Browsing by Subject "Memory Disorders"
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Item Open Access Cognitive and Behavioral Impairments Evoked by Low-Level Exposure to Tobacco Smoke Components: Comparison with Nicotine Alone.(Toxicological sciences : an official journal of the Society of Toxicology, 2016-06) Hall, Brandon J; Cauley, Marty; Burke, Dennis A; Kiany, Abtin; Slotkin, Theodore A; Levin, Edward DActive maternal smoking has adverse effects on neurobehavioral development of the offspring, with nicotine (Nic) providing much of the underlying causative mechanism. To determine whether the lower exposures caused by second-hand smoke are deleterious, we administered tobacco smoke extract (TSE) to pregnant rats starting preconception and continued through the second postnatal week, corresponding to all 3 trimesters of fetal brain development. Dosing was adjusted to produce maternal plasma Nic concentrations encountered with second-hand smoke, an order of magnitude below those seen in active smokers. We then compared TSE effects to those of an equivalent dose of Nic alone, and to a 10-fold higher Nic dose. Gestational exposure to TSE and Nic significantly disrupted cognitive and behavioral function in behavioral tests given during adolescence and adulthood (postnatal weeks 4-40), producing hyperactivity, working memory deficits, and impairments in emotional processing, even at the low exposure levels corresponding to second-hand smoke. Although TSE effects were highly correlated with those of Nic, the effects of TSE were much larger than could be attributed to just the Nic in the mixture. Indeed, TSE effects more closely resembled those of the 10-fold higher Nic levels, but still exceeded their magnitude. In combination with our earlier findings, this study thus completes the chain of causation to prove that second-hand smoke exposure causes neurodevelopmental deficits, originating in disruption of neurodifferentiation, leading to miswiring of neuronal circuits, and as shown here, culminating in behavioral dysfunction. As low level exposure to Nic alone produced neurobehavioral teratology, 'harm reduction' Nic products do not abolish the potential for neurodevelopmental damage.Item Open Access Depressive symptoms among informal caregivers of older adults: insights from the Singapore Survey on Informal Caregiving.(International psychogeriatrics, 2012-08) Malhotra, Chetna; Malhotra, Rahul; Østbye, Truls; Matchar, David; Chan, AngeliqueThis paper determines care recipient and caregiver characteristics and caregiving dimensions - associated with depression among caregivers of older adults, using path analysis and assesses whether the identified path model differs between spousal and adult child caregivers.Data from 1,190 dyads comprising care recipients (community-dwelling adults aged ≥ 75 years with at least one activity of daily living (ADL) limitation) and caregivers (family member/friend most involved in providing care/ensuring provision of care to care recipient), who were interviewed through the Singapore Survey on Informal Caregiving (2010-2011), were used. Using path analysis, we assessed the direct and indirect associations between primary stressors (care recipient's ADL and instrumental ADL status, and memory and behavior problems), caregiver health status, receipt of assistance from a foreign domestic worker/maid, amount of caregiving, negative reaction to caregiving, caregiver's self-esteem, perceived emotional support, and caregiver depressive symptoms.Our analysis showed that primary stressors, receipt of assistance from a foreign domestic worker/maid, perceived emotional support, and caregiver health status were directly or indirectly associated with caregiver depressive symptoms, and this association was mediated by negative reaction to caregiving. Caregiver self-esteem mediated the relationship between perceived emotional support and negative reaction to caregiving only among adult child caregivers.The results provide insights into factors associated with depressive symptoms among spousal and adult child caregivers, and help identify targeted interventions for improving caregiver mood.Item Open Access Entorhinal cortex volume in older adults: reliability and validity considerations for three published measurement protocols.