Diffusion Tensor Imaging-Along the Perivascular-Space Index Is Associated with Disease Progression in Parkinson's Disease.

BACKGROUND: The glymphatic clearance pathway is a waste clearance system that allows for removal of soluble proteins such as amyloid ß (Aß) from the brain. Higher Aß levels are associated with cognitive dysfunction in Parkinson's disease (PD). Diffusion tensor imaging-along the perivascular space (DTI-ALPS) is an imaging measure proposed to indirectly measure glymphatic function. OBJECTIVES: Evaluate differences in DTI-ALPS-index between PD and healthy controls (HC) and characterize relationships between this proposed measure of glymphatic clearance, cognition, and disease severity in PD. METHODS: PD (n = 32) and HC (n = 23) participants underwent brain imaging to assess DTI-ALPS. PD participants were classified as PD-normal cognition (PD-NC; n = 20) or PD-mild cognitive impairment (PD-MCI; n = 12) based on a Level II comprehensive cognitive assessment. A subgroup of PD participants (n = 21) returned for annual assessments for up to 4 years after baseline. Longitudinal outcomes included changes in performance on the comprehensive cognitive assessment and changes in the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). RESULTS: PD participants had lower DTI-ALPS-index compared to HC. PD participants classified as PD-MCI had significantly lower DTI-ALPS-index compared to PD-NC. Lower DTI-ALPS-index at baseline was associated with longitudinal cognitive decline and worse longitudinal disease severity. CONCLUSIONS: Glymphatic clearance, as measured with DTI-ALPS, has potential to serve as a marker of longitudinal disease progression. Interventions targeting glymphatic function should be explored for potential to slow cognitive decline in PD. © 2024 International Parkinson and Movement Disorder Society.

Quantitative sleep electroencephalogram and cognitive performance in Parkinson's disease with and without rapid eye movement sleep behavior disorder.

Introduction: Parkinson's disease (PD) patients with REM sleep behavior disorder (RBD) are at greater risk for cognitive decline and RBD has been associated with alterations in sleep-related EEG oscillations. This study evaluates differences in sleep quantitative EEG (qEEG) and cognition in PD participants with (PD-RBD) and without RBD (PD-no-RBD). Methods: In this cross-sectional study, polysomnography (PSG)-derived qEEG and a comprehensive level II neuropsychological assessment were compared between PD-RBD (n = 21) and PD-no-RBD (n = 31). Following artifact rejection, qEEG analysis was performed in the frontal and central leads. Measures included Scalp-slow wave (SW) density, spindle density, morphological properties of SW and sleep spindles, SW-spindle phase-amplitude coupling, and spectral power analysis in NREM and REM. The neurocognitive battery had at least two tests per domain, covering five cognitive domains as recommended by the Movement Disorders Society Task Force for PD-MCI diagnosis. Differences in qEEG features and cognitive performance were compared between the two groups. Stepwise linear regression was performed to evaluate predictors of cognitive performance. Multiple comparisons were corrected using the Benjamini-Hochberg method. Results: Spindle density and SW-spindle co-occurrence percent were lower in participants with PD-RBD compared to PD-no-RBD. The PD-RBD group also demonstrated higher theta spectral power during REM. Sleep spindles and years of education, but not RBD, were predictors of cognitive performance. Conclusion: PD participants with RBD have alterations in sleep-related qEEG compared to PD participants without RBD. Although PD-RBD participants had worse cognitive performance compared to PD-no-RBD, regression models suggest that lower sleep spindle density, rather than presence of RBD, predicts worse comprehensive cognitive score. Future studies should include longitudinal evaluation to determine whether sleep-related qEEG alterations are associated with more rapid cognitive decline in PD-RBD.

Quantitative Sleep Electroencephalogram in Parkinson's Disease: A Case-Control Study.

