Elsevier

Biological Psychiatry

Volume 72, Issue 1, 1 July 2012, Pages 70-77
Biological Psychiatry

Archival Report
Fear Processing and Social Networking in the Absence of a Functional Amygdala

https://doi.org/10.1016/j.biopsych.2011.11.024Get rights and content

Background

The human amygdala plays a crucial role in processing social signals, such as face expressions, particularly fearful ones, and facilitates responses to them in face-sensitive cortical regions. This contributes to social competence and individual amygdala size correlates with that of social networks. While rare patients with focal bilateral amygdala lesion typically show impaired recognition of fearful faces, this deficit is variable, and an intriguing possibility is that other brain regions can compensate to support fear and social signal processing.

Methods

To investigate the brain's functional compensation of selective bilateral amygdala damage, we performed a series of behavioral, psychophysiological, and functional magnetic resonance imaging experiments in two adult female monozygotic twins (patient 1 and patient 2) with equivalent, extensive bilateral amygdala pathology as a sequela of lipoid proteinosis due to Urbach-Wiethe disease.

Results

Patient 1, but not patient 2, showed preserved recognition of fearful faces, intact modulation of acoustic startle responses by fear-eliciting scenes, and a normal-sized social network. Functional magnetic resonance imaging revealed that patient 1 showed potentiated responses to fearful faces in her left premotor cortex face area and bilaterally in the inferior parietal lobule.

Conclusions

The premotor cortex face area and inferior parietal lobule are both implicated in the cortical mirror-neuron system, which mediates learning of observed actions and may thereby promote both imitation and empathy. Taken together, our findings suggest that despite the pre-eminent role of the amygdala in processing social information, the cortical mirror-neuron system may sometimes adaptively compensate for its pathology.

Section snippets

Methods and Materials

Background information on Urbach-Wiethe disease and a detailed synopsis of all experimental procedures are provided in Supplement 1.

Molecular Genetics

The twins showed the same genotype in all sequenced regions. We found a novel homozygous missense mutation in exon 7 of ECM1, resulting in an exchange of tryptophan to arginine: c.709T>C; p.W237R (Figure S1 in Supplement 1). The alignment of proteins belonging to the ECM1 family confirmed that tryptophan 237 is highly conserved, thus underlining the potential pathogenic relevance of the p.W237R mutation (Figure S2 in Supplement 1).

Structural Imaging

The extracted volumes of interest did not significantly differ

Discussion

There is extensive evidence that patients with focal bilateral amygdala lesions are impaired in recognizing fear from faces (8, 9) and lack any subjective experience of fear ([6], but see [7]). However, substantial interindividual variability in the extent of these impairments (10) suggests the emergence of functional compensation to pathology in at least some amygdala-damaged patients. Here, we demonstrate a potential compensatory mechanism in one of monozygotic adult female twins with LP and

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    Authors BB, YM, and DS contributed equally to this work.

    Authors KMK and JSF contributed equally to this work.

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