Right or bilateral anterior temporal damage can impair face recognition, but whether this is an associative variant of prosopagnosia or part of a multimodal disorder of person recognition is an unsettled question, with implications for cognitive and neuroanatomic models of person recognition. We assessed voice perception and short-term recognition of recently heard voices in 10 subjects with impaired face recognition acquired after cerebral lesions. All 4 subjects with apperceptive prosopagnosia due to lesions limited to fusiform cortex had intact voice discrimination and recognition. One subject with bilateral fusiform and anterior temporal lesions had a combined apperceptive prosopagnosia and apperceptive phonagnosia, the first such described case. Deficits indicating a multimodal syndrome of person recognition were found only in 2 subjects with bilateral anterior temporal lesions. All 3 subjects with right anterior temporal lesions had normal voice perception and recognition, 2 of whom performed normally on perceptual discrimination of faces. This confirms that such lesions can cause a modality-specific associative prosopagnosia.

Neuronal structure and function are rapidly damaged during global ischemia but can in part recover during reperfusion. Despite apparent recovery in the hours/days following an ischemic episode, delayed cell death can be initiated, making it important to understand how initial ischemic events affect potential mediators of apoptosis. Mitochondrial dysfunction and the opening of the mitochondrial permeability transition pore (mPTP) are proposed to link ischemic ionic imbalance to mitochondrially mediated cell death pathways. Using two-photon microscopy, we monitored mitochondrial transmembrane potential (⌬ m ) in vivo within the somatosensory cortex during ischemia and reperfusion in a mouse global ischemia model. Our results indicated a synchronous loss of ⌬ m within 1-3 min of ischemic onset that was linked to within seconds of plasma membrane potential (⌬ p ) depolarization. ⌬ m recovered rapidly upon reperfusion, and no delayed depolarization was observed over 2 h. Cyclosporin A treatment largely blocked ⌬ m collapse during ischemia, suggesting a role for the mPTP. Blocking ⌬ m depolarization did not affect structural damage to dendrites, indicating that the opening of the mPTP and damage to dendrites are separable pathways that are activated during ⌬ p depolarization. Our findings using in vivo imaging suggest that mitochondrial dysfunction and specifically the activation of the mPTP are early reversible events during brain ischemia that could trigger delayed cell death.Ion and water imbalance during stroke are widely accepted as chief contributors to acute ischemic injury, but how these events are linked to more slowly activated cell death pathways is unclear (1). Neurons within the cortex and the hippocampus can recover both structure and function within hours after brief ischemia (2, 3) but are still subject to cell death with apoptotic features days later (4). One mechanism described in vitro that may link intracellular Ca 2ϩ elevation to cell death pathways is the activation of mitochondrial permeability transition pore (mPTP) 2 in response to mitochondrial Ca 2ϩ overload (5-8). mPTP activation can lead to mitochondrial transmembrane potential (⌬ m ) collapse and excessive reactive oxygen species generation (5, 7, 9). Mitochondrial dysfunction, and specifically mPTP opening, has been suggested to contribute to ischemic injury (10, 11), although its exact role and timing are unclear. In vitro studies in neurons suggest that mitochondrial dysfunction occurs during ischemia and excitotoxic ion overload (5, 7, 12-15); however, other evidence suggests that mitochondrial dysfunction may be delayed and occur during reperfusion or after a period of ionic stress (9,16,17). To complicate matters, there are differences between conditions during in vitro ischemia-like events and stroke in vivo (2, 13). Previously, the role of mitochondrial dysfunction has been addressed in stroke in vivo using end point measures of histological and biochemical markers (8, 16) or using potentially less direct methods such as NADH fluo...

Background Developmental prosopagnosia is a disorder of face recognition that is believed to reflect impairments of visual mechanisms. However, voice recognition has rarely been evaluated in developmental prosopagnosia to clarify if it is modality-specific or part of a multi-modal person recognition syndrome. Objective Our goal was to examine whether voice discrimination and/or recognition are impaired in subjects with developmental prosopagnosia. Design/Methods 73 healthy controls and 12 subjects with developmental prosopagnosia performed a match-to-sample test of voice discrimination and a test of short-term voice familiarity, as well as a questionnaire about face and voice identification in daily life. Results Eleven subjects with developmental prosopagnosia scored within the normal range for voice discrimination and voice recognition. One was impaired on discrimination and borderline for recognition, with equivalent scores for face and voice recognition, despite being unaware of voice processing problems. Conclusions Most subjects with developmental prosopagnosia are not impaired in short-term voice familiarity, providing evidence that developmental prosopagnosia is usually a modality-specific disorder of face recognition. However, there may be heterogeneity, with a minority having additional voice processing deficits. Objective tests of voice recognition should be integrated into the diagnostic evaluation of this disorder to distinguish it from a multi-modal person recognition syndrome.

Retinal disease is the major cause of irreversible blindness in developed countries. Transplantation of photoreceptor precursor cells (PPCs) derived from human embryonic stem cells (hESCs) is a promising and widely applicable approach for the treatment of these blinding conditions. Previously, it has been shown that after transplantation into the degenerating retina, the percentage of PPCs that undergo functional integration is low. The factors that inhibit PPC engraftment remain largely unknown, in part, because so many adverse factors could be at play during in vivo experiments. To advance our knowledge in overcoming potential adverse effects and optimize PPC transplantation, we have developed a novel ex vivo system. Harvested neural retina was placed directly on top of cultured retinal pigment epithelial (RPE) cells from a number of different sources. To mimic PPC transplantation into the subretinal space, hESC-derived PPCs were inserted between the retinal explant and underlying RPE. Explants cocultured with hESC-derived RPE maintained normal gross morphology and viability for up to 2 weeks, whereas the explants cultured on ARPE19 and RPE-J failed by 7 days. Furthermore, the proportion of PPCs expressing ribbon synapse-specific proteins BASSOON and RIBEYE was significantly higher when cocultured with hESC-derived RPE (20% and 10%, respectively), than when cocultured with ARPE19 (only 6% and 2%, respectively). In the presence of the synaptogenic factor thrombospondin-1 (TSP-1), the proportion of BASSOON-positive and RIBEYE-positive PPCs cocultured with hESC-derived RPE increased to *30% and 15%, respectively. These data demonstrate the utility of an ex vivo model system to define factors, such as TSP-1, which could influence integration efficiency in future in vivo experiments in models of retinal degeneration.

Objective. Uncertainty analysis (UA) is an important part of simulation model validation. However, literature is imprecise as to how UA should be performed in the context of population-based microsimulation (PMS) models. In this expository paper, we discuss a practical approach to UA for such models. Methods. By adapting common concepts from published UA guidelines, we developed a comprehensive, step-by-step approach to UA in PMS models, including sample size calculation to reduce the computational time.As an illustration, we performed UA for POHEM-OA, a microsimulation model of osteoarthritis (OA) in Canada. Results. The resulting sample size of the simulated population was 500,000 and the number of Monte Carlo (MC) runs was 785 for 12-hour computational time. The estimated 95% uncertainty intervals for the prevalence of OA in Canada in 2021 were 0.09 to 0.18 for men and 0.15 to 0.23 for women. The uncertainty surrounding the sex-specific prevalence of OA increased over time. Conclusion. The proposed approach to UA considers the challenges specific to PMS models, such as selection of parameters and calculation of MC runs and population size to reduce computational burden. Our example of UA shows that the proposed approach is feasible. Estimation of uncertainty intervals should become a standard practice in the reporting of results from PMS models.