Prefrontal Executive Function Research Articles

HIIT 프로그램의 적용이 비만 아동의 전전두엽 실행기능과 스트레스에 미치는 영향

Objectives The aim of this research was to analyze the effect of the HIIT program on the prefrontal executive function and stress in obese children and provide base data needed to develop effective exercise program for obese elementary school students.
 Methods In order to accomplish the aim of this research, 24 obese children(BMI: 23kg/m2 or higher) were selected from the 5th~6th graders of J Elementary School at random to 12 members of exercise and control group respectively. HIIT program was performed for 20 minutes, 3 times per week, during 12 weeks. The measured data in this experiment were analyzed using the SPSS 25.0 statistical program, and the variables were expressed as M±SD and independent t-test was conducted for basic analysis of the general characteristics of the participants and verify the homogeneity between the groups. And 2-way ANOVA with repeated measures was conducted to analyze the interaction effects of groups and timing of measurement.
 Results The results obtained by the experiment are as follows. First, sub-variables of prefrontal executive functions. showed statistically significant differences in measurement time and interaction effects. The post measurements of the exercise group increased statistically significant, resulting in measurements between groups after the experiment. Second, stress variable showed statistically significant differences in measurement time and interaction effects, The post-measurements of the exercise group decreased statistically significant, resulting in statistically significant differences when comparing measurements between groups after the experiment.
 Conclusions In conclusion, the 12-week HIIT program had positive effects on obese children in elementary school for improvement of prefrontal executive function and reduction of stress. Therefore, it is considered that HIIT program can be utilized an effective exercise program for obese children in elementary school.

Demands on perceptual and mnemonic fidelity are a key determinant of age-related cognitive decline throughout the lifespan.

Aging results in less detailed memories, reflecting reduced fidelity of remembered compared to real-world representations. We tested whether poorer representational fidelity across perception, short-term memory (STM), and long-term memory (LTM) are among the earliest signs of cognitive aging. Our paradigm probed target-lure object mnemonic discrimination and precision of object-location binding. Across the lifespan, cognitive deficits were observed in midlife when detailed stimulus representations were required for perceptual and short/long-term forced choice mnemonic discrimination. A continuous metric of object-location source memory combined with computational modeling demonstrated that errors in STM and LTM in middle-aged adults were largely driven by a loss of precision for retrieved memories, not necessarily by forgetting. On a trial-by-trial basis, fidelity of item and spatial information was more tightly bound in LTM compared to STM with this association being unaffected by age. Standard neuropsychological tests without demands on memory quality (digit span, verbal learning) were less sensitive to age effects than STM and LTM precision. Perceptual discrimination predicted mnemonic discrimination. Neuropsychological proxies for prefrontal executive functions correlated with STM, but not LTM fidelity. Conversely, neuropsychological indicators of hippocampal integrity correlated with mnemonic discrimination and precision of both STM and LTM, suggesting partially dissociable mechanisms of interindividual variability in STM and LTM fidelity. These findings suggest that reduced representational fidelity is a hallmark of cognitive aging across perception, STM, and LTM and can be observed from midlife onward. Continuous memory precision tasks may be promising for the early detection of subtle age-related cognitive decline. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Groove Rhythm Enhances Exercise Impact on Prefrontal Cortex Function in Groove Enjoyers.

A positive affective response modulates the effects of aerobic exercise on prefrontal executive function (EF). Groove rhythm (GR), eliciting the feeling of wanting to move to music, is useful for inducing positive affective response during exercise. Three minutes of listening to GR activated the left dorsolateral prefrontal cortex (l-DLPFC) and enhanced EF in participants who had higher psychological responses to GR. This finding prompted us to test the hypothesis that the combination of GR and exercise (GREX) induces positive psychological responses that enhance PFC function through entrainment of body movements and musical beats. 41 participants were administered two experimental conditions: three min of very light-intensity (30% V̇ O2peak) exercise combined with GR and combined with a white-noise metronome (WMEX). Before and after exercise, participants performed a Stroop task and were monitored for l-DLPFC activity with functional near-infrared spectroscopy. GREX enhanced EF and l-DLPFC activity in participants who experienced greater subjective feelings of audiomotor entrainment and increased excitement with GREX. These psychological responses were predictive of the impact of GREX on l-DLPFC activity and EF. These findings, together with previous results, support the hypothesis that GR allows us to boost the cognitive benefits of exercise via l-DLPFC activity only in those who enjoy groove, and suggest that subjective audiomotor entrainment is a key mechanism of this boosting effect.

