Michael Brammer

A specific neural substrate for perceiving facial expressions of disgust

Recognition of facial expressions is critical to our appreciation of the social and physical environment, with separate emotions having distinct facial expressions. Perception of fearful facial expressions has been extensively studied, appearing to depend upon the amygdala. Disgust — literally ‘bad taste’ — is another important emotion, with a distinct evolutionary history, and is conveyed by a characteristic facial expression. We have used functional magnetic resonance imaging (fMRI) to examine the neural substrate for perceiving disgust expressions. Normal volunteers were presented with faces showing mild or strong disgust or fear. Cerebral activation in response to these stimuli was contrasted with that for neutral faces. Results for fear generally confirmed previous positron emission tomography findings of amygdala involvement. Both strong and mild expressions of disgust activated anterior insular cortex but not the amygdala; strong disgust also activated structures linked to a limbic cortico–striatal–thalamic circuit. The anterior insula is known to be involved in responses to offensive tastes. The neural response to facial expressions of disgust in others is thus closely related to appraisal of distasteful stimuli.

Global, voxel, and cluster tests, by theory and permutation, for a difference between two groups of structural MR images of the brain

The authors describe almost entirely automated procedures for estimation of global, voxel, and cluster-level statistics to test the null hypothesis of zero neuroanatomical difference between two groups of structural magnetic resonance imaging (MRI) data. Theoretical distributions under the null hypothesis are available for (1) global tissue class volumes; (2) standardized linear model [analysis of variance (ANOVA and ANCOVA)] coefficients estimated at each voxel; and (3) an area of spatially connected clusters generated by applying an arbitrary threshold to a two-dimensional (2-D) map of normal statistics at voxel level. The authors describe novel methods for economically ascertaining probability distributions under the null hypothesis, with fewer assumptions, by permutation of the observed data. Nominal Type I error control by permutation testing is generally excellent; whereas theoretical distributions may be over conservative. Permutation has the additional advantage that it can be used to test any statistic of interest, such as the sum of suprathreshold voxel statistics in a cluster (or cluster mass), regardless of its theoretical tractability under the null hypothesis. These issues are illustrated by application to MRI data acquired from 18 adolescents with hyperkinetic disorder and 16 control subjects matched for age and gender.

Evidence from functional magnetic resonance imaging of crossmodal binding in the human heteromodal cortex

BACKGROUND Integrating information from the different senses markedly enhances the detection and identification of external stimuli. Compared with unimodal inputs, semantically and/or spatially congruent multisensory cues speed discrimination and improve reaction times. Discordant inputs have the opposite effect, reducing performance and slowing responses. These behavioural features of crossmodal processing appear to have parallels in the response properties of multisensory cells in the superior colliculi and cerebral cortex of non-human mammals. Although spatially concordant multisensory inputs can produce a dramatic, often multiplicative, increase in cellular activity, spatially disparate cues tend to induce a profound response depression. RESULTS Using functional magnetic resonance imaging (fMRI), we investigated whether similar indices of crossmodal integration are detectable in human cerebral cortex, and for the synthesis of complex inputs relating to stimulus identity. Ten human subjects were exposed to varying epochs of semantically congruent and incongruent audio-visual speech and to each modality in isolation. Brain activations to matched and mismatched audio-visual inputs were contrasted with the combined response to both unimodal conditions. This strategy identified an area of heteromodal cortex in the left superior temporal sulcus that exhibited significant supra-additive response enhancement to matched audio-visual inputs and a corresponding sub-additive response to mismatched inputs. CONCLUSIONS The data provide fMRI evidence of crossmodal binding by convergence in the human heteromodal cortex. They further suggest that response enhancement and depression may be a general property of multisensory integration operating at different levels of the neuroaxis and irrespective of the purpose for which sensory inputs are combined.

