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.

Spreading activation in nonverbal memory networks.

Theories of spreading activation primarily involve semantic memory networks. However, the existence of separate verbal and visuospatial memory networks suggests that spreading activation may also occur in visuospatial memory networks. The purpose of the present investigation was to explore this possibility. Specifically, this study sought to create and describe the design frequency corpus and to determine whether this measure of visuospatial spreading activation was related to right hemisphere functioning and spreading activation in verbal memory networks. We used word frequencies taken from the Controlled Oral Word Association Test and design frequencies taken from the Ruff Figural Fluency Test as measures of verbal and visuospatial spreading activation, respectively. Average word and design frequencies were then correlated with measures of left and right cerebral functioning. The results indicated that a significant relationship exists between performance on a test of right posterior functioning (Block Design) and design frequency. A significant negative relationship also exists between spreading activation in semantic memory networks and design frequency. Based on our findings, the hypotheses were supported. Further research will need to be conducted to examine whether spreading activation exists in visuospatial memory networks as well as the parameters that might modulate this spreading activation, such as the influence of neurotransmitters.

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.

Quantitative electroencephalographic and neuropsychological investigation of an alternative measure of frontal lobe executive functions: the Figure Trail Making Test.

The most frequently used measures of executive functioning are either sensitive to left frontal lobe functioning or bilateral frontal functioning. Relatively little is known about right frontal lobe contributions to executive functioning given the paucity of measures sensitive to right frontal functioning. The present investigation reports the development and initial validation of a new measure designed to be sensitive to right frontal lobe functioning, the Figure Trail Making Test (FTMT). The FTMT, the classic Trial Making Test, and the Ruff Figural Fluency Test (RFFT) were administered to 42 right-handed men. The results indicated a significant relationship between the FTMT and both the TMT and the RFFT. Performance on the FTMT was also related to high beta EEG over the right frontal lobe. Thus, the FTMT appears to be an equivalent measure of executive functioning that may be sensitive to right frontal lobe functioning. Applications for use in frontotemporal dementia, Alzheimer's disease, and other patient populations are discussed.

Dopamine does not appear to affect mental rotation in Parkinson's disease.

OBJECTIVE: Patients with Parkinson's disease (PD) often have deficits with mental rotation (MR). The neuropathological factors underlying these deficits, however, remain to be elucidated. One hypothesis suggests that dopamine depletion in nigro-striatal systems adversely influences MR. Another hypothesis suggests that deterioration of cortical (fronto-temporo-parietal basal ganglia) networks that mediate this function are responsible for this deficit. The goal of this study was to test the dopamine hypothesis by determining if dopamine abstinence negatively influences MR performance. METHODS: Thirty three non-demented right-handed individuals with PD were assess for their ability to perform a pencil and paper MR test while "on" and "off" dopaminergic medications. Dopamine abstinence followed the typical overnight withdrawal procedures. RESULTS: No differences in mental rotation abilities were found between "on" and "off" dopaminergic medications. CONCLUSIONS: These results suggest that other neuropathological factors, such as cortical-basal ganglia neurodegeneration, or dysfunction of other neurotransmitters systems, might account for these cognitive deficits and future research will have to test these alternative hypotheses.

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.

Immunological functioning in Alzheimer's disease: differential effects of relative left versus right temporoparietal dysfunction.

The cerebral hemispheres are differentially involved in regulating immunological functioning and the neuropathology associated with Alzheimer's disease (AD) is asymmetrical. Thus, subgroups of AD patients may exhibit different patterns of immunological dysfunction. We explored this possibility in a group of AD patients and found that patients with low white blood cell counts and low lymphocyte numbers exhibited better performance on tests of right temporoparietal functioning. Also, a significant positive relationship exists between lymph numbers and performance on a test of left temporoparietal functioning. Thus, some AD patients have greater immunological dysfunction based on relative left versus right temporoparietal functioning.

Differential lexical and semantic spreading activation in Alzheimer's disease.

Alzheimer's disease (AD) is known to be associated with disruption in semantic networks. Previous studies examining changes in spreading activation in AD have used a lexical decision task paradigm. We have used a paradigm based on average word frequencies obtained from the words generated on the Controlled Oral Word Association Test (COWAT) and the Animal Naming (AN) test. The COWAT and AN tests were administered to a group of 25 patients with AD and 20 control participants. We predicted that the patients with AD would have higher average word frequencies on the COWAT and AN tests than the control participants. The results indicated that the AD group generated words with a higher average word frequency on the AN test but a lower average word frequency on the COWAT. The reasons for the discrepancy in average word frequencies on the AN test and COWAT are discussed.

