The primary aim of this study was to examine the possibility of an emotion-specific reactivity deficit to fear pictures in PD patients, as indexed by startle eyeblink magnitude. In a previous study, we found diminished startle reactivity to aversive pictures in PD patients (Bowers et al., 2006b
). Due to the composition of the pictures in the “aversive” category, we were unable to determine whether this effect was driven by certain emotion categories of unpleasant stimuli (i.e., fear vs. disgust). Based on evidence that the amygdala appears to play a specific role in the processing of fear-eliciting stimuli (Amaral, 2003
; Calder et al., 1996
; Klüver & Bucy, 1939
; Young et al., 1995
), along with prior findings of structural and functional amygdala abnormalities in PD (Braak & Braak, 2000
; Harding, Stimson, Henderson, & Halliday, 2002
; Ouchi et al., 1999
), the current study tested the hypothesis that reduced reactivity to aversive pictures may be more specifically due to reduced reactivity to fear stimuli. This hypothesis was not supported by the current findings. Instead, PD patients demonstrated significantly smaller startle eyeblink magnitudes to a specific subcategory of aversive pictures, mutilations. Startle eyeblink magnitudes to contamination pictures as well as to fear, pleasant, and neutral picture categories did not differ from controls.
What might be the basis for this mutilation-specific hyporeactivity? There are several potential explanations. First, the PD group might find the mutilation pictures less unpleasant, less arousing, or less disgusting compared to controls. This could be due to visuoperception problems, resulting in misperception of pictures, or due to misappraisal of the emotional meaning behind the pictures. These concerns were addressed by examining the valence and arousal ratings made by each participant during the psychophysiology experiment, as well as the post hoc basic emotion ratings made afterwards. The two groups did not significantly differ with regards to their valence or arousal ratings for mutilation pictures or for any of the a priori picture categories (neutral, pleasant, fear, disgust- contamination, disgust- mutilation). Additionally, in their post hoc ratings of degree of happiness, disgust, fear, and sadness associated with mutilation pictures, PD patients' ratings were comparable to controls. This is consistent with prior research showing that PD patients typically report subjective feelings that are comparable to those reported by controls during tasks such as viewing emotional video clips (Simons et al., 2004
; Smith et al., 1996
). Taken together, these findings suggest that the lack of startle potentiation to mutilation pictures is not due to decreased subjective ratings of unpleasantness or arousal from the standpoint of a dimensional model of emotion, or due to inaccurate subjective appraisal
from a discrete categorical approach to emotion.
A second possibility is that PD patients have a deficit in translating their aversive motivational state into a physiological response. To elaborate, Lang (1995)
described emotions as action dispositions associated with a physiological, behavioral, and affective response. According to this model, emotions are driven by two opponent motivational systems. Activation of the appetitive system is associated with behavioral approach as well as attenuation of the startle reflex. Activation of the aversive system is characterized by protective withdrawal/avoidance and increased startle reflex. We previously suggested that perhaps PD patients are able to correctly appraise the emotional significance of a stimulus, but are unable “translate” activation of the aversive motivational system into a physiological response (Bowers et al., 2006b
). We suggested this may be attributable to faulty communication between the amygdala and prefrontal cortex due to low levels of dopamine in PD. This hypothesis was based on a series of animal studies providing evidence that dopamine modulates prefrontal cortex -controlled inhibition and disinhibition of the amygdala in response to stress-inducing stimuli (Amaral, Price, Pitkanen, & Carmichael, 1992
; Inglis & Moghaddam, 1999
; Rosenkranz & Grace, 1999
). Typically, the amygdala is under inhibitory control from the prefrontal cortex (Rosenkranz & Grace, 1999
). In response to sensory-driven stress (e.g., viewing an aversive picture), dopamine is released in the basolateral amygdala (Inglis & Moghaddam, 1999
) causing a chain of neural events resulting in suppression of the prefrontal cortex's inhibition of the amygdala (Marowsky, Yanagawa, Obata, & Vogt, 2005
). According to Bowers et al. (2006b)
, one can speculate that in PD dopaminergic depletion would reduce the extent to which this amygdala disinhibition would occur in response to a highly-arousing, stress-evoking stimulus. Because the amygdala projects to basic startle circuitry within the brainstem as well as the hypothalamus, which mediates sympathetic nervous system arousal (Amaral et al., 1992
) the net effect would potentially be to reduce physiologic reactivity, as indexed by measures such as emotion-modulated startle eyeblink or skin conductance response.
