Chronological Effects of Emotional Valence on the Self-selected Retrieval of Autobiographical Memories.

BACKGROUND AND OBJECTIVE: Salience of emotional autobiographical memories may have temporal patterns associated with valence. Recall of negative emotional memories is often important in survival and well-being. Based on the possible survival value of negative memories, we posited that when given an open-ended request to recall either a sad or a happy memory, people are more likely to recall an older sad memory than a happy one. METHODS: We asked 20 healthy participants, aged 18-63 years, to freely recall happy and sad emotional memories and estimate the length of time that had passed since the recalled event had occurred. We analyzed the age of each memory based on valence. RESULTS: Sixteen of 20 participants volunteered a more remote sad than happy memory (P<0.05). Older participants' sad memories were more remote (P<0.05), but the ratio of happy to sad memories was not affected by age. CONCLUSIONS: Self-selected free retrieval of autobiographical happy and sad emotional memories reveals a time bias. Although the reason for this temporal dichotomy is unknown, it may be that engaging systems involved in defense and survival alters the encoding and/or retrieval characteristics of the memory that modify salience.

The Effects of Chronic Right Hemispheric Damage on the Allocation of Spatial Attention: Alterations of Accuracy and Reliability.

Right hemispheric damage (RHD) caused by strokes often induce attentional disorders such as hemispatial neglect. Most patients with neglect over time have a reduction in their ipsilesional spatial attentional bias. Despite this improvement in spatial bias, many patients remain disabled. The cause of this chronic disability is not fully known, but even in the absence of a directional spatial attentional bias, patients with RHD may have an impaired ability to accurately and precisely allocate their spatial attention. This inaccuracy and variable directional allocation of spatial attention may be revealed by repeated performance on a spatial attentional task, such as line bisection (LBT). Participants with strokes of their right versus left (LHD) hemisphere along with healthy controls (HC) performed 24 consecutive trials of 24 cm horizontal line bisections. A vector analysis of the magnitude and direction of deviations from midline, as well as their standard deviations (SD), were calculated. The results demonstrated no significant difference between the LHD, RHD and HC groups in overall spatial bias (mean bisection including magnitude and direction); however, the RHD group had a significantly larger variability of their spatial errors (SD), and made larger errors (from midline) than did the LHD and HC groups. There was a curvilinear relationship between the RHD participants' performance variability and their severity of their inaccuracy. Therefore, when compared to HC and LHD, the RHD subjects' performance on the LBT is more variable and inaccurate.

Administration of exogenous melatonin increases spreading activation in lexical memory networks.

OBJECTIVE: Several studies have examined the effect of exogenous melatonin on memory and cognitive functioning. Many of these investigations have reported improvement in recall and recognition as well as performance on various other indices of neuropsychological functioning. However, there have been no investigations reported that have examined the effects of exogenous melatonin administration on spreading activation in lexical and semantic memory networks. Hence, the purpose of this investigation was to determine the effects of melatonin on spreading activation. METHODS: Participants were randomly assigned to either a 3-mg or 5-mg dose group, and spreading activation was measured both before and after administration. Spreading activation was measured by calculating the average word frequencies for words generated on the controlled oral word association test and the semantic fluency test. RESULTS: A significant main effect for time was found, with the controlled oral word association test average word frequency being significantly higher at baseline than after taking melatonin. Also, a significant group × time interaction was found when using log transformed data. Multiple comparisons indicated that the 3-mg group exhibited significantly greater spreading activation following melatonin than the 5-mg group. The results indicate that melatonin may produce an increase in spreading activation in lexical memory networks. These results potentially provide an explanation for the benefits of melatonin on memory functioning.

Cerebral asymmetry in the control of cardiovascular functioning: evidence from lateral vibrotactile stimulation.

Research has supported hemispheric specialisation in the regulation of cardiovascular functioning, with the left hemisphere being associated with parasympathetic functioning and the right hemisphere with sympathetic functioning. We sought to investigate this relationship further using vibrotactile stimulation applied to the palms. Our prediction was that vibrotactile stimulation applied to the left hand would result in increased heart rate and blood pressure, and that stimulation applied to the right hand would result in decreased heart rate and blood pressure. The results indicated significant differences in heart rate change scores in the predicted direction. No differences were noted for systolic or diastolic blood pressure. Hence the findings provide partial support for the lateralisation of autonomic functions.

