Age-related alterations in simple declarative memory and the effect of negative stimulus valence

Healthy aging has been shown to modulate the neural circuitry underlying simple declarative memory; however, the functional impact of negative stimulus valence on these changes has not been fully investigated. Using BOLD fMRI, we explored the effects of aging on behavioral performance, neural activity, and functional coupling during the encoding and retrieval of novel aversive and neutral scenes. Behaviorally, there was a main effect of valence with better recognition performance for aversive greater than neutral stimuli in both age groups. There was also a main effect of age with better recognition performance in younger participants compared to older participants. At the imaging level, there was a main effect of valence with increased activity in the medial-temporal lobe (amygdala and hippocampus) during both encoding and retrieval of aversive relative to neutral stimuli. There was also a main effect of age with older participants showing decreased engagement of medial-temporal lobe structures and increased engagement of prefrontal structures during both encoding and retrieval sessions. Interestingly, older participants presented with relatively decreased amygdalar-hippocampal coupling and increased amygdalar-prefrontal coupling when compared to younger participants. Furthermore, older participants showed increased activation in prefrontal cortices and decreased activation in the amygdala when contrasting the retrieval of aversive and neutral scenes. These results suggest that although normal aging is associated with a decline in declarative memory with alterations in the neural activity and connectivity of brain regions underlying simple declarative memory, memory for aversive stimuli is relatively better preserved than for neutral stimuli, possibly through greater compensatory prefrontal cortical activit

Acute tryptophan depletion attenuates conscious appraisal of social emotional signals in healthy female volunteers

Rationale: Acute tryptophan depletion (ATD) decreases levels of central serotonin. ATD thus enables the cognitive effects of serotonin to be studied, with implications for the understanding of psychiatric conditions, including depression. Objective: To determine the role of serotonin in conscious (explicit) and unconscious/incidental processing of emotional information. Materials and methods: A randomized, double-blind, cross-over design was used with 15 healthy female participants. Subjective mood was recorded at baseline and after 4 h, when participants performed an explicit emotional face processing task, and a task eliciting unconscious processing of emotionally aversive and neutral images presented subliminally using backward masking. Results: ATD was associated with a robust reduction in plasma tryptophan at 4 h but had no effect on mood or autonomic physiology. ATD was associated with significantly lower attractiveness ratings for happy faces and attenuation of intensity/arousal ratings of angry faces. ATD also reduced overall reaction times on the unconscious perception task, but there was no interaction with emotional content of masked stimuli. ATD did not affect breakthrough perception (accuracy in identification) of masked images. Conclusions: ATD attenuates the attractiveness of positive faces and the negative intensity of threatening faces, suggesting that serotonin contributes specifically to the appraisal of the social salience of both positive and negative salient social emotional cues. We found no evidence that serotonin affects unconscious processing of negative emotional stimuli. These novel findings implicate serotonin in conscious aspects of active social and behavioural engagement and extend knowledge regarding the effects of ATD on emotional perception

Assessing the long-term sequelae of mild traumatic brain injury

A mild traumatic brain injury (mTBI), also known as a concussion, is defined as an injury that results in an alteration of consciousness or mental status. Previous studies have shown mTBI populations experience a number of chronic (\u3e 1 year) symptoms, such as sleep disturbances (e.g., sleep stage alterations), mood alterations (e.g., depressive symptoms), and cognitive alterations (e.g., poor concentration). The three chapters of this dissertation sought to explore these long-term sequelae and the possible interrelations between them. In the first experiment, sleep-dependent memory consolidation of neutral stimuli was probed in a chronic mTBI sample and a control, uninjured sample. I hypothesized memory consolidation would be reduced in the mTBI sample. However, sleep-dependent consolidation was found to be intact in the mTBI sample, despite differences in sleep architecture between groups. Given that risk for mood disorders is elevated following mTBI, in the second experiment, sleep-dependent memory consolidation of emotional images was assessed in groups that were similar to those assessed in Study 1, with the hypothesis that mTBI participants would have reduced consolidation. The mTBI group had reduced sleep-dependent memory consolidation (i.e., memory considation that occurred over a sleep period) but enhanced wake-dependent consolidation (i.e., memory consolidation that occurred over a wake period) of emotional (but not neutral) images. The mTBI group also unexpectedly exhibited a lack of emotion habituation (i.e., emotion desensitization). The third experiment attempted to replicate the latter (unexpected) finding (i.e., reductions in habituation in the mTBI group) while also probing physiological measures of emotion (e.g., heart rate deceleration), which provide an objective measure of emotion. I theorized that reduced habituation might increase the risk for mood disturbances in this population. I was not able to replicate findings of the second experiment, and, on the contrary, found mTBI participants had enhanced emotion habituation In the three experiments, we failed to find expected cognitive and emotional processing deficits in the mTBI samples. In future work, recruiting alternative subsamples of mTBI individuals (e.g., those with Post-concussive syndrome or those with 3 or more mTBIs) could provide insight into which individuals experience negative outcomes in the chronic stages of mTBI

