The role of the subgenual anterior cingulate cortex in dorsomedial prefrontal–amygdala neural circuitry during positive‐social emotion regulation

Positive‐social emotions mediate one's cognitive performance, mood, well‐being, and social bonds, and represent a critical variable within therapeutic settings. It has been shown that the upregulation of positive emotions in social situations is associated with increased top‐down signals that stem from the prefrontal cortices (PFC) which modulate bottom‐up emotional responses in the amygdala. However, it remains unclear if positive‐social emotion upregulation of the amygdala occurs directly through the dorsomedial PFC (dmPFC) or indirectly linking the bilateral amygdala with the dmPFC via the subgenual anterior cingulate cortex (sgACC), an area which typically serves as a gatekeeper between cognitive and emotion networks. We performed functional MRI (fMRI) experiments with and without effortful positive‐social emotion upregulation to demonstrate the functional architecture of a network involving the amygdala, the dmPFC, and the sgACC. We found that effortful positive‐social emotion upregulation was associated with an increase in top‐down connectivity from the dmPFC on the amygdala via both direct and indirect connections with the sgACC. Conversely, we found that emotion processes without effortful regulation increased network modulation by the sgACC and amygdala. We also found that more anxious individuals with a greater tendency to suppress emotions and intrusive thoughts, were likely to display decreased amygdala, dmPFC, and sgACC activity and stronger connectivity strength from the sgACC onto the left amygdala during effortful emotion upregulation. Analyzed brain network suggests a more general role of the sgACC in cognitive control and sheds light on neurobiological informed treatment interventions.     

Socially excluded individuals fail to recruit medial prefrontal cortex for negative social scenes

Converging behavioral evidence suggests that people respond to experiences of social exclusion with both defensive and affiliative strategies, allowing them to avoid further distress while also encouraging re-establishment of positive social connections. However, there are unresolved questions regarding the cognitive mechanisms underlying people''s responses to social exclusion. Here, we sought to gain insight into these behavioral tendencies by using functional magnetic resonance imaging (fMRI) to examine the impact of social exclusion on neural responses to visual scenes that varied on dimensions of sociality and emotional valence. Compared to socially included participants, socially excluded participants failed to recruit dorsomedial prefrontal cortex (dmPFC), a brain region involved in mentalizing, for negative social scenes. Moreover, following social exclusion, dmPFC demonstrated a linear effect of valence, with greater activity to positive social scenes compared to negative social scenes. These results suggest that, following social exclusion, people display a preference for mentalizing about positive social information and tend to avoid negative aspects of their social world.     

Regulation of emotional responses elicited by threat-related stimuli

The capacity to voluntarily regulate emotions is critical for mental health, especially when coping with aversive events. Several neuroimaging studies of emotion regulation found the amygdala to be a target for downregulation and prefrontal regions to be associated with downregulation. To characterize the role of prefrontal regions in bidirectional emotion regulation and to investigate regulatory influences on amygdala activity and peripheral physiological measures, a functional magnetic resonance imaging (fMRI) study with simultaneous recording of self-report, startle eyeblink, and skin conductance responses was carried out. Subjects viewed threat-related pictures and were asked to up- and downregulate their emotional responses using reappraisal strategies. While startle eyeblink responses (in successful regulators) and skin conductance responses were amplified during upregulation, but showed no consistent effect during downregulation, amygdala activity was increased and decreased according to the regulation instructions. Trial-by-trial ratings of regulation success correlated positively with activity in amygdala during upregulation and orbitofrontal cortex during downregulation. Downregulation was characterized by left-hemispheric activation peaks in anterior cingulate cortex, dorsolateral prefrontal cortex, and orbitofrontal cortex and upregulation was characterized by a pattern of prefrontal activation not restricted to the left hemisphere. Further analyses showed significant overlap of prefrontal activation across both regulation conditions, possibly reflecting cognitive processes underlying both up- and downregulation, but also showed distinct activations in each condition. The present study demonstrates that amygdala responses to threat-related stimuli can be controlled through the use of cognitive strategies depending on recruitment of prefrontal areas, thereby changing the subject's affective state.     

