Dynamic shifts in corticostriatal expression patterns of the immediate early genes Homer 1a and Zif268 during early and late phases of instrumental training

Adaptive motor actions require prior knowledge of instrumental contingencies. With practice, these actions can become highly automatic in nature. However, the molecular and anatomical substrates mediating these related forms of learning are not understood. In the present study, we used in situ hybridization to measure the mRNA levels of two immediate early genes (IEGs) in an instrumental paradigm where rats learned to lever-press for food. We report that after three training sessions, Homer 1a and Zif268 (an effector and regulatory IEG, respectively) were significantly induced within an extensive corticostriatal network relative to untrained controls. With extended training (23 sessions), however, a shift in the expression patterns of the two genes was evident. Expression of Homer 1a (official symbol Homer1) decreased significantly in frontal and cingulate cortices, whereas striatal expression was generally maintained. Interestingly, Homer 1a expression markedly increased with extensive training in the ventrolateral region of the striatum (VLS) relative to early learners, suggesting that plasticity in the VLS is required for the efficient production of the learned behavior or in habit formation. Zif268 (official symbol Egr1) expression generally decreased with extensive training; however, these changes were not significant. These results demonstrate for the first time, on a molecular level, a dynamic shift in the contribution of corticostriatal systems mediating the early acquisition and consolidation of goal-directed responses to those engaged after extensive training.     

Visuospatial function in the beagle dog: an early marker of cognitive decline in a model of human aging and dementia

Visuospatial learning and memory impairments are an early marker for age-related cognitive decline and Alzheimer's disease. Similar to humans, aged dogs show visuospatial learning and memory deficits (). One hundred and nine beagle dogs ranging between 0.25 and 11.99 years were tested on a visuospatial delayed non-matching to position (DNMP) task to better characterize the progression of visuospatial deficits in the dog. Age predicted 48.2% of the variability in learning the DNMP, with dogs ranging from 1 to 11.99 years generally making more errors with increasing age. By contrast, puppies (<1 year) likely were showing developmental deficits, possibly due to an immature prefrontal cortex. Mild visuospatial deficits were detected by 6 years, which precedes the typical onset of amyloid-beta (Abeta) accumulation in the dog brain by two years, and can serve as an early marker for cognitive decline in the dog. These findings suggest that (1) age-related changes in visuospatial function in the dog models that seen in humans, further validating the dog as a model for human aging and dementia; and (2) other mechanisms, such as oxidative stress, soluble Abeta oligomers or cholinergic deficits, are likely contributing to the early impairment.     

Youth-parent consistencies on ratings of difficulties and prosocial behavior: exploration of an at-risk sample

Low informant agreement is of particular concern in clinical settings, since diagnoses and interventions are largely based on reports from parents and/or youths. This study explores youth-parent consistencies in an at-risk sample of youths (n = 42), several from immigrant and refugee families, all with stressful background experiences. Data from a community sample (n = 165) was used to contrast the clinical results. Results showed that correlations between clinical youths and parents were within the same range as those in the community sample. Consistencies concerning absolute level of behavior were higher in the clinical sample. However, interesting differences in informant consistencies were found on difficulties and resources between the two samples. This study adds to the picture that there is no simple relationship between severity of behavior deviance and informant agreement. Asking about behavioral resources as well as difficulties may provide valuable additional information regarding differences in the perspectives of at-risk youths and parents.     

Does attention cause illusory line motion?

Illusory line motion (ILM) has been shown to occur when a line is presented with one end next to a previously stimulated location. The line appears to be drawn away from the site of stimulation. It has been suggested that this is because of the allocation of attention to the stimulated site. Using an endogenous attentional manipulation (a central arrow cue) with no differences in the display between the two ends of the line at the time of line presentation or immediately prior, no ILM was detected, though there was a small effect in the opposite direction. Those who have found endogenously induced ILM have used an endogenous cue based on a property of a location marker that indicated the cued location. Changing the method of cuing to one based on a property of a peripheral marker instead of a central arrow produced a small but significant report of ILM. The small magnitude of the effect, participant self-reports, and the absence of the effect in the purely endogenous condition, suggest that this was merely a bias. ILM is not generated by endogenous attention shifts.     

