Convergent gustatory and viscerosensory processing in the human dorsal mid‐insula

The homeostatic regulation of feeding behavior requires an organism to be able to integrate information from its internal environment, including peripheral visceral signals about the body's current energy needs, with information from its external environment, such as the palatability of energy‐rich food stimuli. The insula, which serves as the brain's primary sensory cortex for representing both visceral signals from the body and taste signals from the mouth and tongue, is a likely candidate region in which this integration might occur. However, to date it has been unclear whether information from these two homeostatically critical faculties is merely co‐represented in the human insula, or actually integrated there. Recent functional neuroimaging evidence of a common substrate for visceral interoception and taste perception within the human dorsal mid‐insula suggests a model whereby a single population of neurons may integrate viscerosensory and gustatory signals. To test this model, we used fMRI‐Adaptation to identify whether insula regions that exhibit repetition suppression following repeated interoception trials would then also exhibit adapted responses to subsequent gustatory stimuli. Multiple mid and anterior regions of the insula exhibited adaptation to interoceptive trials specifically, but only the dorsal mid‐insula regions exhibited an adapted gustatory response following interoception. The discovery of this gustatory‐interoceptive convergence within the neurons of the human insula supports the existence of a heretofore‐undocumented neural pathway by which visceral signals from the periphery modulate the activity of brain regions involved in feeding behavior. Hum Brain Mapp 38:2150–2164, 2017. © 2017 Wiley Periodicals, Inc.     

Interoceptive accuracy and its impact on neuronal responses to olfactory stimulation in the insular cortex

The insular cortex plays a key role in the integration of multimodal information and in interoceptive and exteroceptive processing. For instance, neurons in the central dorsal insula that are active during interoceptive tasks, also show an adaptation to gustatory stimulation. We tested the link between interoception and exteroception for the olfactory system (i.e., the second domain of chemosensation). In a sample of 31 participants, olfactory function was assessed in a two dimensional approach while the Heartbeat Perception Task served as a measurement for cardiac interoceptive accuracy. Subsequent fMRI sessions were performed on a 3‐Tesla MR scanner containing 12–15 olfactory stimulation trials with a mildly pleasant food‐related odor (coffee). Persons scoring high in the cardiac interoceptive accuracy task presented stronger smelling abilities as well as enhanced BOLD responses following olfactory stimulation. The olfactory stimulation triggered enhanced insular activation patterns in the central dorsal insular cortex. Consistent with prior findings on the coherence of gustatory and interoceptive processing in the central dorsal insula, these results base the insula as a common region for the integration of interoception and exteroception. We propose an explanatory model of how exteroception triggers the integration of intero‐ and exteroceptive sensations in the central dorsal insular cortex.     

Two systems of resting state connectivity between the insula and cingulate cortex

The insula and cingulate cortices are implicated in emotional, homeostatic/allostatic, sensorimotor, and cognitive functions. Non‐human primates have specific anatomical connections between sub‐divisions of the insula and cingulate. Specifically, the anterior insula projects to the pregenual anterior cingulate cortex (pACC) and the anterior and posterior mid‐cingulate cortex (aMCC and pMCC); the mid‐posterior insula only projects to the posterior MCC (pMCC). In humans, functional neuroimaging studies implicate the anterior insula and pre/subgenual ACC in emotional processes, the mid‐posterior insula with awareness and interoception, and the MCC with environmental monitoring, response selection, and skeletomotor body orientation. Here, we tested the hypothesis that distinct resting state functional connectivity could be identified between (1) the anterior insula and pACC/aMCC; and (2) the entire insula (anterior, middle, and posterior insula) and the pMCC. Functional connectivity was assessed from resting state fMRI scans in 19 healthy volunteers using seed regions of interest in the anterior, middle, and posterior insula. Highly correlated, low‐frequency oscillations (< 0.05 Hz) were identified between specific insula and cingulate subdivisions. The anterior insula was shown to be functionally connected with the pACC/aMCC and the pMCC, while the mid/posterior insula was only connected with the pMCC. These data provide evidence for a resting state anterior insula–pACC/aMCC cingulate system that may integrate interoceptive information with emotional salience to form a subjective representation of the body; and another system that includes the entire insula and MCC, likely involved in environmental monitoring, response selection, and skeletomotor body orientation. Human Brain Mapp 2009. © 2008 Wiley‐Liss, Inc.     

