Biomedical subjects

Pamela M Greenwood

Publications and source records attributed to Pamela M Greenwood.

6 recordsLinked to original sources

PubMed2006

Interactive effects of APOE and CHRNA4 on attention and white matter volume in healthy middle-aged and older adults.

In the present study, we investigated age-related changes in interactions between efficiency of neuronal repair mechanisms and efficiency of cholinergic neurotransmission in the context of attentional orienting. In addition, we explored white matter volume changes as possible neuronal underpinnings. A sample of 230 healthy middle-aged (53-64 years) and older (65-75 years) adults was genotyped for polymorphisms of APOE and CHRNA4, a nicotinic receptor subunit gene. Participants were administered a visuospatial attention task involving letter discrimination with location cues of varying validity. Genotype effects on white matter volume were also investigated in a subset of participants who received MRI scans. APOE interacted with CHRNA4, such that APOE-epsilon4 carriers who were also CHRNA4 TT homozygotes showed disproportionately slowed reaction time (RT) following invalid location cues. The interaction was stronger in the middle-aged participants than in the older participants. There was also a trend for individuals with combined APOE-epsilon4/CHRNA4 TT genotypes to show both lower white matter volume and slower overall RT on the attention task The interaction of a neurotransmission gene (CHRNA4) and a susceptibility gene (APOE) suggests that the efficiency of neuronal repair mechanisms may modulate the cholinergic system to influence attentional function.

Aged↗

PubMed2005

Brain mechanisms of involuntary visuospatial attention: an event-related potential study.

The brain mechanisms mediating visuospatial attention were investigated by recording event-related potentials (ERPs) during a line-orientation discrimination task. Nonpredictive peripheral cues were used to direct participant's attention involuntarily to a spatial location. The earliest attentional modulation was observed in the P1 component (peak latency about 130 ms), with the valid trials eliciting larger P1 than invalid trials. Moreover, the attentional modulations on both the amplitude and latency of the P1 and N1 components had a different pattern as compared to previous studies with voluntary attention tasks. In contrast, the earliest visual ERP component, C1 (peak latency about 80 ms), was not modulated by attention. Low-resolution brain electromagnetic tomography (LORETA) showed that the earliest attentional modulation occurred in extrastriate cortex (middle occipital gyrus, BA 19) but not in the primary visual cortex. Later attention-related reactivations in the primary visual cortex were found at about 110 ms after stimulus onset. The results suggest that involuntary as well as voluntary attention modulates visual processing at the level of extrastriate cortex; however, at least some different processes are involved by involuntary attention compared to voluntary attention. In addition, the possible feedback from higher visual cortex to the primary visual cortex is faster and occurs earlier in involuntary relative to voluntary attention task.

Adolescent↗

PubMed2005

Event-related potentials reveal dissociable mechanisms for orienting and focusing visuospatial attention.

The neural mechanisms supporting visuospatial orienting and focusing were investigated by recording event-related potentials (ERPs) in a cued, line-orientation discrimination task. Search arrays flashed randomly in the left or right visual field and were preceded by peripheral cues that varied in validity (valid or invalid, with 50% each) and size (large or small, with 50% each). Facilitation of response time was observed for valid trials, regardless of cue size. In contrast to previous cued search studies, however, small (i.e., more precise) cues were associated with delayed responses. Both the timing and the amplitudes of the early ERP components, P1 and N1, were modulated by attentional orienting, with valid trials eliciting a larger and later contralateral vP1 (ventral P1) and a smaller and later contralateral N1 compared to invalid trials. Attentional focusing modulated only the amplitudes of the P1 component, with precisely cued trials eliciting a larger dP1 (dorsal P1) than less precisely cued trials at both contralateral and ipsilateral sites. Thus, both attentional orienting and focusing modulate early stimulus processing stages that overlap in time, but with dissociable effects on the scalp distribution of these components, indicating possibly different underlying mechanisms. In addition, the results support the notion that voluntary and involuntary allocations of visuospatial attention are mediated by different underlying neural processes.

Adult↗

PubMed2005

Beyond heritability: neurotransmitter genes differentially modulate visuospatial attention and working memory.

A cued, visuospatial attention task and a working memory task were administered to 89 healthy adults genotyped for a T-to-C polymorphism in CHRNA4, a nicotinic receptor subunit gene. Increasing gene dose of the C allele of the CHRNA4 gene (i.e., no C alleles, one C allele, two C alleles) was associated with increased reaction time (RT) benefits of valid attentional cuing and reduced RT costs of invalid cues, but was not associated with working memory performance. In a second experiment, 103 healthy persons were genotyped for a G-to-A polymorphism of the dopamine beta-hydroxylase (DBH) gene. Increasing gene dose of the G allele of the DBH gene was associated with increased working memory accuracy at a high memory load. However, there was no consistent association between the DBH gene and visuospatial attention. Thus, a double dissociation was observed, with visuospatial attention associated with CHRNA4 but not the DBH gene and, conversely, working memory associated with the DBH gene but not CHRNA4. The results show that normal allelic variations in single neurotransmitter genes modulate individual differences in processing components of cognitive functions in healthy individuals.

Adult↗

PubMed2005

Specificity of the effect of a nicotinic receptor polymorphism on individual differences in visuospatial attention.

Cortical neurotransmitter availability is known to exert domain-specific effects on cognitive performance. Hence, normal variation in genes with a role in neurotransmission may also have specific effects on cognition. We tested this hypothesis by examining associations between polymorphisms in genes affecting cholinergic and noradrenergic neurotransmission and individual differences in visuospatial attention. Healthy individuals were administered a cued visual search task which varied the size of precues to the location of a target letter embedded in a 15-letter array. Cues encompassed 1, 3, 9, or 15 letters. Search speed increased linearly with precue size, indicative of a spatial attentional scaling mechanism. The strength of attentional scaling increased progressively with the number of C alleles (0, 1, or 2) of the alpha-4 nicotinic receptor gene C1545T polymorphism (n = 104). No association was found for the dopamine beta hydroxylase gene G444A polymorphism (n = 135). These findings point to the specificity of genetic neuromodulation. Whereas variation in a gene linked to cholinergic transmission systematically modulated the ability to scale the focus of visuospatial attention, variation in a gene governing dopamine availability did not. The results show that normal variation in a gene controlling a nicotinic receptor makes a selective contribution to individual differences in visuospatial attention.

Adult↗

PubMed2002

The apolipoprotein E gene, attention, and brain function.

The epsilon4 allele of the apolipoprotein E (ApoE) gene is associated with alterations in brain function and is a risk factor for Alzheimer's disease (AD). Changes in components of visuospatial attention with ApoE-epsilon4, aging, and AD are described. Healthy middle-aged adults without dementia who have the ApoE-epsilon4 gene show deficits in spatial attention and working memory that are qualitatively similar to those seen in clinically diagnosed AD patients. The findings support an association between ApoE polymorphism and specific components of visuospatial attention. Molecular mechanisms that may mediate the ApoE-attention link by modulating cholinergic neurotransmission to the posterior parietal cortex are discussed. Studies of attention and brain function in ApoE-epsilon4 carriers without dementia can advance knowledge of the genetics of visual attention, may enhance understanding of the preclinical phase of AD, and may lead to better methods for early AD detection.

Alzheimer Disease↗