Cerebrospinal fluid markers for Alzheimer's disease in a cognitively healthy cohort of young and old adults.

BACKGROUND: Low amyloid ß42 (Aß42) and high total tau and phosphorylated tau (p-tau) concentrations in the cerebrospinal fluid (CSF) are biomarkers of Alzheimer's disease (AD), reflecting brain deposition of amyloid plaques and tangles. Age and apolipoprotein E allele E4 are two strong risk factors for AD, but few data are still available on their effect on CSF markers in normal aging. OBJECTIVE: To study the effect of age on CSF Aß42, total tau, and p-tau levels in a well-characterized group of cognitively normal subjects. METHODS: CSF Aß42 levels of 81 subjects (27% female, 53 ± 15.3 years, range: 21-88) were determined with sandwich enzyme-linked immunosorbent assay; of these, total tau and p-tau levels were measured in 61 (75%) and 42 (52%) cases, respectively. A linear regression analysis between age and CSF markers was carried out on the whole sample and separately in apolipoprotein E allele ɛ4 carriers and noncarriers. RESULTS: The median levels of all markers were significantly different between young (<65 years) and old (≥65 years) subjects (Aß42: P = .03; tau: P = .02; p-tau: P = .002; tau/Aß42: P = .004; p-tau/Aß42: P = .03). The association of marker levels with age was confirmed in linear regression models, where a positive relationship with age was observed for total tau (B = 2.3; 95% confidence interval [CI]: 0.89 to 3.7; P = .002), p-tau (B = 0.5; 95% CI: 0.1 to 0.9; P = .02), and tau/Aß42 ratio (B = 0.006; 95% CI: 0.002 to 0.01; P = .002). No subjects showed abnormal tau, whereas 19% showed abnormal CSF Aß42 concentrations. CONCLUSION: In cognitively normal subjects, the concentrations of CSF biomarkers of AD are associated with age. Further longitudinal studies could clarify whether Aß42 low levels represent a preclinical AD biomarker.

Increased spreading activation in depression.

The dopaminergic system is implicated in depressive disorders and research has also shown that dopamine constricts lexical/semantic networks by reducing spreading activation. Hence, depression, which is linked to reductions of dopamine, may be associated with increased spreading activation. However, research has generally found no effects of depression on spreading activation, using semantic priming paradigms. We used a different paradigm to investigate the relationship between depression and spreading activation, one based on word frequencies. Our sample included 97 undergraduates who completed the BDI-II and the Controlled Oral Word Association test as well as the Animal Naming test. The results indicated that the group scoring within the depressed ranged evidenced greater spreading activation as compared to those who scored within the normal range on the BDI-II. The implications of these results as they relate to creativity in depression is discussed.

Influence of left versus right hemibody onset Parkinson's disease on cardiovascular control.

Whereas the left hemisphere is involved in regulating the parasympathetic nervous system, the right hemisphere regulates the sympathetic. Given the asymmetrical onset of motor symptoms and neuropathology in PD, differences in cardiovascular functions might be expected between PD patients with left hemibody onset (LHO) versus right hemibody onset (RHO). A total of 66 PD patients served as participants, including 31 LHO patients and 35 RHO PD patients. All participants had their resting heart rate (HR) and blood pressure (BP) recorded. Although the LHO group had lower systolic BP, it had higher resting HR than did the RHO group. The reason for this dissociation is not known but might be related to asymmetrical vagus nerve control of the heart (SA node). Future researchers might want to use additional indices of cardiovascular functioning that are more precise measures of parasympathetic and sympathetic functioning, as well as learn the influence of dopaminergic medications.

Feeling down: idiom or nature?

Different emotions activate different parts of the brain, and different parts of the brain direct actions-intentions as well as attention (AIA) to different portions of space. This pilot study attempted to learn how different emotions elicited by emotional memories altered the voluntary spatial allocation of AIA. Twenty normal participants were asked to mark a large sheet of paper in any place of their choosing following recollection of seven types of emotional memories. The results suggest that different emotional memories-experiences can influence the spatial allocation of AIA with positive emotional memories inducing a distal or superior bias and sad memories inducing a proximal or inferior bias. Although these results support the hypotheses that emotions can influence the spatial direction of AIA, these preliminary results need replication and further exploration.

