Barbara Therrien

Prechemotherapy alterations in brain function in women with breast cancer

Despite clinical reports of cognitive deficits associated with cancer chemotherapy, the underlying brain mechanisms are not clear. This research examined selective attention and working memory using functional magnetic resonance imaging (fMRI) in women before chemotherapy for localized breast cancer. Patients were tested with an established selective attention and working memory task during fMRI. Compared with healthy controls, patients showed (a) bilateral brain activation in high-demand task conditions with recruitment of additional components of attention/working memory circuitry, and (b) less accurate and slower task performance. Results indicate compromised cognitive functioning before any chemotherapy and raise key questions for further research.

Changes in directed attention and short-term memory in depression

This study examined changes in directed attention and short-term memory in depression using a newly constructed battery of computerized measures. A repeated measures design was used with two sample groups; 25 individuals meeting DSM-IV criteria for Major Depression and a group-matched comparison sample of 27. Both groups were tested at three points in time over a 10-week period. Test-retest reliability of the measures was examined. Profile analysis demonstrated that there were differences between the depressed and comparison groups in both directed attention and short-term memory. Recommendations for specific improvements in the testing battery are discussed. The ability to detect changes in directed attention and short-term memory may have clinical utility in early detection of impending onset of depression or subtle residual symptoms of an acute episode that may impair functioning or signal a relapse.

Effects of Environment on Enhancing Functional Plasticity following Cerebral Ischemia

Given the brain’s capacity to recover from injury, plasticity may be enhanced following cerebral ischemia through environmental manipulation. Thus, the purpose of this study was to (1) determine the effects of early exposure to an enriched environment following ischemia on functional plasticity and (2) examine the relationship between morphological and behavioral plasticity. Adult female rats (n = 38) were divided into ischemia and control groups. Each group was further randomized to either standard (SC) or enriched conditions (EC). After 4 days of environmental exposure, rats were tested for 6 days in the water maze. Control and ischemia rats exposed to EC have increased total dendritic length (P < 0.05) as well as increased number of dendritic segments in the apical (P < 0.05) region of the hippocampal area compared to those housed in SC; furthermore, increased dendritic spine density in the apical (P < 0.05) region was also seen. Behavioral testing showed that ischemia rats exposed to SC have longer swim latencies (P < 0.05) and greater directional heading errors (P < 0.05) than ischemic rats exposed to EC; the latter group performed similar to controls. It is concluded that EC may be a potentially useful therapy in the recovery of spatial memory impairments seen after ischemia.

An intervention to reduce care‐resistant behavior in persons with dementia during oral hygiene: a pilot study

The primary purpose of this pilot study was to test the feasibility of an intervention designed to reduce care-resistant behaviors (CRBs) in persons with moderate-to-severe dementia during oral hygiene activities. The intervention, Managing Oral Hygiene Using Threat Reduction (MOUTh), combined best oral hygiene practices with CRB reduction techniques. Oral health was operationalized as the total score obtained from the Oral Health Assessment Tool (OHAT). CRB was measured using a refinement of the Resistiveness to Care Scale. Seven nursing home residents with dementia received twice daily mouth care for 14 days. The baseline OHAT mean score of 7.29 (SD = 1.25) improved to 1.00 (SD = 1.26, p < .001); CRB improved from 2.43 CRBs/minute (SD = 4.26) to 1.09 CRBs/minute (SD = 1.56, t = 1.97, df 41, p= .06). The findings from this pilot study suggest that the MOUTh intervention is feasible and reduced CRBs, thus allowing more effective oral care.

Aging and corticosterone injections affect spatial learning in Fischer-344 X Brown norway rats.

The hippocampus is one of the first brain structures to show age-related changes. Moreover, hippocampal neurons are endangered by prolonged exposure to high circulating levels of corticosterone with stress or aging. We examined the effects of aging and high corticosterone levels on spatial learning, a key hippocampal function. Young (4-6 months), old (23-25 months), and very old (31 months) male Fischer-344xBrown Norway (F-344xBN) rats received six pre-testing days in the Morris water task to determine baseline spatial learning performance. Next, half the animals in each group were given daily corticosterone injections for 15 days. During the last six injection days, all animals underwent post-testing in the Morris water task with the environment and goal location changed. Baseline, peak, and clearance plasma corticosterone levels were determined. During pre-testing, old animals swam as directly to the goal as the young, but very old animals were significantly impaired. During post-testing, both old and very old non-injected animals had significantly greater directional heading errors and flatter learning curves than the young. Among injected animals, the very old performed as well as the young, but the old did not. Old animals who did not show improvement during the first three pre-testing days were responsible for the old impairment during post-testing. Thus, only very old F-344xBN rats are impaired when initially exposed to a spatial learning task, but half the old and all very old animals are impaired when the environment is changed. Very old F-344xBN rats, however, demonstrate enhanced spatial learning when exposed to corticosterone injections.

Behavioral effects of transient cerebral ischemia.

