Although amyloid-beta peptide (Abeta) is the neurotoxic species implicated in the pathogenesis of Alzheimer's disease (AD), mechanisms through which intracellular Abeta impairs cellular properties, resulting in neuronal dysfunction, remain to be clarified. Here we demonstrate that intracellular Abeta is present in mitochondria from brains of transgenic mice with targeted neuronal overexpression of mutant human amyloid precursor protein and AD patients. Abeta progressively accumulates in mitochondria and is associated with diminished enzymatic activity of respiratory chain complexes (III and IV) and a reduction in the rate of oxygen consumption. Importantly, mitochondria-associated Abeta, principally Abeta42, was detected as early as 4 months, before extensive extracellular Abeta deposits. Our studies delineate a new means through which Abeta potentially impairs neuronal energetics, contributing to cellular dysfunction in AD.

Adaptation is ubiquitous in sensory processing. Although sensory processing is hierarchical, with neurons at higher levels exhibiting greater degrees of tuning complexity and invariance than those at lower levels, few experimental or theoretical studies address how adaptation at one hierarchical level affects processing at others. Nevertheless, this issue is critical for understanding cortical coding and computation. Therefore, we examined whether perception of high-level facial expressions can be affected by adaptation to low-level curves (i.e., the shape of a mouth). After adapting to a concave curve, subjects more frequently perceived faces as happy, and after adapting to a convex curve, subjects more frequently perceived faces as sad. We observed this multilevel aftereffect with both cartoon and real test faces when the adapting curve and the mouths of the test faces had the same location. However, when we placed the adapting curve 0.2°below the test faces, the effect disappeared. Surprisingly, this positional specificity held even when real faces, instead of curves, were the adapting stimuli, suggesting that it is a general property for facial-expression aftereffects. We also studied the converse question of whether face adaptation affects curvature judgments, and found such effects after adapting to a cartoon face, but not a real face. Our results suggest that there is a local component in facial-expression representation, in addition to holistic representations emphasized in previous studies. By showing that adaptation can propagate up the cortical hierarchy, our findings also challenge existing functional accounts of adaptation.

When confronted with a scene of emotional faces, our brains automatically average the individual facial expressions together to create the gist of the collective emotion. Here, we tested whether this ensemble averaging could also occur for facial attractiveness, and in turn shape two related face perception phenomena: adaptation and the cheerleader effect. In our first two experiments, we showed that adaptation aftereffects could indeed be shaped by ensemble statistics; viewing an increasingly unattractive group of faces conversely increased attractiveness judgments for a subsequently presented face. Not only did group adaptation aftereffects occur, but their effects were equivalent to those observed from the morphed average face of the group, suggesting that the visual system had averaged the group together.In our last two experiments, we showed that viewing a target face in an increasingly unattractive group led to the target being perceived as increasingly more attractive: a 'cheerleader' effect. Moreover, our results suggest that this cheerleader effect likely comprises of both a social positive effect and a contrastive process, requiring variance between the surrounding and target faces; i.e., the visual system appeared incapable of boosting a target's attractiveness when all of the faces in the scene were identical.Furthermore, the mean group attractiveness ratings strongly predicted both the cheerleader effect and adaptation aftereffects, with the latter two also interrelated. This suggests that ensemble statistics is the common underlying process linking each of these phenomena. In order to be perceived as beautiful, being surrounded by unattractive friends may help.

We report on our efforts to establish an animal model for the development and testing of a cortical visual prostheses. One-hundred-fifty-two electrodes were implanted in the primary visual cortex of a rhesus monkey. The electrodes were made from iridium with an activated iridium oxide film, which has a large charge capacity for a given surface area, and insulated with parylene-C. One-hundred-fourteen electrodes were functional after implantation. The activity of small (2-3) neuronal clusters was first recorded to map the visually responsive region corresponding to each electrode. The animal was then trained in a memory (delayed) saccade task, first with a visual target, then to a target defined by direct cortical stimulation with coordinates specified by the stimulating electrode's mapped receptive field. The SD of saccade endpoints was approximately 2.5 larger for electrically stimulated versus visual saccades; nevertheless, when trial-to-trial scatter was averaged out, the correlation between saccade end points and receptive field locations was highly significant and approached unity after several months of training. Five electrodes were left unused until the monkey was fully trained; when these were introduced, the receptive field-saccade correlations were high on the first day of use (R = 0.85, P = 0.03 for angle, R = 0.98, P < 0.001 for eccentricity), indicating that the monkey had not learned to perform the task empirically by memorizing reward zones. The results of this experiment suggest the potential for rigorous behavioral testing of cortical visual prostheses in the macaque.

How do we interpret the rapidly changing visual stimuli we encounter? How does our past visual experience shape our perception? Recent work has suggested that our visual system is able to interpret multiple faces presented temporally via integration or ensemble coding. Visual adaptation is widely used to probe such short term plasticity. Here we use an adaptation paradigm to investigate whether integration or averaging of emotional faces occurs during a rapid serial visual presentation (RSVP). In four experiments, we tested whether the RSVP of distinct emotional faces could induce adaptation aftereffects and whether these aftereffects were of similar magnitudes as their statistically averaged face. Experiment 1 showed that the RSVP faces could generate significant facial expression aftereffects (FEAs) across happy and sad emotions. Experiment 2 revealed that the magnitudes of the FEAs from RSVP faces and their paired average faces were comparable and significantly correlated. Experiment 3 showed that the FEAs depended on the mean emotion of the face stream, regardless of variations in emotion or the temporal frequency of the stream. Experiment 4 further indicated that the emotion of the average face of the stream, but not the emotion of individual faces matched for identity to the test faces, determined the FEAs. Together, our results suggest that the visual system interprets rapidly presented faces by ensemble coding, and thus implies the formation of a facial expression norm in face space.