Verbal and visuospatial memory in lateral onset Parkinson disease: time is of the essence.

OBJECTIVE: This investigation sought to study immediate and delayed verbal and visuospatial recall in Parkinson disease (PD) patients with left hemibody (LHO) and right hemibody (RHO) onset of motor symptoms and to examine the role of mental processing speed in recall of this information. BACKGROUND: Research is mixed regarding material specific memory impairments in LHO and RHO PD. However, earlier research has not used a factorial approach in investigating material specific memory in LHO and RHO PD. We hypothesized that LHO PD patients would exhibit an increase in performance following the delayed verbal free recall trial and either decline or stability in performance on the delayed visuospatial free recall trial. The opposite pattern was hypothesized for RHO PD patients. METHOD: The Hopkins Verbal Learning Test-revised (HVLT-R) and the Brief Visuospatial Memory Test-revised (BVMT-R) were administered to a sample of 28 LHO PD patients and 36 RHO PD patients. The Stroop Color-word Test was administered as a measure of mental processing speed. RESULTS: The results indicated that the RHO group experienced a significant decline in performance on verbal free recall from the immediate to the delayed trials and a significant improvement in performance from the immediate to the delayed visuospatial free recall trials. Additionally, a significant negative correlation was found between mental processing speed and changes in recall from the immediate to the delayed conditions for the RHO group. CONCLUSIONS: These results indicate that the RHO PD group experienced a significant decline in verbal free recall and a significant improvement in visuospatial free recall from the immediate to the delayed trials and that the LHO PD patients experienced no significant changes. Further, mental processing speed appears to influence the recall of information from the immediate to the delayed conditions.

Anxiety affects working memory only in left hemibody onset Parkinson disease patients.

OBJECTIVE: This investigation sought to examine the potential moderating influence of heightened anxiety on working memory in Parkinson disease (PD) patients. Further, we wanted to determine whether this moderating influence of anxiety differentially affects PD patients with left hemibody (LBH) versus right hemibody (RHB) onset of motor symptoms. BACKGROUND: Research has examined the neurocognitive effects of depression in PD. However, a paucity of research has examined the effects of heightened anxiety in PD. We predicted that LHB PD patients with heightened anxiety would perform worse on a measure of working memory than RHB PD patients. METHOD: A total of 59 PD patients completed the state-trait anxiety inventory and were also administered the digit span subtest of the Wechsler Memory Scale-III. RESULTS: The results supported the hypotheses, indicating that the LHB PD patients with heightened anxiety performed significantly worse than the RHB PD patients with heightened anxiety and the LHB PD patients with low anxiety. CONCLUSIONS: These findings suggest that left hemibody onset PD patients may experience more disability in their activities of daily living. Future research should explore whether differences also exist between PD patients with and without the diagnosed anxiety disorders.

Bilateral restless legs affecting a phantom limb, treated with dopamine agonists.

BACKGROUND: Restless legs syndrome (RLS) is a common condition characterised by unpleasant sensations deep inside the legs, which usually occurs at rest and especially at night. These sensations are accompanied by an urge to move the limb, and movements result in a temporary relief of the symptoms. The pathophysiology of RLS is not completely known, especially the role of afferent feedback. An individual with a below the knee amputation who developed restless legs in his real and phantom limbs is reported. METHODS AND RESULTS: A 54-year-old man with a left leg amputation 22 years ago developed RLS, primarily at night, that met the International RLS Study Group's criteria for RLS. This RLS, however, involved both his real and phantom lower limbs. Movement and phantom movements, as well as treatment with dopamine agonists, relieved this symptom in both the real and amputated limbs. However, creating an image of the limb moving without "moving" the limb did not improve the uncomfortable sensations in either limb. CONCLUSIONS: That restless legs can occur simultaneously in a phantom as well as a real limb and that the perception of movement in a phantom limb as well as dopaminergic treatment improved the symptoms provides further support for the important role of central nervous system dysfunction in the development of this disorder.

Verbal learning in Alzheimer's disease: cumulative word knowledge gains across learning trials.