An explanation for reduced reactivity specifically to mutilation pictures that is consistent with this theory is that the mutilation pictures used in the study were actually more arousing (and thus activated the aversive motivational system to a greater degree) than were the fear and contamination pictures used in the study. Participants in our sample did not rate the mutilation pictures as significantly higher in arousal than other aversive pictures; however, in a large-scale study, Bradley et al. (2001a)
found that mutilation and animal attack pictures were associated with significantly higher skin conductance response (another measure of physiological arousal) and arousal ratings compared to other unpleasant pictures (such as pictures of vehicular accidents or contaminations). It is possible that reduced startle eyeblink magnitude to mutilation pictures may be due to the fact that the mutilation pictures in our study, or perhaps a subset of these mutilation pictures, were the only type of aversive pictures sufficiently arousing to detect a deficit in physiological reactivity in PD patients. At first glance this explanation may appear counterintuitive, as the PD group showed robust startle potentiation to fear pictures, suggesting intact physiological response to arousing negative stimuli. However, when we examined the normative IAPS ratings for the pictures included in the current study, we found that although fear and mutilation pictures had similar mean arousal ratings, at the individual picture level the mutilation picture category had a greater proportion of pictures with very high arousal ratings. The top two negative pictures with the highest arousal ratings were mutilations. Similarly, in our previous study, four of the top five negative pictures with the highest arousal ratings were mutilations (Bowers et al., 2006b
). Thus, it is plausible that these highly arousing pictures, which fall into the “mutilation” category, may have driven the effect of reduced startle eyeblink magnitude in the PD group by bringing down the group mean eyeblink magnitude for mutilation pictures. Unfortunately, it is impossible to discern if this effect is due to the specific mutilation pictures used in our study (and thus represents an artifact of study design and not a mutilation-specific effect), or if the content of mutilation pictures is intrinsically more arousing than other pictures due to their very nature. It would be possible to address this issue through a replication study in which the top few negative pictures with the highest arousal ratings are not mutilations. In either case, our theory that reduced startle eyeblink magnitude in PD is mediated by arousal level of the pictures is supported by an analysis in which we compared startle eyeblink magnitudes for the eight negative pictures with the highest normative arousal ratings versus the eight negative pictures with the lowest arousal ratings. In the control group, arousal level modulated the startle reflex, with the most arousing pictures resulting in larger startle eyeblinks. In contrast, arousal level did not modulate startle response in PD patients. They showed similar startle eyeblink magnitudes to both low arousal and high arousal pictures. As studies have implicated the amygdala in learning and memory of highly arousing positive as well as negative stimuli (see McGaugh, 2004
for a review of this literature), we followed up on this analysis by examining the groups' pattern of eyeblink magnitudes to the pleasant pictures with the highest and lowest normative arousal ratings. For both controls and PD patients, normative arousal ratings did not appear to modulate eyeblink magnitudes. It is possible that this analysis did not reach statistical significance because there were a fewer number of positive than negative pictures in our stimulus set, or because of the fact that the range of normative arousal ratings was smaller for the positive pictures than for the negative pictures. Keeping in mind these limitations, our findings suggest that PD patients and controls respond similarly to positive picture stimuli, but PD patients show a reactivity deficit to certain
highly arousing negative pictures. In further support of an arousal-driven reactivity deficit to aversive stimuli, we recently reported findings with respect to skin conductance response (SCR) in PD patients that mirror these startle reflex results (Bowers et al., 2008
). Generally, viewing arousing emotional stimuli is associated with an increase in SCR. While controls showed the expected increase in SCR during viewing of emotional pictures, PD patients showed no modulation of SCR. Taken together, these findings support the hypothesis of a deficit in translating a motivational state into a physiological response in PD. The high-low arousal analysis in the present study supports a threshold model in which highly arousing and aversive stimuli (such as the mutilation pictures) are needed to detect differences in physiological reactivity between controls and PD patients, whereas less arousing stimuli may not be sufficient to detect this difference. In considering this hypothesis, it is important to point out that the PD group did show normal startle modulation to the fear pictures, suggesting that there is not a complete disconnect between translating an aversive motivational state into a physiological response in these patients. In accounting for this discrepant response to the fear pictures versus the mutilation pictures, one possibility is that some intrinsic aspect of mutilation stimuli makes them particularly threatening to the viewer (discussed in further detail below), thus activating the prefrontal-amygdala circuitry to a greater extent than the a priori “fear” pictures and revealing the subtle dysfunction of this circuitry.
