The thalamic reuniens is associated with consolidation of non-spatial memory too

The nucleus reuniens (RE) is situated in the midline thalamus and provides a key link between the hippocampus and prefrontal cortex. This anatomical relationship positions the Re as an ideal candidate to facilitate memory consolidation. However, there is no evidence that this role extends beyond spatial memory and contextual fear memory, which are both strongly associated with hippocampal function. We, therefore, trained intact male Long–Evans rats on an odor–trace–object paired-associate task where the explicit 10-s delay between paired items renders the task sensitive to hippocampal function. Neurons in the RE showed significantly increased activation of the immediate early gene (Zif268) when rats were re-tested for previous non-spatial memory 25 days after acquisition training, compared to a group tested at 5-days post-acquisition, as well as a control group tested 25 days after acquisition but with a new pair of non-spatial stimuli, and home cage controls. The remote recall group also showed relatively augmented IEG expression in the superficial layers of the medial PFC (anterior cingulate cortex and prelimbic cortex). These findings support the conclusion that the RE is preferentially engaged during remote recall in this non-spatial task and thus has a role beyond spatial memory and contextual fear memory

Behavioural Consequences of Frontal Cortex Grafts and Enriched Environments after Sensorimotor Cortex Lesions

Past studies have experienced difficulty in achieving graft survival and behavioural recovery after sensorimotor cortex lesions. In the present work, adult female rats trained preoperatively to cross a narrow beam for food reward were maintained in standard group cages or an enriched environment, commencing one week after a unilateral lesion. One month post-lesion, half of these rats received multiple suspension grafts of (E20) fetal frontal cortex, placed adjacent to the lesion cavity, and 8 days later recovery of beam-walking skills was examined for a six-week period. The grafts survived in all cases with an appropriate lesion, a notable result given the one month lesion-graft delay, but graft volume was not influenced by postoperative environment. The substantial lesion-induced deficits evident just prior to differential housing showed a marked reduction by the start of post-graft testing, but relative to intact controls a persistent deficit in foot slip errors occurred in all lesion groups. Irrespective of graft status, postoperative enrichment prevented the occurrence of severe foot slips, especially early in retraining. The frontal grafts, however, enhanced beam-walking recovery by reducing the overall frequency of foot slips on early post-grafting sessions, an effect we suggest is related to graft-derived trophic influences, but this measure was not significantly improved by postoperative enrichment

Enriched Environment Procedures for Rodents: Creating a Standardized Protocol for Diverse Enrichment to Improve Consistency across Research Studies.

Exposure to environmental enrichment has beneficial effects on learning and memory, diverse neurobiological effects, and promotes recovery of function after brain injury. The effect of enrichment is produced by a combination of increased social interaction, physical activity, spatial complexity, and novelty. Procedures in the literature have, however, been idiosyncratic with poor consistency in the manner or extent to which protocols provide consistent enrichment. We provide an environmental enrichment protocol that can be easily replicated with minor details determined locally so that animals across cohorts and cages all experience a comparable level of enrichment. Procedures are outlined to generate and use a daily pool of suitably varied objects using a standardized format, with objects systematically varied up to a 40-day continuous period. Together with using a large group of rats in a suitably-sized cage, and regular shifting of the position of food and water and cage location, these procedures have produced robust effects in different laboratories and rat strain, thereby improving comparisons within and across laboratories. Non-enriched comparisons can vary, but typically would include grouped animals in standard laboratory housing without objects and with stable food and water locations. Enrichment is a safe non-pharamacological tool to examine behavioral and neurobiological processes in animal models of the lifespan, brain dysfunction and injury

Self-Rated Distress Related to Medical Conditions is Associated with Future Crashes or Traffic Offences in Older Drivers

Ageing is associated with the development of medical conditions, both acute and chronic. The aim of this study was to determine whether medical factors were associated with subsequent self- and officially-reported crashes and traffic offences in a group of cognitively healthy older drivers. We surveyed medical conditions, medications taken for these conditions, and the amount of subjective distress associated with medical conditions in a group of 56 drivers aged 72-85 years for a period of 24 months. We also compared exposure to driving at baseline to the number of crashes or offences at 24 months. We found no relationship between the number of medical conditions or medications taken and whether a participant had a crash or offence. However, those who reported more subjective distress associated with their condition/s were more likely to have a crash or offence during the study period. Drivers who had a crash or offence also had a higher mean driving exposure. However, there was no relationship between reported distress and driving exposure which indicates that these may be independent risk factors for experiencing a crash or traffic offence