Pupil dynamics during very light exercise predict benefits to prefrontal cognition

Physical exercise, even stress-free very-light-intensity exercise such as yoga and very slow running, can have beneficial effects on executive function, possibly by potentiating prefrontal cortical activity. However, the exact mechanisms underlying this potentiation have not been identified. Evidence from studies using pupillometry demonstrates that pupil changes track the real-time dynamics of activity linked to arousal and attention, including neural circuits from the locus coeruleus to the cortex. This makes it possible to examine whether pupil-linked brain dynamics induced during very-light-intensity exercise mediate benefits to prefrontal executive function in healthy young adults. In this experiment, pupil diameter was measured during 10 min of very-light-intensity exercise (30% V˙o2peak). A Stroop task was used to assess executive function before and after exercise. Prefrontal cortical activation during the task was assessed using multichannel functional near-infrared spectroscopy (fNIRS). We observed that very-light-intensity exercise significantly elicited pupil dilation, reduction of Stroop interference, and task-related left dorsolateral prefrontal cortex activation compared with the resting-control condition. The magnitude of change in pupil dilation predicted the magnitude of improvement in Stroop performance. In addition, causal mediation analysis showed that pupil dilation during very-light-intensity exercise robustly determined subsequent enhancement of Stroop performance. This finding supports our hypothesis that the pupil-linked mechanisms, which may be tied to locus coeruleus activation, are a potential mechanism by which very light exercise enhances prefrontal cortex activation and executive function. It also suggests that pupillometry may be a useful tool to interpret the beneficial impact of exercise on boosting cognition.

클래스핏 트레이닝이 아동의 체력과 전전두엽 실행기능에 미치는 영향

Objectives The purpose of this study is to investigate the impact of the 12-week Class-fit training exercise program on physical fitness and prefrontal executive function in elementary school students and provide base data needed to use Class-fit training as physical fitness and prefrontal executive function improvement program of students.
 Methods In order to accomplish the purpose of this study, 36 sixth-grade students at E elementary school located in Seoul, were selected by convenience sampling and allocated 18 students each for the exercise group and the control group. Each group was measured for physical fitness and prefrontal executive function before and after the exercise. Class-fit training was implemented for 40 minutes of 3 times each week for 12 weeks.
 Results The results obtained through this study are as follows. First, muscle endurance, cardiovascular endurance, flexibility, power showed interaction effects in the group and time. Second, raw color-word score showed interaction effects in the group and time. Word raw score, color raw score showed significant differences in timing, particularly the post score of exercise group increased significantly.
 Conclusions In conclusion, 12-week Class-fit training had positive effect on elementary school students for physical fitness and prefrontal execution function. Class-fit training will make a contribution to the exercise program to help improve physical fitness and cognitive function.

Effects of trihexyphenidyl on prefrontal executive function and spontaneous neural activity in patients with tremor-dominant Parkinson's disease: An fNIRS study

IntroductionThe use of the anti-parkinsonian drug trihexyphenidyl (THP) to treat patients with Parkinson's disease (PD), particularly those with tremor-dominant PD (tdPD), has been well documented. Despite growing concerns about THP causing cognitive decline in tdPD patients, the underlying neural correlates remain unclear. Therefore, we investigated the effects of THP on prefrontal executive function and spontaneous neural activity in patients with tdPD by utilizing functional near-infrared spectroscopy (fNIRS). MethodsWe recruited 30 patients with tdPD, including 15 patients receiving THP and 15 patients not receiving THP. We performed comprehensive neuropsychological and clinical assessments to evaluate each patient's cognitive function, mental status, and clinical symptoms. We measured brain activation elicited from the verbal fluency task (VFT) and changes in amplitude of low-frequency fluctuations (ALFF) at rest to investigate executive function and spontaneous neural activity, respectively. In addition, we examined the relationship between altered activation during task and resting state and neuropsychological and clinical data. ResultsCompared with tdPD patients not taking THP, tdPD patients taking THP showed no differences on neuropsychological tests. However, there was insufficient activity of the dorsolateral prefrontal cortex (DLPFC) during VFT and reduced ALFF values for the DLPFC, ventrolateral prefrontal cortex (VLPFC), and the orbitofrontal cortex (OFC) related to the frontoparietal network (FPN) at rest. Furthermore, ALFF values of the VLPFC were positively correlated with scores of multiple cognitive domain functions. ConclusionThese findings suggest that THP treatment may lead to prefrontal dysfunction in tdPD patients, attenuating brain activation in executive function and cognition-related spontaneous neural activity.

