Treadmill Gait Analysis Does Not Detect Motor Deficits in Animal Models of Parkinson's Disease or Amyotrophic Lateral Sclerosis

Computerized treadmill gait analysis in models of toxicant exposure and neurodegenerative disorders holds much potential for detection and therapeutic intervention in these models, and researchers must validate the technology that assists in that data collection and analysis. The present authors used a commercially available computerized gait analysis system that used (a) a motorized treadmill on retired breeder male C57BL/6J mice, (b) the toxicant-induced (1-methyl-1-, 2-, 3-, 6-tetrahydropyridine) MPTP mouse model of Parkinson's disease (PD), and (c) the superoxide dismutase 1 (SOD1) G93A transgenic mouse model of amyotrophic lateral sclerosis (ALS). The authors compared the detection of deficits by computerized treadmill gait analysis in MPTP-treated mice with inked-paw stride length and correlated these measures to dopamine (DA) loss. The authors found that the computerized treadmill gait analysis system did not distinguish MPTP-treated mice from vehicle controls, despite a nearly 90% deficit of striatal DA. In contrast, decreases in inked-paw stride length correlated strongly with DA losses in these same animals. Computerized treadmill gait analysis could neither reliably distinguish SOD1 G93A mutant mice from controls from 6 to 12 weeks of age nor detect any consistent early motor deficits in these mice. On the basis of the authors' findings, they inferred that computerized gait analysis on a motorized treadmill is not suited to measuring motor deficits in either the MPTP mouse model of PD or the SOD1 G93A mouse model of ALS.     

Narrative retelling in children with neurodevelopmental disorders: Is there a role for nonverbal temporal‐sequencing skills?

Oral narrative retelling is often problematic for children with communicative and neurodevelopmental disorders. However, beyond a suggested role of language level, little is known about the basis of narrative performance. In this study we examine whether oral narrative retelling might be associated not just with language level but also with skills related to nonverbal narrative temporal sequencing. A diagnostically heterogeneous sample of Swedish‐speaking children with a full scale IQ >70 was included in the study (N = 55; age 6–9 years). Narrative retelling skills were measured using the three subscores from the bus story test (BST). Independent predictors included (1) temporal sequencing skills according to a picture arrangement test and (2) a language skills factor consisting of definitional vocabulary and receptive grammar. Regression analyses show that language skills predicted BST Sentence Length and Subordinate Clauses subscores, while both temporal sequencing and language were independently linked with the BST Information subscore. When subdividing the sample based on nonverbal temporal sequencing level, a significant subgroup difference was found only for BST Information. Finally, a principal component analysis shows that temporal sequencing and BST Information loaded on a common factor, separately from the language measures. It is concluded that language level is an important correlate of narrative performance more generally in this diagnostically heterogeneous sample, and that nonverbal temporal sequencing functions are important especially for conveying story information. Theoretical and clinical implications are discussed.     

Semantic clustering as a neuropsychological predictor for amnestic-MCI

ABSTRACT

Recent research has demonstrated that patients with Alzheimer's disease (AD) show deficits in semantic processing when compared to cognitively healthy individuals. This difference is thought to be attributed to losses in higher cortical systems that are predominantly associated with executive functioning. The first aim of the study will be to determine if differences in semantic clustering can accurately differentiate patients with amnestic mild cognitive impairment (aMCI) from cognitively normal (CN) individuals. The second aim will be to determine the extent to which semantic processing might be associated with executive functions. Data from 202 (134 CN, 68 aMCI) participants were analyzed to quantify differences in semantic clustering ratios on the HVLT-R. Study participants ages ranged from 51 to 87 with education ranging from 6 to 20 years. ANCOVA revealed statistically significant differences on semantic clustering ratios (p < .001). Moderate correlations between semantic clustering Category Fluency Test (r = .45) were also found. Statistically significant group differences were also present on Trails-B and WAIS-R Digit Symbol performance (p < .001). Overall, these data indicate that deficits in semantic clustering are present in aMCI patients.     