Differential parametric modulation of self-relatedness and emotions in different brain regions

Our sense of self is strongly colored by emotions although at the same time we are well able to distinguish affect and self. Using functional magnetic resonance imaging, we here tested for the differential effects of self-relatedness and emotion dimensions (valence, intensity) on parametric modulation of neural activity during perception of emotional stimuli. We observed opposite parametric modulation of self-relatedness and emotion dimensions in the dorsomedial prefrontal cortex and the ventral striatum/nucleus accumbens, whereas neural activity in subcortical regions (tectum, right amygdala, hypothalamus) was modulated by self-relatedness and emotion dimensions in the same direction. In sum, our results demonstrate that self-relatedness is closely linked to emotion dimensions of valence and intensity in many lower subcortical brain regions involved in basic emotional systems and, at the same time, distinct from them in higher cortical regions that mediate cognitive processes necessary for becoming aware of one's self, for example self-consciousness. Hum     

Anterior cingulate cortex modulates preparatory activation during certain anticipation of negative picture

We studied the neural activation associated with anticipations of emotional pictures using functional magnetic resonance imaging (fMRI) by directly comparing certain with uncertain anticipation conditions. While being scanned with fMRI, healthy participants (n=18) were cued to anticipate and then perceive emotional stimuli having predictable (i.e., certain) emotional valences (i.e., positive and negative), given a preceding cue, as well as cued stimuli of uncertain valence (positive or negative). During anticipation of pictures with certain negative valence, activities of supracallosal anterior cingulate cortex, ventrolateral prefrontal cortex, insula, and amygdala were enhanced relative activity levels that for the uncertain emotional anticipation condition. This result suggests that these brain regions are involved in anticipation of negative images, and that their activity levels may be enhanced by the certainty of anticipation. Furthermore, the supracallosal anterior cingulate cortex showed functional connectivity with the insula, prefrontal cortex, and occipital cortex during the certain negative anticipation. These findings are consistent with an interpretation that top-down modulation, arising from anterior brain regions, is engaged in certain negative anticipation within the occipital cortex. It is thought that the limbic system involving the amygdala, ACC, and insula, engaged emotional processes, and that the input system involving the visual cortex entered an idling state.     

Fear in dreams and in wakefulness: Evidence for day/night affective homeostasis

Recent neuroscientific theories have proposed that emotions experienced in dreams contribute to the resolution of emotional distress and preparation for future affective reactions. We addressed one emerging prediction, namely that experiencing fear in dreams is associated with more adapted responses to threatening signals during wakefulness. Using a stepwise approach across two studies, we identified brain regions activated when experiencing fear in dreams and showed that frightening dreams modulated the response of these same regions to threatening stimuli during wakefulness. Specifically, in Study 1, we performed serial awakenings in 18 participants recorded throughout the night with high‐density electroencephalography (EEG) and asked them whether they experienced any fear in their dreams. Insula and midcingulate cortex activity increased for dreams containing fear. In Study 2, we tested 89 participants and found that those reporting higher incidence of fear in their dreams showed reduced emotional arousal and fMRI response to fear‐eliciting stimuli in the insula, amygdala and midcingulate cortex, while awake. Consistent with better emotion regulation processes, the same participants displayed increased medial prefrontal cortex activity. These findings support that emotions in dreams and wakefulness engage similar neural substrates, and substantiate a link between emotional processes occurring during sleep and emotional brain functions during wakefulness.     

Brain activity underlying emotional valence and arousal: a response-related fMRI study

Emotional behavior is organized along two psychophysiologic dimensions: (1) valence, varying from negative to positive, and (2) arousal, varying from low to high. Behavioral responses along these dimensions are assumed to be mediated by different brain circuits. We recorded startle reflex modulation and skin conductance responses in healthy volunteers during functional magnetic resonance imaging (fMRI) while they viewed a set of emotional pictures and took verbal ratings of the emotional valence and arousal of each picture after scanning. Response-related multiple correlation analysis revealed differential brain activity in five brain regions. Startle reflex changes, associated with the valence of a stimulus, correlated with activity in the amygdala, while verbal reports of negative emotional valence varied with insular activity. Peripheral physiologic and verbal responses along the arousal dimension varied with thalamic and frontomedial activity. Peripheral physiologic responses along both dimensions correlated with activity in somatosensory association areas in the anterior parietal cortex. In the valence dimension, activity in the left anterior parietal cortex was associated with highly correlating peripheral physiologic and verbal responses, suggesting that verbal reports of emotional valence might depend partly on brain circuits representing peripheral physiologic changes. Our data provide direct evidence for a functional segregation of brain structures underlying peripheral physiologic responses and verbal ratings along the emotional dimensions of valence and arousal.     