Differential functional brain network connectivity during visceral interoception as revealed by independent component analysis of fMRI time‐series

Influential theories of brain‐viscera interactions propose a central role for interoception in basic motivational and affective feeling states. Recent neuroimaging studies have underlined the insula, anterior cingulate, and ventral prefrontal cortices as the neural correlates of interoception. However, the relationships between these distributed brain regions remain unclear. In this study, we used spatial independent component analysis (ICA) and functional network connectivity (FNC) approaches to investigate time course correlations across the brain regions during visceral interoception. Functional magnetic resonance imaging (fMRI) was performed in thirteen healthy females who underwent viscerosensory stimulation of bladder as a representative internal organ at different prefill levels, i.e., no prefill, low prefill (100 ml saline), and high prefill (individually adapted to the sensations of persistent strong desire to void), and with different infusion temperatures, i.e., body warm (～37°C) or ice cold (4–8°C) saline solution. During Increased distention pressure on the viscera, the insula, striatum, anterior cingulate, ventromedial prefrontal cortex, amygdalo‐hippocampus, thalamus, brainstem, and cerebellar components showed increased activation. A second group of components encompassing the insula and anterior cingulate, dorsolateral prefrontal and posterior parietal cortices and temporal‐parietal junction showed increased activity with innocuous temperature stimulation of bladder mucosa. Significant differences in the FNC were found between the insula and amygdalo‐hippocampus, the insula and ventromedial prefrontal cortex, and the ventromedial prefrontal cortex and temporal‐parietal junction as the distention pressure on the viscera increased. These results provide new insight into the supraspinal processing of visceral interoception originating from an internal organ. Hum Brain Mapp 36:4438–4468, 2015. © 2015 Wiley Periodicals, Inc.     

Bilateral Rolandic operculum processing underlying heartbeat awareness reflects changes in bodily self‐consciousness

Exteroceptive bodily signals (including tactile, proprioceptive and visual signals) are important information contributing to self‐consciousness. Moreover, prominent theories proposed that visceral signals about internal bodily states are equally or even more important for self‐consciousness. Neuroimaging studies have described several brain regions which process signals related to bodily self‐consciousness (BSC) based on the integration of exteroceptive signals (e.g. premotor cortex, angular gyrus, supramarginal gyrus and extrastriate body area), and that another brain region, the insula/operculum which is involved in interoception and interoceptive awareness, processes signals critical for self‐awareness. Providing evidence for the integration of exteroceptive and interoceptive bodily signals, recent behavioral experiments have demonstrated that the manipulation of interoceptive (e.g. cardiac) signals, coupled with exteroceptive (e.g. visual) signals, also modulates BSC. Does this integration occur within or outside the structures described above? To this end, we adapted a recently designed protocol that uses cardio‐visual stimulation to induce altered states of BSC to fMRI. Additionally, we measured neural activity in a classical interoceptive task. We found six brain regions (bilateral Rolandic operculum, bilateral supramarginal gyrus, right frontal inferior operculum and left temporal superior gyrus) that were activated differently during the interoception task as opposed to a control task. The brain regions which showed the highest selectivity for BSC based on our cardio‐visual manipulation were found in the bilateral Rolandic operculum. Given our findings, we propose that the Rolandic operculum processes integrated exteroceptive–interoceptive signals that are necessary for interoceptive awareness as well as BSC.     

Multilevel convergence of interoceptive impairments in hypertension: New evidence of disrupted body–brain interactions

