Neural correlates of evaluative compared with passive tasting

We used functional magnetic resonance imaging to test the hypothesis that the nature of the neural response to taste varies as a function of the task the subject is asked to perform. Subjects received sweet, sour, salty and tasteless solutions passively and while evaluating stimulus presence, pleasantness and identity. Within the insula and overlying operculum the location of maximal response to taste vs. tasteless varied as a function of task; however, the primary taste cortex (anterior dorsal insula/frontal operculum – AIFO), as well as a more ventral region of anterior insula, responded to taste vs. tasteless irrespective of task. Although the response here did not depend upon task, preferential connectivity between AIFO and the amygdala (bilaterally) was observed when subjects tasted passively compared with when they performed a task. This suggests that information transfer between AIFO and the amygdala is maximal during implicit processing of taste. In contrast, a region of the left lateral orbitofrontal cortex (OFC) responded preferentially to taste and to tasteless when subjects evaluated pleasantness, and was preferentially connected to earlier gustatory relays (caudomedial OFC and AIFO) when a taste was present. This suggests that processing in the lateral OFC organizes the retrieval of gustatory information from earlier relays in the service of computing perceived pleasantness. These findings show that neural encoding of taste varies as a function of task beyond that of the initial cortical representation.     

Intensity‐related distribution of sweet and bitter taste fMRI responses in the insular cortex

The human gustatory cortex analyzes the chemosensory properties of tastants, particularly the quality, intensity, and affective valence, to determine whether a perceived substance should be ingested or rejected. Among previous studies, the spatial distribution of taste intensity‐related activations within the human insula has been scarcely addressed. To spatially characterize a specialized or distributed nature of the cortical responses to taste intensities, a functional magnetic resonance imaging study was performed at 3 T in 44 healthy subjects where sweet and bitter tastants were administered at five increasing concentrations and cortex‐based factorial and parametric analyses were performed. Two clusters in the right middle‐posterior and left middle insula were found specialized for taste intensity processing, exhibiting a highly nonlinear profile across concentrations. Multiple clusters were found activated by sweet and bitter taste stimuli at most concentrations, in the anterior, middle‐posterior, and inferior portion of the bilateral insula. Across these clusters, respectively, for the right and left insula, a superior‐to‐inferior and an anterior‐to‐posterior spatial gradient for high‐to‐low concentrations were observed for the most responsive intensity of both tastes. These findings may gather new insights regarding how the gustatory cortex is spatially organized during the perceptual processing of taste intensity for two basic tastants.     

An fMRI Study of the Interactions Between the Attention and the Gustatory Networks

In a prior study, we showed that trying to detect a taste in a tasteless solution results in enhanced activity in the gustatory and attention networks. The aim of the current study was to use connectivity analyses to test if and how these networks interact during directed attention to taste. We predicted that the attention network modulates taste cortex, reflecting top-down enhancement of incoming sensory signals that are relevant to goal-directed behavior. fMRI was used to measure brain responses in 14 subjects as they performed two different tasks: (1) trying to detect a taste in a solution or (2) passively perceiving the same solution. We used psychophysiological interaction analysis to identify regions demonstrating increased connectivity during a taste attention task compared to passive tasting. We observed greater connectivity between the anterior cingulate cortex and the frontal eye fields, posterior parietal cortex, and parietal operculum and between the anterior cingulate cortex and the right anterior insula and frontal operculum. These results suggested that selective attention to taste is mediated by a hierarchical circuit in which signals are first sent from the frontal eye fields, posterior parietal cortex, and parietal operculum to the anterior cingulate cortex, which in turn modulates responses in the anterior insula and frontal operculum. We then tested this prediction using dynamic causal modeling. This analysis confirmed a model of indirect modulation of the gustatory cortex, with the strongest influence coming from the frontal eye fields via the anterior cingulate cortex. In summary, the results indicate that the attention network modulates the gustatory cortex during attention to taste and that the anterior cingulate cortex acts as an intermediary processing hub between the attention network and the gustatory cortex.     