(J Int Neuropsychol Soc, 2010-09) Price, CC; Wood, MF; Leonard, CM; Towler, S; Ward, J; Montijo, H; Kellison, I; Bowers, D; Monk, T; Newcomer, JC; Schmalfuss, IMeasuring the entorhinal cortex (ERC) is challenging due to lateral border discrimination from the perirhinal cortex. From a sample of 39 nondemented older adults who completed volumetric image scans and verbal memory indices, we examined reliability and validity concerns for three ERC protocols with different lateral boundary guidelines (i.e., Goncharova, Dickerson, Stoub, & deToledo-Morrell, 2001; Honeycutt et al., 1998; Insausti et al., 1998). We used three novice raters to assess inter-rater reliability on a subset of scans (216 total ERCs), with the entire dataset measured by one rater with strong intra-rater reliability on each technique (234 total ERCs). We found moderate to strong inter-rater reliability for two techniques with consistent ERC lateral boundary endpoints (Goncharova, Honeycutt), with negligible to moderate reliability for the technique requiring consideration of collateral sulcal depth (Insausti). Left ERC and story memory associations were moderate and positive for two techniques designed to exclude the perirhinal cortex (Insausti, Goncharova), with the Insausti technique continuing to explain 10% of memory score variance after additionally controlling for depression symptom severity. Right ERC-story memory associations were nonexistent after excluding an outlier. Researchers are encouraged to consider challenges of rater training for ERC techniques and how lateral boundary endpoints may impact structure-function associations.Item Open Access Event memory: A theory of memory for laboratory, autobiographical, and fictional events.(Psychol Rev, 2015-01) Rubin, David C; Umanath, ShardaAn event memory is a mental construction of a scene recalled as a single occurrence. It therefore requires the hippocampus and ventral visual stream needed for all scene construction. The construction need not come with a sense of reliving or be made by a participant in the event, and it can be a summary of occurrences from more than one encoding. The mental construction, or physical rendering, of any scene must be done from a specific location and time; this introduces a "self" located in space and time, which is a necessary, but need not be a sufficient, condition for a sense of reliving. We base our theory on scene construction rather than reliving because this allows the integration of many literatures and because there is more accumulated knowledge about scene construction's phenomenology, behavior, and neural basis. Event memory differs from episodic memory in that it does not conflate the independent dimensions of whether or not a memory is relived, is about the self, is recalled voluntarily, or is based on a single encoding with whether it is recalled as a single occurrence of a scene. Thus, we argue that event memory provides a clearer contrast to semantic memory, which also can be about the self, be recalled voluntarily, and be from a unique encoding; allows for a more comprehensive dimensional account of the structure of explicit memory; and better accounts for laboratory and real-world behavioral and neural results, including those from neuropsychology and neuroimaging, than does episodic memory.Item Open Access Functional neuroimaging of emotionally intense autobiographical memories in post-traumatic stress disorder.(J Psychiatr Res, 2011-05) St Jacques, Peggy L; Botzung, Anne; Miles, Amanda; Rubin, David CPost-traumatic stress disorder (PTSD) affects regions that support autobiographical memory (AM) retrieval, such as the hippocampus, amygdala and ventral medial prefrontal cortex (PFC). However, it is not well understood how PTSD may impact the neural mechanisms of memory retrieval for the personal past. We used a generic cue method combined with parametric modulation analysis and functional MRI (fMRI) to investigate the neural mechanisms affected by PTSD symptoms during the retrieval of a large sample of emotionally intense AMs. There were three main results. First, the PTSD group showed greater recruitment of the amygdala/hippocampus during the construction of negative versus positive emotionally intense AMs, when compared to controls. Second, across both the construction and elaboration phases of retrieval the PTSD group showed greater recruitment of the ventral medial PFC for negatively intense memories, but less recruitment for positively intense memories. Third, the PTSD group showed greater functional coupling between the ventral medial PFC and the amygdala for negatively intense memories, but less coupling for positively intense memories. In sum, the fMRI data suggest that there was greater recruitment and coupling of emotional brain regions during the retrieval of negatively intense AMs in the PTSD group when compared to controls.Item Open Access Inhibition-Induced Forgetting Results from Resource Competition between Response Inhibition and Memory Encoding Processes.