scholarly journals Inefficiency in Self-organized Attentional Switching in the Normal Aging Population is Associated with Decreased Activity in the Ventrolateral Prefrontal Cortex

2008 ◽  
Vol 20 (9) ◽  
pp. 1670-1686 ◽  
Author(s):  
Adam Hampshire ◽  
Aleksandra Gruszka ◽  
Sean J. Fallon ◽  
Adrian M. Owen

Studies of the aging brain have demonstrated that areas of the frontal cortex, along with their associated top-down executive control processes, are particularly prone to the neurodegenerative effects of age. Here, we investigate the effects of aging on brain and behavior using a novel task, which allows us to examine separate components of an individual's chosen strategy during routine problem solving. Our findings reveal that, contrary to previous suggestions of a specific decrease in cognitive flexibility, older participants show no increased level of perseveration to either the recently rewarded object or the recently relevant object category. In line with this lack of perseveration, lateral and medial regions of the orbito-frontal cortex, which are associated with inhibitory control and reward processing, appear to be functionally intact. Instead, a general loss of efficient problem-solving strategy is apparent with a concomitant decrease in neural activity in the ventrolateral prefrontal cortex and the posterior parietal cortex. The dorsolateral prefrontal cortex is also affected during problem solving, but age-related decline within this region appears to occur at a later stage.

2001 ◽  
Vol 13 (8) ◽  
pp. 1129-1147 ◽  
Author(s):  
Mary Kathryn Colvin ◽  
Kevin Dunbar ◽  
Jordan Grafman

Patients with prefrontal cortex lesions are impaired on a variety of planning and problem-solving tasks. We examined the problem-solving performance of 27 patients with focal frontal lobe damage on the Water Jug task. The Water Jug task has never been used to assess problem-solving ability in neurologically impaired patients nor in functional neuroimaging studies, despite sharing structural similarities with other tasks sensitive to prefrontal cortex function, including the Tower of Hanoi, Tower of London, and Wisconsin Card Sorting Task (WCST). Our results demonstrate that the Water Jug task invokes a unique combination of problem-solving and planning strategies, allowing a more precise identification of frontal lobe lesion patients' cognitive deficits. All participants (patients and matched controls) appear to be utilizing a hill-climbing strategy that does not require sophisticated planning; however, frontal lobe lesion patients (FLLs) struggled to make required “counterintuitive moves” not predicted by this strategy and found within both solution paths. Left and bilateral FLLs were more impaired than right FLLs. Analysis of the left hemisphere brain regions encompassed by the lesions of these patients found that poor performance was linked to left dorsolateral prefrontal cortex damage. We propose that patients with left dorsolateral prefrontal cortex lesions have difficulty making a decision requiring the conceptual comparison of nonverbal stimuli, manipulation of select representations of potential solutions, and are unable to appropriately inhibit a response in keeping with the final goal.


2020 ◽  
Vol 30 (8) ◽  
pp. 4297-4305 ◽  
Author(s):  
Xia Liang ◽  
Li-Ming Hsu ◽  
Hanbing Lu ◽  
Jessica A Ash ◽  
Peter R Rapp ◽  
...  

Abstract The CA3 and CA1 principal cell fields of the hippocampus are vulnerable to aging, and age-related dysfunction in CA3 may be an early seed event closely linked to individual differences in memory decline. However, whether the differential vulnerability of CA3 and CA1 is associated with broader disruption in network-level functional interactions in relation to age-related memory impairment, and more specifically, whether CA3 dysconnectivity contributes to the effects of aging via CA1 network connectivity, has been difficult to test. Here, using resting-state fMRI in a group of aged rats uncontaminated by neurodegenerative disease, aged rats displayed widespread reductions in functional connectivity of CA3 and CA1 fields. Age-related memory deficits were predicted by connectivity between left CA3 and hippocampal circuitry along with connectivity between left CA1 and infralimbic prefrontal cortex. Notably, the effects of CA3 connectivity on memory performance were mediated by CA1 connectivity with prefrontal cortex. We additionally found that spatial learning and memory were associated with functional connectivity changes lateralized to the left CA3 and CA1 divisions. These results provide novel evidence that network-level dysfunction involving interactions of CA3 with CA1 is an early marker of poor cognitive outcome in aging.


2015 ◽  
Vol 206 (2) ◽  
pp. 136-144 ◽  
Author(s):  
Edith Pomarol-Clotet ◽  
Silvia Alonso-Lana ◽  
Noemi Moro ◽  
Salvador Sarró ◽  
Mar C. Bonnin ◽  
...  

BackgroundLittle is known about how functional imaging changes in bipolar disorder relate to different phases of the illness.AimsTo compare cognitive task activation in participants with bipolar disorder examined in different phases of illness.MethodParticipants with bipolar disorder in mania (n = 38), depression (n = 38) and euthymia (n = 38), as well as healthy controls (n = 38), underwent functional magnetic resonance imaging during performance of the n-back working memory task. Activations and de-activations were compared between the bipolar subgroups and the controls, and among the bipolar subgroups. All participants were also entered into a linear mixed-effects model.ResultsCompared with the controls, the mania and depression subgroups, but not the euthymia subgroup, showed reduced activation in the dorsolateral prefrontal cortex, the parietal cortex and other areas. Compared with the euthymia subgroup, the mania and depression subgroups showed hypoactivation in the parietal cortex. All three bipolar subgroups showed failure of de-activation in the ventromedial frontal cortex. Linear mixed-effects modelling revealed a further cluster of reduced activation in the left dorsolateral prefrontal cortex in the patients; this was significantly more marked in the mania than in the euthymia subgroup.ConclusionsBipolar disorder is characterised by mood state-dependent hypoactivation in the parietal cortex. Reduced dorsolateral prefrontal activation is a further feature of mania and depression, which may improve partially in euthymia. Failure of de-activation in the medial frontal cortex shows trait-like characteristics.


