Acute stress and human spatial working memory strategy use.

Acute stress can impair human working memory. Little is known, however, about the effects of acute stress on working memory strategies. The goal of this research was to investigate the effects of acute stress on use of a systematic spatial working memory search strategy. Participants (28 females and 20 males per group) completed the Trier Social Stress Test (TSST) or control tasks. Use of a systematic spatial working memory search strategy was measured through performance on the spatial working memory subtest of the Cambridge Neuropsychological Test Automated Battery (CANTAB). The TSST was effective at producing subjective and cortisol stress responses, but there was no significant stress effect on use of a systematic search strategy or working memory search errors. There were also no significant relationships between subjective and cortisol stress responses and use of a systematic search strategy or working memory search errors within the stress group. These results suggest that acute stress does not impair the self-generation or execution of a systematic spatial working memory search strategy.

Subjective stress and proactive and reactive cognitive control strategies.

Acute stress likely impacts cognitive control. Little is known, however, about the effects that acute stress may have on specific cognitive control strategies. The goal of this research was to investigate the effects of acute stress on proactive and reactive control strategies. Participants completed the Trier Social Stress Test or control tasks. Use of proactive and reactive control strategies was measured with the AX-Continuous Performance Test. The Trier Social Stress Test was effective at producing subjective, cortisol, and heart rate stress responses, but there was no significant effect of stress on use of proactive or reactive control strategies in between-group analyses. However, higher subjective stress responses during performance of the AX-Continuous Performance Test were associated with less frequent use of a proactive control strategy and more frequent use of a reactive control strategy within the stress group.

Left caudal middle frontal gray matter volume mediates the effect of age on self-initiated elaborative encoding strategies.

Aging is associated with decreased self-initiated use of effective elaborative encoding strategies. Little is currently known regarding what factors drive age differences in self-initiated encoding strategies. The present research investigated whether age differences in prefrontal gray matter integrity contribute to age differences in self-initiated elaborative encoding strategies. The relationships between age, prefrontal regional gray matter volumes, and overall use of self-initiated elaborative encoding strategies were examined in healthy younger and older adults. Gray matter volume was calculated from structural MRI scans using Freesurfer. Encoding strategy use was assessed by retrospective item-by-item strategy self-reports given after a verbal intentional encoding task. Left caudal middle frontal gray matter volume mediated the effect of age on overall self-initiated use of elaborative encoding strategies. This suggests that age-associated declines in prefrontal gray matter integrity significantly contribute to age-associated declines in effective encoding strategies.

A longitudinal investigation of cognitive function in children and adolescents with type 1 diabetes mellitus.

OBJECTIVE: Cross-sectional studies find altered cognition in youth with type 1 diabetes mellitus (T1DM). However, few longitudinal studies have examined the trajectories of their cognitive performance over time. The aims of this study were to explore longitudinal change in cognitive function in youth with T1DM as compared with nondiabetic sibling controls, and how glycemic control and age of onset influence cognitive performance over time. METHODS: We assessed crystallized intelligence, visual-spatial ability, delayed memory, and processing speed at 3 time points using the same cognitive tasks in youth with T1DM and sibling controls. Hierarchical linear modeling examined relationships between diabetes, hyperglycemia (HbA1c values), age of onset, and cognition over 5.5 y. RESULTS: Youth with diabetes performed worse than controls on visual-spatial ability and memory tasks over time, and did not improve as much in processing speed. Greater hyperglycemia was associated with lower crystallized intelligence and slower processing speed but better memory across all time points. There was a stronger negative relationship between hyperglycemia and visual-spatial ability for youth with earlier compared with later onset diabetes. Importantly, within-person decreases in hyperglycemia between time points were associated with improved visual-spatial ability and faster processing speed. CONCLUSIONS: On average, differences in cognitive function between youth with T1DM and nondiabetic relatives are maintained or increase during childhood and adolescence. Hyperglycemia and age of onset can have negative effects on the developmental trajectories of cognitive processes in youth with T1DM. However, treatments that lower hyperglycemia may lead to improved cognitive function in youth with T1DM.

Effectiveness of Semantic Encoding Strategy Training after Traumatic Brain Injury is Correlated with Frontal Brain Activation Change.

BACKGROUND: Traumatic Brain Injury (TBI) is frequently associated with chronic, treatment-resistant memory problems, and is one of the leading causes of disability in otherwise healthy adults. Cognitive rehabilitation therapies are used with the goal of improving memory functioning; however, not all patients benefit. Prefrontal cortex (PFC) is critical for employing effective memory strategies. We hypothesized that memory improvement after a brief cognitive intervention would be associated with increases in PFC activation during a memory task. METHODS: The current study used behavioral analyses and functional magnetic resonance imaging (fMRI) to examine the effects of two days of intensive semantic encoding strategy training on memory performance and brain activation patterns in patients in the post-acute stage of TBI. fMRI data were collected before and after training while participants learned word lists. RESULTS: Post-training vs. pre-training changes in total recall and semantic clustering during recall were positively correlated with post-training vs. pre-training changes in neural activation in PFC. CONCLUSIONS: These results suggest that variability in treatment response to cognitive training after TBI may be due in part to variability in PFC function, and that some survivors of TBIs may benefit from treatments specifically targeting the PFC.

