Author Correction: The honeycomb maze provides a novel test to study hippocampal-dependent spatial navigation.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The honeycomb maze provides a novel test to study hippocampal-dependent spatial navigation.

Here we describe the honeycomb maze, a behavioural paradigm for the study of spatial navigation in rats. The maze consists of 37 platforms that can be raised or lowered independently. Place navigation requires an animal to go to a goal platform from any of several start platforms via a series of sequential choices. For each, the animal is confined to a raised platform and allowed to choose between two of the six adjacent platforms, the correct one being the platform with the smallest angle to the goal-heading direction. Rats learn rapidly and their choices are influenced by three factors: the angle between the two choice platforms, the distance from the goal, and the angle between the correct platform and the direction of the goal. Rats with hippocampal damage are impaired in learning and their performance is affected by all three factors. The honeycomb maze represents a marked improvement over current spatial navigation tests, such as the Morris water maze, because it controls the choices of the animal at each point in the maze, provides the ability to assess knowledge of the goal direction from any location, enables the identification of factors influencing task performance and provides the possibility for concomitant single-cell recording.

Allocentric Spatial Memory Testing Predicts Conversion from Mild Cognitive Impairment to Dementia: An Initial Proof-of-Concept Study.

The hippocampus is one of the first regions to exhibit neurodegeneration in Alzheimer's disease (AD), and knowledge of its role in allocentric spatial memory may therefore aid early diagnosis of AD. The 4 Mountains Test (4MT) is a short and easily administered test of spatial memory based on the cognitive map theory of hippocampal function as derived from rodent single cell and behavioral studies. The 4MT has been shown in previous cross-sectional studies to be sensitive and specific for mild cognitive impairment (MCI) due to AD. This report describes the initial results of a longitudinal study testing the hypothesis that allocentric spatial memory is predictive of conversion from MCI to dementia. Fifteen patients with MCI underwent baseline testing on the 4MT in addition to CSF amyloid/tau biomarker studies, volumetric MRI and neuropsychological assessment including the Rey Auditory Verbal Learning Test (RAVLT) and Trail Making Test "B" (TMT-B). At 24 months, 9/15 patients had converted to AD dementia. The 4MT predicted conversion to AD with 93% accuracy (Cohen's d = 2.52). The predictive accuracies of the comparator measures were as follows: CSF tau/ß-amyloid1-42 ratio 92% (d = 1.81), RAVLT 64% (d = 0.41), TMT-B 78% (d = 1.56), and hippocampal volume 77% (d = 0.65). CSF tau levels were strongly negatively correlated with 4MT scores (r = -0.71). This proof-of-concept study provides initial support for the hypothesis that allocentric spatial memory testing is a predictive cognitive marker of hippocampal neurodegeneration in pre-dementia AD. The 4MT is a brief, non-invasive, straightforward spatial memory test and is therefore ideally suited for use in routine clinical diagnostic practice. This is of particular importance given the current unmet need for simple accurate diagnostic tests for early AD and the ongoing development of potential disease-modifying therapeutic agents, which may be more efficacious when given earlier in the disease course. By applying a test based on studies of hippocampal function in rodents to patient populations, this work represents the first step in the development of translatable biomarkers of hippocampal involvement in early AD for use in both animal models and human subjects.

Fifty Percent Prevalence of Extracampine Hallucinations in Parkinson's Disease Patients.

Extracampine hallucinations (EH), the sense of a presence or fleeting movement in the absence of an associated visual percept, have been reported in Parkinson's disease (PD) patients but their prevalence, characteristics, and temporal relationship to visual hallucinations (VH) remain unclear. Given that, VH are predictive of cognitive impairment in PD, improved understanding of EH may have significant prognostic implications. The objective of this study is to evaluate the prevalence and characteristics of EH in a large unselected population with PD and to assess the temporal relationship between EH, VH, and memory decline. Cross-sectional data were collected from 414 PD patients using a questionnaire circulated via an online patient community. Data were obtained regarding the occurrence, timing, and characteristics of VH and EH and symptoms of PD, disease duration, disease severity, and medication history. About 50.4% of respondents reported EH and 15.5% reported VH. EH were typically experienced alongside, rather than behind, the individual (p < 0.001) without clear lateralization (p = 0.438) and were more likely to be of unfamiliar presences (p < 0.001). The occurrence of EH was associated with Hoehn and Yahr score (p = 0.002) but not disease duration (p = 0.158). EH onset was associated with VH onset (p = 0.046) and occurred after the onset of anosmia (p < 0.001), cognitive decline (p = 0.002), and sleep disturbance (p = 0.002). The reported prevalence of EH in PD patients was threefold greater than that of VH, with similar timings of onset, suggesting that EH are under-recognized and under-reported. Further work is needed to determine whether EH are predictive of cognitive decline.