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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Nutr.</journal-id>
<journal-title>Frontiers in Nutrition</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Nutr.</abbrev-journal-title>
<issn pub-type="epub">2296-861X</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fnut.2022.1056692</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Nutrition</subject>
<subj-group>
<subject>Systematic Review</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Neural correlates of food labels on brand, nature, and nutrition: An fMRI meta-analysis</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes">
<name><surname>Yeung</surname> <given-names>Andy Wai Kan</given-names></name>
<xref ref-type="corresp" rid="c001"><sup>&#x002A;</sup></xref>
<uri xlink:href="http://loop.frontiersin.org/people/363181/overview"/>
</contrib>
</contrib-group>
<aff><institution>Oral and Maxillofacial Radiology, Applied Oral Sciences and Community Dental Care, Faculty of Dentistry, The University of Hong Kong</institution>, <addr-line>Hong Kong</addr-line>, <country>Hong Kong SAR, China</country></aff>
<author-notes>
<fn fn-type="edited-by"><p>Edited by: Pengfei Han, Southwest University, China</p></fn>
<fn fn-type="edited-by"><p>Reviewed by: Shao-Wei Xue, The Affiliated Hospital of Hangzhou Normal University, China; Yanming Wang, University of Science and Technology of China, China</p></fn>
<corresp id="c001">&#x002A;Correspondence: Andy Wai Kan Yeung, <email>ndyeung@hku.hk</email></corresp>
<fn fn-type="other" id="fn004"><p>This article was submitted to Nutrition, Psychology and Brain Health, a section of the journal Frontiers in Nutrition</p></fn>
</author-notes>
<pub-date pub-type="epub">
<day>20</day>
<month>12</month>
<year>2022</year>
</pub-date>
<pub-date pub-type="collection">
<year>2022</year>
</pub-date>
<volume>9</volume>
<elocation-id>1056692</elocation-id>
<history>
<date date-type="received">
<day>29</day>
<month>09</month>
<year>2022</year>
</date>
<date date-type="accepted">
<day>29</day>
<month>11</month>
<year>2022</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#x00A9; 2022 Yeung.</copyright-statement>
<copyright-year>2022</copyright-year>
<copyright-holder>Yeung</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/"><p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p></license>
</permissions>
<abstract>
<p>Eating is an essential act of our everyday life, and it involves complicated cognitive appraisal and gustatory evaluation. This study meta-analyzed the functional magnetic resonance imaging (fMRI) studies about food labels on brand, nature and nutrition. Web of Science Core Collection (WoS), Scopus, and PubMed were queried to identify human fMRI studies written in English and published in peer-reviewed journals and used taste or food related labels. Studies were excluded if they reported no results from taste/food related stimuli versus control, no task-based fMRI results, or no results from whole-brain analysis. Nineteen studies entered the analysis. Results for the meta-analysis on food nutrition revealed that the precuneus on the right hemisphere was significantly activated, a brain region related to internal mentation of self-consciousness and nutritional evaluation. Results for the overall analysis on all 19 studies, the analysis on food brand, and the analysis on food nature revealed no significant brain regions. Food nutrition labels were generally processed by brain regions related to internal mentation of self-consciousness and nutritional evaluation. However, the neural correlates of labels of food brand and food nature were inconsistent across studies. More future studies are needed to better understand the cognitive processing of different kinds of food labels in our brain.</p>
</abstract>
<kwd-group>
<kwd>food</kwd>
<kwd>nutrition</kwd>
<kwd>meta-analysis</kwd>
<kwd>gustation</kwd>
<kwd>taste</kwd>
<kwd>CBMA food</kwd>
<kwd>CBMA</kwd>
</kwd-group>
<counts>
<fig-count count="4"/>
<table-count count="4"/>
<equation-count count="0"/>
<ref-count count="60"/>
<page-count count="12"/>
<word-count count="5988"/>
</counts>
</article-meta>
</front>
<body>
<sec id="S1" sec-type="intro">
<title>Introduction</title>
<p>Eating is an essential act of our everyday life, and it involves complicated cognitive appraisal and gustatory evaluation. Multiple meta-analyses have attempted to pool data across studies to identify brain regions responsible for primary tasting (<xref ref-type="bibr" rid="B1">1</xref>&#x2013;<xref ref-type="bibr" rid="B3">3</xref>); for processing visual, taste, and odor food stimuli (<xref ref-type="bibr" rid="B4">4</xref>), food commercials (<xref ref-type="bibr" rid="B5">5</xref>), affect, intensity, and quality of food stimuli (<xref ref-type="bibr" rid="B6">6</xref>), tastants delivered with and without swallowing (<xref ref-type="bibr" rid="B7">7</xref>); for differential processing between hungry and satiated state (<xref ref-type="bibr" rid="B8">8</xref>), male and female (<xref ref-type="bibr" rid="B9">9</xref>), obese and normal weight (<xref ref-type="bibr" rid="B10">10</xref>); and regions targeted by anti-appetite medications (<xref ref-type="bibr" rid="B11">11</xref>). (For a more complete list of meta-analyses on taste and food, please refer to (<xref ref-type="bibr" rid="B12">12</xref>)). Meanwhile, different kinds of food label, such as food brand logo, nutritional label, or label about food nature should modulate the cerebral processing of food information. An obvious analogy is graphic cigarette warning label. Some smokers and potential smokers may refrain from taking the cigarettes upon seeing such warning label printed on a pack of cigarettes. Compared to control warnings, it was reported that such graphic warning labels could significantly improve subjects&#x2019; motivation to quit smoking, and elicited stronger activation in numerous brain regions (<xref ref-type="bibr" rid="B13">13</xref>). The information provided by a nutritional label may similarly influence consumer behavior. For example, consumers were likely to pay 11% more for a box of cookies with a nutritional label compared to its counterpart without a label (<xref ref-type="bibr" rid="B14">14</xref>). There could be more modulating factors such as consumers&#x2019; nutritional knowledge and trust toward the nutrition and health claims (<xref ref-type="bibr" rid="B15">15</xref>, <xref ref-type="bibr" rid="B16">16</xref>). On the other hand, food brand could also affect how much a consumer liked the product and his/her subsequent purchasing behavior (<xref ref-type="bibr" rid="B17">17</xref>). Understanding the neurobiology underlying such food choice and consumption behavior is obviously beneficial for marketing, nutritional advice, and pharmaceuticals. For instance, the cerebral regions highly related to gustatory processing, such as the insula and orbitofrontal cortex, were activated in response to visual cues of shower gel and dish liquid with beverage-imitating packages (<xref ref-type="bibr" rid="B18">18</xref>). This might explain why some people would unintentionally drink shampoo or other poisonous home products. In fact, anti-appetite medications often targeted the gustatory processing at the insula (<xref ref-type="bibr" rid="B11">11</xref>). Besides, it was found that discrete regions of the prefrontal cortex, responsible for decision making and self-control, were activated in response to seeing popular brand logos of foods such as French fries versus corresponding organic brand logos (<xref ref-type="bibr" rid="B19">19</xref>). It is important to know more about the neural correlates of various types of food labels, so that the designs of the food labels can be tested and optimized by neuroimaging evaluations.</p>