BACKGROUND: Sleep disorders are common in Parkinson's disease (PD) and include alterations in sleep-related EEG oscillations. OBJECTIVE: This case-control study tested the hypothesis that patients with PD would have a lower density of Scalp-Slow Wave (SW) oscillations and higher slow-to-fast frequencies ratio in rapid eye movement (REM) sleep than non-PD controls. Other sleep-related quantitative EEG (qEEG) features were also examined, including SW morphology, sleep spindles, and Scalp-SW spindle phase-amplitude coupling. METHODS: Polysomnography (PSG)-derived sleep EEG was compared between PD participants (n = 56) and non-PD controls (n = 30). Following artifact rejection, sleep qEEG analysis was performed in frontal and central leads. Measures included SW density and morphological features of SW and sleep spindles, SW-spindle phase-amplitude coupling, and spectral power analysis in Non-REM (NREM) and REM. Differences in qEEG features between PD and non-PD controls were compared using two-tailed Welch's t-tests, and correction for multiple comparisons was performed per the Benjamini-Hochberg method. RESULTS: SW density was lower in PD than in non-PD controls (F = 13.5, p' = 0.003). The PD group also exhibited higher ratio of slow REM EEG frequencies (F = 4.23, p' = 0.013), higher slow spindle peak frequency (F = 24.7, p' < 0.002), and greater SW-spindle coupling angle distribution non-uniformity (strength) (F = 7.30, p' = 0.034). CONCLUSION: This study comprehensively evaluates sleep qEEG including SW-spindle phase amplitude coupling in PD compared to non-PD controls. These findings provide novel insights into how neurodegenerative disease disrupts electrophysiological sleep rhythms. Considering the role of sleep oscillatory activity on neural plasticity, future studies should investigate the influence of these qEEG markers on cognition in PD.

Effects of exercise on sleep spindles in Parkinson's disease.

Background: In a randomized, controlled trial, we showed that high-intensity rehabilitation, combining resistance training and body-weight interval training, improves sleep efficiency in Parkinson's disease (PD). Quantitative sleep EEG (sleep qEEG) features, including sleep spindles, are altered in aging and in neurodegenerative disease. Objective: The objective of this post-hoc analysis was to determine the effects of exercise, in comparison to a sleep hygiene, no-exercise control group, on the quantitative characteristics of sleep spindle morphology in PD. Methods: We conducted an exploratory post-hoc analysis of 24 PD participants who were randomized to exercise (supervised 3 times/week for 16 weeks) versus 26 PD participants who were assigned to a sleep hygiene, no-exercise control group. At baseline and post-intervention, all participants completed memory testing and underwent polysomnography (PSG). PSG-derived sleep EEG central leads (C3 and C4) were manually inspected, with rejection of movement and electrical artifacts. Sleep spindle events were detected based on the following parameters: (1) frequency filter = 11-16 Hz, (2) event duration = 0.5-3 s, and (3) amplitude threshold 75% percentile. We then calculated spindle morphological features, including density and amplitude. These characteristics were computed and averaged over non-rapid eye movement (NREM) sleep stages N2 and N3 for the full night and separately for the first and second halves of the recording. Intervention effects on these features were analyzed using general linear models with group x time interaction. Significant interaction effects were evaluated for correlations with changes in performance in the memory domain. Results: A significant group x time interaction effect was observed for changes in sleep spindle density due to exercise compared to sleep hygiene control during N2 and N3 during the first half of the night, with a moderate effect size. This change in spindle density was positively correlated with changes in performance on memory testing in the exercise group. Conclusions: This study is the first to demonstrate that high-intensity exercise rehabilitation has a potential role in improving sleep spindle density in PD and leading to better cognitive performance in the memory domain. These findings represent a promising advance in the search for non-pharmacological treatments for this common and debilitating non-motor symptom.

Sex-related differences in violence exposure, neural reactivity to threat, and mental health.

The prefrontal cortex (PFC), hippocampus, and amygdala play an important role in emotional health. However, adverse life events (e.g., violence exposure) affect the function of these brain regions, which may lead to disorders such as depression and anxiety. Depression and anxiety disproportionately affect women compared to men, and this disparity may reflect sex differences in the neural processes that underlie emotion expression and regulation. The present study investigated sex differences in the relationship between violence exposure and the neural processes that underlie emotion regulation. In the present study, 200 participants completed a Pavlovian fear conditioning procedure in which cued and non-cued threats (i.e., unconditioned stimuli) were presented during functional magnetic resonance imaging. Violence exposure was previously assessed at four separate time points when participants were 11-19 years of age. Significant threat type (cued versus non-cued) × sex and sex × violence exposure interactions were observed. Specifically, women and men differed in amygdala and parahippocampal gyrus reactivity to cued versus non-cued threat. Further, dorsolateral PFC (dlPFC) and inferior parietal lobule (IPL) reactivity to threat varied positively with violence exposure among women, but not men. Similarly, threat-elicited skin conductance responses varied positively with violence exposure among women. Finally, women reported greater depression and anxiety symptoms than men. These findings suggest that sex differences in threat-related brain and psychophysiological activity may have implications for mental health.