Research regarding learning in Alzheimer's disease (AD) patients has been mixed. Learning capacity might be better indexed using a score that reflects the interaction between the learning slope and total recall, referred to as the Cumulative Word Learning (CWL) score. We compared a group of AD patients to normal participants using a traditional index of learning and the CWL score that were derived from the Hopkins Verbal Learning Test-Revised (HVLT-R). The HVLT-R is a supra-span, list-learning test containing 12 words from three semantic categories. The results indicated that the sample of AD patients performed within the average range, using the traditional learning z score. Although mild AD patients were not found to differ from controls in the traditional learning z score, a significant difference was noted for the CWL score. The moderate AD patients differed from the normal controls in both learning measures. Furthermore, unlike the traditional learning score, the CWL score was a significant predictor of overall cognitive functioning, as indexed using their Mini-Mental State Examination (MMSE) score. Thus, the CWL score might be a more sensitive indicator overall of total learning capacity and may be useful in staging Alzheimer's disease because of increased resilience to floor effects.

Conceptual hypometria? An evaluation of conceptual mapping of space in Parkinson's disease.

When interacting with objects in their environment, patients with Parkinson's disease (PD) often make hypometric movements (e.g., micrographia). The purpose of this study was to learn if patients with PD, in the absence of overt actions or environmental stimuli, have egocentric (body-centered) conceptual (representational) hypometria. Actions can take place in either proximal or distal peri-personal space. Normally, the right hemisphere has a distal and the right a proximal attentional bias. We also want to learn if a patient with onset of disease in the right hemisphere would have a greater conceptual action hypometria than individuals with left hemispheric onset. Seventeen subjects with PD and 15 age-matched controls were given a questionnaire evaluating subjective perception of personal action space. The questionnaire asked individuals to rate, using a 0-5 scale, the distances between their body and hand when performing the various actions that take place in peri-personal space. When compared to control participants, participants with PD, and especially those with predominant left sided symptoms (right greater than left hemispheric dysfunction) had hypometric mental perceptions for actions that normally occur in far peri-personal space. Individuals with PD appear to demonstrate a conceptual hypometria, suggesting that there is a perturbation of their interactive representational maps and these maps appear to be more disordered by right than left hemisphere dysfunction. However, it is also possible that when making action distance computations, participants used covert actions and it was the hypometric covert actions that induced the computational hypometria.

Greater motor improvement in right hemibody Parkinson's patients after dopaminergic medications.

Due to motor and neuropathological asymmetries, Parkinson's disease (PD) patients with right hemibody onset (RHO) of symptoms may experience greater benefit from dopaminergic enhancing medications, relative to patients with left hemibody onset (LHO). We investigated this possibility by measuring UPDRS scores of 20 PD patients with LHO and 13 patients with RHO, both prior and subsequent to taking dopaminergic enhancing medications. Following treatment, the motor score from the UPDRS improved for both groups of patients. However, PD patients with RHO experienced greater improvement in motor functioning following administration of dopaminergic enhancing medications than those with LHO.

Assessment of nonverbal learning and memory using the Design Learning Test.

The laterality of verbal and nonverbal learning and memory to the left and right temporal lobes, respectively, has received much empirical support. Researchers have often used the Rey Auditory Verbal Learning Test (RAVLT) as a measure of verbal learning and memory in these investigations. However, a precise analog of the RAVLT that uses stimuli difficult to encode verbally has not been reported. Further, although researchers have developed some measures that are essentially visuospatial analogs of the RAVLT, no correlational data have been reported attesting to the relation between the measures. The authors report the development of a nonverbal analog of the RAVLT, referred to as the Design Learning Test (DLT). Also, the authors present correlational data supporting a relation between the DLT and RAVLT, and they hope that the present study will stimulate research investigating whether the DLT is sensitive to right temporal lobe functioning.

Spreading activation of lexical-semantic networks in Parkinson's disease.

Although dopamine may act as a neuromodulator of spreading activation within semantic networks, this role of dopamine in lexical networks has not been investigated. Hence, we sought to investigate the effects of Parkinson's disease (PD), which is associated with dopamine depletion, on spreading activation in the lexical networks. Ten Parkinson's disease patients and 11 normal controls performed the controlled oral word association test and the average word frequency for their responses was calculated and used as an index of spreading activation. The PD patients exhibited a lower average word frequency, suggesting increased spreading activation, and a significant relationship between the strength of the initial activation and subsequent extent of spreading activation. Most patients were taking dopaminergic medication and future studies may benefit from examining the changes in spreading activation in lexical networks in PD patients on versus off medication or in healthy controls taking either a placebo or a dopaminergic medication. Although these alterations in lexical access might be related to the reduction of dopamine, one of the hallmarks of PD, these patients also have alterations of other neurotransmitter systems and further studies are needed to more clearly identify the role played by these neurotransmitter on lexical access.

