Prefrontal over-activation during walking in people with mobility deficits: Interpretation and functional implications.

PubMed

Hawkins, Kelly A; Fox, Emily J; Daly, Janis J; Rose, Dorian K; Christou, Evangelos A; McGuirk, Theresa E; Otzel, Dana M; Butera, Katie A; Chatterjee, Sudeshna A; Clark, David J

2018-06-01

Control of walking by the central nervous system includes contributions from executive control mechanisms, such as attention and motor planning resources. Executive control of walking can be estimated objectively by recording prefrontal cortical activity using functional near infrared spectroscopy (fNIRS). The primary objective of this study was to investigate group differences in prefrontal/executive control of walking among young adults, older adults, and adults post-stroke. Also assessed was the extent to which walking-related prefrontal activity fits existing cognitive frameworks of prefrontal over-activation. Participants included 24 adults post-stroke with moderate to severe walking deficits, 15 older adults with mild gait deficits, and 9 young healthy adults. Executive control of walking was quantified as oxygenated hemoglobin concentration in the prefrontal cortex measured by fNIRS. Three walking tasks were assessed: typical walking, walking over obstacles, and walking while performing a verbal fluency task. Walking performance was assessed by walking speed. There was a significant effect of group for prefrontal activity (p < 0.001) during typical and obstacles walking tasks, with young adults exhibiting the lowest level of prefrontal activity, followed by older adults, and then adults post-stroke. In young adults the prefrontal activity during typical walking was much lower than for the verbal fluency dual-task, suggesting substantial remaining prefrontal resources during typical walking. However, in older and post-stroke adults these remaining resources were significantly less (p < 0.01). Cumulatively, these results are consistent with prefrontal over-activation in the older and stroke groups, which was accompanied by a steeper drop in walking speed as task complexity increased to include obstacles (p < 0.05). There is a heightened use of prefrontal/executive control resources in older adults and post-stroke adults during walking. The level of

Persistent neuronal activity in human prefrontal cortex links perception and action

PubMed Central

Haller, Matar; Case, John; Crone, Nathan E.; Chang, Edward F.; King-Stephens, David; Laxer, Kenneth D.; Weber, Peter B.; Parvizi, Josef; Knight, Robert T.; Shestyuk, Avgusta Y.

2017-01-01

How do humans flexibly respond to changing environmental demands on a sub-second temporal scale? Extensive research has highlighted the key role of the prefrontal cortex in flexible decision-making and adaptive behavior, yet the core mechanisms that translate sensory information into behavior remain undefined. Utilizing direct human cortical recordings, we investigated the temporal and spatial evolution of neuronal activity, indexed by the broadband gamma signal, while sixteen participants performed a broad range of self-paced cognitive tasks. Here we describe a robust domain- and modality-independent pattern of persistent stimulus-to-response neural activation that encodes stimulus features and predicts motor output on a trial-by-trial basis with near-perfect accuracy. Observed across a distributed network of brain areas, this persistent neural activation is centered in the prefrontal cortex and is required for successful response implementation, providing a functional substrate for domain-general transformation of perception into action, critical for flexible behavior.

Aging, self-referencing, and medial prefrontal cortex.

PubMed

Gutchess, Angela H; Kensinger, Elizabeth A; Schacter, Daniel L

2007-01-01

The lateral prefrontal cortex undergoes both structural and functional changes with healthy aging. In contrast, there is little structural change in the medial prefrontal cortex, but relatively little is known about the functional changes to this region with age. Using an event-related fMRI design, we investigated the response of medial prefrontal cortex during self-referencing in order to compare age groups on a task that young and elderly perform similarly and that is known to actively engage the region in young adults. Nineteen young (M age = 23) and seventeen elderly (M age = 72) judged whether adjectives described themselves, another person, or were presented in upper case. We assessed the overlap in activations between young and elderly for the self-reference effect (self vs. other person), and found that both groups engage medial prefrontal cortex and mid-cingulate during self-referencing. The only cerebral differences between the groups in self versus other personality assessment were found in somatosensory and motor-related areas. In contrast, age-related modulations were found in the cerebral network recruited for emotional valence processing. Elderly (but not young) showed increased activity in the dorsal prefrontal cortex for positive relative to negative items, which could reflect an increase in controlled processing of positive information for elderly adults.

Prefrontal activation may predict working-memory training gain in normal aging and mild cognitive impairment.

PubMed

Vermeij, Anouk; Kessels, Roy P C; Heskamp, Linda; Simons, Esther M F; Dautzenberg, Paul L J; Claassen, Jurgen A H R

2017-02-01

Cognitive training has been shown to result in improved behavioral performance in normal aging and mild cognitive impairment (MCI), yet little is known about the neural correlates of cognitive plasticity, or about individual differences in responsiveness to cognitive training. In this study, 21 healthy older adults and 14 patients with MCI received five weeks of adaptive computerized working-memory (WM) training. Before and after training, functional Near-Infrared Spectroscopy (fNIRS) was used to assess the hemodynamic response in left and right prefrontal cortex during performance of a verbal n-back task with varying levels of WM load. After training, healthy older adults demonstrated decreased prefrontal activation at high WM load, which may indicate increased processing efficiency. Although MCI patients showed improved behavioral performance at low WM load after training, no evidence was found for training-related changes in prefrontal activation. Whole-group analyses showed that a relatively strong hemodynamic response at low WM load was related to worse behavioral performance, while a relatively strong hemodynamic response at high WM load was related to higher training gain. Therefore, a 'youth-like' prefrontal activation pattern at older age may be associated with better behavioral outcome and cognitive plasticity.

An exploratory study of the effects of spatial working-memory load on prefrontal activation in low- and high-performing elderly.

PubMed

Vermeij, Anouk; van Beek, Arenda H E A; Reijs, Babette L R; Claassen, Jurgen A H R; Kessels, Roy P C

2014-01-01

Older adults show more bilateral prefrontal activation during cognitive performance than younger adults, who typically show unilateral activation. This over-recruitment has been interpreted as compensation for declining structure and function of the brain. Here we examined how the relationship between behavioral performance and prefrontal activation is modulated by different levels of working-memory load. Eighteen healthy older adults (70.8 ± 5.0 years; MMSE 29.3 ± 0.9) performed a spatial working-memory task (n-back). Oxygenated ([O2Hb]) and deoxygenated ([HHb]) hemoglobin concentration changes were registered by two functional Near-Infrared Spectroscopy (fNIRS) channels located over the left and right prefrontal cortex. Increased working-memory load resulted in worse performance compared to the control condition. [O2Hb] increased with rising working-memory load in both fNIRS channels. Based on the performance in the high working-memory load condition, the group was divided into low and high performers. A significant interaction effect of performance level and hemisphere on [O2Hb] increase was found, indicating that high performers were better able to keep the right prefrontal cortex engaged under high cognitive demand. Furthermore, in the low performers group, individuals with a larger decline in task performance from the control to the high working-memory load condition had a larger bilateral increase of [O2Hb]. The high performers did not show a correlation between performance decline and working-memory load related prefrontal activation changes. Thus, additional bilateral prefrontal activation in low performers did not necessarily result in better cognitive performance. Our study showed that bilateral prefrontal activation may not always be successfully compensatory. Individual behavioral performance should be taken into account to be able to distinguish successful and unsuccessful compensation or declined neural efficiency.

Attention, Emotion, and Deactivation of Default Activity in Inferior Medial Prefrontal Cortex

ERIC Educational Resources Information Center

Geday, Jacob; Gjedde, Albert

2009-01-01

Attention deactivates the inferior medial prefrontal cortex (IMPC), but it is uncertain if emotions can attenuate this deactivation. To test the extent to which common emotions interfere with attention, we measured changes of a blood flow index of brain activity in key areas of the IMPC with positron emission tomography (PET) of labeled water…

Noninvasive imaging of prefrontal activation during attention-demanding tasks performed while walking using a wearable optical topography system

NASA Astrophysics Data System (ADS)

Atsumori, Hirokazu; Kiguchi, Masashi; Katura, Takusige; Funane, Tsukasa; Obata, Akiko; Sato, Hiroki; Manaka, Takaaki; Iwamoto, Mitsumasa; Maki, Atsushi; Koizumi, Hideaki; Kubota, Kisou

2010-07-01

Optical topography (OT) based on near-infrared spectroscopy is a noninvasive technique for mapping the relative concentration changes in oxygenated and deoxygenated hemoglobin (oxy- and deoxy-Hb, respectively) in the human cerebral cortex. In our previous study, we developed a small and light wearable optical topography (WOT) system that covers the entire forehead for monitoring prefrontal activation. In the present study, we examine whether the WOT system is applicable to OT measurement while walking, which has been difficult with conventional OT systems. We conduct OT measurements while subjects perform an attention-demanding (AD) task of balancing a ping-pong ball on a small card while walking. The measured time course and power spectra of the relative concentration changes in oxy- and deoxy-Hb show that the step-related changes in the oxy- and deoxy-Hb signals are negligible compared to the task-related changes. Statistical assessment of the task-related changes in the oxy-Hb signals show that the dorsolateral prefrontal cortex and rostral prefrontal area are significantly activated during the AD task. These results suggest that our functional imaging technique with the WOT system is applicable to OT measurement while walking, and will be a powerful tool for evaluating brain activation in a natural environment.

Enhanced Somatosensory Feedback Reduces Prefrontal Cortical Activity During Walking in Older Adults

PubMed Central

Christou, Evangelos A.; Ring, Sarah A.; Williamson, John B.; Doty, Leilani

2014-01-01

Background. The coordination of steady state walking is relatively automatic in healthy humans, such that active attention to the details of task execution and performance (controlled processing) is low. Somatosensation is a crucial input to the spinal and brainstem circuits that facilitate this automaticity. Impaired somatosensation in older adults may reduce automaticity and increase controlled processing, thereby contributing to deficits in walking function. The primary objective of this study was to determine if enhancing somatosensory feedback can reduce controlled processing during walking, as assessed by prefrontal cortical activation. Methods. Fourteen older adults (age 77.1±5.56 years) with mild mobility deficits and mild somatosensory deficits participated in this study. Functional near-infrared spectroscopy was used to quantify metabolic activity (tissue oxygenation index, TOI) in the prefrontal cortex. Prefrontal activity and gait spatiotemporal data were measured during treadmill walking and overground walking while participants wore normal shoes and under two conditions of enhanced somatosensation: wearing textured insoles and no shoes. Results. Relative to walking with normal shoes, textured insoles yielded a bilateral reduction of prefrontal cortical activity for treadmill walking (ΔTOI = −0.85 and −1.19 for left and right hemispheres, respectively) and for overground walking (ΔTOI = −0.51 and −0.66 for left and right hemispheres, respectively). Relative to walking with normal shoes, no shoes yielded lower prefrontal cortical activity for treadmill walking (ΔTOI = −0.69 and −1.13 for left and right hemispheres, respectively), but not overground walking. Conclusions. Enhanced somatosensation reduces prefrontal activity during walking in older adults. This suggests a less intensive utilization of controlled processing during walking. PMID:25112494

Reduced but broader prefrontal activity in patients with schizophrenia during n-back working memory tasks: a multi-channel near-infrared spectroscopy study.

PubMed

Koike, Shinsuke; Takizawa, Ryu; Nishimura, Yukika; Kinou, Masaru; Kawasaki, Shingo; Kasai, Kiyoto

2013-09-01

Caudal regions of the prefrontal cortex, including the dorsolateral (DLPFC) and ventrolateral (VLPFC) prefrontal cortex, are involved in essential cognitive functions such as working memory. In contrast, more rostral regions, such as the frontopolar cortex (FpC), have integrative functions among cognitive functions and thereby contribute crucially to real-world social activity. Previous functional magnetic resonance imaging studies have shown patients with schizophrenia had different DLPFC activity pattern in response to cognitive load changes compared to healthy controls; however, the spatial relationship between the caudal and rostral prefrontal activation has not been evaluated under less-constrained conditions. Twenty-six patients with schizophrenia and 26 age-, sex-, and premorbid-intelligence-matched healthy controls participated in this study. Hemodynamic changes during n-back working memory tasks with different cognitive loads were measured using multi-channel near-infrared spectroscopy (NIRS). Healthy controls showed significant task-related activity in the bilateral VLPFC and significant task-related decreased activity in the DLPFC, with greater signal changes when the task required more cognitive load. In contrast, patients with schizophrenia showed activation in the more rostral regions, including bilateral DLPFC and FpC. Neither decreased activity nor greater activation in proportion to elevated cognitive load occurred. This multi-channel NIRS study demonstrated that activation intensity did not increase in patients with schizophrenia associated with cognitive load changes, suggesting hypo-frontality as cognitive impairment in schizophrenia. On the other hand, patients had broader prefrontal activity in areas such as the bilateral DLPFC and FpC regions, thus suggesting a hyper-frontality compensatory response. Copyright © 2013 Elsevier Ltd. All rights reserved.

Reducing prefrontal gamma-aminobutyric acid activity induces cognitive, behavioral, and dopaminergic abnormalities that resemble schizophrenia.

PubMed

Enomoto, Takeshi; Tse, Maric T; Floresco, Stan B

2011-03-01

Perturbations in gamma-aminobutyric acid (GABA)-related markers have been reported in the prefrontal cortex of schizophrenic patients. However, a preclinical assessment of how suppression of prefrontal cortex GABA activity may reflect behavioral and cognitive pathologies observed in schizophrenia is forthcoming. We assessed the effects of pharmacologic blockade of prefrontal cortex GABA(A) receptors in rats on executive functions and other behaviors related to schizophrenia, as well as neural activity of midbrain dopamine neurons. Blockade of prefrontal cortex GABA(A) receptors with bicuculline (12.5-50 ng) did not affect working memory accuracy but did increase response latencies, resembling speed of processing deficits observed in schizophrenia. Prefrontal cortex GABA(A) blockade did not impede simple discrimination or reversal learning but did impair set-shifting in a manner dependent on when these treatments were given. Reducing GABA activity before the set-shift impaired the ability to acquire a novel strategy, whereas treatment before the initial discrimination increased perseveration during the shift. Latent inhibition was unaffected by bicuculline infusions before the preexposure/conditioning phases, suggesting that reduced prefrontal cortex GABA activity does not impair "learned irrelevance." GABA(A) blockade increased locomotor activity and showed synergic effects with a subthreshold dose of amphetamine. Furthermore, reducing medial prefrontal cortex GABA activity selectively increased phasic burst firing of ventral tegmental area dopamine neurons, without altering the their overall population activity. These results suggest that prefrontal cortex GABA hypofunction may be a key contributing factor to deficits in speed of processing, cognitive flexibility, and enhanced phasic dopamine activity observed in schizophrenia. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Saccade-related activity in the prefrontal cortex: its role in eye movement control and cognitive functions

PubMed Central

Funahashi, Shintaro

2014-01-01

Prefrontal neurons exhibit saccade-related activity and pre-saccadic memory-related activity often encodes the directions of forthcoming eye movements, in line with demonstrated prefrontal contribution to flexible control of voluntary eye movements. However, many prefrontal neurons exhibit post-saccadic activity that is initiated well after the initiation of eye movement. Although post-saccadic activity has been observed in the frontal eye field, this activity is thought to be a corollary discharge from oculomotor centers, because this activity shows no directional tuning and is observed whenever the monkeys perform eye movements regardless of goal-directed or not. However, prefrontal post-saccadic activities exhibit directional tunings similar as pre-saccadic activities and show context dependency, such that post-saccadic activity is observed only when monkeys perform goal-directed saccades. Context-dependency of prefrontal post-saccadic activity suggests that this activity is not a result of corollary signals from oculomotor centers, but contributes to other functions of the prefrontal cortex. One function might be the termination of memory-related activity after a behavioral response is done. This is supported by the observation that the termination of memory-related activity coincides with the initiation of post-saccadic activity in population analyses of prefrontal activities. The termination of memory-related activity at the end of the trial ensures that the subjects can prepare to receive new and updated information. Another function might be the monitoring of behavioral performance, since the termination of memory-related activity by post-saccadic activity could be associated with informing the correctness of the response and the termination of the trial. However, further studies are needed to examine the characteristics of saccade-related activities in the prefrontal cortex and their functions in eye movement control and a variety of cognitive functions

Inverse association between BMI and prefrontal metabolic activity in healthy adults.

PubMed

Volkow, Nora D; Wang, Gene-Jack; Telang, Frank; Fowler, Joanna S; Goldstein, Rita Z; Alia-Klein, Nelly; Logan, Jean; Wong, Christopher; Thanos, Panayotis K; Ma, Yemine; Pradhan, Kith

2009-01-01

Obesity has been associated with a higher risk for impaired cognitive function, which most likely reflects associated medical complications (i.e., cerebrovascular pathology). However, there is also evidence that in healthy individuals excess weight may adversely affect cognition (executive function, attention, and memory). Here, we measured regional brain glucose metabolism (using positron emission tomography (PET) and 2-deoxy-2[(18)F]fluoro-D-glucose (FDG)) to assess the relationship between BMI and brain metabolism (marker of brain function) in 21 healthy controls (BMI range 19-37 kg/m(2)) studied during baseline (no stimulation) and during cognitive stimulation (numerical calculations). Statistical parametric mapping (SPM) revealed a significant negative correlation between BMI and metabolic activity in prefrontal cortex (Brodmann areas 8, 9, 10, 11, 44) and cingulate gyrus (Brodmann area 32) but not in other regions. Moreover, baseline metabolism in these prefrontal regions was positively associated with performance on tests of memory (California Verbal Learning Test) and executive function (Stroop Interference and Symbol Digit Modality tests). In contrast, the regional brain changes during cognitive stimulation were not associated with BMI nor with neuropsychological performance. The observed association between higher BMI and lower baseline prefrontal metabolism may underlie the impaired performance reported in healthy obese individuals on some cognitive tests of executive function. On the other hand, the lack of an association between BMI and brain metabolic activation during cognitive stimulation indicates that BMI does not influence brain glucose utilization during cognitive performance. These results further highlight the urgency to institute public health interventions to prevent obesity.

Effect of Bilateral Prefrontal rTMS on Left Prefrontal NAA and Glx Levels in Schizophrenia Patients with Predominant Negative Symptoms: An Exploratory Study.

PubMed

Dlabac-de Lange, Jozarni J; Liemburg, Edith J; Bais, Leonie; van de Poel-Mustafayeva, Aida T; de Lange-de Klerk, Elly S M; Knegtering, Henderikus; Aleman, André

Prefrontal repetitive Transcranial Magnetic Stimulation (rTMS) may improve negative symptoms in patients with schizophrenia, but few studies have investigated the underlying neural mechanism. This study aims to investigate changes in the levels of glutamate and glutamine (Glx, neurotransmitter and precursor) and N-Acetyl Aspartate (NAA) in the left dorsolateral prefrontal cortex of patients with schizophrenia treated with active bilateral prefrontal rTMS as compared to sham-rTMS, as measured with 1 H-Magnetic Resonance Spectroscopy ( 1 H-MRS). Patients were randomized to a 3-week course of active or sham high-frequency rTMS. Pre-treatment and post-treatment 1 H-MRS data were available for 24 patients with schizophrenia with moderate to severe negative symptoms (Positive and Negative Syndrome Scale (PANSS) negative subscale ≥ 15). Absolute metabolite concentrations were calculated using LCModel with the water peak as reference. To explore the association between treatment condition and changes in concentration of Glx and NAA, we applied a linear regression model. We observed an increase of Glx concentration in the active treatment group and a decrease of Glx concentration in the group receiving sham treatment. The association between changes in Glx concentration and treatment condition was significant. No significant associations between changes in NAA and treatment condition were found. Noninvasive neurostimulation with high-frequency bilateral prefrontal rTMS may influence Glx concentration in the prefrontal cortex of patients with schizophrenia. Larger studies are needed to confirm these findings and further elucidate the underlying neural working mechanism of rTMS. Copyright © 2016 Elsevier Inc. All rights reserved.

Reduced prefrontal dopaminergic activity in valproic acid-treated mouse autism model.

PubMed

Hara, Yuta; Takuma, Kazuhiro; Takano, Erika; Katashiba, Keisuke; Taruta, Atsuki; Higashino, Kosuke; Hashimoto, Hitoshi; Ago, Yukio; Matsuda, Toshio

2015-08-01

Previous studies suggest that dysfunction of neurotransmitter systems is associated with the pathology of autism in humans and the disease model rodents, but the precise mechanism is not known. Rodent offspring exposed prenatally to VPA shows autism-related behavioral abnormalities. The present study examined the effect of prenatal VPA exposure on brain monoamine neurotransmitter systems in male and female mice. The prenatal VPA exposure did not affect the levels of dopamine (DA), noradrenaline (NA), serotonin (5-HT) and their metabolites in the prefrontal cortex and striatum, while it significantly reduced methamphetamine (METH) (1.0 mg/kg)-induced hyperlocomotion in male offspring. In vivo microdialysis study demonstrated that prenatal VPA exposure attenuated METH-induced increases in extracellular DA levels in the prefrontal cortex, while it did not affect those in extracellular NA and 5-HT levels. Prenatal VPA exposure also decreased METH-induced c-Fos expression in the prefrontal cortex and the mRNA levels of DA D1 and D2 receptors in the prefrontal cortex. These effects of VPA were not observed in the striatum. In contrast to male offspring, prenatal VPA exposure did not affect METH-induced increases in locomotor activity and prefrontal DA levels and the D1 and D2 receptor mRNA levels in the prefrontal cortex in female offspring. These findings suggest that prenatal VPA exposure causes hypofunction of prefrontal DA system in a sex-dependent way. Copyright © 2015 Elsevier B.V. All rights reserved.

Amphetamine Exerts Dose-Dependent Changes in Prefrontal Cortex Attractor Dynamics during Working Memory

PubMed Central

Balaguer-Ballester, Emili; Seamans, Jeremy K.; Phillips, Anthony G.; Durstewitz, Daniel

2015-01-01

Modulation of neural activity by monoamine neurotransmitters is thought to play an essential role in shaping computational neurodynamics in the neocortex, especially in prefrontal regions. Computational theories propose that monoamines may exert bidirectional (concentration-dependent) effects on cognition by altering prefrontal cortical attractor dynamics according to an inverted U-shaped function. To date, this hypothesis has not been addressed directly, in part because of the absence of appropriate statistical methods required to assess attractor-like behavior in vivo. The present study used a combination of advanced multivariate statistical, time series analysis, and machine learning methods to assess dynamic changes in network activity from multiple single-unit recordings from the medial prefrontal cortex (mPFC) of rats while the animals performed a foraging task guided by working memory after pretreatment with different doses of d-amphetamine (AMPH), which increases monoamine efflux in the mPFC. A dose-dependent, bidirectional effect of AMPH on neural dynamics in the mPFC was observed. Specifically, a 1.0 mg/kg dose of AMPH accentuated separation between task-epoch-specific population states and convergence toward these states. In contrast, a 3.3 mg/kg dose diminished separation and convergence toward task-epoch-specific population states, which was paralleled by deficits in cognitive performance. These results support the computationally derived hypothesis that moderate increases in monoamine efflux would enhance attractor stability, whereas high frontal monoamine levels would severely diminish it. Furthermore, they are consistent with the proposed inverted U-shaped and concentration-dependent modulation of cortical efficiency by monoamines. PMID:26180194

Changes in Prefrontal-Limbic Function in Major Depression after 15 Months of Long-Term Psychotherapy

PubMed Central

Buchheim, Anna; Viviani, Roberto; Kessler, Henrik; Kächele, Horst; Cierpka, Manfred; Roth, Gerhard; George, Carol; Kernberg, Otto F.; Bruns, Georg; Taubner, Svenja

2012-01-01

Neuroimaging studies of depression have demonstrated treatment-specific changes involving the limbic system and regulatory regions in the prefrontal cortex. While these studies have examined the effect of short-term, interpersonal or cognitive-behavioural psychotherapy, the effect of long-term, psychodynamic intervention has never been assessed. Here, we investigated recurrently depressed (DSM-IV) unmedicated outpatients (N = 16) and control participants matched for sex, age, and education (N = 17) before and after 15 months of psychodynamic psychotherapy. Participants were scanned at two time points, during which presentations of attachment-related scenes with neutral descriptions alternated with descriptions containing personal core sentences previously extracted from an attachment interview. Outcome measure was the interaction of the signal difference between personal and neutral presentations with group and time, and its association with symptom improvement during therapy. Signal associated with processing personalized attachment material varied in patients from baseline to endpoint, but not in healthy controls. Patients showed a higher activation in the left anterior hippocampus/amygdala, subgenual cingulate, and medial prefrontal cortex before treatment and a reduction in these areas after 15 months. This reduction was associated with improvement in depressiveness specifically, and in the medial prefrontal cortex with symptom improvement more generally. This is the first study documenting neurobiological changes in circuits implicated in emotional reactivity and control after long-term psychodynamic psychotherapy. PMID:22470470

Prefrontal activation during inhibitory control measured by near-infrared spectroscopy for differentiating between autism spectrum disorders and attention deficit hyperactivity disorder in adults.

PubMed

Ishii-Takahashi, Ayaka; Takizawa, Ryu; Nishimura, Yukika; Kawakubo, Yuki; Kuwabara, Hitoshi; Matsubayashi, Junko; Hamada, Kasumi; Okuhata, Shiho; Yahata, Noriaki; Igarashi, Takashi; Kawasaki, Shingo; Yamasue, Hidenori; Kato, Nobumasa; Kasai, Kiyoto; Kano, Yukiko

2014-01-01

The differential diagnosis of autism spectrum disorders (ASDs) and attention deficit hyperactivity disorder (ADHD) based solely on symptomatic and behavioral assessments can be difficult, even for experts. Thus, the development of a neuroimaging marker that differentiates ASDs from ADHD would be an important contribution to this field. We assessed the differences in prefrontal activation between adults with ASDs and ADHD using an entirely non-invasive and portable neuroimaging tool, near-infrared spectroscopy. This study included 21 drug-naïve adults with ASDs, 19 drug-naïve adults with ADHD, and 21 healthy subjects matched for age, sex, and IQ. Oxygenated hemoglobin concentration changes in the prefrontal cortex were assessed during a stop signal task and a verbal fluency task. During the stop signal task, compared to the control group, the ASDs group exhibited lower activation in a broad prefrontal area, whereas the ADHD group showed underactivation of the right premotor area, right presupplementary motor area, and bilateral dorsolateral prefrontal cortices. Significant differences were observed in the left ventrolateral prefrontal cortex between the ASDs and ADHD groups during the stop signal task. The leave-one-out cross-validation method using mean oxygenated hemoglobin changes yielded a classification accuracy of 81.4% during inhibitory control. These results were task specific, as the brain activation pattern observed during the verbal fluency task did not differentiate the ASDs and ADHD groups significantly. This study therefore provides evidence of a difference in left ventrolateral prefrontal activation during inhibitory control between adults with ASDs and ADHD. Thus, near-infrared spectroscopy may be useful as an auxiliary tool for the differential diagnosis of such developmental disorders.

Prefrontal activity and impaired memory encoding strategies in schizophrenia.

PubMed

Guimond, Synthia; Hawco, Colin; Lepage, Martin

2017-08-01

Schizophrenia patients have significant memory difficulties that have far-reaching implications in their daily life. These impairments are partly attributed to an inability to self-initiate effective memory encoding strategies, but its core neurobiological correlates remain unknown. The current study addresses this critical gap in our knowledge of episodic memory impairments in schizophrenia. Schizophrenia patients (n = 35) and healthy controls (n = 23) underwent a Semantic Encoding Memory Task (SEMT) during an fMRI scan. Brain activity was examined for conditions where participants were a) prompted to use semantic encoding strategies, or b) not prompted but required to self-initiate such strategies. When prompted to use semantic encoding strategies, schizophrenia patients exhibited similar recognition performance and brain activity as healthy controls. However, when required to self-initiate these strategies, patients had significant reduced recognition performance and brain activity in the left dorsolateral prefrontal cortex, as well as in the left temporal gyrus, left superior parietal lobule, and cerebellum. When patients were divided based on performance on the SEMT, the subgroup with more severe deficits in self-initiation also showed greater reduction in left dorsolateral prefrontal activity. These results suggest that impaired self-initiation of elaborative encoding strategies is a driving feature of memory deficits in schizophrenia. We also identified the neural correlates of impaired self-initiation of semantic encoding strategies, in which a failure to activate the left dorsolateral prefrontal cortex plays a key role. These findings provide important new targets in the development of novel treatments aiming to improve memory and ultimately patients' outcome. Copyright © 2017. Published by Elsevier Ltd.

Monitoring of prefrontal cortex activation during verbal n-back task with 24-channel functional NIRS imager

NASA Astrophysics Data System (ADS)

Li, Chengjun; Gong, Hui; Gan, Zhuo; Luo, Qingming

2005-01-01

Human prefrontal cortex (PFC) helps mediate working memory (WM), a system that is used for temporary storage and manipulation of information and is involved with many higher-level cognitive functions. Here, we report a functional near-infrared spectroscopy (NIRS) study on the PFC activation caused by verbal WM task. For investigating the effect of memory load on brain activation, we adopted the "n-back" task in which subjects must decide for each present letter whether it matches the letter presented n items back in sequence. 27 subjects (ages 18-24, 13 females) participated in the work. Concentration changes in oxy-Hb (HbO2), deoxy-Hb (Hb), and total-Hb (HbT) in the subjects" prefrontal cortex were monitored by a 24-channel functional NIRS imager. The cortical activations and deactivations were found in left ventrolateral PFC and bilateral dorsolateral PFC. As memory load increased, subjects showed poorer behavioral performance as well as monotonically increasing magnitudes of the activations and deactivations in PFC.

Nicotinic α5 Subunits Drive Developmental Changes in the Activation and Morphology of Prefrontal Cortex Layer VI Neurons

PubMed Central

Bailey, Craig D.C.; Alves, Nyresa C.; Nashmi, Raad; De Biasi, Mariella; Lambe, Evelyn K.

2013-01-01

Background Nicotinic signaling in prefrontal layer VI pyramidal neurons is important to the function of mature attention systems. The normal incorporation of α5 subunits into α4β2* nicotinic acetylcholine receptors augments nicotinic signaling in these neurons and is required for normal attention performance in adult mice. However, the role of α5 subunits in the development of the prefrontal cortex is not known. Methods We sought to answer this question by examining nicotinic currents and neuronal morphology in layer VI neurons of medial prefrontal cortex of wild-type and α5 subunit knockout (α5−/−) mice during postnatal development and in adulthood. Results In wild-type but not in α5−/− mice, there is a developmental peak in nicotinic acetylcholine currents in the third postnatal week. At this juvenile time period, the majority of neurons in all mice have long apical dendrites extending into cortical layer I. Yet, by early adulthood, wild-type but not α5−/− mice show a pronounced shift toward shorter apical dendrites. This cellular difference occurs in the absence of genotype differences in overall cortical morphology. Conclusions Normal developmental changes in nicotinic signaling and dendritic morphology in prefrontal cortex depend on α5-comprising nicotinic acetylcholine receptors. It appears that these receptors mediate a specific developmental retraction of apical dendrites in layer VI neurons. This finding provides novel insight into the cellular mechanisms underlying the known attention deficits in α5−/− mice and potentially also into the pathophysiology of developmental neuropsychiatric disorders such as attention-deficit disorder and autism. PMID:22030359

Real-time monitoring prefrontal activities during online video game playing by functional near-infrared spectroscopy.

PubMed

Li, Yue; Zhang, Lei; Long, Kehong; Gong, Hui; Lei, Hao

2018-02-16

A growing body of literature has suggested that video game playing can induce functional and structural plasticity of the brain. The underlying mechanisms, however, remain poorly understood. In this study, functional near-infrared spectroscopy (fNIRS) was used to record prefrontal activities in 24 experienced game players when they played a massively multiplayer online battle arena video game, League of Legends (LOL), under naturalistic conditions. It was observed that game onset was associated with significant activations in the ventrolateral prefrontal cortex (VLPFC) and concomitant deactivations in the dorsolateral prefrontal cortex (DLPFC) and frontal pole area (FPA). Game events, such as slaying an enemy and being slain by an enemy evoked region-specific time-locked hemodynamic/oxygenation responses in the prefrontal cortex (PFC). It was proposed that the VLPFC activities during LOL playing are likely responses to visuo-motor task load of the game, while the DLPFC/FPA activities may be involved in the constant shifts of attentional states and allocation of cognitive resources required by game playing. The present study demonstrated that it is feasible to use fNIRS to monitor real-time prefrontal activity during online video game playing. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Single unit activity in the medial prefrontal cortex during Pavlovian heart rate conditioning: Effects of peripheral autonomic blockade.

PubMed

Powell, D A; Ginsberg, Jay P

2005-11-01

Electrical activity was recorded from single neurons in the medial prefrontal cortex of rabbits during differential Pavlovian heart rate (HR) conditioning. A heterogeneous population of cells were found, some of which showed CS-evoked increases and others CS-evoked decreases in discharge, while some cells were biphasic. A subset of cells also showed trial-related changes in discharge that were related to acquisition of the HR discrimination between the reinforced CS+ and non-reinforced CS-. Administration of the peripheral cholinergic antagonist, methylscopolamine, and the andrenergic antagonist, atenolol, either increased or decreased maintained baseline activity of many cells, but had little or no effect on the CS-evoked activity of these cells. Waveform changes also did not result from administration of these drugs. This finding suggests that CS-evoked mPFC activity is not being driven by cardiac afferent input to CNS cardiac control centers. Previous studies have shown that ibotenic acid lesions of this area greatly decreases the magnitude of decelerative heart rate conditioned responses; the latter finding, plus the results of the present study, suggest that processing of CS/US contingencies by the prefrontal cortex contributes to the acquisition of autonomic changes during Pavlovian conditioning.

Ventrolateral prefrontal activation during a N-back task assessed with multichannel functional near-infrared spectroscopy

NASA Astrophysics Data System (ADS)

Zhou, Yuan; Zhu, Ye; Jiang, Tianzi

2007-05-01

Functional near-infrared spectroscopy (fNIRS) has been used to investigate the changes in the concentration of oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin in brain issue during several cognitive tasks. In the present study, by means of multichannel dual wavelength light-emitting diode continuous-wave (CW) NIRS, we investigated the blood oxygenation changes of prefrontal cortex in 18 healthy subjects while performing a verbal n-back task (0-back and 2-back), which has been rarely investigated by fNIRS. Compared to the 0-back task (control task), we found a significant increase of O2Hb and total amount of hemoglobin (THb) in left and right ventrolateral prefrontal cortex (VLPFC) during the execution of the 2-back task compared to the 0-back task (p<0.05, FDR corrected). This result is consistent with the previous functional neuroimaging studies that have found the VLPFC activation related to verbal working memory. However, we found no significant hemisphere dominance. In addition, the effects of gender and its interaction with task performance on O2Hb concentration change were suggested in the present study. Our findings not only confirm that multichannel fNIRS is suitable to detect spatially specific activation during the performance of cognitive tasks; but also suggest that it should be cautious of gender-dependent difference in cerebral activation when interpreting the fNIRS data during cognitive tasks.

Forming a negative impression of another person correlates with activation in medial prefrontal cortex and amygdala.

PubMed

Iidaka, Tetsuya; Harada, Tokiko; Sadato, Norihiro

2011-09-01

Neural correlates involved in the formation of negative impression from face were investigated using event-related functional magnetic resonance imaging and a partial conditioning paradigm. Eighteen normal volunteers underwent imaging while they viewed the faces of two unfamiliar individuals: one individual's face was partially accompanied by negative emotion but the other's was not. After the volunteers learned the relationship between the faces and the emotion, they formed a more negative impression of the person's face when the emotion was presented. Subtraction analysis of the individuals' neutral faces revealed activation in the dorsal anterior cingulate cortex and superior temporal sulcus, but this activity did not correlate with the change of impression from face. On the other hand, the response in the left amygdala negatively correlated with the change of impression from face in the first run. Time modulation analysis revealed that activity in the dorsomedial prefrontal cortex associated with negative emotion was the largest in the initial part of the acquisition. These results suggest that a negative impression from face may be formed by orchestrated activity in the dorsomedial prefrontal cortex, dorsal anterior cingulate cortex and amygdala, and that the activity has a prominent role in the initial acquisition of negative emotion.

Positive effect of acute mild exercise on executive function via arousal-related prefrontal activations: an fNIRS study.

PubMed

Byun, Kyeongho; Hyodo, Kazuki; Suwabe, Kazuya; Ochi, Genta; Sakairi, Yosuke; Kato, Morimasa; Dan, Ippeita; Soya, Hideaki

2014-09-01

Despite the practical implication of mild exercise, little is known about its influence on executive function and its neural substrates. To address these issues, the present study examined the effect of an acute bout of mild exercise on executive function and attempted to identify potential neural substrates using non-invasive functional near-infrared spectroscopy (fNIRS). Twenty-five young individuals performed a color-word matching Stroop task (CWST) and a two-dimensional scale to measure changes of psychological mood states both before and after a 10-minute exercise session on a cycle ergometer at light intensity (30% v(·)o2peak) and, for the control session, without exercise. Cortical hemodynamic changes in the prefrontal area were monitored with fNIRS during the CWST in both sessions. The acute bout of mild exercise led to improved Stroop performance, which was positively correlated with increased arousal levels. It also evoked cortical activations regarding Stroop interference on the left dorsolateral prefrontal cortex and frontopolar area. These activations significantly corresponded with both improved cognitive performance and increased arousal levels. Concurrently, this study provides empirical evidence that an acute bout of mild exercise improves executive function mediated by the exercise-induced arousal system, which intensifies cortical activation in task-related prefrontal sub-regions. Copyright © 2014 Elsevier Inc. All rights reserved.

Prefrontal EEG alpha asymmetry changes while observing disaster happening to other people: cardiac correlates and prediction of emotional impact.

PubMed

Papousek, Ilona; Weiss, Elisabeth M; Schulter, Günter; Fink, Andreas; Reiser, Eva M; Lackner, Helmut K

2014-12-01

Changes of EEG alpha asymmetry in terms of increased right versus left sided activity in prefrontal cortex are considered to index activation of the withdrawal/avoidance motivational system. The present study aimed to add evidence of the validity of individual differences in the EEG alpha asymmetry response and their relevance regarding the impact of emotional events. The magnitude of the EEG alpha asymmetry response while watching a film consisting of scenes of real injury and death correlated with components of transient cardiac responses to sudden horrifying events happening to persons in the film which index withdrawal/avoidance motivation and heightened attention and perceptual intake. Additionally, it predicted greater mood deterioration following the film and film-related intrusive memories and avoidance over the following week. The study provides further evidence for prefrontal EEG alpha asymmetry changes in response to relevant stimuli reflecting an individual's sensitivity to negative social-emotional cues encountered in everyday life. Copyright © 2014 Elsevier B.V. All rights reserved.

The Contingency of Cocaine Administration Accounts for Structural and Functional Medial Prefrontal Deficits and Increased Adrenocortical Activation

PubMed Central

Anderson, Rachel M.; Cosme, Caitlin V.; Glanz, Ryan M.; Miller, Mary C.; Romig-Martin, Sara A.; LaLumiere, Ryan T.

2015-01-01

The prelimbic region (PL) of the medial prefrontal cortex (mPFC) is implicated in the relapse of drug-seeking behavior. Optimal mPFC functioning relies on synaptic connections involving dendritic spines in pyramidal neurons, whereas prefrontal dysfunction resulting from elevated glucocorticoids, stress, aging, and mental illness are each linked to decreased apical dendritic branching and spine density in pyramidal neurons in these cortical fields. The fact that cocaine use induces activation of the stress-responsive hypothalamo-pituitary-adrenal axis raises the possibility that cocaine-related impairments in mPFC functioning may be manifested by similar changes in neuronal architecture in mPFC. Nevertheless, previous studies have generally identified increases, rather than decreases, in structural plasticity in mPFC after cocaine self-administration. Here, we use 3D imaging and analysis of dendritic spine morphometry to show that chronic cocaine self-administration leads to mild decreases of apical dendritic branching, prominent dendritic spine attrition in PL pyramidal neurons, and working memory deficits. Importantly, these impairments were largely accounted for in groups of rats that self-administered cocaine compared with yoked-cocaine- and saline-matched counterparts. Follow-up experiments failed to demonstrate any effects of either experimenter-administered cocaine or food self-administration on structural alterations in PL neurons. Finally, we verified that the cocaine self-administration group was distinguished by more protracted increases in adrenocortical activity compared with yoked-cocaine- and saline-matched controls. These studies suggest a mechanism whereby increased adrenocortical activity resulting from chronic cocaine self-administration may contribute to regressive prefrontal structural and functional plasticity. SIGNIFICANCE STATEMENT Stress, aging, and mental illness are each linked to decreased prefrontal plasticity. Here, we show that chronic

Prefrontal, posterior parietal and sensorimotor network activity underlying speed control during walking

PubMed Central

Bulea, Thomas C.; Kim, Jonghyun; Damiano, Diane L.; Stanley, Christopher J.; Park, Hyung-Soon

2015-01-01

Accumulating evidence suggests cortical circuits may contribute to control of human locomotion. Here, noninvasive electroencephalography (EEG) recorded from able-bodied volunteers during a novel treadmill walking paradigm was used to assess neural correlates of walking. A systematic processing method, including a recently developed subspace reconstruction algorithm, reduced movement-related EEG artifact prior to independent component analysis and dipole source localization. We quantified cortical activity while participants tracked slow and fast target speeds across two treadmill conditions: an active mode that adjusted belt speed based on user movements and a passive mode reflecting a typical treadmill. Our results reveal frequency specific, multi-focal task related changes in cortical oscillations elicited by active walking. Low γ band power, localized to the prefrontal and posterior parietal cortices, was significantly increased during double support and early swing phases, critical points in the gait cycle since the active controller adjusted speed based on pelvis position and swing foot velocity. These phasic γ band synchronizations provide evidence that prefrontal and posterior parietal networks, previously implicated in visuo-spatial and somotosensory integration, are engaged to enhance lower limb control during gait. Sustained μ and β band desynchronization within sensorimotor cortex, a neural correlate for movement, was observed during walking thereby validating our methods for isolating cortical activity. Our results also demonstrate the utility of EEG recorded during locomotion for probing the multi-regional cortical networks which underpin its execution. For example, the cortical network engagement elicited by the active treadmill suggests that it may enhance neuroplasticity for more effective motor training. PMID:26029077

Effect of continuous theta burst stimulation of the right dorsolateral prefrontal cortex on cerebral blood flow changes during decision making.