Prediction of Driving Ability in People With Dementia- and Non- Dementia-Related Brain Disorders

Brain disorders can impair physical and cognitive functions necessary for safe driving. Two hundred people with brain disorders referred for a driving assessment were recruited and their performance on a computerized battery of sensory-motor and cognitive tests (SMCTests) and a blinded on-road assessment determined. Based on SMCTests performance, binary logistic regression (BLR) and nonlinear causal resource analysis (NCRA) models classified on-road pass or fail with 70% accuracy. Greater accuracy could be achieved by splitting referrals into two groups: (1) Dementia and (2) Non-dementia-related brain disorders. BLR models classified on-road driving outcome as pass or fail with accuracies of 76% (Dementia) and 75% (Non-dementia), while NCRA models had accuracies of 77% (Dementia) and 80% (Non-dementia). Measures of attention were most critical for predicting driving ability in the dementia group. In the non-dementia group, prediction of driving ability was most accurate with assessment of a broader range of sensory-motor and cognitive functions. Compared to BLR, NCRA was able to identify and use additional measures to improve accuracy. NCRA is also better able to accommodate outliers due to it being a non-linear modelling method based upon individual performance-limiting impairments. We propose three main factors underlying sub-optimal prediction of driving ability based on SMCTests performance: (1) there are one or more functions important for driving ability which are not currently assessed with SMCTests – these could be sensory-motor or cognitive or other (e.g., attitude, confidence, insight, road code knowledge); (2) suboptimal classification/prediction techniques or models; or (3) inaccuracies in the on-road driving assessments

Driving Assessment and Subsequent Driving Outcome: A Prospective Study of Safe and Unsafe Healthy Driver Groups

Older drivers are an increasingly numerous section of the population who are often targeted for driving assessment. Little is known as to whether onroad driving assessments result in an older driver population who have fewer negative driving events. Fifty-eight healthy older drivers (mean age 77, range 71- 84, no diagnosis of neurological disorder), completed a non-enforced on-road driving assessment and detailed sensory-motor and cognitive testing. Selfreported and official data regarding crashes and traffic offences were collected for both the five years prior to the on-road assessment, and the 12 months following in order to determine whether those who received a Fail score on the on-road assessment had higher rates of negative driving events than those who passed (43 passed, 15 failed). No increase in adverse outcomes was found either retrospectively or prospectively for those who failed the on-road assessment. Similarly there were no significant differences in cognitive, sensory-motor, and demographic variables between those who passed and failed. Healthy older drivers who failed the on-road assessment did not show evidence of poorer driving behaviour even at the level of descriptive statistics

Neuron arbor geometry is sensitive to the limited-range fractal properties of their dendrites

12 pagesFractal geometry is a well-known model for capturing the multi-scaled complexity of many natural objects. By analyzing three-dimensional images of pyramidal neurons in the rat hippocampus CA1 region, we examine how the individual dendrites within the neuron arbor relate to the fractal properties of the arbor as a whole. We find that the dendrites reveal unexpectedly mild fractal characteristics quantified by a low fractal dimension. This is confirmed by comparing two fractal methods—a traditional “coastline” method and a novel method that examines the dendrites’ tortuosity across multiple scales. This comparison also allows the dendrites’ fractal geometry to be related to more traditional measures of their complexity. In contrast, the arbor’s fractal characteristics are quantified by a much higher fractal dimension. Employing distorted neuron models that modify the dendritic patterns, deviations from natural dendrite behavior are found to induce large systematic changes in the arbor’s structure and its connectivity within a neural network. We discuss how this sensitivity to dendrite fractality impacts neuron functionality in terms of balancing neuron connectivity with its operating costs. We also consider implications for applications focusing on deviations from natural behavior, including pathological conditions and investigations of neuron interactions with artificial surfaces in human implants

Changes of plasma cGP/IGF-1 molar ratio with age is associated with cognitive status of Parkinson disease