Memory for items and relationships among items embedded in realistic scenes: disproportionate relational memory impairments in amnesia.

OBJECTIVE: The objective of this study was to examine the dependence of item memory and relational memory on medial temporal lobe (MTL) structures. Patients with amnesia, who either had extensive MTL damage or damage that was relatively restricted to the hippocampus, were tested, as was a matched comparison group. Disproportionate relational memory impairments were predicted for both patient groups, and those with extensive MTL damage were also expected to have impaired item memory. METHOD: Participants studied scenes, and were tested with interleaved 2-alternative forced-choice probe trials. Probe trials were either presented immediately after the corresponding study trial (Lag 1), 5 trials later (Lag 5), or 9 trials later (Lag 9) and consisted of the studied scene along with a manipulated version of that scene in which 1 item was replaced with a different exemplar (item memory test) or was moved to a new location (relational memory test). Participants were to identify the exact match of the studied scene. RESULTS: As predicted, patients were disproportionately impaired on the test of relational memory. Item memory performance was marginally poorer among patients with extensive MTL damage, but both groups were impaired relative to matched comparison participants. Impaired performance was evident at all lags, including the shortest possible lag (Lag 1). CONCLUSIONS: The results are consistent with the proposed role of the hippocampus in relational memory binding and representation, even at short delays, and suggest that the hippocampus may also contribute to successful item memory when items are embedded in complex scenes.

Differential effects of antipsychotics on lateral bias and social attention in female rats.

RATIONALE: Prior research has demonstrated that individuals with schizophrenia may exhibit lateral biases in attention and deficits in social behavior. The use of a noninvasive animal model of attentional impairments in schizophrenia and antipsychotic drugs can help elucidate the biological underpinnings of attentional processes and facilitate the study of novel therapeutics. OBJECTIVES: The purpose of this study was to compare the effects of three antipsychotic drugs on measures of lateral bias and social attention in healthy, unoperated female rats. MATERIALS AND METHODS: Female Long-Evans rats selected for a preexisting lateral bias in attention, a right behavioral orientation preference (BOP), were administered clozapine, haloperidol, sulpiride, or vehicle. Lateral bias in attention was assessed by determining which forelimb rats removed a nuisance stimulus from first. Social attention was examined by comparing the latency to remove nuisance stimuli in the presence of a social (inaccessible female rat) versus non-social (blinking clock) distractor. RESULTS: All antipsychotic drugs eliminated right lateral bias in attention, while control animals retained their initial bias. Clozapine eliminated right lateral bias more rapidly than the other drugs. Animals receiving clozapine also selectively displayed increased attention to another rat. CONCLUSIONS: The results suggest that the antipsychotic medication clozapine rapidly alters attentional bias and uniquely influences attention to a social stimulus. The right BOP paradigm is a useful animal model for comparing antipsychotic drug effects on lateralized attentional bias and attention to social stimuli.

Cognitive training-related changes in hippocampal activity associated with recollection in older adults.

Impairments in the ability to recollect specific details of personally experienced events are one of the main cognitive changes associated with aging. Cognitive training can improve older adults' recollection. However, little is currently known regarding the neural correlates of these training-related changes in recollection. Prior research suggests that the hippocampus plays a central role in supporting recollection in young and older adults, and that age-related changes in hippocampal function may lead to age-related changes in recollection. The present study investigated whether cognitive training-related increases in older adults' recollection are associated with changes in their hippocampal activity during memory retrieval. Older adults' hippocampal activity during retrieval was examined before and after they were trained to use semantic encoding strategies to intentionally encode words. Training-related changes in recollection were positively correlated with training-related changes in activity for old words in the hippocampus bilaterally. Positive correlations were also found between training-related changes in activity in prefrontal and left lateral temporal regions associated with self-initiated semantic strategy use during encoding and training-related changes in right hippocampal activity associated with recollection during retrieval. These results suggest that cognitive training-related improvements in older adults' recollection can be supported by changes in their hippocampal activity during retrieval. They also suggest that age differences in cognitive processes engaged during encoding are a significant contributor to age differences in recollection during retrieval.

Individual differences in episodic memory: the role of self-initiated encoding strategies.