Bad and worse: neural systems underlying reappraisal of high- and low-intensity negative emotions

One of the most effective strategies for regulating emotional responses is cognitive reappraisal. While prior work has made great strides in characterizing reappraisal’s neural mechanisms and behavioral outcomes, the key issue of how regulation varies as a function of emotional intensity remains unaddressed. We compared the behavioral and neural correlates of reappraisal of high- and low-intensity emotional responses using functional magnetic resonance imaging (fMRI). We found that successful reappraisal of both high- and low-intensity emotions depends upon recruitment of dorsomedial (dmPFC) as well as left dorsolateral (dlPFC) and ventrolateral (vlPFC) prefrontal cortex. However, reappraisal of high-intensity emotions more strongly activated left dlPFC, and in addition, activated right lateral and dorsomedial PFC regions not recruited by low-intensity reappraisal. No brain regions were more strongly recruited during reappraisal of low when compared with high-intensity emotions. Taken together, these results suggest that reappraisal of high-intensity emotion requires greater cognitive resources as evidenced by quantitative and qualitative differences in prefrontal recruitment. These data have implications for understanding how and when specific PFC systems are needed to regulate different types of emotional responses.     

An fMRI study investigating cognitive modulation of brain regions associated with emotional processing of visual stimuli

Brain regions modulated by cognitive tasks during emotional processing were investigated using fMRI. Participants performed indirect and direct emotional processing tasks on positive and negative faces and pictures. We used a multivariate technique, partial least squares (PLS) to determine spatially distributed patterns of brain activity associated with different tasks and stimulus conditions, as well as the interaction between the two. The pattern of brain activity accounting for the most task-related covariance represented a task x stimulus interaction and distinguished indirect processing of pictures and direct processing of faces from direct processing of pictures and indirect processing of faces. The latter two conditions were characterised by limbic (e.g. amygdala, insula, thalamus) and temporal lobe activity, in addition to greater activity in the ventral prefrontal cortex. Indirect and direct processing of pictures and faces, respectively, were represented by more dorsal prefrontal and parietal activity. These findings indicate that brain activity during processing of emotional content is critically dependent on both the type of stimulus and processing task. In addition, these results support the idea that the pattern of activity in the emotional network can be influenced in a 'top-down' fashion via cognitive factors such as attentional control, and as such, have important clinical implications for emotional disorders, such as depression and anxiety.     

Distributed and interactive brain mechanisms during emotion face perception: evidence from functional neuroimaging

Brain imaging studies in humans have shown that face processing in several areas is modulated by the affective significance of faces, particularly with fearful expressions, but also with other social signals such gaze direction. Here we review haemodynamic and electrical neuroimaging results indicating that activity in the face-selective fusiform cortex may be enhanced by emotional (fearful) expressions, without explicit voluntary control, and presumably through direct feedback connections from the amygdala. fMRI studies show that these increased responses in fusiform cortex to fearful faces are abolished by amygdala damage in the ipsilateral hemisphere, despite preserved effects of voluntary attention on fusiform; whereas emotional increases can still arise despite deficits in attention or awareness following parietal damage, and appear relatively unaffected by pharmacological increases in cholinergic stimulation. Fear-related modulations of face processing driven by amygdala signals may implicate not only fusiform cortex, but also earlier visual areas in occipital cortex (e.g., V1) and other distant regions involved in social, cognitive, or somatic responses (e.g., superior temporal sulcus, cingulate, or parietal areas). In the temporal domain, evoked-potentials show a widespread time-course of emotional face perception, with some increases in the amplitude of responses recorded over both occipital and frontal regions for fearful relative to neutral faces (as well as in the amygdala and orbitofrontal cortex, when using intracranial recordings), but with different latencies post-stimulus onset. Early emotional responses may arise around 120ms, prior to a full visual categorization stage indexed by the face-selective N170 component, possibly reflecting rapid emotion processing based on crude visual cues in faces. Other electrical components arise at later latencies and involve more sustained activities, probably generated in associative or supramodal brain areas, and resulting in part from the modulatory signals received from amygdala. Altogether, these fMRI and ERP results demonstrate that emotion face perception is a complex process that cannot be related to a single neural event taking place in a single brain regions, but rather implicates an interactive network with distributed activity in time and space. Moreover, although traditional models in cognitive neuropsychology have often considered that facial expression and facial identity are processed along two separate pathways, evidence from fMRI and ERPs suggests instead that emotional processing can strongly affect brain systems responsible for face recognition and memory. The functional implications of these interactions remain to be fully explored, but might play an important role in the normal development of face processing skills and in some neuropsychiatric disorders.     