PubMed

Cho, Sang Soo; Pellecchia, Giovanna; Ko, Ji Hyun; Ray, Nicola; Obeso, Ignacio; Houle, Sylvain; Strafella, Antonio P

2012-04-01

Decision making is a cognitive function relaying on a complex neural network. In particular, the right dorsolateral prefrontal cortex (DLPFC) plays a key role within this network. We used positron emission tomography (PET) combined with continuous theta burst transcranial magnetic stimulation (cTBS) to investigate neuronal and behavioral changes in normal volunteers while performing a delay discounting (DD) task. We aimed to test whether stimulation of right DLPFC would modify the activation pattern of the neural circuit underlying decision making during the DD task and influence discounting behavior. We found that cTBS of the right DLPFC influenced decision making by reducing impulsivity and inducing participants to favor large but delayed rewards instead of immediate but small rewards. Stimulation also affected activation in several prefrontal areas associated with DD. In particular, we observed a reduced regional cerebral blood flow (rCBF) in the ipsilateral DLPFC (BA 46) extending into the rostral part of the prefrontal cortex (BA 10) as well as a disrupted relationship between impulsivity (k-value) and rCBF in these and other prefrontal areas. These findings suggest that transcranial magnetic stimulation of the DLPFC influences the neural network underlying impulsive decision making behavior. Copyright © 2012 Elsevier Inc. All rights reserved.

Suppressing Emotions Impairs Subsequent Stroop Performance and Reduces Prefrontal Brain Activation

PubMed Central

Luechinger, Roger; Boesiger, Peter; Rasch, Björn

2013-01-01

Abundant behavioral evidence suggests that the ability to self-control is limited, and that any exertion of self-control will increase the likelihood of subsequent self-control failures. Here we investigated the neural correlates underlying the aftereffects of self-control on future control processes using functional magnetic resonance imaging (fMRI). An initial act of self-control (suppressing emotions) impaired subsequent performance in a second task requiring control (Stroop task). On the neural level, increased activity during emotion suppression was followed by a relative decrease in activity during the Stroop task in a cluster in the right lateral prefrontal cortex (PFC) including the dorsolateral prefrontal cortex (DLPFC), an area engaged in the effortful implementation of control. There was no reliable evidence for reduced activity in the medial frontal cortex (MFC) including the anterior cingulate cortex (ACC), which is involved in conflict detection processes and has previously also been implicated in self-control. Follow-up analyses showed that the detected cluster in the right lateral PFC and an area in the MFC were involved in both the emotion suppression task and the Stroop task, but only the cluster in the right lateral PFC showed reduced activation after emotion suppression during the Stroop task. Reduced activity in lateral prefrontal areas relevant for the implementation of control may be a critical consequence of prior self-control exertion if the respective areas are involved in both self-control tasks. PMID:23565239

A Role for Prefrontal Calcium-Sensitive Protein Phosphatase and Kinase Activities in Working Memory

ERIC Educational Resources Information Center

Runyan, Jason D.; Moore, Anthony N.; Dash, Pramod K.

2005-01-01

The prefrontal cortex is involved in the integration and interpretation of information for directing thoughts and planning action. Working memory is defined as the active maintenance of information in mind and is thought to lie at the core of many prefrontal functions. Although dopamine and other neurotransmitters have been implicated, the…

Too Little and Too Much: Hypoactivation and Disinhibition of Medial Prefrontal Cortex Cause Attentional Deficits

PubMed Central

McGarrity, Stephanie; Mason, Rob; Fone, Kevin C.

2014-01-01

Attentional deficits are core symptoms of schizophrenia, contributing strongly to disability. Prefrontal dysfunction has emerged as a candidate mechanism, with clinical evidence for prefrontal hypoactivation and disinhibition (reduced GABAergic inhibition), possibly reflecting different patient subpopulations. Here, we tested in rats whether imbalanced prefrontal neural activity impairs attention. To induce prefrontal hypoactivation or disinhibition, we microinfused the GABA-A receptor agonist muscimol (C4H6N2O2; 62.5, 125, 250 ng/side) or antagonist picrotoxin (C30H34O13; 75, 150, 300 ng/side), respectively, into the medial prefrontal cortex. Using the five-choice serial reaction time (5CSRT) test, we showed that both muscimol and picrotoxin impaired attention (reduced accuracy, increased omissions). Muscimol also impaired response control (increased premature responses). In addition, muscimol dose dependently reduced open-field locomotor activity, whereas 300 ng of picrotoxin caused locomotor hyperactivity; sensorimotor gating (startle prepulse inhibition) was unaffected. Therefore, infusion effects on the 5CSRT test can be dissociated from sensorimotor effects. Combining microinfusions with in vivo electrophysiology, we showed that muscimol inhibited prefrontal firing, whereas picrotoxin increased firing, mainly within bursts. Muscimol reduced and picrotoxin enhanced bursting and both drugs changed the temporal pattern of bursting. Picrotoxin also markedly enhanced prefrontal LFP power. Therefore, prefrontal hypoactivation and disinhibition both cause attentional deficits. Considering the electrophysiological findings, this suggests that attention requires appropriately tuned prefrontal activity. Apart from attentional deficits, prefrontal disinhibition caused additional neurobehavioral changes that may be relevant to schizophrenia pathophysiology, including enhanced prefrontal bursting and locomotor hyperactivity, which have been linked to psychosis

Prefrontal Neural Activity When Feedback Is Not Relevant to Adjust Performance

PubMed Central

Özyurt, Jale; Rietze, Mareike; Thiel, Christiane M.

2012-01-01

It has been shown that the rostral cingulate zone (RCZ) in humans uses both positive and negative feedback to evaluate performance and to flexibly adjust behaviour. Less is known on how the feedback types are processed by the RCZ and other prefrontal brain areas, when feedback can only be used to evaluate performance, but cannot be used to adjust behaviour. The present fMRI study aimed at investigating feedback that can only be used to evaluate performance in a word-learning paradigm. One group of volunteers (N = 17) received informative, performance-dependent positive or negative feedback after each trial. Since new words had to be learnt in each trial, the feedback could not be used for task-specific adaptations. The other group (N = 17) always received non-informative feedback, providing neither information about performance nor about possible task-specific adaptations. Effects of the informational value of feedback were assessed between-subjects, comparing trials with positive and negative informative feedback to non-informative feedback. Effects of feedback valence were assessed by comparing neural activity to positive and negative feedback within the informative-feedback group. Our results show that several prefrontal regions, including the pre-SMA, the inferior frontal cortex and the insula were sensitive to both, the informational value and the valence aspect of the feedback with stronger activations to informative as compared to non-informative feedback and to informative negative compared to informative positive feedback. The only exception was RCZ which was sensitive to the informational value of the feedback, but not to feedback valence. The findings indicate that outcome information per se is sufficient to activate prefrontal brain regions, with the RCZ being the only prefrontal brain region which is equally sensitive to positive and negative feedback. PMID:22615774

Transcriptomic context of DRD1 is associated with prefrontal activity and behavior during working memory.

PubMed

Fazio, Leonardo; Pergola, Giulio; Papalino, Marco; Di Carlo, Pasquale; Monda, Anna; Gelao, Barbara; Amoroso, Nicola; Tangaro, Sabina; Rampino, Antonio; Popolizio, Teresa; Bertolino, Alessandro; Blasi, Giuseppe

2018-05-22

Dopamine D 1 receptor (D 1 R) signaling shapes prefrontal cortex (PFC) activity during working memory (WM). Previous reports found higher WM performance associated with alleles linked to greater expression of the gene coding for D 1 Rs ( DRD1 ). However, there is no evidence on the relationship between genetic modulation of DRD1 expression in PFC and patterns of prefrontal activity during WM. Furthermore, previous studies have not considered that D 1 Rs are part of a coregulated molecular environment, which may contribute to D 1 R-related prefrontal WM processing. Thus, we hypothesized a reciprocal link between a coregulated (i.e., coexpressed) molecular network including DRD1 and PFC activity. To explore this relationship, we used three independent postmortem prefrontal mRNA datasets (total n = 404) to characterize a coexpression network including DRD1 Then, we indexed network coexpression using a measure (polygenic coexpression index- DRD1 -PCI) combining the effect of single nucleotide polymorphisms (SNPs) on coexpression. Finally, we associated the DRD1 -PCI with WM performance and related brain activity in independent samples of healthy participants (total n = 371). We identified and replicated a coexpression network including DRD1 , whose coexpression was correlated with DRD1 -PCI. We also found that DRD1 -PCI was associated with lower PFC activity and higher WM performance. Behavioral and imaging results were replicated in independent samples. These findings suggest that genetically predicted expression of DRD1 and of its coexpression partners stratifies healthy individuals in terms of WM performance and related prefrontal activity. They also highlight genes and SNPs potentially relevant to pharmacological trials aimed to test cognitive enhancers modulating DRD1 signaling.

Prefrontal electroencephalographic activity during the working memory processes involved in a sexually motivated task in male rats.

PubMed

Hernández-González, Marisela; Almanza-Sepúlveda, Mayra Linné; Olvera-Cortés, María Esther; Gutiérrez-Guzmán, Blanca Erika; Guevara, Miguel Angel

2012-08-01

The prefrontal cortex is involved in working memory functions, and several studies using food or drink as rewards have demonstrated that the rat is capable of performing tasks that involve working memory. Sexual activity is another highly-rewarding, motivated behaviour that has proven to be an efficient incentive in classical operant tasks. The objective of this study was to determine whether the functional activity of the medial prefrontal cortex (mPFC) changes in relation to the working memory processes involved in a sexually motivated task performed in male rats. Thus, male Wistar rats implanted in the mPFC were subjected to a nonmatching-to-sample task in a T-maze using sexual interaction as a reinforcer during a 4-day training period. On the basis of their performance during training, the rats were classified as 'good-learners' or 'bad-learners'. Only the good-learner rats showed an increase in the absolute power of the 8-13 Hz band during both the sample and test runs; a finding that could be related to learning of the working memory elements entailed in the task. During the maintenance phase only (i.e., once the rule had been learned well), the good-learner rats also showed an increased correlation of the 8-13 Hz band during the sample run, indicating that a high degree of coupling between the prefrontal cortices is necessary for the processing required to allow the rats to make correct decisions in the maintenance phase. Taken together, these data show that mPFC activity changes in relation to the working memory processes involved in a sexually motivated task in male rats.

Developmental Differences in Prefrontal Activation during Working Memory Maintenance and Manipulation for Different Memory Loads

ERIC Educational Resources Information Center

Jolles, Dietsje D.; Kleibeuker, Sietske W.; Rombouts, Serge A. R. B.; Crone, Eveline A.

2011-01-01

The ability to keep information active in working memory is one of the cornerstones of cognitive development. Prior studies have demonstrated that regions which are important for working memory performance in adults, such as dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC), and superior parietal cortex, become…

Improved Prefrontal Activity and Chewing Performance as Function of Wearing Denture in Partially Edentulous Elderly Individuals: Functional Near-Infrared Spectroscopy Study

PubMed Central

Kamiya, Kazunobu; Narita, Noriyuki; Iwaki, Sunao

2016-01-01

The purpose of this study was to elucidate the effects of wearing a denture on prefrontal activity during chewing performance. We specifically examined that activity in 12 elderly edentulous subjects [63.1±6.1 years old (mean ± SD)] and 12 young healthy controls (22.1±2.3 years old) using functional near-infrared spectroscopy (fNIRS) in order to evaluate the quality of prefrontal functionality during chewing performance under the conditions of wearing a denture and tooth loss, and then compared the findings with those of young healthy controls. fNIRS and electromyography were used simultaneously to detect prefrontal and masticatory muscle activities during chewing, while occlusal force and masticatory score were also examined by use of a food intake questionnaire. A significant increase in prefrontal activity was observed during chewing while wearing a denture, which was accompanied by increased masticatory muscle activity, occlusal force, and masticatory score, as compared with the tooth loss condition. Prefrontal activation during chewing while wearing a denture in the elderly subjects was not much different from that in the young controls. In contrast, tooth loss in the elderly group resulted in marked prefrontal deactivation, accompanied by decreased masticatory muscle activity, occlusal force, and masticatory score, as compared with the young controls. We concluded that intrinsic prefrontal activation during chewing with a denture may prevent prefrontal depression induced by tooth loss in elderly edentulous patients. PMID:27362255

Theta Synchronizes the Activity of Medial Prefrontal Neurons during Learning

ERIC Educational Resources Information Center

Paz, Rony; Bauer, Elizabeth P.; Pare, Denis

2008-01-01

Memory consolidation is thought to involve the gradual transfer of transient hippocampal-dependent traces to distributed neocortical sites via the rhinal cortices. Recently, medial prefrontal (mPFC) neurons were shown to facilitate this process when their activity becomes synchronized. However, the mechanisms underlying this enhanced synchrony…

Prefrontal Hemodynamics of Physical Activity and Environmental Complexity During Cognitive Work.

PubMed

McKendrick, Ryan; Mehta, Ranjana; Ayaz, Hasan; Scheldrup, Melissa; Parasuraman, Raja

2017-02-01

The aim of this study was to assess performance and cognitive states during cognitive work in the presence of physical work and in natural settings. Authors of previous studies have examined the interaction between cognitive and physical work, finding performance decrements in working memory. Neuroimaging has revealed increases and decreases in prefrontal oxygenated hemoglobin during the interaction of cognitive and physical work. The effect of environment on cognitive-physical dual tasking has not been previously considered. Thirteen participants were monitored with wireless functional near-infrared spectroscopy (fNIRS) as they performed an auditory 1-back task while sitting, walking indoors, and walking outdoors. Relative to sitting and walking indoors, auditory working memory performance declined when participants were walking outdoors. Sitting during the auditory 1-back task increased oxygenated hemoglobin and decreased deoxygenated hemoglobin in bilateral prefrontal cortex. Walking reduced the total hemoglobin available to bilateral prefrontal cortex. An increase in environmental complexity reduced oxygenated hemoglobin and increased deoxygenated hemoglobin in bilateral prefrontal cortex. Wireless fNIRS is capable of monitoring cognitive states in naturalistic environments. Selective attention and physical work compete with executive processing. During executive processing loading of selective attention and physical work results in deactivation of bilateral prefrontal cortex and degraded working memory performance, indicating that physical work and concomitant selective attention may supersede executive processing in the distribution of mental resources. This research informs decision-making procedures in work where working memory, physical activity, and attention interact. Where working memory is paramount, precautions should be taken to eliminate competition from physical work and selective attention.

When giving is good: Ventromedial prefrontal cortex activation for others’ intentions

PubMed Central

Cooper, Jeffrey C.; Kreps, Tamar A.; Wiebe, Taylor; Pirkl, Tristana; Knutson, Brian

2010-01-01

Summary In social decision-making, people care both about others’ outcomes and their intentions to help or harm. How the brain integrates representations of others’ intentions with their outcomes, however, is unknown. In this study, participants inferred others’ decisions in an economic game during functional magnetic resonance imaging. When the game was described in terms of donations, ventromedial prefrontal cortex (VMPFC) activation increased for inferring generous play and decreased for inferring selfish play. When the game was described in terms of individual savings, however, VMPFC activation did not distinguish between strategies. Distinct medial prefrontal regions also encoded consistency with situational norms. A separate network, including right temporoparietal junction and parahippocampal gyrus, was more activated for inferential errors in the donation than in the savings condition. These results for the first time demonstrate that neural responses to others’ generosity or selfishness depend not only on their actions but also on their perceived intentions. PMID:20696386

Distraction decreases prefrontal oxygenation: A NIRS study.

PubMed

Ozawa, Sachiyo; Hiraki, Kazuo

2017-04-01

When near-infrared spectroscopy (NIRS) is used to measure emotion-related cerebral blood flow (CBF) changes in the prefrontal cortex regions, the functional distinction of CBF changes is often difficult because NIRS is unable to measure neural activity in deeper brain regions that play major roles in emotional processing. The CBF changes could represent cognitive control of emotion and emotional responses to emotional materials. Supposing that emotion-related CBF changes in the prefrontal cortex regions during distraction are emotional responses, we examined whether oxygenated hemoglobin (oxyHb) decreases. Attention-demanding tasks cause blood flow decreases, and we thus compared the effects of visually paced tapping with different tempos, on distraction. The results showed that the oxyHb level induced by emotional stimulation decreased with fast-tempo tapping significantly more than slow-tempo tapping in ventral medial prefrontal cortex regions. Moreover, a Global-Local task following tapping showed significantly greater local-minus-global response time (RT) difference scores in the fast- and mid-tempo condition compared with those in the slow-tempo, suggesting an increased attentional focus, and decreased negative emotion. The overall findings indicate that oxyHb changes in a relatively long distraction task, as measured by NIRS, are associated with emotional responses, and oxyHb can be decreased by successfully performing attention-demanding distraction tasks. Copyright © 2017 Elsevier Inc. All rights reserved.

Brain activation during fast driving in a driving simulator: the role of the lateral prefrontal cortex.

PubMed

Jäncke, Lutz; Brunner, Béatrice; Esslen, Michaela

2008-07-16

Little is currently known about the neural underpinnings of the cognitive control of driving behavior in realistic situations and of the driver's speeding behavior in particular. In this study, participants drove in realistic scenarios presented in a high-end driving simulator. Scalp-recorded EEG oscillations in the alpha-band (8-13 Hz) with a 30-electrode montage were recorded while the participants drove under different conditions: (i) excessively fast (Fast), (ii) in a controlled manner at a safe speed (Correct), and (iii) impatiently in the context of testing traffic conditions (Impatient). Intracerebral sources of alpha-band activation were estimated using low resolution electrical tomography. Given that previous studies have shown a strong negative correlation between the Bold response in the frontal cortex and the alpha-band power, we used alpha-band-related activity as an estimation of frontal activation. Statistical analysis revealed more alpha-band-related activity (i.e. less neuronal activation) in the right lateral prefrontal cortex, including the dorsolateral prefrontal cortex, during fast driving. Those participants who speeded most and exhibited greater risk-taking behavior demonstrated stronger alpha-related activity (i.e. less neuronal activation) in the left anterior lateral prefrontal cortex. These findings are discussed in the context of current theories about the role of the lateral prefrontal cortex in controlling risk-taking behavior, task switching, and multitasking.

Altered prefrontal brain activity in persons at risk for Alzheimer's disease: an fMRI study.

PubMed

Elgh, Eva; Larsson, Anne; Eriksson, Sture; Nyberg, Lars

2003-06-01

Early diagnosis of Alzheimer's disease (AD) is critical for adequate treatment and care. Recently it has been shown that functional magnetic resonance imaging (fMRI) can be important in preclinical detection of AD. The purpose of this study was to examine possible differences in memory-related brain activation between persons with high versus low risk for AD. This was achieved by combining a validated neurocognitive screening battery (the 7-minutes test) with memory assessment and fMRI. One hundred two healthy community-living persons with subjective memory complaints were recruited through advertisement and tested with the 7-minutes test. Based on their test performance they were classified as having either high (n = 8) or low risk (n = 94) for AD. Six high-risk individuals and six age-, sex-, and education-matched low-risk individuals were investigated with fMRI while engaged in episodic memory tasks. The high-risk individuals performed worse than low-risk individuals on tests of episodic memory. Patterns of brain activity during episodic encoding and retrieval showed significant group differences (p < .05 corrected). During both encoding and retrieval, the low-risk persons showed increased activity relative to a baseline condition in prefrontal brain regions that previously have been implicated in episodic memory. By contrast, the high-risk persons did not significantly activate any prefrontal regions, but instead showed increased activity in visual occipito-temporal regions. Patterns of prefrontal brain activity related to episodic memory differ between persons with high versus low risk for AD, and lowered prefrontal activity may predict subsequent disease.

Noradrenergic blockade stabilizes prefrontal activity and enables fear extinction under stress

PubMed Central

Fitzgerald, Paul J.; Giustino, Thomas F.; Seemann, Jocelyn R.; Maren, Stephen

2015-01-01

Stress-induced impairments in extinction learning are believed to sustain posttraumatic stress disorder (PTSD). Noradrenergic signaling may contribute to extinction impairments by modulating medial prefrontal cortex (mPFC) circuits involved in fear regulation. Here we demonstrate that aversive fear conditioning rapidly and persistently alters spontaneous single-unit activity in the prelimbic and infralimbic subdivisions of the mPFC in behaving rats. These conditioning-induced changes in mPFC firing were mitigated by systemic administration of propranolol (10 mg/kg, i.p.), a β-noradrenergic receptor antagonist. Moreover, propranolol administration dampened the stress-induced impairment in extinction observed when extinction training is delivered shortly after fear conditioning. These findings suggest that β-adrenoceptors mediate stress-induced changes in mPFC spike firing that contribute to extinction impairments. Propranolol may be a helpful adjunct to behavioral therapy for PTSD, particularly in patients who have recently experienced trauma. PMID:26124100

Dynamic ErbB4 Activity in Hippocampal-Prefrontal Synchrony and Top-Down Attention in Rodents.

PubMed

Tan, Zhibing; Robinson, Heath L; Yin, Dong-Min; Liu, Yu; Liu, Fang; Wang, Hongsheng; Lin, Thiri W; Xing, Guanglin; Gan, Lin; Xiong, Wen-Cheng; Mei, Lin

2018-04-18

Top-down attention is crucial for meaningful behaviors and impaired in various mental disorders. However, its underpinning regulatory mechanisms are poorly understood. We demonstrate that the hippocampal-prefrontal synchrony associates with levels of top-down attention. Both attention and synchrony are reduced in mutant mice of ErbB4, a receptor of neuregulin-1. We used chemical genetic and optogenetic approaches to inactivate ErbB4 kinase and ErbB4+ interneurons, respectively, both of which reduce gamma-aminobutyric acid (GABA) activity. Such inhibitions in the hippocampus impair both hippocampal-prefrontal synchrony and top-down attention, whereas those in the prefrontal cortex alter attention, but not synchrony. These observations identify a role of ErbB4-dependent GABA activity in the hippocampus in synchronizing the hippocampal-prefrontal pathway and demonstrate that acute, dynamic ErbB4 signaling is required to command top-down attention. Because both neuregulin-1 and ErbB4 are susceptibility genes of schizophrenia and major depression, our study contributes to a better understanding of these disorders. VIDEO ABSTRACT. Copyright © 2018 Elsevier Inc. All rights reserved.

Modulating activity in the prefrontal cortex changes decision-making for risky gains and losses: a transcranial direct current stimulation study.

PubMed

Ye, Hang; Chen, Shu; Huang, Daqiang; Wang, Siqi; Luo, Jun

2015-06-01

When making choices under uncertainty, people usually consider both the risks and benefits of each option. Previous studies have found that weighing of risks and benefits during decision-making involves a complex neural network that includes the dorsolateral prefrontal cortex (DLPFC), but the causal effect of this network on risk decision-making has remained unclear. This experiment was based on a risk-measurement table designed to provide a direct measure of risk preference, with a weighted value of the choices (denoted as weighted risk aversion, WRA) as an index of the participant's degree of risk aversion. We studied whether bifrontal transcranial direct current stimulation (tDCS) applied over the right and left prefrontal cortex can change the balance of risky vs. safe responses under both gain frame and loss frame. A total of 60 volunteers performed risk tasks while receiving either anodal over the right with cathodal over the left DLPFC, anodal over the left with cathodal over the right DLPFC, or sham stimulation. The participants tended to choose more risky options in the gain frame and more safe options in the loss frame after the right anodal/left cathodal tDCS. We also found that right anodal/left cathodal tDCS significantly decreased the WRA values compared with those associated with sham stimulation. These findings extend the notion that DLPFC activity is critical for risk decision-making, indicating an asymmetric role of the right DLPFC in the gain frame vs. the loss frame of risk decision-making. Copyright © 2015 Elsevier B.V. All rights reserved.

Prefrontal Activity and Connectivity with the Basal Ganglia during Performance of Complex Cognitive Tasks Is Associated with Apathy in Healthy Subjects.

PubMed

Fazio, Leonardo; Logroscino, Giancarlo; Taurisano, Paolo; Amico, Graziella; Quarto, Tiziana; Antonucci, Linda Antonella; Barulli, Maria Rosaria; Mancini, Marina; Gelao, Barbara; Ferranti, Laura; Popolizio, Teresa; Bertolino, Alessandro; Blasi, Giuseppe

2016-01-01

Convergent evidence indicates that apathy affects cognitive behavior in different neurological and psychiatric conditions. Studies of clinical populations have also suggested the primary involvement of the prefrontal cortex and the basal ganglia in apathy. These brain regions are interconnected at both the structural and functional levels and are deeply involved in cognitive processes, such as working memory and attention. However, it is unclear how apathy modulates brain processing during cognition and whether such a modulation occurs in healthy young subjects. To address this issue, we investigated the link between apathy and prefrontal and basal ganglia function in healthy young individuals. We hypothesized that apathy may be related to sub-optimal activity and connectivity in these brain regions. Three hundred eleven healthy subjects completed an apathy assessment using the Starkstein's Apathy Scale and underwent fMRI during working memory and attentional performance tasks. Using an ROI approach, we investigated the association of apathy with activity and connectivity in the DLPFC and the basal ganglia. Apathy scores correlated positively with prefrontal activity and negatively with prefrontal-basal ganglia connectivity during both working memory and attention tasks. Furthermore, prefrontal activity was inversely related to attentional behavior. These results suggest that in healthy young subjects, apathy is a trait associated with inefficient cognitive-related prefrontal activity, i.e., it increases the need for prefrontal resources to process cognitive stimuli. Furthermore, apathy may alter the functional relationship between the prefrontal cortex and the basal ganglia during cognition.

MRI volumetry of prefrontal cortex

NASA Astrophysics Data System (ADS)

Sheline, Yvette I.; Black, Kevin J.; Lin, Daniel Y.; Pimmel, Joseph; Wang, Po; Haller, John W.; Csernansky, John G.; Gado, Mokhtar; Walkup, Ronald K.; Brunsden, Barry S.; Vannier, Michael W.

1995-05-01

Prefrontal cortex volumetry by brain magnetic resonance (MR) is required to estimate changes postulated to occur in certain psychiatric and neurologic disorders. A semiautomated method with quantitative characterization of its performance is sought to reliably distinguish small prefrontal cortex volume changes within individuals and between groups. Stereological methods were tested by a blinded comparison of measurements applied to 3D MR scans obtained using an MPRAGE protocol. Fixed grid stereologic methods were used to estimate prefrontal cortex volumes on a graphic workstation, after the images are scaled from 16 to 8 bits using a histogram method. In addition images were resliced into coronal sections perpendicular to the bicommissural plane. Prefrontal cortex volumes were defined as all sections of the frontal lobe anterior to the anterior commissure. Ventricular volumes were excluded. Stereological measurement yielded high repeatability and precision, and was time efficient for the raters. The coefficient of error was prefrontal cortex boundaries on 3D images was critical to obtaining accurate measurements. MR prefrontal cortex volumetry by stereology can yield accurate and repeatable measurements. Small frontal lobe volume reductions in patients with brain disorders such as depression and schizophrenia can be efficiently assessed using this method.

Stress-related methylation of the catechol-O-methyltransferase Val 158 allele predicts human prefrontal cognition and activity.

PubMed

Ursini, Gianluca; Bollati, Valentina; Fazio, Leonardo; Porcelli, Annamaria; Iacovelli, Luisa; Catalani, Assia; Sinibaldi, Lorenzo; Gelao, Barbara; Romano, Raffaella; Rampino, Antonio; Taurisano, Paolo; Mancini, Marina; Di Giorgio, Annabella; Popolizio, Teresa; Baccarelli, Andrea; De Blasi, Antonio; Blasi, Giuseppe; Bertolino, Alessandro

2011-05-04

DNA methylation at CpG dinucleotides is associated with gene silencing, stress, and memory. The catechol-O-methyltransferase (COMT) Val(158) allele in rs4680 is associated with differential enzyme activity, stress responsivity, and prefrontal activity during working memory (WM), and it creates a CpG dinucleotide. We report that methylation of the Val(158) allele measured from peripheral blood mononuclear cells (PBMCs) of Val/Val humans is associated negatively with lifetime stress and positively with WM performance; it interacts with stress to modulate prefrontal activity during WM, such that greater stress and lower methylation are related to reduced cortical efficiency; and it is inversely related to mRNA expression and protein levels, potentially explaining the in vivo effects. Finally, methylation of COMT in prefrontal cortex and that in PBMCs of rats are correlated. The relationship of methylation of the COMT Val(158) allele with stress, gene expression, WM performance, and related brain activity suggests that stress-related methylation is associated with silencing of the gene, which partially compensates the physiological role of the high-activity Val allele in prefrontal cognition and activity. Moreover, these results demonstrate how stress-related DNA methylation of specific functional alleles impacts directly on human brain physiology beyond sequence variation.

Making sense: Dopamine activates conscious self‐monitoring through medial prefrontal cortex

PubMed Central

Joensson, Morten; Thomsen, Kristine Rømer; Andersen, Lau M.; Gross, Joachim; Mouridsen, Kim; Sandberg, Kristian; Østergaard, Leif

2015-01-01

Abstract When experiences become meaningful to the self, they are linked to synchronous activity in a paralimbic network of self‐awareness and dopaminergic activity. This network includes medial prefrontal and medial parietal/posterior cingulate cortices, where transcranial magnetic stimulation may transiently impair self‐awareness. Conversely, we hypothesize that dopaminergic stimulation may improve self‐awareness and metacognition (i.e., the ability of the brain to consciously monitor its own cognitive processes). Here, we demonstrate improved noetic (conscious) metacognition by oral administration of 100 mg dopamine in minimal self‐awareness. In a separate experiment with extended self‐awareness dopamine improved the retrieval accuracy of memories of self‐judgment (autonoetic, i.e., explicitly self‐conscious) metacognition. Concomitantly, magnetoencephalography (MEG) showed increased amplitudes of oscillations (power) preferentially in the medial prefrontal cortex. Given that electromagnetic activity in this region is instrumental in self‐awareness, this explains the specific effect of dopamine on explicit self‐awareness and autonoetic metacognition. Hum Brain Mapp 36:1866–1877, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.. PMID:25627861

Plasticity in the prefrontal cortex of adult rats

PubMed Central

Kolb, Bryan; Gibb, Robbin

2015-01-01

We review the plastic changes of the prefrontal cortex of the rat in response to a wide range of experiences including sensory and motor experience, gonadal hormones, psychoactive drugs, learning tasks, stress, social experience, metaplastic experiences, and brain injury. Our focus is on synaptic changes (dendritic morphology and spine density) in pyramidal neurons and the relationship to behavioral changes. The most general conclusion we can reach is that the prefrontal cortex is extremely plastic and that the medial and orbital prefrontal regions frequently respond very differently to the same experience in the same brain and the rules that govern prefrontal plasticity appear to differ for those of other cortical regions. PMID:25691857

Functional Genetic Variation in Dopamine Signaling Moderates Prefrontal Cortical Activity During Risky Decision Making.

PubMed

Kohno, Milky; Nurmi, Erika L; Laughlin, Christopher P; Morales, Angelica M; Gail, Emma H; Hellemann, Gerhard S; London, Edythe D

2016-02-01

Brain imaging has revealed links between prefrontal activity during risky decision-making and striatal dopamine receptors. Specifically, striatal dopamine D2-like receptor availability is correlated with risk-taking behavior and sensitivity of prefrontal activation to risk in the Balloon Analogue Risk Task (BART). The extent to which these associations, involving a single neurochemical measure, reflect more general effects of dopaminergic functioning on risky decision making, however, is unknown. Here, 65 healthy participants provided genotypes and performed the BART during functional magnetic resonance imaging. For each participant, dopamine function was assessed using a gene composite score combining known functional variation across five genes involved in dopaminergic signaling: DRD2, DRD3, DRD4, DAT1, and COMT. The gene composite score was negatively related to dorsolateral prefrontal cortical function during risky decision making, and nonlinearly related to earnings on the task. Iterative permutations of all possible allelic variations (7777 allelic combinations) was tested on brain function in an independently defined region of the prefrontal cortex and confirmed empirical validity of the composite score, which yielded stronger association than 95% of all other possible combinations. The gene composite score also accounted for a greater proportion of variability in neural and behavioral measures than the independent effects of each gene variant, indicating that the combined effects of functional dopamine pathway genes can provide a robust assessment, presumably reflecting the cumulative and potentially interactive effects on brain function. Our findings support the view that the links between dopaminergic signaling, prefrontal function, and decision making vary as a function of dopamine signaling capacity.

Prefrontal Activity and Connectivity with the Basal Ganglia during Performance of Complex Cognitive Tasks Is Associated with Apathy in Healthy Subjects

PubMed Central

Fazio, Leonardo; Logroscino, Giancarlo; Taurisano, Paolo; Amico, Graziella; Quarto, Tiziana; Antonucci, Linda Antonella; Barulli, Maria Rosaria; Mancini, Marina; Gelao, Barbara; Ferranti, Laura; Popolizio, Teresa; Bertolino, Alessandro; Blasi, Giuseppe

2016-01-01

Objective Convergent evidence indicates that apathy affects cognitive behavior in different neurological and psychiatric conditions. Studies of clinical populations have also suggested the primary involvement of the prefrontal cortex and the basal ganglia in apathy. These brain regions are interconnected at both the structural and functional levels and are deeply involved in cognitive processes, such as working memory and attention. However, it is unclear how apathy modulates brain processing during cognition and whether such a modulation occurs in healthy young subjects. To address this issue, we investigated the link between apathy and prefrontal and basal ganglia function in healthy young individuals. We hypothesized that apathy may be related to sub-optimal activity and connectivity in these brain regions. Methods Three hundred eleven healthy subjects completed an apathy assessment using the Starkstein’s Apathy Scale and underwent fMRI during working memory and attentional performance tasks. Using an ROI approach, we investigated the association of apathy with activity and connectivity in the DLPFC and the basal ganglia. Results Apathy scores correlated positively with prefrontal activity and negatively with prefrontal-basal ganglia connectivity during both working memory and attention tasks. Furthermore, prefrontal activity was inversely related to attentional behavior. Conclusions These results suggest that in healthy young subjects, apathy is a trait associated with inefficient cognitive-related prefrontal activity, i.e., it increases the need for prefrontal resources to process cognitive stimuli. Furthermore, apathy may alter the functional relationship between the prefrontal cortex and the basal ganglia during cognition. PMID:27798669

Combined effect of prefrontal transcranial direct current stimulation and a working memory task on heart rate variability

PubMed Central

Boonstra, Tjeerd W.; Loo, Colleen K.; Martin, Donel

2017-01-01

Prefrontal cortex activity has been associated with changes to heart rate variability (HRV) via mediation of the cortico-subcortical pathways that regulate the parasympathetic and sympathetic branches of the autonomic nervous system. Changes in HRV due to altered prefrontal cortex functioning can be predicted using the neurovisceral integration model, which suggests that prefrontal hyperactivity increases parasympathetic tone and decreases contributions from the sympathetic nervous system. Working memory (WM) tasks and transcranial direct current stimulation (tDCS) have been used independently to modulate brain activity demonstrating changes to HRV in agreement with the model. We investigated the combined effects of prefrontal tDCS and a WM task on HRV. Bifrontal tDCS was administered for 15 minutes at 2mA to 20 participants in a sham controlled, single-blind study using parallel groups. A WM task was completed by participants at three time points; pre-, during-, and post-tDCS, with resting state data collected at similar times. Frequency-domain HRV was computed for high frequency (HF; 0.15–0.4Hz) and low frequency (LF; 0.04–0.15Hz) power reflecting parasympathetic and sympathetic branch activity, respectively. Response time on the WM task, but not accuracy, improved from baseline to during-tDCS and post-tDCS with sham, but not active, stimulation. HF-HRV was significantly increased in the active tDCS group compared to sham, lasting beyond cessation of stimulation. Additionally, HF-HRV showed a task-related reduction in power during performance on the WM task. Changes in LF-HRV were moderately inversely correlated (r > 0.4) with changes in WM accuracy during and following tDCS compared to baseline levels. Stimulation of the prefrontal cortex resulted in changes to the parasympathetic branch of the nervous system in agreement with a linearly additive interpretation of effects. Sympathetic activity was not directly altered by tDCS, but was correlated with changes

Diagnosis of occlusal dysesthesia utilizing prefrontal hemodynamic activity with slight occlusal interference.

PubMed

Ono, Yumie; Ishikawa, Yu; Munakata, Motohiro; Shibuya, Tomoaki; Shimada, Atsushi; Miyachi, Hideo; Wake, Hiroyuki; Tamaki, Katsushi

2016-11-01

Clinical diagnosis of occlusal dysesthesia (OD), also referred to as phantom bite syndrome, is currently based on the absence of objective occlusal discrepancy despite the persistent complaint of uncomfortable bite sensation. We previously demonstrated that the subjective feeling of occlusal discomfort generated by artificial occlusal interference can be objectively evaluated using prefrontal hemodynamic activity in young healthy individuals. The aim of this study was to investigate whether dental patients with and without OD show distinct prefrontal activity during grinding behavior with an occlusal interference. Six dental patients with OD (OD group) and eight patients without OD (control group) grinded piled occlusal strips placed between their first molars and reported their perception and discomfort thresholds during continuous monitoring of prefrontal hemodynamic activity with a portable functional near-infrared spectroscopy. Although patients without OD showed the typical hemodynamic pattern of increased oxyhemoglobin and reduced deoxyhemoglobin (HHb) concentration, those with OD showed persistent incremental increases of HHb concentration that began at the loading of occlusal strips on their molars before they executed grinding. The intensities of the task-related HHb activities showed statistically significant differences between OD and control groups, particularly at channel 3, arranged over the left frontal pole cortex. When the discrimination criterion was set using the intensity values of channel 3 from both groups, the overall accuracy of the OD discrimination was 92.9%. Although physiological interpretation has yet to be elucidated, the task-related response of an increase in HHb may be a useful neuronal signature to characterize dental patients with OD.

Diagnosis of occlusal dysesthesia utilizing prefrontal hemodynamic activity with slight occlusal interference

PubMed Central

Ishikawa, Yu; Munakata, Motohiro; Shibuya, Tomoaki; Shimada, Atsushi; Miyachi, Hideo; Wake, Hiroyuki; Tamaki, Katsushi

2016-01-01

Clinical diagnosis of occlusal dysesthesia (OD), also referred to as phantom bite syndrome, is currently based on the absence of objective occlusal discrepancy despite the persistent complaint of uncomfortable bite sensation. We previously demonstrated that the subjective feeling of occlusal discomfort generated by artificial occlusal interference can be objectively evaluated using prefrontal hemodynamic activity in young healthy individuals. The aim of this study was to investigate whether dental patients with and without OD show distinct prefrontal activity during grinding behavior with an occlusal interference. Six dental patients with OD (OD group) and eight patients without OD (control group) grinded piled occlusal strips placed between their first molars and reported their perception and discomfort thresholds during continuous monitoring of prefrontal hemodynamic activity with a portable functional near‐infrared spectroscopy. Although patients without OD showed the typical hemodynamic pattern of increased oxyhemoglobin and reduced deoxyhemoglobin (HHb) concentration, those with OD showed persistent incremental increases of HHb concentration that began at the loading of occlusal strips on their molars before they executed grinding. The intensities of the task‐related HHb activities showed statistically significant differences between OD and control groups, particularly at channel 3, arranged over the left frontal pole cortex. When the discrimination criterion was set using the intensity values of channel 3 from both groups, the overall accuracy of the OD discrimination was 92.9%. Although physiological interpretation has yet to be elucidated, the task‐related response of an increase in HHb may be a useful neuronal signature to characterize dental patients with OD. PMID:29744159

Cognitive behavioral therapy changes functional connectivity between medial prefrontal and anterior cingulate cortices.

PubMed

Yoshimura, Shinpei; Okamoto, Yasumasa; Matsunaga, Miki; Onoda, Keiichi; Okada, Go; Kunisato, Yoshihiko; Yoshino, Atsuo; Ueda, Kazutaka; Suzuki, Shin-Ichi; Yamawaki, Shigeto

2017-01-15

Depression is characterized by negative self-cognition. Our previous study (Yoshimura et al. 2014) revealed changes in brain activity after cognitive behavioral therapy (CBT) for depression, but changes in functional connectivity were not assessed. This study included 29 depressive patients and 15 healthy control participants. Functional Magnetic Resonance Imaging was used to investigate possible CBT-related functional connectivity changes associated with negative emotional self-referential processing. Depressed and healthy participants (overlapping with our previous study, Yoshimura et al. 2014) were included. We defined a seed region (medial prefrontal cortex) and coupled region (ACC) based on our previous study, and we examined changes in MPFC-ACC functional connectivity from pretreatment to posttreatment. CBT was associated with reduced functional connectivity between the MPFC and ACC. Symptom change with CBT was positively correlated with change in MPFC-ACC functional connectivity. Patients received pharmacotherapy including antidepressant. The present sample size was quite small and more study is needed. Statistical threshold in fMRI analysis was relatively liberal. CBT for depression may disrupt MPFC-ACC connectivity, with associated improvements in depressive symptoms and dysfunctional cognition. Copyright © 2016 Elsevier B.V. All rights reserved.

Increased prefrontal hemodynamic change after atomoxetine administration in pediatric attention-deficit/hyperactivity disorder as measured by near-infrared spectroscopy.

PubMed

Ota, Toyosaku; Iida, Junzo; Nakanishi, Yoko; Sawada, Satomi; Matsuura, Hiroki; Yamamuro, Kazuhiko; Ueda, Shotaro; Uratani, Mitsuhiro; Kishimoto, Naoko; Negoro, Hideki; Kishimoto, Toshifumi

2015-03-01

Atomoxetine, approved in Japan for the treatment of pediatric attention-deficit/hyperactivity disorder (ADHD) in April 2009, is a nonstimulant that is thought to act presynaptically via the inhibition of norepinephrine reuptake. Near-infrared spectroscopy is a non-invasive optical tool that can be used to study oxygenation and hemodynamic changes in the cerebral cortex. The present study examined the effects of a clinical dose of atomoxetine on changes in prefrontal hemodynamic activity in children with ADHD, as measured by near-infrared spectroscopy using the Stroop Color-Word Task. Ten children with ADHD participated in the present study. We used 24-channel near-infrared spectroscopy to measure the relative concentrations of oxyhemoglobin in the frontal lobes of participants in the drug-naïve condition and those who had received atomoxetine for 8 weeks. Measurements were conducted every 0.1 s during the Stroop Color-Word Task. We used the ADHD Rating Scale-IV-Japanese version (Home Version) to evaluate ADHD symptoms. We found a significant decrease in ADHD Rating Scale-IV-Japanese version scores, from 30.7 to 22.6 (P=0.003). During the Stroop Color-Word Task, we found significantly higher levels of oxyhemoglobin changes in the prefrontal cortex of participants in the atomoxetine condition compared with those in the drug-naïve condition. This increase in oxyhemoglobin changes might indicate an intensified prefrontal hemodynamic response induced by atomoxetine. Near-infrared spectroscopy is a sensitive tool for measuring the pharmacological effects of atomoxetine in children with ADHD. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

Control of Intermale Aggression by Medial Prefrontal Cortex Activation in the Mouse

PubMed Central

Takahashi, Aki; Nagayasu, Kazuki; Nishitani, Naoya; Kaneko, Shuji; Koide, Tsuyoshi

2014-01-01

Aggressive behavior is widely observed throughout the animal kingdom because of its adaptiveness for social animals. However, when aggressive behavior exceeds the species-typical level, it is no longer adaptive, so there should be a mechanism to control excessive aggression to keep it within the adaptive range. Using optogenetics, we demonstrate that activation of excitatory neurons in the medial prefrontal cortex (mPFC), but not the orbitofrontal cortex (OFC), inhibits inter-male aggression in mice. At the same time, optogenetic silencing of mPFC neurons causes an escalation of aggressive behavior both quantitatively and qualitatively. Activation of the mPFC suppresses aggressive bursts and reduces the intensity of aggressive behavior, but does not change the duration of the aggressive bursts. Our findings suggest that mPFC activity has an inhibitory role in the initiation and execution, but not the termination, of aggressive behavior, and maintains such behavior within the adaptive range. PMID:24740241

Cognitive and metacognitive activity in mathematical problem solving: prefrontal and parietal patterns.