2015 ◽  
Vol 113 (1) ◽  
pp. 44-57 ◽  
Author(s):  
Xue-Lian Qi ◽  
Anthony C. Elworthy ◽  
Bryce C. Lambert ◽  
Christos Constantinidis

Both dorsolateral prefrontal and posterior parietal cortex have been implicated in spatial working memory and representation of task information. Prior experiments training animals to recall the first of a sequence of stimuli and examining the effect of subsequent distractors have identified increased ability of the prefrontal cortex to represent remembered stimuli and filter distractors. It is unclear, however, if this prefrontal functional specialization extends to stimuli appearing earlier in a sequence, when subjects are cued to remember subsequent ones. It is also not known how task information interacts with persistent activity representing remembered stimuli and distractors in the two areas. To address these questions, we trained monkeys to remember either the first or second of two stimuli presented in sequence and recorded neuronal activity from the posterior parietal and dorsolateral prefrontal cortex. The prefrontal cortex was better able to represent the actively remembered stimulus, whereas the posterior parietal cortex was more modulated by distractors; however, task effects interfered with this representation. As a result, large proportions of neurons with persistent activity and task effects exhibited a preference for a stimulus when it appeared as a distractor in both areas. Additionally, prefrontal neurons were modulated to a greater extent by task factors during the delay period of the task. The results indicate that the prefrontal cortex is better able than the posterior parietal cortex to differentiate between distractors and actively remembered stimuli and is more modulated by the task; however, this relative preference is highly context dependent and depends on the specific requirements of the task.


2020 ◽  
Vol 34 (10) ◽  
pp. 915-924 ◽  
Author(s):  
Priscila Nóbrega-Sousa ◽  
Lilian Teresa Bucken Gobbi ◽  
Diego Orcioli-Silva ◽  
Núbia Ribeiro da Conceição ◽  
Victor Spiandor Beretta ◽  
...  

Background Declines in gait parameters are common with aging and more pronounced in tasks with increased executive demand. However, the neural correlates of age-related gait impairments are not fully understood yet. Objectives To investigate ( a) the effects of aging on prefrontal cortex (PFC) activity and gait parameters during usual walking, obstacle crossing and dual-task walking and ( b) the association between PFC activity and measures of gait and executive function. Methods Eighty-eight healthy individuals were distributed into 6 age-groups: 20-25 (G20), 30-35 (G30), 40-45 (G40), 50-55 (G50), 60-65 (G60), and 70-75 years (G70). Participants walked overground under 3 conditions: usual walking, obstacle crossing, and dual-task walking. Changes in oxygenated and deoxygenated hemoglobin in the PFC were recorded using functional near-infrared spectroscopy. Gait spatiotemporal parameters were assessed using an electronic walkway. Executive function was assessed through validated tests. Results Between-group differences on PFC activity were observed for all conditions. Multiple groups (ie, G30, G50, G60, and G70) showed increased PFC activity in at least one of the walking conditions. Young adults (G20 and G30) had the lowest levels of PFC activity while G60 had the highest levels. Only G70 showed reduced executive function and gait impairments (which were more pronounced during obstacle crossing and dual-task walking). PFC activity was related to gait and executive function. Conclusions Aging causes a gradual increase in PFC activity during walking. This compensatory mechanism may reach the resource ceiling in the 70s, when reduced executive function limits its efficiency and gait impairments are observed.


2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Dibyadeep Datta ◽  
Shannon N. Leslie ◽  
Yury M. Morozov ◽  
Alvaro Duque ◽  
Pasko Rakic ◽  
...  

Abstract Background Cognitive impairment in schizophrenia, aging, and Alzheimer’s disease is associated with spine and synapse loss from the dorsolateral prefrontal cortex (dlPFC) layer III. Complement cascade signaling is critical in driving spine loss and disease pathogenesis. Complement signaling is initiated by C1q, which tags synapses for elimination. C1q is thought to be expressed predominately by microglia, but its expression in primate dlPFC has never been examined. The current study assayed C1q levels in aging primate dlPFC and rat medial PFC (mPFC) and used immunoelectron microscopy (immunoEM), immunoblotting, and co-immunoprecipitation (co-IP) to reveal the precise anatomical distribution and interactions of C1q. Methods Age-related changes in C1q levels in rhesus macaque dlPFC and rat mPFC were examined using immunoblotting. High-spatial resolution immunoEM was used to interrogate the subcellular localization of C1q in aged macaque layer III dlPFC and aged rat layer III mPFC. co-IP techniques quantified protein-protein interactions for C1q and proteins associated with excitatory and inhibitory synapses in macaque dlPFC. Results C1q levels were markedly increased in the aged macaque dlPFC. Ultrastructural localization found the expected C1q localization in glia, including those ensheathing synapses, but also revealed extensive localization within neurons. C1q was found near synapses, within terminals and in spines, but was also observed in dendrites, often near abnormal mitochondria. Similar analyses in aging rat mPFC corroborated the findings in rhesus macaques. C1q protein increasingly associated with PSD95 with age in macaque, consistent with its synaptic localization as evidenced by EM. Conclusions These findings reveal novel, intra-neuronal distribution patterns for C1q in the aging primate cortex, including evidence of C1q in dendrites. They suggest that age-related changes in the dlPFC may increase C1q expression and synaptic tagging for glial phagocytosis, a possible mechanism for age-related degeneration.


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