Working memory in Parkinson's disease: the effects of depression and side of onset of motor symptoms.

OBJECTIVE: Previous research has examined the neurocognitive effects of depression in Parkinson's disease (PD), finding worse performance on tests of cognitive functioning in PD patients with depression as compared to those without depression. However, this research has not considered the effect of side of onset of motor symptoms. Hence, we sought to investigate the interaction between depression and side of onset on working memory in patients with PD. METHOD: A total of 66 patients with PD completed the Digit Span Backward subtest of the Wechsler Memory Scale-III as well as two other tests of executive functioning. Groups of left hemibody onset (LHO) with and without depression and right hemibody onset (RHO) with and without depression were created. RESULTS: The results indicated significantly lower performance on the measure of working memory for the LHO with depression group, relative to both the LHO without depression and the RHO with depression groups. CONCLUSION: These findings indicate that working memory is worse in patients with LHO of motor symptoms who are also depressed, and they suggest that this group of patients might experience greater disability and lower quality of life.

Recall of word lists is enhanced with increased spreading activation.

Some evidence exists supporting a relationship between spreading activation in semantic/lexical memory networks and episodic memory. However, the results have been mixed and there have been no investigations examining whether a relationship exists between variability in spreading activation and episodic memory. Hence, we sought to investigate these potential relationships. Thirteen individuals were administered the Hopkins Verbal Learning Test-Revised (HVLT-R) and the Controlled Oral Word Association Test (COWAT). The average word frequency of all the "F" words generated on the COWAT was used as a measure of spreading activation. Variability in spreading activation was assessed by calculating the variability of the word frequencies from the COWAT across time. The results confirmed our hypotheses, with significant negative correlations found between free recall on the HVLT-R and both the average word frequency and measures of variability in spreading activation.

Mood disturbances and cognitive functioning in Parkinson's disease: the effects of disease duration and side of onset of motor symptoms.

Some research has supported differences in mood functioning in patients with Parkinson's disease (PD) whose motor symptoms begin at the left or right hemibody. Also, a relationship between disease duration and mood disturbances has been reported, but only for PD patients with right hemibody onset. There have been no investigations reported examining the potential interactions between side of onset of motor symptoms, mood, and disease duration on cognitive functioning. Hence, the purpose of this investigation was to determine whether the interaction between mood and disease duration differentially affects cognitive functioning in patients with PD whose motor symptoms begin at the left and right hemibody. A total of 33 PD patients with left hemibody onset and 29 PD patients with right hemibody onset were given a battery of tests to evaluate mood functioning and general cognitive functioning. As predicted, the results indicated that the interaction of disease duration and mood significantly predicted cognitive functioning for PD patients with right hemibody onset of symptoms but not for PD patients with left hemibody onset of symptoms. Interestingly, an unexpected finding was a significant positive relationship between disease duration and energy level for patients with left hemibody onset but not for patients with right hemibody onset. These results indicate that mood problems and disease duration interact to significantly affect cognitive functioning but only for those PD patients who experience a right hemibody onset of symptoms.

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.

Acetylcholinesterase inhibitors reduce spreading activation in dementia.

Alzheimer's disease is associated with degeneration of the cholinergic system, which affects memory and attention functioning. Acetylcholinesterase inhibitors (AChEI) have been found to increase attention and given this effect might reduce spreading activation of memory nodes in lexical/semantic networks. We sought to determine whether this effect of AChEIs existed in a group of patients with dementia. A mixed sample of 34 patients with dementia (17 taking AChEIs and 17 not taking these medications) were administered the Controlled Oral Word Association Test and the Animal Naming Test. The average word frequency for their responses was obtained and used as a measure of spreading activation. Patients taking AChEIs had a significantly higher average word frequency for the COWAT as compared to those not taking AChEIs. No difference was found for the average word frequencies for the AN test. Administration of AChEIs appears to reduce spreading activation, possibly due to cholinergic innervations of the frontal cortex.

Disease tracking markers for Alzheimer's disease at the prodromal (MCI) stage.