Distractibility and Alzheimer disease: the "neglected" phenomenon.

Patients with Alzheimer's disease (AD) might have bilateral attentional disorders, such as a reduced spatial attentional window, due to pathological changes in regions important for mediating spatial attention. AD patients may also be highly distractible with the presentation of unilateral novel stimuli or be impaired at disengaging and reallocating their attention with imperative stimuli. This study sought to test these hypotheses by asking AD patients and normal control subjects to bisect 72 horizontal lines of 3 different lengths in three conditions: no lateral stimuli, novel right or left lateral stimuli ('bottom-up'), and imperative left or right lateral stimuli ('top-down'). Regarding the bottom-up condition, no group differences emerged, but the AD patients had a greater rightward bias with short lines and a leftward bias with long lines, independent of distracting stimuli. In the top-down condition, when the patients with AD, versus controls, were presented with imperative stimuli on their left side, they demonstrated a greater attentional bias than when presented with right-sided stimuli. Thus AD patients have a reduced spatial attentional window and while they are not highly distracted by novel stimuli, after allocating their attention to left sided stimuli, they have a reduced capacity to spatially re-allocate their attention.

The APOE epsilon4 allele increases the risk of impaired spatial working memory in obstructive sleep apnea.

BACKGROUND: Contradictory data have been published on the influence of Apolipoprotein E (APOE) epsilon4 allele on obstructive sleep apnea (OSA). The aims of this study were to confirm the presence of specific neuropsychological changes in OSA patients carrying the APOE epsilon4 allele and to clarify if these changes are due to the sole presence of this allele or to its interactions with OSA pathology. METHODS: The APOE genotype was examined in 123 patients with OSA and in 121 controls, together with a series of neuropsychological tests. RESULTS: OSA and control subjects had similar APOE genotype and allele distribution, but when neuropsychological tests were considered, OSA patients showed significantly lower values for verbal long-term (delayed free recall at the Rey auditory-verbal learning test) and working memory (bisyllabic words). Moreover, spatial span was found to be lower in OSA epsilon4 allele carriers than in non-carriers; this difference was not observed in controls. CONCLUSIONS: This study confirms the presence of a verbal memory impairment in OSA patients and provides evidence for a significant interaction of APOE epsilon4 allele and OSA on frontal lobe function in adults, possibly mediated by the presence of specific frontal lobe neuroanatomical changes in these patients.

The slow-wave components of the cyclic alternating pattern (CAP) have a role in sleep-related learning processes.

Slow waves, a key feature of the EEG of NREM sleep, may be causally involved in producing a sleep-dependent, progressive downscaling of synaptic strength, which would lead to several benefits in terms of both cellular function and network performance. Also the A1 subtypes of the so-called cyclic alternating pattern (CAP) are composed mostly of slow waves and map over the frontal and prefrontal regions of the scalp. The aim of this study was to evaluate the eventual changes of CAP induced by an implicit learning paradigm which has already been shown to be able to increase locally sleep slow-wave activity (SWA). Our hypothesis was that learning is accompanied by a change in the components of CAP characterized by SWA (0.5-2.5Hz), i.e. its A1 subtypes. For this reason, in the present study we evaluated sleep recordings obtained in 10 healthy young normal subjects (mean age 25.8+/-1.8 years) who were asked to perform a motor learning task just before going to sleep. Sleep EEG was recorded for 2h and subjects were also tested after the night following the rotation task. Sleep stages and CAP (classified into three subtypes: A1, A2, and A3) were identified in the first hour of each recording. We found a significant increase in the number of CAP A1 subtypes per hour of NREM sleep on the night following the rotation test; the correlation between the change in A1 index and the post-sleep performance improvement after the rotation task was positive. These results confirm our hypothesis that CAP slow components are modified by a learning task during the day preceding sleep and support the idea that these components may play a role in sleep-related cognitive processes.