Automated detection of cognitive impairment in clinical practice.

OBJECTIVE: Cognitive impairment is now recognized as an impending public health crisis. About one-third of adults are concerned about their cognition, and the prevalence of objective cognitive impairment is much higher among those with neurological disorders. Existing screening tools are narrowly focused on detecting dementia in older adults and must be clinician-administered and scored, making them impractical for many neurology practices. This study examined the utility of a brief, self-administered, computerized cognitive screening tool, the Brief Assessment of Cognitive Health (BACH), in identifying cognitive impairment in adults. METHODS: 912 adults (ages 18-84) completed BACH and a neuropsychological battery. Multivariable models were developed to provide a BACH index score reflecting the probability of cognitive impairment for individual patients. Predictive accuracy was compared to that of the Montreal Cognitive Assessment (MoCA) in a subset of 160 older adults from a Memory Disorders clinic. RESULTS: The final multivariable model showed good accuracy in identifying cognitively impaired individuals (c = 0·77). Compared to MoCA, BACH had superior predictive accuracy in identifying older patients with cognitive impairment (c = 0·79 vs. 0·67) as well as differentiating those with MCI or dementia from those without cognitive impairment (c = 0·86 vs. c = 0·67). CONCLUSIONS: Results suggest that cognitive impairment can be identified in adults using a brief, self-administered, automated cognitive screening tool, and BACH provides several advantages over existing screeners: self-administered; automatic scoring; immediate results in health record; easily interpretable score; utility in wide range of patients; and flags for treatable factors that may contribute to cognitive complaints (i.e., depression, sleep problems, and stress).

Utility of automated memory measures in identifying cognitive impairment in adults with epilepsy.

OBJECTIVE: Cognitive impairment is prevalent in epilepsy and often presents at the time of initial diagnosis. This study sought to validate brief, self-administered, iPad-based recognition memory tasks in a sample of patients with epilepsy and to examine their screening utility in identifying patients with cognitive impairment. METHODS: The Words and Faces tests were administered to 145 adult patients with epilepsy along with a neuropsychological battery. Correlation analyses examined the convergent and divergent validity of the Words and Faces tests, and a series of logistic regression analyses examined discriminative ability in identifying patients with and without cognitive impairments on neuropsychological measures. Patient performance was compared to that of a healthy control group (n = 223), and the relationship between the Words and Faces test performance and disease-related variables (i.e., antiepileptic medication burden, seizure lateralization/localization) was examined. RESULTS: The Words and Faces tests were positively correlated with traditional paper-and-pencil neuropsychological measures of episodic memory, with generally moderate to large effect sizes (r > .40), while correlations between the Words and Faces tests and non-memory measures were generally small in magnitude (r < .30). Patients with epilepsy had significantly lower scores on Words and Faces tests compared to healthy controls, and performance was associated with antiepileptic medication burden and seizure localization. The Words and Faces tests demonstrated good predictive accuracy in identifying any cognitive impairment (concordance (c) statistic = .77) and excellent predictive accuracy (c = .85) in identifying patients with impairments on traditional memory measures. The Words and Faces tests also demonstrated reasonable discrimination for impairments in non-memory domains including executive function, language, attention, processing speed, and visuospatial ability (c = .62 -.70). Importantly, the Words and Faces Immediate Index performed just as well as the Total Score (which included delayed memory performance), suggesting a short version of this measure is sufficient for identifying patients with cognitive impairment. CONCLUSIONS: The Words and Faces tests are valid, computerized tools that can be used to screen for memory and other cognitive impairment in adults with epilepsy.

Validation of Self-Administered Visual and Verbal Episodic Memory Tasks in Healthy Controls and a Clinical Sample.

This study evaluated the performance characteristics, construct validity, and reliability of two computerized, self-administered verbal and visual recognition memory tests based on the Remember-Know paradigm. Around 250 healthy control participants and 440 patients referred for neuropsychological assessment used an iPad to complete the Words and Faces recognition memory tests before or after concurrent neuropsychological testing. Performance accuracy was high but without ceiling effects. Education, but not age, was related to overall performance for both samples while the influence of gender and race differed across samples. In the clinical sample, overall performance was worse in those patients demonstrating memory impairment on clinical assessment. Words and Faces subtests demonstrated the strongest correlations with neuropsychological measures of verbal and nonverbal memory, respectively. Both showed moderate correlations with processing speed while Faces was also correlated with visuospatial skills. The memory tests showed good test-retest reliability over two testing sessions. These findings demonstrate acceptable psychometric properties in clinical and community samples and suggest that this computerized format is feasible for memory assessment in clinical contexts.

A prefrontal-bed nucleus of the stria terminalis circuit limits fear to uncertain threat.

In many cases of trauma, the same environmental stimuli that become associated with aversive events are experienced on other occasions without adverse consequence. We examined neural circuits underlying partially reinforced fear (PRF), whereby mice received tone-shock pairings on half of conditioning trials. Tone-elicited freezing was lower after PRF conditioning than fully reinforced fear (FRF) conditioning, despite an equivalent number of tone-shock pairings. PRF preferentially activated medial prefrontal cortex (mPFC) and bed nucleus of the stria terminalis (BNST). Chemogenetic inhibition of BNST-projecting mPFC neurons increased PRF, not FRF, freezing. Multiplexing chemogenetics with in vivo neuronal recordings showed elevated infralimbic cortex (IL) neuronal activity during CS onset and freezing cessation; these neural correlates were abolished by chemogenetic mPFC→BNST inhibition. These data suggest that mPFC→BNST neurons limit fear to threats with a history of partial association with an aversive stimulus, with potential implications for understanding the neural basis of trauma-related disorders.