REM Sleep, Prefrontal Theta, and the Consolidation of Human Emotional Memory

Both emotion and sleep are independently known to modulate declarative memory. Memory can be facilitated by emotion, leading to enhanced consolidation across increasing time delays. Sleep also facilitates offline memory processing, resulting in superior recall the next day. Here we explore whether rapid eye movement (REM) sleep, and aspects of its unique neurophysiology, underlie these convergent influences on memory. Using a nap paradigm, we measured the consolidation of neutral and negative emotional memories, and the association with REM-sleep electrophysiology. Subjects that napped showed a consolidation benefit for emotional but not neutral memories. The No-Nap control group showed no evidence of a consolidation benefit for either memory type. Within the Nap group, the extent of emotional memory facilitation was significantly correlated with the amount of REM sleep and also with right-dominant prefrontal theta power during REM. Together, these data support the role of REM-sleep neurobiology in the consolidation of emotional human memories, findings that have direct translational implications for affective psychiatric and mood disorders

Associations between sleep and cognitive-affective functioning in Posttraumatic Stress Disorder

The current research tested the proposition that the sleep disruption characteristic of posttraumatic stress disorder (PTSD) has discrete, predictable, and significant effects on the processing of neutral declarative memory, emotional memory, and emotional reactivity. Research spanning multiple neuroscientific literatures demonstrates that healthy, uninterrupted sleep is critical for memory consolidation and emotional regulation, and that PTSD-diagnosed individuals experience sleep disruption, memory deficits, and emotional dysregulation. To test whether these behavioral, cognitive, and affective characteristics of PTSD are meaningfully related, I recruited three groups of participants: PTSD (n = 21), trauma-exposed non-PTSD (TE; n = 19), and healthy controls (HC; n = 20). Each participant was assessed before and after an 8-hour period of sleep and an 8-hour period of waking activity. The assessment featured measures of neutral declarative memory (learning of stimuli before the delay, and a free recall task afterward), emotional memory (exposure to highly-arousing negatively valenced, highly-arousing positively valenced, and low arousing neutral pictures before the delay, and a recognition task afterward), and emotional reactivity (physiological responses to the emotional pictures, both before and after the delay). The results are presented under the headings of four investigations. Investigation 1, which focused on objective and subjective sleep quality, suggested that PTSD-diagnosed participants had decreased sleep depth in comparison to HC participants, but presented with no other evidence of objective sleep disruption. Furthermore, PTSD-diagnosed participants reported better subjective sleep quality in the sleep laboratory than in their home environment, an effect not observed in TE and HC participants. Investigation 2, which focused on neutral declarative memory, suggested that after a sleep-filled, but not wake-filled, delay, PTSD-diagnosed participants retained less neutral declarative information than TE and HC participants. Furthermore, increased fragmentation of rapid eye movement (REM) sleep in PTSD-diagnosed individuals was a significant predictor of post-sleep memory retention deficits. In contrast, Investigations 3 and 4 suggested no significant between-group differences in emotional memory or emotional reactivity. However, Investigation 3 suggested that, after a sleep-filled delay, pictures of all valence and arousal categories were recognized equally accurately by all participants. In contrast, after a wake-filled delay all participants had higher recognition accuracy for negative pictures. Furthermore, Investigation 4 suggested that a sleep-filled delay attenuated emotional reactivity to pictures of all arousal and valence categories, whereas a wake-filled delay was associated with a rise in emotional reactivity across the day. Together, these results suggest that fairly small sleep disruptions (specific to REM-related changes) in PTSD-diagnosed individuals will affect retention of neutral declarative information, but will have no significant effects on the processing of, or reactivity toward, arousing and valenced stimuli. Overall, these findings allow the conclusion that, in PTSD, the co-occurrence of sleep and neutral declarative memory difficulties is not accidental – that is, these two symptom clusters are meaningfully related. Furthermore, the results demonstrate that a reasonable, not necessarily perfect, night of sleep in PTSD is associated with intact functioning within certain cognitive and affective domains. The research bolsters the neuroscientific view of sleep as a critical biological process linked integrally to psychological well-being