Older persons with Mild Cognitive Impairment (MCI) feature neurobiological Alzheimer's Disease (AD) in 50% to 70% of the cases and develop dementia within the next 5 to 7 years. Current evidence suggests that biochemical, neuroimaging, electrophysiological, and neuropsychological markers can track the disease over time since the MCI stage (also called prodromal AD). The amount of evidence supporting their validity is of variable strength. We have reviewed the current literature and categorized evidence of validity into three classes: Class A, availability of multiple serial studies; Class B a single serial study or multiple cross sectional studies of patients with increasing disease severity from MCI to probable AD; and class C, multiple cross sectional studies of patients in the dementia stage, not including the MCI stage. Several Class A studies suggest that episodic memory and semantic fluency are the most reliable neuropsychological markers of progression. Hippocampal atrophy, ventricular volume and whole brain atrophy are structural MRI markers with class A evidence. Resting-state fMRI and connectivity, and diffusion MR markers in the medial temporal white matter (parahippocampus and posterior cingulum) and hippocampus are promising but require further validation. Change in amyloid load in MCI patients warrant further investigations, e.g. over longer period of time, to assess its value as marker of disease progression. Several spectral markers of resting state EEG rhythms that might reflect neurodegenerative processes in the prodromal stage of AD (EEG power density, functional coupling, spectral coherence, and synchronization) suffer from lack of appropriately designed studies. Although serial studies on late event-related potentials (ERPs) in healthy elders or MCI patients are inconclusive, others tracking disease progression and effects of cholinesterase inhibiting drugs in AD, and cross-sectional including MCI or predicting development of AD offer preliminary evidence of validity as a marker of disease progression from the MCI stage. CSF Markers, such as Aß 1-42, t-tau and p-tau are valuable markers which support the clinical diagnosis of Alzheimer's disease. However, these markers are not sensitive to disease progression and cannot be used to monitor the severity of Alzheimer's disease. For Isoprostane F2 some evidence exists that its increase correlates with the progression and the severity of AD.

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.

Cyclic alternating pattern in sleep and its relationship to creativity.

BACKGROUND/OBJECTIVES: Sleep has been shown to enhance creativity, but the reason for this enhancement is not entirely known. There are several different physiologic states associated with sleep. In addition to rapid (REM) and non-rapid eye movement (NREM) sleep, NREM sleep can be broken down into Stages (1-4) that are characterized by the degree of EEG slow-wave activity. In addition, during NREM sleep the cyclic alternating pattern (CAPs) of EEG activity has been described which can also be divided into three subtypes (A1-A3) according to the frequency of the EEG waves. Differences in CAP subtype ratios have been previously linked to cognitive performances. The purpose of this study was to asses the relationship between CAP activity during sleep and creativity. METHODS: The participants were eight healthy young adults (four women) who underwent three consecutive nights of polysomnographic recording and took the Abbreviated Torrance Test for Adults (ATTA) on the second and third mornings after the recordings. RESULTS: There were positive correlations between Stage 1 of NREM sleep and some measures of creativity such as fluency (R=.797; p=.029) and flexibility (R=.43; p=.002), between Stage 4 of NREM sleep and originality (R=.779; p=.034) and a global measure of figural creativity (R=.758; p=.040). There was also a negative correlation between REM sleep and originality (R=-.827; p=.042). During NREM sleep the CAP rate, which in young people reflects primarily the A1 subtype, also correlated with originality (R=.765; p=.038). CONCLUSIONS: NREM sleep is associated with low levels of cortical arousal, and low cortical arousal may enhance the ability of people to access to the remote associations that are critical for creative innovations. In addition, A1 CAP subtypes reflect frontal activity, and the frontal lobes are important for divergent thinking, also a critical aspect of creativity.

Anxiety and depression severity are related to right but not left onset Parkinson's disease duration.

Depression and anxiety have both been associated with relative left frontal hypoactivation and the motor symptoms of Parkinson's disease typically begin in a lateral or asymmetrical fashion. Hence, PD patients with right hemibody onset may experience heightened depression and anxiety. However, research is mixed regarding whether right or left hemibody onset PD is associated with elevated levels of depression and anxiety. This literature, though, has not considered the potential moderating variable of disease duration. We hypothesized that disease duration would be positively correlated with measures of depression and anxiety in right but not left hemibody onset PD patients. The results indicated that scores on the Geriatric Depression Scale, Beck Depression Inventory-II, and the State Trait Anxiety Scale - State correlated positively with disease duration, but only in the right hemibody onset group of PD patients. Thus, right hemibody onset PD is associated with more severe depressive and anxiety symptoms, but only when disease duration is considered.

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.