**5. Conclusion**

We have shown that more than half of patients with ALS have unusual response patterns on a paradigm asking participants to judge the approachability of unfamiliar faces, suggesting amygdala dysfunction. Performance on this task did not correlate with frontal-executive dysfunction on cognitive testing. Patients also had significantly reduced semantic fluency suggesting involvement of the temporal cortex. Disease involvement outside the motor cortex in ALS is common, and can manifest as frontal, temporal or frontal and temporal dysfunction. Further studies need to be done to clarify the relationship between histopathological subtypes and cognitive patterns.

### **6. References**


finding in the amygdala (e.g., Yamazaki et al., 2000). Case series of sporadic ALS patients with and without dementia have demonstrated ubiquitinated intraneuronal inclusions and spongiform changes in the neostriatum, the amygdala and the parahippocampal gyrus, as well as the temporal pole, anterior cingulate, orbitofrontal cortex and insula (Kawashima et

We assume that the cognitive findings of decreased semantic fluency and abnormal approachability are the clinical correlate of the changes seen neuroradiologically and neuropathologically and suggest that many ALS patients may, in fact, have both clinically

Performance on the Approachability Paradigm was not related to frontal dysfunction. A similar lack of correlation between amygdala dysfunction and frontal cognitive changes was reported by Zimmerman and colleagues (2007). In their study, among the 8 patients with emotional perceptual impairment, one-half did not have depressive, or memory or cognitive symptoms on screening, whereas the remainder showed dementia symptoms alone or together with depressive symptoms. This finding is important in two ways: First, it suggests the response pattern seen in ALS patients in both studies was in fact due to amygdala involvement as hypothesized and was less likely to be the result of frontal dysfunction Second, FTLD is known to have several subtypes with variable sites of onset, all of which can be seen in conjunction with ALS. Thus, it is not surprising to find that amygdala dysfunction and frontal dysfunction are not associated. It may be that there are groups of ALS patients that have predominantly temporal dysfunction at onset, while other groups have predominantly frontal onset. This also suggests that more ALS patients have clinical involvement outside the motor strip than the rough estimate of 50% percent from prior

We have shown that more than half of patients with ALS have unusual response patterns on a paradigm asking participants to judge the approachability of unfamiliar faces, suggesting amygdala dysfunction. Performance on this task did not correlate with frontal-executive dysfunction on cognitive testing. Patients also had significantly reduced semantic fluency suggesting involvement of the temporal cortex. Disease involvement outside the motor cortex in ALS is common, and can manifest as frontal, temporal or frontal and temporal dysfunction. Further studies need to be done to clarify the relationship between

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