(J Neurosci, 2015-08-26) Chiu, Yu-Chin; Egner, TobiasUNLABELLED: Response inhibition is a key component of executive control, but its relation to other cognitive processes is not well understood. We recently documented the "inhibition-induced forgetting effect": no-go cues are remembered more poorly than go cues. We attributed this effect to central-resource competition, whereby response inhibition saps attention away from memory encoding. However, this proposal is difficult to test with behavioral means alone. We therefore used fMRI in humans to test two neural predictions of the "common resource hypothesis": (1) brain regions associated with response inhibition should exhibit greater resource demands during encoding of subsequently forgotten than remembered no-go cues; and (2) this higher inhibitory resource demand should lead to memory encoding regions having less resources available during encoding of subsequently forgotten no-go cues. Participants categorized face stimuli by gender in a go/no-go task and, following a delay, performed a surprise recognition memory test for those faces. Replicating previous findings, memory was worse for no-go than for go stimuli. Crucially, forgetting of no-go cues was predicted by high inhibitory resource demand, as quantified by the trial-by-trial ratio of activity in neural "no-go" versus "go" networks. Moreover, this index of inhibitory demand exhibited an inverse trial-by-trial relationship with activity in brain regions responsible for the encoding of no-go cues into memory, notably the ventrolateral prefrontal cortex. This seesaw pattern between the neural resource demand of response inhibition and activity related to memory encoding directly supports the hypothesis that response inhibition temporarily saps attentional resources away from stimulus processing. SIGNIFICANCE STATEMENT: Recent behavioral experiments showed that inhibiting a motor response to a stimulus (a "no-go cue") impairs subsequent memory for that cue. Here, we used fMRI to test whether this "inhibition-induced forgetting effect" is caused by competition for neural resources between the processes of response inhibition and memory encoding. We found that trial-by-trial variations in neural inhibitory resource demand predicted subsequent forgetting of no-go cues and that higher inhibitory demand was furthermore associated with lower concurrent activation in brain regions responsible for successful memory encoding of no-go cues. Thus, motor inhibition and stimulus encoding appear to compete with each other: when more resources have to be devoted to inhibiting action, less are available for encoding sensory stimuli.Item Open Access Reduced hippocampal and amygdala activity predicts memory distortions for trauma reminders in combat-related PTSD.(J Psychiatr Res, 2011-05) Hayes, Jasmeet Pannu; LaBar, Kevin S; McCarthy, Gregory; Selgrade, Elizabeth; Nasser, Jessica; Dolcos, Florin; VISN 6 Mid-Atlantic MIRECC workgroup; Morey, Rajendra ANeurobiological models of posttraumatic stress disorder (PTSD) suggest that altered activity in the medial temporal lobes (MTL) during encoding of traumatic memories contribute to the development and maintenance of the disorder. However, there is little direct evidence in the PTSD literature to support these models. The goal of the present study was to examine MTL activity during trauma encoding in combat veterans using the subsequent memory paradigm. Fifteen combat veterans diagnosed with PTSD and 14 trauma-exposed control participants viewed trauma-related and neutral pictures while undergoing event-related fMRI. Participants returned one week after scanning for a recognition memory test. Region-of-interest (ROI) and voxel-wise whole brain analyses were conducted to examine the neural correlates of successful memory encoding. Patients with PTSD showed greater false alarm rates for novel lures than the trauma-exposed control group, suggesting reliance on gist-based representations in lieu of encoding contextual details. Imaging analyses revealed reduced activity in the amygdala and hippocampus in PTSD patients during successful encoding of trauma-related stimuli. Reduction in left hippocampal activity was associated with high arousal symptoms on the Clinician-Administered PTSD Scale (CAPS). The behavioral false alarm rate for traumatic stimuli co-varied with activity in the bilateral precuneus. These results support neurobiological theories positing reduced hippocampal activity under conditions of high stress and arousal. Reduction in MTL activity for successfully encoded stimuli and increased precuneus activity may underlie reduced stimulus-specific encoding and greater gist memory in patients with PTSD, leading to maintenance of the disorder.Item Open Access Targeting Treatments to Improve Cognitive Function in Mood Disorder: Suggestions From Trials Using Erythropoietin.(The Journal of clinical psychiatry, 2016-12) Miskowiak, Kamilla Woznica; Rush, A John; Gerds, Thomas A; Vinberg, Maj; Kessing, Lars VObjective