While walking home alone late one night, you hear footsteps behind you. Your heart starts to beat faster as you wonder whether someone might be following you. Being able to identify and evade threats is essential for survival. A key part of this process is learning to recognize signals that predict potential danger: the sound of footsteps behind you, for example. But many such cues are unreliable. The person behind you might simply be heading in the same general direction as you. And if you spend too much time and energy responding to such false alarms, you may struggle to complete other essential tasks. To be useful, responses to cues that signal potential threats must thus be proportionate to the likelihood that danger is actually present. By studying threat detection in mice, Glover et al. have identified a brain circuit that helps ensure that this is the case. Two groups of mice learned to fear a tone that predicted the delivery of a mild footshock. In one group of animals, the tone was followed by a shock on every trial (it was said to be 'fully reinforced'). But in the other group, the tone was followed by a shock on only 50% of trials ('partially reinforced'). After training, both groups of mice froze whenever they heard the tone ­ freezing being a typical fear response in rodents. But the animals trained with the partially reinforced tone showed less freezing than their counterparts in the fully reinforced group. Moreover, freezing in response to the partially reinforced tone was accompanied by activity in a specific neural pathway connecting the frontal part of the brain to an area called the bed nucleus of the stria terminalis. Inhibiting this pathway made mice respond to the partially reinforced tone as though it had been reinforced on every trial. This suggests that activity in this pathway helps dampen responses to unpredictable threat cues. In people with anxiety disorders, cues that become associated with unpleasant events can trigger anxiety symptoms, even if the association is unreliable. The findings of Glover et al. suggest that reduced activity of circuits that constrain excessive responses to threats might contribute to anxiety disorders.

Touchscreen-based assessment of risky-choice in mice.

Addictions are characterized by choices made to satisfy the addiction despite the risk it could produce an adverse consequence. Here, we developed a murine version of a 'risky decision-making' task (RDT), in which mice could respond on a touchscreen panel to obtain either a large milkshake reward associated with varying probability of footshock, or a smaller amount of the same reward that was never punished. Results showed that (the following font is incorrectly smaller/subscripted) mice shifted choice from the large to small reward stimulus as shock probability increased. Immunohistochemical analysis revealed more Fos-positive cells in prelimbic cortex (PL) and basal amygdala (BA) after RDT testing, and a strong anti-correlation between infralimbic cortex (IL) activity and choice of the large reward stimulus under likely (75-100 % probability) punishment. These findings establish an assay for risky choice in mice and provide preliminary insight into the underlying neural substrates.

Combined administration of MK-801 and cycloheximide produces a delayed potentiation of fear discrimination memory extinction.

Mixed evidence exists regarding the role of N-methyl-D-aspartate (NMDA) receptors in memory reconsolidation. We provide no evidence that NMDA receptors are involved with memory reconsolidation, but instead demonstrate that prereactivation systemic MK-801 injection, combined with postreactivation intrabasolateral amygdala (BLA) cycloheximide infusion, produces a delayed potentiation of extinction learning. These data suggest that an interaction between NMDA antagonism and protein synthesis inhibition may enhance extinction by exerting effects outside of the intended reconsolidation manipulation window. The present work demonstrates a novel pharmacological enhancement of extinction, and underscores the importance of employing proper control procedures in reconsolidation research. (PsycINFO Database Record

The amygdala is critical for trace, delay, and contextual fear conditioning.

Numerous investigations have definitively shown amygdalar involvement in delay and contextual fear conditioning. However, much less is known about amygdala contributions to trace fear conditioning, and what little evidence exists is conflicting as noted in previous studies. This discrepancy may result from selective targeting of individual nuclei within the amygdala. The present experiments further examine the contributions of amygdalar subnuclei to trace, delay, and contextual fear conditioning. Rats were trained using a 10-trial trace, delay, or unpaired fear conditioning procedure. Pretraining lesions targeting the entire basolateral amygdala (BLA) resulted in a deficit in trace, delay, and contextual fear conditioning. Immediate post-training infusions of the protein synthesis inhibitor, cycloheximide, targeting the basal nucleus of the amygdala (BA) attenuated trace and contextual fear memory expression, but had no effect on delay fear conditioning. However, infusions targeting the lateral nucleus of the amygdala (LA) immediately following conditioning attenuated contextual fear memory expression, but had no effect on delay or trace fear conditioning. In follow-up experiments, rats were trained using a three-trial delay conditioning procedure. Immediate post-training infusions targeting the LA produced deficits in both delay tone and context fear, while infusions targeting the BA produced deficits in context but not delay tone fear. These data fully support a role for the BLA in trace, delay, and contextual fear memories. Specifically, these data suggest that the BA may be more critical for trace fear conditioning, whereas the LA may be more critical for delay fear memories.