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<p>The present thesis explored the neurobiological basis of three aspects of defense behaviors in humans. Positron emission tomography methodology was used, and changes in regional cerebral blood flow (rCBF) were measured as an index of neural activity. Firstly, brain function was studied in a group of patients suffering from combat-related posttraumatic stress disorder, using a symptom provocation paradigm with combat sounds in order to elicit fear. Exposure to auditory trauma reminders relative to neutral sounds was associated with increased rCBF in sensorimotor areas, the cerebellar vermis, the periaqueductal gray matter, and the right amygdala, whereas decreased activity was observed in the retrosplenial area of the posterior cingulate cortex. Secondly, the neural circuitry mediating the acoustic startle response and its habituation was studied in a group of healthy subjects. During acoustic startle stimulation as compared to a resting condition, increased rCBF was found in a medial posterior area of the pons corresponding to the nucleus reticularis pontis caudalis. As a result of startle repetition, altered activity was found in the cerebellum, pointing to its involvement in startle habituation. Thirdly, neural activity associated with startle modulation by phobic fear was studied in a group of subjects with specific animal phobias during exposure to pictures of their feared and non-feared objects, paired and unpaired with acoustic startle stimuli. As a result of startle potentiation, increased rCBF was found in the left amygdaloid-hippocampal region, and medially in the affective division of the anterior cingulate cortex. In conclusion, these results provide evidence for the involvement of limbic and paralimbic brain areas during fear provocation and fear-potentiated startle and for a similar neurocircuitry underlying startle in humans and animals.</p>

The present thesis explored the neurobiological basis of three aspects of defense behaviors in humans. Positron emission tomography methodology was used, and changes in regional cerebral blood flow (rCBF) were measured as an index of neural activity. Firstly, brain function was studied in a group of patients suffering from combat-related posttraumatic stress disorder, using a symptom provocation paradigm with combat sounds in order to elicit fear. Exposure to auditory trauma reminders relative to neutral sounds was associated with increased rCBF in sensorimotor areas, the cerebellar vermis, the periaqueductal gray matter, and the right amygdala, whereas decreased activity was observed in the retrosplenial area of the posterior cingulate cortex. Secondly, the neural circuitry mediating the acoustic startle response and its habituation was studied in a group of healthy subjects. During acoustic startle stimulation as compared to a resting condition, increased rCBF was found in a medial posterior area of the pons corresponding to the nucleus reticularis pontis caudalis. As a result of startle repetition, altered activity was found in the cerebellum, pointing to its involvement in startle habituation. Thirdly, neural activity associated with startle modulation by phobic fear was studied in a group of subjects with specific animal phobias during exposure to pictures of their feared and non-feared objects, paired and unpaired with acoustic startle stimuli. As a result of startle potentiation, increased rCBF was found in the left amygdaloid-hippocampal region, and medially in the affective division of the anterior cingulate cortex. In conclusion, these results provide evidence for the involvement of limbic and paralimbic brain areas during fear provocation and fear-potentiated startle and for a similar neurocircuitry underlying startle in humans and animals.

Previous investigations comparing direct versus indirectly cued movements have consistently shown that indirectly cued movements take longer to prepare (Neely and Heath, 2010) and involve the recruitment of additional brain areas (Connolly et al., 2000). This increase in processing time has been associated with the additional cognitive transformations required of the task (Neely and Heath, 2010). In the present study we investigated whether differences between direct versus indirectly cued movements are also reflected in the time course of motor preparation. Participants performed a targeting task, moving directly to the location of a visual cue (i.e., directly cued movement) or to a location that differed by 60˚, 90˚, or 120˚ with respect to the visual cue provided (i.e., indirectly cued movements). Participants were instructed to initiate their movements concurrently with an anticipated go-signal. To examine the time course of motor preparation, a startling acoustic stimulus (SAS, 124dB) was randomly presented 150 ms, 500 ms, or 1000 ms prior to the go-signal. Results from the startle trials revealed that the time course of motor preparation was similar regardless of the angle of rotation required and hence whether it was a direct or indirectly cued trial. Specifically, motor preparation was delayed until less than 500 ms prior to movement initiation for both direct and indirectly cued movements. These findings indicate that similar motor preparation strategies are engaged for both types of cued movements, suggesting that the time to prepare a motor response may be similar regardless of whether a cognitive transformation is required.

