Dissociation of human caudate nucleus activity in spatial and nonspatial working memory: an event-related fMRI study.
ABSTRACT We employed a novel event-related fMRI design and analysis technique to explore caudate nucleus contributions to spatial and nonspatial working memory. The spatial condition of a delayed-response task revealed greater mnemonic activation in four of six subjects when the delay period preceded immediately a probe stimulus requiring an overt motor response, as contrasted with a probe requiring no response. This effect was not seen in frontal or parietal cortical areas, and was seen in the caudate nucleus in a formally identical object condition in just one of six subjects. We hypothesized that this pattern of activity represented spatially dependent motor preparation. A second experiment confirmed this hypothesis: delay-period activity of the caudate nucleus showed greater time dependence in a task that featured spatial and motoric memory demands than in a comparable nonspatial task that featured the same response contingencies. These results suggest an important subcortical locus of the dissociation between spatial and nonspatial working memory, and a role for the human caudate nucleus in the integration of spatially coded mnemonic information with motor preparation to guide behavior.
Full-textDOI: · Available from: Bradley R Postle, Jun 12, 2015
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ABSTRACT: Changes in the nigrostriatal system may be involved with the motor abnormalities seen in aging. These perturbations include alterations in dopamine (DA) release, regulation and transport in the striatum and substantia nigra, striatal atrophy and elevated iron levels in the basal ganglia. However, the relative contribution of these changes to the motor deficits seen in aging is unclear. Thus, using the rhesus monkey as a model, the present study was designed to examine several of these key alterations in the basal ganglia in order to help elucidate the mechanisms contributing to age-related motor decline. First, 32 female rhesus monkeys ranging from 4 to 32 years old were evaluated for their motor capabilities using an automated hand-retrieval task. Second, non-invasive MRI methods were used to estimate brain composition and to indirectly measure relative iron content in the striatum and substantia nigra. Third, in vivo microdialysis was used to evaluate basal and stimulus-evoked levels of DA and its metabolites in the striatum and substantia nigra of the same monkeys. Our results demonstrated significant decreases in motor performance, decreases in striatal DA release, and increases in striatal iron levels in rhesus monkeys as they age from young adulthood. A comprehensive statistical analysis relating age, motor performance, DA release, and iron content indicated that the best predictor of decreases in motor ability, above and beyond levels of performance that could be explained by age alone, was iron accumulation in the striatum. This suggests that striatal iron levels may be a biomarker of motor dysfunction in aging; and as such, can be monitored non-invasively by longitudinal brain MRI scans. The results also suggest that treatments aimed at reducing accumulation of excess iron in the striatum during normal aging may have beneficial effects on age-related deterioration of motor performance.Neurobiology of aging 03/2007; 28(2):258-71. DOI:10.1016/j.neurobiolaging.2005.12.010 · 4.85 Impact Factor
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ABSTRACT: Research on the neural basis of working memory (WM) has generally focused on neocortical regions; comparatively little is known about the role of subcortical structures. There is growing evidence that the basal ganglia are involved in WM, but their contribution to different component processes of WM is poorly understood. We examined the temporal dynamics of basal ganglia response and connectivity during the encoding, maintenance and response phases of a Sternberg WM task. During the encoding and maintenance phases, WM-load-dependent activation was observed in the left anterior caudate, anterior putamen and globus pallidus; activation in the right anterior caudate was observed only during the maintenance phase. During the response phase, the basal ganglia were equally active in both the high-load and low-load WM conditions. Caudate and putamen activations were primarily localized to the (rostral) associative parts of the basal ganglia, consistent with the putative role of these regions in cognitive processing. Effective connectivity analyses revealed increased WM-load-dependent interaction of the left anterior caudate with the left posterior parietal cortex during all three phases of the task; with the visual association cortex, including the fusiform gyrus and inferior temporal gyrus, only during the encoding phase; with the ventrolateral prefrontal cortex during the encoding and maintenance phases; with the pre-supplementary motor area during the maintenance and response phases; and with the dorsolateral prefrontal and anterior cingulate cortices only during the response phase. Taken together with known neuroanatomy of the basal ganglia, these results suggest that the anterior caudate helps to link signals in distinct functional networks during different phases of the WM task. Our study offers new insight into the integrative and adaptive role of the basal ganglia in higher cognitive function.NeuroImage 03/2007; 34(3):1253-69. DOI:10.1016/j.neuroimage.2006.08.056 · 6.13 Impact Factor
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ABSTRACT: Our perception of time depends on multiple psychological processes that allow us to anticipate events. In this study, we used event-related functional magnetic resonance imaging (fMRI) to differentiate neural systems involved in formulating representations of time from processes associated with making decisions about their duration. A time perception task consisting of two randomly presented standard intervals was used to ensure that intervals were encoded on each trial and to enhance memory requirements. During the encoding phase of a trial, activation was observed in the right caudate nucleus, right inferior parietal cortex and left cerebellum. Activation in these regions correlated with timing sensitivity (coefficient of variation). In contrast, encoding-related activity in the right parahippocampus and hippocampus correlated with the bisection point and right precuneus activation was associated with a measure of memory distortion. Decision processes were studied by examining brain activation during the decision phase of a trial that was associated with the difficulty of interval discriminations. Activation in the right parahippocampus was greater for easier than harder discriminations. In contrast, activation was greater for harder than easier discriminations in systems involved in working memory (left middle-frontal and parietal cortex) and auditory rehearsal (left inferior-frontal and superior-temporal cortex). Activity in the auditory rehearsal network correlated with memory distortion. Our results support the independence of systems that mediate interval encoding and decision processes. The results also suggest that distortions in memory for time may be due to strategic processing in cortical systems involved in either encoding or rehearsal.Cognitive Brain Research 11/2004; 21(2):193-205. DOI:10.1016/j.cogbrainres.2004.01.010 · 3.77 Impact Factor