Elisabeth A H von dem Hagen

MRC Cognition and Brain Sciences Unit, Cambridge, England, United Kingdom

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Publications (10)59.05 Total impact

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    ABSTRACT: Eye contact plays a key role in social interaction and is frequently reported to be atypical in individuals with autism spectrum conditions (ASCs). Despite the importance of direct gaze, previous functional magnetic resonance imaging in ASC has generally focused on paradigms using averted gaze. The current study sought to determine the neural processing of faces displaying direct and averted gaze in 18 males with ASC and 23 matched controls. Controls showed an increased response to direct gaze in brain areas implicated in theory-of-mind and gaze perception, including medial prefrontal cortex, temporoparietal junction, posterior superior temporal sulcus region, and amygdala. In contrast, the same regions showed an increased response to averted gaze in individuals with an ASC. This difference was confirmed by a significant gaze direction × group interaction. Relative to controls, participants with ASC also showed reduced functional connectivity between these regions. We suggest that, in the typical brain, perceiving another person gazing directly at you triggers spontaneous attributions of mental states (e.g. he is "interested" in me), and that such mental state attributions to direct gaze may be reduced or absent in the autistic brain.
    Cerebral Cortex 01/2013; · 6.83 Impact Factor
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    ABSTRACT: Albinism, in humans and many animal species, has a major impact on the visual system, leading to reduced acuity, lack of binocular function and nystagmus. In addition to the lack of a foveal pit, there is a disruption to the routing of the nerve fibers crossing at the optic chiasm, resulting in excessive crossing of fibers to the contralateral hemisphere. However, very little is known about the effect of this misrouting on the structure of the post-chiasmatic visual pathway, and the occipital lobes in particular. Whole-brain analyses of cortical thickness in a large cohort of subjects with albinism showed an increase in cortical thickness, relative to control subjects, particularly in posterior V1, corresponding to the foveal representation. Furthermore, mean cortical thickness across entire V1 was significantly greater in these subjects compared to controls and negatively correlated with visual acuity in albinism. Additionally, the group with albinism showed decreased gyrification in the left ventral occipital lobe. While the increase in cortical thickness in V1, also found in congenitally blind subjects, has been interpreted to reflect a lack of pruning, the decreased gyrification in the ventral extrastriate cortex may reflect the reduced input to the foveal regions of the ventral visual stream.
    Cortex 09/2012; · 6.16 Impact Factor
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    Elisabeth A H von dem Hagen, Raliza S Stoyanova, Simon Baron-Cohen, Andrew J Calder
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    ABSTRACT: Individuals with Autism Spectrum Conditions (ASC) have difficulties in social interaction and communication, which is reflected in hypoactivation of brain regions engaged in social processing, such as medial prefrontal cortex (mPFC), amygdala and insula. Resting state studies in ASC have identified reduced connectivity of the default mode network (DMN), which includes mPFC, suggesting that other resting state networks incorporating 'social' brain regions may also be abnormal. Using Seed-based Connectivity and Group Independent Component Analysis (ICA) approaches, we looked at resting functional connectivity in ASC between specific 'social' brain regions, as well as within and between whole networks incorporating these regions. We found reduced functional connectivity within the DMN in individuals with ASC, using both ICA and seed-based approaches. Two further networks identified by ICA, the salience network, incorporating the insula and a medial temporal lobe network, incorporating the amygdala, showed reduced inter-network connectivity. This was underlined by reduced seed-based connectivity between the insula and amygdala. The results demonstrate significantly reduced functional connectivity within and between resting state networks incorporating 'social' brain regions. This reduced connectivity may result in difficulties in communication and integration of information across these networks, which could contribute to the impaired processing of social signals in ASC.
    Social Cognitive and Affective Neuroscience 05/2012; · 5.04 Impact Factor
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    ABSTRACT: The developmental taxonomic theory proposes that neurodevelopmental factors play a critical role in the etiology of early-onset conduct disorder, whereas adolescent-onset conduct disorder arises as a result of social mimicry of deviant peers. Recent studies have challenged this theory by demonstrating that adolescents with both early- and adolescent-onset forms of conduct disorder show impaired emotional learning and abnormal neural activation during facial expression processing. The present study extends this work by investigating brain structure in both subtypes of conduct disorder. Voxel-based morphometry was used to compare gray matter volumes in four regions of interest (amygdala, insula, anterior cingulate, and orbitofrontal cortex) in male adolescents with early-onset (N=36) or adolescent-onset (N=27) conduct disorder and in healthy comparison subjects (N=27). Whole-brain structural analyses were also performed. The combined conduct disorder group displayed gray matter volume reductions in the bilateral amygdala, extending into the insula, relative to healthy comparison subjects. Separate comparisons between healthy subjects and each conduct disorder subgroup revealed lower amygdala volume in both subgroups and reduced right insula volume in the adolescent-onset subgroup. Regression analyses within the conduct disorder subjects alone demonstrated a negative correlation between conduct disorder symptoms and right insula volume. The results demonstrate that gray matter volume reductions in brain regions involved in processing socioemotional stimuli are associated with conduct disorder, regardless of age of onset. Brain structural abnormalities may contribute to the emergence of adolescent-onset as well as early-onset conduct disorder.