<p>Here, three types of food labels were examined: food brand logo, nutritional label, or label about food nature. Food brand logos might trigger a consumer&#x2019;s memory about the past consumption experience and involve social facets such as brand loyalty. In 1985, the Coca Cola company introduced the so-called &#x201C;New Coke&#x201D; into the market, which was rated more superiorly than the original product in blinded taste tests. However, the word &#x201C;new&#x201D; printed on the can was largely rejected by consumers as they preferred the original image of the can and thus the original &#x201C;package&#x201D; of Coca Cola including the drink filled into the can (<xref ref-type="bibr" rid="B20">20</xref>). Similarly, it was found that human brain had differential gustatory processing of Coca Cola relative to Pepsi in multiple regions such as dorsolateral prefrontal cortex and hippocampus, implying differential drink preference (<xref ref-type="bibr" rid="B21">21</xref>). Meanwhile, nutritional label provides nutritional information of the food product that may influence liking, perception of healthiness, and ultimately food choice. There are three main groups of nutritional labels, traffic light, guideline daily amounts (GDA), and health logos/ratings (<xref ref-type="bibr" rid="B22">22</xref>). Consumers were more willing to pay for foods tagged with healthy nutritional labels than foods with unhealthy labels (<xref ref-type="bibr" rid="B23">23</xref>). In particular, seeing foods tagged with red (unhealthy) traffic light nutritional label would activate the inferior frontal gyrus and dorsolateral prefrontal cortex, regions implicated in self-control in food choice (<xref ref-type="bibr" rid="B23">23</xref>). Finally, the remaining type of label is about food nature. Food nature has diverse context. One fundamental aspect is food versus non-food. For instance, isovaleric acid is a chemical with a strong odor. It is present in foods (e.g., cheese and apple juice) and also produced by human body, attributing to sweaty smell and foot odor (<xref ref-type="bibr" rid="B24">24</xref>). The smell of isovaleric acid was rated much more unpleasant when it was labeled as body odor compared to labeled as cheddar cheese, with differential activations at the anterior cingulate, medial orbitofrontal cortex, and the amygdala (<xref ref-type="bibr" rid="B25">25</xref>). Apart from food versus non-food, the social/environment meanings of the food can also be expressed by the labels, such as Halal versus non-Halal for Muslims (<xref ref-type="bibr" rid="B26">26</xref>) was differentiated in the ventromedial prefrontal cortex, organic versus conventional (<xref ref-type="bibr" rid="B27">27</xref>) was differentiated in the ventral striatum, and fair trade versus conventional (<xref ref-type="bibr" rid="B28">28</xref>) was differentiated in the ventral striatum, cingulate cortex, and superior frontal gyrus.</p>
<p>Therefore, this meta-analytic study pooled data across functional magnetic resonance imaging (fMRI) studies. The activation likelihood estimation (ALE) meta-analytic approach was selected, which calculated the consistency of significantly activated brain coordinates reported from published studies by means of probability distribution modeling (<xref ref-type="bibr" rid="B29">29</xref>, <xref ref-type="bibr" rid="B30">30</xref>). Based on the existing literature, it was hypothesized that the neural correlates of food brand logo, nutritional label, and label about food nature would involve the gustatory network, such as the insula and the prefrontal cortex.</p>
</sec>
<sec id="S2" sec-type="materials|methods">
<title>Materials and methods</title>
<sec id="S2.SS1">
<title>Literature search and study selection</title>
<p>In May 2022, three databases, Web of Science Core Collection (WoS), Scopus, and PubMed were queried with the following search string: (taste&#x002A; OR flavo&#x002A; OR food&#x002A;) AND (fMRI OR neuroimaging OR &#x201C;functional MRI&#x201D; OR &#x201C;functional magnetic&#x201D;) AND (brand&#x002A; OR label&#x002A; OR logo&#x002A;). For the former two databases, the title, abstract, and keyword fields were searched. Since PubMed does not index keywords, the title and abstract fields were searched. The search yielded 100 papers from WoS, 149 from Scopus, and 64 from PubMed. After excluding duplicates, 178 papers remained. The titles and abstracts of these 178 papers were reviewed to determine their relevance. Papers were eligible if they were (i) original studies written in English and published in peer-reviewed journals; (ii) human fMRI studies; and (iii) using taste or food related labels. Studies were excluded if they reported (i) no results from taste/food related stimuli versus control; (ii) no task-based fMRI results; or (iii) no results from whole-brain analysis. Finally, 19 studies remained (<xref ref-type="bibr" rid="B19">19</xref>, <xref ref-type="bibr" rid="B21">21</xref>, <xref ref-type="bibr" rid="B23">23</xref>, <xref ref-type="bibr" rid="B25">25</xref>, <xref ref-type="bibr" rid="B27">27</xref>, <xref ref-type="bibr" rid="B28">28</xref>, <xref ref-type="bibr" rid="B31">31</xref>&#x2013;<xref ref-type="bibr" rid="B43">43</xref>) (<xref ref-type="fig" rid="F1">Figure 1</xref> and <xref ref-type="table" rid="T1">Table 1</xref>). This study was not pre-registered in PROSPERO or other databases.</p>
<fig id="F1" position="float">
<label>FIGURE 1</label>
<caption><p>A flow chart that illustrates the literature search.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fnut-09-1056692-g001.tif"/>
</fig>
<table-wrap position="float" id="T1">
<label>TABLE 1</label>
<caption><p>Details of the 19 analyzed studies.</p></caption>
<table cellspacing="5" cellpadding="5" frame="hsides" rules="groups">
<thead>
<tr>
<td valign="top" align="left">References</td>
<td valign="top" align="left">Journal</td>
<td valign="top" align="left">Sample size</td>
<td valign="top" align="center">Handedness</td>
<td valign="top" align="center">Mean age &#x00B1; SD (range)</td>
