Malcolm A. Binns

Multiple frontal systems controlling response speed

This study evaluated a model of attention that postulates several distinct component processes, each mediated by specific neural systems in the human frontal lobes. A series of reaction time (RT) tests (simple, choice, and prepare) examined the hypothesis that different attentional processes are related to distinct regions within the frontal lobes. These tests were given to 38 patients with frontal lesions and 38 age-matched control subjects. Lesions were localized both by general regions (superior medial, inferior medial, left and right lateral) and by individual architectonic areas. Lesions in the superior medial (SM) frontal lobes, particularly involving areas 24 and 32 on the right, were associated with slow RT in all tests and with failure to decrease RT after a warning signal. Lesions in the right lateral (RL) frontal lobe, centred in area 9/46v, prevented the decrease in RT with increasing foreperiod that was seen in normal subjects and in patients with lesions elsewhere in the frontal lobes. The ability to energize a response for rapid RT, either generally or specifically following a warning stimulus, is sensitive to lesions of the right SM. Monitoring of stimulus occurrence and response behaviour in order to enhance the speed of response to upcoming stimuli is sensitive to RL lesions.

The effects of the anti-cancer drugs, methotrexate and 5-fluorouracil, on cognitive function in mice

There is evidence that standard-dose chemotherapy may impact cognitive function in cancer patients. The present study evaluated the effects of a combination of two anti-cancer drugs, methotrexate (37.5 mg/kg) and 5-fluorouracil (5FU, 75 mg/kg) on cognitive function in a mouse model. Drug-induced deficits were observed in adult BALB/C mice on tests of spatial memory, non-matching-to-sample (NMTS) learning and in a delayed-NMTS test of non-spatial memory. There were no group differences on tests of cued memory or discrimination learning. Performance-related variables were ruled out as possible explanations of the observed impairments. The impaired performance of the drug group, which was consistent with cognitive deficits observed in human cancer patients treated with similar types of chemotherapy, was attributed to functional changes in specific brain regions, including the frontal lobes and hippocampus.

Cognitive rehabilitation in the elderly: Effects on strategic behavior in relation to goal management

Executive functions are highly sensitive to the effects of aging and other conditions affecting frontal lobe function. Yet there are few validated interventions specifically designed to address executive functions, and, to our knowledge, none validated in a healthy aging sample. As part of a large-scale cognitive rehabilitation randomized trial in 49 healthy older adults, a modified Goal Management Training program was included to address the real-life deficits caused by executive dysfunction. This program emphasized periodic suspension of ongoing activity to establish goal hierarchies and monitor behavioral output. Tabletop simulated real-life tasks (SRLTs) were developed to measure the processes targeted by this intervention. Participants were randomized to two groups, one of which received the intervention immediately and the other of which was wait-listed prior to rehabilitation. Results indicated improvements in SRLT performance and self-rated executive deficits coinciding with the training in both groups. These gains were maintained at long-term follow-up. Future research will assess the specificity of these effects in patient groups.

An Effect of Spatial-Temporal Association of Response Codes: Understanding the Cognitive Representations of Time.

The present study addresses the question of how such an abstract concept as time is represented by our cognitive system. Specifically, the aim was to assess whether temporal information is cognitively represented through left-to-right spatial coordinates, as already shown for other ordered sequences (e.g., numbers). In Experiment 1, the task-relevant information was the temporal duration of a cross. RTs were shorter when short and long durations had to be responded to with left and right hands, respectively, than with the opposite stimulus-response mapping. The possible explanation that the foreperiod effect (i.e., shorter RTs for longer durations) is greater with right than with left hand responses is discarded by results of Experiment 2, in which right and left hand responses alternated block-wise in a variable foreperiod paradigm. Other explanations concerning manual or hemispheric asymmetries may be excluded based on the results of control experiments, which show that the compatibility effect between response side and cross duration occurs for accuracy when responses are given with crossed hands (Experiment 3), and for RTs when responses are given within one hand (Experiment 4). This pattern suggests that elapsing time, similarly to other ordered information, is represented in some circumstances through an internal spatial reference frame, in a way that may influence motor performance. Finally, in Experiment 5, the temporal duration was parametrically varied using different values for each response category (i.e., 3 short and 3 long durations). The compatibility effect between hand and duration was replicated, but followed a rectangular function of the duration. The shape of this function is discussed in relation to the specific task demands.

