Neural Basis of Genetically Determined Visuospatial Construction Deficit in Williams Syndrome

Meyer‐Lindenberg, Andreas; Kohn, Philip D.; Mervis, Carolyn Β.; Kippenhan, J. Shane; Olsen, Rosanna K.; Morris, Colleen A.; Berman, Karen F.

doi:10.1016/j.neuron.2004.08.014

Cited by 276 publications

(355 citation statements)

References 40 publications

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“…These include the hippocampal formation, IPL, amygdala, and OFC (12,14,17,20,(23)(24)(25)(26)(27)(28)30). Such transmodal cortical systems (51) are composed of subregionally specialized and highly interconnected heteromodal, paralimbic, and limbic cortices (51)(52)(53).…”

Section: Discussionmentioning

confidence: 99%

“…These mouse studies also documented alterations in fear response [for both LIMK1 and GTF2IRD1 (20,22)] and reduced aggression [for GTF2IRD1 (22)]. In parallel with these preclinical observations, research on the neural mechanisms underlying WS-specific behavioral characteristics has identified functional and structural alterations of the intraparietal sulcus (12,(23)(24)(25)(26), hippocampal formation (27), amygdala, and orbitofrontal cortex (OFC) (12,17,28), and aberrant orbitofrontal circuitry has been associated with the syndrome's distinctive pattern of emotional processing: remarkable lack of social fear coupled with a high incidence of nonsocial anxieties and phobias (17,29,30).…”

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confidence: 91%

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The Williams syndrome chromosome 7q11.23 hemideletion confers hypersocial, anxious personality coupled with altered insula structure and function

Jabbi

Kippenhan

Kohn

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Although it is widely accepted that genes can influence complex behavioral traits such as human temperament, the underlying neurogenetic mechanisms remain unclear. Williams syndrome (WS), a rare disorder caused by a hemizygous deletion on chromosome 7q11.23, including genes important for neuronal migration and maturation (LIMK1 and CLIP2), is typified by a remarkable hypersocial but anxious personality and offers a unique opportunity to investigate this open issue. Based on the documented role of the insula in mediating emotional response tendencies and personality, we used multimodal imaging to characterize this region in WS and found convergent anomalies: an overall decrease in dorsal anterior insula (AI) gray-matter volume along with locally increased volume in the right ventral AI; compromised white-matter integrity of the uncinate fasciculus connecting the insula with the amygdala and orbitofrontal cortex; altered regional cerebral blood flow in a pattern reminiscent of the observed gray-matter alterations (i.e., widespread reductions in dorsal AI accompanied by locally increased regional cerebral blood flow in the right ventral AI); and disturbed neurofunctional interactions between the AI and limbic regions. Moreover, these genetically determined alterations of AI structure and function predicted the degree to which the atypical WS personality profile was expressed in participants with the syndrome. The AI's rich anatomical connectivity, its transmodal properties, and its involvement in the behaviors affected in WS make the observed genetically determined insular circuitry perturbations and their association with WS personality a striking demonstration of the means by which neural systems can serve as the interface between genetic variability and alterations in complex behavioral traits.brain | genetics | copy number variant | MRI | PET

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 91%

The Williams syndrome chromosome 7q11.23 hemideletion confers hypersocial, anxious personality coupled with altered insula structure and function

Jabbi

Kippenhan

Kohn

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

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“…Our methods for model fitting, selection and evaluation have been described previously. 42 Briefly, models were fitted from eigenvariates 43 using the software package Mx (http://www.vcu.edu/mx/). Activity from vmPFC, perigenual cingulate and bilateral amygdala was extracted from anatomical masks for all male participants.…”

Section: Functional Connectivity Analysesmentioning

confidence: 99%

Genetic variation in MAOA modulates ventromedial prefrontal circuitry mediating individual differences in human personality

Buckholtz¹,

Callicott²,

Kolachana³

et al. 2007

Mol Psychiatry

198

170

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Little is known about neural mechanisms underlying human personality and temperament, despite their considerable importance as highly heritable risk mediators for somatic and psychiatric disorders. To identify these circuits, we used a combined genetic and imaging approach focused on Monoamine Oxidase A (MAOA), encoding a key enzyme for monoamine metabolism previously associated with temperament and antisocial behavior. Male carriers of a low-expressing genetic variant exhibited dysregulated amygdala activation and increased functional coupling with ventromedial prefrontal cortex (vmPFC). Stronger coupling predicted increased harm avoidance and decreased reward dependence scores, suggesting that this circuitry mediates a part of the association of MAOA with these traits. We utilized path analysis to parse the effective connectivity within this system, and provide evidence that vmPFC regulates amygdala indirectly by influencing rostral cingulate cortex function. Our data implicate a neural circuit for variation in human personality under genetic control, provide an anatomically consistent mechanism for vmPFC-amygdala interactions underlying this variation, and suggest a role for vmPFC as a superordinate regulatory area for emotional arousal and social behavior.

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“…areas of increased cell packing, neuronal size differences), when compared to control brains. MRI studies report increased gyrification (cortical folding) in WS in the right parietal and occipital lobes (Schmitt et al, 2002), and a disproportionate reduction in parietaloccipital regions (Meyer-Lindenberg et al, 2004;Reiss et al, 2000;. At a functional level, ERP investigation has shown that individuals with WS can group by closure, but that this is associated with deviant neural processing in the temporaloccipital areas (Grice et al, 2003).…”

Section: Experimental Trialsmentioning

confidence: 99%

Perceptual grouping and distance estimates in typical and atypical development: Comparing performance across perception, drawing and construction tasks

Farran

Cole

2008

Brain and Cognition

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Perceptual grouping is a pre-attentive process which serves to group local elements into global wholes, based on shared properties. One effect of perceptual grouping is to distort the ability to estimate the distance between two elements. In this study, biases in distance estimates, caused by four types of perceptual grouping, were measured across three tasks, a perception, a drawing and a construction task in both typical development (TD; Experiment 1) and in individuals with Williams syndrome (WS; Experiment 2). In Experiment 1, perceptual grouping distorted distance estimates across all three tasks. Interestingly, the effect of grouping by luminance was in the opposite direction to the effects of the remaining grouping types. We relate this to differences in the ability to inhibit perceptual grouping effects on distance estimates. Additive distorting influences were also observed in the drawing and the construction task, which are explained in terms of the points of reference employed in each task. Experiment 2 demonstrated that the above distortion effects are also observed in WS. Given the known deficit in the ability to use perceptual grouping in WS, this suggests a dissociation between the pre-attentive influence of and the attentive deployment of perceptual grouping in WS. The typical distortion in relation to drawing and construction points towards the presence of some typical location coding strategies in WS. The performance of the WS group differed from the TD participants on two counts. First, the pattern of overall distance estimates (averaged across interior and exterior distances) across the four perceptual grouping types, differed between groups. Second, the distorting influence of perceptual grouping was strongest for grouping by shape similarity in WS, which contrasts to a strength in grouping by proximity observed in the TD participants.

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Neural Basis of Genetically Determined Visuospatial Construction Deficit in Williams Syndrome

Cited by 276 publications

References 40 publications

The Williams syndrome chromosome 7q11.23 hemideletion confers hypersocial, anxious personality coupled with altered insula structure and function

The Williams syndrome chromosome 7q11.23 hemideletion confers hypersocial, anxious personality coupled with altered insula structure and function

Genetic variation in MAOA modulates ventromedial prefrontal circuitry mediating individual differences in human personality

Perceptual grouping and distance estimates in typical and atypical development: Comparing performance across perception, drawing and construction tasks

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