Interoception, the sensing of visceral body signals, involves an interplay between neural and autonomic mechanisms. Clinical studies into this domain have focused on patients with neurological and psychiatric disorders, showing that damage to relevant brain mechanisms can variously alter interoceptive functions. However, the association between peripheral cardiac‐system alterations and neurocognitive markers of interoception remains poorly understood. To bridge this gap, we examined multidimensional neural markers of interoception in patients with early stage of hypertensive disease (HTD) and healthy controls. Strategically, we recruited only HTD patients without cognitive impairment (as shown by neuropsychological tests), brain atrophy (as assessed with voxel‐based morphometry), or white matter abnormalities (as evidenced by diffusion tensor imaging analysis). Interoceptive domains were assessed through (a) a behavioral heartbeat detection task; (b) measures of the heart‐evoked potential (HEP), an electrophysiological cortical signature of attention to cardiac signals; and (c) neuroimaging recordings (MRI and fMRI) to evaluate anatomical and functional connectivity properties of key interoceptive regions (namely, the insula and the anterior cingulate cortex). Relative to controls, patients exhibited poorer interoceptive performance and reduced HEP modulations, alongside an abnormal association between interoceptive performance and both the volume and functional connectivity of the above regions. Such results suggest that peripheral cardiac‐system impairments can be associated with abnormal behavioral and neurocognitive signatures of interoception. More generally, our findings indicate that interoceptive processes entail bidirectional influences between the cardiovascular and the central nervous systems.     

Interoceptive awareness enhances neural activity during empathy

Empathy is a multicomponent function that includes sensorimotor, affective, and cognitive components. Although especially the affective component may implicate interoception and interoceptive awareness, the impact of interoception on empathy has never been evaluated behaviorally or neurophysiologically. Here, we tested how a preceding period of interoceptive awareness impacts and modulates neural activity during subsequent empathy. We used functional magnetic resonance imaging (fMRI) and measured the sequential interaction between interoception and empathy using fMRI in 18 healthy subjects. We found that the preceding interoceptive awareness period significantly enhanced neural activity during empathy in bilateral anterior insula and various cortical midline regions. The enhancement of neural activity during empathy in both interoceptive and empathy networks by preceding interoceptive awareness suggests a close relationship between interoception and empathy; thereby, interoception seems to be implicated to yielding empathy. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

Neural correlates of interoception: Effects of interoceptive focus and relationship to dimensional measures of body awareness

Interoception has been defined as the sensing of the physiological condition of the body, with interoceptive sensibility (IS) characterizing an individual's self‐reported awareness of internal sensation. IS is a multidimensional construct including not only the tendency to be aware of sensation but also how sensations are interpreted, regulated, and used to inform behavior, with different dimensions relating to different aspects of health and disease. Here we investigated neural mechanisms of interoception when healthy individuals attended to their heartbeat and skin temperature, and examined the relationship between neural activity during interoception and individual differences in self‐reported IS using the Multidimensional Scale of Interoceptive Awareness (MAIA). Consistent with prior work, interoception activated a network involving insula and sensorimotor regions but also including occipital, temporal, and prefrontal cortex. Differences based on interoceptive focus (heartbeat vs skin temperature) were found in insula, sensorimotor regions, occipital cortex, and limbic areas. Factor analysis of MAIA dimensions revealed 3 dissociable components of IS in our dataset, only one of which was related to neural activity during interoception. Reduced scores on the third factor, which reflected reduced ability to control attention to body sensation and increased tendency to distract from and worry about aversive sensations, was associated with greater activation in many of the same regions as those involved in interoception, including insula, sensorimotor, anterior cingulate, and temporal cortex. These data suggest that self‐rated interoceptive sensibility is related to altered activation in regions involved in monitoring body state, which has implications for disorders associated with abnormality of interoception. Hum Brain Mapp 38:6068–6082, 2017. © 2017 Wiley Periodicals, Inc.     

How task demands shape brain responses to visual food cues

Several previous imaging studies have aimed at identifying the neural basis of visual food cue processing in humans. However, there is little consistency of the functional magnetic resonance imaging (fMRI) results across studies. Here, we tested the hypothesis that this variability across studies might – at least in part – be caused by the different tasks employed. In particular, we assessed directly the influence of task set on brain responses to food stimuli with fMRI using two tasks (colour vs. edibility judgement, between‐subjects design). When participants judged colour, the left insula, the left inferior parietal lobule, occipital areas, the left orbitofrontal cortex and other frontal areas expressed enhanced fMRI responses to food relative to non‐food pictures. However, when judging edibility, enhanced fMRI responses to food pictures were observed in the superior and middle frontal gyrus and in medial frontal areas including the pregenual anterior cingulate cortex and ventromedial prefrontal cortex. This pattern of results indicates that task sets can significantly alter the neural underpinnings of food cue processing. We propose that judging low‐level visual stimulus characteristics – such as colour – triggers stimulus‐related representations in the visual and even in gustatory cortex (insula), whereas discriminating abstract stimulus categories activates higher order representations in both the anterior cingulate and prefrontal cortex. Hum Brain Mapp 38:2897–2912, 2017. © 2017 Wiley Periodicals, Inc.     