Surprisingly, we found no correlation between subjective arousal ratings and objective startle eyeblink magnitudes in the control or PD groups. One explanation for lack of significant correlations may be restricted range or small sample size. Another possibility is that participants may have been responding to demand characteristics when making their subjective ratings. For example, participants may have rated a picture of a snake high in arousal simply because they thought it was intended to evoke high arousal, not because they actually felt this way. A final possibility that must be considered is that participants did not understand exactly what was meant by rating “arousal;” although all participants were given sample pictures to rate prior to the start of the study and all made reasonable arousal ratings. However, the concept of “arousal level” is arguably more difficult to understand than is the concept of valence ratings.
The reason underlying the emotional intensity as well as the motivational relevance of the mutilation pictures is unknown; however, our results suggest these stimuli strongly activate the aversive motivational system. In considering how an individual's appraisal of a stimulus affects their physiological response to it, Springer, Rosas, McGetrick, & Bowers (2007)
recently pointed out that an experimenter's a priori categorization of a stimulus (e.g. “fear” or “disgust”) may be less important than its functional impact upon the viewer. For example, studies employing IAPS pictures stimuli often include a “fear” stimulus set that places “victim” pictures (in which one person is directly victimizing another person in the picture by pointing a gun at them or hitting them, etc.) in the same category as “direct threat” pictures (in which a gun or other weapon is pointed directly at the viewer); however, Bernat, Patrick, Benning, & Tellegen (2006)
have shown that emotion-modulated startle eyeblink magnitudes are larger for the “direct threat” pictures. This suggests that subtle nuances within the picture contents themselves may affect how participants appraise, and consequently respond to, a stimulus. Along this line of reasoning, we can speculate that from an evolutionary standpoint that it might be highly arousing and aversive to see a mutilated person. Because mutilation pictures depict a destruction of bodily integrity, seeing an injured/mutilated conspecific may signal “direct threat” to one's own bodily integrity.
There are several limitations to the current study that should be acknowledged. First, the patient sample may not be representative of the typical person with PD. The sample was highly educated (average of 16 years of education), although it is unlikely that educational status influenced the emotion-modulated startle eyeblink, which it is thought to be an automatic reaction (Bradley, 2000
The sample also had an imbalance of men and women (14 men and 10 women per group). Although preliminary analyses including “sex” as an independent variable revealed no significant effect of sex for any of the key study aims, the study was not designed to be sufficiently powered to examine sex differences. In a large study of sex differences in physiologic reactivity examining men and women's responses to a wide variety of picture contents, Bradley et al. (2001b)
reported that women tended to respond with greater defensive activation (i.e. larger emotion-modulated startle
eyeblink, more cardiac deceleration, increased facial EMG activity changes) compared to men when viewing unpleasant pictures. This raises the possibility that sex may interact with startle potentiation to the fear, contamination, or mutilation pictures.
The present study is also limited by the fact that participants were limited to PD patients in Hoehn and Yahr stage 2 or 3, and the majority of patients had on-medication UPDRS motor scores falling in the 20s (range: 4-41). Although startle eyeblink magnitudes were not significantly associated with UPDRS motor score, this finding is limited by the fact that persons with severe PD were not included in the study. It is possible that a linear relationship between disease severity and startle eyeblink magnitude exists (as was found by Bowers et al., 2006b
), but was not detected because of the restricted range in the current study. As the disease progresses, we would expect further pathological changes to the amygdala, which may increase the magnitude of any emotional reactivity deficits. Future studies should include patients with a broader range of disease severity in order to more fully examine the impact of disease progression upon emotion-modulated startle. Finally, there are some methodological limitations to our study that should be acknowledged. A formal assessment of visuoperception was not conducted, and it is possible that poor visuoperception could affect participants' ability to correctly perceive the stimulus pictures. In terms of participants' emotion ratings, two different rating scales of subjective emotional reaction were used in the study, which may have potentially been confusing to participants. Additionally, the post-experimental emotion ratings included “disgust,” “fear,” “happiness,” and “sadness,” even though sadness was not a target emotion, and it is possible that having these as the only emotion rating options could have biased participants' towards a particular response set (e.g. “angry” and “surprised” were not provided).
In conclusion, our data do not support the hypothesis of an emotion-specific reactivity deficit to PD. Instead, our results suggest PD patients display diminished reactivity to highly arousing aversive stimuli, regardless of the specific emotions experienced. We previously suggested this may be due to impairment in translating their motivational state into a physiological response. Based on the data from the current study, we expanded upon our earlier theory by suggesting a threshold model in which only highly arousing negative stimuli, such as mutilation pictures, are sufficient to detect this impairment. Future studies should investigate whether this hyporeactivity is caused by peripheral autonomic nervous system changes in PD, such as Lewy bodies within the sympathetic ganglion, or central nervous system dysfunction. Our results add to the growing literature indicating that PD is not simply a movement disorder, but a disease that also affects emotional and physiological responses.