Anorexia nervosa and obesity are associated with opposite brain reward response

Anorexia nervosa (AN) is a severe psychiatric disorder associated with food avoidance and malnutrition. In this study, we wanted to test whether we would find brain reward alterations in AN, compared with individuals with normal or increased body weight. We studied 21 underweight, restricting-type AN (age M 22.5, SD 5.8 years), 19 obese (age M 27.1, SD 6.7 years), and 23 healthy control women (age M 24.8, SD 5.6 years), using blood oxygen level-dependent functional magnetic resonance brain imaging together with a reward-conditioning task. This paradigm involves learning the association between conditioned visual stimuli and unconditioned taste stimuli, as well as the unexpected violation of those learned associations. The task has been associated with activation of brain dopamine reward circuits, and it allows the comparison of actual brain response with expected brain activation based on established neuronal models. A group-by-task condition analysis (family-wise-error-corrected P<0.05) indicated that the orbitofrontal cortex differentiated all three groups. The dopamine model reward-learning signal distinguished groups in the anteroventral striatum, insula, and prefrontal cortex (P<0.001, 25 voxel cluster threshold), with brain responses that were greater in the AN group, but lesser in the obese group, compared with controls. These results suggest that brain reward circuits are more responsive to food stimuli in AN, but less responsive in obese women. The mechanism for this association is uncertain, but these brain reward response patterns could be biomarkers for the respective weight state.     

Prediction error and somatosensory insula activation in women recovered from anorexia nervosa

BackgroundPrevious research in patients with anorexia nervosa showed heightened brain response during a taste reward conditioning task and heightened sensitivity to rewarding and punishing stimuli. Here we tested the hypothesis that individuals recovered from anorexia nervosa would also experience greater brain activation during this task as well as higher sensitivity to salient stimuli than controls.MethodsWomen recovered from restricting-type anorexia nervosa and healthy control women underwent fMRI during application of a prediction error taste reward learning paradigm.ResultsTwenty-four women recovered from anorexia nervosa (mean age 30.3 ± 8.1 yr) and 24 control women (mean age 27.4 ± 6.3 yr) took part in this study. The recovered anorexia nervosa group showed greater left posterior insula activation for the prediction error model analysis than the control group (family-wise error– and small volume–corrected p < 0.05). A group × condition analysis found greater posterior insula response in women recovered from anorexia nervosa than controls for unexpected stimulus omission, but not for unexpected receipt. Sensitivity to punishment was elevated in women recovered from anorexia nervosa.LimitationsThis was a cross-sectional study, and the sample size was modest.ConclusionAnorexia nervosa after recovery is associated with heightened prediction error–related brain response in the posterior insula as well as greater response to unexpected reward stimulus omission. This finding, together with behaviourally increased sensitivity to punishment, could indicate that individuals recovered from anorexia nervosa are particularly responsive to punishment. The posterior insula processes somatosensory stimuli, including unexpected bodily states, and greater response could indicate altered perception or integration of unexpected or maybe unwanted bodily feelings. Whether those findings develop during the ill state or whether they are biological traits requires further study.     

Altered processing of rewarding and aversive basic taste stimuli in symptomatic women with anorexia nervosa and bulimia nervosa: An fMRI study

Functional magnetic resonance imaging (fMRI) studies have displayed a dysregulation in the way in which the brain processes pleasant taste stimuli in patients with anorexia nervosa (AN) and bulimia nervosa (BN). However, exactly how the brain processes disgusting basic taste stimuli has never been investigated, even though disgust plays a role in food intake modulation and AN and BN patients exhibit high disgust sensitivity. Therefore, we investigated the activation of brain areas following the administration of pleasant and aversive basic taste stimuli in symptomatic AN and BN patients compared to healthy subjects. Twenty underweight AN women, 20 symptomatic BN women and 20 healthy women underwent fMRI while tasting 0.292 M sucrose solution (sweet taste), 0.5 mM quinine hydrochloride solution (bitter taste) and water as a reference taste. In symptomatic AN and BN patients the pleasant sweet stimulus induced a higher activation in several brain areas than that induced by the aversive bitter taste. The opposite occurred in healthy controls. Moreover, compared to healthy controls, AN patients showed a decreased response to the bitter stimulus in the right amygdala and left anterior cingulate cortex, while BN patients showed a decreased response to the bitter stimulus in the right amygdala and left insula. These results show an altered processing of rewarding and aversive taste stimuli in ED patients, which may be relevant for understanding the pathophysiology of AN and BN.     