Dissociations Within the Anterior Attentional System: Effects of Task Complexity and Irrelevant Information on Reaction Time Speed and Accuracy

Patients with focal frontal or nonfrontal lesions were compared with control participants on 4 reaction time (RT) tasks varying in levels of complexity based on a feature-integration model of detection. Superior medial lesions affected simple RT speed. Increasing the demands of feature detection did not differentially affect speed of correct responses among the groups. Frontal structures appear to play little role in correct integration of features during detection. The analysis of error types within the complex task revealed a frontal lobe hemispheric distinction between sensitivity and bias: right dorsolateral-decreased sensitivity; left dorsolateral-altered response bias. The frontal lobes, particularly right dorsolateral, were required to inhibit an incorrect response. There are at least 3 functionally and anatomically separable anterior attentional processes.

Cognitive rehabilitation in the elderly: Effects on memory

This study reports the effects of a 12-week multimodular cognitive rehabilitation training program on memory performance in two groups of older adults. In the Memory Training module, participants were instructed on the nature of memory and how to improve memory performance; internal and external strategies were described and practiced over the training sessions. Memory performance was assessed by four tests: Alpha Span, Brown-Peterson, Hopkins Verbal Learning Test - Revised (HVLT-R), and Logical Stories. One group received training on entry into the study (Early Training Group, ETG), the other after a 3-month delay (Late Training Group, LTG). The results showed no training-related improvement in working memory (Alpha Span), primary memory (Brown-Peterson, HVLT-R), or recognition memory (HVLT-R). While the most direct analyses of a training effect (analyses of covariance) rarely demonstrated significant effects, exploratory analyses provided some evidence for a training benefit in several measures of secondary memory (Logical Stories; HVLT-R) and strategic processing (Brown-Peterson; Logical Stories; HVLT-R). Positive results were largely restricted to the ETG, possibly because the LTG lost motivation as a consequence of their delayed training. The results need to be treated with caution, but are promising for the rehabilitation of memory functioning in older adults.

Potential Interactions between Herbal Medicines and Conventional Drug Therapies Used by Older Adults Attending a Memory Clinic

ObjectiveHerbal medicines and conventional drug therapies are often taken in combination. The objective of our study was to identify the range of natural health products and conventional drug therapies used by older adults (aged 65 years and over) attending a memory clinic, and to specifically evaluate the frequency of potential interactions between herbal medicines and conventional drug therapies.DesignWe interviewed consecutive patients attending the Memory Disorders Clinic at the Baycrest Centre for Geriatric Care, a University of Toronto teaching hospital, between 4 July and 15 August 2000. Patients were asked to bring to their appointment all natural health products (i.e. herbal medicines, vitamins and minerals) and conventional drug therapies (i.e. prescription and over-the-counter) they were currently using. We collected information on current and previously used natural health products and current conventional drug therapies. Patients were classified as having the potential for an interaction if they were using a current herbal medicine in combination with a conventional drug therapy and the interaction had been reported previously in the medical literature.ParticipantsWe interviewed 195 consecutive patients attending the Memory Disorders Clinic at the Baycrest Centre for Geriatric Care, Toronto, Ontario, Canada.ResultsOf the 195 patients in our sample, 33 (17%) were ‘current users’, 19 (10%) were ‘past users’, and 143 (73%) were ‘never users’ of herbal medicines. Among the 52 patients who were ‘current or past users’, the most frequently used herbal medicines were ginkgo (Ginkgo biloba) [39 users], garlic (n = 10), glucosamine sulphate (n = 9) and echinacea (n = 8). Among the 33 patients who were current users, the most commonly used herbal medicines were Ginkgo biloba (n = 22), glucosamine sulphate (n = 8) and garlic (n = 6). Among the 33 current users, we identified 11 potential herb-drug interactions in nine patients. The 11 herb-drug interactions we identified were between ginkgo and aspirin (acetylsalicylic acid) [n = 8], ginkgo and trazodone (n = 1), ginseng and amlodipine (n = 1) and valerian and lorazepam (n = 1).ConclusionsHerbal medicines are widely used. Almost one-third of current users of herbal medicines were at risk of a herb-drug interaction. The most common potential herb-drug interaction was between ginkgo and aspirin. This finding has important potential implications because both of these products are regularly used by older people. Physicians and other healthcare providers should be aware of potential herb-drug interactions and should monitor and inform their patients accordingly.

