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Biomedical subjects

S W Anderson

Publications and source records attributed to S W Anderson.

At least 19 recordsLinked to original sources

Amnesia and driving.

Two experienced drivers who developed severe amnesia due to bilateral hippocampal lesions participated in a series of standardized challenges of driving performance and knowledge of driving rules. During drives in a high fidelity simulator and on the road in an instrumented vehicle, they demonstrated vehicle control similar to that of normal drivers on measures of steering, speed control, safety errors, and driving with distraction. Their knowledge of driving rules, safety procedures, and road sign meaning also was normal. However, both participants were impaired at following route directions, and both had unsafe responses in a difficult crash avoidance scenario on the simulator. These findings suggest that memory impairment acquired by experienced drivers does not impair most aspects of driving performance, but may increase safety risk under some challenging circumstances.

Amnesia↗

Driving with distraction in Parkinson disease.

OBJECTIVE: To assess the effects of auditory-verbal distraction on driving performance in Parkinson disease (PD). METHODS: We tested licensed, currently active drivers with mild-to-moderate PD (n = 71) and elderly controls with no neurologic disease (n = 147) on a battery of cognitive, visual, and motor tests. While they drove on a four-lane interstate freeway in an instrumented vehicle, we determined at-fault safety errors and vehicle control measures during a distracter task (Paced Auditory Serial Addition Task [PASAT]) and on an uneventful baseline segment. RESULTS: Compared with controls, drivers with PD committed more errors during both baseline and distraction, and drove slower with higher speed variability during distraction. Although the average effect of distraction on driving performance compared with baseline was not different between the groups, the drivers with PD showed a more heterogeneous response to distraction (p < 0.001): the error count increased in 28.2% of drivers with PD (vs 15.8% in controls), decreased in 16.9% (vs 3.4%), and remained stable in 54.9% (vs 80.8%). The odds of increase in safety errors due to distraction was higher in the PD group even after adjusting for baseline errors, level of engagement in PASAT, sex, and education (odds ratio [95% CI] = 2.62 [1.19 to 5.74], p = 0.016). Decreased performance on tests of cognitive flexibility, verbal memory, postural control, and increased daytime sleepiness predicted worsening of driving performance due to distraction within the PD group. CONCLUSION: The quantitative effect of an auditory-verbal distracter task on driving performance was not significantly different between Parkinson disease (PD) and control groups. However, a significantly larger subset of drivers with PD had worsening of their driving safety errors during distraction. Measures of cognition, motor function, and sleepiness predicted effects of distraction on driving performance within the PD group.

Accidents, Traffic↗

Visual dysfunction in Parkinson disease without dementia.

OBJECTIVE: To determine the profiles of visual dysfunction and their relationship to motor and cognitive dysfunction and to disability in mild to moderate Parkinson disease (PD) without dementia. METHODS: Seventy-six independently living participants with mild to moderate PD and 161 neurologically normal older adults were studied using a comprehensive battery to assess visual acuity, contrast sensitivity (CS), visual speed of processing and attention, spatial and motion perception, visual and verbal memory, visuoconstructional abilities, executive functions, depression, and motor function. RESULTS: Participants with PD scored significantly worse on all tests of vision and cognition compared with normal elderly persons. Reduced CS contributed to deficits on tests of spatial and motion perception and attention in participants with PD. Impairments in visual attention and spatial perception predicted worse cognitive function. Worse performances on tests of visual speed of processing and attention, spatial and motion perception, visual construction, and executive functions correlated with measures of postural instability and gait difficulty (in the Motor section of the Unified Parkinson's Disease Rating Scale). Impairments in motor function, visual memory, mood, and executive functions predicted worse disability as measured by Schwab-England Activities of Daily Living Scale. CONCLUSIONS: Patients with mild to moderate Parkinson disease showed impaired visual perception and cognition compared with elderly control subjects. Visual dysfunction contributes to parkinsonian disability through its influences on cognition and locomotion.

Aged↗

Driver landmark and traffic sign identification in early Alzheimer's disease.

OBJECTIVE: To assess visual search and recognition of roadside targets and safety errors during a landmark and traffic sign identification task in drivers with Alzheimer's disease. METHODS: 33 drivers with probable Alzheimer's disease of mild severity and 137 neurologically normal older adults underwent a battery of visual and cognitive tests and were asked to report detection of specific landmarks and traffic signs along a segment of an experimental drive. RESULTS: The drivers with mild Alzheimer's disease identified significantly fewer landmarks and traffic signs and made more at-fault safety errors during the task than control subjects. Roadside target identification performance and safety errors were predicted by scores on standardised tests of visual and cognitive function. CONCLUSIONS: Drivers with Alzheimer's disease are impaired in a task of visual search and recognition of roadside targets; the demands of these targets on visual perception, attention, executive functions, and memory probably increase the cognitive load, worsening driving safety.