<td valign="top" align="center">Mean BMI &#x00B1; SD (range)</td>
<td valign="top" align="center">Hours fasted</td>
<td valign="top" align="center">Dimensions investigated</td>
<td valign="top" align="left">Test stimuli</td>
<td valign="top" align="left">Control stimuli</td>
<td valign="top" align="center">Contrast with significant results</td>
<td valign="top" align="center">Foci</td>
<td valign="top" align="center">Data location in the original paper</td>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B21">21</xref>)</td>
<td valign="top" align="left">Neuron</td>
<td valign="top" align="left">16 (?M ?F)</td>
<td valign="top" align="center">?</td>
<td valign="top" align="center">28.0 &#x00B1; 7.6 (19&#x2013;50)</td>
<td valign="top" align="center">?</td>
<td valign="top" align="center">?</td>
<td valign="top" align="left">Food brand</td>
<td valign="top" align="left">Coca Cola image + Coca Cola tasting</td>
<td valign="top" align="left">Colored circle + Coca Cola tasting</td>
<td valign="top" align="center">Test &#x003E; Control</td>
<td valign="top" align="center">7</td>
<td valign="top" align="center">Table 1</td>
</tr>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B25">25</xref>)</td>
<td valign="top" align="left">Neuron</td>
<td valign="top" align="left">12 (12M)</td>
<td valign="top" align="center">R</td>
<td valign="top" align="center">(23&#x2013;35)</td>
<td valign="top" align="center">?</td>
<td valign="top" align="center">?</td>
<td valign="top" align="left">Food nature</td>
<td valign="top" align="left">Words of &#x201C;cheddar cheese&#x201D; + odor (isovaleric acid combined with cheddar cheese flavor)</td>
<td valign="top" align="left">Words of &#x201C;body odor&#x201D; + odor (isovaleric acid combined with cheddar cheese flavor)</td>
<td valign="top" align="center">Test &#x003E; Control</td>
<td valign="top" align="center">3</td>
<td valign="top" align="center">P673</td>
</tr>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B27">27</xref>)</td>
<td valign="top" align="left">NeuroImage</td>
<td valign="top" align="left">30 (15M 15F)</td>
<td valign="top" align="center">R</td>
<td valign="top" align="center">26.0 (23&#x2013;38)</td>
<td valign="top" align="center">?</td>
<td valign="top" align="center">4</td>
<td valign="top" align="left">Food nature</td>
<td valign="top" align="left">Food images with organic food emblem</td>
<td valign="top" align="left">Food images with conventional food emblem</td>
<td valign="top" align="center">Test &#x003E; Control</td>
<td valign="top" align="center">2</td>
<td valign="top" align="center">P217</td>
</tr>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B31">31</xref>)</td>
<td valign="top" align="left">Brain Res</td>
<td valign="top" align="left">12 (7M 5F)</td>
<td valign="top" align="center">R</td>
<td valign="top" align="center">25 (21&#x2013;31)</td>
<td valign="top" align="center">?</td>
<td valign="top" align="center">?</td>
<td valign="top" align="left">Food brand</td>
<td valign="top" align="left">Chocolate images from brands attractive to subjects</td>
<td valign="top" align="left">Chocolate images from non-attractive brands</td>
<td valign="top" align="center">Test &#x003E; Control</td>
<td valign="top" align="center">2</td>
<td valign="top" align="center">P84</td>
</tr>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B32">32</xref>)</td>
<td valign="top" align="left">PLOS One</td>
<td valign="top" align="left">15 (8M 7F)</td>
<td valign="top" align="center">?</td>
<td valign="top" align="center">31.4 (23&#x2013;50)</td>
<td valign="top" align="center">?</td>
<td valign="top" align="center">?</td>
<td valign="top" align="left">Food brand</td>
<td valign="top" align="left">Images + tasting of famous brands Cola</td>
<td valign="top" align="left">Images + tasting of unfamous brands Cola</td>
<td valign="top" align="center">Test &#x003E; Control</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">3rd page</td>
</tr>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B33">33</xref>)</td>
<td valign="top" align="left">Soc Cogn Affect Neurosci</td>
<td valign="top" align="left">17 (10M 7F)</td>
<td valign="top" align="center">?</td>
<td valign="top" align="center">11.8 &#x00B1; 1.4 (10&#x2013;14)</td>
<td valign="top" align="center">?</td>
<td valign="top" align="center">4</td>
<td valign="top" align="left">Food brand/nature</td>
<td valign="top" align="left">Images of food brand logos</td>
<td valign="top" align="left">Images of non-food brand logos</td>
<td valign="top" align="center">Test &#x003E; Control</td>
<td valign="top" align="center">4</td>
<td valign="top" align="center">Table 2</td>
</tr>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B34">34</xref>)</td>
<td valign="top" align="left">Obesity</td>
<td valign="top" align="left">25 (13M 12F)</td>
<td valign="top" align="center">24R 1L</td>
<td valign="top" align="center">15.2 &#x00B1; 0.8</td>
<td valign="top" align="center">22.8 &#x00B1; 4.4</td>
<td valign="top" align="center">4</td>
<td valign="top" align="left">Food brand</td>
<td valign="top" align="left">Images of Coca Cola product and logo</td>
<td valign="top" align="left">Images of non-food images</td>
<td valign="top" align="center">Test &#x003E; Control</td>
<td valign="top" align="center">19</td>
<td valign="top" align="center">Table 4<xref ref-type="table-fn" rid="t1fna"><sup>a</sup></xref></td>
</tr>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B23">23</xref>)</td>
<td valign="top" align="left">Obesity</td>
<td valign="top" align="left">25 (11M 14F)</td>
<td valign="top" align="center">?</td>
<td valign="top" align="center">23.3 &#x00B1; 4.4 (19&#x2013;37)</td>
<td valign="top" align="center">23.1 &#x00B1; 3.4 (17&#x2013;33)</td>
<td valign="top" align="center">Did not fast</td>
<td valign="top" align="left">Food nutrition</td>
<td valign="top" align="left">Food images with healthy nutritional labels</td>
<td valign="top" align="left">Food images with unhealthy nutritional labels</td>
<td valign="top" align="center">Both ways</td>
<td valign="top" align="center">9</td>
<td valign="top" align="center">Supplementary Table 1<xref ref-type="table-fn" rid="t1fnb"><sup>b</sup></xref></td>
</tr>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B28">28</xref>)</td>
<td valign="top" align="left">Front Behav Neurosci</td>
<td valign="top" align="left">33 (?M ?F)</td>
<td valign="top" align="center">Mostly R</td>
<td valign="top" align="center">24.1 &#x00B1; 3.6 (19&#x2013;33)</td>
<td valign="top" align="center">?</td>
<td valign="top" align="center">?</td>
<td valign="top" align="left">Food nature</td>
<td valign="top" align="left">Food images with Fair Trade emblem</td>
<td valign="top" align="left">Food images with no emblem</td>
<td valign="top" align="center">Test &#x003E; Control</td>
<td valign="top" align="center">9</td>
<td valign="top" align="center">Table 1</td>
