Impaired cognitive flexibility in amyotrophic lateral sclerosis.

BACKGROUND AND OBJECTIVE: Up to half of patients with amyotrophic lateral sclerosis (ALS) may have cognitive difficulty, but most cognitive measures are confounded by a motor component. Studies relating impaired cognition in ALS to disease in gray matter and white matter are rare. Our objective was to assess executive function in patients with ALS using a simple, untimed measure with minimal motor demands, and to relate performance to structural disease. METHODS: We gave the Visual-Verbal Test to 56 patients with ALS and 29 matched healthy controls. This brief, untimed measure of cognitive flexibility first assesses participants' ability to identify a feature shared by 3 of 4 simple geometric designs. The participants' cognitive flexibility is challenged when they are next asked to identify a different feature shared by another combination of 3 of the same 4 geometric designs. In a subset of 17 patients who underwent magnetic resonance imaging, regression analyses related test performance to gray matter atrophy and reduced white matter fractional anisotropy. RESULTS: The patients with ALS showed significant impairment in cognitive flexibility (P<0.01), with 48.2% making an error on the test. Regression analyses related impaired cognitive flexibility to gray matter atrophy in inferior frontal and insular regions, and to reduced fractional anisotropy in white matter projections in the inferior fronto-occipital and uncinate fasciculi and corpus callosum. CONCLUSIONS: Our patients with ALS had impaired cognitive flexibility on an untimed measure with minimal motor demands, a finding related in part to a large-scale frontal network that is degraded in ALS.

Use of medial axis for reorientation by the Clark's nutcracker (Nucifraga columbiana).

Many animals are challenged with the task of reorientation. Considerable research over the years has shown a diversity of species extract geometric information (e.g., distance and direction) from continuous surfaces or boundaries to reorient. How this information is extracted from the environment is less understood. Three encoding strategies that have received the most study are the use of principal axes, medial axis or local geometric cues. We used a modeling approach to investigate which of these three general strategies best fit the spatial search data of a highly-spatial corvid, the Clark's nutcracker (Nucifraga columbiana). Individual nutcrackers were trained in a rectangular-shaped arena, and once accurately locating a hidden goal, received non-reinforced tests in an L-shaped arena. The specific shape of this arena allowed us to dissociate among the three general encoding strategies. Furthermore, we reanalyzed existing data from chicks, pigeons and humans using our modeling approach. Overall, we found the most support for the use of the medial axis, although we additionally found that pigeons and humans may have engaged in random guessing. As with our previous studies, we find no support for the use of principal axes.

Dissociation of quantifiers and object nouns in speech in focal neurodegenerative disease.

Quantifiers such as many and some are thought to depend in part on the conceptual representation of number knowledge, while object nouns such as cookie and boy appear to depend in part on visual feature knowledge associated with object concepts. Further, number knowledge is associated with a frontal-parietal network while object knowledge is related in part to anterior and ventral portions of the temporal lobe. We examined the cognitive and anatomic basis for the spontaneous speech production of quantifiers and object nouns in non-aphasic patients with focal neurodegenerative disease associated with corticobasal syndrome (CBS, n=33), behavioral variant frontotemporal degeneration (bvFTD, n=54), and semantic variant primary progressive aphasia (svPPA, n=19). We recorded a semi-structured speech sample elicited from patients and healthy seniors (n=27) during description of the Cookie Theft scene. We observed a dissociation: CBS and bvFTD were significantly impaired in the production of quantifiers but not object nouns, while svPPA were significantly impaired in the production of object nouns but not quantifiers. MRI analysis revealed that quantifier production deficits in CBS and bvFTD were associated with disease in a frontal-parietal network important for number knowledge, while impaired production of object nouns in all patient groups was related to disease in inferior temporal regions important for representations of visual feature knowledge of objects. These findings imply that partially dissociable representations in semantic memory may underlie different segments of the lexicon.

Factors modulating social influence on spatial choice in rats.

Three experiments examined the conditions under which the spatial choices of rats searching for food are influenced by the choices made by other rats. Model rats learned a consistent set of baited locations in a 5 × 5 matrix of locations, some of which contained food. In Experiment 1, subject rats could determine the baited locations after choosing 1 location because all of the baited locations were on the same side of the matrix during each trial (the baited side varied over trials). Under these conditions, the social cues provided by the model rats had little or no effect on the choices made by the subject rats. The lack of social influence on choices occurred despite a simultaneous social influence on rats' location in the testing arena (Experiment 2). When the outcome of the subject rats' own choices provided no information about the positions of other baited locations, on the other hand, social cues strongly controlled spatial choices (Experiment 3). These results indicate that social information about the location of food influences spatial choices only when those cues provide valid information that is not redundant with the information provided by other cues. This suggests that social information is learned about, processed, and controls behavior via the same mechanisms as other kinds of stimuli.

Five on one side: personal and social information in spatial choice.

To examine whether the outcome of a rat's own choices ("personal information") and the choice behavior of another rat ("social information") can jointly control spatial choices, rats were tested in an open field task in which they searched for food. For the rats of primary interest (Subject Rats), the baited locations were all on one side of the arena, but the specific locations baited and the side on which they occurred varied over trials. The Subject Rats were sometimes tested together with an informed "Model" rat that had learned to find food in the same five locations (all on the same side of the arena) on every trial. Unintended perceptual cues apparently controlled spatial choices at first, but when perceptual cues to food location were not available, choices were controlled by both personal information (allowing the baited side of the arena to be determined) and social information (allowing baited locations to be determined more precisely). This shows that control by personal and social information are not mutually exclusive and supports the view that these two kinds of information can be used flexibly and adaptively to guide spatial choices. This article is part of a Special Issue entitled: tribute to Tom Zentall.

Estimating frontal and parietal involvement in cognitive estimation: a study of focal neurodegenerative diseases.

We often estimate an unknown value based on available relevant information, a process known as cognitive estimation. In this study, we assess the cognitive and neuroanatomic basis for quantitative estimation by examining deficits in patients with focal neurodegenerative disease in frontal and parietal cortex. Executive function and number knowledge are key components in cognitive estimation. Prefrontal cortex has been implicated in multilevel reasoning and planning processes, and parietal cortex has been associated with number knowledge required for such estimations. We administered the Biber cognitive estimation test (BCET) to assess cognitive estimation in 22 patients with prefrontal disease due to behavioral variant frontotemporal dementia (bvFTD), to 17 patients with parietal disease due to corticobasal syndrome (CBS) or posterior cortical atrophy (PCA) and 11 patients with mild cognitive impairment (MCI). Both bvFTD and CBS/PCA patients had significantly more difficulty with cognitive estimation than controls. MCI were not impaired on BCET relative to controls. Regression analyses related BCET performance to gray matter atrophy in right lateral prefrontal and orbital frontal cortices in bvFTD, and to atrophy in right inferior parietal cortex, right insula, and fusiform cortices in CBS/PCA. These results are consistent with the hypothesis that a frontal-parietal network plays a crucial role in cognitive estimation.