PubMed

Anderson, John R; Betts, Shawn; Ferris, Jennifer L; Fincham, Jon M

2011-03-01

Students were taught an algorithm for solving a new class of mathematical problems. Occasionally in the sequence of problems, they encountered exception problems that required that they extend the algorithm. Regular and exception problems were associated with different patterns of brain activation. Some regions showed a Cognitive pattern of being active only until the problem was solved and no difference between regular or exception problems. Other regions showed a Metacognitive pattern of greater activity for exception problems and activity that extended into the post-solution period, particularly when an error was made. The Cognitive regions included some of parietal and prefrontal regions associated with the triple-code theory of (Dehaene, S., Piazza, M., Pinel, P., & Cohen, L. (2003). Three parietal circuits for number processing. Cognitive Neuropsychology, 20, 487-506) and associated with algebra equation solving in the ACT-R theory (Anderson, J. R. (2005). Human symbol manipulation within an 911 integrated cognitive architecture. Cognitive science, 29, 313-342. Metacognitive regions included the superior prefrontal gyrus, the angular gyrus of the triple-code theory, and frontopolar regions.

Maternal prefrontal cortex activation by newborn infant odors.

PubMed

Nishitani, Shota; Kuwamoto, Saori; Takahira, Asuka; Miyamura, Tsunetake; Shinohara, Kazuyuki

2014-03-01

Mothers are attracted by infant cues of a variety of different modalities. To clarify the possible neural mechanisms underlying maternal attraction to infant odor cues, we used near-infrared spectroscopy to examine prefrontal cortex (PFC) activity during odor detection tasks in which 19 mothers and 19 nulliparous females (nonmothers) were presented with infant or adult male odors. They were instructed to make a judgment about whether they smelled an odor during each task. We estimated the PFC activity by measuring the relative oxyhemoglobin (oxyHb) concentrations. The results showed that while detecting the infant odors, bilateral PFC activities were increased in mothers but not in nonmothers. In contrast, adult male odors activated the PFC similarly in mothers and nonmothers. These findings suggest that maternal activation of the PFC in response to infant odors explains a part of the neural mechanisms for maternal attraction to infant odors.

Prefrontal EEG correlation during Tower of Hanoi and WCST performance: effect of emotional visual stimuli.

PubMed

Ruiz-Díaz, Marina; Hernández-González, Marisela; Guevara, Miguel Angel; Amezcua, Claudia; Ågmo, Anders

2012-10-01

Emotional stimuli elicit changes in the electroencephalographic (EEG) activity of several brain structures. Prefrontal cortex is involved in the processing of emotional stimuli and executive functions. The correlation analysis of EEG provides information about the functional coupling between areas. It is reasonable to expect that emotional activation will modify prefrontal coupling during the performance of executive tasks such as Tower of Hanoi or Wisconsin Card Sorting Test (WCST). Determine whether the prefrontal EEG correlation during the performance of the Tower of Hanoi and WCST is affected by previous exposure to videos with sexual or aggressive content. Prefrontal EEG coupling was determined by the Pearson correlation. Valence and general arousal were evaluated by the Self-Assessment Manikin Scale and sexual arousal with a Sexual Arousal Scale. Computerized versions of the Towers of Hanoi and WCST provided data on prefrontal executive functions. EEG from the left and right prefrontal zones was recorded during the performance of the Tower of Hanoi and WCST immediately after the subjects were exposed to one of the videos (neutral, aggressive, and erotic). There was no difference between videos in the task performance parameters. Only the erotic video produced an increased prefrontal coupling in the slow bands (delta and theta) during the performance of the Tower of Hanoi, whereas a decreased coupling in the delta, theta, and alpha bands was observed during the WCST. Prefrontal coupling was changed after exposure to the erotic video, and it is likely that enhanced sexual arousal was the main cause of this change. The correlation patterns obtained could be associated with particular cognitive strategies or to functional adaptations while being sexually aroused. The results of this study may contribute to an understanding of the central nervous mechanisms underlying the cognitive effects of sexual arousal. © 2012 International Society for Sexual Medicine.

Time course of recovery showing initial prefrontal cortex changes at 16 weeks, extending to subcortical changes by 3 years in pediatric bipolar disorder.

PubMed

Yang, Hongyu; Lu, Lisa H; Wu, Minjie; Stevens, Michael; Wegbreit, Ezra; Fitzgerald, Jacklynn; Levitan, Bryn; Shankman, Stewart; Pavuluri, Mani N

2013-09-05

Activation changes at the interface of affective and cognitive systems are examined over a 3 year period in pediatric bipolar disorder (PBD). Thirteen participants with PBD and 10 healthy controls (HC) matched on demographics and IQ were scanned at baseline, at 16 weeks, and after 3 years. All patients received pharmacotherapy based on a medication algorithm. A pediatric affective color matching paradigm was used to probe cognitive processing under emotional challenge. At baseline, in response to emotional vs. neutral words, patients with PBD showed greater activation than HC in the right dorsal lateral prefrontal cortex (DLPFC) and amygdala, ventral lateral prefrontal cortex (VLPFC), bilateral anterior cingulate cortex (ACC), and ventral striatum. Increased activation in DLPFC in the PBD group normalized by 16 weeks. By 3 years, normalization was observed in VLPFC, ACC, amygdala, and striatum. Small sample size renders the present findings preliminary. Greater activation in fronto-striatal and fronto-limbic circuits were observed in unmedicated patients with PBD. Present findings suggest the possibility that DLPFC is most malleable to pharmacological intervention with systematic pharmacotherapy leading to immediate response, which extended to amygdalostriatal and ventral cortical regions at 3 years. The seminal observation from this study is the prolonged length of recovery time in the normalization of subcortical activity along with their interfacing cortical regions. Findings from this proof of concept study need to be replicated in a larger sample. Copyright © 2013 Elsevier B.V. All rights reserved.

Deep brain stimulation reveals emotional impact processing in ventromedial prefrontal cortex.

PubMed

Gjedde, Albert; Geday, Jacob

2009-12-07

We tested the hypothesis that modulation of monoaminergic tone with deep-brain stimulation (DBS) of subthalamic nucleus would reveal a site of reactivity in the ventromedial prefrontal cortex that we previously identified by modulating serotonergic and noradrenergic mechanisms by blocking serotonin-noradrenaline reuptake sites. We tested the hypothesis in patients with Parkinson's disease in whom we had measured the changes of blood flow everywhere in the brain associated with the deep brain stimulation of the subthalamic nucleus. We determined the emotional reactivity of the patients as the average impact of emotive images rated by the patients off the DBS. We then searched for sites in the brain that had significant correlation of the changes of blood flow with the emotional impact rated by the patients. The results indicate a significant link between the emotional impact when patients are not stimulated and the change of blood flow associated with the DBS. In subjects with a low emotional impact, activity measured as blood flow rose when the electrode was turned on, while in subjects of high impact, the activity at this site in the ventromedial prefrontal cortex declined when the electrode was turned on. We conclude that changes of neurotransmission in the ventromedial prefrontal cortex had an effect on the tissue that depends on changes of monoamine concentration interacting with specific combinations of inhibitory and excitatory monoamine receptors.

Neuropeptide S overcomes short term memory deficit induced by sleep restriction by increasing prefrontal cortex activity.

PubMed

Thomasson, Julien; Canini, Frédéric; Poly-Thomasson, Betty; Trousselard, Marion; Granon, Sylvie; Chauveau, Frédéric

2017-12-01

Sleep restriction (SR) impairs short term memory (STM) that might be related to different processes. Neuropeptide S (NPS), an endogenous neuropeptide that improves short term memory, activates arousal and decreases anxiety is likely to counteract the SR-induced impairment of STM. The objective of the present study was to find common cerebral pathways in sleep restriction and NPS action in order to ultimately antagonize SR effect on memory. The STM was assessed using a spontaneous spatial alternation task in a T-maze. C57-Bl/6J male mice were distributed in 4 groups according to treatment (0.1nmol of NPS or vehicle intracerebroventricular injection) and to 20h-SR. Immediately after behavioural testing, regional c-fos immunohistochemistry was performed and used as a neural activation marker for spatial short term memory (prefrontal cortex, dorsal hippocampus) and emotional reactivity (basolateral amygdala and ventral hippocampus). Anxiety-like behaviour was assessed using elevated-plus maze task. Results showed that SR impaired short term memory performance and decreased neuronal activation in cingular cortex.NPS injection overcame SR-induced STM deficits and increased neuronal activation in infralimbic cortex. SR spared anxiety-like behavior in the elevated-plus maze. Neural activation in basolateral nucleus of amygdala and ventral hippocampus were not changed after SR.In conclusion, the present study shows that NPS overcomes SR-induced STM deficits by increasing prefrontal cortex activation independently of anxiety-like behaviour. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Activation of prefrontal cortex and anterior thalamus in alcoholic subjects on exposure to alcohol-specific cues.

PubMed

George, M S; Anton, R F; Bloomer, C; Teneback, C; Drobes, D J; Lorberbaum, J P; Nahas, Z; Vincent, D J

2001-04-01

Functional imaging studies have recently demonstrated that specific brain regions become active in cocaine addicts when they are exposed to cocaine stimuli. To test whether there are regional brain activity differences during alcohol cue exposure between alcoholic subjects and social drinkers, we designed a functional magnetic resonance imaging (fMRI) protocol involving alcohol-specific cues. Ten non-treatment-seeking adult alcoholic subjects (2 women) (mean [SD] age, 29.9 [9.9] years) as well as 10 healthy social drinking controls of similar age (2 women) (mean [SD] age, 29.4 [8.9] years) were recruited, screened, and scanned. In the 1.5-T magnetic resonance imaging scanner, subjects were serially rated for alcohol craving before and after a sip of alcohol, and after a 9-minute randomized presentation of pictures of alcoholic beverages, control nonalcoholic beverages, and 2 different visual control tasks. During picture presentation, changes in regional brain activity were measured with the blood oxygen level-dependent technique. Alcoholic subjects, compared with the social drinking subjects, reported higher overall craving ratings for alcohol. After a sip of alcohol, while viewing alcohol cues compared with viewing other beverage cues, only the alcoholic subjects had increased activity in the left dorsolateral prefrontal cortex and the anterior thalamus. The social drinkers exhibited specific activation only while viewing the control beverage pictures. When exposed to alcohol cues, alcoholic subjects have increased brain activity in the prefrontal cortex and anterior thalamus-brain regions associated with emotion regulation, attention, and appetitive behavior.

High social desirability and prefrontal cortical activity in cancer patients: a preliminary study.

PubMed

Tashiro, Manabu; Juengling, Freimut D; Moser, Ernst; Reinhardt, Michael J; Kubota, Kazuo; Yanai, Kazuhiko; Sasaki, Hidetada; Nitzsche, Egbert U; Kumano, Hiroaki; Itoh, Masatoshi

2003-04-01

Social desirability is sometimes associated with poor prognosis in cancer patients. Psycho-neuro-immune interaction has been hypothesized as an underlying mechanism of the negative clinical outcome. Purpose of this study was to examine possible effects of high social desirability on the regional brain activity in patients with malignant diseases. Brain metabolism of 16 patients with various malignant diseases was measured by PET with 18F-fluorodeoxyglucose (FDG). Patients were divided into 2 groups using median split on Marlowe & Crown's Social Desirability Scale (MC), controlling for age, gender, and for severity of depression and anxiety, the possible two major influential factors. A group comparison of the regional cerebral activity was calculated on a voxel-by-voxel basis using statistical parametric mapping (SPM). The subgroup comparison showed that the high social desirability was associated with relatively increased metabolism in the cortical regions in the prefrontal, temporal and occipital lobes as well as in the anterior cingulate gyrus. High social desirability seems to be associated with increased activity in the prefrontal and other cortical areas. The finding is in an accordance with previous studies that demonstrated an association between prefrontal damage and anti-social behavior. Functional neuroimaging seems to be useful not only for psychiatric evaluation of major factors such as depression and anxiety but also for further psychosocial factors in cancer patients.

Neurochemical changes in the rat prefrontal cortex following acute phencyclidine treatment: an in vivo localized (1)H MRS study.

PubMed

Iltis, Isabelle; Koski, Dee M; Eberly, Lynn E; Nelson, Christopher D; Deelchand, Dinesh K; Valette, Julien; Ugurbil, Kamil; Lim, Kelvin O; Henry, Pierre-Gilles

2009-08-01

Acute phencyclidine (PCP) administration mimics some aspects of schizophrenia in rats, such as behavioral alterations, increased dopaminergic activity and prefrontal cortex dysfunction. In this study, we used single-voxel (1)H-MRS to investigate neurochemical changes in rat prefrontal cortex in vivo before and after an acute injection of PCP. A short-echo time sequence (STEAM) was used to acquire spectra in a 32-microL voxel positioned in the prefrontal cortex area of 12 rats anesthetized with isoflurane. Data were acquired for 30 min before and for 140 min after a bolus of PCP (10 mg/kg, n = 6) or saline (n = 6). Metabolites were quantified with the LCModel. Time courses for 14 metabolites were obtained with a temporal resolution of 10 min. The glutamine/glutamate ratio was significantly increased after PCP injection (p < 0.0001, pre- vs. post-injection), while the total concentration of these two metabolites remained constant. Glucose was transiently increased (+70%) while lactate decreased after the injection (both p < 0.0001). Lactate, but not glucose and glutamine, returned to baseline levels after 140 min. These results show that an acute injection of PCP leads to changes in glutamate and glutamine concentrations, similar to what has been observed in schizophrenic patients, and after ketamine administration in humans. MRS studies of this pharmacological rat model may be useful for assessing the effects of potential anti-psychotic drugs in vivo. 2009 John Wiley & Sons, Ltd.

NMDA receptor subunits change in the prefrontal cortex of pure-opioid and multi-drug abusers: a post-mortem study.

PubMed

Daneshparvar, Hamidreza; Sadat-Shirazi, Mitra-Sadat; Fekri, Monir; Khalifeh, Solmaz; Ziaie, Ali; Esfahanizadeh, Nasrin; Vousooghi, Nasim; Zarrindast, Mohammad-Reza

2018-05-16

Addiction is a chronic relapsing disorder and is one of the most important issues in the world. Changing the level of neurotransmitters and the activities of their receptors, play a major role in the pathophysiology of substance abuse disorders. It is well-established that N-methyl-D-aspartate receptors (NMDARs) play a significant role in the molecular basis of addiction. NMDAR has two obligatory GluN1 and two regionally localized GluN2 subunits. This study investigated changes in the protein level of GluN1, GluN2A, and GluN2B in the prefrontal cortex of drug abusers. The medial prefrontal cortex (mPFC), lateral prefrontal cortex (lPFC), and orbitofrontal cortex (OFC) were dissected from the brain of 101 drug addicts brains and were compared with the brains of non-addicts (N = 13). Western blotting technique was used to show the alteration in NMDAR subunits level. Data obtained using Western blotting technique showed a significant increase in the level of GluN1 and GluN2B, but not in GluN2A subunits in all the three regions (mPFC, lPFC, and OFC) of men whom suffered from addiction as compared to the appropriate controls. These findings showed a novel role for GluN1, GluN2B subunits, rather than the GluN2A subunit of NMDARs, in the pathophysiology of addiction and suggested their role in the drug-induced plasticity of NMDARs.

Perceived Occupational Stress is associated with Decreased Cortical Activity of the Prefrontal Cortex: A Multichannel Near-infrared Spectroscopy Study.

PubMed

Chou, Po-Han; Lin, Wei-Hao; Hung, Chao-An; Chang, Chiung-Chih; Li, Wan-Rung; Lan, Tsuo-Hung; Huang, Min-Wei

2016-12-13

Despite an increasing number of reports on the associations between chronic occupational stress and structural and functional changes of the brain, the underlying neural correlates of perceived occupational stress is still not clear. Perceived stress reflects the extents to which situations are appraised as stressful at a given point in one's life. Using near-infrared spectroscopy, we investigated the associations between perceived occupational stress and cortical activity over the bilateral frontotemporal regions during a verbal fluency test. Sixty-eight participants (17 men, 51 women), 20-62 years of age were recruited. Perceived occupational stress was measured using the Chinese version of Job Content Questionnaire, and the Chinese version of the Copenhagen Burnout Inventory. We found statistically significant negative associations between occupational burnout and brain cortical activity over the fronto-polar and dorsolateral prefrontal cortex during the VFT (r = -0.343 to -0.464). In conclusion, our research demonstrated a possible neural basis of perceived occupational stress that are distributed across the prefrontal cortex.

Changes in brain activity in response to problem solving during the abstinence from online game play.

PubMed

Kim, Sun Mi; Han, Doug Hyun; Lee, Young Sik; Kim, Jieun E; Renshaw, Perry F

2012-06-01

Several studies have suggested that addictive disorders including substance abuse and pathologic gambling might be associated with dysfunction on working memory and prefrontal activity. We hypothesized that excessive online game playing is associated with deficits in prefrontal cortex function and that recovery from excessive online game playing might improve prefrontal cortical activation in response to working memory stimulation. Thirteen adolescents with excessive online game playing (AEOP) and ten healthy adolescents (HC) agreed to participate in this study. The severity of online game play and playing time were evaluated for a baseline measurement and again following four weeks of treatment. Brain activation in response to working memory tasks (simple and complex calculations) at baseline and subsequent measurements was assessed using BOLD functional magnetic resonance imaging (fMRI). Compared to the HC subjects, the AEOP participants exhibited significantly greater activity in the right middle occipital gyrus, left cerebellum posterior lobe, left premotor cortex and left middle temporal gyrus in response to working memory tasks during baseline measurements. After four weeks of treatment, the AEOP subjects showed increased activity within the right dorsolateral prefrontal cortex and left occipital fusiform gyrus. After four weeks of treatment, changes in the severity of online game playing were negatively correlated with changes in the mean β value of the right dorsolateral prefrontal cortex in response to complex stimulation. We suggest that the effects of online game addiction on working memory may be similar to those observed in patients with substance dependence.

Exposure to Blue Light Increases Subsequent Functional Activation of the Prefrontal Cortex During Performance of a Working Memory Task

PubMed Central

Alkozei, Anna; Smith, Ryan; Pisner, Derek A.; Vanuk, John R.; Berryhill, Sarah M.; Fridman, Andrew; Shane, Bradley R.; Knight, Sara A.; Killgore, William D.S.

2016-01-01

Study Objectives: Prolonged exposure to blue wavelength light has been shown to have an alerting effect, and enhances performance on cognitive tasks. A small number of studies have also shown that relatively short exposure to blue light leads to changes in functional brain responses during the period of exposure. The extent to which blue light continues to affect brain functioning during a cognitively challenging task after cessation of longer periods of exposure (i.e., roughly 30 minutes or longer), however, has not been fully investigated. Methods: A total of 35 healthy participants (18 female) were exposed to either blue (469 nm) (n = 17) or amber (578 nm) (n = 18) wavelength light for 30 minutes in a darkened room, followed immediately by functional magnetic resonance imaging (fMRI) while undergoing a working memory task (N-back task). Results: Participants in the blue light condition were faster in their responses on the N-back task and showed increased activation in the dorsolateral (DLPFC) and ventrolateral (VLPFC) prefrontal cortex compared to those in the amber control light condition. Furthermore, greater activation within the VLPFC was correlated with faster N-back response times. Conclusions: This is the first study to suggest that a relatively brief, single exposure to blue light has a subsequent beneficial effect on working memory performance, even after cessation of exposure, and leads to temporarily persisting functional brain changes within prefrontal brain regions associated with executive functions. These findings may have broader implication for using blue-enriched light in a variety of work settings where alertness and quick decision-making are important. Citation: Alkozei A, Smith R, Pisner DA, Vanuk JR, Berryhill SM, Fridman A, Shane BR, Knight SA, Killgore WD. Exposure to blue light increases subsequent functional activation of the prefrontal cortex during performance of a working memory task. SLEEP 2016;39(9):1671–1680. PMID:27253770

Reduced prefrontal cortex activation in the color-word Stroop task for Chinese dyslexic children: a near-infrared spectroscopy study

NASA Astrophysics Data System (ADS)

Sun, Jinyan; Zhai, Jiahuan; Song, Ranran; Zou, Li; Gong, Hui

2011-01-01

Behavioral studies have investigated the performance of children with developmental dyslexia in conflict resolution, a function connected with the prefrontal cortex (PFC) closely. However, little is known about the prefrontal activation in conflict resolution for dyslexic children. In the present study, the involvement of the PFC in resolving conflict was evaluated for Chinese dyslexic children by means of near-infrared spectroscopy (NIRS). The NIRS instrument is a portable, continuous-wave system and can measure concentration changes of hemodynamic parameters (including oxy-, deoxy-, and total hemoglobin). Considering better sensitivity, the oxy-hemoglobin (oxy-Hb) was chosen to indicate the prefrontal activation. Ten dyslexic children and 11 normal children were recruited to perform the Chinese-character color-word Stroop task, which included the neutral and color (incongruent) tasks. In behavioral performance, both groups showed significant Stroop effect, longer response time or higher error rate for the color task. In particular, the Stroop interference effect was marginally larger for dyslexic children than normal children in response time. What's more, the two groups showed distinct pattern of oxy-Hb activation during the Stroop tasks. The normal group recruited the bilateral PFC to perform the tasks, while the dyslexic group couldn't activate the bilateral PFC in the difficult color task. Moreover, significantly less color Stroop effect was found in the left PFC for the dyslexic group, showing their disability in coping with the Stroop interference. These findings suggest that the PFC is dysfunctional in conflict resolution for Chinese dyslexic children and that NIRS can be an effective tool in neurological research and clinical application.

Enhanced oscillatory activity in the hippocampal-prefrontal network is related to short-term memory function after early-life seizures

PubMed Central

Kleen, Jonathan K.; Wu, Edie X.; Holmes, Gregory L.; Scott, Rod C.; Lenck-Santini, Pierre-Pascal

2011-01-01

Neurological insults during development are associated with later impairments in learning and memory. Although remedial training can help restore cognitive function, the neural mechanisms of this recovery in memory systems are largely unknown. To examine this issue we measured electrophysiological oscillatory activity in the hippocampus (both CA3 and CA1) and prefrontal cortex of adult rats that had experienced repeated seizures in the first weeks of life, while they were remedially trained on a delayed-nonmatch-to-sample memory task. Seizure-exposed rats showed initial difficulties learning the task but performed similar to control rats after extra training. Whole-session analyses illustrated enhanced theta power in all three structures while seizure rats learned response tasks prior to the memory task. Whilst performing the memory task, dynamic oscillation patterns revealed that prefrontal cortex theta power was increased among seizure-exposed rats. This enhancement appeared after the first memory training steps using short delays and plateaued at the most difficult steps which included both short and long delays. Further, seizure rats showed enhanced CA1-prefrontal theta coherence in correct trials compared to incorrect trials when long delays were imposed, suggesting increased hippocampal-prefrontal synchrony for the task in this group when memory demand was high. Seizure-exposed rats also showed heightened gamma power and coherence among all three structures during the trials. Our results demonstrate the first evidence of hippocampal-prefrontal enhancements following seizures in early development. Dynamic compensatory changes in this network and interconnected circuits may underpin cognitive rehabilitation following other neurological insults to higher cognitive systems. PMID:22031886

Changes of heart rate variability and prefrontal oxygenation during Tai Chi practice versus arm ergometer cycling.

PubMed

Lu, Xi; Hui-Chan, Christina Wan-Ying; Tsang, William Wai-Nam

2016-11-01

[Purpose] Exercise has been shown to improve cardiovascular fitness and cognitive function. Whether the inclusion of mind over exercise would increase parasympathetic control of the heart and brain activities more than general exercise at a similar intensity is not known. The aim of this study was to compare the effects of Tai Chi (mind-body exercise) versus arm ergometer cycling (body-focused exercise) on the heart rate variability and prefrontal oxygenation level. [Subjects and Methods] A Tai Chi master was invited to perform Tai Chi and arm ergometer cycling with similar exercise intensity on two separate days. Heart rate variability and prefrontal oxyhemoglobin levels were measured continuously by a RR recorder and near-infrared spectroscopy, respectively. [Results] During Tai Chi exercise, spectral analysis of heart rate variability demonstrated a higher high-frequency power as well as a lower low-frequency/high-frequency ratio than during ergometer cycling, suggesting increased parasympathetic and decreased sympathetic control of the heart. Also, prefrontal oxyhemoglobin and total hemoglobin levels were higher than those during arm ergometer exercise. [Conclusion] These findings suggest that increased parasympathetic control of the heart and prefrontal activities may be associated with Tai Chi practice. Having a "mind" component in Tai Chi could be more beneficial for older adults' cardiac health and cognitive function than body-focused ergometer cycling.

Phencyclidine administration during neurodevelopment alters network activity in prefrontal cortex and hippocampus in adult rats.

PubMed

Kjaerby, Celia; Hovelsø, Nanna; Dalby, Nils Ole; Sotty, Florence

2017-08-01

Symptoms of schizophrenia have been linked to insults during neurodevelopment such as NMDA receptor (NMDAR) antagonist exposure. In animal models, this leads to schizophrenia-like behavioral symptoms as well as molecular and functional changes within hippocampal and prefrontal regions. The aim of this study was to determine how administration of the NMDAR antagonist phencyclidine (PCP) during neurodevelopment affects functional network activity within the hippocampus and medial prefrontal cortex (mPFC). We recorded field potentials in vivo after electrical brain stem stimulation and observed a suppression of evoked theta power in ventral hippocampus, while evoked gamma power in mPFC was enhanced in rats administered with PCP neonatally. In addition, increased gamma synchrony elicited by acute administration of the NMDAR antagonist MK-801 was exaggerated in neonatal PCP animals. These data suggest that NMDAR antagonist exposure during brain development alters functional networks within hippocampus and mPFC possibly contributing to the reported behavioral symptoms of this animal model of schizophrenia. NEW & NOTEWORTHY We show that insults with a NMDA receptor antagonist during neurodevelopment lead to suppressed evoked theta oscillations in ventral hippocampus in adult rats, while evoked gamma oscillations are enhanced and hypersensitive to an acute challenge with a NMDA receptor antagonist in prefrontal cortex. These observations reveal the significance of neurodevelopmental disturbances in the evolvement of schizophrenia-like symptoms and contribute to the understanding of the functional deficits underlying aberrant behavior in this disease. Copyright © 2017 the American Physiological Society.

Genetically determined measures of striatal D2 signaling predict prefrontal activity during working memory performance.

PubMed

Bertolino, Alessandro; Taurisano, Paolo; Pisciotta, Nicola Marco; Blasi, Giuseppe; Fazio, Leonardo; Romano, Raffaella; Gelao, Barbara; Lo Bianco, Luciana; Lozupone, Madia; Di Giorgio, Annabella; Caforio, Grazia; Sambataro, Fabio; Niccoli-Asabella, Artor; Papp, Audrey; Ursini, Gianluca; Sinibaldi, Lorenzo; Popolizio, Teresa; Sadee, Wolfgang; Rubini, Giuseppe

2010-02-22

Variation of the gene coding for D2 receptors (DRD2) has been associated with risk for schizophrenia and with working memory deficits. A functional intronic SNP (rs1076560) predicts relative expression of the two D2 receptors isoforms, D2S (mainly pre-synaptic) and D2L (mainly post-synaptic). However, the effect of functional genetic variation of DRD2 on striatal dopamine D2 signaling and on its correlation with prefrontal activity during working memory in humans is not known. Thirty-seven healthy subjects were genotyped for rs1076560 (G>T) and underwent SPECT with [123I]IBZM (which binds primarily to post-synaptic D2 receptors) and with [123I]FP-CIT (which binds to pre-synaptic dopamine transporters, whose activity and density is also regulated by pre-synaptic D2 receptors), as well as BOLD fMRI during N-Back working memory. Subjects carrying the T allele (previously associated with reduced D2S expression) had striatal reductions of [123I]IBZM and of [123I]FP-CIT binding. DRD2 genotype also differentially predicted the correlation between striatal dopamine D2 signaling (as identified with factor analysis of the two radiotracers) and activity of the prefrontal cortex during working memory as measured with BOLD fMRI, which was positive in GG subjects and negative in GT. Our results demonstrate that this functional SNP within DRD2 predicts striatal binding of the two radiotracers to dopamine transporters and D2 receptors as well as the correlation between striatal D2 signaling with prefrontal cortex activity during performance of a working memory task. These data are consistent with the possibility that the balance of excitatory/inhibitory modulation of striatal neurons may also affect striatal outputs in relationship with prefrontal activity during working memory performance within the cortico-striatal-thalamic-cortical pathway.

Genetically Determined Measures of Striatal D2 Signaling Predict Prefrontal Activity during Working Memory Performance

PubMed Central

Bertolino, Alessandro; Taurisano, Paolo; Pisciotta, Nicola Marco; Blasi, Giuseppe; Fazio, Leonardo; Romano, Raffaella; Gelao, Barbara; Bianco, Luciana Lo; Lozupone, Madia; Di Giorgio, Annabella; Caforio, Grazia; Sambataro, Fabio; Niccoli-Asabella, Artor; Papp, Audrey; Ursini, Gianluca; Sinibaldi, Lorenzo; Popolizio, Teresa; Sadee, Wolfgang; Rubini, Giuseppe

2010-01-01

Background Variation of the gene coding for D2 receptors (DRD2) has been associated with risk for schizophrenia and with working memory deficits. A functional intronic SNP (rs1076560) predicts relative expression of the two D2 receptors isoforms, D2S (mainly pre-synaptic) and D2L (mainly post-synaptic). However, the effect of functional genetic variation of DRD2 on striatal dopamine D2 signaling and on its correlation with prefrontal activity during working memory in humans is not known. Methods Thirty-seven healthy subjects were genotyped for rs1076560 (G>T) and underwent SPECT with [123I]IBZM (which binds primarily to post-synaptic D2 receptors) and with [123I]FP-CIT (which binds to pre-synaptic dopamine transporters, whose activity and density is also regulated by pre-synaptic D2 receptors), as well as BOLD fMRI during N-Back working memory. Results Subjects carrying the T allele (previously associated with reduced D2S expression) had striatal reductions of [123I]IBZM and of [123I]FP-CIT binding. DRD2 genotype also differentially predicted the correlation between striatal dopamine D2 signaling (as identified with factor analysis of the two radiotracers) and activity of the prefrontal cortex during working memory as measured with BOLD fMRI, which was positive in GG subjects and negative in GT. Conclusions Our results demonstrate that this functional SNP within DRD2 predicts striatal binding of the two radiotracers to dopamine transporters and D2 receptors as well as the correlation between striatal D2 signaling with prefrontal cortex activity during performance of a working memory task. These data are consistent with the possibility that the balance of excitatory/inhibitory modulation of striatal neurons may also affect striatal outputs in relationship with prefrontal activity during working memory performance within the cortico-striatal-thalamic-cortical pathway. PMID:20179754

[Effects of prefrontal ablations on the reaction of the active choice of feeder under different probability and value of the reinforcement on dog].

PubMed

Preobrazhenskaia, L A; Ioffe, M E; Mats, V N

2004-01-01

The role of the prefrontal cortex was investigated on the reaction of the active choice of the two feeders under changes value and probability reinforcement. The experiments were performed on 2 dogs with prefrontal ablation (g. proreus). Before the lesions the dogs were taught to receive food in two different feeders to conditioned stimuli with equally probable alimentary reinforcement. After ablation in the inter-trial intervals the dogs were running from the one feeder to another. In the answer to conditioned stimuli for many times the dogs choose the same feeder. The disturbance of the behavior after some times completely restored. In the experiments with competition of probability events and values of reinforcement the dogs chose the feeder with low-probability but better quality of reinforcement. In the experiments with equal value but different probability the intact dogs chose the feeder with higher probability. In our experiments the dogs with prefrontal lesions chose the each feeder equiprobably. Thus in condition of free behavior one of different functions of the prefrontal cortex is the reactions choose with more probability of reinforcement.

4 Hz oscillations synchronize prefrontal-amygdala circuits during fear behaviour

PubMed Central

Karalis, Nikolaos; Dejean, Cyril; Chaudun, Fabrice; Khoder, Suzana; Rozeske, Robert R.; Wurtz, Hélène; Bagur, Sophie; Benchenane, Karim; Sirota, Anton; Courtin, Julien; Herry, Cyril

2016-01-01

Fear expression relies on the coordinated activity of prefrontal and amygdala circuits, yet the mechanisms allowing long-range network synchronization during fear remain unknown. Using a combination of extracellular recordings, pharmacological, and optogenetic manipulations we report that freezing, a behavioural expression of fear, temporally coincides with the development of sustained, internally generated 4 Hz oscillations within prefrontal-amygdala circuits. 4 Hz oscillations predict freezing onset and offset and synchronize prefrontal-amygdala circuits. Optogenetic induction of prefrontal 4 Hz oscillations coordinates prefrontal-amygdala activity and elicits fear behaviour. These results unravel a novel sustained oscillatory mechanism mediating prefrontal-amygdala coupling during fear behaviour. PMID:26878674

Semantic strategy training increases memory performance and brain activity in patients with prefrontal cortex lesions.

PubMed

Miotto, Eliane C; Savage, Cary R; Evans, Jonathan J; Wilson, Barbara A; Martin, Maria G M; Balardin, Joana B; Barros, Fabio G; Garrido, Griselda; Teixeira, Manoel J; Amaro Junior, Edson

2013-03-01

Memory deficit is a frequent cognitive disorder following acquired prefrontal cortex lesions. In the present study, we investigated the brain correlates of a short semantic strategy training and memory performance of patients with distinct prefrontal cortex lesions using fMRI and cognitive tests. Twenty-one adult patients with post-acute prefrontal cortex (PFC) lesions, twelve with left dorsolateral PFC (LPFC) and nine with bilateral orbitofrontal cortex (BOFC) were assessed before and after a short cognitive semantic training using a verbal memory encoding paradigm during scanning and neuropsychological tests outside the scanner. After the semantic strategy training both groups of patients showed significant behavioral improvement in verbal memory recall and use of semantic strategies. In the LPFC group, greater activity in left inferior and medial frontal gyrus, precentral gyrus and insula was found after training. For the BOFC group, a greater activation was found in the left parietal cortex, right cingulated and precuneus after training. The activation of these specific areas in the memory and executive networks following cognitive training was associated to compensatory brain mechanisms and application of the semantic strategy. Copyright © 2012 Elsevier B.V. All rights reserved.

Mapping Prefrontal Cortex Functions in Human Infancy

ERIC Educational Resources Information Center

Grossmann, Tobias

2013-01-01

It has long been thought that the prefrontal cortex, as the seat of most higher brain functions, is functionally silent during most of infancy. This review highlights recent work concerned with the precise mapping (localization) of brain activation in human infants, providing evidence that prefrontal cortex exhibits functional activation much…

Women with Premenstrual Dysphoria Lack the Seemingly Normal Premenstrual Right-Sided Relative Dominance of 5-HTP-Derived Serotonergic Activity in the Dorsolateral Prefrontal Cortices - A Possible Cause of Disabling Mood Symptoms

PubMed Central

Wall, Anders; Olsson, Ulf; Marteinsdottir, Ina; Holstad, Maria; Ågren, Hans; Långström, Bengt; Naessén, Tord

2016-01-01

Study Objective To investigate potential quantitative and qualitative differences in brain serotonergic activity between women with Premenstrual Dysphoria (PMD) and asymptomatic controls. Background Serotonin-augmenting drugs alleviate premenstrual mood symptoms in the majority of women with PMD while serotonin-depleting diets worsen PMD symptoms, both indicating intrinsic differences in brain serotonergic activity in women with PMD compared to asymptomatic women. Methods Positron-emission tomography with the immediate precursor of serotonin, 5-hydroxytryptophan (5-HTP), radiolabelled by 11C in the beta-3 position, was performed in the follicular and luteal phases for 12 women with PMD and 8 control women. Brain radioactivity–a proxy for serotonin precursor uptake and synthesis–was measured in 9 regions of interest (ROIs): the right and left sides of the medial prefrontal cortex, dorsolateral prefrontal cortex, putamen and caudate nucleus, and the single “whole brain”. Results There were no significant quantitative differences in brain 5-HTP-derived activity between the groups in either of the menstrual phases for any of the 9 ROIs. However, multivariate analysis revealed a significant quantitative and qualitative difference between the groups. Asymptomatic control women showed a premenstrual right sided relative increase in dorsolateral prefrontal cortex 5-HTP derived activity, whereas PMD women displayed the opposite (p = 0.0001). Menstrual phase changes in this asymmetry (premenstrual—follicular) correlated with changes in self ratings of ‘irritability’ for the entire group (rs = -0.595, p = 0.006). The PMD group showed a strong inverse correlation between phase changes (premenstrual—follicular) in plasma levels of estradiol and phase changes in the laterality (dx/sin) of radiotracer activity in the dorsolateral prefrontal ROI (rs = -0.635; 0.027). The control group showed no such correlation. Conclusion Absence of increased premenstrual right

DRD2 genotype predicts prefrontal activity during working memory after stimulation of D2 receptors with bromocriptine.

PubMed

Gelao, Barbara; Fazio, Leonardo; Selvaggi, Pierluigi; Di Giorgio, Annabella; Taurisano, Paolo; Quarto, Tiziana; Romano, Raffaella; Porcelli, Annamaria; Mancini, Marina; Masellis, Rita; Ursini, Gianluca; De Simeis, Giuseppe; Caforio, Grazia; Ferranti, Laura; Lo Bianco, Luciana; Rampino, Antonio; Todarello, Orlando; Popolizio, Teresa; Blasi, Giuseppe; Bertolino, Alessandro

2014-06-01

Pharmacological stimulation of D2 receptors modulates prefrontal neural activity associated with working memory (WM) processing. The T allele of a functional single-nucleotide polymorphism (SNP) within DRD2 (rs1076560 G > T) predicts reduced relative expression of the D2S receptor isoform and less efficient neural cortical responses during WM tasks. We used functional MRI to test the hypothesis that DRD2 rs1076560 genotype interacts with pharmacological stimulation of D2 receptors with bromocriptine on prefrontal responses during different loads of a spatial WM task (N-Back). Fifty-three healthy subjects (38 GG and 15 GT) underwent two 3-T functional MRI scans while performing the 1-, 2- and 3-Back versions of the N-Back WM task. Before the imaging sessions, either bromocriptine or placebo was administered to all subjects in a counterbalanced order. A factorial repeated-measures ANOVA within SPM8 (p < 0.05, family-wise error corrected) was used. On bromocriptine, GG subjects had reduced prefrontal activity at 3-Back together with a significant decrement in performance, compared with placebo. On the other hand, GT subjects had lower activity for the same level of performance at 1-Back but a trend for reduced behavioral performance in the face of unchanged activity at 2-Back. These results indicate that bromocriptine stimulation modulates prefrontal activity in terms of disengagement or of efficiency depending on DRD2 genotype and working memory load.

Working Memory in the Prefrontal Cortex

PubMed Central

Funahashi, Shintaro

2017-01-01

The prefrontal cortex participates in a variety of higher cognitive functions. The concept of working memory is now widely used to understand prefrontal functions. Neurophysiological studies have revealed that stimulus-selective delay-period activity is a neural correlate of the mechanism for temporarily maintaining information in working memory processes. The central executive, which is the master component of Baddeley’s working memory model and is thought to be a function of the prefrontal cortex, controls the performance of other components by allocating a limited capacity of memory resource to each component based on its demand. Recent neurophysiological studies have attempted to reveal how prefrontal neurons achieve the functions of the central executive. For example, the neural mechanisms of memory control have been examined using the interference effect in a dual-task paradigm. It has been shown that this interference effect is caused by the competitive and overloaded recruitment of overlapping neural populations in the prefrontal cortex by two concurrent tasks and that the information-processing capacity of a single neuron is limited to a fixed level, can be flexibly allocated or reallocated between two concurrent tasks based on their needs, and enhances behavioral performance when its allocation to one task is increased. Further, a metamemory task requiring spatial information has been used to understand the neural mechanism for monitoring its own operations, and it has been shown that monitoring the quality of spatial information represented by prefrontal activity is an important factor in the subject's choice and that the strength of spatially selective delay-period activity reflects confidence in decision-making. Although further studies are needed to elucidate how the prefrontal cortex controls memory resource and supervises other systems, some important mechanisms related to the central executive have been identified. PMID:28448453

Activation of the prefrontal cortex while performing a task at preferred slow pace and metronome slow pace: a functional near-infrared spectroscopy study.

PubMed

Shimoda, Kaori; Moriguchi, Yoshiya; Tsuchiya, Kenji; Katsuyama, Shiori; Tozato, Fusae

2014-01-01

Individuals have a preferred pace at which they perform voluntary repetitive movements. Previous studies have reported that greater activation of the prefrontal cortex was observed during self-initiated movements than during externally triggered movements. The purpose of the present study is to compare the activation of the prefrontal cortex induced when the subjects performed a peg-board task at their preferred slow pace (PSP, the self-initiated condition) with that induced when they performed the same task at metronome slow pace (MSP, the externally triggered condition) using functional near-infrared spectroscopy. Healthy subjects performed the task while sitting in a chair. By assessing the activated channels individually, we confirmed that all of the prefrontal regions of interest were activated by both tasks. In the second-level analyses, we found that the activation detected in the frontopolar cortex (FPPFC; Brodmann area 10) was higher during the PSP task than during the MSP task. The FPPFC is known to be at the top of prefrontal hierarchy, and specifically involved in evaluating self-generated information. In addition, the FPPFC plays a role in coordinating lateral prefrontal cortex. In the present study, the subjects evaluated and managed the internally generated PSP by coordinating the activity of other lower level prefrontal regions.

