The effect of dopamine agonists on adaptive and aberrant salience in Parkinson's disease

Clinical evidence suggests that after initiation of dopaminergic medications some patients with Parkinson's disease (PD) develop psychotic symptoms, such as hallucinations and delusions. Here, we tested the hypothesis that the neurocognitive basis of this phenomenon can be defined as the formation of arbitrary and illusory associations between conditioned stimuli and reward signals, called aberrant salience. Young, never-medicated PD patients and matched controls were assessed on a speeded reaction time task in which the probe stimulus was preceded by conditioned stimuli that could signal monetary reward by color or shape. The patients and controls were re-evaluated after 12 weeks during which the patients received a dopamine agonist (pramipexole or ropinirole). Results indicated that dopamine agonists increased both adaptive and aberrant salience in PD patients, that is, formation of real and illusory associations between conditioned stimuli and reward, respectively. This effect was present when associations were assessed by means of faster responding after conditioned stimuli signaling reward (implicit salience) and overt rating of stimulus-reward links (explicit salience). However, unusual feelings and experiences, which are subclinical manifestations of psychotic-like symptoms, were specifically related to irrelevant and illusory stimulus-reward associations (aberrant salience) in PD patients receiving dopamine agonists. The learning of relevant and real stimulus-reward associations (adaptive salience) was not related to unusual experiences. These results suggest that dopamine agonists may increase psychotic-like experiences in young patients with PD, possibly by facilitating dopaminergic transmission in the ventral striatum, which results in aberrant associations between conditioned stimuli and reward

Falling out of time: enhanced memory for scenes presented at behaviorally irrelevant points in time in posttraumatic stress disorder (PTSD)

Spontaneous encoding of the visual environment depends on the behavioral relevance of the task performed simultaneously. If participants identify target letters or auditory tones while viewing a series of briefly presented natural and urban scenes, they demonstrate effective scene recognition only when a target, but not a behaviorally irrelevant distractor, appears together with the scene. Here, we show that individuals with posttraumatic stress disorder (PTSD), who witnessed the red sludge disaster in Hungary, show the opposite pattern of performance: enhanced recognition of scenes presented together with distractors and deficient recognition of scenes presented with targets. The recognition of trauma-related and neutral scenes was not different in individuals with PTSD. We found a positive correlation between memory for scenes presented with auditory distractors and re-experiencing symptoms (memory intrusions and flashbacks). These results suggest that abnormal encoding of visual scenes at behaviorally irrelevant events might be associated with intrusive experiences by disrupting the flow of time

The hidden price of repeated traumatic exposure: different cognitive deficits in different first-responders

Studies on first responders who are repeatedly exposed to traumatic events report low levels of PTSD symptoms and diagnosis. However, neuroimaging and behavioral studies show that traumatic exposure is associated with brain and cognitive dysfunctions. Taking together it may suggest that traumatic exposure have a price, which is not sufficiently defined by the standard PTSD measures. In a recent study we revealed that similar to individuals with PTSD, non-PTSD highly exposed firefighters display a selective impairment in hippocampal related functions. In the current study we aimed to test whether different first responders display a similar impairment. We concentrated on unique populations of active duty firefighters and criminal scene-investigators (CSI) police, who are frequently exposed to similar levels and types of traumatic events, and compared them to civilian matched-controls with no history of trauma-exposure. We used a hippocampal dependent cue-context reversal paradigm, which separately evaluates reversal of negative and positive outcomes of cue and context related information. We predicted and found that all participants were equally able to acquire and retain stimulus-outcome associations. However, there were significant differences in reversal learning between the groups. Performance among firefighters replicated our prior findings; they struggled to learn that a previously negative context is later associated with a positive outcome. CSI police on the other hand showed a selective impairment in reversing the outcome of a negative cue. Hence after learning that a specific cue is associated with a negative outcome, they could not learn that later it is associated with a positive outcome. Performance in both groups did not correlate with levels of PTSD, anxiety, depression or behavioral inhibition symptoms. The results provide further evidence of the hidden price of traumatic exposure, suggesting that this price may differ as a function of occupation

Association among clinical response, hippocampal volume, and FKBP5 gene expression in individuals with posttraumatic stress disorder receiving cognitive behavioral therapy

