Attentional set-shifting deficit in Parkinson's disease is associated with prefrontal dysfunction: an FDG-PET study.
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ABSTRACT:
SUBMITTER: Sawada Y
PROVIDER: S-EPMC3369918 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Chronic methamphetamine abusers exhibit deficits in tasks requiring intact prefrontal cortex function, and prefrontal cortex dysfunction has been implicated in the loss of control over drug use. This study used a combination of behavioral and electrophysiologic assessments in rats with a history of long access methamphetamine self-administration to determine methamphetamine-induced changes in prefrontal cortex-dependent attentional set-shifting performance, drug-seeking, and prefrontal cortex neuronal activity.Male Long-Evans rats self-administered methamphetamine (.02 mg/infusion, intravenous) or received yoked saline infusions for 6 hours a day for 14 days. Cognitive flexibility was assessed using an attentional set-shifting task before 2 weeks of self-administration and 1 day after self-administration. Animals then underwent 11 days of abstinence, followed by three subsequent tests for context-induced drug seeking. Finally, animals were anesthetized, and single-unit in vivo extracellular recordings were performed in the dorsomedial prefrontal cortex.Methamphetamine-experienced rats showed escalated drug intake and context-induced drug-seeking following abstinence. During the extradimensional set-shift component, meth-experienced rats showed selective impairments that were identical to deficits produced by excitotoxic lesions of the prefrontal cortex. Rats with a history of chronic methamphetamine intake also exhibited higher basal firing frequency and a significantly greater proportion of burst-firing cells in the prefrontal cortex compared with yoked-saline controls.Prefrontal cortex-specific alterations in neuronal function may play a key role in methamphetamine-induced attentional deficits and drug-seeking. These data support the possibility that targeting prefrontal cortex pathology may improve treatment outcome in methamphetamine addiction.
| S-EPMC3052930 | biostudies-literature
Project description:In this work we address key phenomena observed with classical set shifting tasks as the "Wisconsin Card Sorting Test" or the "Stroop" task: Different types of errors and increased response times reflecting decreased attention. A component of major importance in these tasks is referred to as the "attentional control" thought to be implemented by the prefrontal cortex which acts primarily by an amplification of task relevant information. This mode of operation is illustrated by a neurodynamical model developed for a new kind of set shifting experiment: The Wisconsin-Delayed-Match-to-Sample task combines uninstructed shifts as investigated in Wisconsin-like tasks with a Delayed-Match-to-Sample paradigm. These newly developed WDMS experiments in conjunction with the neurodynamical simulations are able to explain the reason for decreased attention in set shifting experiments as well the different consequences of decreased attention in tasks requiring bivalent yes/no responses compared to tasks requiring multivalent responses.
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Project description:Early detection of danger is highly adaptive, yet fast orientation towards safety is also key to survival. This study aimed to explore how human brain searches for safety by manipulating subjects' attentional set. Subjects were asked to judge random dots motion (RDM) direction and could be shocked for incorrect responses (RDM trials) while keeping alert in detecting shock probability cues (cue detection trials). Relative to safe condition, where attention was set to search cues associated with no shock, incorrect responses to 'dangerous+' cues would increase and correct responses to 'dangerous-' cues would decrease shock probability. In RDM trials, relative to the 'dangerous+', the safe and 'dangerous-' attentional set induced stronger activation in the ventral medial prefrontal cortex (vmPFC), a core region involved in flexible threat assessment and safety signalling. In cue detection trials, shorter response times and greater accuracy were observed for 'dangerous+' than 'dangerous-' and safe cues. At neural level 'dangerous+' cues induced stronger activity in the frontoparietal attention network than safe cues. Overall, our findings demonstrate that attentional set for searching safety recruits the vmPFC, while detection of threat-related cues elicits activity in the frontoparietal attention network, suggesting new roles for these regions in human defensive survival circuitry.