Activation of the Prefrontal Cortex While Performing a Task at Preferred Slow Pace and Metronome Slow Pace: A Functional Near-Infrared Spectroscopy Study

PubMed Central

Moriguchi, Yoshiya

2014-01-01

Individuals have a preferred pace at which they perform voluntary repetitive movements. Previous studies have reported that greater activation of the prefrontal cortex was observed during self-initiated movements than during externally triggered movements. The purpose of the present study is to compare the activation of the prefrontal cortex induced when the subjects performed a peg-board task at their preferred slow pace (PSP, the self-initiated condition) with that induced when they performed the same task at metronome slow pace (MSP, the externally triggered condition) using functional near-infrared spectroscopy. Healthy subjects performed the task while sitting in a chair. By assessing the activated channels individually, we confirmed that all of the prefrontal regions of interest were activated by both tasks. In the second-level analyses, we found that the activation detected in the frontopolar cortex (FPPFC; Brodmann area 10) was higher during the PSP task than during the MSP task. The FPPFC is known to be at the top of prefrontal hierarchy, and specifically involved in evaluating self-generated information. In addition, the FPPFC plays a role in coordinating lateral prefrontal cortex. In the present study, the subjects evaluated and managed the internally generated PSP by coordinating the activity of other lower level prefrontal regions. PMID:25436155

Extrapunitive and intropunitive individuals activate different parts of the prefrontal cortex under an ego-blocking frustration.

PubMed

Minamoto, Takehiro; Osaka, Mariko; Yaoi, Ken; Osaka, Naoyuki

2014-01-01

Different people make different responses when they face a frustrating situation: some punish others (extrapunitive), while others punish themselves (intropunitive). Few studies have investigated the neural structures that differentiate extrapunitive and intropunitive individuals. The present fMRI study explored these neural structures using two different frustrating situations: an ego-blocking situation which blocks a desire or goal, and a superego-blocking situation which blocks self-esteem. In the ego-blocking condition, the extrapunitive group (n = 9) showed greater activation in the bilateral ventrolateral prefrontal cortex, indicating that these individuals prefer emotional processing. On the other hand, the intropunitive group (n = 9) showed greater activation in the left dorsolateral prefrontal cortex, possibly reflecting an effortful control for anger reduction. Such patterns were not observed in the superego-blocking condition. These results indicate that the prefrontal cortex is the source of individual differences in aggression direction in the ego-blocking situation.

Effects of bright light exposure on human fear conditioning, extinction, and associated prefrontal activation.

PubMed

Yoshiike, Takuya; Honma, Motoyasu; Yamada, Naoto; Kim, Yoshiharu; Kuriyama, Kenichi

2018-06-18

Bright light (BL) not only regulates human emotion and circadian physiology but can also directly modulate emotional memories. Impaired fear extinction and enhanced fear acquisition and consolidation are hallmarks of fear-circuitry disorders; thus, we tested whether BL facilitates fear extinction and inhibits fear acquisition. We randomly exposed 29 healthy humans to high- (9000 lx) or low-intensity light (<500 lx) for 15 min, near the nadir of the phase response to light, in a single-blind manner. Simultaneously with the light exposure, subjects performed fear extinction training and second fear acquisition, where a visual conditioned stimulus (CS), previously paired with an electric shock unconditioned stimulus (US), was presented without the US, while another CS was newly paired with the US. Conditioned responses (CRs) and changes in prefrontal cortex (PFC) activity were determined during encoding and delayed recall sessions. BL-exposed subjects exhibited lower extinction-related PFC activity and marginally higher acquisition-related PFC activity during light exposure than subjects exposed to control light. Twenty-four hours later, BL reduced CRs to both the extinguished and non-extinguished CSs with marginally lower extinction-related PFC activation, suggesting that BL enhanced fear extinction, while suppressing fear acquisition. Further, BL sustained tolerance to fear re-conditioning. Our results demonstrate that a single and brief BL exposure, synchronized with fear extinction and acquisition, instantaneously influences prefrontal hemodynamic responses and alleviates fear expression after 24 h. Although the specificity of BL effects deems further investigation, our findings indicate the clinical relevance of adjunctive BL intervention in exposure-based cognitive-behavioral therapy for fear-circuitry disorders. Copyright © 2018 Elsevier Inc. All rights reserved.

Diminished medial prefrontal cortex activation during the recollection of stressful events is an acquired characteristic of PTSD.

PubMed

Dahlgren, M K; Laifer, L M; VanElzakker, M B; Offringa, R; Hughes, K C; Staples-Bradley, L K; Dubois, S J; Lasko, N B; Hinojosa, C A; Orr, S P; Pitman, R K; Shin, L M

2018-05-01

Previous research has shown relatively diminished medial prefrontal cortex activation and heightened psychophysiological responses during the recollection of personal events in post-traumatic stress disorder (PTSD), but the origin of these abnormalities is unknown. Twin studies provide the opportunity to determine whether such abnormalities reflect familial vulnerabilities, result from trauma exposure, or are acquired characteristics of PTSD. In this case-control twin study, 26 male identical twin pairs (12 PTSD; 14 non-PTSD) discordant for PTSD and combat exposure recalled and imagined trauma-unrelated stressful and neutral life events using a standard script-driven imagery paradigm during functional magnetic resonance imaging and concurrent skin conductance measurement. Diminished activation in the medial prefrontal cortex during Stressful v. Neutral script-driven imagery was observed in the individuals with PTSD, relative to other groups. Diminished medial prefrontal cortex activation during Stressful v. Neutral script-driven imagery may be an acquired characteristic of PTSD. If replicated, this finding could be used prospectively to inform diagnosis and the assessment of treatment response.

Prefrontal oxygenation correlates to the responses in facial skin blood flows during exposure to pleasantly charged movie.

PubMed

Matsukawa, Kanji; Endo, Kana; Asahara, Ryota; Yoshikawa, Miho; Kusunoki, Shinya; Ishida, Tomoko

2017-11-01

Our laboratory reported that facial skin blood flow may serve as a sensitive tool to assess an emotional status. Cerebral neural correlates during emotional interventions should be sought in relation to the changes in facial skin blood flow. To test the hypothesis that prefrontal activity has positive relation to the changes in facial skin blood flow during emotionally charged stimulation, we examined the dynamic changes in prefrontal oxygenation (with near-infrared spectroscopy) and facial skin blood flows (with two-dimensional laser speckle and Doppler flowmetry) during emotionally charged audiovisual challenges for 2 min (by viewing comedy, landscape, and horror movie) in 14 subjects. Hand skin blood flow and systemic hemodynamics were simultaneously measured. The extents of pleasantness and consciousness for each emotional stimulus were estimated by subjective rating from -5 (the most unpleasant; the most unconscious) to +5 (the most pleasant; the most conscious). Positively charged emotional stimulation (comedy) simultaneously decreased ( P  <   0.05) prefrontal oxygenation and facial skin blood flow, whereas negatively charged (horror) or neutral (landscape) emotional stimulation did not alter or slightly decreased them. Any of hand skin blood flow and systemic cardiovascular variables did not change significantly during positively charged emotional stimulation. The changes in prefrontal oxygenation had a highly positive correlation with the changes in facial skin blood flow without altering perfusion pressure, and they were inversely correlated with the subjective rating of pleasantness. The reduction in prefrontal oxygenation during positively charged emotional stimulation suggests a decrease in prefrontal neural activity, which may in turn elicit neurally mediated vasoconstriction of facial skin blood vessels. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American

Lateral prefrontal cortex: architectonic and functional organization

PubMed Central

Petrides, Michael

2005-01-01

A comparison of the architecture of the human prefrontal cortex with that of the macaque monkey showed a very similar architectonic organization in these two primate species. There is no doubt that the prefrontal cortical areas of the human brain have undergone considerable development, but it is equally clear that the basic architectonic organization is the same in the two species. Thus, a comparative approach to the study of the functional organization of the primate prefrontal cortex is more likely to reveal the essential aspects of the various complex control processes that are the domain of frontal function. The lateral frontal cortex appears to be functionally organized along both a rostral–caudal axis and a dorsal–ventral axis. The most caudal frontal region, the motor region on the precentral gyrus, is involved in fine motor control and direct sensorimotor mappings, whereas the caudal lateral prefrontal region is involved in higher order control processes that regulate the selection among multiple competing responses and stimuli based on conditional operations. Further rostrally, the mid-lateral prefrontal region plays an even more abstract role in cognitive control. The mid-lateral prefrontal region is itself organized along a dorsal–ventral axis of organization, with the mid-dorsolateral prefrontal cortex being involved in the monitoring of information in working memory and the mid-ventrolateral prefrontal region being involved in active judgments on information held in posterior cortical association regions that are necessary for active retrieval and encoding of information. PMID:15937012

Single Session Low Frequency Left Dorsolateral Prefrontal Transcranial Magnetic Stimulation Changes Neurometabolite Relationships in Healthy Humans

PubMed Central

Bridges, Nathaniel R.; McKinley, Richard A.; Boeke, Danielle; Sherwood, Matthew S.; Parker, Jason G.; McIntire, Lindsey K.; Nelson, Justin M.; Fletchall, Catherine; Alexander, Natasha; McConnell, Amanda; Goodyear, Chuck; Nelson, Jeremy T.

2018-01-01

Background: Dorsolateral prefrontal cortex (DLPFC) low frequency repetitive transcranial magnetic stimulation (LF-rTMS) has shown promise as a treatment and investigative tool in the medical and research communities. Researchers have made significant progress elucidating DLPFC LF-rTMS effects—primarily in individuals with psychiatric disorders. However, more efforts investigating underlying molecular changes and establishing links to functional and behavioral outcomes in healthy humans are needed. Objective: We aimed to quantify neuromolecular changes and relate these to functional changes following a single session of DLPFC LF-rTMS in healthy participants. Methods: Eleven participants received sham-controlled neuronavigated 1 Hz rTMS to the region most activated by a 7-letter Sternberg working memory task (SWMT) within the left DLPFC. We quantified SWMT performance, functional magnetic resonance activation and proton Magnetic resonance spectroscopy (MRS) neurometabolite measure changes before and after stimulation. Results: A single LF-rTMS session was not sufficient to change DLPFC neurometabolite levels and these changes did not correlate with DLPFC activation changes. Real rTMS, however, significantly altered neurometabolite correlations (compared to sham rTMS), both with baseline levels and between the metabolites themselves. Additionally, real rTMS was associated with diminished reaction time (RT) performance improvements and increased activation within the motor, somatosensory and lateral occipital cortices. Conclusion: These results show that a single session of LF-rTMS is sufficient to influence metabolite relationships and causes widespread activation in healthy humans. Investigating correlational relationships may provide insight into mechanisms underlying LF-rTMS. PMID:29632477

Prefrontal-hippocampal-fusiform activity during encoding predicts intraindividual differences in free recall ability: an event-related functional-anatomic MRI study.

PubMed

Dickerson, B C; Miller, S L; Greve, D N; Dale, A M; Albert, M S; Schacter, D L; Sperling, R A

2007-01-01

The ability to spontaneously recall recently learned information is a fundamental mnemonic activity of daily life, but has received little study using functional neuroimaging. We developed a functional MRI (fMRI) paradigm to study regional brain activity during encoding that predicts free recall. In this event-related fMRI study, ten lists of fourteen pictures of common objects were shown to healthy young individuals and regional brain activity during encoding was analyzed based on subsequent free recall performance. Free recall of items was predicted by activity during encoding in hippocampal, fusiform, and inferior prefrontal cortical regions. Within-subject variance in free recall performance for the ten lists was predicted by a linear combination of condition-specific inferior prefrontal, hippocampal, and fusiform activity. Recall performance was better for lists in which prefrontal activity was greater for all items of the list and hippocampal and fusiform activity were greater specifically for items that were recalled from the list. Thus, the activity of medial temporal, fusiform, and prefrontal brain regions during the learning of new information is important for the subsequent free recall of this information. These fronto-temporal brain regions act together as a large-scale memory-related network, the components of which make distinct yet interacting contributions during encoding that predict subsequent successful free recall performance.

Atomoxetine Enhances Connectivity of Prefrontal Networks in Parkinson's Disease

PubMed Central

Borchert, Robin J; Rittman, Timothy; Passamonti, Luca; Ye, Zheng; Sami, Saber; Jones, Simon P; Nombela, Cristina; Vázquez Rodríguez, Patricia; Vatansever, Deniz; Rae, Charlotte L; Hughes, Laura E; Robbins, Trevor W; Rowe, James B

2016-01-01

Cognitive impairment is common in Parkinson's disease (PD), but often not improved by dopaminergic treatment. New treatment strategies targeting other neurotransmitter deficits are therefore of growing interest. Imaging the brain at rest (‘task-free') provides the opportunity to examine the impact of a candidate drug on many of the brain networks that underpin cognition, while minimizing task-related performance confounds. We test this approach using atomoxetine, a selective noradrenaline reuptake inhibitor that modulates the prefrontal cortical activity and can facilitate some executive functions and response inhibition. Thirty-three patients with idiopathic PD underwent task-free fMRI. Patients were scanned twice in a double-blind, placebo-controlled crossover design, following either placebo or 40-mg oral atomoxetine. Seventy-six controls were scanned once without medication to provide normative data. Seed-based correlation analyses were used to measure changes in functional connectivity, with the right inferior frontal gyrus (IFG) a critical region for executive function. Patients on placebo had reduced connectivity relative to controls from right IFG to dorsal anterior cingulate cortex and to left IFG and dorsolateral prefrontal cortex. Atomoxetine increased connectivity from the right IFG to the dorsal anterior cingulate. In addition, the atomoxetine-induced change in connectivity from right IFG to dorsolateral prefrontal cortex was proportional to the change in verbal fluency, a simple index of executive function. The results support the hypothesis that atomoxetine may restore prefrontal networks related to executive functions. We suggest that task-free imaging can support translational pharmacological studies of new drug therapies and provide evidence for engagement of the relevant neurocognitive systems. PMID:26837463

Atomoxetine Enhances Connectivity of Prefrontal Networks in Parkinson's Disease.

PubMed

Borchert, Robin J; Rittman, Timothy; Passamonti, Luca; Ye, Zheng; Sami, Saber; Jones, Simon P; Nombela, Cristina; Vázquez Rodríguez, Patricia; Vatansever, Deniz; Rae, Charlotte L; Hughes, Laura E; Robbins, Trevor W; Rowe, James B

2016-07-01

Cognitive impairment is common in Parkinson's disease (PD), but often not improved by dopaminergic treatment. New treatment strategies targeting other neurotransmitter deficits are therefore of growing interest. Imaging the brain at rest ('task-free') provides the opportunity to examine the impact of a candidate drug on many of the brain networks that underpin cognition, while minimizing task-related performance confounds. We test this approach using atomoxetine, a selective noradrenaline reuptake inhibitor that modulates the prefrontal cortical activity and can facilitate some executive functions and response inhibition. Thirty-three patients with idiopathic PD underwent task-free fMRI. Patients were scanned twice in a double-blind, placebo-controlled crossover design, following either placebo or 40-mg oral atomoxetine. Seventy-six controls were scanned once without medication to provide normative data. Seed-based correlation analyses were used to measure changes in functional connectivity, with the right inferior frontal gyrus (IFG) a critical region for executive function. Patients on placebo had reduced connectivity relative to controls from right IFG to dorsal anterior cingulate cortex and to left IFG and dorsolateral prefrontal cortex. Atomoxetine increased connectivity from the right IFG to the dorsal anterior cingulate. In addition, the atomoxetine-induced change in connectivity from right IFG to dorsolateral prefrontal cortex was proportional to the change in verbal fluency, a simple index of executive function. The results support the hypothesis that atomoxetine may restore prefrontal networks related to executive functions. We suggest that task-free imaging can support translational pharmacological studies of new drug therapies and provide evidence for engagement of the relevant neurocognitive systems.

Age-Dependent Relationships between Prefrontal Cortex Activation and Processing Efficiency

PubMed Central

Motes, Michael A.; Biswal, Bharat B.; Rypma, Bart

2012-01-01

fMRI was used in the present study to examine the neural basis for age-related differences in processing efficiency, particularly targeting prefrontal cortex (PFC). During scanning, older and younger participants completed a processing efficiency task in which they determined on each trial whether a symbol-number pair appeared in a simultaneously presented array of nine symbol-number pairs. Estimates of task-related BOLD signal-change were obtained for each participant. These estimates were then correlated with the participants’ performance on the task. For younger participants, BOLD signal-change within PFC decreased with better performance, but for older participants, BOLD signal-change within PFC increased with better performance. The results support the hypothesis that the availability and use of PFC resources mediates age-related changes in processing efficiency. PMID:22792129

Age-Dependent Relationships between Prefrontal Cortex Activation and Processing Efficiency.

PubMed

Motes, Michael A; Biswal, Bharat B; Rypma, Bart

2011-01-01

fMRI was used in the present study to examine the neural basis for age-related differences in processing efficiency, particularly targeting prefrontal cortex (PFC). During scanning, older and younger participants completed a processing efficiency task in which they determined on each trial whether a symbol-number pair appeared in a simultaneously presented array of nine symbol-number pairs. Estimates of task-related BOLD signal-change were obtained for each participant. These estimates were then correlated with the participants' performance on the task. For younger participants, BOLD signal-change within PFC decreased with better performance, but for older participants, BOLD signal-change within PFC increased with better performance. The results support the hypothesis that the availability and use of PFC resources mediates age-related changes in processing efficiency.

Transcranial direct current stimulation over prefrontal cortex diminishes degree of risk aversion.

PubMed

Ye, Hang; Chen, Shu; Huang, Daqiang; Wang, Siqi; Jia, Yongmin; Luo, Jun

2015-06-26

Previous studies have established that transcranial direct current stimulation (tDCS) is a powerful technique for manipulating the activity of the human cerebral cortex. Many studies have found that weighing the risks and benefits in decision-making involves a complex neural network that includes the dorsolateral prefrontal cortex (DLPFC). We studied whether participants change the balance of risky and safe responses after receiving tDCS applied over the right and left prefrontal cortex. A total of 60 healthy volunteers performed a risk task while they received either anodal tDCS over the right prefrontal cortex, with cathodal over the left; anodal tDCS over the left prefrontal cortex, with cathodal over the right; or sham stimulation. The participants tended to choose less risky options after receiving sham stimulation, demonstrating that the task might be highly influenced by the "wealth effect". There was no statistically significant change after either right anodal/left cathodal or left anodal/right cathodal tDCS, indicating that both types of tDCS impact the participants' degrees of risk aversion, and therefore, counteract the wealth effect. We also found gender differences in the participants' choices. These findings extend the notion that DLPFC activity is critical for risk decision-making. Application of tDCS to the right/left DLPFC may impact a person's attitude to taking risks. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Task-Dependent Modulations of Prefrontal and Hippocampal Activity during Intrinsic Word Production

ERIC Educational Resources Information Center

Whitney, Carin; Weis, Susanne; Krings, Timo; Huber, Walter; Grossman, Murray; Kircher, Tilo

2009-01-01

Functional imaging studies of single word production have consistently reported activation of the lateral prefrontal and cingulate cortex. Its contribution has been shown to be sensitive to task demands, which can be manipulated by the degree of response specification. Compared with classical verbal fluency, free word association relies less on…

Extrapunitive and Intropunitive Individuals Activate Different Parts of the Prefrontal Cortex under an Ego-Blocking Frustration

PubMed Central

Minamoto, Takehiro; Osaka, Mariko; Yaoi, Ken; Osaka, Naoyuki

2014-01-01

Different people make different responses when they face a frustrating situation: some punish others (extrapunitive), while others punish themselves (intropunitive). Few studies have investigated the neural structures that differentiate extrapunitive and intropunitive individuals. The present fMRI study explored these neural structures using two different frustrating situations: an ego-blocking situation which blocks a desire or goal, and a superego-blocking situation which blocks self-esteem. In the ego-blocking condition, the extrapunitive group (n = 9) showed greater activation in the bilateral ventrolateral prefrontal cortex, indicating that these individuals prefer emotional processing. On the other hand, the intropunitive group (n = 9) showed greater activation in the left dorsolateral prefrontal cortex, possibly reflecting an effortful control for anger reduction. Such patterns were not observed in the superego-blocking condition. These results indicate that the prefrontal cortex is the source of individual differences in aggression direction in the ego-blocking situation. PMID:24454951

Murine GRPR and Stathmin Control in Opposite Directions both Cued Fear Extinction and Neural Activities of the Amygdala and Prefrontal Cortex

PubMed Central

Martel, Guillaume; Hevi, Charles; Wong, Alexandra; Zushida, Ko; Uchida, Shusaku; Shumyatsky, Gleb P.

2012-01-01

Extinction is an integral part of normal healthy fear responses, while it is compromised in several fear-related mental conditions in humans, such as post-traumatic stress disorder (PTSD). Although much research has recently been focused on fear extinction, its molecular and cellular underpinnings are still unclear. The development of animal models for extinction will greatly enhance our approaches to studying its neural circuits and the mechanisms involved. Here, we describe two gene-knockout mouse lines, one with impaired and another with enhanced extinction of learned fear. These mutant mice are based on fear memory-related genes, stathmin and gastrin-releasing peptide receptor (GRPR). Remarkably, both mutant lines showed changes in fear extinction to the cue but not to the context. We performed indirect imaging of neuronal activity on the second day of cued extinction, using immediate-early gene c-Fos. GRPR knockout mice extinguished slower (impaired extinction) than wildtype mice, which was accompanied by an increase in c-Fos activity in the basolateral amygdala and a decrease in the prefrontal cortex. By contrast, stathmin knockout mice extinguished faster (enhanced extinction) and showed a decrease in c-Fos activity in the basolateral amygdala and an increase in the prefrontal cortex. At the same time, c-Fos activity in the dentate gyrus was increased in both mutant lines. These experiments provide genetic evidence that the balance between neuronal activities of the amygdala and prefrontal cortex defines an impairment or facilitation of extinction to the cue while the hippocampus is involved in the context-specificity of extinction. PMID:22312434

Murine GRPR and stathmin control in opposite directions both cued fear extinction and neural activities of the amygdala and prefrontal cortex.

PubMed

Martel, Guillaume; Hevi, Charles; Wong, Alexandra; Zushida, Ko; Uchida, Shusaku; Shumyatsky, Gleb P

2012-01-01

Extinction is an integral part of normal healthy fear responses, while it is compromised in several fear-related mental conditions in humans, such as post-traumatic stress disorder (PTSD). Although much research has recently been focused on fear extinction, its molecular and cellular underpinnings are still unclear. The development of animal models for extinction will greatly enhance our approaches to studying its neural circuits and the mechanisms involved. Here, we describe two gene-knockout mouse lines, one with impaired and another with enhanced extinction of learned fear. These mutant mice are based on fear memory-related genes, stathmin and gastrin-releasing peptide receptor (GRPR). Remarkably, both mutant lines showed changes in fear extinction to the cue but not to the context. We performed indirect imaging of neuronal activity on the second day of cued extinction, using immediate-early gene c-Fos. GRPR knockout mice extinguished slower (impaired extinction) than wildtype mice, which was accompanied by an increase in c-Fos activity in the basolateral amygdala and a decrease in the prefrontal cortex. By contrast, stathmin knockout mice extinguished faster (enhanced extinction) and showed a decrease in c-Fos activity in the basolateral amygdala and an increase in the prefrontal cortex. At the same time, c-Fos activity in the dentate gyrus was increased in both mutant lines. These experiments provide genetic evidence that the balance between neuronal activities of the amygdala and prefrontal cortex defines an impairment or facilitation of extinction to the cue while the hippocampus is involved in the context-specificity of extinction.

Monkey prefrontal neurons during Sternberg task performance: full contents of working memory or most recent item?

PubMed

Konecky, R O; Smith, M A; Olson, C R

2017-06-01

To explore the brain mechanisms underlying multi-item working memory, we monitored the activity of neurons in the dorsolateral prefrontal cortex while macaque monkeys performed spatial and chromatic versions of a Sternberg working-memory task. Each trial required holding three sequentially presented samples in working memory so as to identify a subsequent probe matching one of them. The monkeys were able to recall all three samples at levels well above chance, exhibiting modest load and recency effects. Prefrontal neurons signaled the identity of each sample during the delay period immediately following its presentation. However, as each new sample was presented, the representation of antecedent samples became weak and shifted to an anomalous code. A linear classifier operating on the basis of population activity during the final delay period was able to perform at approximately the level of the monkeys on trials requiring recall of the third sample but showed a falloff in performance on trials requiring recall of the first or second sample much steeper than observed in the monkeys. We conclude that delay-period activity in the prefrontal cortex robustly represented only the most recent item. The monkeys apparently based performance of this classic working-memory task on some storage mechanism in addition to the prefrontal delay-period firing rate. Possibilities include delay-period activity in areas outside the prefrontal cortex and changes within the prefrontal cortex not manifest at the level of the firing rate. NEW & NOTEWORTHY It has long been thought that items held in working memory are encoded by delay-period activity in the dorsolateral prefrontal cortex. Here we describe evidence contrary to that view. In monkeys performing a serial multi-item working memory task, dorsolateral prefrontal neurons encode almost exclusively the identity of the sample presented most recently. Information about earlier samples must be encoded outside the prefrontal cortex or

Empathy Is Associated with Dynamic Change in Prefrontal Brain Electrical Activity during Positive Emotion in Children

ERIC Educational Resources Information Center

Light, Sharee N.; Coan, James A.; Zahn-Waxler, Carolyn; Frye, Corrina; Goldsmith, H. Hill; Davidson, Richard J.

2009-01-01

Empathy is the combined ability to interpret the emotional states of others and experience resultant, related emotions. The relation between prefrontal electroencephalographic asymmetry and emotion in children is well known. The association between positive emotion (assessed via parent report), empathy (measured via observation), and…

A Detailed Data-Driven Network Model of Prefrontal Cortex Reproduces Key Features of In Vivo Activity

PubMed Central

Hass, Joachim; Hertäg, Loreen; Durstewitz, Daniel

2016-01-01

The prefrontal cortex is centrally involved in a wide range of cognitive functions and their impairment in psychiatric disorders. Yet, the computational principles that govern the dynamics of prefrontal neural networks, and link their physiological, biochemical and anatomical properties to cognitive functions, are not well understood. Computational models can help to bridge the gap between these different levels of description, provided they are sufficiently constrained by experimental data and capable of predicting key properties of the intact cortex. Here, we present a detailed network model of the prefrontal cortex, based on a simple computationally efficient single neuron model (simpAdEx), with all parameters derived from in vitro electrophysiological and anatomical data. Without additional tuning, this model could be shown to quantitatively reproduce a wide range of measures from in vivo electrophysiological recordings, to a degree where simulated and experimentally observed activities were statistically indistinguishable. These measures include spike train statistics, membrane potential fluctuations, local field potentials, and the transmission of transient stimulus information across layers. We further demonstrate that model predictions are robust against moderate changes in key parameters, and that synaptic heterogeneity is a crucial ingredient to the quantitative reproduction of in vivo-like electrophysiological behavior. Thus, we have produced a physiologically highly valid, in a quantitative sense, yet computationally efficient PFC network model, which helped to identify key properties underlying spike time dynamics as observed in vivo, and can be harvested for in-depth investigation of the links between physiology and cognition. PMID:27203563

Accelerated aging-related transcriptome changes in the female prefrontal cortex

PubMed Central

Yuan, Yuan; Chen, Yi-Ping Phoebe; Boyd-Kirkup, Jerome; Khaitovich, Philipp; Somel, Mehmet

2012-01-01

Human female life expectancy is higher than that of males. Intriguingly, it has been reported that women display faster rates of age-related cognitive decline and a higher prevalence of Alzheimer’s disease (AD). To assess the molecular bases of these contradictory trends, we analyzed differences in expression changes with age between adult males and females, in four brain regions. In the superior frontal gyrus (SFG), a part of the prefrontal cortex, we observed manifest differences between the two sexes in the timing of age-related changes, that is, sexual heterochrony. Intriguingly, age-related expression changes predominantly occurred earlier, or at a faster pace, in females compared to men. These changes included decreased energy production and neural function and up-regulation of the immune response, all major features of brain aging. Furthermore, we found that accelerated expression changes in the female SFG correlated with expression changes observed in AD, as well as stress effects in the frontal cortex. Accelerated aging-related changes in the female SFG transcriptome may provide a link between a higher stress exposure or sensitivity in women and the higher prevalence of AD. PMID:22783978

Prefrontal-Hippocampal-Fusiform Activity During Encoding Predicts Intraindividual Differences in Free Recall Ability: An Event-Related Functional-Anatomic MRI Study

PubMed Central

Dickerson, B.C.; Miller, S.L.; Greve, D.N.; Dale, A.M.; Albert, M.S.; Schacter, D.L.; Sperling, R.A.

2009-01-01

The ability to spontaneously recall recently learned information is a fundamental mnemonic activity of daily life, but has received little study using functional neuroimaging. We developed a functional MRI (fMRI) paradigm to study regional brain activity during encoding that predicts free recall. In this event-related fMRI study, ten lists of fourteen pictures of common objects were shown to healthy young individuals and regional brain activity during encoding was analyzed based on subsequent free recall performance. Free recall of items was predicted by activity during encoding in hippocampal, fusiform, and inferior prefrontal cortical regions. Within-subject variance in free recall performance for the ten lists was predicted by a linear combination of condition-specific inferior prefrontal, hippocampal, and fusiform activity. Recall performance was better for lists in which pre-frontal activity was greater for all items of the list and hippocampal and fusi-form activity were greater specifically for items that were recalled from the list. Thus, the activity of medial temporal, fusiform, and prefrontal brain regions during the learning of new information is important for the subsequent free recall of this information. These fronto-temporal brain regions act together as a large-scale memory-related network, the components of which make distinct yet interacting contributions during encoding that predict subsequent successful free recall performance. PMID:17604356

Guanfacine potentiates the activation of prefrontal cortex evoked by warning signals.

PubMed

Clerkin, Suzanne M; Schulz, Kurt P; Halperin, Jeffrey M; Newcorn, Jeffrey H; Ivanov, Iliyan; Tang, Cheuk Y; Fan, Jin

2009-08-15

Warning signals evoke an alert state of readiness that prepares for a rapid response by priming a thalamo-frontal-striatal network that includes the dorsolateral prefrontal cortex (DLPFC). Animal models indicate that noradrenergic input is essential for this stimulus-driven activation of DLPFC, but the precise mechanisms involved have not been determined. We tested the role that postsynaptic alpha(2A) adrenoceptors play in the activation of DLPFC evoked by warning cues using a placebo-controlled challenge with the alpha(2A) agonist guanfacine. Sixteen healthy young adults were scanned twice with event-related functional magnetic resonance imaging (fMRI), while performing a simple cued reaction time (RT) task following administration of a single dose of oral guanfacine (1 mg) and placebo in counterbalanced order. The RT task temporally segregates the neural effects of warning cues and motor responses and minimizes mnemonic demands. Warning cues produced a marked reduction in RT accompanied by significant activation in a distributed thalamo-frontal-striatal network, including bilateral DLPFC. Guanfacine selectively increased the cue-evoked activation of the left DLPFC and right anterior cerebellum, although this increase was not accompanied by further reductions in RT. The effects of guanfacine on DLPFC activation were specifically associated with the warning cue and were not seen for visual- or target-related activation. Guanfacine produced marked increases in the cue-evoked activation of DLPFC that correspond to the well-described actions of postsynaptic alpha(2) adrenoceptor stimulation. The current procedures provide an opportunity to test postsynaptic alpha(2A) adrenoceptor function in the prefrontal cortex in the pathophysiology of several psychiatric disorders.

Age-Related Brain Activation Changes during Rule Repetition in Word-Matching.

PubMed

Methqal, Ikram; Pinsard, Basile; Amiri, Mahnoush; Wilson, Maximiliano A; Monchi, Oury; Provost, Jean-Sebastien; Joanette, Yves

2017-01-01

Objective: The purpose of this study was to explore the age-related brain activation changes during a word-matching semantic-category-based task, which required either repeating or changing a semantic rule to be applied. In order to do so, a word-semantic rule-based task was adapted from the Wisconsin Sorting Card Test, involving the repeated feedback-driven selection of given pairs of words based on semantic category-based criteria. Method: Forty healthy adults (20 younger and 20 older) performed a word-matching task while undergoing a fMRI scan in which they were required to pair a target word with another word from a group of three words. The required pairing is based on three word-pair semantic rules which correspond to different levels of semantic control demands: functional relatedness, moderately typical-relatedness (which were considered as low control demands), and atypical-relatedness (high control demands). The sorting period consisted of a continuous execution of the same sorting rule and an inferred trial-by-trial feedback was given. Results: Behavioral performance revealed increases in response times and decreases of correct responses according to the level of semantic control demands (functional vs. typical vs. atypical) for both age groups (younger and older) reflecting graded differences in the repetition of the application of a given semantic rule. Neuroimaging findings of significant brain activation showed two main results: (1) Greater task-related activation changes for the repetition of the application of atypical rules relative to typical and functional rules, and (2) Changes (older > younger) in the inferior prefrontal regions for functional rules and more extensive and bilateral activations for typical and atypical rules. Regarding the inter-semantic rules comparison, only task-related activation differences were observed for functional > typical (e.g., inferior parietal and temporal regions bilaterally) and atypical > typical (e

Abnormal Amygdala and Prefrontal Cortex Activation to Facial Expressions in Pediatric Bipolar Disorder

ERIC Educational Resources Information Center

Garrett, Amy S.; Reiss, Allan L.; Howe, Meghan E.; Kelley, Ryan G.; Singh, Manpreet K.; Adleman, Nancy E.; Karchemskiy, Asya; Chang, Kiki D.

2012-01-01

Objective: Previous functional magnetic resonance imaging (fMRI) studies in pediatric bipolar disorder (BD) have reported greater amygdala and less dorsolateral prefrontal cortex (DLPFC) activation to facial expressions compared to healthy controls. The current study investigates whether these differences are associated with the early or late…

Anomalous prefrontal-limbic activation and connectivity in youth at high-risk for bipolar disorder.

PubMed

Chang, Kiki; Garrett, Amy; Kelley, Ryan; Howe, Meghan; Sanders, Erica Marie; Acquaye, Tenah; Bararpour, Layla; Li, Sherrie; Singh, Manpreet; Jo, Booil; Hallmayer, Joachim; Reiss, Allan

2017-11-01

Abnormal prefrontal-limbic brain activation in response to facial expressions has been reported in pediatric bipolar disorder (BD). However, it is less clear whether these abnormalities exist prior to onset of mania, thus representing a biomarker predicting development of BD. We examined brain activation in 50 youth at high risk for BD (HR-BD), compared with 29 age- and gender-matched healthy control (HC) subjects. HR-BD was defined as having a parent with BD, as well as current mood or attentiondeficit/ hyperactivity disorder (ADHD) symptoms, or a history of at least one depressive episode. FMRI data were collected during an implicit emotion perception task using facial expression stimuli. Activation to fearful faces versus calm faces was compared between HR-BD and HC groups, including analyses of functional connectivity, and comparison of allele subgroups of the serotonin transporter (5-HTTLPR) gene. While viewing fearful versus calm faces, HR-BD youth had significantly greater activation than HC youth in the right amygdala, ventrolateral prefrontal cortex (VLPFC), superior frontal cortex, cerebellum, and lingual gyrus. HR-BD youth, relative to HC youth, had greater functional connectivity between the right amygdala and the VLPFC as well as visual cortical regions Within the HR-BD group, youth with the s-allele had a trend for greater activation in the right amygdala and subgenual cingulate cortex CONCLUSIONS: Similar to youth with BD, youth at high risk for BD have greater activation than healthy controls in the amygdala and ventrolateral prefrontal cortex in response to fearful faces, as well greater functional connectivity between these regions. HR-BD youth with the s-allele of the 5-HTTLPR gene may be at greatest risk for developing BD. Copyright © 2017. Published by Elsevier B.V.

Dissociable patterns of medial prefrontal and amygdala activity to face identity versus emotion in bipolar disorder.

PubMed

Keener, M T; Fournier, J C; Mullin, B C; Kronhaus, D; Perlman, S B; LaBarbara, E; Almeida, J C; Phillips, M L

2012-09-01

Individuals with bipolar disorder demonstrate abnormal social function. Neuroimaging studies in bipolar disorder have shown functional abnormalities in neural circuitry supporting face emotion processing, but have not examined face identity processing, a key component of social function. We aimed to elucidate functional abnormalities in neural circuitry supporting face emotion and face identity processing in bipolar disorder. Twenty-seven individuals with bipolar disorder I currently euthymic and 27 healthy controls participated in an implicit face processing, block-design paradigm. Participants labeled color flashes that were superimposed on dynamically changing background faces comprising morphs either from neutral to prototypical emotion (happy, sad, angry and fearful) or from one identity to another identity depicting a neutral face. Whole-brain and amygdala region-of-interest (ROI) activities were compared between groups. There was no significant between-group difference looking across both emerging face emotion and identity. During processing of all emerging emotions, euthymic individuals with bipolar disorder showed significantly greater amygdala activity. During facial identity and also happy face processing, euthymic individuals with bipolar disorder showed significantly greater amygdala and medial prefrontal cortical activity compared with controls. This is the first study to examine neural circuitry supporting face identity and face emotion processing in bipolar disorder. Our findings of abnormally elevated activity in amygdala and medial prefrontal cortex (mPFC) during face identity and happy face emotion processing suggest functional abnormalities in key regions previously implicated in social processing. This may be of future importance toward examining the abnormal self-related processing, grandiosity and social dysfunction seen in bipolar disorder.

Protein Kinase C Overactivity Impairs Prefrontal Cortical Regulation of Working Memory

NASA Astrophysics Data System (ADS)

Birnbaum, S. G.; Yuan, P. X.; Wang, M.; Vijayraghavan, S.; Bloom, A. K.; Davis, D. J.; Gobeske, K. T.; Sweatt, J. D.; Manji, H. K.; Arnsten, A. F. T.

2004-10-01

The prefrontal cortex is a higher brain region that regulates thought, behavior, and emotion using representational knowledge, operations often referred to as working memory. We tested the influence of protein kinase C (PKC) intracellular signaling on prefrontal cortical cognitive function and showed that high levels of PKC activity in prefrontal cortex, as seen for example during stress exposure, markedly impair behavioral and electrophysiological measures of working memory. These data suggest that excessive PKC activation can disrupt prefrontal cortical regulation of behavior and thought, possibly contributing to signs of prefrontal cortical dysfunction such as distractibility, impaired judgment, impulsivity, and thought disorder.

Protein kinase C overactivity impairs prefrontal cortical regulation of working memory.

PubMed

Birnbaum, S G; Yuan, P X; Wang, M; Vijayraghavan, S; Bloom, A K; Davis, D J; Gobeske, K T; Sweatt, J D; Manji, H K; Arnsten, A F T

2004-10-29

The prefrontal cortex is a higher brain region that regulates thought, behavior, and emotion using representational knowledge, operations often referred to as working memory. We tested the influence of protein kinase C (PKC) intracellular signaling on prefrontal cortical cognitive function and showed that high levels of PKC activity in prefrontal cortex, as seen for example during stress exposure, markedly impair behavioral and electrophysiological measures of working memory. These data suggest that excessive PKC activation can disrupt prefrontal cortical regulation of behavior and thought, possibly contributing to signs of prefrontal cortical dysfunction such as distractibility, impaired judgment, impulsivity, and thought disorder.

Alterations in visual cortical activation and connectivity with prefrontal cortex during working memory updating in major depressive disorder.

PubMed

Le, Thang M; Borghi, John A; Kujawa, Autumn J; Klein, Daniel N; Leung, Hoi-Chung

2017-01-01

The present study examined the impacts of major depressive disorder (MDD) on visual and prefrontal cortical activity as well as their connectivity during visual working memory updating and related them to the core clinical features of the disorder. Impairment in working memory updating is typically associated with the retention of irrelevant negative information which can lead to persistent depressive mood and abnormal affect. However, performance deficits have been observed in MDD on tasks involving little or no demand on emotion processing, suggesting dysfunctions may also occur at the more basic level of information processing. Yet, it is unclear how various regions in the visual working memory circuit contribute to behavioral changes in MDD. We acquired functional magnetic resonance imaging data from 18 unmedicated participants with MDD and 21 age-matched healthy controls (CTL) while they performed a visual delayed recognition task with neutral faces and scenes as task stimuli. Selective working memory updating was manipulated by inserting a cue in the delay period to indicate which one or both of the two memorized stimuli (a face and a scene) would remain relevant for the recognition test. Our results revealed several key findings. Relative to the CTL group, the MDD group showed weaker postcue activations in visual association areas during selective maintenance of face and scene working memory. Across the MDD subjects, greater rumination and depressive symptoms were associated with more persistent activation and connectivity related to no-longer-relevant task information. Classification of postcue spatial activation patterns of the scene-related areas was also less consistent in the MDD subjects compared to the healthy controls. Such abnormalities appeared to result from a lack of updating effects in postcue functional connectivity between prefrontal and scene-related areas in the MDD group. In sum, disrupted working memory updating in MDD was revealed by

Context Memory Decline in Middle Aged Adults is Related to Changes in Prefrontal Cortex Function

PubMed Central

Kwon, Diana; Maillet, David; Pasvanis, Stamatoula; Ankudowich, Elizabeth; Grady, Cheryl L.; Rajah, M. Natasha

2016-01-01

The ability to encode and retrieve spatial and temporal contextual details of episodic memories (context memory) begins to decline at midlife. In the current study, event-related fMRI was used to investigate the neural correlates of context memory decline in healthy middle aged adults (MA) compared with young adults (YA). Participants were scanned while performing easy and hard versions of spatial and temporal context memory tasks. Scans were obtained at encoding and retrieval. Significant reductions in context memory retrieval accuracy were observed in MA, compared with YA. The fMRI results revealed that overall, both groups exhibited similar patterns of brain activity in parahippocampal cortex, ventral occipito-temporal regions and prefrontal cortex (PFC) during encoding. In contrast, at retrieval, there were group differences in ventral occipito-temporal and PFC activity, due to these regions being more activated in MA, compared with YA. Furthermore, only in YA, increased encoding activity in ventrolateral PFC, and increased retrieval activity in occipital cortex, predicted increased retrieval accuracy. In MA, increased retrieval activity in anterior PFC predicted increased retrieval accuracy. These results suggest that there are changes in PFC contributions to context memory at midlife. PMID:25882039

Correlations between prefrontal neurons form a small-world network that optimizes the generation of multineuron sequences of activity

PubMed Central

Luongo, Francisco J.; Zimmerman, Chris A.; Horn, Meryl E.

2016-01-01

Sequential patterns of prefrontal activity are believed to mediate important behaviors, e.g., working memory, but it remains unclear exactly how they are generated. In accordance with previous studies of cortical circuits, we found that prefrontal microcircuits in young adult mice spontaneously generate many more stereotyped sequences of activity than expected by chance. However, the key question of whether these sequences depend on a specific functional organization within the cortical microcircuit, or emerge simply as a by-product of random interactions between neurons, remains unanswered. We observed that correlations between prefrontal neurons do follow a specific functional organization—they have a small-world topology. However, until now it has not been possible to directly link small-world topologies to specific circuit functions, e.g., sequence generation. Therefore, we developed a novel analysis to address this issue. Specifically, we constructed surrogate data sets that have identical levels of network activity at every point in time but nevertheless represent various network topologies. We call this method shuffling activity to rearrange correlations (SHARC). We found that only surrogate data sets based on the actual small-world functional organization of prefrontal microcircuits were able to reproduce the levels of sequences observed in actual data. As expected, small-world data sets contained many more sequences than surrogate data sets with randomly arranged correlations. Surprisingly, small-world data sets also outperformed data sets in which correlations were maximally clustered. Thus the small-world functional organization of cortical microcircuits, which effectively balances the random and maximally clustered regimes, is optimal for producing stereotyped sequential patterns of activity. PMID:26888108

Age differences in medial prefrontal activity for subsequent memory of truth value

PubMed Central

Cassidy, Brittany S.; Hedden, Trey; Yoon, Carolyn; Gutchess, Angela H.