BACKGROUND: Posttraumatic stress disorder (PTSD) is characterized by a reduced expression of FKBP5, a key modulator of the glucocorticoid receptor. Smaller hippocampal volume has also been documented in PTSD. We explored possible changes in FKBP5 gene expression and brain structure in patients with PTSD after cognitive behavioral therapy (CBT). METHODS: We measured peripheral FKBP5 RNA and volumes of the hippocampus, amygdala, and medial orbitofrontal cortex in 39 patients with PTSD before and after CBT. The control subjects were 31 trauma-exposed individuals without PTSD who were also assessed twice. Gene expression changes were screened with a microarray toolkit, which was followed by quantitative polymerase chain reaction for FKBP5 RNA. Brain volumes were measured using FreeSurfer. RESULTS: At baseline, patients with PTSD showed lower FKBP5 gene expression and smaller hippocampal and medial orbitofrontal cortex, but not amygdala, volumes relative to control subjects. At follow-up, we found significantly increased FKBP5 expression and increased hippocampal volume in patients with PTSD. At follow-up, patients did not differ from control subjects in hippocampal volume. Improvement in PTSD symptoms was predicted by increased FKBP5 expression and increased hippocampal volume, but the primary predictor was FKBP5 expression. The most significantly altered gene expression in patients with PTSD relative to control subjects was found for ribosomal protein S6 kinase, which did not change after CBT and did not correlate with hippocampal volume. CONCLUSIONS: Clinical improvement in individuals with PTSD was associated with increased expression of FKBP5 and increased hippocampal volume, which were positively correlated

Affect labeling: The role of timing and intensity

A growing number of studies have shown that labeling negative feelings can down-regulate distress. The present study aimed to test the effectiveness of affect labeling while manipulating two factors known to influence the emotion regulation process, namely timing, and emotional intensity. In Experiment 1, sixty-three participants completed a performance-based affect labeling paradigm in which they had to choose between two labels that best describe their feeling. Participants were randomly assigned to one of three experimental conditions: (1) Simultaneous labeling- the labeling occurs while watching the aversive picture. (2) Subsequent labeling- the labeling occurs immediately after watching the aversive picture. (3) Delayed labeling- the labeling occurs 10 seconds after watching the aversive picture. We found that affect labeling efficiently down-regulated distress independent of the labeling timing. In Experiment 2, seventy-nine participants utilized simultaneous labeling for aversive pictures with low and high intensity. We revealed that while affect labeling reduces distress in high-intensity aversive conditions, it increases distress in low-intensity conditions. The results question the standard advice, which calls to count to 10 before you speak in highly aversive states. In addition, it suggests that affect labeling can be beneficial in high-intensity conditions. However, it should be used with caution in low-intensity conditions

Impaired context reversal learning, but not cue reversal learning, in patients with amnestic mild cognitive impairment

It has been proposed that reversal learning is impaired following damage to the orbitofrontal and ventromedial frontal cortex (OFC/VMFC) and to the medial temporal lobe (MTL), including the hippocampal formation. However, the exact characteristics of the MTL-associated reversal learning deficit are not known. To investigate this issue, we assessed 30 newly diagnosed patients with amnestic mild cognitive impairment (aMCI) and 30 matched healthy controls. All patients fulfilled the aMCI criteria of the Mayo Clinic Alzheimer's Disease Research Center and underwent head magnetic resonance imaging that confirmed MTL atrophy. Reversal learning was assessed using a novel reinforcement learning task. Participants first acquired and then reversed stimulus-outcome associations based on negative and positive feedback (losing and gaining points). Stimuli consisted of a cue (geometric shapes) and a spatial context (background color or pattern). Neuropsychological assessment included tasks related to the MTL (paired associates learning), dorsolateral prefrontal cortex (DLPFC) (extradimensional shift, One-touch Stockings of Cambridge), and OFC/VMFC (Holiday Apartment Task). Results revealed that, relative to controls, patients with aMCI exhibited a marked reversal learning deficit, which was highly selective for the reversal of context. The acquisition of stimulus-outcome associations and cue reversal learning were spared. Performance on the context reversal learning task significantly correlated with the right hippocampal volume. In addition, patients with aMCI had deficits on tests related to DLPFC but not to OFC/VMFC. However, DLPFC dysfunctions were not associated with context reversal learning. These results suggest that MTL deficits in aMCI selectively affect context reversal learning when OFC/VMFC functions are spared. This deficit is not influenced by the valence of the outcome (positive or negative feedback) and by executive dysfunctions