</tr>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B35">35</xref>)</td>
<td valign="top" align="left">J Culin Sci Technol</td>
<td valign="top" align="left">9 (9M)</td>
<td valign="top" align="center">R</td>
<td valign="top" align="center">26 &#x00B1; 9 (18&#x2013;45)</td>
<td valign="top" align="center">?</td>
<td valign="top" align="center">?</td>
<td valign="top" align="left">Food nature</td>
<td valign="top" align="left">Images of unfamiliar food with name label</td>
<td valign="top" align="left">Images of unfamiliar food with no label</td>
<td valign="top" align="center">Both ways</td>
<td valign="top" align="center">10</td>
<td valign="top" align="center">Table 2<xref ref-type="table-fn" rid="t1fnb"><sup>b</sup></xref></td>
</tr>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B36">36</xref>)</td>
<td valign="top" align="left">Am J Clin Nutr</td>
<td valign="top" align="left">20 (10M 10F)</td>
<td valign="top" align="center">?</td>
<td valign="top" align="center">23.3 &#x00B1; 3.4</td>
<td valign="top" align="center">22.1 &#x00B1; 1.9</td>
<td valign="top" align="center">?</td>
<td valign="top" align="left">Food brand</td>
<td valign="top" align="left">Images of familiarized food brand logo</td>
<td valign="top" align="left">Images of unfamiliar food brand logo</td>
<td valign="top" align="center">Test &#x003E; Control</td>
<td valign="top" align="center">3</td>
<td valign="top" align="center">Table 1</td>
</tr>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B19">19</xref>)</td>
<td valign="top" align="left">Cogent Psychol</td>
<td valign="top" align="left">23 (14M 9F)</td>
<td valign="top" align="center">R</td>
<td valign="top" align="center">37.1 &#x00B1; 7.6 (27&#x2013;47)</td>
<td valign="top" align="center">23.6 &#x00B1; 1.7</td>
<td valign="top" align="center">2</td>
<td valign="top" align="left">Food brand/nature</td>
<td valign="top" align="left">Images of conventional food brand logo</td>
<td valign="top" align="left">Images of organic food brand logo</td>
<td valign="top" align="center">Both ways</td>
<td valign="top" align="center">4</td>
<td valign="top" align="center">Tables 3, 4<xref ref-type="table-fn" rid="t1fnb"><sup>b</sup></xref></td>
</tr>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B37">37</xref>)</td>
<td valign="top" align="left">PLoS One</td>
<td valign="top" align="left">42 (9M 33F)</td>
<td valign="top" align="center">Mostly R</td>
<td valign="top" align="center">19.6 &#x00B1; 1.4 (18&#x2013;22)</td>
<td valign="top" align="center">23.4 &#x00B1; 3.4</td>
<td valign="top" align="center">?</td>
<td valign="top" align="left">Food nutrition</td>
<td valign="top" align="left">Food images with calorie content label</td>
<td valign="top" align="left">Food images with no label</td>
<td valign="top" align="left">Both ways</td>
<td valign="top" align="left">11</td>
<td valign="top" align="left">Table 3<xref ref-type="table-fn" rid="t1fnb"><sup>b</sup></xref></td>
</tr>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B38">38</xref>)</td>
<td valign="top" align="left">Nutr Neurosci</td>
<td valign="top" align="left">50 (23M 27F)</td>
<td valign="top" align="center">48R 2L</td>
<td valign="top" align="center">26.5 &#x00B1; 4.9</td>
<td valign="top" align="center">?</td>
<td valign="top" align="center">?</td>
<td valign="top" align="left">Food nutrition</td>
<td valign="top" align="left">Food images with 5 pieces of nutritional information displayed</td>
<td valign="top" align="left">Food images with 1 piece of nutritional information displayed</td>
<td valign="top" align="center">Test &#x003E; Control</td>
<td valign="top" align="center">12</td>
<td valign="top" align="center">Tables 3, 4<xref ref-type="table-fn" rid="t1fna"><sup>a</sup></xref></td>
</tr>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B39">39</xref>)</td>
<td valign="top" align="left">NeuroImage</td>
<td valign="top" align="left">31 (15M 16F)</td>
<td valign="top" align="center">R</td>
<td valign="top" align="center">24 (20&#x2013;32)</td>
<td valign="top" align="center">23.1 (20.3&#x2013;28.1)</td>
<td valign="top" align="center">6</td>
<td valign="top" align="left">Food nutrition</td>
<td valign="top" align="left">Words of &#x201C;high calorie&#x201D;</td>
<td valign="top" align="left">Words of &#x201C;low calorie&#x201D;</td>
<td valign="top" align="center">Test &#x003E; Control</td>
<td valign="top" align="center">4</td>
<td valign="top" align="center">Table 3<xref ref-type="table-fn" rid="t1fna"><sup>a</sup></xref></td>
</tr>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B40">40</xref>)</td>
<td valign="top" align="left">Neuropsychologia</td>
<td valign="top" align="left">40 (20M 20F)</td>
<td valign="top" align="center">R</td>
<td valign="top" align="center">20.7 &#x00B1; 2.3 (18&#x2013;27)</td>
<td valign="top" align="center">?</td>
<td valign="top" align="center">?</td>
<td valign="top" align="left">Food nature</td>
<td valign="top" align="left">Potato chip packaging image with a wrong match between flavor type and color</td>
<td valign="top" align="left">Potato chip packaging image with a correct match between flavor type and color</td>
<td valign="top" align="center">Test &#x003E; Control</td>
<td valign="top" align="center">3</td>
<td valign="top" align="center">Table 2<xref ref-type="table-fn" rid="t1fna"><sup>a</sup></xref></td>
</tr>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B41">41</xref>)</td>
<td valign="top" align="left">Brain Imaging Behav</td>
<td valign="top" align="left">25 (12M 13F)</td>
<td valign="top" align="center">R</td>
<td valign="top" align="center">8.6 &#x00B1; 1.1 (7&#x2013;10)</td>
<td valign="top" align="center">17.7 &#x00B1; 2.8</td>
<td valign="top" align="center">2</td>
<td valign="top" align="left">Food brand/nature</td>
<td valign="top" align="left">Images of food brand logos</td>
<td valign="top" align="left">Images of non-food brand logos</td>
<td valign="top" align="center">Test &#x003E; Control</td>
<td valign="top" align="center">2</td>
<td valign="top" align="center">Tables 4, 5</td>
</tr>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B42">42</xref>)</td>
<td valign="top" align="left">Nutrients</td>
<td valign="top" align="left">44 (44F)</td>
<td valign="top" align="center">R</td>
<td valign="top" align="center">20.0 &#x00B1; 1.5</td>
<td valign="top" align="center">?</td>
<td valign="top" align="center">?</td>
<td valign="top" align="left">Food nutrition</td>
<td valign="top" align="left">Unhealthy food images with &#x201C;traffic light&#x201D; nutrition label</td>
<td valign="top" align="left">Unhealthy food images with &#x201C;guideline-daily amount&#x201D; nutrition label</td>
<td valign="top" align="center">Test &#x003E; Control</td>
<td valign="top" align="center">6</td>
<td valign="top" align="center">Table 1</td>
</tr>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B43">43</xref>)</td>
<td valign="top" align="left">Cogn Affect Behav Neurosci</td>