Taking the Time to Assess Cognition in Parkinson's Disease: The Clock Drawing Test.

BACKGROUND: Cognitive impairment is common and disabling in Parkinson's disease (PD). Cognitive testing can be time consuming in the clinical setting. One rapid test to detect cognitive impairment in non-PD populations is the Clock Drawing Test (CDT), which calls upon the brain's executive and visuospatial abilities to draw a clock designating a certain time. OBJECTIVE: Test the hypothesis that PD participants would perform worse on CDT compared to controls and that CDT would correlate with other measures of cognition. METHODS: This study evaluated two independent CDT scoring systems and differences in CDT performance between PD (N = 97) and control (N = 54) participants using a two-sample t-test. Pearson's correlations were conducted between the CDT and tests of sleepiness (Epworth Sleepiness Scale) and vigilance (Psychomotor Vigilance Test); executive function (Trails B-A); and global cognition (Montreal Cognitive Assessment). Receiver operating characteristic curves were used to determine cut points on the CDT that identify individuals who need additional cognitive testing. RESULTS: PD participants had worse performance on CDT compared to controls. The CDT was correlated with executive function (Trails B-A) and global cognition (Montreal Cognitive Assessment). The CDT correlated with vigilance (Psychomotor Vigilance Task) only in healthy controls. However, the CDT was not correlated with measures of sleepiness (Epworth Sleepiness Scale) in either group. A cut point of 9 on the Rouleau scale and 18 on the Mendez scale identified PD participants with cognitive impairment. CONCLUSION: The CDT is a rapid clinical cognitive assessment that is feasible in PD and correlates with other measures of cognition.

Slow Wave Sleep and EEG Delta Spectral Power are Associated with Cognitive Function in Parkinson's Disease.

BACKGROUND: Cognitive and sleep dysfunction are common non-motor symptoms in Parkinson's disease (PD). OBJECTIVE: Determine the relationship between slow wave sleep (SWS) and cognitive performance in PD. METHODS: Thirty-two PD participants were evaluated with polysomnography and a comprehensive level II neurocognitive battery, as defined by the Movement Disorders Society Task Force for diagnosis of PD-mild cognitive impairment. Raw scores for each test were transformed into z-scores using normative data. Z-scores were averaged to obtain domain scores, and domain scores were averaged to determine the Composite Cognitive Score (CCS), the primary outcome. Participants were grouped by percent of SWS into High SWS and Low SWS groups and compared on CCS and other outcomes using 2-sided t-tests or Mann-Whitney U. Correlations of cognitive outcomes with sleep architecture and EEG spectral power were performed. RESULTS: Participants in the High SWS group demonstrated better global cognitive function (CCS) (p = 0.01, effect size: r = 0.45). In exploratory analyses, the High SWS group showed better performance in domains of executive function (effect size: Cohen's d = 1.05), language (d = 0.95), and processing speed (d = 1.12). Percentage of SWS was correlated with global cognition and executive function, language, and processing speed. Frontal EEG delta power during N3 was correlated with the CCS and executive function. Cognition was not correlated with subjective sleep quality. CONCLUSION: Increased SWS and higher delta spectral power are associated with better cognitive performance in PD. This demonstrates the significant relationship between sleep and cognitive function and suggests that interventions to improve sleep might improve cognition in individuals with PD.

Randomized, Controlled Trial of Exercise on Objective and Subjective Sleep in Parkinson's Disease.