Cognitive and emotional modulation of brain default operation

Goal-directed behavior lowers activity in brain areas that include the medial frontal cortex, the medial and lateral parietal cortex, and limbic and paralimbic brain regions, commonly referred to as the "default network." These activity decreases are believed to reflect the interruption of processes that are ongoing when the mind is in a restful state. Previously, the nature of these processes was probed by varying cognitive task parameters, but the presence of emotional processes, while often assumed, was little investigated. With fMRI, we studied the effect of systematic variations of both cognitive load and emotional stimulus connotation on task-related decreases in the default network by employing an auditory working memory (WM) task with musical sounds. The performance of the WM task, compared to passive listening, lowered the activity in medial and lateral, prefrontal, parietal, temporal, and limbic regions. In a subset of these regions, the magnitude of decrease depended on the memory load; the greater the cognitive load, the larger the magnitude of the observed decrease. Furthermore, in the right amygdala and the left precuneus, areas previously associated with processing of unpleasant dissonant musical sounds, there was an interaction between the experimental condition and the stimulus type. The current results are consistent with the previously reported effect of task difficulty on task-related brain activation decreases. The results also indicate that task-related decreases may be further modulated by the emotional stimulus connotation.     

Activity in medial prefrontal cortex during cognitive evaluation of threatening stimuli as a function of personality style

Cognitive evaluation of emotional stimuli involves a network of brain regions including the medial prefrontal cortex (mPFC). However, threatening stimuli may be perceived with differential salience in different individuals. The goal of our study was to evaluate how different personality styles are associated with differential modulation of brain activity during explicit recognition of fearful and angry facial expressions. Twenty-eight healthy subjects underwent fMRI. Based on a cognitivist model, subjects were categorized according to how they attribute salience to emotional stimuli and how they regulate their emotional activation. We compared 14 phobic prone (PP) subjects, whose identity is more centered on the inner experience ("inward") and around control of environmental threat, and 14 eating disorders prone (EDP) subjects, whose identity is more centered on external referential contexts ("outward") and much less around control of threatening stimuli. During fMRI subjects either matched the identity of one of two angry and fearful faces to that of a simultaneously presented target face or identified the expression of a target face by choosing one of two simultaneously presented linguistic labels. The fMRI results indicated that PP subjects had greater mPFC activation when compared with EDP subjects during cognitive labeling of threatening stimuli. Activity in the mPFC also correlated with personality style scores. These results demonstrate that PP subjects recruit greater neuronal resources in mPFC whose activity is associated with cognitive aspects that are closely intertwined with emotional processing. These findings are consistent with the contention that cognitive evaluation and salience of emotional stimuli are associated with different personality styles.     

Cognitive influences on the affective representation of touch and the sight of touch in the human brain

We show that the affective experience of touch and the sight of touch can be modulated by cognition, and investigate in an fMRI study where top-down cognitive modulations of bottom-up somatosensory and visual processing of touch and its affective value occur in the human brain. The cognitive modulation was produced by word labels, ‘Rich moisturizing cream’ or ‘Basic cream’, while cream was being applied to the forearm, or was seen being applied to a forearm. The subjective pleasantness and richness were modulated by the word labels, as were the fMRI activations to touch in parietal cortex area 7, the insula and ventral striatum. The cognitive labels influenced the activations to the sight of touch and also the correlations with pleasantness in the pregenual cingulate/orbitofrontal cortex and ventral striatum. Further evidence of how the orbitofrontal cortex is involved in affective aspects of touch was that touch to the forearm [which has C fiber Touch (CT) afferents sensitive to light touch] compared with touch to the glabrous skin of the hand (which does not) revealed activation in the mid-orbitofrontal cortex. This is of interest as previous studies have suggested that the CT system is important in affiliative caress-like touch between individuals.     

The transition from childhood to adolescence is marked by a general decrease in amygdala reactivity and an affect-specific ventral-to-dorsal shift in medial prefrontal recruitment

Understanding how and why affective responses change with age is central to characterizing typical and atypical emotional development. Prior work has emphasized the role of the amygdala and prefrontal cortex (PFC), which show age-related changes in function and connectivity. However, developmental neuroimaging research has only recently begun to unpack whether age effects in the amygdala and PFC are specific to affective stimuli or may be found for neutral stimuli as well, a possibility that would support a general, rather than affect-specific, account of amygdala-PFC development. To examine this, 112 individuals ranging from 6 to 23 years of age viewed aversive and neutral images while undergoing fMRI scanning. Across age, participants reported more negative affect and showed greater amygdala responses for aversive than neutral stimuli. However, children were generally more sensitive to both neutral and aversive stimuli, as indexed by affective reports and amygdala responses. At the same time, the transition from childhood to adolescence was marked by a ventral-to-dorsal shift in medial prefrontal responses to aversive, but not neutral, stimuli. Given the role that dmPFC plays in executive control and higher-level representations of emotion, these results suggest that adolescence is characterized by a shift towards representing emotional events in increasingly cognitive terms.     