    American Journal of Psychiatry 03/2011; 168(6):624-33. · 14.72 Impact Factor
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    ABSTRACT: Previous research has found that a common polymorphism in the serotonin transporter gene (5-HTTLPR) is an important mediator of individual differences in brain responses associated with emotional behaviour. In particular, relative to individuals homozygous for the l-allele, carriers of the s-allele display heightened amygdala activation to emotional compared to non-emotional stimuli. However, there is some debate as to whether this difference is driven by increased activation to emotional stimuli, resting baseline differences between the groups, or decreased activation to neutral stimuli. We performed functional imaging during an implicit facial expression processing task in which participants viewed angry, sad and neutral faces. In addition to neutral faces, we included two further baseline conditions, houses and fixation. We found increased amygdala activation in s-allele carriers relative to l-homozygotes in response to angry faces compared to neutral faces, houses and fixation. When comparing neutral faces to houses or fixation, we found no significant difference in amygdala response between the two groups. In addition, there was no significant difference between the groups in response to fixation when compared with a houses baseline. Overall, these results suggest that the increased amygdala response observed in s-allele carriers to emotional faces is primarily driven by an increased response to emotional faces rather than a decreased response to neutral faces or an increased resting baseline. The results are discussed in relation to the tonic and phasic hypotheses of 5-HTTLPR-mediated modulation of amygdala activity.
    Neuropsychologia 12/2010; 49(4):674-80. · 3.48 Impact Factor
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    ABSTRACT: Autism spectrum disorders (ASDs) are typically characterized by impaired social interaction and communication, narrow interests, and repetitive behaviors. The heterogeneity in the severity of these characteristics across individuals with ASD has led some researchers to suggest that these disorders form a continuum which extends into the general, or "typical," population, and there is growing evidence that the extent to which typical adults display autistic traits, as measured using the autism-spectrum quotient (AQ), predicts performance on behavioral tasks that are impaired in ASD. Here, we show that variation in autism spectrum traits is related to cortical structure and function within the typical population. Voxel-based morphometry showed that increased AQ scores were associated with decreased white matter volume in the posterior superior temporal sulcus (pSTS), a region important in processing socially relevant stimuli and associated with structural and functional impairments in ASD. In addition, AQ was correlated with the extent of cortical deactivation of an adjacent area of pSTS during a Stroop task relative to rest, reflecting variation in resting state function. The results provide evidence that autism spectrum characteristics are reflected in neural structure and function across the typical (non-ASD) population.
    Cerebral Cortex 05/2010; 21(3):493-500. · 6.83 Impact Factor
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    ABSTRACT: Previous research has implicated regions of anterior insula/frontal operculum in processing conspecific facial expressions of disgust. It has been suggested however that there are a variety of disgust facial expression components which relate to the disgust-eliciting stimulus. The nose wrinkle is predominantly associated with irritating or offensive smells, the mouth gape and tongue extrusion with distaste and oral irritation, while a broader range of disgust elicitors including aversive interpersonal contacts and certain moral offenses are associated primarily with the upper lip curl. Using functional magnetic resonance imaging, we show that activity in the anterior insula/frontal operculum is seen only in response to canonical disgust faces, exhibiting the nose wrinkle and upper lip curl, and not in response to distaste facial expressions, exhibiting a mouth gape and tongue protrusion. Canonical disgust expressions also result in activity in brain regions linked to social cognition more broadly, including dorsal medial prefrontal cortex, posterior cingulate cortex, temporo-parietal junction and superior temporal sulcus. We interpret these differences in relation to the relative functional and communicative roles of the different disgust expressions and suggest a significant role for appraisal processes in the insula activation to facial expressions of disgust.
    Social Cognitive and Affective Neuroscience 07/2009; 4(4):379-86. · 5.04 Impact Factor
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    Elisabeth A H von dem Hagen, Michael B Hoffmann, Antony B Morland