BACKGROUND: Sleep dysfunction is common and disabling in persons with Parkinson's Disease (PD). Exercise improves motor symptoms and subjective sleep quality in PD, but there are no published studies evaluating the impact of exercise on objective sleep outcomes. The goal of this study was to to determine if high-intensity exercise rehabilitation combining resistance training and body-weight interval training, compared with a sleep hygiene control improved objective sleep outcomes in PD. METHODS: Persons with PD (Hoehn & Yahr stages 2-3; aged ≥45 years, not in a regular exercise program) were randomized to exercise (supervised 3 times a week for 16 weeks; n = 27) or a sleep hygiene, no-exercise control (in-person discussion and monthly phone calls; n = 28). Participants underwent polysomnography at baseline and post-intervention. Change in sleep efficiency was the primary outcome, measured from baseline to post-intervention. Intervention effects were evaluated with general linear models with measurement of group × time interaction. As secondary outcomes, we evaluated changes in other aspects of sleep architecture and compared the effects of acute and chronic training on objective sleep outcomes. RESULTS: The exercise group showed significant improvement in sleep efficiency compared with the sleep hygiene group (group × time interaction: F = 16.0, P < 0.001, d = 1.08). Other parameters of sleep architecture also improved in exercise compared with sleep hygiene, including total sleep time, wake after sleep onset, and slow-wave sleep. Chronic but not acute exercise improved sleep efficiency compared with baseline. CONCLUSIONS: High-intensity exercise rehabilitation improves objective sleep outcomes in PD. Exercise is an effective nonpharmacological intervention to improve this disabling nonmotor symptom in PD. © 2020 International Parkinson and Movement Disorder Society.

Negative life experiences contribute to racial differences in the neural response to threat.

Threat-related emotional function is supported by a neural circuit that includes the prefrontal cortex (PFC), hippocampus, and amygdala. The function of this neural circuit is altered by negative life experiences, which can potentially affect threat-related emotional processes. Notably, Black-American individuals disproportionately endure negative life experiences compared to White-American individuals. However, the relationships among negative life experiences, race, and the neural substrates that support threat-related emotional function remains unclear. Therefore, the current study investigated whether the brain function that supports threat-related emotional processes varies with racial differences in negative life experiences. In the present study, adolescent violence exposure, family income, and neighborhood disadvantage were measured prospectively (i.e., at 11-19 years of age) for Black-American and White-American volunteers. Participants then, as young adults (i.e., 18-23 years of age), completed a Pavlovian fear conditioning task during functional magnetic resonance imaging (fMRI). Cued and non-cued threats were presented during the conditioning task and behavioral (threat expectancy) and psychophysiological responses (skin conductance response; SCR) were recorded simultaneously with fMRI. Racial differences were observed in neural (fMRI activity), behavioral (threat expectancy), and psychophysiological (SCR) responses to threat. These threat-elicited responses also varied with negative life experiences (violence exposure, family income, and neighborhood disadvantage). Notably, racial differences in brain activity to threat were smaller after accounting for negative life experiences. The present findings suggest that racial differences in the neural and behavioral response to threat are due, in part, to exposure to negative life experiences and may provide new insight into the mechanisms underlying racial disparities in mental health.

Amygdala and prefrontal cortex activity varies with individual differences in the emotional response to psychosocial stress.

Stress elicits a variety of psychophysiological responses that show large interindividual variability. Determining the neural mechanisms that mediate individual differences in the emotional response to stress would provide new insight that would have important implications for understanding stress-related disorders. Therefore, the present study examined individual differences in the relationship between brain activity and the emotional response to stress. In the largest stress study to date, 239 participants completed the Montreal Imaging Stress Task (MIST) while heart rate, skin conductance response (SCR), cortisol, self-reported stress, and blood oxygen level dependent (BOLD) functional MRI (fMRI) signal responses were measured. The relationship between differential responses (heart rate, SCR, cortisol, and self-reported stress) and differential BOLD fMRI data was analyzed. Dorsolateral prefrontal cortex (PFC), dorsomedial PFC, ventromedial PFC, and amygdala activity varied with the behavioral response (i.e., SCR and self-reported stress). These results suggest the PFC and amygdala support processes that are important for the expression and regulation of the emotional response to stress, and that stress-related PFC and amygdala activity underlie interindividual variability in peripheral physiologic measures of the stress response. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Psychosocial stress reactivity is associated with decreased whole-brain network efficiency and increased amygdala centrality.