Aged↗

Driver route-following and safety errors in early Alzheimer disease.

OBJECTIVE: To assess navigation and safety errors during a route-following task in drivers with Alzheimer disease (AD). DESIGN/METHODS: Thirty-two subjects with probable AD (by National Institute of Neurological and Communicative Disorders criteria) of mild severity and 136 neurologically normal older adults were tested on a battery of visual and cognitive tests of abilities that are critical to safe automobile driving. Each driver also performed a route-finding task administered on the road in an instrumented vehicle. Main outcome variables were number of 1) incorrect turns; 2) times lost; and 3) at-fault safety errors. RESULTS: The drivers with mild AD made significantly more incorrect turns, got lost more often, and made more at-fault safety errors than control subjects, although their basic vehicular control abilities were normal. The navigational and safety errors were predicted using scores on standardized tests sensitive to visual and cognitive decline in early AD. CONCLUSIONS: Drivers with Alzheimer disease made more errors than neurologically normal drivers on a route-following task that placed demands on driver memory, attention, and perception. The demands of following route directions probably increased the cognitive load during driving, which might explain the higher number of safety errors.

Aged↗

Incidence of nondextrality in the NAS/NRC Twin Registry.

Genetic theories still flounder on the fact that similarity of hand preference is the same in monozygotic (MZ) and dizygotic (DZ) twins. Lateral preference on a well-designed set of 5 activities was obtained from 2,131 male pairs. On item analysis, only "throw" discriminated zygosity, attributable to "excess" nondextral MZ pairs. This item is remarkably free of the intense cultural bias against sinistrality.

Adult↗

Decision-making deficits, linked to a dysfunctional ventromedial prefrontal cortex, revealed in alcohol and stimulant abusers.

A decision-making instrument known as the "gambling task" was used, which has been shown to be sensitive to the decision-making impairment of patients with bilateral lesions of the ventromedial prefrontal cortex (VM). Three groups of subjects were tested, substance dependent individuals (SD) (n=41), normal controls (n=40), and VM patients (n=5). All SD met the DSM-IV criteria for dependence, with either alcohol or stimulants (metamphetamine or cocaine) as the primary substance of choice. The results revealed a significant impairment in the performance of SD relative to normal controls. A significantly high proportion of SD (61 vs. only 32.5% of normal controls) performed within the range of the VM patients, while the rest performed within the range of normal controls. General demographic factors such as age, sex, and level of education could not explain these differences in performance. As well, differences in performance were not explained by intelligence (IQ), memory, or performance on standard executive function/frontal lobe tests. Performance on the gambling task was best predicted by a combination of factors, including duration of abstinence, years of abuse, relapses and times in treatment, and the ability to hold gainful employment. The results support the hypothesis that impairment in decision-making linked to a dysfunctional VM cortex is associated with at least a sub-group of SD.

Adult↗

Pathological laughter and crying: a link to the cerebellum.

Patients with pathological laughter and crying (PLC) are subject to relatively uncontrollable episodes of laughter, crying or both. The episodes occur either without an apparent triggering stimulus or following a stimulus that would not have led the subject to laugh or cry prior to the onset of the condition. PLC is a disorder of emotional expression rather than a primary disturbance of feelings, and is thus distinct from mood disorders in which laughter and crying are associated with feelings of happiness or sadness. The traditional and currently accepted view is that PLC is due to the damage of pathways that arise in the motor areas of the cerebral cortex and descend to the brainstem to inhibit a putative centre for laughter and crying. In that view, the lesions 'disinhibit' or 'release' the laughter and crying centre. The neuroanatomical findings in a recently studied patient with PLC, along with new knowledge on the neurobiology of emotion and feeling, gave us an opportunity to revisit the traditional view and propose an alternative. Here we suggest that the critical PLC lesions occur in the cerebro-ponto-cerebellar pathways and that, as a consequence, the cerebellar structures that automatically adjust the execution of laughter or crying to the cognitive and situational context of a potential stimulus, operate on the basis of incomplete information about that context, resulting in inadequate and even chaotic behaviour.

Cerebellum↗

A small-molecule nitroimidazopyran drug candidate for the treatment of tuberculosis.