A Predictive Processing Account of Card Sorting: Fast Proactive and Reactive Frontoparietal Cortical Dynamics during Inference and Learning of Perceptual Categories.

For decades, a common assumption in cognitive neuroscience has been that prefrontal executive control is mainly engaged during target detection [Posner, M. I., & Petersen, S. E. The attention system of the human brain. Annual Review of Neuroscience, 13, 25-42, 1990]. More recently, predictive processing theories of frontal function under the Bayesian brain hypothesis emphasize a key role of proactive control for anticipatory action selection (i.e., planning as active inference). Here, we review evidence of fast and widespread EEG and magnetoencephalographic fronto-temporo-parietal cortical activations elicited by feedback cues and target cards in the Wisconsin Card Sorting Test. This evidence is best interpreted when considering negative and positive feedback as predictive cues (i.e., sensory outcomes) for proactively updating beliefs about unknown perceptual categories. Such predictive cues inform posterior beliefs about high-level hidden categories governing subsequent response selection at target onset. Quite remarkably, these new views concur with Don Stuss' early findings concerning two broad classes of P300 cortical responses evoked by feedback cues and target cards in a computerized Wisconsin Card Sorting Test analogue. Stuss' discussion of those P300 responses-in terms of the resolution of uncertainty about response (policy) selection as well as the participants' expectancies for future perceptual or motor activities and their timing-was prescient of current predictive processing and active (Bayesian) inference theories. From these new premises, a domain-general frontoparietal cortical network is rapidly engaged during two temporarily distinct stages of inference and learning of perceptual categories that underwrite goal-directed card sorting behavior, and they each engage prefrontal executive functions in fundamentally distinct ways.

Abstract 2560: Plasticity-related signaling pathways in the medial prefrontal cortex and hippocampus as potential targets of the antidepressant vortioxetine in reversing cognitive impairments after androgen deprivation therapy for prostate cancer

Abstract Androgen deprivation therapy (ADT) is a frontline treatment for prostate cancer but induces profound cognitive impairment in more than half of patients. This significantly reduces quality of life for cancer survivors and their families. Deficits occur in cognitive domains associated with function of the hippocampus (Hipp) and medial prefrontal cortex (mPFC) and increase in severity with duration of treatment. Therefore, it may be possible to slow or reverse the impairment. In preclinical studies, we reported that vortioxetine, a novel multi-modal antidepressant that has been shown to improve cognitive impairment in depressed patients, may reverse the ADT-induced impairment. Our lab established a rodent model of ADT in which surgically castrated rats display deficits in cognitive flexibility and visuospatial recognition, measures of prefrontal executive function and hippocampal spatial learning, respectively. We also found that castration reduces response of the mPFC to activation of the afferent pathway from the vHipp in anesthetized animals. Chronic dietary vortioxetine (28mg/kg/day) normalized response in this pathway and reversed the cognitive impairments associated with both the mPFC and Hipp. In a microarray study (Agilent Technologies, Inc.) of tissue collected from the mPFC, dorsal-, and ventral-Hipp, we found that castration altered over 1,000 genes in each of these regions (adjusted p <0.05). Vortioxetine did not have a significant main effect on individual genes, but pathway analysis revealed significant changes in processes involved in synaptic plasticity, such as synapse formation, axonogenesis, and MAPK signaling. In the present study, qPCR and western blot analyses were used to investigate potential ADT- and vortioxetine-induced changes in candidate factors. Factors were identified in the top-hit pathways from the vortioxetine x castration microarray analysis and confirmed by qPCR. These included plasticity-related proteins such as Arc, Akt, CREB, mGlur1, and PSD95, among others. Changes in expression and phosphorylation were further determined using western blots. Early results indicate that vortioxetine selectively reversed the reduced expression induced by castration for some, but not all, of these proteins, including CREB and mGlur1 (p<0.05). Experiments are underway to identify potential alterations in protein phosphorylation, as changes in activation rather than expression may also be important to the beneficial effects of vortioxetine. These results suggest that vortioxetine may reverse deficits in executive function and visuospatial recognition after ADT by modulating structural and functional plasticity in mPFC and Hipp. Citation Format: Alexandra M. Vaiana, Roman Fernandez, Jonathan Gelfond, Teresa L. Johnson-Pais, Robin Leach, Chethan Ramamurthy, Ian Thompson, David A. Morilak. Plasticity-related signaling pathways in the medial prefrontal cortex and hippocampus as potential targets of the antidepressant vortioxetine in reversing cognitive impairments after androgen deprivation therapy for prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2560.