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Project description:BACKGROUND:Individuals with Parkinson's disease (PD) are at increased risk for falls, which lead to substantial morbidity and mortality. Understanding the motor and non-motor impairments associated with falls in PD is critical to informing prevention strategies. In addition to motor symptoms, individuals with PD exhibit non-motor deficits, including impaired set shifting, an aspect of executive function related to cognitive flexibility that can be measured quickly with the Trailmaking Test. RESEARCH QUESTION:To determine whether impaired set shifting is associated with fall history in people with and without PD. METHODS:We examined associations between set shifting, PD status, and fall history (?1 falls in the previous 6 months) in data from PD patients (n?=?65) with and without freezing of gait (FOG) and community-dwelling neurologically-normal older adults (NON-PD) (n?=?73) who had participated in our rehabilitation studies. RESULTS:Impaired set shifting was associated with previous falls after controlling for age, sex, overall cognitive function, PD status, FOG, and PD disease duration (OR?=?1.29 [1.03-1.60]; P?=?0.02). Consistent with literature, PD and FOG were also independently associated with increased fall prevalence (PD OR?=?4.15 [95% CI 1.65-10.44], P?<?0.01; FOG OR?=?3.63 [1.22-10.80], P?=?0.02). Although the strongest associations between set shifting and falling were observed among PD without FOG (OR?=?2.11) compared to HOA (OR?=?1.14) and PD with FOG (OR?=?1.46), no statistically-significant differences were observed across groups. SIGNIFICANCE:Impaired set shifting is associated with previous falls in older adults with and without PD. Set shifting may be useful to include in fall risk assessments, particularly when global cognitive measures are within reference limits.
| S-EPMC5960619 | biostudies-literature
Project description:BackgroundCognitive impairment is a common symptom of Parkinson's disease (PD) that increases in risk and severity as the disease progresses. An accurate prediction of the risk of progression from the mild cognitive impairment (MCI) stage to the dementia (PDD) stage is an unmet clinical need.MethodsWe investigated the use of a supervised learning algorithm called the support vector machine (SVM) to retrospectively stratify patients on the basis of brain fluorodeoxyglucose-PET (FDG-PET) scans. Of 43 patients with PD-MCI according to the baseline scan, 23 progressed to PDD within a 5-year period, whereas 20 maintained stable MCI. The baseline scans were used to train a model, which separated patients identified as PDD converters versus those with stable MCI with 95% sensitivity and 91% specificity.ResultsIn an independent validation data set of 19 patients, the AUC was 0.73, with 67% sensitivity and 80% specificity. The SVM model was topographically characterized by hypometabolism in the temporal and parietal lobes and hypermetabolism in the anterior cingulum and putamen and the insular, mesiotemporal, and postcentral gyri. The performance of the SVM model was further tested on 2 additional data sets, which confirmed that the model was also sensitive to later-stage PDD (17 of 19 patients; 89% sensitivity) and dementia with Lewy bodies (DLB) (16 of 17 patients; 94% sensitivity), but not to normal cognition PD (2 of 17 patients). Finally, anti-PD medication status did not change the SVM classification of the other set of 10 patients with PD who were scanned twice, ON and OFF medication.ConclusionsThese results potentially indicate that the proposed FDG-PET-based SVM classifier has utility for providing an accurate prognosis of dementia development in patients with PD-MCI.
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Project description:Adolescent exposure to cannabinoids in vulnerable individuals is proposed to be a risk factor for psychiatric conditions later in life, particularly schizophrenia. Evidence from studies in animals has indicated that a combination of repeated pubertal cannabinoid administration with either neonatal prefrontocortical lesion, isolation rearing, or chronic NMDA receptor antagonism administration induces enhanced schizophrenia-like behavioral disruptions. The effects of adolescent exposure to CB1 receptor agonists, however, have not been tested in a developmental disruption model of schizophrenia. This was tested in the methylazoxymethanol (MAM) model, in which repeated treatment with the synthetic cannabinoid agonist WIN 55,212-2 (WIN; 1.2mg/kg) was extended over 25 days throughout puberty (postnatal days 40-65) in control and MAM rats. The rats received 20 injections, which were delivered irregularly to mimic the human condition. Adult rats were tested for attentional set-shifting task and locomotor response to amphetamine, which was compared with in vivo recording from ventral tegmental area (VTA) dopamine (DA) neurons. MAM-treated rats showed impairment in the attentional set-shifting task, augmented locomotor response to amphetamine administration, and an increased number of spontaneously active DA neurons in the VTA. Interestingly, pubertal WIN treatment in normal animals induced similar changes at adulthood as those observed in MAM-treated rats, supporting the notion that adolescence exposure to cannabinoids may represent a risk factor for developing schizophrenia-like signs at adulthood. However, contrary to expectations, pubertal WIN administration did not exacerbate the behavioral and electrophysiological changes in MAM-treated rats beyond that observed in WIN-treated saline rats (Sal). Indeed, WIN treatment actually attenuated the locomotor response to amphetamine in MAM rats without impacting DA neuron activity states. Taken together, the present results indicate that the impact of cannabinoids during puberty/adolescence on schizophrenia models is more complex than may be predicted.