Cognitive and emotional functions are supported by the coordinated activity of a distributed network of brain regions. This coordinated activity may be disrupted by psychosocial stress, resulting in the dysfunction of cognitive and emotional processes. Graph theory is a mathematical approach to assess coordinated brain activity that can estimate the efficiency of information flow and determine the centrality of brain regions within a larger distributed neural network. However, limited research has applied graph-theory techniques to the study of stress. Advancing our understanding of the impact stress has on global brain networks may provide new insight into factors that influence individual differences in stress susceptibility. Therefore, the present study examined the brain connectivity of participants that completed the Montreal Imaging Stress Task (Goodman et al., 2016; Wheelock et al., 2016). Salivary cortisol, heart rate, skin conductance response, and self-reported stress served as indices of stress, and trait anxiety served as an index of participant's disposition toward negative affectivity. Psychosocial stress was associated with a decrease in the efficiency of the flow of information within the brain. Further, the centrality of brain regions that mediate emotion regulation processes (i.e., hippocampus, ventral prefrontal cortex, and cingulate cortex) decreased during stress exposure. Interestingly, individual differences in cortisol reactivity were negatively correlated with the efficiency of information flow within this network, whereas cortisol reactivity was positively correlated with the centrality of the amygdala within the network. These findings suggest that stress reduces the efficiency of information transfer and leaves the function of brain regions that regulate the stress response vulnerable to disruption. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Trauma exposure acutely alters neural function during Pavlovian fear conditioning.

Posttraumatic stress disorder (PTSD) is associated with dysfunction of the neural circuitry that supports fear learning and memory processes. However, much of what is known about neural dysfunction in PTSD is based on research in chronic PTSD populations. Less is known about neural function that supports fear learning acutely following trauma exposure. Determining the acute effects of trauma exposure on brain function would provide new insight into the neural processes that mediate the cognitive-affective dysfunction associated with PTSD. Therefore, the present study investigated neural activity that supports fear learning and memory processes in recently Trauma-Exposed (TE) and Non-Trauma-Exposed (NTE) participants. Participants completed a Pavlovian fear conditioning procedure during functional magnetic resonance imaging (fMRI). During fMRI, participants' threat expectancy was continuously monitored. NTE participants showed greater threat expectancy during warning than safety cues, while no difference was observed in the TE group. This finding suggests TE participants overgeneralized the fear association to the safety cue. Further, only the TE group showed a negative relationship between fMRI signal responses within dorsomedial prefrontal cortex (PFC) and threat expectancy during safety cues. These results suggest the dorsomedial PFC mediates overgeneralization of learned fear as an acute result of trauma exposure. Finally, neural activity within the PFC and inferior parietal lobule showed a negative relationship with PTSD symptom severity assessed three months posttrauma. Thus, neural activity measured acutely following trauma exposure predicted future PTSD symptom severity. The present findings elucidate the acute effects of trauma exposure on cognitive-affective function and provide new insight into the neural mechanisms of PTSD.

Anticipatory stress associated with functional magnetic resonance imaging: Implications for psychosocial stress research.

Stress tasks performed during functional magnetic resonance imaging (fMRI) elicit a relatively small cortisol response compared to stress tasks completed in a traditional behavioral laboratory, which may be due to apprehension of fMRI that elicits an anticipatory stress response. The present study investigated whether anticipatory stress is greater prior to research completed in an MRI environment than in a traditional behavioral laboratory. Anticipatory stress (indexed by cortisol) was greater prior to testing in the MRI environment than traditional behavioral laboratory. Furthermore, anticipation of fMRI elicited a cortisol response commensurate with the response to the stress task in the behavioral laboratory. However, in the MRI environment, post-stress cortisol was significantly lower than baseline cortisol. Taken together, these findings suggest the stress elicited by anticipation of fMRI may lead to acute elevations in cortisol prior to scanning, which may in turn disrupt the cortisol response to stress tasks performed during scanning.

High-Intensity Exercise Acutely Increases Substantia Nigra and Prefrontal Brain Activity in Parkinson's Disease.