Taste-olfactory convergence, and the representation of the pleasantness of flavour, in the human brain

The functional architecture of the central taste and olfactory systems in primates provides evidence that the convergence of taste and smell information onto single neurons is realized in the caudal orbitofrontal cortex (and immediately adjacent agranular insula). These higher-order association cortical areas thus support flavour processing. Much less is known, however, about homologous regions in the human cortex, or how taste-odour interactions, and thus flavour perception, are implemented in the human brain. We performed an event-related fMRI study to investigate where in the human brain these interactions between taste and odour stimuli (administered retronasally) may be realized. The brain regions that were activated by both taste and smell included parts of the caudal orbitofrontal cortex, amygdala, insular cortex and adjoining areas, and anterior cingulate cortex. It was shown that a small part of the anterior (putatively agranular) insula responds to unimodal taste and to unimodal olfactory stimuli, and that a part of the anterior frontal operculum is a unimodal taste area (putatively primary taste cortex) not activated by olfactory stimuli. Activations to combined olfactory and taste stimuli where there was little or no activation to either alone (providing positive evidence for interactions between the olfactory and taste inputs) were found in a lateral anterior part of the orbitofrontal cortex. Correlations with consonance ratings for the smell and taste combinations, and for their pleasantness, were found in a medial anterior part of the orbitofrontal cortex. These results provide evidence on the neural substrate for the convergence of taste and olfactory stimuli to produce flavour in humans, and where the pleasantness of flavour is represented in the human brain.     

Ventral striatum/nucleus accumbens activation to smoking-related pictorial cues in smokers and nonsmokers: a functional magnetic resonance imaging study.

BACKGROUND: Converging evidence from several theories of the development of incentive-sensitization to smoking-related environmental stimuli suggests that the ventral striatum plays an important role in the processing of smoking-related cue reactivity. METHODS: Twenty-six healthy right-handed volunteers (14 smokers and 12 nonsmoking controls) underwent functional magnetic resonance imaging (fMRI) during which neutral and smoking-related images were presented. Region of interest analyses were performed within the ventral striatum/nucleus accumbens (VS/NAc) for the contrast between smoking-related (SR) and nonsmoking related neutral (N) cues. RESULTS: Group activation for SR versus N cues was observed in smokers but not in nonsmokers in medial orbitofrontal cortex, superior frontal gyrus, anterior cingulate cortex, and posterior fusiform gyrus using whole-brain corrected Z thresholds and in the ventral VS/NAc using uncorrected Z-statistics (smokers Z = 3.2). Region of interest analysis of signal change within ventral VS/NAc demonstrated significantly greater activation to SR versus N cues in smokers than controls. CONCLUSIONS: This is the first demonstration of greater VS/NAc activation in addicted smokers than nonsmokers presented with smoking-related cues using fMRI. Smokers, but not controls, demonstrated activation to SR versus N cues in a distributed reward signaling network consistent with cue reactivity studies of other drugs of abuse.     

It’s in the eye of the beholder: selective attention to drink properties during tasting influences brain activation in gustatory and reward regions

Statements regarding pleasantness, taste intensity or caloric content on a food label may influence the attention consumers pay to such characteristics during consumption. There is little research on the effects of selective attention on taste perception and associated brain activation in regular drinks. The aim of this study was to investigate the effect of selective attention on hedonics, intensity and caloric content on brain responses during tasting drinks. Using functional MRI brain responses of 27 women were measured while they paid attention to the intensity, pleasantness or caloric content of fruit juice, tomato juice and water. Brain activation during tasting largely overlapped between the three selective attention conditions and was found in the rolandic operculum, insula and overlying frontal operculum, striatum, amygdala, thalamus, anterior cingulate cortex and middle orbitofrontal cortex (OFC). Brain activation was higher during selective attention to taste intensity compared to calories in the right middle OFC and during selective attention to pleasantness compared to intensity in the right putamen, right ACC and bilateral middle insula. Intensity ratings correlated with brain activation during selective attention to taste intensity in the anterior insula and lateral OFC. Our data suggest that not only the anterior insula but also the middle and lateral OFC are involved in evaluating taste intensity. Furthermore, selective attention to pleasantness engaged regions associated with food reward. Overall, our results indicate that selective attention to food properties can alter the activation of gustatory and reward regions. This may underlie effects of food labels on the consumption experience of consumers.     