<td valign="top" align="left">28 (15M 13F)</td>
<td valign="top" align="center">R</td>
<td valign="top" align="center">21.2 &#x00B1; 2.1</td>
<td valign="top" align="center">21.7 &#x00B1; 3.6</td>
<td valign="top" align="center">1</td>
<td valign="top" align="left">Food nature</td>
<td valign="top" align="left">Unhealthy food images + words of &#x201C;eating together&#x201D;</td>
<td valign="top" align="left">Unhealthy food images + words of &#x201C;eating alone&#x201D;</td>
<td valign="top" align="center">Test &#x003E; Control</td>
<td valign="top" align="center">2</td>
<td valign="top" align="center">7th page</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="t1fna"><p><sup>a</sup>Foci from 2 contrasts merged into 1 for the meta-analysis.</p></fn>
<fn id="t1fnb"><p><sup>b</sup>Two contrasts extracted for the meta-analysis.</p></fn>
</table-wrap-foot>
</table-wrap>
</sec>
<sec id="S2.SS2">
<title>ALE meta-analysis</title>
<p>Brain coordinates of reported activations were collected from the included studies. They were subjected to probability distribution modeling to unveil brain regions consistently activated across studies (<xref ref-type="bibr" rid="B29">29</xref>). Some studies mentioned that their coordinates were reported in Talairach space, while other studies reported their coordinates in Montreal Neurological Institute (MNI) space. For those coordinates reported in Talairach space, the Lancaster transformation (<xref ref-type="bibr" rid="B44">44</xref>) was applied to convert them into MNI space before the analysis. The software GingerALE (version 3.0.2) (<xref ref-type="bibr" rid="B45">45</xref>) was used for such conversion and to conduct the activation likelihood estimation (ALE) meta-analysis. The Turkeltaub non-additive ALE method was selected (<xref ref-type="bibr" rid="B46">46</xref>), and subject-based full-width half-maximum values were applied as default (<xref ref-type="bibr" rid="B29">29</xref>). For statistical threshold, a cluster-level inference was used. In other words, a cluster of voxels was considered significantly activated across the studies if it survived a cluster-level <italic>P</italic> &#x003C; 0.05, familywise error (FWE) rate-corrected for multiple comparisons, with a cluster-defining threshold of uncorrected voxel-level <italic>P</italic> &#x003C; 0.001. This is the standard statistical threshold recommended for ALE meta-analysis (<xref ref-type="bibr" rid="B47">47</xref>). A meta-analysis was performed independently for: (1) all 19 included studies, (2) 8 studies that involved food brand, (3) 9 studies that involved food nature, and (4) 5 studies that involved food nutrition. The thresholded ALE maps were overlaid onto the standard Colin T1 brain template in MNI space (<xref ref-type="bibr" rid="B48">48</xref>) and visualized with Mango 4.0 (<xref ref-type="bibr" rid="B49">49</xref>). The cluster size of brain regions was outputted by GingerALE from the ALE map. <xref ref-type="fig" rid="F2">Figure 2</xref> shows a flow chat that illustrated the process of this ALE meta-analysis.</p>
<fig id="F2" position="float">
<label>FIGURE 2</label>
<caption><p>Flow chart that illustrates the process of activation likelihood estimation (ALE) meta-analysis.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fnut-09-1056692-g002.tif"/>
</fig>
</sec>
<sec id="S2.SS3">
<title>Label-based meta-analysis</title>
<p>In addition, a &#x201C;label-based meta-analysis&#x201D; [method based on (<xref ref-type="bibr" rid="B50">50</xref>)] was performed to tabulate/summarize the activated brain regions commonly reported across the studies. The extracted activation foci were re-surveyed by entering them into Mango 4.0, which provided a label to each focus (coordinate) to the nearest gray matter in a standardized way (<xref ref-type="bibr" rid="B50">50</xref>). This qualitative analysis would provide additional information to the readers in case the quantitative ALE analysis yielded insignificant results.</p>
</sec>
</sec>
<sec id="S3" sec-type="results">
<title>Results</title>
<p>The details of the 19 fMRI studies on food labels are listed in <xref ref-type="table" rid="T1">Table 1</xref>. Each study recruited 9&#x2013;50 subjects, with two studies recruiting men only and one study women only. Regarding subject handedness, 10 studies recruited right-handed subjects only, whereas 4 studies recruited mostly right-handed subjects and 5 studies did not report details. Regarding subject age, most of the studies recruited young and middle-aged adults, whereas 3 studies focused on children and adolescents below the age of 18, and no study involved the elderly above the age of 65. For body mass index (BMI) of the subjects, 8 studies provided the mean data that ranged from 17.7 to 23.6. Meanwhile, 7 studies reported the number of hours the subjects fasted prior to the fMRI scan (1&#x2013;6 h) and 1 study reported that the subjects did not fast. For the dimensions investigated, 5 studies investigated food brand, 6 studies investigated food nature, 5 studies investigated food nutrition, and 3 studies investigated food brand/nature.</p>
<p>For ALE meta-analysis, the overall analysis on all 19 studies, the analysis on food brand, and the analysis on food nature revealed no significant brain regions. Results remained insignificant even when a more liberal threshold of <italic>P</italic> &#x003C; 0.05 (false-discovery rate corrected) with cluster size &#x003E; 200 mm<sup>3</sup> was applied.</p>
<p>The ALE meta-analysis on food nutrition revealed that the precuneus on the right hemisphere was significantly activated (<xref ref-type="fig" rid="F3">Figure 3</xref>). The peak voxel of the activated cluster was at [6, &#x2212;68, 40], with ALE value of 1.75 &#x00D7; 10<sup>&#x2013;2</sup> and cluster size of 520 mm<sup>3</sup>.</p>
<fig id="F3" position="float">
<label>FIGURE 3</label>
<caption><p>The right precuneus was significantly activated across studies that investigated food nutrition labels. The peak voxel of the activated cluster was at [6, &#x2013;68, 40], with ALE value of 1.75 &#x00D7; 10<sup>&#x2013;2</sup> and cluster size of 520 mm<sup>3</sup>.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fnut-09-1056692-g003.tif"/>
</fig>
<p>The additional label-based meta-analysis showed that the activated brain regions for food brand processing seemed to be more diverse/inconsistent compared to food nature and food nutrition (<xref ref-type="table" rid="T2">Tables 2</xref>&#x2013;<xref ref-type="table" rid="T4">4</xref>). <xref ref-type="fig" rid="F4">Figure 4</xref> shows the unthresholded ALE brain map for food brand. It illustrated that multiple brain regions were reported from the included studies, though none of them reached statistical significance.</p>
<table-wrap position="float" id="T2">
<label>TABLE 2</label>
<caption><p>Qualitative label-based meta-analysis of the eight studies concerning food brand.</p></caption>