BACKGROUND Pathologic alterations in resting-state brain activity patterns exist among individuals with Parkinson's disease (PD). Since physical exercise alters resting-state brain activity in non-PD populations and improves PD symptoms, we assessed the acute effect of exercise on resting-state brain activity in exercise-trained individuals with PD. MATERIAL AND METHODS Resting-state functional magnetic resonance imaging (fMRI) was collected twice for 17 PD participants at the conclusion of an exercise intervention. The acute effect of exercise was examined for PD participants using the amplitude of low frequency fluctuation (ALFF) before and after a single bout of exercise. Correlations of clinical variables (i.e., PDQ-39 quality of life and MDS-UPDRS) with ALFF values were examined for the exercise-trained PD participants. RESULTS An effect of acute exercise was observed as an increased ALFF signal within the right ventromedial prefrontal cortex (PFC), left ventrolateral PFC, and bilaterally within the substantia nigra (SN). Quality of life was positively correlated with ALFF values within the vmPFC and vlPFC. CONCLUSIONS Given the role of the SN and PFC in motor and non-motor symptoms in PD, the acute increases in brain activity within these regions, if repeated frequently over time (i.e., exercise training), may serve as a potential mechanism underlying exercise-induced PD-specific clinical benefits.

Pedestrian safety in patients with Parkinson's disease: A case-control study.

BACKGROUND: Patients with Parkinson's disease experience debilitating motor symptoms as well as nonmotor symptoms, such as cognitive dysfunction and sleep disorders. This constellation of symptoms has the potential to negatively influence pedestrian safety. The objective of this study was to investigate the association of motor symptoms, daytime sleepiness, impaired vigilance, and cognitive dysfunction with pedestrian behavior in patients with Parkinson's disease and healthy older adults. METHODS: Fifty Parkinson's disease and 25 control participants were evaluated within a virtual reality pedestrian environment and completed assessments of motor performance, daytime sleepiness (Epworth Sleepiness Scale), vigilance (psychomotor vigilance task), and visual processing speed (Useful Field of View) outside the virtual reality environment. The primary outcome measure was time to contact, defined as the time remaining until a participant would have been hit by an approaching vehicle while crossing the virtual street. RESULTS: The virtual reality pedestrian environment was feasible in all participants. Patients with Parkinson's disease demonstrated riskier pedestrian behavior compared with controls. Among Parkinson's disease participants, walking speed, objective measures of vigilance, and visual processing speed were correlated with pedestrian behavior, with walking speed the strongest predictor of time to contact, explaining 48% of the variance. Vigilance explained an additional 8% of the variance. In controls, vigilance was also important for street-crossing safety, but older age was the most robust predictor of pedestrian safety. CONCLUSIONS: Walking speed is associated with unsafe pedestrian behavior in patients with Parkinson's disease. In contrast, age was the strongest predictor of pedestrian safety in healthy older adults. © 2017 International Parkinson and Movement Disorder Society.

Glutamate/glutamine concentrations in the dorsal anterior cingulate vary with Post-Traumatic Stress Disorder symptoms.

Trauma and stress-related disorders (e.g., Acute Stress Disorder; ASD and Post-Traumatic Stress Disorder; PTSD) that develop following a traumatic event are characterized by cognitive-affective dysfunction. The cognitive and affective functions disrupted by stress disorder are mediated, in part, by glutamatergic neural systems. However, it remains unclear whether neural glutamate concentrations, measured acutely following trauma, vary with ASD symptoms and/or future PTSD symptom expression. Therefore, the current study utilized proton magnetic resonance spectroscopy (1H-MRS) to investigate glutamate/glutamine (Glx) concentrations within the dorsal anterior cingulate cortex (ACC) of recently (i.e., within one month) traumatized individuals and non-traumatized controls. Although Glx concentrations within dorsal ACC did not differ between recently traumatized and non-traumatized control groups, a positive linear relationship was observed between Glx concentrations and current stress disorder symptoms in traumatized individuals. Further, Glx concentrations showed a positive linear relationship with future stress disorder symptoms (i.e., assessed 3 months post-trauma). The present results suggest glutamate concentrations may play a role in both acute and future post-traumatic stress symptoms following a traumatic experience. The current results expand our understanding of the neurobiology of stress disorder and suggest glutamate within the dorsal ACC plays an important role in cognitive-affective dysfunction following a traumatic experience.

Prefrontal Cortex Activity Is Associated with Biobehavioral Components of the Stress Response.

