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Exaggerated pupil response to dilute tropicamide has been suggested as an early biological marker for Alzheimer’s disease. The current study links apolipoprotein E (ApoE) allelic variability to the magnitude of pupil response in a sample of community-dwelling elderly without a diagnosis of Alzheimer’s disease or dementia. Possession of an ℇ4 allele influences both the likelihood of exhibiting an exaggerated pupil response above a predetermined cut-off (13% above baseline diameter) and the absolute overall magnitude of the response. Allelic variability was also shown to correlate with cognitive impairments in memory and attention. The data in this study further elucidate the nature of the biological bond between an exaggerated pupil response and the pathology of Alzheimer’s disease. ApoE allelic variability is probably linked to pupil response through its influence on tau hyperphosphorylation. The early Alzheimer’s pathology seen in the Edinger–Westphal area of cranial nerve III, a major centre for pupil control, is primarily tau-based with significant cell loss in this nucleus leading to central denervation hypersensitivity even in elderly who are clinically silent but who have early pathology. [ABSTRACT FROM AUTHOR]

Despite the important role that attending to novel events plays in human behavior, there is limited information about the neuroanatomical underpinnings of this vital activity. This study investigated the relative contributions of the frontal and posterior parietal lobes to the differential processing of novel and target stimuli under an experimental condition in which subjects actively directed attention to novel events. Event-related potentials were recorded from well-matched frontal patients, parietal patients, and non-brain-injured subjects who controlled their viewing duration (by button press) of line drawings that included a frequent, repetitive background stimulus, an infrequent target stimulus, and infrequent, novel visual stimuli. Subjects also responded to target stimuli by pressing a foot pedal. Damage to the frontal cortex resulted in a much greater disruption of response to novel stimuli than to designated targets. Frontal patients exhibited a widely distributed, profound reduction of the novelty P3 response and a marked diminution of the viewing duration of novel events. In contrast, damage to posterior parietal lobes was associated with a substantial reduction of both target P3 and novelty P3 amplitude; however, there was less disruption of the processing of novel than of target stimuli. We conclude that two nodes of the neuroanatomical network for responding to and processing novelty are the prefrontal and posterior parietal regions, which participate in the voluntary allocation of attention to novel events. Injury to this network is indexed by reduced novelty P3 amplitude, which is tightly associated with diminished attention to novel stimuli. The prefrontal cortex may serve as the central node in determining the allocation of attentional resources to novel events, whereas the posterior parietal lobe may provide the neural substrate for the dynamic process of updating one's internal model of the environment to take into account a novel event. [ABSTRACT FROM AUTHOR]

This study investigated the role of stimulus deviance in determining electrophysiologic and behavioral responses to "novelty." Stimulus deviance was defined in terms of differences either from the immediately preceding context or from long-term experience. Subjects participated in a visual event-related potential (ERP) experiment, in which they controlled the duration of stimulus viewing with a button press, which served as a measure of exploratory behavior. Each of the three experimental conditions included a frequent repetitive background stimulus and infrequent stimuli that deviated from the background stimulus. In one condition, both background and deviant stimuli were simple, easily recognizable geometric figures. In another condition, both background and deviant stimuli were unusual/unfamiliar figures, and in a third condition, the background stimulus was a highly unusual figure, and the deviant stimuli were simple, geometric shapes. Deviant stimuli elicited larger N2-P3 amplitudes and longer viewing durations than the repetitive background stimulus, even when the deviant stimuli were simple, familiar shapes and the background stimulus was a highly unusual figure. Compared to simple, familiar deviant stimuli, unusual deviant stimuli elicited larger N2-P3 amplitudes and longer viewing times. Within subjects, the deviant stimuli that evoked the largest N2-P3 responses also elicited the longest viewing durations. We conclude that deviance from both immediate context and long-term prior experience contribute to the response to novelty, with the combination generating the largest N2-P3 amplitude and the most sustained attention. The amplitude of the N2-P3 may reflect how much "uncertainty" is evoked by a novel visual stimulus and signal the need for further exploration and cognitive processing. [ABSTRACT FROM AUTHOR]

From March 1993 to February 1997, 43 eligible patients with inoperable stage IIIA (ten patients) and stage IIIB (33 patients), histologically confirmed NSCLC received 3 courses of the ICE combination (ifosfamide 1.5 g m[SUP-2] and mesna 750 mg m[SUP-2] two times a day, cisplatin 25 mg m[SUP-2] and etoposide 100 mg m[SUP-2], all administered intravenously (i.v.) on days 1-3 every 3 weeks) with G-CSF support. After three cycles, patients were submitted to radical surgery or received two additional courses of the ICE regimen and/or curative radiotherapy. Grade 3-4 neutropenia occurred in 21% of 114 evaluable courses, but was of short duration, leading to neutropenic fever in 5% of the courses. Severe thrombocytopenia and anaemia were observed in 13% and 3% of the courses respectively. Non-haematological toxicity was generally mild with only two episodes of reversible renal impairment. The overall response rate after three chemotherapy courses was 69% (28 partial responses, one complete response). Ten patients (8/10 patients in stage IIIA, 2/33 patients in stage IIIB) underwent radical surgery. Median TTP for patients not undergoing surgery (n = 33) was 8 months (range 3-34+); median DFS for patients rendered NED by surgery (n = 10) was 26 months (range 1-54+). Median OS for the entire group was 12.5 months (range 2-57+). The ICE regimen is active in locally advanced NSCLC with acceptable toxicity and warrants further exploration as induction chemotherapy in larger series. [ABSTRACT FROM AUTHOR]