Altered brain activation and connectivity during anticipation of uncertain threat in trait anxiety

In the research field of anxiety, previous studies generally focus on emotional responses following threat. A recent model of anxiety proposes that altered anticipation prior to uncertain threat is related with the development of anxiety. Behavioral findings have built the relationship between anxiety and distinct anticipatory processes including attention, estimation of threat, and emotional responses. However, few studies have characterized the brain organization underlying anticipation of uncertain threat and its role in anxiety. In the present study, we used an emotional anticipation paradigm with functional magnetic resonance imaging (fMRI) to examine the aforementioned topics by employing brain activation and general psychophysiological interactions (gPPI) analysis. In the activation analysis, we found that high trait anxious individuals showed significantly increased activation in the thalamus, middle temporal gyrus (MTG), and dorsomedial prefrontal cortex (dmPFC), as well as decreased activation in the precuneus, during anticipation of uncertain threat compared to the certain condition. In the gPPI analysis, the key regions including the amygdala, dmPFC, and precuneus showed altered connections with distributed brain areas including the ventromedial prefrontal cortex (vmPFC), dorsolateral prefrontal cortex (dlPFC), inferior parietal sulcus (IPS), insula, para‐hippocampus gyrus (PHA), thalamus, and MTG involved in anticipation of uncertain threat in anxious individuals. Taken together, our findings indicate that during the anticipation of uncertain threat, anxious individuals showed altered activations and functional connectivity in widely distributed brain areas, which may be critical for abnormal perception, estimation, and emotion reactions during the anticipation of uncertain threat.     

Emotional brain rhythms and their impairment in post‐traumatic patients

Patients with post‐traumatic stress disorder (PTSD) suffer from a failure of cognitive control over emotional distracters. The physiological substrates of cognitive‐emotional interactions and their breakdown in disease are, however, unknown. Here, we studied brain activity in PTSD patients and healthy controls in response to emotion‐provoking pictures using electroencephalography and functional magnetic resonance imaging (fMRI). We demonstrate that in healthy individuals, emotion‐induced frontal theta rhythm modulates activity in the beta rhythm mainly in sensory‐motor regions. In contrast, in PTSD patients, beta activity is elevated irrespective of emotion, and is not modulated by frontal theta activity in response to negative emotion. EEG source localization and fMRI findings suggest that theta activity is localized to the prefrontal and anterior cingulate cortices while beta activity is localized to sensory‐motor regions. We further found that beta activity in sensory‐motor regions is related to the emotion‐induced slowing of the motor response in healthy controls while the excess frontal theta activity in PTSD is related to the intensity of negative emotional experience. These findings reveal for the first time the importance of brain electrical oscillations and coherence in emotional top‐down modulation and point to specific failure of these mechanisms in PTSD. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

Functional connections between activated and deactivated brain regions mediate emotional interference during externally directed cognition

Recent evidence shows that task‐deactivations are functionally relevant for cognitive performance. Indeed, higher cognitive engagement has been associated with higher suppression of activity in task‐deactivated brain regions ‐ usually ascribed to the Default Mode Network (DMN). Moreover, a negative correlation between these regions and areas actively engaged by the task is associated with better performance. DMN regions show positive modulation during autobiographical, social, and emotional tasks. However, it is not clear how processing of emotional stimuli affects the interplay between the DMN and executive brain regions. We studied this interplay in an fMRI experiment using emotional negative stimuli as distractors. Activity modulations induced by the emotional interference of negative stimuli were found in frontal, parietal, and visual areas, and were associated with modulations of functional connectivity between these task‐activated areas and DMN regions. A worse performance was predicted both by lower activity in the superior parietal cortex and higher connectivity between visual areas and frontal DMN regions. Connectivity between right inferior frontal gyrus and several DMN regions in the left hemisphere was related to the behavioral performance. This relation was weaker in the negative than in the neutral condition, likely suggesting less functional inhibitions of DMN regions during emotional processing. These results show that both executive and DMN regions are crucial for the emotional interference process and suggest that DMN connections are related to the interplay between externally‐directed and internally‐focused processes. Among DMN regions, superior frontal gyrus may be a key node in regulating the interference triggered by emotional stimuli.     