Alterations in working memory networks in amnestic mild cognitive impairment

Patients with amnestic mild cognitive impairment (aMCI) show preserved or mildly impaired working memory, despite their deficits in episodic memory. We aimed to identify performance and/or neural differences between aMCI patients and matched controls on a standard working memory fMRI task. Neuropsychological assessment demonstrated aMCI impairments in verbal and visual episodic long-term memory, with intact IQ and executive function. Participants completed a standard three-level N-back task where patients were unimpaired. Functional activations in the control group were found in expected areas, including the inferior parietal lobule and dorsolateral prefrontal cortex. Group differences were found in the insula and lingual gyrus and, in a region of interest analysis, in the hippocampus. In all cases, these were caused by an absence of task-related deactivations in the aMCI group. The results are consistent with reports of failure in task-related deacivations in aMCI and could be early indications of pathology.     

Repetition-lag training to improve recollection memory in older people with amnestic mild cognitive impairment. A randomized controlled trial

The results of a randomized controlled trial of repetition-lag training in older adults with amnestic mild cognitive impairment (aMCI) are reported. A modified repetition-lag training procedure with extended encoding time and strategy choice was used. The training required discriminating studied words from non-studied lures that were repeated at varying intervals during the test phase. Participants were assessed pre/post using untrained measures of cognition and self-report questionnaires. Primary outcome measures were recall of unrelated word pairs both immediately following presentation and following a delay. Secondary outcomes were a measure of attention, cognitive flexibility, and visual working memory. Participants were also asked to report on the frequency of cognitive failures and mood before and after training. Participants (N = 31) were randomized into either the treatment or a no-contact control group and attended the clinic twice per week over a four week period. Twenty-four participants completed the study (twelve in each group). Results indicated that the training group improved at recalling unrelated word pairs after a delay. There were no significant effects of training on other outcomes, self-reported cognitive failures or mood. The results are discussed along with suggestions for future research.     

Mindfulness,physical impairment and psychological well-being in people with amyotrophic lateral sclerosis

Objective: Mindfulness is the process of actively making new distinctions, rather than relying on habitual or automatic categorisations from the past. Mindfulness has been positively associated with physical well-being, better recovery rates from disease or infections, pain reduction and overall quality of life (QOL). Amyotrophic lateral sclerosis (ALS) is a rare, progressive and fatal neurodegenerative disease, clinically characterised by progressively increasing weakness leading to death, usually within five years. There is presently no cure for ALS, and it is considered one of the most genetically and biologically driven illnesses. Thus far, the aims of psychological studies on ALS have focused on understanding patient – and, to a lesser extent, caregiver – QOL and psychological well-being. No previous study has investigated the influence of psychological factors on ALS.

Methods: A sample of 197 subjects with ALS were recruited and assessed online twice, with a duration of four months between the two assessments. Assessments included measurements of trait mindfulness, physical impairment, QOL, anxiety and depression. The influence of mindfulness as predictor of changes in physical impairments was evaluated with a mixed-effects model.

Results: Mindfulness positively influenced the change of physical symptoms. Subjects with higher mindfulness experienced a slower progression of the disease after four months. Moreover, mindfulness at first assessment predicted higher QOL and psychological well-being.

Conclusions: The available data indicate that a psychological construct – mindfulness – can attenuate the progress of a disease that is believed to be almost solely biologically driven. The potential implications of these results extend well beyond ALS.     