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    ABSTRACT: To compare VEP and fMRI as a means of detecting the abnormal visual projections in albinism in different stimulation conditions. Cortical response to monocular full-field pattern-onset and hemifield pattern-onset and -reversal stimulation of 18 subjects with a known diagnosis of albinism, 17 control subjects, and 6 control subjects with infantile nystagmus syndrome (INS) was determined by VEP and fMRI. An asymmetry index was used to quantify the extent of response lateralization as measured by both VEP and fMRI. The extent to which each method and stimulus combination differentiated participant groups was summarized with a receiver operating characteristic (ROC) analysis, where A(A-C) and A(A-N) refer to areas under the ROC curve for albino versus control and albino versus nystagmus comparisons. Cortical response to full-field monocular stimulation conditions offered robust detection of the abnormal response lateralization in albinism, with fMRI (A(A-C) = 1.00; A(A-N) = 0.91) being slightly more robust than the VEP under these conditions (A(A-C) = 0.91; A(A-N) = 0.79). Hemifield stimulation paradigms were somewhat poorer at differentiating between groups, particularly when VEP was used in combination with pattern-reversal stimulation (pattern-onset fMRI A(A-C) = 0.94, A(A-N) = 0.84, and VEP A(A-C) = 0.86, A(A-N) = 0.86; pattern-reversal fMRI A(A-C) = 0.90, A(A-N) = 0.88, and VEP A(A-C) = 0.69, A(A-N) = 0.64). However, when only the most posterior aspects of the occipital lobe were considered with hemifield stimulation, fMRI achieved the best differentiation between the subject groups, most notably with hemifield pattern-reversal stimulation (A(A-C) = 1.00; A(A-N) = 1.00). An interocular comparison between the lateralization of cortical responses elicited by full-field stimulation reliably distinguished between those with albinism and control groups, when both fMRI and VEP were used to assess cortical responses. Hemifield stimulation of one eye offers an alternative method for assessing misrouting associated with albinism and is highly effective when cortical signals are assessed with fMRI, but less so when VEP is used.
    Investigative Ophthalmology &amp Visual Science 02/2008; 49(1):238-49. · 3.44 Impact Factor
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    Elisabeth A H von dem Hagen, Gavin C Houston, Michael B Hoffmann, Antony B Morland
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    ABSTRACT: In albinism a large proportion of nerve fibres originating in temporal retina cross the midline at the chiasm and project to the contralateral hemisphere. Studies in rodents with albinism have suggested that the extent of this misrouting at the chiasm is inversely related to pigmentation levels. Here, we examine whether there is evidence for a similar relationship in humans with albinism. Functional MRI was performed on 18 subjects with albinism, 17 control subjects and six controls with nystagmus as they underwent hemifield visual stimulation of nasal or temporal retina. Functional activation in 16 coronal slices beginning at the posterior occipital lobes were analysed and the extent of hemispheric response lateralization at each slice position was determined. During temporal retina stimulation, the control response was lateralized to the hemisphere ipsilateral to the stimulated eye for all slices. In albinos, the response in posterior slices was predominantly in the contralateral hemisphere, consistent with misrouting of temporal retina fibres. However, as slice location became progressively anterior, response lateralization reverted to the ipsilateral hemisphere. The slice location at which the transition from contra- to ipsilateralization occurred provided an estimate of the extent of fibre misrouting in the individual. The slice transition location correlated negatively with pigmentation level, providing the first evidence for a relationship between pigmentation and the extent of misrouting in humans with albinism.
    European Journal of Neuroscience 02/2007; 25(2):503-11. · 3.75 Impact Factor
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    ABSTRACT: Albinism is a genetic condition associated with abnormalities of the visual system. Defects in melanin production cause underdevelopment of the fovea, reduced retinal cell numbers and abnormal routing of ganglion cell nerve fibres at the optic chiasm. We examined 19 subjects with albinism and 26 control subjects to determine whether retinal abnormalities affect the structure of the visual cortex. Whole-brain, high-resolution anatomical magnetic resonance imaging volumes from each subject were obtained on a 1.5-T scanner and segmented into grey and white matter. A voxel-wise statistical comparison of grey and white matter volumes in the occipital lobes between the two groups was performed using voxel-based morphometry. Our analysis revealed a regionally specific decrease in grey matter volume at the occipital poles in albinism. The location of the decrease in grey matter corresponds to the cortical representation of the central visual field. This reduction is likely to be a direct result of decreased ganglion cell numbers in central retina in albinism.
    European Journal of Neuroscience 12/2005; 22(10):2475-80. · 3.75 Impact Factor

Publication Stats

145 Citations
59.05 Total Impact Points


  • 2009–2013
    • MRC Cognition and Brain Sciences Unit
      Cambridge, England, United Kingdom
  • 2012
    • Oxford University Hospitals NHS Trust
      Oxford, England, United Kingdom
  • 2011–2012
    • University of Cambridge
      • • MRC Cognition and Brain Sciences Unit
      • • Department of Psychology
      Cambridge, ENG, United Kingdom
  • 2008
    • The University of York
      • Department of Psychology
      York, ENG, United Kingdom
  • 2005–2007
    • Royal Holloway, University of London
      • Department of Psychology
      London, ENG, United Kingdom