There is no established efficacious treatment for cognitive dysfunction in unipolar and bipolar disorder. This may be partially due to lack of consensus regarding the need to screen for cognitive impairment in cognition trials or which screening criteria to use. We have demonstrated in 2 randomized placebo-controlled trials that 8 weeks of erythropoietin (EPO) treatment has beneficial effects on verbal memory across unipolar and bipolar disorder, with 58% of EPO-treated patients displaying a clinically relevant memory improvement as compared to 15% of those treated with placebo.Methods
We reassessed the data from our 2 EPO trials conducted between September 2009 and October 2012 to determine whether objective performance-based memory impairment or subjective self-rated cognitive impairment at baseline was related to the effect of EPO on cognitive function as assessed by Rey Auditory Verbal Learning Test (RAVLT) total recall with multiple logistic regression adjusted for diagnosis, age, gender, symptom severity, and education levels.Results
We included 79 patients with an ICD-10 diagnosis of unipolar or bipolar disorder, of whom 39 received EPO and 40 received placebo (saline). For EPO-treated patients with objective memory dysfunction at baseline (n = 16) (defined as RAVLT total recall ≤ 43), the odds of a clinically relevant memory improvement were increased by a factor of 290.6 (95% CI, 2.7-31,316.4; P = .02) compared to patients with no baseline impairment (n = 23). Subjective cognitive complaints (measured with the Cognitive and Physical Functioning Questionnaire) and longer illness duration were associated with small increases in patients' chances of treatment efficacy on memory (53% and 16% increase, respectively; P ≤ .04). Diagnosis, gender, age, baseline depression severity, and number of mood episodes did not significantly change the chances of EPO treatment success (P ≥ .06). In the placebo-treated group, the odds of memory improvement were not significantly different for patients with or without objectively defined memory dysfunction (P ≥ .59) or subjective complaints at baseline (P ≥ .06).Conclusions
Baseline objectively assessed memory impairments and-to a lesser degree-subjective cognitive complaints increased the chances of treatment efficacy on cognition in unipolar and bipolar disorder.Trial registration
ClinicalTrials.gov identifier: NCT00916552.Item Open Access Xenon and sevoflurane provide analgesia during labor and fetal brain protection in a perinatal rat model of hypoxia-ischemia.(PloS one, 2012-01) Yang, Ting; Zhuang, Lei; Rei Fidalgo, António M; Petrides, Evgenia; Terrando, Niccolo; Wu, Xinmin; Sanders, Robert D; Robertson, Nicola J; Johnson, Mark R; Maze, Mervyn; Ma, DaqingIt is not possible to identify all pregnancies at risk of neonatal hypoxic-ischemic encephalopathy (HIE). Many women use some form of analgesia during childbirth and some anesthetic agents have been shown to be neuroprotective when used as analgesics at subanesthetic concentrations. In this study we sought to understand the effects of two anesthetic agents with presumptive analgesic activity and known preconditioning-neuroprotective properties (sevoflurane or xenon), in reducing hypoxia-induced brain damage in a model of intrauterine perinatal asphyxia. The analgesic and neuroprotective effects at subanesthetic levels of sevoflurane (0.35%) or xenon (35%) were tested in a rat model of intrauterine perinatal asphyxia. Analgesic effects were measured by assessing maternal behavior and spinal cord dorsal horn neuronal activation using c-Fos. In separate experiments, intrauterine fetal asphyxia was induced four hours after gas exposure; on post-insult day 3 apoptotic cell death was measured by caspase-3 immunostaining in hippocampal neurons and correlated with the number of viable neurons on postnatal day (PND) 7. A separate cohort of pups was nurtured by a surrogate mother for 50 days when cognitive testing with Morris water maze was performed. Both anesthetic agents provided analgesia as reflected by a reduction in the number of stretching movements and decreased c-Fos expression in the dorsal horn of the spinal cord. Both agents also reduced the number of caspase-3 positive (apoptotic) neurons and increased cell viability in the hippocampus at PND7. These acute histological changes were mirrored by improved cognitive function measured remotely after birth on PND 50 compared to control group. Subanesthetic doses of sevoflurane or xenon provided both analgesia and neuroprotection in this model of intrauterine perinatal asphyxia. These data suggest that anesthetic agents with neuroprotective properties may be effective in preventing HIE and should be tested in clinical trials in the future.