Atypical Neuropsychological Profile in a Boy with 22q11.2 Deletion Syndrome Keywords:

In this article the general and specific cognitive impairments of the boy R.H. with a de novo deletion 22q11.2 are described. His full-scale IQ was 73, and he obtained only slightly better verbal than non-verbal subtest scores. Neuropsychological assessment revealed specific impairments in perceptual categorization of objects presented suboptimal, matching of unfamiliar faces, and verbal learning and memory. In contrast, he performed in accordance with his intelligence level on other visual perceptual tasks, on non-verbal learning and memory tasks, and on attention tasks. Voxel-wise statistical comparison of a high-resolution T1-weighted magnetic resonance image of R.H’s brain with similar images obtained from 14 normal control children revealed as major abnormalities a reduction of the right inferior parietal and superior occipital lobe, and a bilateral reduction of deep white matter behind the inferior frontal gyrus. These cognitive impairments and MRI abnormalities are not commonly described in 22q11.2 Deletion Syndrome and may indicate a larger heterogeneity in the neurocognitive phenotype than currently evidenced. At least in this boy the microdeletion seems to have interfered with the development and functioning of particular neural subsystems, while the structure and functioning of other subsystems was left intact.     

The effects of presentation and content on syllogistic reasoning by children with and without specific language impairment

This study examines performance at a syllogistic reasoning task for a group of children (age 10 years) with specific language impairment (SLI) along with age- and language-matched controls. The syllogisms were presented either verbally or verbally/pictorially, and contained two types of item: imaginary versus real, both intended not to evoke strong beliefs. Children with SLI performed worse than age-matched controls, and equivalently to language-matched controls. Patterns of performance indicate this may be due to cognitive ability deficits rather than specific language deficits. For all groups, pictorial presentation interfered with reasoning processes. It is suggested that, for syllogisms, this pictorial information contextualises the interpretation of the task, and that in turn either raises working memory load or evokes belief bias. Additionally, these results suggest that caution should be exhibited before using visual aids to help children with SLI in the classroom.     

Does visual experience influence the spatial distribution of auditory attention?

Sighted individuals are less accurate and slower to localize sounds coming from the peripheral space than sounds coming from the frontal space. This specific bias in favour of the frontal auditory space seems reduced in early blind individuals, who are particularly better than sighted individuals at localizing sounds coming from the peripheral space. Currently, it is not clear to what extent this bias in the auditory space is a general phenomenon or if it applies only to spatial processing (i.e. sound localization). In our approach we compared the performance of early blind participants with that of sighted subjects during a frequency discrimination task with sounds originating either from frontal or peripheral locations. Results showed that early blind participants discriminated faster than sighted subjects both peripheral and frontal sounds. In addition, sighted subjects were faster at discriminating frontal sounds than peripheral ones, whereas early blind participants showed equal discrimination speed for frontal and peripheral sounds. We conclude that the spatial bias observed in sighted subjects reflects an unbalance in the spatial distribution of auditory attention resources that is induced by visual experience.     

Synchrony,complexity and directiveness in mothers’ interactions with infants pre- and post-cochlear implantation

This study investigated effects of profound hearing loss on mother–infant interactions before and after cochlear implantation with a focus on maternal synchrony, complexity, and directiveness. Participants included two groups of mother–infant dyads: 9 dyads of mothers and infants with normal hearing; and 9 dyads of hearing mothers and infants with profound hearing loss. Dyads were observed at two time points: Time 1, scheduled to occur before cochlear implantation for infants with profound hearing loss (mean age = 13.6 months); and Time 2 (mean age = 23.3 months), scheduled to occur approximately six months after cochlear implantation. Hearing infants were age-matched to infants with hearing loss at both time points. Dependent variables included the proportion of maternal utterances that overlapped infant vocalizations, maternal mean length of utterance, infant word use, and combined maternal directives and prohibitions. Results showed mothers’ utterances overlapped the vocalizations of infants with hearing loss more often before cochlear implantation than after, mothers used less complex utterances with infants with cochlear implants compared to hearing peers (Time 2), and mothers of infants with profound hearing loss used frequent directives and prohibitions both before and after cochlear implantation. Together, mothers and infants adapted relatively quickly to infants’ access to cochlear implants, showing improved interactional synchrony, increased infant word use, and levels of maternal language complexity compatible with infants’ word use, all within seven months of cochlear implant activation.