2014-01-01

Much research has demonstrated that aging is marked by decreased source memory relative to young adults, yet a smaller body of work has demonstrated that increasing the socioemotional content of source information may be one way to reduce age-related performance differences. Although dorsomedial prefrontal cortex (dmPFC) activity may support source memory among young and older adults, the extent to which one activates dorsal vs. ventral mPFC may reflect one's personal connection with incoming information. Because truth value may be one salient marker that impacts one's connection with information and allocation of attention toward incoming material, we investigated whether the perceived truth value of information differently impacts differences in mPFC activity associated with encoding source information, particularly with age. Twelve young (18–23 years) and 12 older adults (63–80 years) encoded true and false statements. Behavioral results showed similar memory performance between the age groups. With respect to neural activity associated with subsequent memory, young adults, relative to older adults, exhibited greater activity in dmPFC while older adults displayed enhanced ventromedial prefrontal cortex (vmPFC) and insula engagement relative to young. These results may potentially indicate that young adults focus on a general knowledge acquisition goal, while older adults focus on emotionally relevant aspects of the material. The findings demonstrate that age-related differences in recruitment of mPFC associated with encoding source information may in some circumstances underlie age-equivalent behavioral performance. PMID:24570672

Trace and contextual fear conditioning require neural activity and NMDA receptor-dependent transmission in the medial prefrontal cortex

PubMed Central

Gilmartin, Marieke R.; Helmstetter, Fred J.

2010-01-01

The contribution of the medial prefrontal cortex (mPFC) to the formation of memory is a subject of considerable recent interest. Notably, the mechanisms supporting memory acquisition in this structure are poorly understood. The mPFC has been implicated in the acquisition of trace fear conditioning, a task that requires the association of a conditional stimulus (CS) and an aversive unconditional stimulus (UCS) across a temporal gap. In both rat and human subjects, frontal regions show increased activity during the trace interval separating the CS and UCS. We investigated the contribution of prefrontal neural activity in the rat to the acquisition of trace fear conditioning using microinfusions of the γ-aminobutyric acid type A (GABAA) receptor agonist muscimol. We also investigated the role of prefrontal N-methyl-d-aspartate (NMDA) receptor-mediated signaling in trace fear conditioning using the NMDA receptor antagonist 2-amino-5-phosphonovaleric acid (APV). Temporary inactivation of prefrontal activity with muscimol or blockade of NMDA receptor-dependent transmission in mPFC impaired the acquisition of trace, but not delay, conditional fear responses. Simultaneously acquired contextual fear responses were also impaired in drug-treated rats exposed to trace or delay, but not unpaired, training protocols. Our results support the idea that synaptic plasticity within the mPFC is critical for the long-term storage of memory in trace fear conditioning. PMID:20504949

Cognitive deficits caused by prefrontal cortical and hippocampal neural disinhibition.

PubMed

Bast, Tobias; Pezze, Marie; McGarrity, Stephanie

2017-10-01

We review recent evidence concerning the significance of inhibitory GABA transmission and of neural disinhibition, that is, deficient GABA transmission, within the prefrontal cortex and the hippocampus, for clinically relevant cognitive functions. Both regions support important cognitive functions, including attention and memory, and their dysfunction has been implicated in cognitive deficits characterizing neuropsychiatric disorders. GABAergic inhibition shapes cortico-hippocampal neural activity, and, recently, prefrontal and hippocampal neural disinhibition has emerged as a pathophysiological feature of major neuropsychiatric disorders, especially schizophrenia and age-related cognitive decline. Regional neural disinhibition, disrupting spatio-temporal control of neural activity and causing aberrant drive of projections, may disrupt processing within the disinhibited region and efferent regions. Recent studies in rats showed that prefrontal and hippocampal neural disinhibition (by local GABA antagonist microinfusion) dysregulates burst firing, which has been associated with important aspects of neural information processing. Using translational tests of clinically relevant cognitive functions, these studies showed that prefrontal and hippocampal neural disinhibition disrupts regional cognitive functions (including prefrontal attention and hippocampal memory function). Moreover, hippocampal neural disinhibition disrupted attentional performance, which does not require the hippocampus but requires prefrontal-striatal circuits modulated by the hippocampus. However, some prefrontal and hippocampal functions (including inhibitory response control) are spared by regional disinhibition. We consider conceptual implications of these findings, regarding the distinct relationships of distinct cognitive functions to prefrontal and hippocampal GABA tone and neural activity. Moreover, the findings support the proposition that prefrontal and hippocampal neural disinhibition

Familial Vulnerability to ADHD Affects Activity in the Cerebellum in Addition to the Prefrontal Systems

ERIC Educational Resources Information Center

Mulder, Martijn J.; Baeyens, Dieter; Davidson, Matthew C.; Casey, B. J.; Van Den Ban, Els; Van Engeland, Herman; Durston, Sarah

2008-01-01

The study examines whether cerebellar systems are sensitive to familial risk for ADHD in addition to frontostriatal circuitry. The results conclude that familial vulnerability to ADHD affects activity in both the prefrontal cortex and cerebellum.

Diminished Medial Prefrontal Activity behind Autistic Social Judgments of Incongruent Information

PubMed Central

Watanabe, Takamitsu; Yahata, Noriaki; Abe, Osamu; Kuwabara, Hitoshi; Inoue, Hideyuki; Takano, Yosuke; Iwashiro, Norichika; Natsubori, Tatsunobu; Aoki, Yuta; Takao, Hidemasa; Sasaki, Hiroki; Gonoi, Wataru; Murakami, Mizuho; Katsura, Masaki; Kunimatsu, Akira; Kawakubo, Yuki; Matsuzaki, Hideo; Tsuchiya, Kenji J.; Kato, Nobumasa; Kano, Yukiko; Miyashita, Yasushi; Kasai, Kiyoto; Yamasue, Hidenori

2012-01-01

Individuals with autism spectrum disorders (ASD) tend to make inadequate social judgments, particularly when the nonverbal and verbal emotional expressions of other people are incongruent. Although previous behavioral studies have suggested that ASD individuals have difficulty in using nonverbal cues when presented with incongruent verbal-nonverbal information, the neural mechanisms underlying this symptom of ASD remain unclear. In the present functional magnetic resonance imaging study, we compared brain activity in 15 non-medicated adult males with high-functioning ASD to that of 17 age-, parental-background-, socioeconomic-, and intelligence-quotient-matched typically-developed (TD) male participants. Brain activity was measured while each participant made friend or foe judgments of realistic movies in which professional actors spoke with conflicting nonverbal facial expressions and voice prosody. We found that the ASD group made significantly less judgments primarily based on the nonverbal information than the TD group, and they exhibited significantly less brain activity in the right inferior frontal gyrus, bilateral anterior insula, anterior cingulate cortex/ventral medial prefrontal cortex (ACC/vmPFC), and dorsal medial prefrontal cortex (dmPFC) than the TD group. Among these five regions, the ACC/vmPFC and dmPFC were most involved in nonverbal-information-biased judgments in the TD group. Furthermore, the degree of decrease of the brain activity in these two brain regions predicted the severity of autistic communication deficits. The findings indicate that diminished activity in the ACC/vmPFC and dmPFC underlies the impaired abilities of individuals with ASD to use nonverbal content when making judgments regarding other people based on incongruent social information. PMID:22745788

Guanfacine modulates the influence of emotional cues on prefrontal cortex activation for cognitive control.

PubMed

Schulz, Kurt P; Clerkin, Suzanne M; Fan, Jin; Halperin, Jeffrey M; Newcorn, Jeffrey H

2013-03-01

Functional interactions between limbic regions that process emotions and frontal networks that guide response functions provide a substrate for emotional cues to influence behavior. Stimulation of postsynaptic α₂ adrenoceptors enhances the function of prefrontal regions in these networks. However, the impact of this stimulation on the emotional biasing of behavior has not been established. This study tested the effect of the postsynaptic α₂ adrenoceptor agonist guanfacine on the emotional biasing of response execution and inhibition in prefrontal cortex. Fifteen healthy young adults were scanned twice with functional magnetic resonance imaging while performing a face emotion go/no-go task following counterbalanced administration of single doses of oral guanfacine (1 mg) and placebo in a double-blind, cross-over design. Lower perceptual sensitivity and less response bias for sad faces resulted in fewer correct responses compared to happy and neutral faces but had no effect on correct inhibitions. Guanfacine increased the sensitivity and bias selectively for sad faces, resulting in response accuracy comparable to happy and neutral faces, and reversed the valence-dependent variation in response-related activation in left dorsolateral prefrontal cortex (DLPFC), resulting in enhanced activation for response execution cued by sad faces relative to happy and neutral faces, in line with other frontoparietal regions. These results provide evidence that guanfacine stimulation of postsynaptic α₂ adrenoceptors moderates DLPFC activation associated with the emotional biasing of response execution processes. The findings have implications for the α₂ adrenoceptor agonist treatment of attention-deficit hyperactivity disorder.

Association between glutamate/glutamine and blood oxygen level dependent signal in the left dorsolateral prefrontal region during verbal working memory.

PubMed

Vijayakumari, Anupa A; Thomas, Bejoy; Menon, Ramshekhar N; Kesavadas, Chandrasekharan

2018-04-11

Functional MRI (fMRI) has provided much insight into the changes in the neuronal activity on the basis of blood oxygen level dependent (BOLD) phenomenon. The dynamic changes in the metabolites can be detected using functional proton magnetic resonance spectroscopy (H-fMRS). The strategy of combining fMRI and H-fMRS would facilitate the understanding of the neurochemical interpretation of the BOLD signal. The dorsolateral prefrontal region is critically involved in the processing of working memory (WM), as demonstrated by the studies involving the neuroimaging, neuropsychological, and electrophysiological experiments. In this study, we tested the association between BOLD signal and changes in brain metabolites in the left dorsolateral prefrontal region using N-back verbal WM task. We used single-voxel task-based H-MRS acquired in the left dorsolateral prefrontal region and fMRI during the performance of N-back verbal WM task to investigate the association between changes in metabolites and BOLD response in 10 healthy participants. The correlation between changes in metabolites and percent signal change was examined by the Pearson correlation. The Pearson correlation analysis revealed a significant positive correlation between the BOLD signal and glutamate/glutamine in the left dorsolateral prefrontal region during the verbal WM. Our finding suggests that glutamate/glutamine cycle plays a critical role in the neuronal activation as reflected by the changes in the BOLD response.

Prefrontal cortical and striatal activity to happy and fear faces in bipolar disorder is associated with comorbid substance abuse and eating disorder.

PubMed

Hassel, Stefanie; Almeida, Jorge R; Frank, Ellen; Versace, Amelia; Nau, Sharon A; Klein, Crystal R; Kupfer, David J; Phillips, Mary L

2009-11-01

The spectrum approach was used to examine contributions of comorbid symptom dimensions of substance abuse and eating disorder to abnormal prefrontal-cortical and subcortical-striatal activity to happy and fear faces previously demonstrated in bipolar disorder (BD). Fourteen remitted BD-type I and sixteen healthy individuals viewed neutral, mild and intense happy and fear faces in two event-related fMRI experiments. All individuals completed Substance-Use and Eating-Disorder Spectrum measures. Region-of-Interest analyses for bilateral prefrontal and subcortical-striatal regions were performed. BD individuals scored significantly higher on these spectrum measures than healthy individuals (p<0.05), and were distinguished by activity in prefrontal and subcortical-striatal regions. BD relative to healthy individuals showed reduced dorsal prefrontal-cortical activity to all faces. Only BD individuals showed greater subcortical-striatal activity to happy and neutral faces. In BD individuals, negative correlations were shown between substance use severity and right PFC activity to intense happy faces (p<0.04), and between substance use severity and right caudate nucleus activity to neutral faces (p<0.03). Positive correlations were shown between eating disorder and right ventral putamen activity to intense happy (p<0.02) and neutral faces (p<0.03). Exploratory analyses revealed few significant relationships between illness variables and medication upon neural activity in BD individuals. Small sample size of predominantly medicated BD individuals. This study is the first to report relationships between comorbid symptom dimensions of substance abuse and eating disorder and prefrontal-cortical and subcortical-striatal activity to facial expressions in BD. Our findings suggest that these comorbid features may contribute to observed patterns of functional abnormalities in neural systems underlying mood regulation in BD.

A dorsolateral prefrontal cortex semi-automatic segmenter

NASA Astrophysics Data System (ADS)

Al-Hakim, Ramsey; Fallon, James; Nain, Delphine; Melonakos, John; Tannenbaum, Allen

2006-03-01

Structural, functional, and clinical studies in schizophrenia have, for several decades, consistently implicated dysfunction of the prefrontal cortex in the etiology of the disease. Functional and structural imaging studies, combined with clinical, psychometric, and genetic analyses in schizophrenia have confirmed the key roles played by the prefrontal cortex and closely linked "prefrontal system" structures such as the striatum, amygdala, mediodorsal thalamus, substantia nigra-ventral tegmental area, and anterior cingulate cortices. The nodal structure of the prefrontal system circuit is the dorsal lateral prefrontal cortex (DLPFC), or Brodmann area 46, which also appears to be the most commonly studied and cited brain area with respect to schizophrenia. 1, 2, 3, 4 In 1986, Weinberger et. al. tied cerebral blood flow in the DLPFC to schizophrenia.1 In 2001, Perlstein et. al. demonstrated that DLPFC activation is essential for working memory tasks commonly deficient in schizophrenia. 2 More recently, groups have linked morphological changes due to gene deletion and increased DLPFC glutamate concentration to schizophrenia. 3, 4 Despite the experimental and clinical focus on the DLPFC in structural and functional imaging, the variability of the location of this area, differences in opinion on exactly what constitutes DLPFC, and inherent difficulties in segmenting this highly convoluted cortical region have contributed to a lack of widely used standards for manual or semi-automated segmentation programs. Given these implications, we developed a semi-automatic tool to segment the DLPFC from brain MRI scans in a reproducible way to conduct further morphological and statistical studies. The segmenter is based on expert neuroanatomist rules (Fallon-Kindermann rules), inspired by cytoarchitectonic data and reconstructions presented by Rajkowska and Goldman-Rakic. 5 It is semi-automated to provide essential user interactivity. We present our results and provide details on

Transitions between Multiband Oscillatory Patterns Characterize Memory-Guided Perceptual Decisions in Prefrontal Circuits.

PubMed

Wimmer, Klaus; Ramon, Marc; Pasternak, Tatiana; Compte, Albert

2016-01-13

Neuronal activity in the lateral prefrontal cortex (LPFC) reflects the structure and cognitive demands of memory-guided sensory discrimination tasks. However, we still do not know how neuronal activity articulates in network states involved in perceiving, remembering, and comparing sensory information during such tasks. Oscillations in local field potentials (LFPs) provide fingerprints of such network dynamics. Here, we examined LFPs recorded from LPFC of macaques while they compared the directions or the speeds of two moving random-dot patterns, S1 and S2, separated by a delay. LFP activity in the theta, beta, and gamma bands tracked consecutive components of the task. In response to motion stimuli, LFP theta and gamma power increased, and beta power decreased, but showed only weak motion selectivity. In the delay, LFP beta power modulation anticipated the onset of S2 and encoded the task-relevant S1 feature, suggesting network dynamics associated with memory maintenance. After S2 onset the difference between the current stimulus S2 and the remembered S1 was strongly reflected in broadband LFP activity, with an early sensory-related component proportional to stimulus difference and a later choice-related component reflecting the behavioral decision buildup. Our results demonstrate that individual LFP bands reflect both sensory and cognitive processes engaged independently during different stages of the task. This activation pattern suggests that during elementary cognitive tasks, the prefrontal network transitions dynamically between states and that these transitions are characterized by the conjunction of LFP rhythms rather than by single LFP bands. Neurons in the brain communicate through electrical impulses and coordinate this activity in ensembles that pulsate rhythmically, very much like musical instruments in an orchestra. These rhythms change with "brain state," from sleep to waking, but also signal with different oscillation frequencies rapid changes

Sensitivity of the prefrontal GABAergic system to chronic stress in male and female mice: Relevance for sex differences in stress-related disorders.

PubMed

Shepard, Ryan; Page, Chloe E; Coutellier, Laurence

2016-09-22

Stress-induced modifications of the prefrontal cortex (PFC) are believed to contribute to the onset of mood disorders, such as depression and anxiety, which are more prevalent in women. In depression, the PFC is hypoactive; however the origin of this hypoactivity remains unclear. Possibly, stress could impact the prefrontal GABAergic inhibitory system that, as a result, impairs the functioning of downstream limbic structures controlling emotions. Preclinical evidence indicates that the female PFC is more sensitive to the effects of stress. These findings suggest that exposure to stress could lead to sex-specific alterations in prefrontal GABAergic signaling, which contribute to sex-specific abnormal functioning of limbic regions. These limbic changes could promote the onset of depressive and anxiety behaviors in a sex-specific manner, providing a possible mechanism mediating sex differences in the clinical presentation of stress-related mood disorders. We addressed this hypothesis using a mouse model of stress-induced depressive-like behaviors: the unpredictable chronic mild stress (UCMS) paradigm. We observed changes in prefrontal GABAergic signaling after exposure to UCMS most predominantly in females. Increased parvalbumin (PV) expression and decreased prefrontal neuronal activity were correlated in females with severe emotionality deficit following UCMS, and with altered activity of the amygdala. In males, small changes in emotionality following UCMS were associated with minor changes in prefrontal PV expression, and with hypoactivity of the nucleus accumbens. Our data suggest that prefrontal hypoactivity observed in stress-related mood disorders could result from stress-induced increases in PV expression, particularly in females. This increased vulnerability of the female prefrontal PV system to stress could underlie sex differences in the prevalence and symptomatology of stress-related mood disorders. Copyright © 2016 IBRO. Published by Elsevier Ltd. All

The Working Memory and Dorsolateral Prefrontal-Hippocampal Functional Connectivity Changes in Long-Term Survival Breast Cancer Patients Treated with Tamoxifen

PubMed Central

Chen, Xingui; Tao, Longxiang; Li, Jingjing; Wu, Jiaonan; Zhu, Chunyan; Yu, Fengqiong; Zhang, Lei; Zhang, Jingjie; Qiu, Bensheng; Yu, Yongqiang; He, Xiaoxuan

2017-01-01

Abstract Background: Tamoxifen is the most widely used drug for treating patients with estrogen receptor-sensitive breast cancer. There is evidence that breast cancer patients treated with tamoxifen exhibit cognitive dysfunction. However, the underlying neural mechanism remains unclear. The present study aimed to investigate the neural mechanisms underlying working memory deficits in combination with functional connectivity changes in premenopausal women with breast cancer who received long-term tamoxifen treatment. Methods: A total of 31 premenopausal women with breast cancer who received tamoxifen and 32 matched healthy control participants were included. The participants completed n-back tasks and underwent resting-state functional magnetic resonance imaging, which measure working memory performance and brain functional connectivity, respectively. A seed-based functional connectivity analysis within the whole brain was conducted, for which the dorsolateral prefrontal cortex was chosen as the seed region. Results: Our results indicated that the tamoxifen group had significant deficits in working memory and general executive function performance and significantly lower functional connectivity of the right dorsolateral prefrontal cortex with the right hippocampus compared with the healthy controls. There were no significant changes in functional connectivity in the left dorsolateral prefrontal cortex within the whole brain between the tamoxifen group and healthy controls. Moreover, significant correlations were found in the tamoxifen group between the functional connectivity strength of the dorsolateral prefrontal cortex with the right hippocampus and decreased working memory performance. Conclusion: This study demonstrates that the prefrontal cortex and hippocampus may be affected by tamoxifen treatment, supporting an antagonistic role of tamoxifen in the long-term treatment of breast cancer patients. PMID:28177081

The prefrontal oxygenation and ventilatory responses at start of one-legged cycling exercise have relation to central command.

PubMed

Asahara, Ryota; Matsukawa, Kanji; Ishii, Kei; Liang, Nan; Endo, Kana

2016-11-01

When performing exercise arbitrarily, activation of central command should start before the onset of exercise, but when exercise is forced to start with cue, activation of central command should be delayed. We examined whether the in-advance activation of central command influenced the ventilatory response and reflected in the prefrontal oxygenation, by comparing the responses during exercise with arbitrary and cued start. The breath-by-breath respiratory variables and the prefrontal oxygenated-hemoglobin concentration (Oxy-Hb) were measured during one-legged cycling. Minute ventilation (V̇e) at the onset of arbitrary one-legged cycling was augmented to a greater extent than cued cycling, while end-tidal carbon dioxide tension (ETco 2 ) decreased irrespective of arbitrary or cued start. Symmetric increase in the bilateral prefrontal Oxy-Hb occurred before and at the onset of arbitrary one-legged cycling, whereas such an increase was absent with cued start. The time course and magnitude of the increased prefrontal oxygenation were not influenced by the extent of subjective rating of perceived exertion and were the same as those of the prefrontal oxygenation during two-legged cycling previously reported. Mental imagery or passive performance of the one-legged cycling increased V̇e and decreased ETco 2 Neither intervention, however, augmented the prefrontal Oxy-Hb. The changes in ETco 2 could not explain the prefrontal oxygenation response during voluntary or passive one-legged cycling. Taken together, it is likely that the in-advance activation of central command influenced the ventilatory response by enhancing minute ventilation at the onset of one-legged cycling exercise and reflected in the preexercise increase in the prefrontal oxygenation. Copyright © 2016 the American Physiological Society.

Prefrontal Cortex Networks Shift from External to Internal Modes during Learning.

PubMed

Brincat, Scott L; Miller, Earl K

2016-09-14

As we learn about items in our environment, their neural representations become increasingly enriched with our acquired knowledge. But there is little understanding of how network dynamics and neural processing related to external information changes as it becomes laden with "internal" memories. We sampled spiking and local field potential activity simultaneously from multiple sites in the lateral prefrontal cortex (PFC) and the hippocampus (HPC)-regions critical for sensory associations-of monkeys performing an object paired-associate learning task. We found that in the PFC, evoked potentials to, and neural information about, external sensory stimulation decreased while induced beta-band (∼11-27 Hz) oscillatory power and synchrony associated with "top-down" or internal processing increased. By contrast, the HPC showed little evidence of learning-related changes in either spiking activity or network dynamics. The results suggest that during associative learning, PFC networks shift their resources from external to internal processing. As we learn about items in our environment, their representations in our brain become increasingly enriched with our acquired "top-down" knowledge. We found that in the prefrontal cortex, but not the hippocampus, processing of external sensory inputs decreased while internal network dynamics related to top-down processing increased. The results suggest that during learning, prefrontal cortex networks shift their resources from external (sensory) to internal (memory) processing. Copyright © 2016 the authors 0270-6474/16/369739-16$15.00/0.

Prefrontal Cortex Networks Shift from External to Internal Modes during Learning

PubMed Central

Brincat, Scott L.

2016-01-01

As we learn about items in our environment, their neural representations become increasingly enriched with our acquired knowledge. But there is little understanding of how network dynamics and neural processing related to external information changes as it becomes laden with “internal” memories. We sampled spiking and local field potential activity simultaneously from multiple sites in the lateral prefrontal cortex (PFC) and the hippocampus (HPC)—regions critical for sensory associations—of monkeys performing an object paired-associate learning task. We found that in the PFC, evoked potentials to, and neural information about, external sensory stimulation decreased while induced beta-band (∼11–27 Hz) oscillatory power and synchrony associated with “top-down” or internal processing increased. By contrast, the HPC showed little evidence of learning-related changes in either spiking activity or network dynamics. The results suggest that during associative learning, PFC networks shift their resources from external to internal processing. SIGNIFICANCE STATEMENT As we learn about items in our environment, their representations in our brain become increasingly enriched with our acquired “top-down” knowledge. We found that in the prefrontal cortex, but not the hippocampus, processing of external sensory inputs decreased while internal network dynamics related to top-down processing increased. The results suggest that during learning, prefrontal cortex networks shift their resources from external (sensory) to internal (memory) processing. PMID:27629722

Adaptation to conflict via context-driven anticipatory signals in the dorsomedial prefrontal cortex.

PubMed

Horga, Guillermo; Maia, Tiago V; Wang, Pengwei; Wang, Zhishun; Marsh, Rachel; Peterson, Bradley S

2011-11-09

Behavioral interference elicited by competing response tendencies adapts to contextual changes. Recent nonhuman primate research suggests a key mnemonic role of distinct prefrontal cells in supporting such context-driven behavioral adjustments by maintaining conflict information across trials, but corresponding prefrontal functions have yet to be probed in humans. Using event-related functional magnetic resonance imaging, we investigated the human neural substrates of contextual adaptations to conflict. We found that a neural system comprising the rostral dorsomedial prefrontal cortex and portions of the dorsolateral prefrontal cortex specifically encodes the history of previously experienced conflict and influences subsequent adaptation to conflict on a trial-by-trial basis. This neural system became active in anticipation of stimulus onsets during preparatory periods and interacted with a second neural system engaged during the processing of conflict. Our findings suggest that a dynamic interaction between a system that represents conflict history and a system that resolves conflict underlies the contextual adaptation to conflict.

Adaptation to Conflict via Context-Driven Anticipatory Signals in the Dorsomedial Prefrontal Cortex

PubMed Central

Horga, Guillermo; Maia, Tiago V.; Wang, Pengwei; Wang, Zhishun; Marsh, Rachel; Peterson, Bradley S.

2011-01-01

Behavioral interference elicited by competing response tendencies adapts to contextual changes. Recent nonhuman primate research suggests a key mnemonic role of distinct prefrontal cells in supporting such context-driven behavioral adjustments by maintaining conflict information across trials, but corresponding prefrontal functions have yet to be probed in humans. Using event-related functional magnetic resonance imaging (fMRI), we investigated the human neural substrates of contextual adaptations to conflict. We found that a neural system comprising the rostral dorsomedial prefrontal cortex and portions of the dorsolateral prefrontal cortex specifically encodes the history of previously experienced conflict and influences subsequent adaptation to conflict on a trial-by-trial basis. This neural system became active in anticipation of stimulus onsets during preparatory periods and interacted with a second neural system engaged during the processing of conflict. Our findings suggest that a dynamic interaction between a system that represents conflict history and a system that resolves conflict underlies the contextual adaptation to conflict. PMID:22072672

Dissociable prefrontal brain systems for attention and emotion

NASA Astrophysics Data System (ADS)

Yamasaki, Hiroshi; Labar, Kevin S.; McCarthy, Gregory

2002-08-01

The prefrontal cortex has been implicated in a variety of attentional, executive, and mnemonic mental operations, yet its functional organization is still highly debated. The present study used functional MRI to determine whether attentional and emotional functions are segregated into dissociable prefrontal networks in the human brain. Subjects discriminated infrequent and irregularly presented attentional targets (circles) from frequent standards (squares) while novel distracting scenes, parametrically varied for emotional arousal, were intermittently presented. Targets differentially activated middle frontal gyrus, posterior parietal cortex, and posterior cingulate gyrus. Novel distracters activated inferior frontal gyrus, amygdala, and fusiform gyrus, with significantly stronger activation evoked by the emotional scenes. The anterior cingulate gyrus was the only brain region with equivalent responses to attentional and emotional stimuli. These results show that attentional and emotional functions are segregated into parallel dorsal and ventral streams that extend into prefrontal cortex and are integrated in the anterior cingulate. These findings may have implications for understanding the neural dynamics underlying emotional distractibility on attentional tasks in affective disorders. novelty | prefrontal cortex | amygdala | cingulate gyrus

Identification of prefrontal cortex (BA10) activation while performing Stroop test using diffuse optical tomography

NASA Astrophysics Data System (ADS)

Khadka, Sabin; Chityala, Srujan R.; Tian, Fenghua; Liu, Hanli

2011-03-01

Stroop test is commonly used as a behavior-testing tool for psychological examinations that are related to attention and cognitive control of the human brain. Studies have shown activations in Broadmann area 10 (BA10) of prefrontal cortex (PFC) during attention and cognitive process. The use of diffuse optical tomography (DOT) for human brain mapping is becoming more prevalent. In this study we expect to find neural correlates between the performed cognitive tasks and hemodynamic signals detected by a DOT system. Our initial observation showed activation of oxy-hemoglobin concentration in BA 10, which is consistent with some results seen by positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). Our study demonstrates the possibility of combining DOT with Stroop test to quantitatively investigate cognitive functions of the human brain at the prefrontal cortex.

Association of GSK-3β genetic variation with GSK-3β expression, prefrontal cortical thickness, prefrontal physiology, and schizophrenia.

PubMed

Blasi, Giuseppe; Napolitano, Francesco; Ursini, Gianluca; Di Giorgio, Annabella; Caforio, Grazia; Taurisano, Paolo; Fazio, Leonardo; Gelao, Barbara; Attrotto, Maria Teresa; Colagiorgio, Lucia; Todarello, Giovanna; Piva, Francesco; Papazacharias, Apostolos; Masellis, Rita; Mancini, Marina; Porcelli, Annamaria; Romano, Raffaella; Rampino, Antonio; Quarto, Tiziana; Giulietti, Matteo; Lipska, Barbara K; Kleinman, Joel E; Popolizio, Teresa; Weinberger, Daniel R; Usiello, Alessandro; Bertolino, Alessandro

2013-08-01

OBJECTIVE Glycogen synthase kinase 3β (GSK-3β) is an enzyme implicated in neurodevelopmental processes with a broad range of substrates mediating several canonical signaling pathways in the brain. The authors investigated the association of variation in the GSK-3β gene with a series of progressively more complex phenotypes of relevance to schizophrenia, a neurodevelopmental disorder with strong genetic risk. METHOD Based on computer predictions, the authors investigated in humans the association of GSK-3β functional variation with 1) GSK-3β mRNA expression from postmortem prefrontal cortex, 2) GSK-3β and β-catenin protein expression from peripheral blood mononuclear cells (PBMCs), 3) prefrontal imaging phenotypes, and 4) diagnosis of schizophrenia. RESULTS Consistent with predictions, the TT genotype of a single-nucleotide polymorphism in GSK-3β (rs12630592) was associated with reduced GSK-3β mRNA from postmortem prefrontal cortex. Furthermore, this genotype was associated with GSK-3β protein expression and kinase activity, as well as with downstream effects on β-catenin expression in PBMCs. Finally, the TT genotype was associated with attenuated functional MRI prefrontal activity, reduced prefrontal cortical thickness, and diagnosis of schizophrenia. CONCLUSIONS These results suggest that GSK-3β variation is implicated in multiple phenotypes relevant to schizophrenia.

Microbiota-driven transcriptional changes in prefrontal cortex override genetic differences in social behavior

PubMed Central

Gacias, Mar; Gaspari, Sevasti; Santos, Patricia-Mae G; Tamburini, Sabrina; Andrade, Monica; Zhang, Fan; Shen, Nan; Tolstikov, Vladimir; Kiebish, Michael A; Dupree, Jeffrey L; Zachariou, Venetia; Clemente, Jose C; Casaccia, Patrizia

2016-01-01

Gene-environment interactions impact the development of neuropsychiatric disorders, but the relative contributions are unclear. Here, we identify gut microbiota as sufficient to induce depressive-like behaviors in genetically distinct mouse strains. Daily gavage of vehicle (dH2O) in nonobese diabetic (NOD) mice induced a social avoidance behavior that was not observed in C57BL/6 mice. This was not observed in NOD animals with depleted microbiota via oral administration of antibiotics. Transfer of intestinal microbiota, including members of the Clostridiales, Lachnospiraceae and Ruminococcaceae, from vehicle-gavaged NOD donors to microbiota-depleted C57BL/6 recipients was sufficient to induce social avoidance and change gene expression and myelination in the prefrontal cortex. Metabolomic analysis identified increased cresol levels in these mice, and exposure of cultured oligodendrocytes to this metabolite prevented myelin gene expression and differentiation. Our results thus demonstrate that the gut microbiota modifies the synthesis of key metabolites affecting gene expression in the prefrontal cortex, thereby modulating social behavior. DOI: http://dx.doi.org/10.7554/eLife.13442.001 PMID:27097105

Egalitarian reward contingency in competitive games and primate prefrontal neuronal activity.

PubMed

Hosokawa, Takayuki; Watanabe, Masataka

2015-01-01

How people work to obtain a reward depends on the context of the reward delivery, such as the presence/absence of competition and the contingency of reward delivery. Since resources are limited, winning a competition is critically important for organisms' obtaining a reward. People usually expect ordinary performance-reward contingency, with better performers obtaining better rewards. Unordinary reward contingency, such as egalitarianism (equal rewards/no-rewards to both good and poor performers), dampens people's motivation. We previously reported that monkeys were more motivated, and neurons in the lateral prefrontal cortex (LPFC) showed higher outcome-related activity in a competitive than in a noncompetitive game (Hosokawa and Watanabe, 2012). However, monkey's behavior and LPFC neuronal activity have not been examined in a competitive situation with an unordinary performance-reward contingency. Also, the fixed performance-reward contingency in the previous study did not allow us to examine effects of win/loss separately from those of reward/no-reward on prefrontal neuronal activity. Here, we employed the egalitarian competitive situation in which both the winner and loser, or neither of them, got a reward as well as the normal competitive situation in which only the winner got a reward. Monkey's behavioral performance greatly deteriorated in trials with the egalitarian outcome conditions. LPFC neurons showed activities that reflected the normal or egalitarian outcome condition while very few neurons coded win/loss independent of reward/no-reward. Importantly, we found neurons that showed reward-related activity in the normal, but not in the egalitarian outcome conditions, even though the same reward was given to the animal. These results indicate that LPFC may play an important role in monitoring the current reward contingency and integrating it with the performance outcome (win-loss) for better performing the competitive game, and thus for better survival.

Context Memory Decline in Middle Aged Adults is Related to Changes in Prefrontal Cortex Function.

PubMed

Kwon, Diana; Maillet, David; Pasvanis, Stamatoula; Ankudowich, Elizabeth; Grady, Cheryl L; Rajah, M Natasha

2016-06-01

The ability to encode and retrieve spatial and temporal contextual details of episodic memories (context memory) begins to decline at midlife. In the current study, event-related fMRI was used to investigate the neural correlates of context memory decline in healthy middle aged adults (MA) compared with young adults (YA). Participants were scanned while performing easy and hard versions of spatial and temporal context memory tasks. Scans were obtained at encoding and retrieval. Significant reductions in context memory retrieval accuracy were observed in MA, compared with YA. The fMRI results revealed that overall, both groups exhibited similar patterns of brain activity in parahippocampal cortex, ventral occipito-temporal regions and prefrontal cortex (PFC) during encoding. In contrast, at retrieval, there were group differences in ventral occipito-temporal and PFC activity, due to these regions being more activated in MA, compared with YA. Furthermore, only in YA, increased encoding activity in ventrolateral PFC, and increased retrieval activity in occipital cortex, predicted increased retrieval accuracy. In MA, increased retrieval activity in anterior PFC predicted increased retrieval accuracy. These results suggest that there are changes in PFC contributions to context memory at midlife. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Time to pay attention: attentional performance time-stamped prefrontal cholinergic activation, diurnality and performance

PubMed Central

Paolone, Giovanna; Lee, Theresa M.; Sarter, Martin

2012-01-01

Although the impairments in cognitive performance that result from shifting or disrupting daily rhythms have been demonstrated, the neuronal mechanisms that optimize fixed time daily performance are poorly understood. We previously demonstrated that daily practice of a sustained attention task (SAT) evokes a diurnal activity pattern in rats. Here we report that SAT practice at a fixed time produced practice time-stamped increases in prefrontal cholinergic neurotransmission that persisted after SAT practice was terminated and in a different environment. SAT time-stamped cholinergic activation occurred irrespective of whether the SAT was practiced during the light or dark phase or in constant light conditions. In contrast, prior daily practice of an operant schedule of reinforcement, albeit generating more rewards and lever presses per session than the SAT, neither activated the cholinergic system nor affected the animals' nocturnal activity pattern. Likewise, food-restricted animals exhibited strong food anticipatory activity (FAA) and attenuated activity during the dark period but FAA was not associated with increases in prefrontal cholinergic activity. Removal of cholinergic neurons impaired SAT performance and facilitated the reemergence of nocturnality. Shifting SAT practice away from a fixed time resulted in significantly lower performance. In conclusion, these experiments demonstrated that fixed time, daily practice of a task assessing attention generates a precisely practice time-stamped activation of the cortical cholinergic input system. Time-stamped cholinergic activation benefits fixed time performance and, if practiced during the light phase, contributes to a diurnal activity pattern. PMID:22933795

Time to pay attention: attentional performance time-stamped prefrontal cholinergic activation, diurnality, and performance.

PubMed

Paolone, Giovanna; Lee, Theresa M; Sarter, Martin

2012-08-29

Although the impairments in cognitive performance that result from shifting or disrupting daily rhythms have been demonstrated, the neuronal mechanisms that optimize fixed-time daily performance are poorly understood. We previously demonstrated that daily practice of a sustained attention task (SAT) evokes a diurnal activity pattern in rats. Here, we report that SAT practice at a fixed time produced practice time-stamped increases in prefrontal cholinergic neurotransmission that persisted after SAT practice was terminated and in a different environment. SAT time-stamped cholinergic activation occurred regardless of whether the SAT was practiced during the light or dark phase or in constant-light conditions. In contrast, prior daily practice of an operant schedule of reinforcement, albeit generating more rewards and lever presses per session than the SAT, neither activated the cholinergic system nor affected the animals' nocturnal activity pattern. Likewise, food-restricted animals exhibited strong food anticipatory activity (FAA) and attenuated activity during the dark phase but FAA was not associated with increases in prefrontal cholinergic activity. Removal of cholinergic neurons impaired SAT performance and facilitated the reemergence of nocturnality. Shifting SAT practice away from a fixed time resulted in significantly lower performance. In conclusion, these experiments demonstrated that fixed-time, daily practice of a task assessing attention generates a precisely practice time-stamped activation of the cortical cholinergic input system. Time-stamped cholinergic activation benefits fixed-time performance and, if practiced during the light phase, contributes to a diurnal activity pattern.

Prefrontal transcranial direct current stimulation alters activation and connectivity in cortical and subcortical reward systems: a tDCS-fMRI study.

PubMed

Weber, Matthew J; Messing, Samuel B; Rao, Hengyi; Detre, John A; Thompson-Schill, Sharon L

2014-08-01

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique used both experimentally and therapeutically to modulate regional brain function. However, few studies have directly measured the aftereffects of tDCS on brain activity or examined changes in task-related brain activity consequent to prefrontal tDCS. To investigate the neural effects of tDCS, we collected fMRI data from 22 human subjects, both at rest and while performing the Balloon Analog Risk Task (BART), before and after true or sham transcranial direct current stimulation. TDCS decreased resting blood perfusion in orbitofrontal cortex and the right caudate and increased task-related activity in the right dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) in response to losses but not wins or increasing risk. Network analysis showed that whole-brain connectivity of the right ACC correlated positively with the number of pumps subjects were willing to make on the BART, and that tDCS reduced connectivity between the right ACC and the rest of the brain. Whole-brain connectivity of the right DLPFC also correlated negatively with pumps on the BART, as prior literature would suggest. Our results suggest that tDCS can alter activation and connectivity in regions distal to the electrodes. Copyright © 2014 Wiley Periodicals, Inc.

Prefrontal Engagement during Source Memory Retrieval Depends on the Prior Encoding Task

PubMed Central

Kuo, Trudy Y.; Van Petten, Cyma

2008-01-01

The prefrontal cortex is strongly engaged by some, but not all, episodic memory tests. Prior work has shown that source recognition tests—those that require memory for conjunctions of studied attributes—yield deficient performance in patients with prefrontal damage and greater prefrontal activity in healthy subjects, as compared to simple recognition tests. Here, we tested the hypothesis that there is no intrinsic relationship between the prefrontal cortex and source memory, but that the prefrontal cortex is engaged by the demand to retrieve weakly encoded relationships. Subjects attempted to remember object/color conjunctions after an encoding task that focused on object identity alone, and an integrative encoding task that encouraged attention to object/color relationships. After the integrative encoding task, the late prefrontal brain electrical activity that typically occurs in source memory tests was eliminated. Earlier brain electrical activity related to successful recognition of the objects was unaffected by the nature of prior encoding. PMID:16839287

Increased noradrenergic activity in prefrontal cortex slices of an animal model for attention-deficit hyperactivity disorder--the spontaneously hypertensive rat.

PubMed

Russell, V; Allie, S; Wiggins, T

2000-12-20

Spontaneously hypertensive rats (SHR) are used as a model for attention-deficit/hyperactivity disorder (ADHD) since SHR are hyperactive and they show defective sustained attention in behavioral tasks. Using an in vitro superfusion technique we showed that norepinephrine (NE) release from prefrontal cortex slices of SHR was not different from that of their Wistar-Kyoto (WKY) control rats when stimulated either electrically or by exposure to buffer containing 25 mM K(+). The monoamine vesicle transporter is, therefore, unlikely to be responsible for the deficiency in DA observed in SHR, since, in contrast to DA, vesicle stores of NE do not appear to be depleted in SHR. In addition, alpha(2)-adrenoceptor mediated inhibition of NE release was reduced in SHR, suggesting that autoreceptor function was deficient in prefrontal cortex of SHR. So, while DA neurotransmission appears to be down-regulated in SHR, the NE system appears to be under less inhibitory control than in WKY suggesting hypodopaminergic and hypernoradrenergic activity in prefrontal cortex of SHR. These findings are consistent with the hypothesis that the behavioral disturbances of ADHD are the result of an imbalance between NE and DA systems in the prefrontal cortex, with inhibitory DA activity being decreased and NE activity increased relative to controls.

Association of Oxytocin and Parental Prefrontal Activation during Reunion with Infant: A Functional Near-Infrared Spectroscopy Study.

PubMed

Ito, Jun; Fujiwara, Takeo; Monden, Yukifumi; Yamagata, Takanori; Ohira, Hideki

2017-01-01

Although previous studies have revealed the role of oxytocin (OT) in parental behavior, the role of OT has not been investigated through the direct assessment of prefrontal brain activation during parenting. By using functional near-infrared spectroscopy, we aimed to show the relationship between parental [maternal ( N  = 15) and paternal ( N  = 21)] OT levels and the activation of the prefrontal cortex (PFC), while holding their infants after separation. Baseline OT levels were measured in the subjects' saliva samples before the experiment. Prefrontal brain activation was assessed in participants sitting alone on a chair (i.e., separation from their infant for 120 s) and during the target period (i.e., holding their infant for 45 s), which was done in triplicate. The oxygen hemoglobin (oxy-Hb) dissociation curve significantly increased in 9 out of 22 channels on the PFC when maternal and paternal samples were combined. However, only the fathers showed a correlation between salivary OT and oxy-Hb signal. Furthermore, while holding their infants, high-OT fathers showed left hemispheric dominance compared to low-OT fathers, while high-OT mothers showed right hemispheric dominance compared to low-OT mothers. This study showed that fathers with high-OT levels showed neural activation with left hemispheric dominance, while holding their infants, suggesting that increase of OT level might activate paternal PFC related to parenting behavior, although the same is not true for mothers.