Introduction. Callous-unemotional (CU) traits predict socially debilitating outcomes including Antisocial Personality Disorder and violent crime in adulthood. Despite significant research, the etiology of CU traits is not well understood. This dissertation incorporates genetic, physiological, neuroanatomical, and self-report measures to investigate the etiology of CU traits. Specifically, this project focuses on measures previously found to associate with impaired fear-processing observed in individuals high on CU. Brain morphometry for paralimbic regions of interest (ROIs) and electromyographic facial eyeblink reflex to startle and fear-potentiated startle probes were investigated as potential endophenotypes for CU traits. Methods. Two genetically informative (ages 9-20) twin samples (N=1696 individuals; 848 twin pairs) were used to estimate the changing heritable and environmental influences on CU over the age range of 9-20 using age-moderated biometric structural equation modeling (SEM). To determine potential endophenotypes, shared genetic variance with CU was examined for baseline and fear-potentiated startle reflex and morphometric measures of brain ROIs. Results. The heritability of CU increases over the ages of 9-20, from approximately 34% at age 9 to 47% at age 20. Therefore, environmental mechanisms for CU are most influential at younger ages. Although there were no significant associations after correction for multiple testing, there was some evidence to suggest potential positive associations between CU traits and baseline and fear-potentiated startle in younger (9-14) females. There was also evidence suggesting potential negative associations between CU traits and right anterior cingulate cortex thickness as well as right posterior cingulate cortex thickness in females only. There was no genetic covariance between CU and any of the examined physiological or neuroanatomical phenotypes. Discussion. These results suggest that middle childhood may be the most salient time for environmental interventions associated with preventing or ameliorating CU traits. Furthermore, these results suggest that the cingulate cortex may play a role in the development of CU traits, possibly in females specifically. The cingulate cortex may influence CU traits through its roles in emotional processing, learning, and memory. Larger samples will likely be needed to determine the genetic relationship between CU traits and the structural development of the cingulate cortex.

This study examined the effects of genetic background on the acoustic startle response (ASR) and its modulation by prepulse inhibition (PPI) by comparing nine inbred strains of mice. The ASR, a jerk-like motor reflex, is elicited by bursts of noise or tones with sound pressure levels of 80-90 dB and greater. PPI is a type of modulation of the ASR, requires no training, and results in observable response in both mice and humans. Data were obtained from nine inbred mouse strains, sixteen per strain, which were shipped at approximately 3-5 weeks old from The Jackson Laboratory. In general, ASRs were generally smaller when the startle stimulus was less intense. PPI was relatively weak for the 4 kHz prepulse, and stronger with prepulses of 12 kHz and 20 kHz. However, means varied widely across strains for both ASR and PPI, suggesting a strong influence of genetic background on these behaviors. In addition to genetic influences, peripheral hearing loss and central auditory processing factors must be taken into consideration.

Previous investigations comparing direct versus indirectly cued movements have consistently shown that indirectly cued movements take longer to prepare (Neely and Heath, 2010) and involve the recruitment of additional brain areas (Connolly et al., 2000). This increase in processing time has been associated with the additional cognitive transformations required of the task (Neely and Heath, 2010). In the present study we investigated whether differences between direct versus indirectly cued movements are also reflected in the time course of motor preparation. Participants performed a targeting task, moving directly to the location of a visual cue (i.e., directly cued movement) or to a location that differed by 60˚, 90˚, or 120˚ with respect to the visual cue provided (i.e., indirectly cued movements). Participants were instructed to initiate their movements concurrently with an anticipated go-signal. To examine the time course of motor preparation, a startling acoustic stimulus (SAS, 124dB) was randomly presented 150 ms, 500 ms, or 1000 ms prior to the go-signal. Results from the startle trials revealed that the time course of motor preparation was similar regardless of the angle of rotation required and hence whether it was a direct or indirectly cued trial. Specifically, motor preparation was delayed until less than 500 ms prior to movement initiation for both direct and indirectly cued movements. These findings indicate that similar motor preparation strategies are engaged for both types of cued movements, suggesting that the time to prepare a motor response may be similar regardless of whether a cognitive transformation is required.

Infrared thermal imaging of the periorbital regions of the face shows promise as an input signal modality for an alternative communication system for individuals with conditions that preclude speech or voluntary movement, such as total locked-in syndrome. However, it was unknown if the startle response triggers a change in the skin temperature of these regions; such a change could generate false positives in a thermography-based access system. This study presents an examination of the temperature characteristics of the periorbital regions of 11 able-bodied adult participants before and after an auditory startle stimulus. The results show that the startle response has no substantial effect on the mean temperature of the periorbital regions. This indicates that thermography-based access solutions would be insensitive to startle reactions in their user, an important advantage over other modalities being considered in the context of access solutions for individuals with a severe motor disability.

Infrared thermal imaging of the periorbital regions of the face shows promise as an input signal modality for an alternative communication system for individuals with conditions that preclude speech or voluntary movement, such as total locked-in syndrome. However, it was unknown if the startle response triggers a change in the skin temperature of these regions; such a change could generate false positives in a thermography-based access system. This study presents an examination of the temperature characteristics of the periorbital regions of 11 able-bodied adult participants before and after an auditory startle stimulus. The results show that the startle response has no substantial effect on the mean temperature of the periorbital regions. This indicates that thermography-based access solutions would be insensitive to startle reactions in their user, an important advantage over other modalities being considered in the context of access solutions for individuals with a severe motor disability.

Thesis (M.A.)--The University of North Carolina at Greensboro, 2008. / Directed by George Michel; submitted to the Dept. of Psychology. Title from PDF t.p. (viewed Jan. 28, 2010). Includes bibliographical references (p. 66-86).