Individuals' abilities to form and retrieve episodic memories vary widely. Consistent with this, there are substantial individual differences in brain activity during encoding and retrieval that are associated with individual differences in memory performance. Growing evidence suggests that individual differences in self-initiated encoding strategy use play an important role in individual differences in episodic memory and brain activity during intentional encoding. This review examines the role of individual differences in self-initiated encoding strategy use in individual differences in episodic memory, and outlines the major findings of brain lesion and functional neuroimaging studies that characterize the neural correlates of individual differences in self-initiated encoding strategy use. The relevance of individual differences in self-initiated encoding strategy use to understanding episodic memory impairments and alterations in brain activity in clinical populations such as individuals with schizophrenia is also discussed.

Functional-anatomic correlates of individual differences in memory.

Memory abilities differ greatly across individuals. To explore a source of these differences, we characterized the varied strategies people adopt during unconstrained encoding. Participants intentionally encoded object pairs during functional MRI. Principal components analysis applied to a strategy questionnaire revealed that participants variably used four main strategies to aid learning. Individuals' use of verbal elaboration and visual inspection strategies independently correlated with their memory performance. Verbal elaboration correlated with activity in a network of regions that included prefrontal regions associated with controlled verbal processing, while visual inspection correlated with activity in a network of regions that included an extrastriate region associated with object processing. Activity in regions associated with use of these strategies was also correlated with memory performance. This study reveals functional-anatomic correlates of verbal and perceptual strategies that are variably used by individuals during encoding. These strategies engage distinct brain regions and may separately influence memory performance.

Orthographic distinctiveness and semantic elaboration provide separate contributions to memory.

Orthographic distinctiveness and semantic elaboration both enhance memory. The present behavioral and functional magnetic resonance imaging (fMRI) studies examined the relationship between the influences of orthographic distinctiveness and semantic elaboration on memory, and explored whether they make independent contributions. As is typical for manipulations of processing levels, words studied during semantic encoding were better remembered than words studied during nonsemantic encoding. Notably, orthographically distinct words were better recalled and received more remember responses on recognition memory tests than orthographically common words regardless of encoding task, suggesting that orthographic distinctiveness has an additive effect to that of semantic elaboration on memory. In the fMRI study, orthographic distinctiveness and semantic elaboration engaged separate networks of brain regions. Semantic elaboration modulated activity in left inferior prefrontal and lateral temporal regions. In contrast, orthographic distinctiveness modulated activity in distinct bilateral inferior prefrontal, extrastriate, and parietal regions. Orthographic distinctiveness and semantic elaboration appear to have separate behavioral and functional-anatomic contributions to memory.

Common and dissociable activation patterns associated with controlled semantic and phonological processing: evidence from FMRI adaptation.

Recent evidence suggests specialization of anterior left inferior prefrontal cortex (aLIPC; approximately BA 45/47) for controlled semantics and of posterior LIPC (pLIPC; approximately BA 44/6) for controlled phonology. However, the more automated phonological tasks commonly used raise the possibility that some of the typically extensive aLIPC activation during semantic tasks may relate to controlled language processing beyond the semantic domain. In the present study, an event-related fMRI adaptation paradigm was employed that used a standard controlled semantic task and a phonological task that also emphasized controlled processing. When compared with letter (baseline) processing, significant fMRI task and adaptation effects in the aLIPC and pLIPC regions ( approximately BA 45/47, approximately BA 44) were observed during both semantic and phonological processing, with aLIPC showing the strongest effects during semantic processing. A left frontal region ( approximately BA 6) showed task and relative adaptation effects preferential for phonological processing, and a left temporal region ( approximately BA 21) showed task and relative adaptation effects preferential for semantic processing. Our results demonstrate that aLIPC and pLIPC regions are involved in controlled processing across multiple language domains, arguing against a domain-specific LIPC model and for domain-preferentiality in left posterior frontal and temporal regions.

Blockade of central cholinergic receptors impairs new learning and increases proactive interference in a word paired-associate memory task.

Experimental data and computational models suggest that blockade of muscarinic cholinergic receptors impairs paired-associate learning and increases proactive interference (E. DeRosa & M. E. Hasselmo, 2000; M. E. Hasselmo & J. M. Bower, 1993). The results presented here provide evidence in humans supporting these hypotheses. Young healthy subjects first learned baseline word pairs (A-B) and, after a delay, learned additional overlapping (A-C) and nonoverlapping (D-E) word pairs. As predicted, when compared with subjects who received the active placebo glycopyrrolate (4 microg/kg) and subjects who were not injected, those who received scopolamine (8 microg/kg) showed (a) overall impairment in new word paired-associate learning, but no impairment in cued recall of previously learned associates; and (b) greater impairment in learning overlapping (A-C) compared with nonoverlapping (D-E) paired associates.