Prefrontal activity during response inhibition decreases over time in the postpartum period.

PubMed

Bannbers, Elin; Gingnell, Malin; Engman, Jonas; Morell, Arvid; Sylvén, Sara; Skalkidou, Alkistis; Kask, Kristiina; Bäckström, Torbjörn; Wikström, Johan; Poromaa, Inger Sundström

2013-03-15

The postpartum period is characterized by complex hormonal changes, but human imaging studies in the postpartum period have thus far predominantly focused on the neural correlates of maternal behavior or postpartum depression, whereas longitudinal studies on neural correlates of cognitive function across the postpartum period in healthy women are lacking. The aim of this study was to longitudinally examine response inhibition, as a measure of executive function, during the postpartum period and its neural correlates in healthy postpartum women and non-postpartum controls. Thirteen healthy postpartum women underwent event-related functional magnetic resonance imaging while performing a Go/NoGo task. The first assessment was made within 48 h of delivery, and the second at 4-7 weeks postpartum. In addition, 13 healthy women examined twice during the menstrual cycle were included as non-postpartum controls. In postpartum women region of interest analyses revealed task-related decreased activations in the right inferior frontal gyrus, right anterior cingulate, and bilateral precentral gyri at the late postpartum assessment. Generally, postpartum women displayed lower activity during response inhibition in the bilateral inferior frontal gyri and precentral gyri compared to non-postpartum controls. No differences in performance on the Go/NoGo task were found between time-points or between groups. In conclusion, this study has discovered that brain activity in prefrontal areas during a response inhibition task decreases throughout the course of the first postpartum weeks and is lower than in non-postpartum controls. Further studies on the normal adaptive brain activity changes that occur during the postpartum period are warranted. Copyright © 2012 Elsevier B.V. All rights reserved.

On short-term memory of prefrontal cortex using near-infrared spectroscopy

NASA Astrophysics Data System (ADS)

Li, Chengjun; Gan, Zhuo; Gong, Hui; Luo, Qingming; Zeng, Shaoqun

2003-12-01

For studying prefrontal cortical function in short-term memory two tasks were designed. In task one, a plus expression appears on screen for 300 milliseconds every other 2 seconds and the subject is required to give it"s answer but not to remember it. In task two, an Arabic numeral presents on screen as the same frequency as in task one. While a number is present, the subject need adding it to the sum he got last time. As subjects, 26 children participated in the work. Blood volume changes(BVCs) of right prefrontal cortex(PC) under two cognitive tasks were examined using functional near infrared imaging(fNIRI), a noninvasive technique for localizing regional BVCs which correlate with neural activities. The BVCs caused by short-term memory for numbers were retrieved from BVCs by task one and task two. Results revealed that short-term memory is related to PC and the near-infrared spectroscopy(NIRS) can be used to study prefrontal cortical function in short-term memory.

DRD2/CHRNA5 Interaction on Prefrontal Biology and Physiology during Working Memory

PubMed Central

Fazio, Leonardo; D'Ambrosio, Enrico; Gelao, Barbara; Tomasicchio, Aldo; Selvaggi, Pierluigi; Taurisano, Paolo; Quarto, Tiziana; Masellis, Rita; Rampino, Antonio; Caforio, Grazia; Popolizio, Teresa; Blasi, Giuseppe; Sadee, Wolfgang; Bertolino, Alessandro

2014-01-01

Background Prefrontal behavior and activity in humans are heritable. Studies in animals demonstrate an interaction between dopamine D2 receptors and nicotinic acetylcholine receptors on prefrontal behavior but evidence in humans is weak. Therefore, we hypothesize that genetic variation regulating dopamine D2 and nicotinic acetylcholine receptor signaling impact prefrontal cortex activity and related cognition. To test this hypothesis in humans, we explored the interaction between functional genetic variants in the D2 receptor gene (DRD2, rs1076560) and in the nicotinic receptor α5 gene (CHRNA5, rs16969968) on both dorsolateral prefrontal cortex mediated behavior and physiology during working memory and on prefrontal gray matter volume. Methods A large sample of healthy subjects was compared for genotypic differences for DRD2 rs1076560 (G>T) and CHNRA5 rs16969968 (G>A) on prefrontal phenotypes, including cognitive performance at the N-Back task, prefrontal physiology with BOLD fMRI during performance of the 2-Back working memory task, and prefrontal morphometry with structural MRI. Results We found that DRD2 rs1076560 and CHNRA5 rs16969968 interact to modulate cognitive function, prefrontal physiology during working memory, and prefrontal gray matter volume. More specifically, CHRNA5-AA/DRD2-GT subjects had greater behavioral performance, more efficient prefrontal cortex activity at 2Back working memory task, and greater prefrontal gray matter volume than the other genotype groups. Conclusions The present data extend previous studies in animals and enhance our understanding of dopamine and acetylcholine signaling in the human prefrontal cortex, demonstrating interactions elicited by working memory that are modulated by genetic variants in DRD2 and CHRNA5. PMID:24819610

DRD2/CHRNA5 interaction on prefrontal biology and physiology during working memory.

PubMed

Di Giorgio, Annabella; Smith, Ryan M; Fazio, Leonardo; D'Ambrosio, Enrico; Gelao, Barbara; Tomasicchio, Aldo; Selvaggi, Pierluigi; Taurisano, Paolo; Quarto, Tiziana; Masellis, Rita; Rampino, Antonio; Caforio, Grazia; Popolizio, Teresa; Blasi, Giuseppe; Sadee, Wolfgang; Bertolino, Alessandro

2014-01-01

Prefrontal behavior and activity in humans are heritable. Studies in animals demonstrate an interaction between dopamine D2 receptors and nicotinic acetylcholine receptors on prefrontal behavior but evidence in humans is weak. Therefore, we hypothesize that genetic variation regulating dopamine D2 and nicotinic acetylcholine receptor signaling impact prefrontal cortex activity and related cognition. To test this hypothesis in humans, we explored the interaction between functional genetic variants in the D2 receptor gene (DRD2, rs1076560) and in the nicotinic receptor α5 gene (CHRNA5, rs16969968) on both dorsolateral prefrontal cortex mediated behavior and physiology during working memory and on prefrontal gray matter volume. A large sample of healthy subjects was compared for genotypic differences for DRD2 rs1076560 (G>T) and CHNRA5 rs16969968 (G>A) on prefrontal phenotypes, including cognitive performance at the N-Back task, prefrontal physiology with BOLD fMRI during performance of the 2-Back working memory task, and prefrontal morphometry with structural MRI. We found that DRD2 rs1076560 and CHNRA5 rs16969968 interact to modulate cognitive function, prefrontal physiology during working memory, and prefrontal gray matter volume. More specifically, CHRNA5-AA/DRD2-GT subjects had greater behavioral performance, more efficient prefrontal cortex activity at 2Back working memory task, and greater prefrontal gray matter volume than the other genotype groups. The present data extend previous studies in animals and enhance our understanding of dopamine and acetylcholine signaling in the human prefrontal cortex, demonstrating interactions elicited by working memory that are modulated by genetic variants in DRD2 and CHRNA5.

Hippocampal and ventral medial prefrontal activation during retrieval-mediated learning supports novel inference.

PubMed

Zeithamova, Dagmar; Dominick, April L; Preston, Alison R

2012-07-12

Memory enables flexible use of past experience to inform new behaviors. Although leading theories hypothesize that this fundamental flexibility results from the formation of integrated memory networks relating multiple experiences, the neural mechanisms that support memory integration are not well understood. Here, we demonstrate that retrieval-mediated learning, whereby prior event details are reinstated during encoding of related experiences, supports participants' ability to infer relationships between distinct events that share content. Furthermore, we show that activation changes in a functionally coupled hippocampal and ventral medial prefrontal cortical circuit track the formation of integrated memories and successful inferential memory performance. These findings characterize the respective roles of these regions in retrieval-mediated learning processes that support relational memory network formation and inferential memory in the human brain. More broadly, these data reveal fundamental mechanisms through which memory representations are constructed into prospectively useful formats. Copyright © 2012 Elsevier Inc. All rights reserved.

Hippocampal and ventral medial prefrontal activation during retrieval-mediated learning supports novel inference

PubMed Central

Zeithamova, Dagmar; Dominick, April L.; Preston, Alison R.

2012-01-01

SUMMARY Memory enables flexible use of past experience to inform new behaviors. Though leading theories hypothesize that this fundamental flexibility results from the formation of integrated memory networks relating multiple experiences, the neural mechanisms that support memory integration are not well understood. Here, we demonstrate that retrieval-mediated learning, whereby prior event details are reinstated during encoding of related experiences, supports participants’ ability to infer relationships between distinct events that share content. Furthermore, we show that activation changes in a functionally coupled hippocampal and ventral medial prefrontal cortical circuit track the formation of integrated memories and successful inferential memory performance. These findings characterize the respective roles of these regions in retrieval-mediated learning processes that support relational memory network formation and inferential memory in the human brain. More broadly, these data reveal fundamental mechanisms through which memory representations are constructed into prospectively useful formats. PMID:22794270

Adolescent exposure to THC in female rats disrupts developmental changes in the prefrontal cortex.

PubMed

Rubino, Tiziana; Prini, Pamela; Piscitelli, Fabiana; Zamberletti, Erica; Trusel, Massimo; Melis, Miriam; Sagheddu, Claudia; Ligresti, Alessia; Tonini, Raffaella; Di Marzo, Vincenzo; Parolaro, Daniela

2015-01-01

Current concepts suggest that exposure to THC during adolescence may act as a risk factor for the development of psychiatric disorders later in life. However, the molecular underpinnings of this vulnerability are still poorly understood. To analyze this, we investigated whether and how THC exposure in female rats interferes with different maturational events occurring in the prefrontal cortex during adolescence through biochemical, pharmacological and electrophysiological means. We found that the endocannabinoid system undergoes maturational processes during adolescence and that THC exposure disrupts them, leading to impairment of both endocannabinoid signaling and endocannabinoid-mediated LTD in the adult prefrontal cortex. THC also altered the maturational fluctuations of NMDA subunits, leading to larger amounts of gluN2B at adulthood. Adult animals exposed to THC during adolescence also showed increased AMPA gluA1 with no changes in gluA2 subunits. Finally, adolescent THC exposure altered cognition at adulthood. All these effects seem to be triggered by the disruption of the physiological role played by the endocannabinoid system during adolescence. Indeed, blockade of CB1 receptors from early to late adolescence seems to prevent the occurrence of pruning at glutamatergic synapses. These results suggest that vulnerability of adolescent female rats to long-lasting THC adverse effects might partly reside in disruption of the pivotal role played by the endocannabinoid system in the prefrontal cortex maturation. Copyright © 2014 Elsevier Inc. All rights reserved.

Prefrontal cerebral blood volume patterns while playing video games--a near-infrared spectroscopy study.

PubMed

Nagamitsu, Shinichiro; Nagano, Miki; Yamashita, Yushiro; Takashima, Sachio; Matsuishi, Toyojiro

2006-06-01

Video game playing is an attractive form of entertainment among school-age children. Although this activity reportedly has many adverse effects on child development, these effects remain controversial. To investigate the effect of video game playing on regional cerebral blood volume, we measured cerebral hemoglobin concentrations using near-infrared spectroscopy in 12 normal volunteers consisting of six children and six adults. A Hitachi Optical Topography system was used to measure hemoglobin changes. For all subjects, the video game Donkey Kong was played on a Game Boy device. After spectroscopic probes were positioned on the scalp near the target brain regions, the participants were asked to play the game for nine periods of 15s each, with 15-s rest intervals between these task periods. Significant increases in bilateral prefrontal total-hemoglobin concentrations were observed in four of the adults during video game playing. On the other hand, significant decreases in bilateral prefrontal total-hemoglobin concentrations were seen in two of the children. A significant positive correlation between mean oxy-hemoglobin changes in the prefrontal region and those in the bilateral motor cortex area was seen in adults. Playing video games gave rise to dynamic changes in cerebral blood volume in both age groups, while the difference in the prefrontal oxygenation patterns suggested an age-dependent utilization of different neural circuits during video game tasks.

Prefrontal cortical network activity: Opposite effects of psychedelic hallucinogens and D1/D5 dopamine receptor activation

PubMed Central

Lambe, Evelyn K.; Aghajanian, George K.

2007-01-01

The fine-tuning of network activity provides a modulating influence on how information is processed and interpreted in the brain. Here, we use brain slices of rat prefrontal cortex to study how recurrent network activity is affected by neuromodulators known to alter normal cortical function. We previously determined that glutamate spillover and stimulation of extrasynaptic NMDA receptors are required to support hallucinogen-induced cortical network activity. Since microdialysis studies suggest that psychedelic hallucinogens and dopamine D1/D5 receptor agonists have opposite effects on extracellular glutamate in prefrontal cortex, we hypothesized that these two families of psychoactive drugs would have opposite effects on cortical network activity. We found that network activity can be enhanced by DOI (a psychedelic hallucinogen that is a partial agonist of serotonin 5-HT2A/2C receptors) and suppressed by the selective D1/D5 agonist SKF 38393. This suppression could be mimicked by direct activation of adenylyl cyclase with forskolin or by addition of a cAMP analog. These findings are consistent with previous work showing that activation of adenylyl cyclase can upregulate neuronal glutamate transporters, thereby decreasing synaptic spillover of glutamate. Consistent with this hypothesis, a low concentration of the glutamate transporter inhibitor TBOA restored electrically-evoked recurrent activity in the presence of a selective D1/D5 agonist, whereas recurrent activity in the presence of a low level of the GABAA antagonist bicuculline was not resistant to suppression by the D1/D5 agonist. The tempering of network UP states by D1/D5 receptor activation may have implications for the proposed use of D1/D5 agonists in the treatment of schizophrenia. PMID:17293055

Task-dependent modulations of prefrontal and hippocampal activity during intrinsic word production.

PubMed

Whitney, Carin; Weis, Susanne; Krings, Timo; Huber, Walter; Grossman, Murray; Kircher, Tilo

2009-04-01

Functional imaging studies of single word production have consistently reported activation of the lateral prefrontal and cingulate cortex. Its contribution has been shown to be sensitive to task demands, which can be manipulated by the degree of response specification. Compared with classical verbal fluency, free word association relies less on response restrictions but to a greater extent on associative binding processes, usually subserved by the hippocampus. To elucidate the relevance of the frontal and medial-temporal areas during verbal retrieval tasks, we applied varying degrees of response specification. During fMRI data acquisition, 18 subjects performed a free verbal association (FVA), a semantic verbal fluency (SVF) task, and a phonological verbal fluency (PVF) task. Externally guided word production served as a baseline condition to control for basic articulatory and reading processes. As expected, increased brain activity was observed in the left lateral and bilateral medial frontal cortices for SVF and PVF. The anterior cingulate gyrus was the only structure common to both fluency tasks in direct comparison to the less restricted FVA task. The hippocampus was engaged during associative and semantic retrieval. Interestingly, hippocampal activity was selectively evident during FVA in direct comparison to SVF when it was controlled for stimulus-response relations. The current data confirm the role of the left prefrontal-cingulate network in constrained word production. Hippocampal activity during spontaneous word production is a novel finding and seems to be dependent on the retrieval process (free vs. constrained) rather than the variety of stimulus-response relationships that is involved.

Pedophilia is linked to reduced activation in hypothalamus and lateral prefrontal cortex during visual erotic stimulation.

PubMed

Walter, Martin; Witzel, Joachim; Wiebking, Christine; Gubka, Udo; Rotte, Michael; Schiltz, Kolja; Bermpohl, Felix; Tempelmann, Claus; Bogerts, Bernhard; Heinze, Hans Jochen; Northoff, Georg

2007-09-15

Although pedophilia is of high public concern, little is known about underlying neural mechanisms. Although pedophilic patients are sexually attracted to prepubescent children, they show no sexual interest toward adults. This study aimed to investigate the neural correlates of deficits of sexual and emotional arousal in pedophiles. Thirteen pedophilic patients and 14 healthy control subjects were tested for differential neural activity during visual stimulation with emotional and erotic pictures with functional magnetic resonance imaging. Regions showing differential activations during the erotic condition comprised the hypothalamus, the periaqueductal gray, and dorsolateral prefrontal cortex, the latter correlating with a clinical measure. Alterations of emotional processing concerned the amygdala-hippocampus and dorsomedial prefrontal cortex. Hypothesized regions relevant for processing of erotic stimuli in healthy individuals showed reduced activations during visual erotic stimulation in pedophilic patients. This suggests an impaired recruitment of key structures that might contribute to an altered sexual interest of these patients toward adults.

Medial prefrontal brain activation to anticipated reward and loss in obsessive–compulsive disorder☆

PubMed Central

Kaufmann, C.; Beucke, J.C.; Preuße, F.; Endrass, T.; Schlagenhauf, F.; Heinz, A.; Juckel, G.; Kathmann, N.

2013-01-01

Obsessive–compulsive disorder (OCD) is associated with dysfunctional brain activity in several regions which are also involved in the processing of motivational stimuli. Processing of reward and punishment appears to be of special importance to understand clinical symptoms. There is evidence for higher sensitivity to punishment in patients with OCD which raises the question how avoidance of punishment relates to activity within the brain's reward circuitry. We employed the monetary incentive delay task paradigm optimized for modeling the anticipation phase of immediate reward and punishment, in the context of a cross-sectional event-related FMRI study comparing OCD patients and healthy control participants (n = 19 in each group). While overall behavioral performance was similar in both groups, patients showed increased activation upon anticipated losses in a medial and superior frontal cortex region extending into the cingulate cortex, and decreased activation upon anticipated rewards. No evidence was found for altered activation of dorsal or ventral striatal regions. Patients also showed more delayed responses for anticipated rewards than for anticipated losses whereas the reverse was true in healthy participants. The medial prefrontal cortex has been shown to implement a domain-general process comprising negative affect, pain and cognitive control. This process uses information about punishment to control aversively motivated actions by integrating signals arriving from subcortical regions. Our results support the notion that OCD is associated with altered sensitivity to anticipated rewards and losses in a medial prefrontal region whereas there is no significant aberrant activation in ventral or dorsal striatal brain regions during processing of reinforcement anticipation. PMID:24179774

Medial prefrontal brain activation to anticipated reward and loss in obsessive-compulsive disorder.

PubMed

Kaufmann, C; Beucke, J C; Preuße, F; Endrass, T; Schlagenhauf, F; Heinz, A; Juckel, G; Kathmann, N

2013-01-01

Obsessive-compulsive disorder (OCD) is associated with dysfunctional brain activity in several regions which are also involved in the processing of motivational stimuli. Processing of reward and punishment appears to be of special importance to understand clinical symptoms. There is evidence for higher sensitivity to punishment in patients with OCD which raises the question how avoidance of punishment relates to activity within the brain's reward circuitry. We employed the monetary incentive delay task paradigm optimized for modeling the anticipation phase of immediate reward and punishment, in the context of a cross-sectional event-related FMRI study comparing OCD patients and healthy control participants (n = 19 in each group). While overall behavioral performance was similar in both groups, patients showed increased activation upon anticipated losses in a medial and superior frontal cortex region extending into the cingulate cortex, and decreased activation upon anticipated rewards. No evidence was found for altered activation of dorsal or ventral striatal regions. Patients also showed more delayed responses for anticipated rewards than for anticipated losses whereas the reverse was true in healthy participants. The medial prefrontal cortex has been shown to implement a domain-general process comprising negative affect, pain and cognitive control. This process uses information about punishment to control aversively motivated actions by integrating signals arriving from subcortical regions. Our results support the notion that OCD is associated with altered sensitivity to anticipated rewards and losses in a medial prefrontal region whereas there is no significant aberrant activation in ventral or dorsal striatal brain regions during processing of reinforcement anticipation.

Socioeconomic disparities affect prefrontal function in children.

PubMed

Kishiyama, Mark M; Boyce, W Thomas; Jimenez, Amy M; Perry, Lee M; Knight, Robert T

2009-06-01

Social inequalities have profound effects on the physical and mental health of children. Children from low socioeconomic status (SES) backgrounds perform below children from higher SES backgrounds on tests of intelligence and academic achievement, and recent findings indicate that low SES (LSES) children are impaired on behavioral measures of prefrontal function. However, the influence of socioeconomic disparity on direct measures of neural activity is unknown. Here, we provide electrophysiological evidence indicating that prefrontal function is altered in LSES children. We found that prefrontal-dependent electrophysiological measures of attention were reduced in LSES compared to high SES (HSES) children in a pattern similar to that observed in patients with lateral prefrontal cortex (PFC) damage. These findings provide neurophysiological evidence that social inequalities are associated with alterations in PFC function in LSES children. There are a number of factors associated with LSES rearing conditions that may have contributed to these results such as greater levels of stress and lack of access to cognitively stimulating materials and experiences. Targeting specific prefrontal processes affected by socioeconomic disparity could be helpful in developing intervention programs for LSES children.

Age-related differences in prefrontal cortex activity during retrieval monitoring: testing the compensation and dysfunction accounts.

PubMed

McDonough, Ian M; Wong, Jessica T; Gallo, David A

2013-05-01

Current theories of cognitive aging emphasize that the prefrontal cortex might not only be a major source of dysfunction but also a source of compensation. We evaluated neural activity associated with retrieval monitoring--or the selection and evaluation of recollected information during memory retrieval--for evidence of dysfunction or compensation. Younger and older adults studied pictures and words and were subsequently given criterial recollection tests during event-related functional magnetic resonance imaging. Although memory accuracy was greater on the picture test than the word test in both groups, activity in right dorsolateral prefrontal cortex (DLPFC) was associated with greater retrieval monitoring demands (word test > picture test) only in younger adults. Similarly, DLPFC activity was consistently associated with greater item difficulty (studied > nonstudied) only in younger adults. Older adults instead exhibited high levels of DLPFC activity for all of these conditions, and activity was greater than younger adults even when test performance was naturally matched across the groups (picture test). Correlations also differed between DLPFC activity and test performance across the groups. Collectively, these findings are more consistent with accounts of DLPFC dysfunction than compensation, suggesting that aging disrupts the otherwise beneficial coupling between DLPFC recruitment and retrieval monitoring demands.

Increases in the right dorsolateral prefrontal cortex and decreases the rostral prefrontal cortex activation after-8 weeks of focused attention based mindfulness meditation.

PubMed

Tomasino, Barbara; Fabbro, Franco

2016-02-01

Mindfulness meditation is a form of attention control training. The training exercises the ability to repeatedly focus attention. We addressed the activation changes related to an 8-weeks mindfulness-oriented focused attention meditation training on an initially naïve subject cohort. Before and after training participants underwent an fMRI experiment, thus, although not strictly a cross over design, they served as their internal own control. During fMRI they exercised focused attention on breathing and body scan as compared to resting. We found increased and decreased activation in different parts of the prefrontal cortex (PFC) by comparing pre- vs. post-mindfulness training (MT) during breathing and body scan meditation exercises that were compared against their own resting state. In the post-MT (vs. pre-MT) meditation increased activation in the right dorsolateral PFC and in the left caudate/anterior insula and decreased activation in the rostral PFC and right parietal area 3b. Thus a brief mindfulness training caused increased activation in areas involved in sustaining and monitoring the focus of attention (dorsolateral PFC), consistent with the aim of mindfulness that is exercising focused attention mechanisms, and in the left caudate/anterior insula involved in attention and corporeal awareness and decreased activation in areas part of the "default mode" network and is involved in mentalizing (rostral PFC), consistent with the ability trained by mindfulness of reducing spontaneous mind wandering. Copyright © 2015 Elsevier Inc. All rights reserved.

Evidence for a neural correlate of a framing effect: bias-specific activity in the ventromedial prefrontal cortex during credibility judgments.

PubMed

Deppe, M; Schwindt, W; Krämer, J; Kugel, H; Plassmann, H; Kenning, P; Ringelstein, E B

2005-11-15

Neural processes within the medial prefrontal cortex play a crucial role in assessing and integrating emotional and other implicit information during decision-making. Phylogenetically, it was important for the individual to assess the relevance of all kinds of environmental stimuli in order to adapt behavior in a flexible manner. Consequently, we can in principle not exclude that environmental information covertly influences the evaluation of actually decision relevant facts ("framing effect"). To test the hypothesis that the medial prefrontal cortex is involved into a framing effect we employed functional magnetic resonance imaging (fMRI) during a binary credibility judgment task. Twenty-one subjects were asked to judge 30 normalized news magazine headlines by forced answers as "true" or "false". To confound the judgments by formally irrelevant framing information we presented each of the headlines in four different news magazines characterized by varying credibility. For each subject the susceptibility to the judgment confounder (framing information) was assessed by magazine-specific modifications of the answers given. We could show that individual activity changes of the ventromedial prefrontal cortex during the judgments correlate with the degree of an individual's susceptibility to the framing information. We found (i) a neural correlate of a framing effect as postulated by behavioral decision theorists that (ii) reflects interindividual differences in the degree of the susceptibility to framing information.

Simultaneous fNIRS and thermal infrared imaging during cognitive task reveal autonomic correlates of prefrontal cortex activity

NASA Astrophysics Data System (ADS)

Pinti, Paola; Cardone, Daniela; Merla, Arcangelo

2015-12-01

Functional Near Infrared-Spectroscopy (fNIRS) represents a powerful tool to non-invasively study task-evoked brain activity. fNIRS assessment of cortical activity may suffer for contamination by physiological noises of different origin (e.g. heart beat, respiration, blood pressure, skin blood flow), both task-evoked and spontaneous. Spontaneous changes occur at different time scales and, even if they are not directly elicited by tasks, their amplitude may result task-modulated. In this study, concentration changes of hemoglobin were recorded over the prefrontal cortex while simultaneously recording the facial temperature variations of the participants through functional infrared thermal (fIR) imaging. fIR imaging provides touch-less estimation of the thermal expression of peripheral autonomic. Wavelet analysis revealed task-modulation of the very low frequency (VLF) components of both fNIRS and fIR signals and strong coherence between them. Our results indicate that subjective cognitive and autonomic activities are intimately linked and that the VLF component of the fNIRS signal is affected by the autonomic activity elicited by the cognitive task. Moreover, we showed that task-modulated changes in vascular tone occur both at a superficial and at larger depth in the brain. Combined use of fNIRS and fIR imaging can effectively quantify the impact of VLF autonomic activity on the fNIRS signals.

Limbic and prefrontal responses to facial emotion expressions in depersonalization.

PubMed

Lemche, Erwin; Surguladze, Simon A; Giampietro, Vincent P; Anilkumar, Ananthapadmanabha; Brammer, Michael J; Sierra, Mauricio; Chitnis, Xavier; Williams, Steven C R; Gasston, David; Joraschky, Peter; David, Anthony S; Phillips, Mary L

2007-03-26

Depersonalization disorder, characterized by emotional detachment, has been associated with increased prefrontal cortical and decreased autonomic activity to emotional stimuli. Event-related fMRI with simultaneous measurements of skin conductance levels occurred in nine depersonalization disorder patients and 12 normal controls to neutral, mild and intense happy and sad facial expressions. Patients, but not controls, showed decreases in subcortical limbic activity to increasingly intense happy and sad facial expressions, respectively. For both happy and sad expressions, negative correlations between skin conductance measures in bilateral dorsal prefrontal cortices occurred only in depersonalization disorder patients. Abnormal decreases in limbic activity to increasingly intense emotional expressions, and increases in dorsal prefrontal cortical activity to emotionally arousing stimuli may underlie the emotional detachment of depersonalization disorder.

Medial Prefrontal Cortex Activity When Thinking About Others Depends on Their Age

PubMed Central

Ebner, Natalie C.; Gluth, Sebastian; Johnson, Matthew R.; Raye, Carol L.; Mitchell, Karen J.; Johnson, Marcia K.

2011-01-01

This functional magnetic resonance imaging (fMRI) study examined medial prefrontal cortex (mPFC) activity as young and older participants rated an unknown young and older person, and themselves, on personality characteristics. For both young and older participants, there was greater activation in ventral mPFC (anterior cingulate) when they made judgments about own-age than other-age individuals. Additionally, across target age and participant age, there was greater activity in a more anterior region of ventral mPFC (largely medial frontal gyrus, anterior cingulate) when participants rated others than when they rated themselves. We discuss potential interpretations of these findings in the context of previous results suggesting functional specificity of subregions of ventral mPFC. PMID:21432722

Exposure to Blue Light Increases Subsequent Functional Activation of the Prefrontal Cortex During Performance of a Working Memory Task.

PubMed

Alkozei, Anna; Smith, Ryan; Pisner, Derek A; Vanuk, John R; Berryhill, Sarah M; Fridman, Andrew; Shane, Bradley R; Knight, Sara A; Killgore, William D S

2016-09-01

Prolonged exposure to blue wavelength light has been shown to have an alerting effect, and enhances performance on cognitive tasks. A small number of studies have also shown that relatively short exposure to blue light leads to changes in functional brain responses during the period of exposure. The extent to which blue light continues to affect brain functioning during a cognitively challenging task after cessation of longer periods of exposure (i.e., roughly 30 minutes or longer), however, has not been fully investigated. A total of 35 healthy participants (18 female) were exposed to either blue (469 nm) (n = 17) or amber (578 nm) (n = 18) wavelength light for 30 minutes in a darkened room, followed immediately by functional magnetic resonance imaging (fMRI) while undergoing a working memory task (N-back task). Participants in the blue light condition were faster in their responses on the N-back task and showed increased activation in the dorsolateral (DLPFC) and ventrolateral (VLPFC) prefrontal cortex compared to those in the amber control light condition. Furthermore, greater activation within the VLPFC was correlated with faster N-back response times. This is the first study to suggest that a relatively brief, single exposure to blue light has a subsequent beneficial effect on working memory performance, even after cessation of exposure, and leads to temporarily persisting functional brain changes within prefrontal brain regions associated with executive functions. These findings may have broader implication for using blue-enriched light in a variety of work settings where alertness and quick decision-making are important. © 2016 Associated Professional Sleep Societies, LLC.

SPECT (HMPAO) support for activation of the medial prefrontal cortices during toe graphaesthesia.

PubMed

Persinger, M A; Webster, D; Tiller, S G

1998-08-01

This experiment was designed to test the construct validity of psychometric analyses that suggested a strong functional association between the accuracy for toe graphaesthesia and selective activation of neurons within the medial prefrontal regions. Single Photon Emission Computerized Tomography (SPECT) profiles were obtained for three volunteers (2 men, 1 woman) after they had been exposed to a toe graphaesthesia task or had been exposed to the control setting. The two measurements for each participant were separated by at least one week. Qualitative evaluation, using criteria employed for clinical diagnoses, of serial coronal, sagittal, and horizontal sections clearly indicated a specific increase in uptake of tracer within the rostral one-third to one-half of the medial prefrontal cortices of all three subjects during the toe graphaesthesia task compared to that during baseline conditions. The results are consistent with our neuropsychological research which indicates that toe graphaesthesia may be an accurate and useful indicator of the functional integrity of the medial surfaces of the anterior cerebral hemispheres.

Striatum-medial prefrontal cortex connectivity predicts developmental changes in reinforcement learning.

PubMed

van den Bos, Wouter; Cohen, Michael X; Kahnt, Thorsten; Crone, Eveline A

2012-06-01

During development, children improve in learning from feedback to adapt their behavior. However, it is still unclear which neural mechanisms might underlie these developmental changes. In the current study, we used a reinforcement learning model to investigate neurodevelopmental changes in the representation and processing of learning signals. Sixty-seven healthy volunteers between ages 8 and 22 (children: 8-11 years, adolescents: 13-16 years, and adults: 18-22 years) performed a probabilistic learning task while in a magnetic resonance imaging scanner. The behavioral data demonstrated age differences in learning parameters with a stronger impact of negative feedback on expected value in children. Imaging data revealed that the neural representation of prediction errors was similar across age groups, but functional connectivity between the ventral striatum and the medial prefrontal cortex changed as a function of age. Furthermore, the connectivity strength predicted the tendency to alter expectations after receiving negative feedback. These findings suggest that the underlying mechanisms of developmental changes in learning are not related to differences in the neural representation of learning signals per se but rather in how learning signals are used to guide behavior and expectations.

Relational complexity modulates activity in the prefrontal cortex during numerical inductive reasoning: an fMRI study.

PubMed

Feng, Xiao; Peng, Li; Chang-Quan, Long; Yi, Lei; Hong, Li

2014-09-01

Most previous studies investigating relational reasoning have used visuo-spatial materials. This fMRI study aimed to determine how relational complexity affects brain activity during inductive reasoning, using numerical materials. Three numerical relational levels of the number series completion task were adopted for use: 0-relational (e.g., "23 23 23"), 1-relational ("32 30 28") and 2-relational ("12 13 15") problems. The fMRI results revealed that the bilateral dorsolateral prefrontal cortex (DLPFC) showed enhanced activity associated with relational complexity. Bilateral inferior parietal lobule (IPL) activity was greater during the 1- and 2-relational level problems than during the 0-relational level problems. In addition, the left fronto-polar cortex (FPC) showed selective activity during the 2-relational level problems. The bilateral DLPFC may be involved in the process of hypothesis generation, whereas the bilateral IPL may be sensitive to calculation demands. Moreover, the sensitivity of the left FPC to the multiple relational problems may be related to the integration of numerical relations. The present study extends our knowledge of the prefrontal activity pattern underlying numerical relational processing. Copyright © 2014 Elsevier B.V. All rights reserved.

Intracerebroventricular administration of growth hormone induces morphological changes in pyramidal neurons of the hippocampus and prefrontal cortex in adult rats.

PubMed

Olivares-Hernández, Juan David; García-García, Fabio; Camacho-Abrego, Israel; Flores, Gonzalo; Juárez-Aguilar, Enrique

2018-07-01

A growing body of evidence suggests that growth hormone (GH) affects synaptic plasticity at both the molecular and electrophysiological levels. However, unclear is whether plasticity that is stimulated by GH is associated with changes in neuron structure. This study investigated the effect of intracerebroventricular (ICV) administration of GH on the morphology of pyramidal neurons of the CA1 region of the dorsal hippocampus and layer III of the prefrontal cortex. Male Wistar rats received daily ICV injections of GH (120 ng) for 7 days, and they were euthanized 21 days later. Changes in neuronal morphology were evaluated using Golgi-Cox staining and subsequent Sholl analysis. GH administration increased total dendritic length in the CA1 region of the dorsal hippocampus and prefrontal cortex. The Sholl analysis revealed an increase in dendritic length of the third to eighth branch orders in the hippocampus and from the third to sixth branch orders in the prefrontal cortex. Interestingly, GH treatment increased the density of dendritic spines in both brain regions, favoring the presence of mushroom-like spines only in the CA1 hippocampal region. Our results indicated that GH induces changes in the length of dendritic trees and the density of dendritic spines in two high-plasticity brain regions, suggesting that GH-induced synaptic plasticity at the molecular and electrophysiological levels may be associated with these structural changes in neurons. © 2018 Wiley Periodicals, Inc.

Dimensional change card sort performance associated with age-related differences in functional connectivity of lateral prefrontal cortex.

PubMed

Ezekiel, Fredrick; Bosma, Rachael; Morton, J Bruce

2013-07-01

The Dimensional Change Card Sort (DCCS) is a standard procedure for assessing executive functioning early in development. In the task, participants switch from sorting cards one way (e.g., by color) to sorting them a different way (e.g., by shape). Traditional accounts associate age-related changes in DCCS performance with circumscribed changes in lateral prefrontal cortex (lPFC) functioning, but evidence of age-related differences in the modulation of lPFC activity by switching is mixed. The current study therefore tested for possible age-related differences in functional connectivity of lPFC with regions that comprise a larger cognitive control network. Functional magnetic resonance imaging (fMRI) data collected from children and adults performing the DCCS were analyzed by means of independent components analysis (ICA). The analysis revealed several important age-related differences in functional connectivity of lPFC. In particular, lPFC was more strongly connected with the anterior cingulate, inferior parietal cortex, and the ventral tegmental area in adults than in children. Theoretical implications are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

Neuroadaptive technology enables implicit cursor control based on medial prefrontal cortex activity.

PubMed

Zander, Thorsten O; Krol, Laurens R; Birbaumer, Niels P; Gramann, Klaus

2016-12-27

The effectiveness of today's human-machine interaction is limited by a communication bottleneck as operators are required to translate high-level concepts into a machine-mandated sequence of instructions. In contrast, we demonstrate effective, goal-oriented control of a computer system without any form of explicit communication from the human operator. Instead, the system generated the necessary input itself, based on real-time analysis of brain activity. Specific brain responses were evoked by violating the operators' expectations to varying degrees. The evoked brain activity demonstrated detectable differences reflecting congruency with or deviations from the operators' expectations. Real-time analysis of this activity was used to build a user model of those expectations, thus representing the optimal (expected) state as perceived by the operator. Based on this model, which was continuously updated, the computer automatically adapted itself to the expectations of its operator. Further analyses showed this evoked activity to originate from the medial prefrontal cortex and to exhibit a linear correspondence to the degree of expectation violation. These findings extend our understanding of human predictive coding and provide evidence that the information used to generate the user model is task-specific and reflects goal congruency. This paper demonstrates a form of interaction without any explicit input by the operator, enabling computer systems to become neuroadaptive, that is, to automatically adapt to specific aspects of their operator's mindset. Neuroadaptive technology significantly widens the communication bottleneck and has the potential to fundamentally change the way we interact with technology.

White matter integrity deficits in prefrontal-amygdala pathways in Williams syndrome.

PubMed

Avery, Suzanne N; Thornton-Wells, Tricia A; Anderson, Adam W; Blackford, Jennifer Urbano

2012-01-16

Williams syndrome is a neurodevelopmental disorder associated with significant non-social fears. Consistent with this elevated non-social fear, individuals with Williams syndrome have an abnormally elevated amygdala response when viewing threatening non-social stimuli. In typically-developing individuals, amygdala activity is inhibited through dense, reciprocal white matter connections with the prefrontal cortex. Neuroimaging studies suggest a functional uncoupling of normal prefrontal-amygdala inhibition in individuals with Williams syndrome, which might underlie both the extreme amygdala activity and non-social fears. This functional uncoupling might be caused by structural deficits in underlying white matter pathways; however, prefrontal-amygdala white matter deficits have yet to be explored in Williams syndrome. We used diffusion tensor imaging to investigate prefrontal-amygdala white matter integrity differences in individuals with Williams syndrome and typically-developing controls with high levels of non-social fear. White matter pathways between the amygdala and several prefrontal regions were isolated using probabilistic tractography. Within each pathway, we tested for between-group differences in three measures of white matter integrity: fractional anisotropy (FA), radial diffusivity (RD), and parallel diffusivity (λ(1)). Individuals with Williams syndrome had lower FA, compared to controls, in several of the prefrontal-amygdala pathways investigated, indicating a reduction in white matter integrity. Lower FA in Williams syndrome was explained by significantly higher RD, with no differences in λ(1), suggestive of lower fiber density or axon myelination in prefrontal-amygdala pathways. These results suggest that deficits in the structural integrity of prefrontal-amygdala white matter pathways might underlie the increased amygdala activity and extreme non-social fears observed in Williams syndrome. Copyright © 2011 Elsevier Inc. All rights reserved.

Altered medial prefrontal activity during dynamic face processing in schizophrenia spectrum patients.

PubMed

Mothersill, Omar; Morris, Derek W; Kelly, Sinead; Rose, Emma Jane; Bokde, Arun; Reilly, Richard; Gill, Michael; Corvin, Aiden P; Donohoe, Gary

2014-08-01

Processing the emotional content of faces is recognised as a key deficit of schizophrenia, associated with poorer functional outcomes and possibly contributing to the severity of clinical symptoms such as paranoia. At the neural level, fMRI studies have reported altered limbic activity in response to facial stimuli. However, previous studies may be limited by the use of cognitively demanding tasks and static facial stimuli. To address these issues, the current study used a face processing task involving both passive face viewing and dynamic social stimuli. Such a task may (1) lack the potentially confounding effects of high cognitive demands and (2) show higher ecological validity. Functional MRI was used to examine neural activity in 25 patients with a DSM-IV diagnosis of schizophrenia/schizoaffective disorder and 21 age- and gender-matched healthy controls while they participated in a face processing task, which involved viewing videos of angry and neutral facial expressions, and a non-biological baseline condition. While viewing faces, patients showed significantly weaker deactivation of the medial prefrontal cortex, including the anterior cingulate, and decreased activation in the left cerebellum, compared to controls. Patients also showed weaker medial prefrontal deactivation while viewing the angry faces relative to baseline. Given that the anterior cingulate plays a role in processing negative emotion, weaker deactivation of this region in patients while viewing faces may contribute to an increased perception of social threat. Future studies examining the neurobiology of social cognition in schizophrenia using fMRI may help establish targets for treatment interventions. Copyright © 2014 Elsevier B.V. All rights reserved.

Central as well as Peripheral Attentional Bottlenecks in Dual-Task Performance Activate Lateral Prefrontal Cortices

PubMed Central

Szameitat, André J.; Vanloo, Azonya; Müller, Hermann J.

2016-01-01

Human information processing suffers from severe limitations in parallel processing. In particular, when required to respond to two stimuli in rapid succession, processing bottlenecks may appear at central and peripheral stages of task processing. Importantly, it has been suggested that executive functions are needed to resolve the interference arising at such bottlenecks. The aims of the present study were to test whether central attentional limitations (i.e., bottleneck at the decisional response selection stage) as well as peripheral limitations (i.e., bottleneck at response initiation) both demand executive functions located in the lateral prefrontal cortex. For this, we re-analyzed two previous studies, in which a total of 33 participants performed a dual-task according to the paradigm of the psychological refractory period (PRP) during functional magnetic resonance imaging (fMRI). In one study (N = 17), the PRP task consisted of two two-choice response tasks known to suffer from a central bottleneck (CB group). In the other study (N = 16), the PRP task consisted of two simple-response tasks known to suffer from a peripheral bottleneck (PB group). Both groups showed considerable dual-task costs in form of slowing of the second response in the dual-task (PRP effect). Imaging results are based on the subtraction of both single-tasks from the dual-task within each group. In the CB group, the bilateral middle frontal gyri and inferior frontal gyri were activated. Higher activation in these areas was associated with lower dual-task costs. In the PB group, the right middle frontal and inferior frontal gyrus (IFG) were activated. Here, higher activation was associated with higher dual-task costs. In conclusion we suggest that central and peripheral bottlenecks both demand executive functions located in lateral prefrontal cortices (LPFC). Differences between the CB and PB groups with respect to the exact prefrontal areas activated and the correlational patterns

Effect of metabotropic glutamate receptor-3 variants on prefrontal brain activity in schizophrenia: An imaging genetics study using multi-channel near-infrared spectroscopy.

