Modulatory Influences of Negative and Positive Emotion on the Acoustic Startle Eyeblink Reflex: An Examination of their Neural and Behavioral Correlates in Patients with Neurodegenerative Disease

The startle reflex is a primitive defensive response. Research has shown that the strength of its expression varies as a function of the organism's internal state. The startle response is enhanced in the context of negative emotions (negative-potentiation) and inhibited in the context of positive emotions (positive-attenuation). Based on animal studies, emotional influences on startle responding are thought to be mediated by subcortical systems in the brain (e.g., amygdala and nucleus accumbens). However, the neuroanatomical basis for the emotion modulated startle not been well-characterized in humans. Furthermore, researchers have not examined the consequences of impairments in the emotion modulated startle for functioning in everyday life. The present study attempted to clarify these issues.The neuroanatomical and real-world behavioral correlates of the emotion modulated startle were examined in patients with neurodegenerative disease, who display a range of impairments in both the brain and behavior. The patient group primarily consisted of patients with frontotemporal lobar degeneration, a disease that causes profound changes in social and emotional functioning, and which selectively targets frontal, temporal, and subcortical systems in the brain - regions that have been implicated in the emotion modulated startle. A smaller group of patients with Alzheimer's disease was included to determine whether findings generalized to patients with more posterior neural atrophy. Finally, neurologically healthy controls were included to ensure that the typical emotion modulated startle pattern was obtained using the procedures applied in this study.Participants viewed a series of negative, neutral, and positive pictures, and were intermittently exposed to a 105 dB acoustic startle stimulus while the magnitude of their startle eyeblink reflex was measured. Negative-potentiation and positive-attenuation scores were related to three brain regions of interest in the right- and left- hemisphere: the amygdala, nucleus accumbens, and orbitofrontal cortex (OFC). Finally, emotion modulation scores were related to caregiver-ratings of behavioral disturbance seen in patients' everyday lives.The control group displayed the typical startle modulation pattern, with the largest startle eyeblink responses in the negative, followed by neutral, followed by positive condition. The patient group, as a whole, did not differ from the control group in terms of overall modulation pattern. However, among the patients, variability in startle modulation was related to neural loss in specific brain regions. Consistent with the animal literature, neural loss in the right amygdala was associated with diminished negative-potentiation of the startle, but had no effect on positive-attenuation of the startle. Contrary to the animal literature, there was no association between the nucleus accumbens and positive-attenuation. However, neural loss in the left medial orbitofrontal cortex (OFC), a region that is functionally connected with the nucleus accumbens and involved in contextually-sensitive appraisals of positive/rewarding stimuli, was associated with enhanced positive-attenuation of the startle. Finally, when real-world behavioral correlates of the emotion-modulated startle were investigated, caregiver ratings of patients' day-to-day anxiety correlated with the level of negative-potentiation they displayed in the lab.These findings support the idea that negative-potentiation and positive-attenuation of the startle response have distinct neuroanatomical bases. They also provide evidence of hemispheric specialization in the emotion modulated startle, with the right hemisphere supporting negative-potentiation, and the left-hemisphere supporting positive-attenuation. Finally, this study demonstrated that variation in the simple modulatory responses measured in the emotion modulated startle task can predict functional disturbances in real-world behavior