Mycobacterium tuberculosis, which causes tuberculosis, is the greatest single infectious cause of mortality worldwide, killing roughly two million people annually. Estimates indicate that one-third of the world population is infected with latent M. tuberculosis. The synergy between tuberculosis and the AIDS epidemic, and the surge of multidrug-resistant clinical isolates of M. tuberculosis have reaffirmed tuberculosis as a primary public health threat. However, new antitubercular drugs with new mechanisms of action have not been developed in over thirty years. Here we report a series of compounds containing a nitroimidazopyran nucleus that possess antitubercular activity. After activation by a mechanism dependent on M. tuberculosis F420 cofactor, nitroimidazopyrans inhibited the synthesis of protein and cell wall lipid. In contrast to current antitubercular drugs, nitroimidazopyrans exhibited bactericidal activity against both replicating and static M. tuberculosis. Lead compound PA-824 showed potent bactericidal activity against multidrugresistant M. tuberculosis and promising oral activity in animal infection models. We conclude that nitroimidazopyrans offer the practical qualities of a small molecule with the potential for the treatment of tuberculosis.

Animals↗

Visual attention impairments in Alzheimer's disease.

BACKGROUND: Impaired attention can hinder information processing at multiple levels and may explain aspects of functional decline in aging and dementia. Impairments of attention in early AD may contribute to performance reductions in other cognitive domains, including memory and executive functions. METHOD: - The authors analyzed the scores on a battery of tests of attention and cognitive abilities in 64 older individuals: 42 with mild AD and 22 control subjects without dementia. The authors tested the hypotheses that patients with AD would have impairments of visual attention, and that these impairments would correlate with dysfunction in other key cognitive domains. RESULTS: Patients with AD performed significantly worse than control subjects on measures of sustained attention, divided attention, selective attention, and visual processing speed. The differences were not due to differences in age, education, or basic visual function. Strong relationships were identified between reduced attention skills and overall cognitive impairment. CONCLUSIONS: Deterioration of attention abilities occurs in early stages of AD, and likely contributes to functional decline in these patients. More routine assessment of visual attention deficits could give a more accurate measure of functionally useful perception in patients with AD who show normal visual acuity and visual fields, perhaps providing useful clues to diagnosis and staging.

Aged↗

Vision and cognition in Alzheimer's disease.

Alzheimer's disease (AD) is known to affect visual pathways, but potential concomitant effects on vision and cognitive performance are not well understood. We studied 43 individuals with AD of mild severity and 22 individuals without dementia on a battery of tests designed to measure multiple aspects of basic and higher-order visual perception and cognition. All subjects performed on the same visual and cognitive test batteries. The results showed no differences between groups on tests of static visual acuity, stereoacuity, dynamic visual acuity or motion direction discrimination. However, individuals with AD performed significantly worse on tests of static spatial contrast sensitivity, visual attention, shape-from-motion, color, visuospatial construction and visual memory. Correlation analyses showed strong relationships between visual and cognitive scores. The findings show that AD affects several aspects of vision and are compatible with the hypothesis that visual dysfunction in AD may contribute to performance decrements in other cognitive domains. The pattern of involvement indicates that AD affects multiple visual neural pathways and regions. It is possible that better understanding of vision-related dysfunction could aid diagnosis and interventions to improve functional capacity in patients with dementia.

Aged↗

Long-term sequelae of prefrontal cortex damage acquired in early childhood.

Frontal lobe dysfunction is often invoked as a contributing factor in developmental disorders characterized by chronic maladaptive behavior, but interpretation of relevant neuropsychological findings has been hampered by the limited information available regarding the consequences of focal prefrontal damage early in life. We describe here the long-term behavioral and cognitive sequelae of damage to prefrontal cortex in two young adult patients who had sustained their brain damage prior to 16 months of age. In the context of normal neurological examinations, both cases had remarkable histories of impaired decision making, behavioral dyscontrol, social defects, and abnormal emotion. Performances were primarily normal on a broad range of neuropsychological measures (intellect, memory, language, academic achievement, visual perception, and visuoconstruction), but selective impairments of executive function were evident. Early dysfunction in the prefrontal region may result in severe and chronic social maladjustment despite largely normal cognitive abilities. These findings can help inform neuropsychological evaluation of patients with possible prefrontal dysfunction in the setting of developmental disabilities or early brain trauma.

Adult↗

Acquired personality disturbances associated with bilateral damage to the ventromedial prefrontal region.