<table cellspacing="5" cellpadding="5" frame="hsides" rules="groups">
<thead>
<tr>
<td valign="top" align="left"></td>
<td valign="top" align="center">Parahippocampus</td>
<td valign="top" align="center">Substantia nigra</td>
<td valign="top" align="center">Superior frontal G</td>
<td valign="top" align="center">Thalamus</td>
<td valign="top" align="center">Anterior cingulate</td>
<td valign="top" align="center">Posterior cingulate</td>
<td valign="top" align="center">Lentiform nucleus</td>
<td valign="top" align="center">Caudate</td>
<td valign="top" align="center">Middle occipital G</td>
<td valign="top" align="center">Lingual G</td>
<td valign="top" align="center">Paracentral lobule</td>
<td valign="top" align="center">Postcentral G</td>
<td valign="top" align="center">Declive</td>
<td valign="top" align="center">Fusiform G</td>
<td valign="top" align="center">Precuneus</td>
<td valign="top" align="center">Middle temporal G</td>
<td valign="top" align="center">Inferior parietal lobule</td>
<td valign="top" align="center">Claustrum</td>
<td valign="top" align="center">Medial frontal G</td>
<td valign="top" align="center">Inferior frontal G</td>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B21">21</xref>)</td>
<td valign="top" align="center">B</td>
<td valign="top" align="center">L</td>
<td valign="top" align="center">R</td>
<td valign="top" align="center">R</td>
<td valign="top" align="center"/><td valign="top" align="center">L</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/></tr>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B31">31</xref>)</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center">R</td>
<td valign="top" align="center"/><td valign="top" align="center">R</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/></tr>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B32">32</xref>)</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center">L</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/></tr>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B33">33</xref>)</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center">R</td>
<td valign="top" align="center">L</td>
<td valign="top" align="center">R</td>
<td valign="top" align="center">L</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/></tr>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B34">34</xref>)</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center">L</td>
<td valign="top" align="center"/><td valign="top" align="center">L</td>
<td valign="top" align="center">L</td>
<td valign="top" align="center"/><td valign="top" align="center">R</td>
<td valign="top" align="center">B</td>
<td valign="top" align="center">B</td>
<td valign="top" align="center">R</td>
<td valign="top" align="center">R</td>
<td valign="top" align="center">B</td>
<td valign="top" align="center">L</td>
<td valign="top" align="center"/><td valign="top" align="center"/></tr>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B36">36</xref>)</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center">L</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center">R</td>
<td valign="top" align="center"/></tr>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B19">19</xref>)</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center">R</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center">L</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center">B</td>
</tr>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B41">41</xref>)</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center">R</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center">R</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn><p>G, gyrus; B, both sides; R, right side; L, left side.</p></fn>
</table-wrap-foot>
</table-wrap>
<table-wrap position="float" id="T3">
<label>TABLE 3</label>
<caption><p>Qualitative label-based meta-analysis of the nine studies concerning food nature.</p></caption>
<table cellspacing="5" cellpadding="5" frame="hsides" rules="groups">
<thead>
<tr>
<td valign="top" align="left"></td>
<td valign="top" align="center">Middle occipital G</td>
<td valign="top" align="center">Inferior occipital G</td>
<td valign="top" align="center">Lingual G</td>
<td valign="top" align="center">Fusiform G</td>
<td valign="top" align="center">Paracentral lobule</td>
<td valign="top" align="center">Postcentral G</td>
<td valign="top" align="center">Precentral G</td>
<td valign="top" align="center">Lentiform nucleus</td>
<td valign="top" align="center">Middle frontal G</td>
<td valign="top" align="center">Medial frontal G</td>
<td valign="top" align="center">Inferior frontal G</td>
<td valign="top" align="center">Anterior cingulate</td>
<td valign="top" align="center">Cuneus</td>
<td valign="top" align="center">Culmen</td>
<td valign="top" align="center">Insula</td>
<td valign="top" align="center">Caudate</td>
<td valign="top" align="center">Claustrum</td>
<td valign="top" align="center">Transverse temporal G</td>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B25">25</xref>)</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center">R</td>
<td valign="top" align="center">R</td>
<td valign="top" align="center">L</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/></tr>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B27">27</xref>)</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center">L</td>
<td valign="top" align="center">R</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/></tr>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B33">33</xref>)</td>
<td valign="top" align="center">R</td>
<td valign="top" align="center"/><td valign="top" align="center">L</td>
<td valign="top" align="center"/><td valign="top" align="center">R</td>
<td valign="top" align="center">L</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/></tr>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B28">28</xref>)</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center">B</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center">L</td>
<td valign="top" align="center"/><td valign="top" align="center">L</td>
<td valign="top" align="center">R</td>
<td valign="top" align="center">R</td>
<td valign="top" align="center"/><td valign="top" align="center">L</td>
<td valign="top" align="center">L</td>
<td valign="top" align="center"/><td valign="top" align="center"/></tr>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B35">35</xref>)</td>
<td valign="top" align="center"/><td valign="top" align="center">R</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center">L</td>
<td valign="top" align="center"/><td valign="top" align="center">B</td>
<td valign="top" align="center">R</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center">L</td>
<td valign="top" align="center">L</td>