Expecting unpleasant stimuli – An fMRI study

Expecting forthcoming events and preparing adequate responses are important cognitive functions that help the individual to deal with the environment. The emotional valence of an event is decisive for the resulting action. Revealing the underlying mechanisms may help to understand the dysfunctional information processing in depression and anxiety that are associated with negative expectation of the future. We were interested in selective brain activity during the expectation of unpleasant visual stimuli. Twelve healthy female subjects were biased to expect and then perceive emotionally unpleasant, pleasant or neutral stimuli during functional magnetic resonance imaging. Expecting unpleasant stimuli relative to expecting pleasant and neutral stimuli resulted in activation of mainly cingulate cortex, insula, prefrontal areas, thalamus, hypothalamus and striatum. While certain areas were also active during subsequent presentation of the emotional stimuli, distinct regions of the anterior cingulate gyrus and the thalamus were solely active during expectation of the unpleasant stimuli. The identified areas may reflect a network for internal adaptation and preparation processes in order to react adequately to expected unpleasant events. They are known as well to be altered in depression. Disorders of this network may be relevant for psychiatric disorders such as depression.     

The neural coding of expected and unexpected monetary performance outcomes: dissociations between active and observational learning

Successful adaptation to the environment requires the learning of stimulus-response-outcome associations. Such associations can be learned actively by trial and error or by observing the behaviour and accompanying outcomes in other persons. The present study investigated similarities and differences in the neural mechanisms of active and observational learning from monetary feedback using functional magnetic resonance imaging. Two groups of 15 subjects each - active and observational learners - participated in the experiment. On every trial, active learners chose between two stimuli and received monetary feedback. Each observational learner observed the choices and outcomes of one active learner. Learning performance as assessed via active test trials without feedback was comparable between groups. Different activation patterns were observed for the processing of unexpected vs. expected monetary feedback in active and observational learners, particularly for positive outcomes. Activity for unexpected vs. expected reward was stronger in the right striatum in active learning, while activity in the hippocampus was bilaterally enhanced in observational and reduced in active learning. Modulation of activity by prediction error (PE) magnitude was observed in the right putamen in both types of learning, whereas PE related activations in the right anterior caudate nucleus and in the medial orbitofrontal cortex were stronger for active learning. The striatum and orbitofrontal cortex thus appear to link reward stimuli to own behavioural reactions and are less strongly involved when the behavioural outcome refers to another person's action. Alternative explanations such as differences in reward value between active and observational learning are also discussed.     

Expecting unpleasant stimuli--an fMRI study

Expecting forthcoming events and preparing adequate responses are important cognitive functions that help the individual to deal with the environment. The emotional valence of an event is decisive for the resulting action. Revealing the underlying mechanisms may help to understand the dysfunctional information processing in depression and anxiety that are associated with negative expectation of the future. We were interested in selective brain activity during the expectation of unpleasant visual stimuli. Twelve healthy female subjects were biased to expect and then perceive emotionally unpleasant, pleasant or neutral stimuli during functional magnetic resonance imaging. Expecting unpleasant stimuli relative to expecting pleasant and neutral stimuli resulted in activation of mainly cingulate cortex, insula, prefrontal areas, thalamus, hypothalamus and striatum. While certain areas were also active during subsequent presentation of the emotional stimuli, distinct regions of the anterior cingulate gyrus and the thalamus were solely active during expectation of the unpleasant stimuli. The identified areas may reflect a network for internal adaptation and preparation processes in order to react adequately to expected unpleasant events. They are known as well to be altered in depression. Disorders of this network may be relevant for psychiatric disorders such as depression.     

Identification of human gustatory cortex by activation likelihood estimation

Over the last two decades, neuroimaging methods have identified a variety of taste-responsive brain regions. Their precise location, however, remains in dispute. For example, taste stimulation activates areas throughout the insula and overlying operculum, but identification of subregions has been inconsistent. Furthermore, literature reviews and summaries of gustatory brain activations tend to reiterate rather than resolve this ambiguity. Here, we used a new meta-analytic method [activation likelihood estimation (ALE)] to obtain a probability map of the location of gustatory brain activation across 15 studies. The map of activation likelihood values can also serve as a source of independent coordinates for future region-of-interest analyses. We observed significant cortical activation probabilities in: bilateral anterior insula and overlying frontal operculum, bilateral mid dorsal insula and overlying Rolandic operculum, and bilateral posterior insula/parietal operculum/postcentral gyrus, left lateral orbitofrontal cortex (OFC), right medial OFC, pregenual anterior cingulate cortex (prACC) and right mediodorsal thalamus. This analysis confirms the involvement of multiple cortical areas within insula and overlying operculum in gustatory processing and provides a functional "taste map" which can be used as an inclusive mask in the data analyses of future studies. In light of this new analysis, we discuss human central processing of gustatory stimuli and identify topics where increased research effort is warranted.     