Auricular transcutaneous vagus nerve stimulation modulates the heart-evoked potential

BackgroundThere is active interest in biomarker discovery for transcutaneous auricular vagus nerve stimulation (taVNS). However, greater understanding of the neurobiological mechanisms is needed to identify candidate markers. Accumulating evidence suggests that taVNS influences activity in solitary and parabrachial nuclei, the primary brainstem relays for the transmission of visceral sensory afferents to the insula. The insula mediates interoception, which concerns the representation and regulation of homeostatic bodily states. Consequently, interoceptive pathways may be relevant to taVNS mechanisms of action.HypothesesWe hypothesized that taVNS would modulate an EEG-derived marker of interoceptive processing known as the heart-evoked potential (HEP). We also hypothesized that taVNS-induced HEP effects would be localizable to the insula.MethodsUsing a within-subject, sham-controlled design, we recorded EEG and ECG concurrent to taVNS in 43 healthy adults. Using ECG and EEG data, we extracted HEPs. Estimation of the cortical sources of the taVNS-dependent HEP responses observed at the scalp were computed using the Boundary Element Method and weighted Minimum Norm Estimation. Statistics were calculated using cluster-based permutation methods.ResultstaVNS altered HEP amplitudes at frontocentral and centroparietal electrode sites at various latencies. The taVNS-dependent HEP effect was localized to the insula, operculum, somatosensory cortex, and orbital and ventromedial prefrontal regions.ConclusionThe results support the hypothesis that taVNS can access the insula as well as functionally and anatomically connected brain regions. HEPs may serve as an objective, non-invasive outcome parameter for the cortical effects of taVNS.     

Your pain or mine? Common and distinct neural systems supporting the perception of pain in self and other

Humans possess a remarkable capacity to understand the suffering of others. Cognitive neuroscience theories of empathy suggest that this capacity is supported by ‘shared representations’ of self and other. Consistent with this notion, a number of studies have found that perceiving others in pain and experiencing pain oneself recruit overlapping neural systems. Perception of pain in each of these conditions, however, may also cause unique patterns of activation, that may reveal more about the processing steps involved in each type of pain. To address this issue, we examined neural activity while participants experienced heat pain and watched videos of other individuals experiencing injuries. Results demonstrated (i) that both tasks activated anterior cingulate cortex and anterior insula, consistent with prior work; (ii) whereas self-pain activated anterior and mid insula regions implicated in interoception and nociception, other pain activated frontal, premotor, parietal and amygdala regions implicated in emotional learning and processing social cues; and (iii) that levels of trait anxiety correlated with activity in rostral lateral prefrontal cortex during perception of other pain but not during self-pain. Taken together, these data support the hypothesis that perception of pain in self and other, while sharing some neural commonalities, differ in their recruitment of systems specifically associated with decoding and learning about internal or external cues.     

Abnormal body perception and neural activity in the insula in depression: An fMRI study of the depressed “material me”

Abstract

Objectives. In addition to affective-cognitive symptoms, patients with major depressive disorder (MDD) suffer from somato-vegetative symptoms, suggesting abnormal interoceptive awareness of their “material me”. While recent imaging studies have extensively investigated affective-cognitive symptoms in MDD, the neural correlates of somato-vegetative symptoms and abnormal interoception remain unclear. Since the “material me” has been especially associated with the anterior insula in healthy subjects, we hypothesized abnormalities in this region during interoceptive awareness in MDD. Methods. We therefore investigated behavioural and neural correlates of interoception in healthy and depressed subjects using the Body Perception Questionnaire (BPQ) and a well established heartbeat perception task in fMRI. Results. MDD patients showed significantly higher scores in the BPQ and reduced neural activity during rest periods, particularly in the bilateral anterior insula. In contrast to healthy subjects, BPQ scores no longer correlated with activity during rest periods in the anterior insula. Both BPQ scores and left anterior insula signal changes correlated with depression severity. Conclusions. We demonstrate for the first time abnormal body perception and altered activity in the insula during rest in MDD. Our results suggest that these behavioural and neural abnormalities are closely related to these patients’ somato-vegetative abnormalities and their abnormal “material me”.     