True and False Memories: Neuropsychological and Neuropharmacological Approaches

Some recent studies have explored the false memory and its mechanisms. True memories depend on draw in the past, retrieve of the information, remember past events plus recombine (reorganize) them with new information to finally re-encode these elements creating a new memory. But, sometimes failures in this system lead to memory errors collaborating to false memory formation. This chapter will address new neuropsychological tools to evaluate true and false memory performance. Some neuropharmacological aspects as possible mechanisms of agonist and antagonist modulation of false memory will be discussed

Dose-Dependent Effects of Endotoxin on Neurobehavioral Functions in Humans

Clinical and experimental evidence document that inflammation and increased peripheral cytokine levels are associated with depression-like symptoms and neuropsychological disturbances in humans. However, it remains unclear whether and to what extent cognitive functions like memory and attention are affected by and related to the dose of the inflammatory stimulus. Thus, in a cross-over, double-blind, experimental approach, healthy male volunteers were administered with either placebo or bacterial lipopolysaccharide (LPS) at doses of 0.4 (n = 18) or 0.8 ng/kg of body weight (n = 16). Pro- and anti-inflammatory cytokines, norephinephrine and cortisol concentrations were analyzed before and 1, 1.75, 3, 4, 6, and 24 h after injection. In addition, changes in mood and anxiety levels were determined together with working memory (n-back task) and long term memory performance (recall of emotional and neutral pictures of the International Affective Picture System). Endotoxin administration caused a profound transient physiological response with dose-related elevations in body temperature and heart rate, increases in plasma interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α and IL-1 receptor antagonist (IL-1ra), salivary and plasma cortisol, and plasma norepinephrine. These changes were accompanied by dose-related decreased mood and increased anxiety levels. LPS administration did not affect accuracy in working memory performance but improved reaction time in the high-dose LPS condition compared to the control conditon. In contrast, long-term memory performance was impaired selectively for emotional stimuli after administration of the lower but not of the higher dose of LPS. These data suggest the existence of at least two counter-acting mechanisms, one promoting and one inhibiting cognitive performance during acute systemic inflammation

Fear from the heart: sensitivity to fear stimuli depends on individual heartbeats

Cognitions and emotions can be influenced by bodily physiology. Here, we investigated whether the processing of brief fear stimuli is selectively gated by their timing in relation to individual heartbeats. Emotional and neutral faces were presented to human volunteers at cardiac systole, when ejection of blood from the heart causes arterial baroreceptors to signal centrally the strength and timing of each heartbeat, and at diastole, the period between heartbeats when baroreceptors are quiescent. Participants performed behavioral and neuroimaging tasks to determine whether these interoceptive signals influence the detection of emotional stimuli at the threshold of conscious awareness and alter judgments of emotionality of fearful and neutral faces. Our results show that fearful faces were detected more easily and were rated as more intense at systole than at diastole. Correspondingly, amygdala responses were greater to fearful faces presented at systole relative to diastole. These novel findings highlight a major channel by which short-term interoceptive fluctuations enhance perceptual and evaluative processes specifically related to the processing of fear and threat and counter the view that baroreceptor afferent signaling is always inhibitory to sensory perception