Apathy Symptom Profile and Behavioral Associations in Frontotemporal Dementia vs Dementia of Alzheimer Type

BACKGROUND Apathy is a common and significant problem in patients with dementia, regardless of its cause. Observations about frontosubcortical circuit syndromes indicate that apathy may have affective, behavioral, or cognitive manifestations. OBJECTIVES To explore whether the apathy manifested in frontotemporal dementia (FTD), with its predominantly anterior brain neuropathologic features, differs from the apathy in dementia of Alzheimer type (DAT), with its predominantly hippocampal- and temporoparietal-based neuropathologic features, and to determine whether other behavioral disturbances reported in frontosubcortical circuit syndromes correlate with apathy. DESIGN Analyses included individual items within Neuropsychiatric Inventory subscale items. Items of the apathy/indifference subscale were designated by consensus as affective (lacking in emotions), behavioral (inactive, chores abandoned), or cognitive (no interest in the activities of others). Proportions of correlated nonapathy Neuropsychiatric Inventory items were calculated. SETTING Several neurology specialty clinics contributed to our data set. PARTICIPANTS A total of 92 participants with FTD and 457 with DAT. MAIN OUTCOME MEASURES The Neuropsychiatric Inventory was analyzed. RESULTS Apathy was more prevalent in patients with FTD than in those with DAT, but when present, the specific apathy symptoms associated with both types of dementia were rarely restricted to 1 of the 3 domains of apathy. Dysphoria concurrent with apathy was unique to the DAT group and negatively correlated in the FTD group. Participants with affective apathy more frequently copresented with an orbital frontosubcortical syndrome in FTD (impulsivity and compulsions). Affective apathy also copresented with uncooperative agitation, anger, and physical agitation in both types of dementia. CONCLUSIONS Apathy is common in patients with FTD and DAT, although it is more common in those with FTD. When present, it usually involves changes in affect, behavior, and cognition. It is associated with behaviors that have previously been shown to affect patient safety, independence, and quality of life.

Cognitive rehabilitation in the elderly: A randomized trial to evaluate a new protocol

This study provides an introduction to, and overview of, several papers that resulted from a randomized control trial that evaluated a new cognitive rehabilitation protocol. The program was designed to improve general strategic abilities in ways that would be expressed in a broad range of functional domains. The trial, which was conducted on a sample of older adults who had experienced normal age-related cognitive decline, assessed performance in the following domains: memory, goal management, and psychosocial status. The general rationale for the trial, the overall experimental design, and the approach to statistical analyses that are relevant to each paper are described here. The results for each functional domain are reported in separate papers in this series.

Providing Nutrition Supplements to Institutionalized Seniors with Probable Alzheimer's Disease Is Least Beneficial to Those with Low Body Weight Status

Objectives: To examine whether providing a midmorning nutrition supplement increases habitual energy intake in seniors with probable Alzheimers disease (AD) and to investigate the effects of body weight status and cognitive and behavioral function on the response to the intervention.