Autonomic Activity during a Daytime Nap Facilitates Working Memory Improvement.

Recent investigations have implicated the parasympathetic branch of the autonomic nervous system in higher-order executive functions. These actions are purported to occur through autonomic nervous system's modulation of the pFC, with parasympathetic activity during wake associated with working memory (WM) ability. Compared with wake, sleep is a period with substantially greater parasympathetic tone. Recent work has reported that sleep may also contribute to improvement in WM. Here, we examined the role of cardiac parasympathetic activity during sleep on WM improvement in healthy young adults. Participants were tested in an operation span task in the morning and evening, and during the intertest period, participants experienced either a nap or wake. We measured high-frequency heart rate variability as an index of cardiac, parasympathetic activity during both wake and sleep. Participants showed the expected boost in parasympathetic activity during nap, compared with wake. Furthermore, parasympathetic activity during sleep, but not wake, was significantly correlated with WM improvement. Together, these results indicate that the natural boost in parasympathetic activity during sleep may benefit gains in prefrontal executive function in young adults. We present a conceptual model illustrating the interaction between sleep, autonomic activity, and prefrontal brain function and highlight open research questions that will facilitate understanding of the factors that contribute to executive abilities in young adults as well as in cognitive aging.

Positive Mood while Exercising Influences Beneficial Effects of Exercise with Music on Prefrontal Executive Function: A Functional NIRS Study

Much attention has been focused on physical exercise benefits to mental health such as mood and cognitive function. Our recent studies have consistently shown that a single bout of exercise elicits increased task-related brain activation mainly in the dorsolateral part of the prefrontal cortex (DLPFC), which results in improved executive performance. As the DLPFC is associated with the modulation of mood as well as executive function, it is tempting to hypothesize that exercising while in a positive mood would facilitate the beneficial effects of exercise on executive function via DLPFC activation. Thus, we conceived an experiment that used music to elicit a positive mood during exercise. Thirty-three young adults performed ten minutes of moderate-intensity (50% V.O2peak) pedaling exercise with two experimental conditions: listening to music and listening to beeps at a steady tempo. Mood and executive function were respectively assessed using the Two-Dimensional Mood Scale and a color-word-matching Stroop task before and after the exercise sessions. Prefrontal activation during the Stroop task was monitored using functional near-infrared spectroscopy. Exercise with music elicited greater enhancement of a positive mood (vitality) than did exercise with beeps. Contrary to our hypothesis, there were no significant differences between conditions in improvement in Stroop task performance and task-related cortical activation in the left-DLPFC. The correlation analyses, however, revealed significant correlations among increased vitality, shortened Stroop interference time and increased activation in the left-DLPFC. These results support the hypothesis that positive mood while exercising influences the benefit of exercise on prefrontal activation and executive performance.