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.     

Keeping the body in mind: Insula functional organization and functional connectivity integrate interoceptive,exteroceptive, and emotional awareness

Relatively discrete experimental literatures have grown to support the insula's role in the domains of interoception, focal exteroceptive attention and cognitive control, and the experience of anxiety, even as theoretical accounts have asserted that the insula is a critical zone for integrating across these domains. Here we provide the first experimental demonstration that there exists a functional topography across the insula, with distinct regions in the same participants responding in a highly selective fashion for interoceptive, exteroceptive, and affective processing. Although each insular region is associated with areas of differential resting state functional connectivity relative to the other regions, overall their functional connectivity profiles are quite similar, thereby providing a map of how interoceptive, exteroceptive, and emotional awareness are integrated within the insular cortex. Hum Brain Mapp 34:2944–2958, 2013. © 2012 Wiley Periodicals, Inc.     

Superadditive opercular activation to food flavor is mediated by enhanced temporal and limbic coupling

Food perception is characterized by a transition from initially separate sensations of the olfactory and gustatory properties of the object toward their combined sensory experience during consumption. The holistic flavor experience, which occurs as the smell and taste merge, extends beyond the mere addition of the two chemosensory modalities, being usually perceived as more object‐like, intense and rewarding. To explore the cortical mechanisms which give rise to olfactory–gustatory binding during natural food consumption, brain activation during consumption of a pleasant familiar beverage was contrasted with presentation of its taste and orthonasal smell alone. Convergent activation to all presentation modes was observed in executive and chemosensory association areas. Flavor, but not orthonasal smell or taste alone, stimulated the frontal operculum, supporting previous accounts of its central role in the formation of the flavor percept. A functional dissociation was observed in the insula: the anterior portion was characterized by sensory convergence, while mid‐dorsal sections activated exclusively to the combined flavor stimulus. psycho‐physiological interaction analyses demonstrated increased neural coupling between the frontal operculum and the anterior insula during flavor presentation. Connectivity was also increased with the lateral entorhinal cortex, a relay to memory networks and central node for contextual modulation of olfactory processing. These findings suggest a central role of the insular cortex in the transition from mere detection of chemosensory convergence to a superadditive flavor representation. The increased connections between the frontal operculum and medial temporal memory structures during combined olfactory–gustatory stimulation point to a potential mechanism underlying the acquisition and modification of flavor preferences. Hum Brain Mapp 36:1662–1676, 2015. © 2014 Wiley Periodicals, Inc.     

Brain connection pattern under interoceptive attention state predict interoceptive intensity and subjective anxiety feeling

Interoception involves the processing of a variety of different types of information ascending from the body. Accumulating evidence has indicated that interoception plays a fundamental role in cognitive and emotional processes, such as anxiety, but how different functional connectivity patterns contribute to emotions and visceral feelings during an interoceptive attention state is still unclear. In the present study, an interoceptive attention task was performed during functional magnetic resonance imaging of healthy subjects, and the participants' subjective ratings of the intensity of interoception and feelings of anxiety were recorded. Several network nodes were selected, based on previous studies, to construct task‐dependent functional connectivity patterns, which were processed by support vector regression to predict the corresponding feeling scores. The results showed that for interoception, the cingulo‐opercular task control network provided the greatest contribution, whereas the most important feature for anxiety was the connections between the sensorimotor area (SSM) and the salience network (SN). There existed four overlapping connections between the two predictions: two negative connections between the default mode network (DMN) and the SSM, one negative connection between the DMN and the SN, and one positive connection between the ventral attention network and the SN; this overlap might suggest common bodily attention processing that is involved in both interoception and anxiety. This study remediates the lack of network‐level biomarkers of interoception and provides a reference at the level of the brain for further understanding anxiety from an interoceptive perspective.     