Neural patterns underlying social comparisons of personal performance

Humans often evaluate their abilities by comparing their personal performance with that of others. For this process, it is critical whether the comparison turns out in one’s favor or against it. Here, we investigate how social comparisons of performance are encoded and integrated on the neural level. We collected functional magnetic resonance images while subjects answered questions in a knowledge quiz that was related to their profession. After each question, subjects received a feedback about their personal performance, followed by a feedback about the performance of a reference group who had been quizzed beforehand. Based on the subjects’ personal performance, we divided trials in downward and upward comparisons. We found that upward comparisons correlated with activity in the dorsolateral prefrontal cortex and the anterior insula. Downward comparisons were associated with increased activation in the ventral striatum (VS), the medial orbitofrontal cortex and the ventral anterior cingulate cortex (ACC). The extent to which subjects outperformed the reference group modulated the activity in the VS and in the dorsal ACC. We suggest that the co-activation of the VS and the dorsal ACC contributes to the integration of downward comparisons into the evaluation of personal performance.     

Expected taste intensity affects response to sweet drinks in primary taste cortex

Expectations about a food can impact on its taste, but this may represent a perceptual change or a bias in response at the decision-making stage. We hypothesised that expectation of taste intensity should be underpinned by modulation of activity in primary taste cortex. Using functional magnetic resonance imaging, we found that expecting a very sweet drink, but receiving a less sweet drink, enhanced the reported sweetness and bolstered activity in taste cortex, relative to a less sweet drink without this expectation. The activation overlapped with primary taste cortex activation found in 11 recent taste studies. Our findings provide evidence that taste expectation modulates activity in an area consistently reported as primary taste cortex, implying that expectation effects do indeed impact on taste perception.     

Neural mechanisms of automatic and direct processing of phobogenic stimuli in specific phobia.

BACKGROUND: The study aimed to identify brain activation during direct and automatic processing of phobogenic stimuli in specific phobia. METHODS: Responses to phobia-related and neutral pictures (spiders and mushrooms) were measured by means of event-related functional magnetic resonance imaging during two different tasks. In the identification task, subjects were asked to identify the object (spider or mushroom). In a demanding distraction task, subjects had to match geometric figures displayed in the foreground of the pictures. RESULTS: Phobics showed greater responses to spiders versus mushrooms in the left amygdala, left insula, left anterior cingulate gyrus (ACC), and left dorsomedial prefrontal cortex (DMPFC) during the identification task and in the left and right amygdala during the distraction task. All of these activations were also significantly increased compared to control subjects who did not show stronger brain activation to spiders versus mushrooms under any task condition. CONCLUSIONS: Our findings propose specific neural correlates of automatic versus direct evaluation of phobia-relevant threat. While the amygdala, especially the right amygdala, seems to be crucially involved in automatic stimuli processing, activation of areas such as the insula, ACC and DMPFC is rather associated with direct threat evaluation and requires sufficient attentional resources.     

Brain mechanisms of expectation associated with insula and amygdala response to aversive taste: implications for placebo

The experience of aversion is shaped by multiple physiological and psychological factors including one's expectations. Recent work has shown that expectancy manipulation can alter perceptions of aversive events and concomitant brain activation. Accruing evidence indicates a primary role of altered expectancies in the placebo effect. Here, we probed the mechanism by which expectation attenuates sensory taste transmission by examining how brain areas activated by misleading information during an expectancy period modulate insula and amygdala activation to a highly aversive bitter taste. In a rapid event-related fMRI design, we showed that activations in the rostral anterior cingulate cortex (rACC), orbitofrontal cortex (OFC), and dorsolateral prefrontal cortex to a misleading cue that the taste would be mildly aversive predicted decreases in insula and amygdala activation to the highly aversive taste. OFC and rACC activation to the misleading cue were also associated with less aversive ratings of that taste. Additional analyses revealed consistent results demonstrating functional connectivity among the OFC, rACC, and insula. Altering expectancies of upcoming aversive events are shown here to depend on robust functional associations among brain regions implicated in prior work on the placebo effect.     