0263 Later Bedtime is Associated with Differences in Prefrontal Gray Matter Volume and Executive Function Deficits

Abstract Introduction Evening chronotypes tend to have reduced white matter integrity within their axonal tracts and reduced functional connectivity compared to morning types, a pattern that has been attributed to chronic “social jet lag” and its attendant disrupted sleep patterns. It is not clear whether brain differences are due to chronotype, total sleep time (TST), or whether they are associated with actual bedtime exclusive of these other factors. Here we examined morphometric gray matter volume (GMV) and its correlation with bedtime, after controlling for confounding factors. Methods Forty-five healthy adults (22 female; aged 20 to 43), completed the Horne-Ostberg Morningness-Eveningness Questionnaire (MEQ) and the Tower of London (TOL), an executive function task of planning and sequencing. Participants wore an actigraph for 7 days and completed structural MRI imaging during the period of actigraphy. Morphometric GMV data were processed using standard procedures in SPM12. After controlling for age, sex, and intracranial volume, actigraphic bedtime was entered into a regression analysis to predict orbitofrontal GMV. Regional GMV was extracted and correlated with TOL performance. Effects of TST and MEQ were also examined during regression. Results Later bedtime was associated with increased GMV in the left superior orbitofrontal gyrus (p=.044, FWE corrected). This association remained significant after controlling for TST and MEQ. Moreover, greater GMV in this cluster was associated with poorer planning and sequencing on TOL in terms of excess moves (r=.357, p=.017), and faster response times (r=-.356, p=.018), suggesting impulsivity. Conclusion Later bedtime was associated with greater GMV of the orbitofrontal cortex, even after controlling for TST and chronotype, and this pattern was associated with greater impulsiveness and poorer planning. The causal direction of the relationship between bedtime and executive deficits remains unclear and will require further research. However, it is clear that sleep patterns, brain structure, and behavior are intimately related. Support Defense Advanced Research Projects Agency Young Faculty Award: DARPA-12-12-11-YFA11-FP-029

Effects of Hidden Picture Game Activity on Self-control and Prefrontal Executive Function in Middle School Boys

Effects of Hidden Picture Game Activity on Self-control and Prefrontal Executive Function in Middle School Boys

Acute anxiety and autonomic arousal induced by CO2 inhalation impairs prefrontal executive functions in healthy humans

Acute anxiety impacts cognitive performance. Inhalation of air enriched with carbon dioxide (CO2) in healthy humans provides a novel experimental model of generalised anxiety, but has not previously been used to assess cognition. We used inhalation of 7.5% CO2 to induce acute anxiety and autonomic arousal in healthy volunteers during neuropsychological tasks of cognitive flexibility, emotional processing and spatial working memory in a single-blind, placebo-controlled, randomized, crossover, within-subjects study. In Experiment 1 (n = 44), participants made significantly more extra-dimensional shift errors on the Cambridge Neuropsychological Test Automated Battery (CANTAB) Intra-Extra Dimensional Set Shift task under CO2 inhalation compared with ‘normal’ air. Participants also had slower latencies when responding to positive words and made significantly more omission errors for negative words on the CANTAB Affective Go/No-go task. In Experiment 2 (n = 28), participants made significantly more total errors and had poorer heuristic search strategy on the CANTAB Spatial Working Memory task. In both experiments, CO2 inhalation significantly increased negative affect; state anxiety and fear; symptoms of panic; and systolic blood pressure/heart rate. Overall, CO2 inhalation produced robust anxiogenic effects and impaired fronto-executive functions of cognitive flexibility and working memory. Effects on emotional processing suggested a mood-congruent slowing in processing speed in the absence of a negative attentional bias. State-dependent effects of anxiety on cognitive-emotional interactions in the prefrontal cortex warrant further investigation.

The Effect of HIIT Program on Self-control and Prefrontal executive Function in Middle School Male Students

The Effect of HIIT Program on Self-control and Prefrontal executive Function in Middle School Male Students

Neuropsychological impacts of indirect revascularization for pediatric moyamoya disease.

Moyamoya disease (MMD) commonly leads to neurocognitive impairment. This study was carried out to show that temporal encephaloduroarteriosynangiosis (EDAS) has a positive neuropsychological impact on pediatric MMD patients. Fifty-five participants diagnosed with MMD from 2008 to 2014 were included in this retrospective study. The mean age at the preoperative evaluation was 9.5years and the mean age at postoperative evaluation was 10.4. The average interval of initial and follow-up test was 10months. K-WISC-III, Rey-Kim memory test, Children's Color Trails test (CCTT), Wisconsin Card Sorting Test (WCST), and Advanced Test of Attention (ATA) were used to evaluate patient's neurocognitive profile. In this study, preoperative and postoperative neuropsychological fields were compared. Prior operation, pediatric MMD patients showed 54.2% deficit of inattention but only around 2.5% deficit in verbal memory recall function. There was a significant increase of performance IQ and PO score component of PIQ improved almost 10 scores after surgery. For memorial function, there was an improvement of approximately 10 scores in MQ after the surgery. This study also showed parietal activation following surgical treatment which enhanced the ability to interpret visual materials, to register and to retrieve visual information. Interestingly, despite the parietal cover surgery, there was a significant improvement of performance on WCST and CCTT measuring the prefrontal executive function. Concerning failure to maintain set, no significant postoperative improvements were made. However, simple and selective visual attention on ATA was significantly improved postoperatively. The results from neuropsychological field comparison testifies the effectiveness of temporal EDAS in pediatric MMD patients. The surgery not only enhances the blood flow in operative regions, but it also improves the broad cerebral function including frontoparietal domains. Such alteration leads to overall advancement in cognitive function which are impaired due to MMD.

