Previous research has shown that head direction (HD) cells in both the anterior dorsal thalamus (ADN) and the postsubiculum (PoS) in rats discharge in relation to familiar, visual landmarks in the environment. This study assessed whether PoS and ADN HD cells would be similarly responsive to nonvisual or unfamiliar environmental cues. After visual input was eliminated by blindfolding the rats, HD cells maintained direction-specific discharge, but their preferred firing directions became less stable. In addition, rotations of the behavioral apparatus indicated that some nonvisual cues (presumably tactile, olfactory, or both) exerted above chance stimulus control over a cell's preferred firing direction. However, a prominent auditory cue was not effective in exerting stimulus control over a cell's preferred direction. HD cell activity also was assessed after rotation of a novel visual cue exposed to the rat for 1, 3, or 8 min. An 8-min exposure was enough time for a novel visual cue to gain control over a cell's preferred direction, whereas an exposure of 1 or 3 min led to control in only about half the sessions. These latter results indicate that HD cells rely on a rapid learning mechanism to develop associations with landmark cues. Previous studies have identified neurons in the postsubiculum (PoS) and anterior dorsal nucleus of the thalamus (ADN) of the rat that discharge as a function of the animal's head direction (HD) in the horizontal plane (Taube, 1995; Taube, Mullei, & Ranck, 1990a). HD cells are maximally active when the rat is pointing its head in one particular direction (the "preferred direction"), and their firing rate declines gradually as its head turns away from this direction. In addition to the PoS and ADN, HD cells have been identified in the lateral dorsal thalamus (LDN; Mizumori & Williams, 1993), striatum (Wiener, 1993), lateral mammillary nuclei (Stackman & Taube, 1998), and retrosplenial cortex (Chen et al., 1994). Research also has shown that PoS and ADN HD cells are responsive to the position of familiar visual landmarks (Taube, 1995; Taube, Muller, & Ranck, 1990b). For example, when a familiar visual cue is rotated, the cell's preferred direction usually shifts by a corresponding amount. The current study was designed to explore two issues concerning external landmark control over HD cell discharge. First, we examined the role of nonvisual, environmental cues (e.g., tactile, olfactory, or auditory) in influencing

No abstract

Mild cognitive impairment (MCI) patients have a high risk of converting to Alzheimer's disease. The most common diagnostic subtypes of MCI have an episodic memory disorder (amnestic MCI) occurring either alone [single domain (SD)] or with other cognitive impairments [multiple domain (MD)]. Previous studies report increased amplitudes of auditory cortical potentials in MCI, but their relationships to MCI subtypes and clinical outcomes were not defined. We studied subjects with amnestic MCI (n = 41: 28 SD, 13 MD), Alzheimer's disease (n = 14), and both younger (n = 22) and age-matched older controls (n = 44). Baseline auditory sensory (P50, N100) and cognitive potentials (P300) were recorded during an auditory discrimination task. MCI patients were followed for up to 5 years, and outcomes were classified as (i) continued diagnosis of MCI (MCI-stable, n = 16), (ii) probable Alzheimer's disease (MCI-convert, n = 18), or other outcomes (n = 7). Auditory potentials were analysed as a function of MCI diagnosis and outcomes, and compared with young, older controls, and mild Alzheimer's disease subjects. P50 amplitude increased with normal ageing, and had additional increases in MCI as a function of both initial diagnosis (MD > than SD) and outcome (MCI-convert > MCI-stable). P300 latency increased with normal ageing, and had additional increases in MCI but did not differ among outcomes. We conclude that auditory cortical sensory potentials differ among amnestic MCI subtypes and outcomes occurring up to 5 years later.

No abstract

A subset of neurons in the rat limbic system encodes head direction (HD) by selectively discharging when the rat points its head in a preferred direction in the horizontal plane. The preferred firing direction is sensitive to the location of landmark cues, as well as idiothetic or self-motion cues (i.e., vestibular, motor efference copy, proprioception, and optic flow). Previous studies have shown that the preferred firing direction remains relatively stable (average shift +/- 18 degrees ) after the rat walks from a familiar environment into a novel one, suggesting that without familiar landmarks, the preferred firing direction can be maintained using idiothetic cues, a process called directional path integration. This study repeated this experiment and manipulated the idiothetic cues available to the rat as it moved between the familiar and novel environment. Motor efference copy/proprioceptive cues were disrupted by passively transporting the animal between the familiar and novel environment. Darkening the room as the animal moved to the novel environment eliminated optic flow cues. HD cell preferred firing directions shifted in the novel environment by an average of 30 degrees after locomotion from the familiar environment with the room lights off; by an average of 70 degrees after passive transport from the familiar environment with the room lights on; and by an average of 67 degrees after passive transport with the room lights off. These findings are consistent with the view that motor efference copy/proprioception cues are important for maintaining the preferred firing direction of HD cells under conditions requiring path integration.

Objective: To define brain activity and behavioral changes in mild cognitive impairment (MCI), an isolated memory deficit in the elderly that is a major risk factor for Alzheimer's disease.Methods: Brain potentials and reaction time were examined in elderly controls (n ¼ 12) and MCI (n ¼ 15) using a target detection paradigm. Subjects listened to a sequence of tones and responded to high-pitched target tones (P ¼ 0:20) that were randomly mixed with low-pitched tones (P ¼ 0:80

Purpose: To measure the cerebrovascular volume and blood-brain barrier (BBB) permeability indices in hippocampus and cerebellum of patients with mild cognitive impairment (MCI) using dynamic contrast-enhanced MRI (DCE-MRI), and compare to that of normal controls. Materials and Methods:A total of 11 MCI subjects and 11 healthy elderly controls participated in this prospective study. DCE-MRI was performed to measure the contrast enhancement kinetics. The early enhancement percentage (at 50 seconds after injection) was defined as the vascular volume index, and the ratio between the four to five-minute enhancement relative to the 50-second enhancement was defined as the BBB permeability index. Results:The enhancement kinetics measured from hippocampus of MCI individuals demonstrated a lower magnitude and slower decay than healthy controls, suggesting that they had a smaller vascular volume (significant in the right side; P Ͻ0.001) and a higher BBB permeability (not reaching significance level). The vascular volume index was significantly correlated with naming ability (P 0.05). Conclusion:These results suggest that changes in cerebrovasculature may occur in hippocampus of MCI. DCE-MRI may provide a noninvasive means to measure the subtle BBB leakage associated with the cerebrovascular pathology commonly found in Alzheimer's disease.

Auditory sensory and cognitive cortical potentials in persons with familial Alzheimer disease (FAD) mutations are abnormal approximately 10 years before dementia will be manifest. Longer event-related potential latencies suggest slowing of cortical information processing in FAD mutation carriers.