PubMed

Kinoshita, Akihide; Takizawa, Ryu; Koike, Shinsuke; Satomura, Yoshihiro; Kawasaki, Shingo; Kawakubo, Yuki; Marumo, Kohei; Tochigi, Mamoru; Sasaki, Tsukasa; Nishimura, Yukika; Kasai, Kiyoto

2015-10-01

The glutamatergic system is essential for learning and memory through its crucial role in neural development and synaptic plasticity. Genes associated with the glutamatergic system, including metabotropic glutamate receptor (mGluR or GRM) genes, have been implicated in the pathophysiology of schizophrenia. Few studies, however, have investigated a relationship between polymorphism of glutamate-related genes and cortical function in vivo in patients with schizophrenia. We thus explored an association between genetic variations in GRM3 and brain activation driven by a cognitive task in the prefrontal cortex in patients with schizophrenia. Thirty-one outpatients with schizophrenia and 48 healthy controls participated in this study. We measured four candidate single nucleotide polymorphisms (rs274622, rs2299225, rs1468412, and rs6465084) of GRM3, and activity in the prefrontal and temporal cortices during a category version of a verbal fluency task, using a 52-channel near-infrared spectroscopy instrument. The rs274622 C carriers with schizophrenia were associated with significantly smaller prefrontal activation than patients with TT genotype. This between-genotype difference tended to be confined to the patient group. GRM3 polymorphisms are associated with prefrontal activation during cognitive task in schizophrenia. Copyright © 2015 Elsevier Inc. All rights reserved.

Informal Face-to-Face Interaction Improves Mood State Reflected in Prefrontal Cortex Activity

PubMed Central

Watanabe, Jun-ichiro; Atsumori, Hirokazu; Kiguchi, Masashi

2016-01-01

Recent progress with wearable sensors has enabled researchers to capture face-to-face interactions quantitatively and given great insight into human dynamics. One attractive field for applying such sensors is the workplace, where the relationship between the face-to-face behaviors of employees and the productivity of the organization has been investigated. One interesting result of previous studies showed that informal face-to-face interaction among employees, captured by wearable sensors that the employees wore, significantly affects their performance. However, the mechanism behind this relationship has not yet been adequately explained, though experiences at the job scene might qualitatively support the finding. We hypothesized that informal face-to-face interaction improves mood state, which in turn affects the task performance. To test this hypothesis, we evaluated the change of mood state before and after break time for two groups of participants, one that spent their breaks alone and one that spent them with other participants, by administering questionnaires and taking brain activity measurements. Recent neuroimaging studies have suggested a significant relationship between mood state and brain activity. Here, we show that face-to-face interaction during breaks significantly improved mood state, which was measured by Profiles of Mood States (POMS). We also observed that the verbal working memory (WM) task performance of participants who did not have face-to-face interaction during breaks decreased significantly. In this paper, we discuss how the change of mood state was evidenced in the prefrontal cortex (PFC) activity accompanied by WM tasks measured by near-infrared spectroscopy (NIRS). PMID:27199715

Distributed coding of actual and hypothetical outcomes in the orbital and dorsolateral prefrontal cortex

PubMed Central

Abe, Hiroshi; Lee, Daeyeol

2011-01-01

SUMMARY Knowledge about hypothetical outcomes from unchosen actions is beneficial only when such outcomes can be correctly attributed to specific actions. Here, we show that during a simulated rock-paper-scissors game, rhesus monkeys can adjust their choice behaviors according to both actual and hypothetical outcomes from their chosen and unchosen actions, respectively. In addition, neurons in both dorsolateral prefrontal cortex and orbitofrontal cortex encoded the signals related to actual and hypothetical outcomes immediately after they were revealed to the animal. Moreover, compared to the neurons in the orbitofrontal cortex, those in the dorsolateral prefrontal cortex were more likely to change their activity according to the hypothetical outcomes from specific actions. Conjunctive and parallel coding of multiple actions and their outcomes in the prefrontal cortex might enhance the efficiency of reinforcement learning and also contribute to their context-dependent memory. PMID:21609828

Age-related changes in parietal lobe activation during an episodic memory retrieval task.

PubMed

Oedekoven, Christiane S H; Jansen, Andreas; Kircher, Tilo T; Leube, Dirk T

2013-05-01

The crucial role of lateral parietal regions in episodic memory has been confirmed in previous studies. While aging has an influence on retrieval of episodic memory, it remains to be examined how the involvement of lateral parietal regions in episodic memory changes with age. We investigated episodic memory retrieval in two age groups, using faces as stimuli and retrieval success as a measure of episodic memory. Young and elderly participants showed activation within a similar network, including lateral and medial parietal as well as prefrontal regions, but elderly showed a higher level of brain activation regardless of condition. Furthermore, we examined functional connectivity in the two age groups and found a more extensive network in the young group, including correlations of parietal and prefrontal regions. In the elderly, the overall stronger activation related to memory performance may indicate a compensatory process for a less extensive functional network.

Exceptional Evolutionary Expansion of Prefrontal Cortex in Great Apes and Humans.

PubMed

Smaers, Jeroen B; Gómez-Robles, Aida; Parks, Ashley N; Sherwood, Chet C

2017-03-06

One of the enduring questions that has driven neuroscientific enquiry in the last century has been the nature of differences in the prefrontal cortex of humans versus other animals [1]. The prefrontal cortex has drawn particular interest due to its role in a range of evolutionarily specialized cognitive capacities such as language [2], imagination [3], and complex decision making [4]. Both cytoarchitectonic [5] and comparative neuroimaging [6] studies have converged on the conclusion that the proportion of prefrontal cortex in the human brain is greatly increased relative to that of other primates. However, considering the tremendous overall expansion of the neocortex in human evolution, it has proven difficult to ascertain whether this extent of prefrontal enlargement follows general allometric growth patterns, or whether it is exceptional [1]. Species' adherence to a common allometric relationship suggests conservation through phenotypic integration, while species' deviations point toward the occurrence of shifts in genetic and/or developmental mechanisms. Here we investigate prefrontal cortex scaling across anthropoid primates and find that great ape and human prefrontal cortex expansion are non-allometrically derived features of cortical organization. This result aligns with evidence for a developmental heterochronic shift in human prefrontal growth [7, 8], suggesting an association between neurodevelopmental changes and cortical organization on a macroevolutionary scale. The evolutionary origin of non-allometric prefrontal enlargement is estimated to lie at the root of great apes (∼19-15 mya), indicating that selection for changes in executive cognitive functions characterized both great ape and human cortical organization. Copyright © 2017 Elsevier Ltd. All rights reserved.

Variability in prefrontal hemodynamic response during exposure to repeated self-selected music excerpts, a near-infrared spectroscopy study.

PubMed

Moghimi, Saba; Schudlo, Larissa; Chau, Tom; Guerguerian, Anne-Marie

2015-01-01

Music-induced brain activity modulations in areas involved in emotion regulation may be useful in achieving therapeutic outcomes. Clinical applications of music may involve prolonged or repeated exposures to music. However, the variability of the observed brain activity patterns in repeated exposures to music is not well understood. We hypothesized that multiple exposures to the same music would elicit more consistent activity patterns than exposure to different music. In this study, the temporal and spatial variability of cerebral prefrontal hemodynamic response was investigated across multiple exposures to self-selected musical excerpts in 10 healthy adults. The hemodynamic changes were measured using prefrontal cortex near infrared spectroscopy and represented by instantaneous phase values. Based on spatial and temporal characteristics of these observed hemodynamic changes, we defined a consistency index to represent variability across these domains. The consistency index across repeated exposures to the same piece of music was compared to the consistency index corresponding to prefrontal activity from randomly matched non-identical musical excerpts. Consistency indexes were significantly different for identical versus non-identical musical excerpts when comparing a subset of repetitions. When all four exposures were compared, no significant difference was observed between the consistency indexes of randomly matched non-identical musical excerpts and the consistency index corresponding to repetitions of the same musical excerpts. This observation suggests the existence of only partial consistency between repeated exposures to the same musical excerpt, which may stem from the role of the prefrontal cortex in regulating other cognitive and emotional processes.

Variability in Prefrontal Hemodynamic Response during Exposure to Repeated Self-Selected Music Excerpts, a Near-Infrared Spectroscopy Study

PubMed Central

Moghimi, Saba; Schudlo, Larissa; Chau, Tom; Guerguerian, Anne-Marie

2015-01-01

Music-induced brain activity modulations in areas involved in emotion regulation may be useful in achieving therapeutic outcomes. Clinical applications of music may involve prolonged or repeated exposures to music. However, the variability of the observed brain activity patterns in repeated exposures to music is not well understood. We hypothesized that multiple exposures to the same music would elicit more consistent activity patterns than exposure to different music. In this study, the temporal and spatial variability of cerebral prefrontal hemodynamic response was investigated across multiple exposures to self-selected musical excerpts in 10 healthy adults. The hemodynamic changes were measured using prefrontal cortex near infrared spectroscopy and represented by instantaneous phase values. Based on spatial and temporal characteristics of these observed hemodynamic changes, we defined a consistency index to represent variability across these domains. The consistency index across repeated exposures to the same piece of music was compared to the consistency index corresponding to prefrontal activity from randomly matched non-identical musical excerpts. Consistency indexes were significantly different for identical versus non-identical musical excerpts when comparing a subset of repetitions. When all four exposures were compared, no significant difference was observed between the consistency indexes of randomly matched non-identical musical excerpts and the consistency index corresponding to repetitions of the same musical excerpts. This observation suggests the existence of only partial consistency between repeated exposures to the same musical excerpt, which may stem from the role of the prefrontal cortex in regulating other cognitive and emotional processes. PMID:25837268

Correlation of within-individual fluctuation of depressed mood with prefrontal cortex activity during verbal working memory task: optical topography study

NASA Astrophysics Data System (ADS)

Sato, Hiroki; Aoki, Ryuta; Katura, Takusige; Matsuda, Ryoichi; Koizumi, Hideaki

2011-12-01

Previous studies showed that interindividual variations in mood state are associated with prefrontal cortex (PFC) activity. In this study, we focused on the depressed-mood state under natural circumstances and examined the relationship between within-individual changes over time in this mood state and PFC activity. We used optical topography (OT), a functional imaging technique based on near-infrared spectroscopy, to measure PFC activity for each participant in three experimental sessions repeated at 2-week intervals. In each session, the participants completed a self-report questionnaire of mood state and underwent OT measurement while performing verbal and spatial working memory (WM) tasks. The results showed that changes in the depressed-mood score between successive sessions were negatively correlated with those in the left PFC activation for the verbal WM task (ρ = -0.56, p < 0.05). In contrast, the PFC activation for the spatial WM task did not co-vary with participants' mood changes. We thus demonstrated that PFC activity during a verbal WM task varies depending on the participant's depressed mood state, independent of trait factors. This suggests that using optical topography to measure PFC activity during a verbal WM task can be used as a potential state marker for an individual's depressed mood state.

When seeing outweighs feeling: a role for prefrontal cortex in passive control of negative affect in blindsight.

PubMed

Anders, Silke; Eippert, Falk; Wiens, Stefan; Birbaumer, Niels; Lotze, Martin; Wildgruber, Dirk

2009-11-01

Affective neuroscience has been strongly influenced by the view that a 'feeling' is the perception of somatic changes and has consequently often neglected the neural mechanisms that underlie the integration of somatic and other information in affective experience. Here, we investigate affective processing by means of functional magnetic resonance imaging in nine cortically blind patients. In these patients, unilateral postgeniculate lesions prevent primary cortical visual processing in part of the visual field which, as a result, becomes subjectively blind. Residual subcortical processing of visual information, however, is assumed to occur in the entire visual field. As we have reported earlier, these patients show significant startle reflex potentiation when a threat-related visual stimulus is shown in their blind visual field. Critically, this was associated with an increase of brain activity in somatosensory-related areas, and an increase in experienced negative affect. Here, we investigated the patients' response when the visual stimulus was shown in the sighted visual field, that is, when it was visible and cortically processed. Despite the fact that startle reflex potentiation was similar in the blind and sighted visual field, patients reported significantly less negative affect during stimulation of the sighted visual field. In other words, when the visual stimulus was visible and received full cortical processing, the patients' phenomenal experience of affect did not closely reflect somatic changes. This decoupling of phenomenal affective experience and somatic changes was associated with an increase of activity in the left ventrolateral prefrontal cortex and a decrease of affect-related somatosensory activity. Moreover, patients who showed stronger left ventrolateral prefrontal cortex activity tended to show a stronger decrease of affect-related somatosensory activity. Our findings show that similar affective somatic changes can be associated with

When seeing outweighs feeling: a role for prefrontal cortex in passive control of negative affect in blindsight

PubMed Central

Eippert, Falk; Wiens, Stefan; Birbaumer, Niels; Lotze, Martin; Wildgruber, Dirk

2009-01-01

Affective neuroscience has been strongly influenced by the view that a ‘feeling’ is the perception of somatic changes and has consequently often neglected the neural mechanisms that underlie the integration of somatic and other information in affective experience. Here, we investigate affective processing by means of functional magnetic resonance imaging in nine cortically blind patients. In these patients, unilateral postgeniculate lesions prevent primary cortical visual processing in part of the visual field which, as a result, becomes subjectively blind. Residual subcortical processing of visual information, however, is assumed to occur in the entire visual field. As we have reported earlier, these patients show significant startle reflex potentiation when a threat-related visual stimulus is shown in their blind visual field. Critically, this was associated with an increase of brain activity in somatosensory-related areas, and an increase in experienced negative affect. Here, we investigated the patients’ response when the visual stimulus was shown in the sighted visual field, that is, when it was visible and cortically processed. Despite the fact that startle reflex potentiation was similar in the blind and sighted visual field, patients reported significantly less negative affect during stimulation of the sighted visual field. In other words, when the visual stimulus was visible and received full cortical processing, the patients’ phenomenal experience of affect did not closely reflect somatic changes. This decoupling of phenomenal affective experience and somatic changes was associated with an increase of activity in the left ventrolateral prefrontal cortex and a decrease of affect-related somatosensory activity. Moreover, patients who showed stronger left ventrolateral prefrontal cortex activity tended to show a stronger decrease of affect-related somatosensory activity. Our findings show that similar affective somatic changes can be associated with

Mindful attention to breath regulates emotions via increased amygdala-prefrontal cortex connectivity.

PubMed

Doll, Anselm; Hölzel, Britta K; Mulej Bratec, Satja; Boucard, Christine C; Xie, Xiyao; Wohlschläger, Afra M; Sorg, Christian

2016-07-01

Mindfulness practice is beneficial for emotion regulation; however, the neural mechanisms underlying this effect are poorly understood. The current study focuses on effects of attention-to-breath (ATB) as a basic mindfulness practice on aversive emotions at behavioral and brain levels. A key finding across different emotion regulation strategies is the modulation of amygdala and prefrontal activity. It is unclear how ATB relevant brain areas in the prefrontal cortex integrate with amygdala activation during emotional stimulation. We proposed that, during emotional stimulation, ATB down-regulates activation in the amygdala and increases its integration with prefrontal regions. To address this hypothesis, 26 healthy controls were trained in mindfulness-based attention-to-breath meditation for two weeks and then stimulated with aversive pictures during both attention-to-breath and passive viewing while undergoing fMRI. Data were controlled for breathing frequency. Results indicate that (1) ATB was effective in regulating aversive emotions. (2) Left dorso-medial prefrontal cortex was associated with ATB in general. (3) A fronto-parietal network was additionally recruited during emotional stimulation. (4) ATB down regulated amygdala activation and increased amygdala-prefrontal integration, with such increased integration being associated with mindfulness ability. Results suggest amygdala-dorsal prefrontal cortex integration as a potential neural pathway of emotion regulation by mindfulness practice. Copyright © 2016 Elsevier Inc. All rights reserved.

Lucid Dreaming and Ventromedial versus Dorsolateral Prefrontal Task Performance

PubMed Central

Neider, Michelle; Pace-Schott, Edward F.; Forselius, Erica; Pittman, Brian; Morgan, Peter T.

2010-01-01

Activity in the prefrontal cortex may distinguish the meta-awareness experienced during lucid dreams from its absence in normal dreams. To examine a possible relationship between dream lucidity and prefrontal task performance, we carried out a prospective study in 28 high school students. Participants performed the Wisconsin Card Sort and Iowa Gambling tasks, then for one week kept dream journals and reported sleep quality and lucidity-related dream characteristics. Participants who exhibited a greater degree of lucidity performed significantly better on the task that engages the ventromedial prefrontal cortex (the Iowa Gambling Task), but degree of lucidity achieved did not distinguish performance on the task that engages the dorsolateral prefrontal cortex (the Wisconsin Card Sort Task), nor did it distinguish self-reported sleep quality or baseline characteristics. The association between performance on the Iowa Gambling Task and lucidity suggests a connection between lucid dreaming and ventromedial prefrontal function. PMID:20829072

Online effects of transcranial direct current stimulation on prefrontal metabolites in gambling disorder.

PubMed

Dickler, Maya; Lenglos, Christophe; Renauld, Emmanuelle; Ferland, Francine; Edden, Richard A; Leblond, Jean; Fecteau, Shirley

2018-03-15

Gambling disorder is characterized by persistent maladaptive gambling behaviors and is now considered among substance-related and addictive disorders. There is still unmet therapeutic need for these clinical populations, however recent advances indicate that interventions targeting the Glutamatergic/GABAergic system hold promise in reducing symptoms in substance-related and addictive disorders, including gambling disorder. There is some data indicating that transcranial direct current stimulation may hold clinical benefits in substance use disorders and modulate levels of brain metabolites including glutamate and GABA. The goal of the present work was to test whether this non-invasive neurostimulation method modulates key metabolites in gambling disorder. We conducted a sham-controlled, crossover, randomized study, blinded at two levels in order to characterize the effects of transcranial direct current stimulation over the dorsolateral prefrontal cortex on neural metabolites levels in sixteen patients with gambling disorder. Metabolite levels were measured with magnetic resonance spectroscopy from the right dorsolateral prefrontal cortex and the right striatum during active and sham stimulation. Active as compared to sham stimulation elevated prefrontal GABA levels. There were no significant changes between stimulation conditions in prefrontal glutamate + glutamine and N-acetyl Aspartate, or in striatal metabolite levels. Results also indicated positive correlations between metabolite levels during active, but not sham, stimulation and levels of risk taking, impulsivity and craving. Our findings suggest that transcranial direct current stimulation can modulate GABA levels in patients with gambling disorder which may represent an interesting future therapeutic avenue. Copyright © 2017 Elsevier Ltd. All rights reserved.

Improper activation of D1 and D2 receptors leads to excess noise in prefrontal cortex

PubMed Central

Avery, Michael C.; Krichmar, Jeffrey L.

2015-01-01

The dopaminergic system has been shown to control the amount of noise in the prefrontal cortex (PFC) and likely plays an important role in working memory and the pathophysiology of schizophrenia. We developed a model that takes into account the known receptor distributions of D1 and D2 receptors, the changes these receptors have on neuron response properties, as well as identified circuitry involved in working memory. Our model suggests that D1 receptor under-stimulation in supragranular layers gates internal noise into the PFC leading to cognitive symptoms as has been proposed in attention disorders, while D2 over-stimulation gates noise into the PFC by over-activation of cortico-striatal projecting neurons in infragranular layers. We apply this model in the context of a memory-guided saccade paradigm and show deficits similar to those observed in schizophrenic patients. We also show set-shifting impairments similar to those observed in rodents with D1 and D2 receptor manipulations. We discuss how the introduction of noise through changes in D1 and D2 receptor activation may account for many of the symptoms of schizophrenia depending on where this dysfunction occurs in the PFC. PMID:25814948

Glucose-monitoring neurons in the mediodorsal prefrontal cortex.

PubMed

Nagy, Bernadett; Szabó, István; Papp, Szilárd; Takács, Gábor; Szalay, Csaba; Karádi, Zoltán

2012-03-20

The mediodorsal prefrontal cortex (mdPFC), a key structure of the limbic neural circuitry, plays important roles in the central regulation of feeding. As an integrant part of the forebrain dopamine (DA) system, it performs complex roles via interconnections with various brain areas where glucose-monitoring (GM) neurons have been identified. The main goal of the present experiments was to examine whether similar GM neurons exist in the mediodorsal prefrontal cortex. To search for such chemosensory cells here, and to estimate their involvement in the DA circuitry, extracellular single neuron activity of the mediodorsal prefrontal cortex of anesthetized Wistar and Sprague-Dawley rats was recorded by means of tungsten wire multibarreled glass microelectrodes during microelectrophoretic administration of d-glucose and DA. One fourth of the neurons tested changed in firing rate in response to glucose, thus, proved to be elements of the forebrain GM neural network. DA responsive neurons in the mdPFC were found to represent similar proportion of all cells; the glucose-excited units were shown to display excitatory whereas the glucose-inhibited neurons were demonstrated to exert mainly inhibitory responses to dopamine. The glucose-monitoring neurons of the mdPFC and their distinct DA sensitivity are suggested to be of particular significance in adaptive processes of the central feeding control. Copyright © 2012 Elsevier B.V. All rights reserved.

Reduced prefrontal and increased subcortical brain functioning assessed using positron emission tomography in predatory and affective murderers.

PubMed

Raine, A; Meloy, J R; Bihrle, S; Stoddard, J; LaCasse, L; Buchsbaum, M S

1998-01-01

There appear to be no brain imaging studies investigating which brain mechanisms subserve affective, impulsive violence versus planned, predatory violence. It was hypothesized that affectively violent offenders would have lower prefrontal activity, higher subcortical activity, and reduced prefrontal/subcortical ratios relative to controls, while predatory violent offenders would show relatively normal brain functioning. Glucose metabolism was assessed using positron emission tomography in 41 comparisons, 15 predatory murderers, and nine affective murderers in left and right hemisphere prefrontal (medial and lateral) and subcortical (amygdala, midbrain, hippocampus, and thalamus) regions. Affective murderers relative to comparisons had lower left and right prefrontal functioning, higher right hemisphere subcortical functioning, and lower right hemisphere prefrontal/subcortical ratios. In contrast, predatory murderers had prefrontal functioning that was more equivalent to comparisons, while also having excessively high right subcortical activity. Results support the hypothesis that emotional, unplanned impulsive murderers are less able to regulate and control aggressive impulses generated from subcortical structures due to deficient prefrontal regulation. It is hypothesized that excessive subcortical activity predisposes to aggressive behaviour, but that while predatory murderers have sufficiently good prefrontal functioning to regulate these aggressive impulses, the affective murderers lack such prefrontal control over emotion regulation.

An integrative theory of prefrontal cortex function.

PubMed

Miller, E K; Cohen, J D

2001-01-01

The prefrontal cortex has long been suspected to play an important role in cognitive control, in the ability to orchestrate thought and action in accordance with internal goals. Its neural basis, however, has remained a mystery. Here, we propose that cognitive control stems from the active maintenance of patterns of activity in the prefrontal cortex that represent goals and the means to achieve them. They provide bias signals to other brain structures whose net effect is to guide the flow of activity along neural pathways that establish the proper mappings between inputs, internal states, and outputs needed to perform a given task. We review neurophysiological, neurobiological, neuroimaging, and computational studies that support this theory and discuss its implications as well as further issues to be addressed

The hemodynamic changes in the human prefrontal cortex during the Flanker and Simon tasks: a fNIRS study

NASA Astrophysics Data System (ADS)

Yuan, Zhen; Lin, Xiaohong

2016-03-01

Functional near-infrared spectroscopy (fNIRS) is a low-cost, portable and noninvasive functional neuroimaging technique by measuring the change in the concentrations of oxyhemoglobin (HbO) and deoxyhemoglobin (HbR). The aim of present study is to reveal the different brain activity pattern of adult subjects during the completion of flanker and Simon tasks underlying the congruent and incongruent test conditions so as to identify the basic neural mechanism of inhibitory control in executive function. In the study, we utilized fNIRS to explore the hemodynamic changes in the prefrontal cortex and our imaging results suggested that there were notable differences for the hemodynamic responses between the flank and Simon task. A striking difference is that for the flank task, the increase in the HbO concentration during incongruent trials was larger than that during congruent trials for the channels across middle frontal cortex while for the Simon task, the hemodynamic response was stronger for the congruent condition compared to that from the incongruent one. Interestingly, the hemodynamic response exhibited similar task-related activation in the superior frontal cortex for both the congruent and incongruent conditions. Further, independent component analysis showed that different brain activation patterns were identified to accomplish different inhibitory control tasks underlying the congruent and incongruent conditions.

Music improves verbal memory encoding while decreasing prefrontal cortex activity: an fNIRS study.

PubMed

Ferreri, Laura; Aucouturier, Jean-Julien; Muthalib, Makii; Bigand, Emmanuel; Bugaiska, Aurelia

2013-01-01

Listening to music engages the whole brain, thus stimulating cognitive performance in a range of non-purely musical activities such as language and memory tasks. This article addresses an ongoing debate on the link between music and memory for words. While evidence on healthy and clinical populations suggests that music listening can improve verbal memory in a variety of situations, it is still unclear what specific memory process is affected and how. This study was designed to explore the hypothesis that music specifically benefits the encoding part of verbal memory tasks, by providing a richer context for encoding and therefore less demand on the dorsolateral prefrontal cortex (DLPFC). Twenty-two healthy young adults were subjected to functional near-infrared spectroscopy (fNIRS) imaging of their bilateral DLPFC while encoding words in the presence of either a music or a silent background. Behavioral data confirmed the facilitating effect of music background during encoding on subsequent item recognition. fNIRS results revealed significantly greater activation of the left hemisphere during encoding (in line with the HERA model of memory lateralization) and a sustained, bilateral decrease of activity in the DLPFC in the music condition compared to silence. These findings suggest that music modulates the role played by the DLPFC during verbal encoding, and open perspectives for applications to clinical populations with prefrontal impairments, such as elderly adults or Alzheimer's patients.

Music improves verbal memory encoding while decreasing prefrontal cortex activity: an fNIRS study

PubMed Central

Ferreri, Laura; Aucouturier, Jean-Julien; Muthalib, Makii; Bigand, Emmanuel; Bugaiska, Aurelia

2013-01-01

Listening to music engages the whole brain, thus stimulating cognitive performance in a range of non-purely musical activities such as language and memory tasks. This article addresses an ongoing debate on the link between music and memory for words. While evidence on healthy and clinical populations suggests that music listening can improve verbal memory in a variety of situations, it is still unclear what specific memory process is affected and how. This study was designed to explore the hypothesis that music specifically benefits the encoding part of verbal memory tasks, by providing a richer context for encoding and therefore less demand on the dorsolateral prefrontal cortex (DLPFC). Twenty-two healthy young adults were subjected to functional near-infrared spectroscopy (fNIRS) imaging of their bilateral DLPFC while encoding words in the presence of either a music or a silent background. Behavioral data confirmed the facilitating effect of music background during encoding on subsequent item recognition. fNIRS results revealed significantly greater activation of the left hemisphere during encoding (in line with the HERA model of memory lateralization) and a sustained, bilateral decrease of activity in the DLPFC in the music condition compared to silence. These findings suggest that music modulates the role played by the DLPFC during verbal encoding, and open perspectives for applications to clinical populations with prefrontal impairments, such as elderly adults or Alzheimer’s patients. PMID:24339807

Prefrontal atrophy, disrupted NREM slow waves, and impaired hippocampal-dependent memory in aging

PubMed Central

Mander, Bryce A.; Rao, Vikram; Lu, Brandon; Saletin, Jared M.; Lindquist, John R.; Ancoli-Israel, Sonia; Jagust, William; Walker, Matthew P.

2014-01-01

Aging has independently been associated with regional brain atrophy, reduced non-rapid eye movement (NREM) slow-wave activity (SWA), and impaired long-term retention of episodic memories. However, that the interaction of these factors represents a neuropatholgical pathway associated with cognitive decline in later life remains unknown. Here, we show that age-related medial prefrontal cortex (mPFC) grey-matter atrophy is associated with reduced NREM SWA activity in older adults, the extent to which statistically mediates the impairment of overnight sleep-dependent memory retention. Moreover, this memory impairment was further associated with persistent hippocampal activation and reduced task-related hippocampal-prefrontal cortex connectivity, potentially representing impoverished hippocampal-neocortical memory transformation. Together, these data support a model in which age-related mPFC atrophy diminishes SWA, the functional consequence of which is impaired long-term memory. Such findings suggest that sleep disruption in the elderly, mediated by structural brain changes, represent a novel contributing factor to age-related cognitive decline in later life. PMID:23354332

The Role of the Rat Medial Prefrontal Cortex in Adapting to Changes in Instrumental Contingency

PubMed Central

Coutureau, Etienne; Esclassan, Frederic; Di Scala, Georges; Marchand, Alain R.

2012-01-01

In order to select actions appropriate to current needs, a subject must identify relationships between actions and events. Control over the environment is determined by the degree to which action consequences can be predicted, as described by action-outcome contingencies – i.e. performing an action should affect the probability of the outcome. We evaluated in a first experiment adaptation to contingency changes in rats with neurotoxic lesions of the medial prefrontal cortex. Results indicate that this brain region is not critical to adjust instrumental responding to a negative contingency where the rats must refrain from pressing a lever, as this action prevents reward delivery. By contrast, this brain region is required to reduce responding in a non-contingent situation where the same number of rewards is freely delivered and actions do not affect the outcome any more. In a second experiment, we determined that this effect does not result from a different perception of temporal relationships between actions and outcomes since lesioned rats adapted normally to gradually increasing delays in reward delivery. These data indicate that the medial prefrontal cortex is not directly involved in evaluating the correlation between action-and reward-rates or in the perception of reward delays. The deficit in lesioned rats appears to consist of an abnormal response to the balance between contingent and non-contingent rewards. By highlighting the role of prefrontal regions in adapting to the causal status of actions, these data contribute to our understanding of the neural basis of choice tasks. PMID:22496747

Theta synchronizes the activity of medial prefrontal neurons during learning

PubMed Central

Paz, Rony; Bauer, Elizabeth P.; Paré, Denis

2008-01-01

Memory consolidation is thought to involve the gradual transfer of transient hippocampal-dependent traces to distributed neocortical sites via the rhinal cortices. Recently, medial prefrontal (mPFC) neurons were shown to facilitate this process when their activity becomes synchronized. However, the mechanisms underlying this enhanced synchrony remain unclear. Because the hippocampus projects to the mPFC, we tested whether theta oscillations contribute to synchronize mPFC neurons during learning. Thus, we obtained field (LFP) and unit recordings from multiple mPFC sites during the acquisition of a trace-conditioning task, where a visual conditioned stimulus (CS) predicted reward delivery. In quiet waking, the activity of mPFC neurons was modulated by theta oscillations. During conditioning, CS presentation caused an increase in mPFC theta power that augmented as the CS gained predictive value for reward delivery. This increased theta power coincided with a transient theta phase locking at distributed mPFC sites, an effect that was also manifest in the timing of mPFC unit activity. Overall, these results show that theta oscillations contribute to synchronize neuronal activity at distributed mPFC sites, suggesting that the hippocampus, by generating a stronger theta source during learning, can synchronize mPFC activity, in turn facilitating rhinal transfer of its activity to the neocortex. PMID:18612069

Prefrontal Contribution to Decision-Making under Free-Choice Conditions

PubMed Central

Funahashi, Shintaro

2017-01-01

Executive function is thought to be the coordinated operation of multiple neural processes and allows to accomplish a current goal flexibly. The most important function of the prefrontal cortex is the executive function. Among a variety of executive functions in which the prefrontal cortex participates, decision-making is one of the most important. Although the prefrontal contribution to decision-making has been examined using a variety of behavioral tasks, recent studies using fMRI have shown that the prefrontal cortex participates in decision-making under free-choice conditions. Since decision-making under free-choice conditions represents the very first stage for any kind of decision-making process, it is important that we understand its neural mechanism. Although few studies have examined this issue while a monkey performed a free-choice task, those studies showed that, when the monkey made a decision to subsequently choose one particular option, prefrontal neurons showing selectivity to that option exhibited transient activation just before presentation of the imperative cue. Further studies have suggested that this transient increase is caused by the irregular fluctuation of spontaneous firing just before cue presentation, which enhances the response to the cue and biases the strength of the neuron's selectivity to the option. In addition, this biasing effect was observed only in neurons that exhibited sustained delay-period activity, indicating that this biasing effect not only influences the animal's decision for an upcoming choice, but also is linked to working memory mechanisms in the prefrontal cortex. PMID:28798662

Imitation and observational learning of hand actions: prefrontal involvement and connectivity.

PubMed

Higuchi, S; Holle, H; Roberts, N; Eickhoff, S B; Vogt, S

2012-01-16

The first aim of this event-related fMRI study was to identify the neural circuits involved in imitation learning. We used a rapid imitation task where participants directly imitated pictures of guitar chords. The results provide clear evidence for the involvement of dorsolateral prefrontal cortex, as well as the fronto-parietal mirror circuit (FPMC) during action imitation when the requirements for working memory are low. Connectivity analyses further indicated a robust connectivity between left prefrontal cortex and the components of the FPMC bilaterally. We conclude that a mechanism of automatic perception-action matching alone is insufficient to account for imitation learning. Rather, the motor representation of an observed, complex action, as provided by the FPMC, only serves as the 'raw material' for higher-order supervisory and monitoring operations associated with the prefrontal cortex. The second aim of this study was to assess whether these neural circuits are also recruited during observational practice (OP, without motor execution), or only during physical practice (PP). Whereas prefrontal cortex was not consistently activated in action observation across all participants, prefrontal activation intensities did predict the behavioural practice effects, thus indicating a crucial role of prefrontal cortex also in OP. In addition, whilst OP and PP produced similar activation intensities in the FPMC when assessed during action observation, during imitative execution, the practice-related activation decreases were significantly more pronounced for PP than for OP. This dissociation indicates a lack of execution-related resources in observationally practised actions. More specifically, we found neural efficiency effects in the right motor cingulate-basal ganglia circuit and the FPMC that were only observed after PP but not after OP. Finally, we confirmed that practice generally induced activation decreases in the FPMC during both action observation and

Decreasing Ventromedial Prefrontal Cortex Activity During Sequential Risk-Taking: An fMRI Investigation of the Balloon Analog Risk Task

PubMed Central

Schonberg, Tom; Fox, Craig R.; Mumford, Jeanette A.; Congdon, Eliza; Trepel, Christopher; Poldrack, Russell A.

2012-01-01

Functional imaging studies examining the neural correlates of risk have mainly relied on paradigms involving exposure to simple chance gambles and an economic definition of risk as variance in the probability distribution over possible outcomes. However, there is little evidence that choices made during gambling tasks predict naturalistic risk-taking behaviors such as drug use, extreme sports, or even equity investing. To better understand the neural basis of naturalistic risk-taking, we scanned participants using fMRI while they completed the Balloon Analog Risk Task, an experimental measure that includes an active decision/choice component and that has been found to correlate with a number of naturalistic risk-taking behaviors. In the task, as in many naturalistic settings, escalating risk-taking occurs under uncertainty and might be experienced either as the accumulation of greater potential rewards, or as exposure to increasing possible losses (and decreasing expected value). We found that areas previously linked to risk and risk-taking (bilateral anterior insula, anterior cingulate cortex, and right dorsolateral prefrontal cortex) were activated as participants continued to inflate balloons. Interestingly, we found that ventromedial prefrontal cortex (vmPFC) activity decreased as participants further expanded balloons. In light of previous findings implicating the vmPFC in value calculation, this result suggests that escalating risk-taking in the task might be perceived as exposure to increasing possible losses (and decreasing expected value) rather than the increasing potential total reward relative to the starting point of the trial. A better understanding of how neural activity changes with risk-taking behavior in the task offers insight into the potential neural mechanisms driving naturalistic risk-taking. PMID:22675289

Medial prefrontal cortex supports source memory accuracy for self-referenced items

PubMed Central

Leshikar, Eric D.; Duarte, Audrey

2013-01-01

Previous behavioral work suggests that processing information in relation to the self enhances subsequent item recognition. Neuroimaging evidence further suggests that regions along the cortical midline, particularly those of the medial prefrontal cortex, underlie this benefit. There has been little work to date, however, on the effects of self-referential encoding on source memory accuracy or whether the medial prefrontal cortex might contribute to source memory for self-referenced materials. In the current study, we used fMRI to measure neural activity while participants studied and subsequently retrieved pictures of common objects superimposed on one of two background scenes (sources) under either self-reference or self-external encoding instructions. Both item recognition and source recognition were better for objects encoded self-referentially than self-externally. Neural activity predictive of source accuracy was observed in the medial prefrontal cortex (BA 10) at the time of study for self-referentially but not self-externally encoded objects. The results of this experiment suggest that processing information in relation to the self leads to a mnemonic benefit for source level features, and that activity in the medial prefrontal cortex contributes to this source memory benefit. This evidence expands the purported role that the medial prefrontal cortex plays in self-referencing. PMID:21936739

Plastic changes to dendritic spines on layer V pyramidal neurons are involved in the rectifying role of the prefrontal cortex during the fast period of motor learning.

PubMed

González-Tapia, David; Martínez-Torres, Nestor I; Hernández-González, Marisela; Guevara, Miguel Angel; González-Burgos, Ignacio

2016-02-01

The prefrontal cortex participates in the rectification of information related to motor activity that favors motor learning. Dendritic spine plasticity is involved in the modifications of motor patterns that underlie both motor activity and motor learning. To study this association in more detail, adult male rats were trained over six days in an acrobatic motor learning paradigm and they were subjected to a behavioral evaluation on each day of training. Also, a Golgi-based morphological study was carried out to determine the spine density and the proportion of the different spine types. In the learning paradigm, the number of errors diminished as motor training progressed. Concomitantly, spine density increased on days 1 and 3 of training, particularly reflecting an increase in the proportion of thin (day 1), stubby (day 1) and branched (days 1, 2 and 5) spines. Conversely, mushroom spines were less prevalent than in the control rats on days 5 and 6, as were stubby spines on day 6, together suggesting that this plasticity might enhance motor learning. The increase in stubby spines on day 1 suggests a regulation of excitability related to the changes in synaptic input to the prefrontal cortex. The plasticity to thin spines observed during the first 3 days of training could be related to the active rectification induced by the information relayed to the prefrontal cortex -as the behavioral findings indeed showed-, which in turn could be linked to the lower proportion of mushroom and stubby spines seen in the last days of training. Copyright © 2015 Elsevier B.V. All rights reserved.

Disruption of Prefrontal Cortex Large Scale Neuronal Activity by Different Classes of Psychotomimetic Drugs

PubMed Central

Wood, Jesse; Kim, Yunbok; Moghaddam, Bita

2012-01-01

In the absence of overt cellular pathology but profound perceptual disorganization and cognitive deficits, schizophrenia is increasingly considered a disorder of neural coordination. Thus, different causal factors can similarly interrupt the dynamic function of neuronal ensembles and networks, in particular in the prefrontal cortex (PFC), leading to behavioral disorganization. The importance of establishing preclinical biomarkers for this aberrant function has prompted investigations into the nature of psychotomimetic drug effects on PFC neuronal activity. The drugs used in this context include serotonergic hallucinogens, amphetamine, and NMDA receptor antagonists. A prominent line of thinking is that these drugs create psychotomimetic states by similarly disinhibiting the activity of PFC pyramidal neurons. In the present study we did not find evidence in support of this mechanism in PFC subregions of freely moving rats. Whereas the NMDA receptor antagonist MK801 increased PFC population activity, the serotonergic hallucinogen DOI dose-dependently decreased population activity. Amphetamine did not strongly affect this measure. Despite different effects on the direction of change in activity, all three drugs caused similar net disruptions of population activity and modulated gamma oscillations. We also observed reduced correlations between spikerate and LFP power selectively in the gamma band suggesting that these drugs disconnect spike-discharge from PFC gamma oscillators. Gamma band oscillations support cognitive functions affected in schizophrenia. These findings provide insight into mechanisms that may lead to cortical processing deficits in schizophrenia and provide a novel electrophysiological approach for phenotypic characterization of animal models of this disease. PMID:22378875

Right prefrontal rTMS treatment for refractory auditory command hallucinations - a neuroSPECT assisted case study.

PubMed

Schreiber, Shaul; Dannon, Pinhas N; Goshen, Elinor; Amiaz, Revital; Zwas, Tzila S; Grunhaus, Leon

2002-11-30

Auditory command hallucinations probably arise from the patient's failure to monitor his/her own 'inner speech', which is connected to activation of speech perception areas of the left cerebral cortex and to various degrees of dysfunction of cortical circuits involved in schizophrenia as supported by functional brain imaging. We hypothesized that rapid transcranial magnetic stimulation (rTMS), by increasing cortical activation of the right prefrontal brain region, would bring about a reduction of the hallucinations. We report our first schizophrenic patient affected with refractory command hallucinations treated with 10 Hz rTMS. Treatment was performed over the right dorsolateral prefrontal cortex, with 1200 magnetic stimulations administered daily for 20 days at 90% motor threshold. Regional cerebral blood flow changes were monitored with neuroSPECT. Clinical evaluation and scores on the Positive and Negative Symptoms Scale and the Brief Psychiatric Rating Scale demonstrated a global improvement in the patient's condition, with no change in the intensity and frequency of the hallucinations. NeuroSPECT performed at intervals during and after treatment indicated a general improvement in cerebral perfusion. We conclude that right prefrontal rTMS may induce a general clinical improvement of schizophrenic brain function, without directly influencing the mechanism involved in auditory command hallucinations.

Enhanced activation of reward mediating prefrontal regions in response to food stimuli in Prader-Willi syndrome.

PubMed

Miller, Jennifer L; James, G Andrew; Goldstone, Anthony P; Couch, Jessica A; He, Guojun; Driscoll, Daniel J; Liu, Yijun

2007-06-01

Individuals with Prader-Willi syndrome (PWS) exhibit severe disturbances in appetite regulation, including delayed meal termination, early return of hunger after a meal, seeking and hoarding food and eating of non-food substances. Brain pathways involved in the control of appetite in humans are thought to include the hypothalamus, frontal cortex (including the orbitofrontal, ventromedial prefrontal, dorsolateral prefrontal and anterior cingulate areas), insula, and limbic and paralimbic areas. We hypothesised that the abnormal appetite in PWS results from aberrant reward processing of food stimuli in these neural pathways. We compared functional MRI blood oxygen level dependent (BOLD) responses while viewing pictures of food in eight adults with PWS and eight normal weight adults after ingestion of an oral glucose load. Subjects with PWS demonstrated significantly greater BOLD activation in the ventromedial prefrontal cortex than controls when viewing food pictures. No significant differences were found in serum insulin, glucose or triglyceride levels between the groups at the time of the scan. Individuals with PWS had an increased BOLD response in the ventromedial prefrontal cortex compared with normal weight controls when viewing pictures of food after an oral glucose load. These findings suggest that an increased reward value for food may underlie the excessive hunger in PWS, and support the significance of the frontal cortex in modulating the response to food in humans. Our findings in the extreme appetite phenotype of PWS support the importance of the neural pathways that guide reward related behaviour in modulating the response to food in humans.