D3 Receptors Regulate Excitability in a Unique Class of Prefrontal Pyramidal Cells.

The D3 dopamine receptor, a member of the Gi-coupled D2 family of dopamine receptors, is expressed throughout limbic circuits affected in neuropsychiatric disorders, including prefrontal cortex (PFC). These receptors are important for prefrontal executive function because pharmacological and genetic manipulations that affect prefrontal D3 receptors alter anxiety, social interaction, and reversal learning. However, the mechanisms by which D3 receptors regulate prefrontal circuits and whether D3 receptors regulate specific prefrontal subnetworks remains unknown. Here, we combine dopamine receptor reporter lines, anatomical tracing techniques, and electrophysiology to show that D3 receptor expression defines a novel subclass of layer 5 glutamatergic pyramidal cell in mouse PFC (either sex). D3-receptor-expressing pyramidal neurons are electrophysiologically and anatomically separable from neighboring neurons expressing D1 or D2 receptors based on their dendritic morphology and subthreshold and suprathreshold intrinsic excitability. D3-receptor-expressing neurons send axonal projections to intratelencephalic (IT) targets, including contralateral cortex, nucleus accumbens, and basolateral amygdala. Within these neurons, D3 receptor activation was found to regulate low-voltage-activated CaV3.2 calcium channels localized to the axon initial segment, which suppressed action potential (AP) excitability, particularly when APs occurred at high frequency. Therefore, these data indicate that D3 receptors regulate the excitability of a unique, IT prefrontal cell population, thereby defining novel circuitry and cellular actions for D3 receptors in PFC.SIGNIFICANCE STATEMENT The D3 dopamine receptor, a member of the Gi-coupled D2 family of dopamine receptors, are expressed throughout limbic circuits, including prefrontal cortex (PFC). They are of broad interest as a site for therapeutic intervention in serious mental illness, yet we know very little about their distribution or function within PFC. Here, we show that D3 receptors define a unique population of glutamatergic principal cells in mouse PFC that largely lack expression of D1 or D2 receptors. Within these cells, we find that D3 receptors regulate the ability to generate high-frequency action potential bursts through mechanisms not supported by other dopamine receptors. These results define unique circuitry and cellular actions for D3 receptors in regulating PFC networks.

A Neuroanatomical Framework for Understanding Dream Content

The neurostructural model of dreaming avers that dreams are actively generated by the neural network formed by the mesolimbic-dopaminergic pathway, the ventromesial-orbitofrontal cortex, and the inferomesial temporal-limbic-occipital pathway as a result of the disengagement of the frontal convexity. Although the narrative content of dreams usually appears to be uncanny and unintelligible, there are typical dream themes that are similarly experienced by most people. On the other hand, some common waking-life activities that entail prefrontal executive functions rarely emerge in dreams. The cross-cultural resemblance of prevalence profiles for typical dream themes suggests that the formation of dream images is regularly biased toward a specific group of themes and is operated on by highly stable mechanisms and predispositions. In this article, I propose that the functional architecture of dreaming as depicted by the neurostructural model can provide a framework for understanding these predispositions.

