Processing facial emotions in adults with velo-cardio-facial syndrome: functional magnetic resonance imaging

We studied the functional neuroanatomy of social behaviour in velo-cardio-facial syndrome (VCFS) using a facial emotionalprocessing task and functional magnetic resonance imaging inadults with this syndrome and controls matched for age andIQ. The VCFS group had less activation in the right insulaand frontal brain regions and more activation in occipital regions.Genetically determined abnormalities in pathways including those involved in emotional processing may underlie deficitsin socialcognition in people with VCFS.

INTRODUCTION

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INTRODUCTION

Velo-cardio-facial syndrome (VCFS) is associated with intellectual impairments and with IQ-independent deficits in visuoperceptualfunction and social and abstract reasoning (Henry et al, 2002).These deficits may underlie the social impairments of VCFS(Swillen et al, 1997). Facial expressions are important socialcues. As explicit processing of facial emotions is positivelycorrelated with IQ and involves higher cognitive processes(Kroeger et al, 2001), we used functional magnetic resonanceimaging (fMRI) to investigate implicit processing, which involves(para)limbic areas in an automatic, attention-independent manner (Critchley et al, 2000). We predicted that compared with controls,people with VCFS have less activation of brain regions normallyactivated during implicit emotional processing (the amygdala,insula and frontal cortex).

METHOD

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METHOD

Our sample included eight right-handed adults – sevenwomen and one man (mean age 34 years, s.d.=9; mean IQ 72, s.d.=10),three of whom had schizophrenia and five had no mental illness– with clinical features of VCFS and a 22q11 deletionconfirmed by fluorescence in situ hybridisation (Oncor Inc.,Gaithersburg, Maryland, USA). Our control group comprised ninehealthy individuals (five women and four men; mean age 37 years,s.d.=11, mean IQ 73, s.d.=16). Details of inclusion criteria, recruitment methods and psychiatric and neuropsychologicalassessments are described elsewhere (Murphy et al, 1999; van Amelsvoort et al, 2004).The control group did not differ significantly in age, IQ andgender from the VCFS group. The study was approved by the local research ethics committee. Written informed consent was obtainedfrom all participants (or their guardians).

All participants were familiarised with the scanner and thetask. Ten blocks of eight facial stimuli from the Ekman series (Ekman & Friesen, 1975) were used, as described previouslyby Critchley et al (2000). The participants viewed a pseudo-randomisedmixture of happy or angry (‘on’ phase) and neutral(‘off’ phase) facial expressions, with instructionsto attend to and judge the gender of each face. During thistask 100 T₂*-weighted echoplanar images, depicting blood oxygenationlevel-dependent contrast (14 non-continuous slices, thickness7 mm (gap 0.7 mm), inplane resolution 3.1 mm, echo time (TE)40 ms, repetition time (TR) 3000 ms), and one T₁-weighted whole-brainanatomical image (43 continuous slices, thickness 3 mm, in-planeresolution 1.5 mm, TE=73 ms, TR=1600 ms) were acquired usinga 1.5 T GE Signa System 7(General Electric, Milwaukee, Wisconsin,USA). Data were analysed using Statistical Parametric Mapping99 (http://www.fil.ion.ucl.ac.uk/spm). Functional images weremovement corrected, normalised into standard space and smoothedwith 12 mm full width at half maximum gaussian kernel priorto statistical comparisons. Condition-specific task effectswere assessed by comparing the ‘on’ phases of eachtask with their respective ‘off’ condition. Changesin regional blood flow were determined by applying the generallinear model. Between-group comparisons of brain activationpatterns were performed using t statistics. The resulting statisticalparametric (SPM (t)) maps were transformed to SPM {Z} values.

RESULTS

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RESULTS

Participants were task-compliant, and debriefed after scanning.Responses were made in the required time window, and therewas no group difference in task performance. Between-groupanalysis revealed an anterior–posterior dichotomy inactivation patterns during emotional processing (on>off). Compared with the control group, the VCFS group showed lessactivity in the right insula and frontal regions. In contrast,people with VCFS had more activity in bilateral occipital regions (Table 1).

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Table 1 Between-group differences in brain activity during emotional processing task in the velo-cardio-facial syndrome group (n=8) compared with IQ-matched controls (n=9)

DISCUSSION

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DISCUSSION

To our knowledge this is the first fMRI study investigatingfacial emotional processing in VCFS. Compared with controls,people with VCFS had more activation of the bilateral occipitalbrain regions involved in early visual processing (includingface perception) (Haxby et al, 2002). In contrast, peoplewith VCFS showed less activation in the right insula and premotorcortex – areas implicated in emotional processing (Critchley et al, 2000;Haxby et al, 2002).

The neural network mediating face perception includes a ‘core system’ for visual face analysis, in which occipitalgyri provide input into fusiform and superior temporal regions.These then interact with an extended system (e.g. amygdala,insula, limbic system) to process the meaning of information(including emotions) from faces (Haxby et al, 2002). Ventralstream disruption could be one explanation for social impairmentsin VCFS (Lajiness-O’Neill et al, 2005). Moreover, adultswith VCFS perform poorly on object perception tasks (relyingon the ventral ‘what’ pathway), whereas they performbetter on space perception tasks (relying on the dorsal ‘where’pathway) (Henry et al, 2002). Our results suggest that in VCFSthe pathways between ‘face perception’ areas andthe extended ventral ‘what’ pathway for processingemotional expressions may be dysfunctional.

A consistent finding in face expression neuroimaging researchis increased extrastriate activation in association with facialemotional expressions. Hence, our results may also reflectgreater modulation of visual cortices by emotional faces inVCFS compared with controls, with downstream areas involved in attributing the social significance of faces being hypoactive.Hence, people with VCFS may show normal or enhanced affectiveresponses to facial expressions (intact affective empathy),but an impaired ability to identify the social and contextualsignificance of socioemotional cues (impaired cognitive empathy).This could partially explain why people with VCFS have highlevels of anxiety and affective symptoms.

In our between-group analysis, we observed an anterior–posterior dichotomy in brain activation patterns. This dichotomy hasbeen reported previously in anatomical studies of VCFS (Kates et al, 2001) and might be partially explained by dysmaturation of white-mattertracts in this syndrome (van Amelsvoort et al, 2004). White-matterintegrity is associated with better performance on cognitivetasks; for example, improvement in working memory is associatedwith increased frontal fractional anisotropy (Nagy et al, 2004). Thus, people with VCFS may need to activate occipital brainregions more in order to process visual stimuli, owing to reducedwhite-matter integrity or connectivity. This ‘compensation’hypothesis is supported by the findings of Eliez et al (2001),who reported increased activation in parietal regions of childrenwith VCFS compared with controls during mathematical reasoning.

Limitations of our study include the use of a block design includingboth ‘happy’ and ‘angry’ faces; weare therefore unable to comment on brain activations to separateemotions or neutral faces. Event-related fMRI is needed toevaluate this. Our results did not survive correction for multiplecomparisons and should be interpreted as preliminary. Men andwomen were included in the study, but there was no differencein gender distribution. Inclusion in the VCFS group of threepeople receiving medication for psychosis could have confoundedour results. Given the high prevalence of psychiatric disordersin VCFS, however, a population without any psychiatric problemis rare.

In summary, the results of our preliminary study of emotionalprocessing in VCFS suggest that social impairments in thissyndrome may be associated with abnormal connectivity betweenearly visual processing areas and limbic brain regions.

REFERENCES

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