CA1 neurons in the hippocampus, a brain structure involved in learning and memory, are selectively vulnerable to ischemic effects. In this study, the authors examined if duration of ischemia is directly related to extent of CA1 damage and degree of spatial learning deficit. Adult female Wistar rats received either 5-min or 10-min ischemia or sham surgery. Following recovery, rats were tested in the Morris water maze. Histological analysis showed moderate cell loss in CA1 (31%) and CA3 (12%) and minimal cell loss in CA2 (4%) with 5-min ischemia. Increased cell loss was seen in CA1 (68%), CA2 (16%), and CA3 (23%) with 10-min ischemia. Behavioral testing revealed that animals with 10-min ischemia have greater spatial learning deficits and they remain impaired across the test days compared to the 5-min ischemic group. Furthermore, degree of CA1 cell loss accounted for approximately 45% of the variance in spatial learning deficits in the ischemic group. The authors conclude that cell loss is largely confined to CA1 region in rats who received 5 and 10 min of ischemia and that increased ischemic duration results in persistent learning deficits in female rats; also, the degree of behavioral impairment is related to extent of CA1 cell loss.

Reducing care-resistant behaviors during oral hygiene in persons with dementia

BackgroundNursing home residents with dementia are often dependent on others for mouth care, yet will react with care-resistant behavior when receiving assistance. The oral health of these elders deteriorates in the absence of daily oral hygiene, predisposing them to harmful systemic problems such as pneumonia, hyperglycemia, cardiac disease, and cerebral vascular accidents. The purpose of this study is to determine whether care-resistant behaviors can be reduced, and oral health improved, through the application of an intervention based on the neurobiological principles of threat perception and fear response. The intervention, called Managing Oral Hygiene Using Threat Reduction, combines best mouth care practices with a constellation of behavioral techniques that reduce threat perception and thereby prevent or de-escalate care-resistant behaviors.Methods/DesignUsing a randomized repeated measures design, 80 elders with dementia from 5 different nursing homes will be randomized at the individual level to the experimental group, which will receive the intervention, or to the control group, which will receive standard mouth care from research team members who receive training in the proper methods for providing mouth care but no training in resistance recognition or prevention/mediation. Oral health assessments and care-resistant behavior measurements will be obtained during a 7-day observation period and a 21-day intervention period. Individual growth models using multilevel analysis will be used to estimate the efficacy of the intervention for reducing care-resistant behaviors in persons with dementia, and to estimate the overall efficacy of the intervention using oral health outcomes. Activity-based costing methods will be used to determine the cost of the proposed intervention.DiscussionAt the conclusion of this study, the research team anticipates having a proven intervention that prevents and reduces care-resistant within the context of mouth care. Long-term objectives include testing the effect of the intervention on systemic illnesses among persons with dementia; examining the transferability of this intervention to other activities of daily living; and disseminating threat reduction interventions to nursing home staff, which may radically change the manner in which care is provided to persons with dementia.Trial RegistrationClinicalTrials.gov: NCT01363258

Mild traumatic brain injury (MTBI) leads to spatial learning deficits

Primary objective: The aim of this study was to investigate the effect of mild and severe TBI on young male Wistar rats’ spatial learning. Research design: Randomized repeated measure experimental design was used to examine spatial learning in three independent animal groups. Methods and procedures: Twenty-four (severe n = 9, mild n = 8, sham n = 7) male rats were included in the study. Animals received controlled mild (1.5 mm), severe (2.5 mm) cortical impact injury or sham surgery. Spatial learning was assessed daily using a modified Morris water maze test, 20 days post-trauma, for 5 consecutive days. Percentage time travelled within each quadrant and escape latency were calculated. All animals’ hippocampal brain regions were examined post-injury using neuron (MAP2) and pre-synaptic protein (Synaptophysin) biomarkers. Main outcomes and results: It took the animals with mild injury until day 3 to reach the platform; and animals with mild and severe injury spent significantly less time in the target quadrant than the sham. The hippocampal neuron numbers differed proportionately between animals with severe and mild injury, but the percentage of synaptophysin density was significantly less in the dentate gyrus of both animals with mild and severe injury than sham group. Conclusion: Persistent spatial learning deficits exist after mild TBI; these deficits appear equivalent to deficits exhibited after a more severe injury.

No more fighting and biting during mouth care: applying the theoretical constructs of threat perception to clinical practice.

The purpose of this article is to describe how the neurobiological principles of threat perception and fear response can support clinical approaches to prevent and reduce care-resistant behaviors during mouth care. Nursing home residents who exhibit care-resistant behavior are at risk for poor oral health because daily oral hygiene may not be consistently provided. Poor oral health predisposes these older people to systemic problems such as pneumonia, cerebral vascular accidents, and hyperglycemia. Care-resistant behavior is a fear-evoked response to nurses’ unintentionally threatening behavior during mouth care. Nurses can safely and effectively provide mouth care to persons with dementia who resist care by using personalized combinations of 15 threat reduction strategies.

Working Memory, Cues, and Wayfinding in Older Women

Individuals create cognitive maps based on relationships between cues in the environment. Older individuals are often impaired in wayfinding, especially in environments that lack distinctive features. This study examines how working memory ability in older women is related to wayfinding performance in the presence of salient (distinctive, prominent) or nonsalient cues. The degree of salient cue complexity is also examined, thus leading to the hypothesis that salient, complex cues are important in wayfinding and that working memory capacity is related to wayfinding performance. The virtual computer-generated arena is used to test this hypothesis in 20 healthy older women in three different environmental cue conditions varying in salience and complexity. Data analyses indicate that older women perform best in salient cue conditions. A greater working memory capacity is related to improved performance in the nonsalient cue condition. These findings offer preliminary evidence that cue salience is especially important in wayfinding.