<td valign="top" align="center">R</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/></tr>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B19">19</xref>)</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center">L</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center">B</td>
<td valign="top" align="center">R</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/></tr>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B40">40</xref>)</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center">L</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center">R</td>
<td valign="top" align="center">R</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/></tr>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B41">41</xref>)</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center">R</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center">R</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/></tr>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B43">43</xref>)</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center">L</td>
<td valign="top" align="center">R</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn><p>G, gyrus; B, both sides; R, right side; L, left side.</p></fn>
</table-wrap-foot>
</table-wrap>
<table-wrap position="float" id="T4">
<label>TABLE 4</label>
<caption><p>Qualitative label-based meta-analysis of the five studies concerning food nutrition.</p></caption>
<table cellspacing="5" cellpadding="5" frame="hsides" rules="groups">
<thead>
<tr>
<td valign="top" align="left"></td>
<td valign="top" align="center">Middle occipital G</td>
<td valign="top" align="center">Inferior occipital G</td>
<td valign="top" align="center">Lingual G</td>
<td valign="top" align="center">Fusiform G</td>
<td valign="top" align="center">Superior parietal lobule</td>
<td valign="top" align="center">Inferior parietal lobule</td>
<td valign="top" align="center">Postcentral G</td>
<td valign="top" align="center">Precentral G</td>
<td valign="top" align="center">Lentiform nucleus</td>
<td valign="top" align="center">Superior frontal G</td>
<td valign="top" align="center">Middle frontal G</td>
<td valign="top" align="center">Medial frontal G</td>
<td valign="top" align="center">Inferior frontal G</td>
<td valign="top" align="center">Anterior cingulate</td>
<td valign="top" align="center">Precuneus</td>
<td valign="top" align="center">Cuneus</td>
<td valign="top" align="center">Fusiform gyrus</td>
<td valign="top" align="center">Culmen</td>
<td valign="top" align="center">Insula</td>
<td valign="top" align="center">Declive</td>
<td valign="top" align="center">Middle temporal G</td>
<td valign="top" align="center">Superior temporal G</td>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B23">23</xref>)</td>
<td valign="top" align="center"/><td valign="top" align="center">L</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center">R</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center">R</td>
<td valign="top" align="center">L</td>
<td valign="top" align="center"/><td valign="top" align="center">R</td>
<td valign="top" align="center">L</td>
<td valign="top" align="center">R</td>
<td valign="top" align="center">R</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/></tr>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B37">37</xref>)</td>
<td valign="top" align="center">L</td>
<td valign="top" align="center"/><td valign="top" align="center">L</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center">B</td>
<td valign="top" align="center">R</td>
<td valign="top" align="center">R</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center">R</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center">R</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center">R</td>
<td valign="top" align="center"/><td valign="top" align="center">R</td>
<td valign="top" align="center"/></tr>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B38">38</xref>)</td>
<td valign="top" align="center">R</td>
<td valign="top" align="center">L</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center">R</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center">R</td>
<td valign="top" align="center">R</td>
<td valign="top" align="center"/><td valign="top" align="center">R</td>
<td valign="top" align="center"/><td valign="top" align="center">L</td>
<td valign="top" align="center"/><td valign="top" align="center">R</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center">L</td>
<td valign="top" align="center"/><td valign="top" align="center"/></tr>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B39">39</xref>)</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center">R</td>
<td valign="top" align="center">B</td>
</tr>
<tr>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B42">42</xref>)</td>
<td valign="top" align="center">R</td>
<td valign="top" align="center"/><td valign="top" align="center">R</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center">R</td>
<td valign="top" align="center"/><td valign="top" align="center">L</td>
<td valign="top" align="center"/><td valign="top" align="center">L</td>
<td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center"/><td valign="top" align="center">R</td>
<td valign="top" align="center"/><td valign="top" align="center"/></tr>
</tbody>
</table>
<table-wrap-foot>
<fn><p>G, gyrus; B, both sides; R, right side; L, left side.</p></fn>
</table-wrap-foot>
</table-wrap>
<fig id="F4" position="float">
<label>FIGURE 4</label>
<caption><p>Unthresholded ALE brain map resulted from food brand studies showing the diverse brain regions involved. It is overlaid on a glass brain for visualization. None of the clusters reached statistical significance.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fnut-09-1056692-g004.tif"/>
</fig>
</sec>
<sec id="S4" sec-type="discussion">
<title>Discussion</title>
<p>This is the first meta-analysis on fMRI studies regarding brain responses to food labels. Surprisingly, results did not yield significant activations in the hypothesized brain regions of the insula and the prefrontal cortex. Results have shown that the cerebral processing of food labels on nutrition significantly activated the right precuneus. The processing of food labels on food brand and food nature did not yield significant results.</p>
<p>The insula is known to be the primary taste cortex that processes neural signals relayed from taste receptors in the oral cavity (<xref ref-type="bibr" rid="B51">51</xref>). The meta-analytic results here did not find significant activation of it, which might be partly explained by the fact that the analyzed studies did not involve actual tasting or stimulation of the taste receptors. Instead, the stimuli involved visual and cognitive aspects of food processing. Meanwhile, the prefrontal cortex is responsible for top-down affective modulation (<xref ref-type="bibr" rid="B51">51</xref>) and should be activated. The insignificant results might be attributed to heterogeneous designs of the studies.</p>