Monetary reward suppresses anterior insula activity during social pain

Social pain after exclusion by others activates brain regions also involved in physical pain. Here we evaluated whether monetary reward could compensate for the negative feeling of social pain in the brain. To address this question we used the unique technique of intracranial electroencephalography in subjects with drug resistant epilepsy. Specifically, we recorded theta activity from intracranial electrodes implanted in the insular cortex while subjects experienced conditions of social inclusion and exclusion associated with monetary gain and loss. Our study confirmed that theta rhythm in the insular cortex is the neural signature of social exclusion. We found that while monetary gain suppresses the effect of social pain in the anterior insula, there is no such effect in the posterior insula. These results imply that the anterior insula can use secondary reward signals to compensate for the negative feeling of social pain. Hence, here we propose that the anterior insula plays a pivotal role in integrating contingencies to update social pain feelings. Finally, the possibility to modulate the theta rhythm through the reward system might open new avenues of research for treating pathologies related to social exclusion.     

Effect of Magnitude Estimation of Pleasantness and Intensity on fMRI Activation to Taste

The goal of the present study was to investigate whether the psychophysical evaluation of taste stimuli using magnitude estimation influences the pattern of cortical activation observed with neuroimaging. That is, whether different brain areas are involved in the magnitude estimation of pleasantness relative to the magnitude estimation of intensity. fMRI was utilized to examine the patterns of cortical activation involved in magnitude estimation of pleasantness and intensity during hunger in response to taste stimuli. During scanning, subjects were administered taste stimuli orally and were asked to evaluate the perceived pleasantness or intensity using the general Labeled Magnitude Scale (Green et al., Chem Senses, 21(3), 323-334, 1996; Bartoshuk et al., Physiol Behav, 82(1), 109-114, 2004). Image analysis was conducted using Analysis of Functional NeuroImage software. Magnitude estimation of intensity and pleasantness shared common activations in the insula, rolandic operculum, and the medio-dorsal nucleus of the thalamus. Globally, magnitude estimation of pleasantness produced significantly more activation than magnitude estimation of intensity. Areas differentially activated during magnitude estimation of pleasantness versus intensity included, e.g., the insula, the anterior cingulate gyrus, and putamen, suggesting that different brain areas were recruited when subjects made magnitude estimates of intensity and pleasantness. These findings demonstrate significant differences in brain activation during magnitude estimation of intensity and pleasantness to taste stimuli. An appreciation for the complexity of brain response to taste stimuli may facilitate a clearer understanding of the neural mechanisms underlying eating behavior and overconsumption.     

Reward anticipation in the adolescent and aging brain

Processing of reward is the basis of adaptive behavior of the human being. Neural correlates of reward processing seem to be influenced by developmental changes from adolescence to late adulthood. The aim of this study is to uncover these neural correlates during a slot machine gambling task across the lifespan. Therefore, we used functional magnetic resonance imaging to investigate 102 volunteers in three different age groups: 34 adolescents, 34 younger adults, and 34 older adults. We focused on the core reward areas ventral striatum (VS) and ventromedial prefrontal cortex (VMPFC), the valence processing associated areas, anterior cingulate cortex (ACC) and insula, as well as information integration associated areas, dorsolateral prefrontal cortex (DLPFC), and inferior parietal lobule (IPL). Results showed that VS and VMPFC were characterized by a hyperactivation in adolescents compared with younger adults. Furthermore, the ACC and insula were characterized by a U‐shape pattern (hypoactivation in younger adults compared with adolescents and older adults), whereas the DLPFC and IPL were characterized by a J‐shaped form (hyperactivation in older adults compared with younger groups). Furthermore, a functional connectivity analysis revealed an elevated negative functional coupling between the inhibition‐related area rIFG and VS in younger adults compared with adolescents. Results indicate that lifespan‐related changes during reward anticipation are characterized by different trajectories in different reward network modules and support the hypothesis of an imbalance in maturation of striatal and prefrontal cortex in adolescents. Furthermore, these results suggest compensatory age‐specific effects in fronto‐parietal regions. Hum Brain Mapp 35:5153–5165, 2014. © 2014 Wiley Periodicals, Inc .