Dynamic functional network connectivity reveals unique and overlapping profiles of insula subdivisions

The human insular cortex consists of functionally diverse subdivisions that engage during tasks ranging from interoception to cognitive control. The multiplicity of functions subserved by insular subdivisions calls for a nuanced investigation of their functional connectivity profiles. Four insula subdivisions (dorsal anterior, dAI; ventral, VI; posterior, PI; middle, MI) derived using a data‐driven approach were subjected to static‐ and dynamic functional network connectivity (s‐FNC and d‐FNC) analyses. Static‐FNC analyses replicated previous work demonstrating a cognition‐emotion‐interoception division of the insula, where the dAI is functionally connected to frontal areas, the VI to limbic areas, and the PI and MI to sensorimotor areas. Dynamic‐FNC analyses consisted of k‐means clustering of sliding windows to identify variable insula connectivity states. The d‐FNC analysis revealed that the most frequently occurring dynamic state mirrored the cognition‐emotion‐interoception division observed from the s‐FNC analysis, with less frequently occurring states showing overlapping and unique subdivision connectivity profiles. In two of the states, all subdivisions exhibited largely overlapping profiles, consisting of subcortical, sensory, motor, and frontal connections. Two other states showed the dAI exhibited a unique connectivity profile compared with other insula subdivisions. Additionally, the dAI exhibited the most variable functional connections across the s‐FNC and d‐FNC analyses, and was the only subdivision to exhibit dynamic functional connections with regions of the default mode network. These results highlight how a d‐FNC approach can capture functional dynamics masked by s‐FNC approaches, and reveal dynamic functional connections enabling the functional flexibility of the insula across time. Hum Brain Mapp 37:1770–1787, 2016. © 2016 Wiley Periodicals, Inc .     

Cerveau maternel : Théorie bayésienne de l’intéroception maternelle pendant la grossesse et le postpartum

The perinatal period, including pregnancy and postpartum, causes major morphological, endocrinal, and thermal transitions in women. As the fetus grows, abdominal muscle fibers stretch, internal organs such as the bladder or colon move, and the uterine anatomy changes. Many of these changes involve interoception, the perception of internal body signals such as muscle and visceral sensations. Despite the importance of these interoceptive signals, few studies have explored perinatal interoception. We propose an innovative theory of maternal interoception based on recent findings in neuroscience. We show that interoceptive signals processing during pregnancy is crucial for understanding perinatal phenomenology and psychopathology, such as maternal perception of fetal movements, maternal-infant bonding, denial of pregnancy, phantom fetal movements after childbirth, pseudocyesis or even puerperal delusion. Knowing the importance of these interoceptive mechanisms, clinicians in obstetrics, gynecology and mental health should be particularly vigilant to maternal interoception during the perinatal period.     

Neurofunctional maps of the ‘maternal brain’ and the effects of oxytocin: A multimodal voxel‐based meta‐analysis

Several studies have tried to understand the possible neurobiological basis of mothering. The putative involvement of oxytocin, in this regard, has been deeply investigated. Performing a voxel‐based meta‐analysis, we aimed at testing the hypothesis of overlapping brain activation in functional magnetic resonance imaging (fMRI) studies investigating the mother–infant interaction and the oxytocin modulation of emotional stimuli in humans. We performed two systematic literature searches: fMRI studies investigating the neurofunctional correlates of the ‘maternal brain’ by employing mother–infant paradigms; and fMRI studies employing oxytocin during emotional tasks. A unimodal voxel‐based meta‐analysis was performed on each database, whereas a multimodal voxel‐based meta‐analytical tool was adopted to assess the hypothesis that the neurofunctional effects of oxytocin are detected in brain areas implicated in the ‘maternal brain.’ We found greater activation in the bilateral insula extending to the inferior frontal gyrus, basal ganglia and thalamus during mother–infant interaction and greater left insular activation associated with oxytocin administration versus placebo. Left insula extending to basal ganglia and frontotemporal gyri as well as bilateral thalamus and amygdala showed consistent activation across the two paradigms. Right insula also showed activation across the two paradigms, and dorsomedial frontal cortex activation in mothers but deactivation with oxytocin. Significant activation in areas involved in empathy, emotion regulation, motivation, social cognition and theory of mind emerged from our multimodal meta‐analysis, supporting the need for further studies directly investigating the neurobiology of oxytocin in the mother–infant relationship.