Contemporary theory suggests that prefrontal cortex (PFC) function is associated with individual variability in the psychobiology of the stress response. Advancing our understanding of this complex biobehavioral pathway has potential to provide insight into processes that determine individual differences in stress susceptibility. The present study used functional magnetic resonance imaging to examine brain activity during a variation of the Montreal Imaging Stress Task (MIST) in 53 young adults. Salivary cortisol was assessed as an index of the stress response, trait anxiety was assessed as an index of an individual's disposition toward negative affectivity, and self-reported stress was assessed as an index of an individual's subjective psychological experience. Heart rate and skin conductance responses were also assessed as additional measures of physiological reactivity. Dorsomedial PFC, dorsolateral PFC, and inferior parietal lobule demonstrated differential activity during the MIST. Further, differences in salivary cortisol reactivity to the MIST were associated with ventromedial PFC and posterior cingulate activity, while trait anxiety and self-reported stress were associated with dorsomedial and ventromedial PFC activity, respectively. These findings underscore that PFC activity regulates behavioral and psychobiological components of the stress response.

Exploring the Neurocircuitry Underpinning Predictability of Threat in Soldiers with PTSD Compared to Deployment Exposed Controls.

BACKGROUND: Prior work examining emotional dysregulation observed in posttraumatic stress disorder (PTSD) has primarily been limited to fear-learning processes specific to anticipation, habituation, and extinction of threat. In contrast, the response to threat itself has not been systematically evaluated. OBJECTIVE: To explore potential disruption in fear conditioning neurocircuitry in service members with PTSD, specifically in response to predictable versus unpredictable threats. METHOD: In the current study, active-duty U.S. Army soldiers with (PTSD group; n = 38) and without PTSD (deployment-exposed controls; DEC; n = 40), participated in a fear-conditioning study in which threat predictability was manipulated by presenting an aversive unconditioned stimulus (UCS) that was either preceded by a conditioned stimulus (i.e., predictable) or UCS alone (i.e., unpredictable). Threat expectation, skin conductance response (SCR), and functional magnetic resonance imaging (fMRI) signal to predictable and unpredictable threats (i.e., UCS) were assessed. RESULTS: Both groups showed greater threat expectancy and diminished threat-elicited SCRs to predictable compared to unpredictable threat. Significant group differences were observed within the amygdala, hippocampus, insula, and superior and middle temporal gyri. Contrary to our predictions, the PTSD group showed a diminished threat-related response within each of these brain regions during predictable compared to unpredictable threat, whereas the DEC group showed increased activation. CONCLUSION: Although, the PTSD group showed greater threat-related diminution, hypersensitivity to unpredictable threat cannot be ruled out. Furthermore, pre-trauma, trait-like factors may have contributed to group differences in activation of the neurocircuitry underpinning fear conditioning.

Neural mechanisms of human temporal fear conditioning.

Learning the temporal relationship between a warning cue (conditioned stimulus; CS) and aversive threat (unconditioned stimulus; UCS) is an important aspect of Pavlovian conditioning. Although prior functional magnetic resonance imaging (fMRI) research has identified brain regions that support Pavlovian conditioning, it remains unclear whether these regions support time-related processes important for this type of associative learning. Elucidating the neural substrates of temporal conditioning is important for a complete understanding of the Pavlovian conditioning process. Therefore, the present study used a temporal Pavlovian conditioning procedure to investigate brain activity that mediates the formation of temporal associations. During fMRI, twenty-three healthy volunteers completed a temporal conditioning procedure and a control task that does not support conditioning. Specifically, during the temporal conditioning procedure, the UCS was presented at fixed intervals (ITI: 20s) while in the control condition the UCS was presented at random intervals (Average ITI: 20s, ITI Range: 6-34s). We observed greater skin conductance responses and expectancy of the UCS during fixed (i.e., temporal conditioning) relative to random (i.e., control procedure) interval trials. These findings demonstrate fixed trials support temporal conditioning, while random trials do not. During fixed interval trials, greater conditioned fMRI signal responses were observed within dorsolateral prefrontal cortex, inferior parietal lobule, inferior and middle temporal cortex, hippocampus, and amygdala. The current findings suggest these brain regions constitute a neural circuit that encodes the temporal information necessary for Pavlovian fear conditioning.