<p>The precuneus was reported to consume much more glucose than other parts of the cerebral cortex and thus sensitive to and easily affected by malnutrition (<xref ref-type="bibr" rid="B52">52</xref>). Among healthy subjects, precuneus was found to activate more in response to personalized nutritional messages compared to untailored nutritional messages (<xref ref-type="bibr" rid="B53">53</xref>). Meanwhile, its cortical thickness correlated with nutritional state and cognitive functions in patients with anorexia nervosa (<xref ref-type="bibr" rid="B54">54</xref>). Hence, the results of current meta-analysis on food nutrition labels were consistent to the existing literature that the precuneus seems to play an important role in nutritional evaluation.</p>
<p>At first glance, the insignificant result from food brand was unexpected. However, a prior fMRI study that presented visual cues of car brands showed that the cerebral processing of brands indeed involved diverse brain regions, e.g., familiar brands preferentially activated superior frontal gyrus, hippocampus and posterior cingulate; sports and luxury brands activated medial prefrontal cortex and precuneus; whereas brands deemed value products activated superior frontal gyrus and anterior cingulate (<xref ref-type="bibr" rid="B55">55</xref>). Therefore, the heterogeneity of subject background and the exact instructions given to them during fMRI scan might have attributed to the inconsistency across the analyzed studies. As a matter of fact, one of the analyzed studies on food brand did investigated Coca Cola and Pepsi separately, and compared brand-cued drink delivery to light-cued (colored circle) delivery (<xref ref-type="bibr" rid="B21">21</xref>). Significant results were only found for Coca Cola but not Pepsi. Another study similarly found that Coca Cola elicited greater activation than Pepsi in the right amygdala, whereas the opposite comparison resulted in no significant activation (<xref ref-type="bibr" rid="B32">32</xref>). This illustrated that the cerebral processing of food brand(s) could be complicated and not easily elicited in a consistent manner.</p>
<p>The heterogeneous situation was more obvious for food nature studies. Three studies investigated food versus non-food labels, followed by two investigated organic versus conventional food. Other comparisons were each investigated in one study, such as fair-trade label versus no label, food name label versus no label, eating alone label versus eating together label, and a correct match between flavor name and color on potato chip packaging versus a wrong match. It could be reasonably argued that different brain regions could be utilized for the cognitive processing of such distinct group of labels about food nature, rendering the results insignificant. There were even other labels on food nature being investigated. For instance, it was reported that there was a significant difference in the ventromedial prefrontal cortex activity level between viewing meat images labeled with Halal logo and those labeled with non-Halal logo, though this study was not included in the present analysis due to its lack of description on whether whole-brain analysis was performed (and also no brain coordinates provided) (<xref ref-type="bibr" rid="B26">26</xref>).</p>
<p>This meta-analysis has several limitations. First, the participants involved in the analyzed studies were mainly young and middle-aged adults with some children and adolescents. The results therefore might not be well applied to the elderly population, especially that aging was shown to associate with decreasing activation in the precuneus in response to food stimuli in a previous study (<xref ref-type="bibr" rid="B56">56</xref>). In addition, the analyses on the food brand and food nature subsets did not reveal significant results, so that potential follow-up analyses to compare between food brand, food nature, and food nutrition could not be conducted. Moreover, the majority of the analyzed studies exclusively recruited right-handed subjects or did not report subject handedness, similar to the scenario revealed by a prior survey on nutritional neuroscience literature (<xref ref-type="bibr" rid="B57">57</xref>). It was established that handedness would affect the lateralization of cerebral processing of tasting (<xref ref-type="bibr" rid="B58">58</xref>, <xref ref-type="bibr" rid="B59">59</xref>). However, the methodology to gauge and determine subject handedness lacked a consensus and remained disputable (<xref ref-type="bibr" rid="B60">60</xref>). Regardless, due to the lack of results from exclusively left-handed subjects, it was not possible to test and determine if handedness would affect cerebral processing of food labels. Readers should be aware of these limitations during results interpretation. Finally, ALE meta-analysis can only compute the consistency of brain coordinates activated across studies but it cannot compute the effect size (<xref ref-type="bibr" rid="B30">30</xref>). Subsequently, future studies should include left-handed subjects in their sample. Moreover, the elderly people should be recruited so that the results could be more representative of the whole population. Researchers should share the statistical brain maps resulted from future original studies or report their effect size, so that the effect size could also be meta-analyzed.</p>
<p>In conclusion, the cerebral processing of food labels on nutrition significantly activated the right precuneus, a brain region related to nutritional evaluation. The peak voxel of the activated cluster was at [6, &#x2212;68, 40], with ALE value of 1.75 &#x00D7; 10<sup>&#x2013;2</sup> and cluster size of 520mm<sup>3</sup>. The processing of food labels on food brand and food nature did not yield significant results. More future studies are needed to better understand the cognitive processing of different kinds of food labels in our brain. They should include left-handed subjects as well as the elderly people, so that results could be more generalizable.</p>
</sec>
<sec id="S5" sec-type="data-availability">
<title>Data availability statement</title>
<p>The original contributions presented in this study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.</p>
</sec>
<sec id="S6" sec-type="author-contributions">
<title>Author contributions</title>
<p>The author confirms being the sole contributor of this work and has approved it for publication.</p>
</sec>
</body>
<back>
<sec id="S7" sec-type="funding-information">
<title>Funding</title>
<p>This work was supported by the departmental funds only.</p>
</sec>
<sec id="S8" sec-type="COI-statement">
<title>Conflict of interest</title>
<p>The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec id="S9" sec-type="disclaimer">
<title>Publisher&#x2019;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
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