NEURAL RESPONSES TO FACIAL AND VOCAL EXPRESSIONS OF FEAR AND DISGUST

Neuropsychological studies report more impaired responses to facial expressions of fear than disgust in people with amygdala lesions, and vice versa in people with Huntingtons disease. Experiments using functional magnetic resonance imaging (fMRI) have confirmed the role of the amygdala in the response to fearful faces and have implicated the anterior insula in the response to facial expressions of disgust. We used fMRI to extend these studies to the perception of fear and disgust from both facial and vocal expressions. Consistent with neuropsychological findings, both types of fearful stimuli activated the amygdala. Facial expressions of disgust activated the anterior insula and the caudate–putamen; vocal expressions of disgust did not significantly activate either of these regions. All four types of stimuli activated the superior temporal gyrus. Our findings therefore (i) support the differential localization of the neural substrates of fear and disgust; (ii) confirm the involvement of the amygdala in the emotion of fear, whether evoked by facial or vocal expressions; (iii) confirm the involvement of the anterior insula and the striatum in reactions to facial expressions of disgust; and (iv) suggest a possible general role for the perception of emotional expressions for the superior temporal gyrus.

Right inferior prefrontal cortex mediates response inhibition while mesial prefrontal cortex is responsible for error detection

Inhibitory control and error detection are among the highest evolved human self-monitoring functions. Attempts in functional neuroimaging to effectively isolate inhibitory motor control from other cognitive functions have met with limited success. Different brain regions in inferior, mesial, and dorsolateral prefrontal cortices and parietal and temporal lobes have been related to inhibitory control in go/no-go and stop tasks. The widespread activation reflects the fact that the designs used so far have comeasured additional noninhibitory cognitive functions such as selective attention, response competition, decision making, target detection, and inhibition failure. Here we use rapid, mixed trial, event-related functional magnetic resonance imaging to correlate brain activation with an extremely difficult situation of inhibitory control in a challenging stop task that controls for noninhibitory functions. The difficulty of the stop task, requiring withholding of a triggered motor response, was assured by an algorithm that adjusted the task individually so that each subject only succeeded on half of all stop trials, failing on the other half. This design allowed to elegantly separate brain activation related to successful motor response inhibition and to inhibition failure or error detection. Brain activation correlating with successful inhibitory control in 20 healthy volunteers could be isolated in right inferior prefrontal cortex. Failure to inhibit was associated with activation in mesial frontopolar and bilateral inferior parietal cortices, presumably reflecting an attention network for error detection.

A differential pattern of neural response toward sad versus happy facial expressions in major depressive disorder

BACKGROUND Accurate recognition of facial expressions is crucial for social functioning. In depressed individuals, implicit and explicit attentional biases away from happy and toward sad stimuli have been demonstrated. These may be associated with the negative cognitions in these individuals. METHODS Using event-related functional magnetic resonance imaging (fMRI), neural responses to happy and sad facial expressions were measured in 14 healthy individuals and 16 individuals with major depressive disorder. RESULTS Healthy but not depressed individuals demonstrated linear increases in response in bilateral fusiform gyri and right putamen to expressions of increasing happiness, while depressed individuals demonstrated linear increases in response in left putamen, left parahippocampal gyrus/amygdala, and right fusiform gyrus to expressions of increasing sadness. There was a negative correlation in depressed individuals between depression severity and magnitude of neural response within right fusiform gyrus to happy expressions. CONCLUSIONS Our findings indicate preferential increases in neural response to sad but not happy facial expressions in neural regions involved in the processing of emotional stimuli in depressed individuals. These findings may be associated with the above pattern of implicit and explicit attentional biases in these individuals and suggest a potential neural basis for the negative cognitions and social dysfunction in major depression.