Effects of repetition and response deadline on associative recognition in young and older adults

The present study examined the joint effects of repetition and response deadline on associative recognition in older adults. Young and older adults studied lists of unrelated word pairs, half presented once (weak pairs) and half presented four times (strong pairs). Test lists contained old (intact) pairs, pairs consisting of old words that had been studied with other partners (rearranged lures), and unstudied pairs (new lures), and participants were asked to respond "old" only to intact pairs. In Experiment 1, participants were tested with both short and long deadlines. In Experiment 2, the tests were unpaced. In both experiments, repetition increased hit rates for young and older adults. Young adults tested with a long deadline showed reduced (Experiment 1) or invariant (Experiment 2) false alarms to rearranged lures when word pairs were studied more often. Young adults tested with a short deadline and older adults tested under all conditions had increased false alarm rates forstrong rearranged pairs. Implications of these results for theories of associative recognition and cognitive aging are explored.     

Demonstration of nondeclarative sequence learning in mice: development of an animal analog of the human serial reaction time task

In this paper, we demonstrate nondeclarative sequence learning in mice using an animal analog of the human serial reaction time task (SRT) that uses a within-group comparison of behavior in response to a repeating sequence versus a random sequence. Ten female B6CBA mice performed eleven 96-trial sessions containing 24 repetitions of a 4-trial sequence. During the 12th session, the repeating sequence was replaced with the random sequence halfway through the session. Reaction time (RT) to respond to an illuminated nose-poke was recorded, and performance was compared at the halfway point in each session to test for any change in behavior. For learning effect, RTs decreased over the no-switch repeating-sequence sessions. For interference effect, behavior did not change appreciably at the halfway point during the last repeating-sequence session. However, RTs deteriorated significantly after the switch from repeating to random sequences halfway through session 12. The mice demonstrated a robust interference effect when switched from repeating to random sequences. This pattern of behavior in humans performing the SRT is interpreted as evidence of nondeclarative sequence learning. The similarity between the human and mouse SRTs will enable more direct comparisons of mouse-human nondeclarative memory behavior and will provide a useful behavioral end-point in mouse-models of basal ganglia dysfunction.     

The Relation Between Sluggish Cognitive Tempo and DSM-IV ADHD

To test the relation between sluggish cognitive tempo (SCT) and DSM-IV ADHD symptoms, parent and teacher ratings of the 18 DSM-IV ADHD items and five potential SCT items were obtained in a community sample of 8-18 year-old twins that was overselected for ADHD and learning disabilities (n = 296). Confirmatory factor analyses revealed that a three-factor model provided the best fit to the data for both parent and teacher ratings. DSM-IV inattention and hyperactivity-impulsivity symptoms loaded on two factors consistent with the DSM-IV model, and five SCT symptoms loaded primarily on a third factor. The SCT and inattention factors were highly correlated, whereas SCT and hyperactivity-impulsivity were weakly related. Both raters indicated that children meeting symptom criteria for the combined and inattentive subtypes exhibited significantly more SCT symptoms than those meeting symptom criteria for hyperactive-impulsive type and the comparison group without ADHD. Children meeting symptom criteria for the inattentive type exhibited significantly more SCT symptoms than those meeting criteria for the combined type, based on teacher ratings. These results suggest that SCT is an internally consistent construct that is significantly associated with DSM-IV inattention.     

Phonological memory and vocabulary learning in children with focal lesions

Eleven children with early focal lesions were compared with 70 age-matched controls to assess their performance in repeating non-words, in learning new words, and in immediate serial recall, a triad of abilities that are believed to share a dependence on serial ordering mechanisms (e.g.,; ). Results for the experimental group were also compared with other assessments previously reported for the same children by. The children with brain injury showed substantial impairment relative to controls in the experimental tasks, in contrast with relatively unimpaired performance on measures of vocabulary and non-verbal intelligence. The relationships between word learning, non-word repetition, and immediate serial recall were similar to those observed in several other populations. These results support previous reports that there are persistent processing impairments following early brain injury, despite developmental plasticity. They also suggest that word learning, non-word repetition, and immediate serial recall may be relatively demanding tasks, and that their relationship is a fundamental aspect of the cognitive system.     

Children's understanding of the relation between addition and subtraction: inversion, identity, and decomposition.

In order to understand addition and subtraction fully, children have to know about the relation between these two operations. We looked at this knowledge in two studies. In one we asked whether 5- and 6-year-old children understand that addition and subtraction cancel each other out and whether this understanding is based on the identity of the addend and subtrahend or on their quantity. We showed that children at this age use the inversion principle even when the addend and subtrahend are the same in quantity but involve different material. In our second study we showed that 6- to 8-year-old children also use the inversion in combination with decomposition to solve a + b - (b + 1) problems. In both studies, factor analyses suggested that the children were using different strategies in the control problems, which require computation, than in the inversion problems, which do not. We conclude that young children understand the relations between addition and subtraction and that this understanding may not be based on their computational skills.