Objective: Cognitive impairment is a common feature of Parkinson disease (PD), for which age is a major contributing factor. Insulin-like growth factor-1 (IGF-1) declines with age and contributes to age-related cognitive impairment in PD. Cyclic glycine-proline (cGP) is a metabolite of IGF-1 and normalizes bioavailable IGF-1. Plasma cGP/IGF-1 molar ratio that represents bioactive IGF-1 in circulation, may associate with the cognitive status in PD. Methods: We examined the association of plasma cGP/IGF-1 molar ratio with the cognitive scores or age in PD patients with normal cognition (PD-N, n = 74), mild cognitive impairment (PD-MCI, n = 71), or dementia (PD-D, n = 33), and with the cognitive scores in 23 age-matched healthy controls. Plasma concentrations of IGF-1, IGF binding protein-3, and cGP were evaluated using enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography-mass spectrometry (HPLC-MS), respectively. Results: The cGP/IGF-1 molar ratio was positively correlated with the age of PD-N group, negatively correlated with the age of PD-D group, and not associated with the age of PD-MCI group. Independent of age, the cGP/IGF-1 molar ratio was positively correlated with the cognitive scores of healthy controls, but not in PD groups. Conclusion: Old healthy people with a higher cGP/IGF-1 molar ratio showed better preserved cognition, possibly due to improved IGF-1 function. Increased cGP/IGF-1 molar ratio with age may contribute to cognitive retention in the PD-N group. The absence or reversal of such association with age in the PD-MCI and PD-D groups may indicate the conversion of cognitive status in PD, if confirmed through longitudinal investigations within the individuals with advancing cognitive impairment

Investigating Fractal Analysis as a Diagnostic Tool That Probes the Connectivity of Hippocampal Neurons

12 pagesMany of nature’s fractal objects benefit from the favorable functionality that results from their pattern repetition at multiple scales. Our recent research focused on the importance of fractal scaling in establishing connectivity between neurons. Fractal dimension DA of the neuron arbors was shown to relate to the optimization of competing functional constraints—the ability of dendrites to connect to other neurons versus the costs associated with building the dendrites. Here, we consider whether pathological states of neurons might affect this fractal optimization and if changes in DA might therefore be used as a diagnostic tool in parallel with traditional measures like Sholl analyses. We use confocal microscopy to obtain images of CA1 pyramidal neurons in the coronal plane of the dorsal rat hippocampus and construct 3-dimensional models of the dendritic arbors using Neurolucida software. We examine six rodent groups which vary in brain condition (whether they had lesions in the anterior thalamic nuclei, ATN) and experience (their housing environment and experience in a spatial task). Previously, we showed ATN lesions reduced spine density in hippocampal CA1 neurons, whereas enriched housing increased spine density in both ATN lesion and sham rats. Here, we investigate whether ATN lesions and experience also effect the complexity and connectivity of CA1 dendritic arbors. We show that sham rats exposed to enriched housing and spatial memory training exhibited higher complexity (as measured by DA) and connectivity compared to other groups. When we categorize the rodent groups into those with or without lesions, we find that both categories achieve an optimal balance of connectivity with respect to material cost. However, the DA value used to achieve this optimization does not change between these two categories, suggesting any morphological differences induced by the lesions are too small to influence the optimization process. Accordingly, we highlight considerations associated with applying our technique to publicly accessible repositories of neuron images with a broader range of pathological conditions

Arterial spin labelling reveals an abnormal cerebral perfusion pattern in Parkinson's disease

There is a need for objective imaging markers of Parkinson's disease status and progression. Positron emission tomography and single photon emission computed tomography studies have suggested patterns of abnormal cerebral perfusion in Parkinson's disease as potential functional biomarkers. This study aimed to identify an arterial spin labelling magnetic resonance-derived perfusion network as an accessible, non-invasive alternative. We used pseudo-continuous arterial spin labelling to measure cerebral grey matter perfusion in 61 subjects with Parkinson's disease with a range of motor and cognitive impairment, including patients with dementia and 29 age- and sex-matched controls. Principal component analysis was used to derive a Parkinson's disease-related perfusion network via logistic regression. Region of interest analysis of absolute perfusion values revealed that the Parkinson's disease pattern was characterized by decreased perfusion in posterior parieto-occipital cortex, precuneus and cuneus, and middle frontal gyri compared with healthy controls. Perfusion was preserved in globus pallidus, putamen, anterior cingulate and post- and pre-central gyri. Both motor and cognitive statuses were significant factors related to network score. A network approach, supported by arterial spin labelling-derived absolute perfusion values may provide a readily accessible neuroimaging method to characterize and track progression of both motor and cognitive status in Parkinson's diseas