Development and validation of the Heidelberg Neurological Triage System (HEINTS).

BACKGROUND/OBJECTIVE: Neurological syndromes are underrepresented in existing triage systems which are not validated for neurological patients; therefore, we developed and validated the new Heidelberg Neurological Triage System (HEINTS) in a prospective, single-center observational study. METHODS: Patients were triaged according to the new triage system by nurses and physicians (stage 1) as well as trained nurses (stage 2). In stage 1, all patients presenting to the neurological emergency room (ER) were triaged by nurses and physicians. In stage 2, three specially trained nurses triaged patients according to HEINTS. The main outcomes comprised interrater agreement between nurses' and physicians' triage (stage 1), sensitivity and specificity to detect emergencies (stages 1 and 2), and improvement in triage quality as a result of training (stage 2), as well as correlation of HEINTS with hospital admissions and resource utilization. RESULTS: In stage 1 (n = 2423 patients), sensitivity and specificity to detect neurological emergencies were 84.2% (SD 0.8%) and 85.4% (SD 0.8%) for nurses, as well as 92.4% (SD 0.6%) and 84.1% (SD 0.9%) for physicians, respectively. The interrater-reliability between nurses and physicians in stage 1 was moderate [Cohen's kappa 0.44, standard deviation (SD) 0.02]. In stage 2 (n = 506 patients), sensitivity of trained nurses increased to 94.3% (SD 1.0%), while specificity decreased to 74.8% (SD 1.9%). Correlation of HEINTS triage with hospital admission and resource utilization in both stages was highly significant. CONCLUSIONS: HEINTS predicted hospital admissions and resource utilization. Agreement between nurses and physicians was moderate. HEINTS, applied by physicians and by nurses after training, reliably detected neurological emergencies.

Lost in transition: aging-related changes in executive control by the medial prefrontal cortex.

Neural correlates of aging in the medial prefrontal cortex (mPFC) were studied using an operant delayed response task. The task used blocks of trials with memory-guided (delayed alternation) and visually-guided (stimulus-response) responding. Older rats (24 months) performed at a slow pace compared with younger rats (6 months). They wasted time engaged in nonessential behaviors (e.g., licking on spouts beyond the period of reward delivery) and were slow to respond at the end of the delay period. Aged mPFC neurons showed normal spatial processing. They differed from neurons in younger rats by having reduced modulations by imperative stimuli indicating reward availability and reduced activity associated with response latencies for reward collection. Older rats showed reduced sensitivity to imperative stimuli at three levels of neural activity: reduced fractions of neurons with changes in firing rate around the stimulus, reduced correlation over neurons at the time of the stimulus as measured with analysis of population activity, and reduced amplitudes of event-related fluctuations in intracortical field potentials at the time of the imperative stimulus. Our findings suggest that aging alters the encoding of time-sensitive information and impairs the ability of prefrontal networks to keep subjects "on task."

Noradrenergic control of error perseveration in medial prefrontal cortex.

The medial prefrontal cortex (mPFC) plays a key role in behavioral variability, action monitoring, and inhibitory control. The functional role of mPFC may change over the lifespan due to a number of aging-related issues, including dendritic regression, increased cAMP signaling, and reductions in the efficacy of neuromodulators to influence mPFC processing. A key neurotransmitter in mPFC is norepinephrine. Previous studies have reported aging-related changes in the sensitivity of mPFC-dependent tasks to noradrenergic agonist drugs, such as guanfacine. Here, we assessed the effects of yohimbine, an alpha-2 noradrenergic antagonist, in cohorts of younger and older rats in a classic test of spatial working memory (using a T-maze). Older rats (23-29 mo.) were impaired by a lower dose of yohimbine compared to younger animals (5-10 mo.). To determine if the drug acts on alpha-2 noradrenergic receptors in mPFC and if its effects are specific to memory-guided performance, we made infusions of yohimbine into mPFC of a cohort of young rats (6 mo.) using an operant delayed response task. The task involved testing rats in blocks of trials with memory- and stimulus-guided performance. Yohimbine selectively impaired memory-guided performance and was associated with error perseveration. Infusions of muscimol (a GABA-A agonist) at the same sites also selectively impaired memory-guided performance, but did not lead to error perseveration. Based on these results, we propose several potential interpretations for the role for the noradrenergic system in the performance of delayed response tasks, including the encoding of previous response locations, task rules (i.e., using a win-stay strategy instead of a win-shift strategy), and performance monitoring (e.g., prospective encoding of outcomes).