Neuropsychological functions and visual contrast sensitivity in schizophrenia: the potential impact of comorbid posttraumatic stress disorder (PTSD)

Previous studies have revealed a high prevalence of posttraumatic stress disorder (PTSD) in patients with other severe mental disorders, including schizophrenia. However, the neuropsychological and psychophysical correlates of comorbid PTSD are less exactly defined. The purpose of the present study was to assess immediate and delayed memory, attention, visuospatial skills, language, and basic visual information processing in patients with schizophrenia with or without PTSD. We recruited 125 patients with schizophrenia and 70 healthy controls matched for visual acuity, age, gender, education, and socioeconomic status. Twenty-one of patients with schizophrenia exhibited comorbid PTSD. We administered the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and visual contrast sensitivity tasks for low spatial/high temporal frequency (0.3 cycle/degree and 18 Hz) and high spatial/low temporal frequency (10 cycles/degree and 1Hz) sinusoidal gratings. All patients were clinically stable and received antipsychotic medications. Results revealed that relative to healthy controls, patients with schizophrenia exhibited significant and generalized neuropsychological dysfunctions and reduced visual contrast sensitivity, which was more pronounced at low spatial/high temporal frequency. When we compared schizophrenia patients with and without PTSD, we found that patients with comorbid PTSD displayed lower scores for RBANS attention, immediate and delayed memory, and visuospatial scores. Schizophrenia patients with or without PTSD displayed similar visual contrast sensitivity. In conclusion, comorbid PTSD in schizophrenia may be associated with worse neuropsychological functions, whereas it does not affect basic visual information processing

CD 38 expression, attachment style and habituation of arousal in relation to trust-related oxytocin release

Oxytocin plays an important role in human attachment, trust, social perception, memory, and fear regulation. Evidence suggests that CD38, a regulator of oxytocin release, may also be critical in these processes. The purpose of this study was to investigate the predictors of plasma oxytocin level measured after a task requiring intimate trust (secret sharing), modeling psychotherapeutic processes, and a neutral social interaction. Results revealed that peripheral CD38 expression positively predicted both trust-related and trust-unrelated oxytocin levels. In addition, habituation of arousal, as measured by skin conductance response, and attachment anxiety also emerged as predictors of oxytocin level in the trust-related condition. These results suggest that CD38 plays a general role in oxytocin secretion, whereas habituation of arousal and attachment anxiety are specifically related to situations involving intimate trust

The role of cognitive flexibility in moderating the effect of school-related stress exposure

Abstract Educators are exposed to various stressful events as part of their ongoing work, including violence, sexual assaults, suicidal behavior, and loss or illness of students or their family members. Previous studies revealed an increased risk of developing PTSD symptoms in healthcare and supportive professionals exposed to repeated stress as part of their work. Cognitive flexibility might be a protective factor against the negative effect of such stress. The current study aimed to examine the interactive effects of school-related stress exposure and cognitive flexibility on the tendency to develop Post Traumatic Stress Disorder (PTSD) symptoms and the coping abilities of educators. One hundred and fifty educators (86.5% female; M age = 43.08, M teaching_experience = 12.90) volunteered to participate in this study. They completed questionnaires measuring levels of stress exposure, cognitive flexibility, coping ability, and PTSD symptoms. Analyses revealed that cognitive flexibility moderated the relationship between school-related stress exposure and both PTSD symptoms severity and maladaptive coping. Specifically, whereas educators with low cognitive flexibility exhibited positive associations between continuous stress exposure and both levels of PTSD symptoms and maladaptive coping, no such association was found among educators with high cognitive flexibility. The results highlight the importance of cognitive flexibility as a protective factor against the harmful effects of possible stress exposure in school environments. Awareness of the crucial role of cognitive flexibility as a protective factor for educators can be a breakthrough in improving educators' well-being and adaptive functioning

Correlation between recognition performance for scenes with auditory distractors and re-experiencing symptoms in PTSD. r = 0.41, p<0.05.

<p>Correlation between recognition performance for scenes with auditory distractors and re-experiencing symptoms in PTSD. r = 0.41, p<0.05.</p