Catechol-O-methyltransferase Val158Met polymorphism influences prefrontal executive function in early Parkinson's disease

ObjectiveThe catechol-O-methyltransferase (COMT) Val158Met polymorphism has been proposed to be associated with increased risk of Parkinson's disease (PD) and have a specific impact on dopamine-mediated prefrontal executive function in an inverted-U curve manner. We explored the influence of this genetic polymorphism on prefrontal executive function in a well-established Chinese cohort of early PD patients with no current or past history of motor fluctuations or dyskinesias. MethodsCognitive functions were assessed in 250 patients with early PD using Wechsler Adult Intelligence Scale-Chinese Revision (WAIS-RC) and Wechsler Memory Scale-Chinese Revision (WMS-RC). These patients and 300 healthy controls were subsequently genotyped for the COMT gene Val158Met polymorphism. We employed analysis of covariance (ANCOVA) and a stratified analysis to determine the associations between the COMT Val158Met genotype and cognitive functions. ResultsThe COMT Val158Met allele frequency and genotype distributions showed no statistically significant differences between PD patients and controls. However, patients with met/met genotype performed significantly worse on WAIS-RC similarities, a measure of executive function, compared to individuals with val/val genotype. Subsequent ANCOVA analysis revealed that COMT genotype interacted with sex and daily levodopa equivalent dose (LED) to influence executive function. Further stratified analysis showed that the lower-activity COMT met/met genotype has a detrimental effect on executive function among women. ConclusionsOur results demonstrate that COMT Val158Met polymorphism is probably not associated with increased risk of PD, but has an effect on prefrontal executive function interacting with gender and dopaminergic medication.

Lesions of the ventral midline thalamus produce deficits in reversal learning and attention on an odor texture set shifting task

The nucleus reuniens (RE) of the ventral midline thalamus is strongly reciprocally connected with the hippocampus (HF) and the medial prefrontal cortex (mPFC) and has been shown to mediate the transfer of information between these structures. It has become increasingly well established that RE serves a critical role in mnemonic tasks requiring the interaction of the HF and mPFC, but essentially not tasks relying solely on the HF. Very few studies have addressed the independent actions of RE on prefrontal executive functioning. The present report examined the effects of lesions of the ventral midline thalamus, including RE and the dorsally adjacent rhomboid nucleus (RH) in rats on attention and behavioral flexibility using the attentional set shifting task (AST). The task uses odor and tactile stimuli to test for attentional set formation, attentional set shifting, behavioral flexibility and reversal learning. By comparison with sham controls, lesioned rats were significantly impaired on reversal learning and intradimensional (ID) set shifting. Specifically, RE/RH lesioned rats were impaired on the first reversal stage of the task which required a change in response strategy to select a previously non-rewarded stimulus for reward. RE/RH lesioned rats also exhibited deficits in the ability to transfer or generalize rules of the task which requires making the same modality-based choices (e.g., odor vs. tactile) to different sets of stimuli in the ID stage of the task. These results demonstrate that in addition to its role in tasks dependent on HF-mPFC interactions, nucleus reuniens is also critically involved cognitive/executive functions associated with the medial prefrontal cortex. As such, the deficits in the AST task produced by RE/RH lesions suggest the ventral midline thalamus directly contributes to flexible goal directed behavior.

Executive function in parents of patients with familial versus sporadic bipolar disorder

ObjectiveStudies investigating the cognitive function of healthy relatives of patients with bipolar disorder are conflicting, and the neurocognitive profile of relatives of bipolar disorder probands is still unclear. We aimed to evaluate executive function in unaffected parents of familial and sporadic patients with bipolar disorder. MethodsThe study included 24 unaffected familial parents (FP) of patients with bipolar disorder, 26 unaffected sporadic parents (SP) of patients with bipolar disorder and 26 controls matched with the parents for gender, age and duration of education (76 subjects in total). All of the subjects were interviewed with the Structured Clinical Interview for DSM-IV-Axis I. Executive function was assessed using the California Verbal Learning Test (CVLT), the Trail Making Test (TMT), the Wisconsin Card Sorting Test (WCST) and the Stroop test. ResultsIn comparison to their respective matched controls, FP performed significantly worse on the CVLT, TMT, WCST and Stroop test, whereas SP performed significantly worse only on WCST perseverative errors and Stroop color test. FP performed significantly worse than SP on the CVLT, TMT, and WCST. ConclusionThe present study investigated relatives with and without a family history of bipolar disorder separately and found that executive function was impaired in parents with a positive family history of bipolar disorder. These findings bring more evidence suggesting that deficits in prefrontal executive function and verbal memory are associated with familial vulnerability to bipolar disorder and that executive function and verbal memory impairments may represent a potential endophenotype of bipolar disorder.