increase in methodological rigor necessary for the field. We argue that the influence of technical confounders as raised by Weinberger and Radulescu (independent of issues related to the interpretation of a given measure) can be addressed given sufficient sample size and the use and documentation of well-established methods.
4.
Replication: whether through direct replications, meta-analyses, or other forms of critical integration of previous findings, the literature can be consolidated by revealing the points of convergence (or lack thereof) across studies (3). Given the heterogeneity of psychiatric populations and the flexibility of neuroimaging experiments at the design and analytic levels, establishing robust convergence and identifying discrepancies will be crucial to the advancement of knowledge.
5.
Causation rather than correlation: a central and often unspoken issue in the field is the inability of a correlative measure like neuroimaging to unravel causal mechanisms (2). While this limitation is true for most measures in clinical science (including behavior, genetic associations, blood measurements, etc.), the maturation of neuroimaging as a field arguably depends heavily on the link being made to causation. Thus, neuromodulation and pharmacological interventions coupled with neuroimaging may offer avenues for understanding causation while also serving as potential novel interventions.
Understanding that many of these steps will take time to fully develop, we agree with Weinberger and Radulescu that psychiatric neuroimaging is at a crossroads, but we argue that the maturation of our field has irreversibly started (2).
References
1.
Weinberger DR, Radulescu E: Finding the elusive psychiatric “lesion” with 21st-century neuroanatomy: a note of caution. Am J Psychiatry 2016; 173:27–33
2.
Poldrack RA, Farah MJ: Progress and challenges in probing the human brain. Nature 2015; 526:371–379
3.
Nickl-Jockschat T, Janouschek H, Eickhoff SB, et al: Lack of meta-analytic evidence for an impact of COMT Val158Met genotype on brain activation during working memory tasks. Biol Psychiatry 2015; 78:e43–e46
Information & Authors
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Published In
History
Accepted: December 2015
Published online: 1 March 2016
Published in print: March 01, 2016
Authors
Funding Information
Dr. Etkin has been a consultant for Otsuka and has received grant support from Brain Resource, Inc. Dr. Eickhoff reports no financial relationships with commercial interests.
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