Subcortical and ventral prefrontal cortical neural responses to facial expressions distinguish patients with bipolar disorder and major depression

BACKGROUND Bipolar disorder (BD) is characterised by abnormalities in mood and emotional processing, but the neural correlates of these, their relationship to depressive symptoms, and the similarities with deficits in major depressive disorder (MDD) remain unclear. We compared responses within subcortical and prefrontal cortical regions to emotionally salient material in patients with BP and MDD using functional magnetic resonance imaging. METHODS We measured neural responses to mild and intense expressions of fear, happiness, and sadness in euthymic and depressed BD patients, healthy control subjects, and depressed MDD patients. RESULTS Bipolar disorder patients demonstrated increased subcortical (ventral striatal, thalamic, hippocampal) and ventral prefrontal cortical responses particularly to mild and intense fear, mild happy, and mild sad expressions. Healthy control subjects demonstrated increased subcortical responses to intense happy and mild fear, and increased dorsal prefrontal cortical responses to intense sad expressions. Overall, MDD patients showed diminished neural responses to all emotional expressions except mild sadness. Depression severity correlated positively with hippocampal response to mild sadness in both patient groups. CONCLUSIONS Compared with healthy controls and MDD patients, BD patients demonstrated increased subcortical and ventral prefrontal cortical responses to both positive and negative emotional expressions.

Generic brain activation mapping in functional magnetic resonance imaging : A nonparametric approach

We report a novel method to identify brain regions generically activated by periodic experimental design in functional magnetic resonance imaging data. This involves: 1) registering each of N individual functional magnetic resonance imaging datasets in a standard space; 2) computing the median standardised power of response to the experimental design; 3) testing median standardised power at each voxel against its nonparametrically ascertained distribution under the null hypothesis of no experimental effect; and 4) constructing a generic brain activation map. The method is validated by analysis of 6 null images, acquired under conditions when the null hypothesis was known to be true; 8 images acquired during periodic auditory-verbal stimulation; and 6 images acquired during periodic performance of a covert verbal fluency task.

Detection of audio-visual integration sites in humans by application of electrophysiological criteria to the BOLD effect.

Electrophysiological studies in nonhuman primates and other mammals have shown that sensory cues from different modalities that appear at the same time and in the same location can increase the firing rate of multisensory cells in the superior colliculus to a level exceeding that predicted by summing the responses to the unimodal inputs. In contrast, spatially disparate multisensory cues can induce a profound response depression. We have previously demonstrated using functional magnetic resonance imaging (fMRI) that similar indices of crossmodal facilitation and inhibition are detectable in human cortex when subjects listen to speech while viewing visually congruent and incongruent lip and mouth movements. Here, we have used fMRI to investigate whether similar BOLD signal changes are observable during the crossmodal integration of nonspeech auditory and visual stimuli, matched or mismatched solely on the basis of their temporal synchrony, and if so, whether these crossmodal effects occur in similar brain areas as those identified during the integration of audio-visual speech. Subjects were exposed to synchronous and asynchronous auditory (white noise bursts) and visual (B/W alternating checkerboard) stimuli and to each modality in isolation. Synchronous and asynchronous bimodal inputs produced superadditive BOLD response enhancement and response depression across a large network of polysensory areas. The most highly significant of these crossmodal gains and decrements were observed in the superior colliculi. Other regions exhibiting these crossmodal interactions included cortex within the superior temporal sulcus, intraparietal sulcus, insula, and several foci in the frontal lobe, including within the superior and ventromedial frontal gyri. These data demonstrate the efficacy of using an analytic approach informed by electrophysiology to identify multisensory integration sites in humans and suggest that the particular network of brain areas implicated in these crossmodal integrative processes are dependent on the nature of the correspondence between the different sensory inputs (e.g. space, time, and/or form).

The anatomy of conscious vision: an fMRI study of visual hallucinations

Despite recent advances in functional neuroimaging, the apparently simple question of how and where we see—the neurobiology of visual consciousness—continues to challenge neuroscientists. Without a method to differentiate neural processing specific to consciousness from unconscious afferent sensory signals, the issue has been difficult to resolve experimentally. Here we use functional magnetic resonance imaging (fMRI) to study patients with the Charles Bonnet syndrome, for whom visual perception and sensory input have become dissociated. We found that hallucinations of color, faces, textures and objects correlate with cerebral activity in ventral extrastriate visual cortex, that the content of the hallucinations reflects the functional specializations of the region and that patients who hallucinate have increased ventral extrastriate activity, which persists between hallucinations.