| S-EPMC4368886 | biostudies-literature
Project description:Recent studies suggest that attention samples space rhythmically through oscillatory interactions in the frontoparietal network. How these attentional fluctuations coincide with spatial exploration/displacement and exploitation/selection by a dynamic attentional spotlight under top-down control is unclear. Here, we show a direct contribution of prefrontal attention selection mechanisms to a continuous space exploration. Specifically, we provide a direct high spatio-temporal resolution prefrontal population decoding of the covert attentional spotlight. We show that it continuously explores space at a 7-12 Hz rhythm. Sensory encoding and behavioral reports are increased at a specific optimal phase w/ to this rhythm. We propose that this prefrontal neuronal rhythm reflects an alpha-clocked sampling of the visual environment in the absence of eye movements. These attentional explorations are highly flexible, how they spatially unfold depending both on within-trial and across-task contingencies. These results are discussed in the context of exploration-exploitation strategies and prefrontal top-down attentional control.
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Project description:ObjectiveTo examine the effect of education (a surrogate measure of cognitive reserve) on FDG-PET brain metabolism in elderly cognitively healthy (HC) subjects with preclinical Alzheimer disease (AD).MethodsFifty-two HC subjects (mean age 75 years) with FDG-PET and CSF measurement of Aβ1-42 were included from the prospective Alzheimer's Disease Neuroimaging Initiative biomarker study. HC subjects received a research classification of preclinical AD if CSF Aβ1-42 was <192 pg/mL (Aβ1-42 [+]) vs HC with normal Aβ (Aβ1-42 [-]). In regression analyses, we tested the interaction effect between education and CSF Aβ1-42 status (Aβ1-42 [+] vs Aβ1-42 [-]) on FDG-PET metabolism in regions of interest (ROIs) (posterior cingulate, angular gyrus, inferior/middle temporal gyrus) and the whole brain (voxel-based).ResultsAn interaction between education and CSF Aβ1-42 status was observed for FDG-PET in the posterior cingulate (p < 0.001) and angular gyrus ROIs (p = 0.03), but was not significant for the inferior/middle temporal gyrus ROI (p = 0.06), controlled for age, sex, and global cognitive ability (Alzheimer's Disease Assessment Scale-cognitive subscale). The interaction effect was such that higher education was associated with lower FDG-PET in the Aβ1-42 (+) group, but with higher FDG-PET in the Aβ1-42 (-) group. Voxel-based analysis showed that this interaction effect was primarily restricted to temporo-parietal and ventral prefrontal brain areas.ConclusionsHigher education was associated with lower FDG-PET in preclinical AD (Aβ1-42 [+]), suggesting that cognitive reserve had a compensatory function to sustain cognitive ability in presence of early AD pathology that alters FDG-PET metabolism.
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Project description:Mild behavioral impairment (MBI) is a neurobehavioral syndrome characterized by later life emergence of sustained neuropsychiatric symptoms, as an at-risk state for incident cognitive decline and dementia. Prior studies have reported that neuropsychiatric symptoms are associated with cognitive abilities in Parkinson's disease (PD) patients, and we have recently found a strong correlation between MBI and cognitive performance. However, the underlying neural activity patterns of cognitive performance linked to MBI in PD are unknown. Fifty-nine non-demented PD patients and 26 healthy controls were scanned using fMRI during performance of a modified version of the Wisconsin card sorting task. MBI was evaluated using the MBI-checklist, and PD patients were divided into two groups, PD-MBI and PD-noMBI. Compared to the PD-noMBI group and healthy controls, the PD-MBI group revealed less activation in the prefrontal and posterior parietal cortices, and reduced deactivation in the medial temporal region. These results suggest that in PD, MBI reflects deficits in the frontoparietal control network and the hippocampal memory system.
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Project description:The literature on human and animal learning suggests that individuals attend to and act on cues differently based on the order in which they were learned. Recent studies have proposed that one specific type of learning outcome, the highlighting effect, can serve as a framework for understanding a number of early cognitive milestones. However, little is known how this learning effect itself emerges among children, whose memory and attention are much more limited compared to adults. Two experiments were conducted using different versions of the general highlighting paradigm: Experiment 1 tested 3 to 6 year olds with a newly developed image-based version of the paradigm, which was designed specifically to test young children. Experiment 2 tested the validity of an image-based implementation of the highlighting paradigm with adult participants. The results from Experiment 1 provide evidence for the highlighting effect among children 3-6 years old, and they suggest age-related differences in dividing attention among multiple cues during learning. Experiment 2 replicated results from previous studies by showing robust biases for both image-based and text-based versions of the highlighting task. This study suggests that sensitivity to learning order emerges early through the process of cued attention, and the role of the highlighting effect in early language learning is discussed.
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