Empathic neural responses to others' pain are modulated by emotional contexts

Recent brain imaging studies indicate that empathy for pain relies upon both the affective and/or the sensorimotor nodes of the pain matrix, and empathic neural responses are modulated by stimulus reality, personal experience, and affective link with others. The current work investigated whether and how empathic neural responses are modulated by emotional contexts in which painful stimulations are perceived. Using functional magnetic resonance imaging (fMRI), we first showed that perceiving a painful stimulation (needle penetration) applied to a face with neutral expression induced activation in the anterior cingulate cortex (ACC) relative to nonpainful stimulation (Q‐tip touch). However, when observation of the painful stimuli delivered to a neutral face was intermixed with observation of painful or happy faces, the ACC activity decreased while the activity in the face area of the secondary somatosensory cortex increased to the painful stimulation. Moreover, the secondary somatosensory activity associated with the painful stimulation decreased when the painful stimulation was applied to faces with happy and painful expressions. The findings suggest that observing painful stimuli in an emotional context weakens affective responses but increases sensory responses to perceived pain and implies possible interactions between the affective and sensory components of the pain matrix during empathy for pain. Hum Brain Mapp 2009. © 2009 Wiley‐Liss, Inc.     

Event-related functional magnetic resonance imaging of reward-related brain circuitry in children and adolescents.

BACKGROUND: Functional disturbances in reward-related brain systems are thought to play a role in the development of mood, impulse, and substance-abuse disorders. Studies in nonhuman primates have identified brain regions, including the dorsal/ventral striatum and orbital-frontal cortex, in which neural activity is modulated by reward. Recent studies in adults have concurred with these findings by observing reward-contingent blood oxygen level-dependent (BOLD) responses in these regions during functional magnetic resonance imaging (fMRI) paradigms; however, no previous studies indicate whether comparable modulations of neural activity exist in the brain reward systems of children and adolescents. METHODS: We used event-related fMRI and a behavioral paradigm modeled on previous work in adults to study brain responses to monetary gains and losses in psychiatrically healthy children and adolescents as part of a program examining the neural substrates of anxiety and depression in youth. RESULTS: Regions and time-courses of reward-related activity were similar to those observed in adults with condition-dependent BOLD changes in the ventral striatum and lateral and medial orbital-frontal cortex; specifically, these regions showed larger responses to positive than to negative feedback. CONCLUSIONS: These results provide further evidence for the value of event-related fMRI in examining reward systems of the brain, demonstrate the feasibility of this approach in children and adolescents, and establish a baseline from which to understand the pathophysiology of reward-related psychiatric disorders in youth.     

Addressing challenges of high spatial resolution UHF fMRI for group analysis of higher‐order cognitive tasks: An inter‐sensory task directing attention between visual and somatosensory domains

Functional MRI at ultra‐high field (UHF, ≥7 T) provides significant increases in BOLD contrast‐to‐noise ratio (CNR) compared with conventional field strength (3 T), and has been exploited for reduced field‐of‐view, high spatial resolution mapping of primary sensory areas. Applying these high spatial resolution methods to investigate whole brain functional responses to higher‐order cognitive tasks leads to a number of challenges, in particular how to perform robust group‐level statistical analyses. This study addresses these challenges using an inter‐sensory cognitive task which modulates top‐down attention at graded levels between the visual and somatosensory domains. At the individual level, highly focal functional activation to the task and task difficulty (modulated by attention levels) were detectable due to the high CNR at UHF. However, to assess group level effects, both anatomical and functional variability must be considered during analysis. We demonstrate the importance of surface over volume normalisation and the requirement of no spatial smoothing when assessing highly focal activity. Using novel group analysis on anatomically parcellated brain regions, we show that in higher cognitive areas (parietal and dorsal‐lateral‐prefrontal cortex) fMRI responses to graded attention levels were modulated quadratically, whilst in visual cortex and VIP, responses were modulated linearly. These group fMRI responses were not seen clearly using conventional second‐level GLM analyses, illustrating the limitations of a conventional approach when investigating such focal responses in higher cognitive regions which are more anatomically variable. The approaches demonstrated here complement other advanced analysis methods such as multivariate pattern analysis, allowing UHF to be fully exploited in cognitive neuroscience.