Personality changes in 7 participants with bilateral ventromedial prefrontal lesions (PF-BVM), 14 participants with prefrontal lesions but not bilateral ventromedial involvement (PF-NBVM), and 36 with nonprefrontal lesions (NPF) were investigated with the Iowa Rating Scales of Personality Change. Informants rated 30 specific characteristics for degree of disturbance and change from premorbid personality. PF-BVM participants showed a higher rate of acquired disturbances than NPF participants in blunted emotional experience, apathy, low emotional expressiveness, inappropriate affect, poor frustration tolerance, irritability, lability, indecisiveness, poor judgment, social inappropriateness, lack of planning, lack of initiation and persistence, and lack of insight. Differences between the PF-BVM and PF-NBVM groups were significant for several of these characteristics. All 7 PF-BVM participants developed a syndrome, including general dampening of emotional experience; poorly modulated emotional reactions; defective decision making, especially in the social realm; impaired goal-directed behavior; and striking lack of insight. Similarities between this syndrome of "acquired sociopathy" and developmental psychopathy in characteristic personality disturbances and psychophysiological abnormalities suggest that diminished emotionality, impaired decision making, and psychosocial dysfunction may be related to ventromedial prefrontal dysfunction in both groups.

Aged↗

Impairment of social and moral behavior related to early damage in human prefrontal cortex.

The long-term consequences of early prefrontal cortex lesions occurring before 16 months were investigated in two adults. As is the case when such damage occurs in adulthood, the two early-onset patients had severely impaired social behavior despite normal basic cognitive abilities, and showed insensitivity to future consequences of decisions, defective autonomic responses to punishment contingencies and failure to respond to behavioral interventions. Unlike adult-onset patients, however, the two patients had defective social and moral reasoning, suggesting that the acquisition of complex social conventions and moral rules had been impaired. Thus early-onset prefrontal damage resulted in a syndrome resembling psychopathy.

Adult↗

Dissociation Of working memory from decision making within the human prefrontal cortex.

We tested the hypothesis that cognitive functions related to working memory (assessed with delay tasks) are distinct from those related to decision making (assessed with a gambling task), and that working memory and decision making depend in part on separate anatomical substrates. Normal controls (n = 21), subjects with lesions in the ventromedial (VM) (n = 9) or dorsolateral/high mesial (DL/M) prefrontal cortices (n = 10), performed on (1) modified delay tasks that assess working memory and (2) a gambling task designed to measure decision making. VM subjects with more anterior lesions (n = 4) performed defectively on the gambling but not the delay task. VM subjects with more posterior lesions (n = 5) were impaired on both tasks. Right DL/M subjects were impaired on the delay task but not the gambling task. Left DL/M subjects were not impaired on either task. The findings reveal a cognitive and anatomic double dissociation between deficits in decision making (anterior VM) and working memory (right DL/M). This presents the first direct evidence of such effects in humans using the lesion method and underscores the special importance of the VM prefrontal region in decision making, independent of a direct role in working memory.

Adult↗

Hallucinations following occipital lobe damage: the pathological activation of visual representations.

Neuropsychological investigation of hallucinations may provide insight into the nature of these subjective phenomena, as well as inform theories of perception and recall. We studied a man who described continuous visual hallucinations of object fragments (e.g., lines, corners, patterns) in the left visual field following a stroke in the right occipital cortex. The subject performed normally on standardized measures of visual perception and other cognitive abilities. He had no personality disturbance, and EEG during hallucinations was normal. Review of our records of 211 cases with focal lesions involving visual cortex revealed 5 patients with similar complaints. The hallucinatory experience of such patients probably reflects pathological activation of neural ensembles in the regions bordering an occipital lesion. These regions are presumed to contain records of visual feature fragments which are co-activated by feedback projections in the earliest visual association cortices, where they produce meaningful patterns during normal recall.

Aged↗

Acquired agraphia caused by focal brain damage.

Motor and linguistic aspects of writing were evaluated in 31 subjects with focal damage in 1 of 3 regions of the left hemisphere: (1) dorsolateral frontal lobe sparing primary motor cortex (group FL), (2) parietal lobe (group PL), or (3) temporal lobe (group TL). A standard procedure was used to evaluate writing for grapheme formation, spatial arrangement, spelling, word selection, grammar, and perseveration. It was predicted that agraphia would be observed in all 3 groups, and that the most severe impairments would be associated with frontal lobe damage, particularly in aspects of writing dependent on sequencing (grapheme formation, spelling, and grammar). It was found that agraphia was common in all groups, particularly in the acute epoch, and that all groups showed considerable recovery of writing by the chronic epoch. Few differences were found between groups. However, the FL group was impaired on spelling and grammar relative to the PL group in the acute epoch and impaired on grammar relative to the TL group in the chronic epoch. The findings are consistent with the notion that writing relies on a distributed neuroanatomical network, which acts in concert to link fragments of visuomotor activity with component linguistic elements.

Adult↗