Does rTMS Alter Neurocognitive Functioning in Patients with Panic Disorder/Agoraphobia? An fNIRS-Based Investigation of Prefrontal Activation during a Cognitive Task and Its Modulation via Sham-Controlled rTMS

PubMed Central

Sickinger, Stephanie; Haeussinger, Florian B.; Laeger, Inga; Arolt, Volker; Zwanzger, Peter; Fallgatter, Andreas J.

2014-01-01

Objectives. Neurobiologically, panic disorder (PD) is supposed to be characterised by cerebral hypofrontality. Via functional near-infrared spectroscopy (fNIRS), we investigated whether prefrontal hypoactivity during cognitive tasks in PD-patients compared to healthy controls (HC) could be replicated. As intermittent theta burst stimulation (iTBS) modulates cortical activity, we furthermore investigated its ability to normalise prefrontal activation. Methods. Forty-four PD-patients, randomised to sham or verum group, received 15 iTBS-sessions above the left dorsolateral prefrontal cortex (DLPFC) in addition to psychoeducation. Before first and after last iTBS-treatment, cortical activity during a verbal fluency task was assessed via fNIRS and compared to the results of 23 HC. Results. At baseline, PD-patients showed hypofrontality including the DLPFC, which differed significantly from activation patterns of HC. However, verum iTBS did not augment prefrontal fNIRS activation. Solely after sham iTBS, a significant increase of measured fNIRS activation in the left inferior frontal gyrus (IFG) during the phonological task was found. Conclusion. Our results support findings that PD is characterised by prefrontal hypoactivation during cognitive performance. However, verum iTBS as an “add-on” to psychoeducation did not augment prefrontal activity. Instead we only found increased fNIRS activation in the left IFG after sham iTBS application. Possible reasons including task-related psychophysiological arousal are discussed. PMID:24757668

Does rTMS alter neurocognitive functioning in patients with panic disorder/agoraphobia? An fNIRS-based investigation of prefrontal activation during a cognitive task and its modulation via sham-controlled rTMS.

PubMed

Deppermann, Saskia; Vennewald, Nadja; Diemer, Julia; Sickinger, Stephanie; Haeussinger, Florian B; Notzon, Swantje; Laeger, Inga; Arolt, Volker; Ehlis, Ann-Christine; Zwanzger, Peter; Fallgatter, Andreas J

2014-01-01

Neurobiologically, panic disorder (PD) is supposed to be characterised by cerebral hypofrontality. Via functional near-infrared spectroscopy (fNIRS), we investigated whether prefrontal hypoactivity during cognitive tasks in PD-patients compared to healthy controls (HC) could be replicated. As intermittent theta burst stimulation (iTBS) modulates cortical activity, we furthermore investigated its ability to normalise prefrontal activation. Forty-four PD-patients, randomised to sham or verum group, received 15 iTBS-sessions above the left dorsolateral prefrontal cortex (DLPFC) in addition to psychoeducation. Before first and after last iTBS-treatment, cortical activity during a verbal fluency task was assessed via fNIRS and compared to the results of 23 HC. At baseline, PD-patients showed hypofrontality including the DLPFC, which differed significantly from activation patterns of HC. However, verum iTBS did not augment prefrontal fNIRS activation. Solely after sham iTBS, a significant increase of measured fNIRS activation in the left inferior frontal gyrus (IFG) during the phonological task was found. Our results support findings that PD is characterised by prefrontal hypoactivation during cognitive performance. However, verum iTBS as an "add-on" to psychoeducation did not augment prefrontal activity. Instead we only found increased fNIRS activation in the left IFG after sham iTBS application. Possible reasons including task-related psychophysiological arousal are discussed.

Epigenetic signatures of autism: trimethylated H3K4 landscapes in prefrontal neurons.

PubMed

Shulha, Hennady P; Cheung, Iris; Whittle, Catheryne; Wang, Jie; Virgil, Daniel; Lin, Cong L; Guo, Yin; Lessard, Andree; Akbarian, Schahram; Weng, Zhiping

2012-03-01

Neuronal dysfunction in cerebral cortex and other brain regions could contribute to the cognitive and behavioral defects in autism. To characterize epigenetic signatures of autism in prefrontal cortex neurons. We performed fluorescence-activated sorting and separation of neuronal and nonneuronal nuclei from postmortem prefrontal cortex, digested the chromatin with micrococcal nuclease, and deeply sequenced the DNA from the mononucleosomes with trimethylated H3K4 (H3K4me3), a histone mark associated with transcriptional regulation. Approximately 15 billion base pairs of H3K4me3-enriched sequences were collected from 32 brains. Academic medical center. A total of 16 subjects diagnosed as having autism and 16 control subjects ranging in age from 0.5 to 70 years. Identification of genomic loci showing autism-associated H3K4me3 changes in prefrontal cortex neurons. Subjects with autism showed no evidence for generalized disruption of the developmentally regulated remodeling of the H3K4me3 landscape that defines normal prefrontal cortex neurons in early infancy. However, excess spreading of H3K4me3 from the transcription start sites into downstream gene bodies and upstream promoters was observed specifically in neuronal chromatin from 4 of 16 autism cases but not in controls. Variable subsets of autism cases exhibit altered H3K4me3 peaks at numerous genes regulating neuronal connectivity, social behaviors, and cognition, often in conjunction with altered expression of the corresponding transcripts. Autism-associated H3K4me3 peaks were significantly enriched in genes and loci implicated in neurodevelopmental diseases. Prefrontal cortex neurons from subjects with autism show changes in chromatin structures at hundreds of loci genome-wide, revealing considerable overlap between genetic and epigenetic risk maps of developmental brain disorders.

Cognitive and affective theory of mind share the same local patterns of activity in posterior temporal but not medial prefrontal cortex

PubMed Central

Hofstetter, Christoph; Vuilleumier, Patrik

2014-01-01

Understanding emotions in others engages specific brain regions in temporal and medial prefrontal cortices. These activations are often attributed to more general cognitive ‘mentalizing’ functions, associated with theory of mind and also necessary to represent people’s non-emotional mental states, such as beliefs or intentions. Here, we directly investigated whether understanding emotional feelings recruit similar or specific brain systems, relative to other non-emotional mental states. We used functional magnetic resonance imaging with multivoxel pattern analysis in 46 volunteers to compare activation patterns in theory-of-mind tasks for emotions, relative to beliefs or somatic states accompanied with pain. We found a striking dissociation between the temporoparietal cortex, that exhibited a remarkable voxel-by-voxel pattern overlap between emotions and beliefs (but not pain), and the dorsomedial prefrontal cortex, that exhibited distinct (and yet nearby) patterns of activity during the judgment of beliefs and emotions in others. Pain judgment was instead associated with activity in the supramarginal gyrus, middle cingulate cortex and middle insular cortex. Our data reveal for the first time a functional dissociation within brain networks sub-serving theory of mind for different mental contents, with a common recruitment for cognitive and affective states in temporal regions, and distinct recruitment in prefrontal areas. PMID:23770622

Prefrontal neural correlates of memory for sequences.

PubMed

Averbeck, Bruno B; Lee, Daeyeol

2007-02-28

The sequence of actions appropriate to solve a problem often needs to be discovered by trial and error and recalled in the future when faced with the same problem. Here, we show that when monkeys had to discover and then remember a sequence of decisions across trials, ensembles of prefrontal cortex neurons reflected the sequence of decisions the animal would make throughout the interval between trials. This signal could reflect either an explicit memory process or a sequence-planning process that begins far in advance of the actual sequence execution. This finding extended to error trials such that, when the neural activity during the intertrial interval specified the wrong sequence, the animal also attempted to execute an incorrect sequence. More specifically, we used a decoding analysis to predict the sequence the monkey was planning to execute at the end of the fore-period, just before sequence execution. When this analysis was applied to error trials, we were able to predict where in the sequence the error would occur, up to three movements into the future. This suggests that prefrontal neural activity can retain information about sequences between trials, and that regardless of whether information is remembered correctly or incorrectly, the prefrontal activity veridically reflects the animal's action plan.

Effects of Positive and Negative Mood Induction on the Prefrontal Cortex Activity Measured by Near Infrared Spectroscopy.

PubMed

Compare, A; Brugnera, Agostino; Adorni, R; Sakatani, K

2016-01-01

The neurophysiological mechanism of positive versus negative emotions is insufficiently understood. In the present study, we examined the effect of event recall tasks on the prefrontal cortex (PFC) activity using near infrared spectroscopy (NIRS). Nine healthy adults were instructed to recall episodes of their life associated with positive (happiness) and negative (anger) emotion, both silently and verbally. Heart rate (HR) changes were simultaneously measured. NIRS showed an increased oxyhemoglobin (oxy-Hb) in the bilateral PFC during silent and verbal recall of both positive and negative episodes. The changes of oxy-Hb in the bilateral PFC during silent recall of negative episodes were significantly larger than those during silent recall of positive episodes (p < 0.01). There was no difference in average changes of oxy-Hb between silent and verbal recall of negative episodes (p > 0.95), while changes of oxy-Hb during verbal recall of positive episodes were larger than those during silent recall of positive episodes (p < 0.05). Both verbal and silent recall of positive and negative episodes increased HR; however, verbal recall caused larger increases of HR than silent recall (p < 0.01). The present results suggest that recall of negative episodes affect the PFC activity, which plays a key role in cognitive control of emotions, more than positive episodes.

Decreased free d-aspartate levels are linked to enhanced d-aspartate oxidase activity in the dorsolateral prefrontal cortex of schizophrenia patients.

PubMed

Nuzzo, Tommaso; Sacchi, Silvia; Errico, Francesco; Keller, Simona; Palumbo, Orazio; Florio, Ermanno; Punzo, Daniela; Napolitano, Francesco; Copetti, Massimiliano; Carella, Massimo; Chiariotti, Lorenzo; Bertolino, Alessandro; Pollegioni, Loredano; Usiello, Alessandro

2017-01-01

It is long acknowledged that the N -methyl d-aspartate receptor co-agonist, d-serine, plays a crucial role in several N -methyl d-aspartate receptor-mediated physiological and pathological processes, including schizophrenia. Besides d-serine, another free d-amino acid, d-aspartate, is involved in the activation of N -methyl d-aspartate receptors acting as an agonist of this receptor subclass, and is abundantly detected in the developing human brain. Based on the hypothesis of N -methyl d-aspartate receptor hypofunction in the pathophysiology of schizophrenia and considering the ability of d-aspartate and d-serine to stimulate N -methyl d-aspartate receptor-dependent transmission, in the present work we assessed the concentration of these two d-amino acids in the post-mortem dorsolateral prefrontal cortex and hippocampus of patients with schizophrenia and healthy subjects. Moreover, in this cohort of post-mortem brain samples we investigated the spatiotemporal variations of d-aspartate and d-serine. Consistent with previous work, we found that d-aspartate content was selectively decreased by around 30% in the dorsolateral prefrontal cortex, but not in the hippocampus, of schizophrenia-affected patients, compared to healthy subjects. Interestingly, such selective reduction was associated to greater (around 25%) cortical activity of the enzyme responsible for d-aspartate catabolism, d-aspartate oxidase. Conversely, no significant changes were found in the methylation state and transcription of DDO gene in patients with schizophrenia, compared to control individuals, as well as in the expression levels of serine racemase, the major enzyme responsible for d-serine biosynthesis, which also catalyzes aspartate racemization. These results reveal the potential involvement of altered d-aspartate metabolism in the dorsolateral prefrontal cortex as a factor contributing to dysfunctional N -methyl d-aspartate receptor-mediated transmission in schizophrenia.

Basal Forebrain Gating by Somatostatin Neurons Drives Prefrontal Cortical Activity.

PubMed

Espinosa, Nelson; Alonso, Alejandra; Morales, Cristian; Espinosa, Pedro; Chávez, Andrés E; Fuentealba, Pablo

2017-11-17

The basal forebrain provides modulatory input to the cortex regulating brain states and cognitive processing. Somatostatin-expressing neurons constitute a heterogeneous GABAergic population known to functionally inhibit basal forebrain cortically projecting cells thus favoring sleep and cortical synchronization. However, it remains unclear if somatostatin cells can regulate population activity patterns in the basal forebrain and modulate cortical dynamics. Here, we demonstrate that somatostatin neurons regulate the corticopetal synaptic output of the basal forebrain impinging on cortical activity and behavior. Optogenetic inactivation of somatostatin neurons in vivo rapidly modified neural activity in the basal forebrain, with the consequent enhancement and desynchronization of activity in the prefrontal cortex, reflected in both neuronal spiking and network oscillations. Cortical activation was partially dependent on cholinergic transmission, suppressing slow waves and potentiating gamma oscillations. In addition, recruitment dynamics was cell type-specific, with interneurons showing similar temporal profiles, but stronger responses than pyramidal cells. Finally, optogenetic stimulation of quiescent animals during resting periods prompted locomotor activity, suggesting generalized cortical activation and increased arousal. Altogether, we provide physiological and behavioral evidence indicating that somatostatin neurons are pivotal in gating the synaptic output of the basal forebrain, thus indirectly controlling cortical operations via both cholinergic and non-cholinergic mechanisms. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

fNIRS Evidence of Prefrontal Regulation of Frustration in Early Childhood

PubMed Central

Perlman, Susan B.; Luna, Beatriz; Hein, Tyler C.; Huppert, Theodore J.

2013-01-01

The experience of frustration is common in early childhood, yet some children seem to possess a lower tolerance for frustration than others. Characterizing the biological mechanisms underlying a wide range of frustration tolerance observed in early childhood may inform maladaptive behavior and psychopathology that is associated with this construct. The goal of this study was to measure prefrontal correlates of frustration in 3–5 year-old children, who are not readily adaptable for typical neuroimaging approaches, using functional near infrared spectroscopy (fNIRS). fNIRS of frontal regions were measured as frustration was induced in children through a computer game where a desired and expected prize was “stolen” by an animated dog. A fNIRS general linear model (GLM) was used to quantify the correlation of brain regions with the task and identify areas that were statistically different between the winning and frustrating test conditions. A second-level voxel-based ANOVA analysis was then used to correlate the amplitude of each individual’s brain activation with measure of parent-reported frustration. Experimental results indicated increased activity in the middle prefrontal cortex during winning of a desired prize, while lateral prefrontal cortex activity increased during frustration. Further, activity increase in lateral prefrontal cortex during frustration correlated positively with parent-reported frustration tolerance. These findings point to the role of the lateral prefrontal cortex as a potential region supporting the regulation of emotion during frustration. PMID:23624495

Lateral prefrontal cortex activity during cognitive control of emotion predicts response to social stress in schizophrenia

PubMed Central

Tully, Laura M.; Lincoln, Sarah Hope; Hooker, Christine I.

2014-01-01

LPFC dysfunction is a well-established neural impairment in schizophrenia and is associated with worse symptoms. However, how LPFC activation influences symptoms is unclear. Previous findings in healthy individuals demonstrate that lateral prefrontal cortex (LPFC) activation during cognitive control of emotional information predicts mood and behavior in response to interpersonal conflict, thus impairments in these processes may contribute to symptom exacerbation in schizophrenia. We investigated whether schizophrenia participants show LPFC deficits during cognitive control of emotional information, and whether these LPFC deficits prospectively predict changes in mood and symptoms following real-world interpersonal conflict. During fMRI, 23 individuals with schizophrenia or schizoaffective disorder and 24 healthy controls completed the Multi-Source Interference Task superimposed on neutral and negative pictures. Afterwards, schizophrenia participants completed a 21-day online daily-diary in which they rated the extent to which they experienced mood and schizophrenia-spectrum symptoms, as well as the occurrence and response to interpersonal conflict. Schizophrenia participants had lower dorsal LPFC activity (BA9) during cognitive control of task-irrelevant negative emotional information. Within schizophrenia participants, DLPFC activity during cognitive control of emotional information predicted changes in positive and negative mood on days following highly distressing interpersonal conflicts. Results have implications for understanding the specific role of LPFC in response to social stress in schizophrenia, and suggest that treatments targeting LPFC-mediated cognitive control of emotion could promote adaptive response to social stress in schizophrenia. PMID:25379415

GABAA receptor subunit gene expression in human prefrontal cortex: comparison of schizophrenics and controls

NASA Technical Reports Server (NTRS)

Akbarian, S.; Huntsman, M. M.; Kim, J. J.; Tafazzoli, A.; Potkin, S. G.; Bunney, W. E. Jr; Jones, E. G.; Bloom, F. E. (Principal Investigator)

1995-01-01

The prefrontal cortex of schizophrenics is hypoactive and displays changes related to inhibitory, GABAergic neurons, and GABAergic synapses. These changes include decreased levels of glutamic acid decarboxylase (GAD), the enzyme for GABA synthesis, upregulation of muscimol binding, and downregulation of benzodiazepine binding to GABAA receptors. Studies in the visual cortex of nonhuman primates have demonstrated that gene expression for GAD and for several GABAA receptor subunit polypeptides is under control of neuronal activity, raising the possibility that similar mechanisms in the hypoactive prefrontal cortex of schizophrenics may explain the abnormalities in GAD and in GABAA receptor regulation. In the present study, which is the first of its type on human cerebral cortex, levels of mRNAs for six GABAA receptor subunits (alpha 1, alpha 2, alpha 5, beta 1, beta 2, gamma 2) and their laminar expression patterns were analyzed in the prefrontal cortex of schizophrenics and matched controls, using in situ hybridization histochemistry and densitometry. Three types of laminar expression pattern were observed: mRNAs for the alpha 1, beta 2, and gamma 2 subunits, which are the predominant receptor subunits expressed in the mature cortex, were expressed at comparatively high levels by cells of all six cortical layers, but most intensely by cells in lower layer III and layer IV. mRNAs for the alpha 2, alpha 5, and beta 1 subunits were expressed at lower levels; alpha 2 and beta 1 were expressed predominantly by cells in layers II, III, and IV; alpha 5 was expressed predominantly in layers IV, V, and VI. There were no significant changes in overall mRNA levels for any of the receptor subunits in the prefrontal cortex of schizophrenics, and the laminar expression pattern of all six receptor subunit mRNAs did not differ between schizophrenics and controls. Because gene expression for GABAA receptor subunits is not consistently altered in the prefrontal cortex of

Chronic administration of resveratrol prevents morphological changes in prefrontal cortex and hippocampus of aged rats.

PubMed

Monserrat Hernández-Hernández, Elizabeth; Serrano-García, Carolina; Antonio Vázquez-Roque, Rubén; Díaz, Alfonso; Monroy, Elibeth; Rodríguez-Moreno, Antonio; Florán, Benjamin; Flores, Gonzalo

2016-05-01

Resveratrol may induce its neuroprotective effects by reducing oxidative damage and chronic inflammation apart from improving vascular function and activating longevity genes, it also has the ability to promote the activity of neurotrophic factors. Morphological changes in dendrites of the pyramidal neurons of the prefrontal cortex (PFC) and hippocampus have been reported in the brain of aging humans, or in humans with neurodegenerative diseases such as Alzheimer's disease. These changes are reflected particularly in the decrement of both the dendritic tree and spine density. Here we evaluated the effect of resveratrol on the dendrites of pyramidal neurons of the PFC (Layers 3 and 5), CA1- and CA3-dorsal hippocampus (DH) as well as CA1-ventral hippocampus, dentate gyrus (DG), and medium spiny neurons of the nucleus accumbens of aged rats. 18-month-old rats were administered resveratrol (20 mg/kg, orally) daily for 60 days. Dendritic morphology was studied by the Golgi-Cox stain procedure, followed by Sholl analysis on 20-month-old rats. In all resveratrol-treated rats, a significant increase in dendritic length and spine density in pyramidal neurons of the PFC, CA1, and CA3 of DH was observed. Interestingly, the enhancement in dendritic length was close to the soma in pyramidal neurons of the PFC, whereas in neurons of the DH and DG, the increase in dendritic length was further from the soma. Our results suggest that resveratrol induces modifications of dendritic morphology in the PFC, DH, and DG. These changes may explain the therapeutic effect of resveratrol in aging and in Alzheimer's disease. © 2016 Wiley Periodicals, Inc.

Modulation of Limbic and Prefrontal Connectivity by Electroconvulsive Therapy in Treatment-resistant Depression: A Preliminary Study.

PubMed

Cano, Marta; Cardoner, Narcís; Urretavizcaya, Mikel; Martínez-Zalacaín, Ignacio; Goldberg, Ximena; Via, Esther; Contreras-Rodríguez, Oren; Camprodon, Joan; de Arriba-Arnau, Aida; Hernández-Ribas, Rosa; Pujol, Jesús; Soriano-Mas, Carles; Menchón, José M

2016-01-01

Although current models of depression suggest that a sequential modulation of limbic and prefrontal connectivity is needed for illness recovery, neuroimaging studies of electroconvulsive therapy (ECT) have focused on assessing functional connectivity (FC) before and after an ECT course, without characterizing functional changes occurring at early treatment phases. To assess sequential changes in limbic and prefrontal FC during the course of ECT and their impact on clinical response. Longitudinal intralimbic and limbic-prefrontal networks connectivity study. We assessed 15 patients with treatment-resistant depression at four different time-points throughout the entire course of an ECT protocol and 10 healthy participants at two functional neuroimaging examinations. Furthermore, a path analysis to test direct and indirect predictive effects of limbic and prefrontal FC changes on clinical response measured with the Hamilton Rating Scale for Depression was also performed. An early significant intralimbic FC decrease significantly predicted a later increase in limbic-prefrontal FC, which in turn significantly predicted clinical improvement at the end of an ECT course. Our data support that treatment response involves sequential changes in FC within regions of the intralimbic and limbic-prefrontal networks. This approach may help in identifying potential early biomarkers of treatment response. Copyright © 2015 Elsevier Inc. All rights reserved.

Abnormal network connectivity in frontotemporal dementia: evidence for prefrontal isolation.

PubMed

Farb, Norman A S; Grady, Cheryl L; Strother, Stephen; Tang-Wai, David F; Masellis, Mario; Black, Sandra; Freedman, Morris; Pollock, Bruce G; Campbell, Karen L; Hasher, Lynn; Chow, Tiffany W

2013-01-01

Degraded social function, disinhibition, and stereotypy are defining characteristics of frontotemporal dementia (FTD), manifesting in both the behavioral variant of frontotemporal dementia (bvFTD) and semantic dementia (SD) subtypes. Recent neuroimaging research also associates FTD with alterations in the brain's intrinsic connectivity networks. The present study explored the relationship between neural network connectivity and specific behavioral symptoms in FTD. Resting-state functional magnetic resonance imaging was employed to investigate neural network changes in bvFTD and SD. We used independent components analysis (ICA) to examine changes in frontolimbic network connectivity, as well as several metrics of local network strength, such as the fractional amplitude of low-frequency fluctuations, regional homogeneity, and seed-based functional connectivity. For each analysis, we compared each FTD subgroup to healthy controls, characterizing general and subtype-unique network changes. The relationship between abnormal connectivity in FTD and behavior disturbances was explored. Across multiple analytic approaches, both bvFTD and SD were associated with disrupted frontolimbic connectivity and elevated local connectivity within the prefrontal cortex. Even after controlling for structural atrophy, prefrontal hyperconnectivity was robustly associated with apathy scores. Frontolimbic disconnection was associated with lower disinhibition scores, suggesting that abnormal frontolimbic connectivity contributes to positive symptoms in dementia. Unique to bvFTD, stereotypy was associated with elevated default network connectivity in the right angular gyrus. The behavioral variant was also associated with marginally higher apathy scores and a more diffuse pattern of prefrontal hyperconnectivity than SD. The present findings support a theory of FTD as a disorder of frontolimbic disconnection leading to unconstrained prefrontal connectivity. Prefrontal hyperconnectivity may

Medial Prefrontal Cortex Reduces Memory Interference by Modifying Hippocampal Encoding

PubMed Central

Guise, Kevin G.; Shapiro, Matthew L.

2017-01-01

Summary The prefrontal cortex (PFC) is crucial for accurate memory performance when prior knowledge interferes with new learning, but the mechanisms that minimize proactive interference are unknown. To investigate these, we assessed the influence of medial PFC (mPFC) activity on spatial learning and hippocampal coding in a plus maze task that requires both structures. mPFC inactivation did not impair spatial learning or retrieval per se, but impaired the ability to follow changing spatial rules. mPFC and CA1 ensembles recorded simultaneously predicted goal choices and tracked changing rules; inactivating mPFC attenuated CA1 prospective coding. mPFC activity modified CA1 codes during learning, which in turn predicted how quickly rats adapted to subsequent rule changes. The results suggest that task rules signaled by the mPFC become incorporated into hippocampal representations and support prospective coding. By this mechanism, mPFC activity prevents interference by “teaching” the hippocampus to retrieve distinct representations of similar circumstances. PMID:28343868

The Analgesic and Anxiolytic Effect of Souvenaid, a Novel Nutraceutical, Is Mediated by Alox15 Activity in the Prefrontal Cortex.

PubMed

Shalini, Suku-Maran; Herr, Deron R; Ong, Wei-Yi

2017-10-01

Pain and anxiety have a complex relationship and pain is known to share neurobiological pathways and neurotransmitters with anxiety. Top-down modulatory pathways of pain have been shown to originate from cortical and subcortical regions, including the dorsolateral prefrontal cortex. In this study, a novel docosahexaenoic acid (DHA)-containing nutraceutical, Souvenaid, was administered to mice with infraorbital nerve ligation-induced neuropathic pain and behavioral responses recorded. Infraorbital nerve ligation resulted in increased face wash strokes of the face upon von Frey hair stimulation, indicating increased nociception. Part of this response involves general pain sensitization that is dependent on the CNS, since increased nociception was also found in the paws during the hot plate test. Mice receiving oral gavage of Souvenaid, a nutraceutical containing DHA; choline; and other cell membrane components, showed significantly reduced pain sensitization. The mechanism of Souvenaid's activity involves supraspinal antinociception, originating in the prefrontal cortex, since inhibition of the DHA-metabolizing enzyme 15-lipoxygenase (Alox15) in the prefrontal cortex attenuated the antinociceptive effect of Souvenaid. Alox15 inhibition also modulated anxiety behavior associated with pain after infraorbital nerve ligation. The effects of Souvenaid components and Alox15 on reducing central sensitization of pain may be due to strengthening of a known supraspinal antinociceptive pathway from the prefrontal cortex to the periaqueductal gray. Together, results indicate the importance of the prefrontal cortex and DHA/Alox15 in central antinociceptive pathways and suggest that Souvenaid may be a novel therapeutic for neuropathic pain.

Withholding response in the face of a smile: age-related differences in prefrontal sensitivity to Nogo cues following happy and angry faces.

PubMed

Todd, Rebecca M; Lee, Wayne; Evans, Jennifer W; Lewis, Marc D; Taylor, Margot J

2012-07-01

The modulation of control processes by stimulus salience, as well as associated neural activation, changes over development. We investigated age-related differences in the influence of facial emotion on brain activation when an action had to be withheld, focusing on a developmental period characterized by rapid social-emotional and cognitive change. Groups of kindergarten and young school-aged children and a group of young adults performed a modified Go/Nogo task. Response cues were preceded by happy or angry faces. After controlling for task performance, left orbitofrontal regions discriminated trials with happy vs. angry faces in children but not in adults when a response was withheld, and this effect decreased parametrically with age group. Age-related changes in prefrontal responsiveness to facial expression were not observed when an action was required, nor did this region show age-related activation changes with the demand to withhold a response in general. Such results reveal age-related differences in prefrontal activation that are specific to stimulus valence and depend on the action required. Copyright © 2012 Elsevier Ltd. All rights reserved.

Association between severe dorsolateral prefrontal dysfunction during random number generation and earlier onset in schizophrenia.

PubMed

Koike, Shinsuke; Takizawa, Ryu; Nishimura, Yukika; Marumo, Kohei; Kinou, Masaru; Kawakubo, Yuki; Rogers, Mark A; Kasai, Kiyoto

2011-08-01

Schizophrenia involves impairment in attention, working memory and executive processes associated with prefrontal cortical function, an essential contributor of social functioning. Age at onset is a major factor for predicting social outcome in schizophrenia. In clinical settings, we need an objective assessment tool for evaluating prefrontal function and social outcome. Participants included 22 right-handed patients with schizophrenia and 40 gender- and age-matched healthy controls. We used a 52-channel near-infrared spectroscopy (NIRS) instrument to measure oxygenated haemoglobin ([oxy-Hb]) changes over the prefrontal cortex during a random number generation (RNG) task. In healthy controls, we found significant [oxy-Hb] increase in the bilateral dorsolateral (DLPFC; BA9 and BA46) and ventrolateral prefrontal cortex (VLPFC; BA44, 45 and 47). The patients with schizophrenia showed significantly smaller activation than the healthy controls in the same approximate regions. In the patient group, a smaller [oxy-Hb] increase in the right DLPFC region (BA9) was significantly correlated with earlier age at onset. NIRS can detect prefrontal cortical dysfunction associated with an executive task, which was coupled with earlier age at onset in schizophrenia. Multichannel NIRS, a non-invasive and user-friendly instrument, may be useful in evaluating cognitive function and social outcome in clinical settings in psychiatry. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Decreased leftward bias of prefrontal activity in autism spectrum disorder revealed by functional near-infrared spectroscopy.

PubMed

Tamura, Ryu; Kitamura, Hideaki; Endo, Taro; Abe, Ryo; Someya, Toshiyuki

2012-01-01

Hemodynamic responses in rostral prefrontal cortex (RoPFC) were measured by functional near-infrared spectroscopy. Although performance level was equal, autistic patients showed a decrease in leftward bias of the balance between right and left RoPFC activity when compared with typically developing children when anatomical imitation was contrasted with mirror-image imitation. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Hippocampal-prefrontal input supports spatial encoding in working memory.

PubMed

Spellman, Timothy; Rigotti, Mattia; Ahmari, Susanne E; Fusi, Stefano; Gogos, Joseph A; Gordon, Joshua A

2015-06-18

Spatial working memory, the caching of behaviourally relevant spatial cues on a timescale of seconds, is a fundamental constituent of cognition. Although the prefrontal cortex and hippocampus are known to contribute jointly to successful spatial working memory, the anatomical pathway and temporal window for the interaction of these structures critical to spatial working memory has not yet been established. Here we find that direct hippocampal-prefrontal afferents are critical for encoding, but not for maintenance or retrieval, of spatial cues in mice. These cues are represented by the activity of individual prefrontal units in a manner that is dependent on hippocampal input only during the cue-encoding phase of a spatial working memory task. Successful encoding of these cues appears to be mediated by gamma-frequency synchrony between the two structures. These findings indicate a critical role for the direct hippocampal-prefrontal afferent pathway in the continuous updating of task-related spatial information during spatial working memory.

Stress amplifies sex differences in primate prefrontal profiles of gene expression.

PubMed

Lee, Alex G; Hagenauer, Megan; Absher, Devin; Morrison, Kathleen E; Bale, Tracy L; Myers, Richard M; Watson, Stanley J; Akil, Huda; Schatzberg, Alan F; Lyons, David M

2017-11-02

Stress is a recognized risk factor for mood and anxiety disorders that occur more often in women than men. Prefrontal brain regions mediate stress coping, cognitive control, and emotion. Here, we investigate sex differences and stress effects on prefrontal cortical profiles of gene expression in squirrel monkey adults. Dorsolateral, ventrolateral, and ventromedial prefrontal cortical regions from 18 females and 12 males were collected after stress or no-stress treatment conditions. Gene expression profiles were acquired using HumanHT-12v4.0 Expression BeadChip arrays adapted for squirrel monkeys. Extensive variation between prefrontal cortical regions was discerned in the expression of numerous autosomal and sex chromosome genes. Robust sex differences were also identified across prefrontal cortical regions in the expression of mostly autosomal genes. Genes with increased expression in females compared to males were overrepresented in mitogen-activated protein kinase and neurotrophin signaling pathways. Many fewer genes with increased expression in males compared to females were discerned, and no molecular pathways were identified. Effect sizes for sex differences were greater in stress compared to no-stress conditions for ventromedial and ventrolateral prefrontal cortical regions but not dorsolateral prefrontal cortex. Stress amplifies sex differences in gene expression profiles for prefrontal cortical regions involved in stress coping and emotion regulation. Results suggest molecular targets for new treatments of stress disorders in human mental health.

Decreased prefrontal Myo-inositol in major depressive disorder.

PubMed

Coupland, Nick J; Ogilvie, Catherine J; Hegadoren, Kathleen M; Seres, Peter; Hanstock, Chris C; Allen, Peter S

2005-06-15

Postmortem studies have shown robust prefrontal cortex glial losses and more subtle neuronal changes in major depressive disorder (MDD). Earlier proton magnetic resonance spectroscopy (1H-MRS) studies of the glial marker myo-inositol in MDD were subject to potential confounds. The primary hypothesis of this study was that MDD patients would show reduced prefrontal/anterior cingulate cortex levels of myo-inositol. Thirteen nonmedicated moderate-severe MDD patients and 13 matched control subjects were studied (six male, seven female per group). Proton magnetic resonance spectroscopy stimulated echo acquisition mode spectra (3.0 T; echo time=168 msec; mixing time=28 msec; repetition time=3000 msec) were obtained from prefrontal/anterior cingulate cortex. Metabolite data were adjusted for tissue composition. Patients with MDD showed significantly lower myo-inositol/creatine ratios (.94+/-.23) than control subjects (1.32+/-.37) [F(1,23)=6.9; p=.016]. These data suggest a reduction of myo-inositol in prefrontal/anterior cingulate cortex in MDD, which could be a consequence of glial loss or altered glial metabolism. Additional in vivo studies of glial markers could add to the understanding of the pathophysiology of MDD.

Ventromedial prefrontal cortex activity and pathological worry in generalised anxiety disorder.

PubMed

Via, E; Fullana, M A; Goldberg, X; Tinoco-González, D; Martínez-Zalacaín, I; Soriano-Mas, C; Davey, C G; Menchón, J M; Straube, B; Kircher, T; Pujol, J; Cardoner, N; Harrison, B J

2018-05-09

Pathological worry is a hallmark feature of generalised anxiety disorder (GAD), associated with dysfunctional emotional processing. The ventromedial prefrontal cortex (vmPFC) is involved in the regulation of such processes, but the link between vmPFC emotional responses and pathological v. adaptive worry has not yet been examined.AimsTo study the association between worry and vmPFC activity evoked by the processing of learned safety and threat signals. In total, 27 unmedicated patients with GAD and 56 healthy controls (HC) underwent a differential fear conditioning paradigm during functional magnetic resonance imaging. Compared to HC, the GAD group demonstrated reduced vmPFC activation to safety signals and no safety-threat processing differentiation. This response was positively correlated with worry severity in GAD, whereas the same variables showed a negative and weak correlation in HC. Poor vmPFC safety-threat differentiation might characterise GAD, and its distinctive association with GAD worries suggests a neural-based qualitative difference between healthy and pathological worries.Declaration of interestNone.

Adaptive Encoding of Outcome Prediction by Prefrontal Cortex Ensembles Supports Behavioral Flexibility.

PubMed

Del Arco, Alberto; Park, Junchol; Wood, Jesse; Kim, Yunbok; Moghaddam, Bita

2017-08-30

The prefrontal cortex (PFC) is thought to play a critical role in behavioral flexibility by monitoring action-outcome contingencies. How PFC ensembles represent shifts in behavior in response to changes in these contingencies remains unclear. We recorded single-unit activity and local field potentials in the dorsomedial PFC (dmPFC) of male rats during a set-shifting task that required them to update their behavior, among competing options, in response to changes in action-outcome contingencies. As behavior was updated, a subset of PFC ensembles encoded the current trial outcome before the outcome was presented. This novel outcome-prediction encoding was absent in a control task, in which actions were rewarded pseudorandomly, indicating that PFC neurons are not merely providing an expectancy signal. In both control and set-shifting tasks, dmPFC neurons displayed postoutcome discrimination activity, indicating that these neurons also monitor whether a behavior is successful in generating rewards. Gamma-power oscillatory activity increased before the outcome in both tasks but did not differentiate between expected outcomes, suggesting that this measure is not related to set-shifting behavior but reflects expectation of an outcome after action execution. These results demonstrate that PFC neurons support flexible rule-based action selection by predicting outcomes that follow a particular action. SIGNIFICANCE STATEMENT Tracking action-outcome contingencies and modifying behavior when those contingencies change is critical to behavioral flexibility. We find that ensembles of dorsomedial prefrontal cortex neurons differentiate between expected outcomes when action-outcome contingencies change. This predictive mode of signaling may be used to promote a new response strategy at the service of behavioral flexibility. Copyright © 2017 the authors 0270-6474/17/378363-11$15.00/0.

Deficits in process-specific prefrontal and hippocampal activations contribute to adult age differences in episodic memory interference.

PubMed

Fandakova, Yana; Lindenberger, Ulman; Shing, Yee Lee

2014-07-01

The ability to distinguish currently relevant from familiar but irrelevant memories is important in everyday life. We used functional magnetic resonance imaging to examine the neural correlates of age differences in the ability to withstand interference from similar past events. Younger and older adults worked on a continuous recognition task consisting of 3 consecutive runs. Each run was composed of the same set of word pairs, and participants were instructed to recognize word pair repetitions within runs. The monitoring demands associated with rejecting familiar, but currently irrelevant information were assumed to increase over consecutive runs. Over runs, older, but not younger adults showed decline in memory performance, whereas younger, but not older adults showed increasing engagement of anterior prefrontal cortex. Individual differences in cortical thickness and task-related activation of anterior prefrontal areas predicted performance differences within and across age groups. Compared with younger adults, older adults also showed a reduced hippocampal response to novel associations of familiar stimuli. We conclude that monitoring deficits due to impaired involvement of prefrontal regions and reduced hippocampal responses to associative novelty contribute to aging-related deficits in disambiguating the contextual information of familiar events. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Role of Prefrontal and Parietal Cortices in Associative Learning

PubMed Central

Anderson, John R.; Byrne, Dana; Fincham, Jon M.; Gunn, Pat

2017-01-01

Two studies were performed that compared a “Paired” condition in which participants studied paired associates with a “Generated” condition in which participants completed word fragments to produce paired associates. In both tasks, participants were responsible for memory of the material either studied or generated. The experiments revealed significant differences between the responses of a predefined prefrontal region and a predefined parietal region. The parietal region responded more in the Generated condition than the Paired condition, whereas there was no difference in the prefrontal region. On the other hand, the prefrontal region responded to the delay between study and test in both the Paired and Generated conditions, whereas the parietal region only responded to delay in the Generated condition. This pattern of results is consistent with the hypothesis that the parietal region is responsive to changes in problem representation and the prefrontal region to retrieval operations. An information-processing model embodying these assumptions was fit to the blood oxygen level–dependent responses in these regions. PMID:17675369

Prefrontal Transcranial Direct Current Stimulation for Treatment of Schizophrenia With Predominant Negative Symptoms: A Double-Blind, Sham-Controlled Proof-of-Concept Study

PubMed Central

Palm, Ulrich; Keeser, Daniel; Hasan, Alkomiet; Kupka, Michael J.; Blautzik, Janusch; Sarubin, Nina; Kaymakanova, Filipa; Unger, Ina; Falkai, Peter; Meindl, Thomas; Ertl-Wagner, Birgit; Padberg, Frank

2016-01-01

Negative symptoms are highly relevant in the long-term course of schizophrenia and are an important target domain for the development of novel interventions. Recently, transcranial direct current stimulation (tDCS) of the prefrontal cortex has been investigated as a treatment option in schizophrenia. In this proof-of-concept study, 20 schizophrenia patients with predominantly negative symptoms were randomized to either 10 sessions of add-on active (2 mA, 20min) or sham tDCS (anode: left DLPFC/F3; cathode: right supraorbital/F4). Primary outcome measure was the change in the Scale for the Assessment of Negative Symptoms (SANS) sum score; secondary outcomes included reduction in Positive and Negative Syndrome Scale (PANSS) scores and improvement of depressive symptoms, cognitive processing speed, and executive functioning. Sixteen patients underwent 4 functional connectivity magnetic resonance imaging (fcMRI) scans (pre and post 1st and pre and post 10th tDCS) to investigate changes in resting state network connectivity after tDCS. Per-protocol analysis showed a significantly greater decrease in SANS score after active (−36.1%) than after sham tDCS (−0.7%). PANSS sum scores decreased significantly more with active (−23.4%) than with sham stimulation (−2.2%). Explorative analysis of fcMRI data indicated changes in subgenual cortex and dorsolateral prefrontal cortex (DLPFC) connectivity within frontal-thalamic-temporo-parietal networks. The results of this first proof-of-concept study indicate that prefrontal tDCS may be a promising intervention for treatment of schizophrenia with predominant negative symptoms. Large-scale randomized controlled studies are needed to further establish prefrontal tDCS as novel treatment for negative symptoms in schizophrenia. PMID:27098066

Differential involvement of left prefrontal cortex in inductive and deductive reasoning.

PubMed

Goel, Vinod; Dolan, Raymond J

2004-10-01

While inductive and deductive reasoning are considered distinct logical and psychological processes, little is known about their respective neural basis. To address this issue we scanned 16 subjects with fMRI, using an event-related design, while they engaged in inductive and deductive reasoning tasks. Both types of reasoning were characterized by activation of left lateral prefrontal and bilateral dorsal frontal, parietal, and occipital cortices. Neural responses unique to each type of reasoning determined from the Reasoning Type (deduction and induction) by Task (reasoning and baseline) interaction indicated greater involvement of left inferior frontal gyrus (BA 44) in deduction than induction, while left dorsolateral (BA 8/9) prefrontal gyrus showed greater activity during induction than deduction. This pattern suggests a dissociation within prefrontal cortex for deductive and inductive reasoning.

Dorsolateral prefrontal cortex activation during emotional anticipation and neuropsychological performance in posttraumatic stress disorder.

PubMed

Aupperle, Robin L; Allard, Carolyn B; Grimes, Erin M; Simmons, Alan N; Flagan, Taru; Behrooznia, Michelle; Cissell, Shadha H; Twamley, Elizabeth W; Thorp, Steven R; Norman, Sonya B; Paulus, Martin P; Stein, Murray B

2012-04-01

Posttraumatic stress disorder (PTSD) has been associated with executive or attentional dysfunction and problems in emotion processing. However, it is unclear whether these two domains of dysfunction are related to common or distinct neurophysiological substrates. To examine the hypothesis that greater neuropsychological impairment in PTSD relates to greater disruption in prefrontal-subcortical networks during emotional anticipation. Case-control, cross-sectional study. General community and hospital and community psychiatric clinics. Volunteer sample of 37 women with PTSD related to intimate partner violence and 34 age-comparable healthy control women. We used functional magnetic resonance imaging (fMRI) to examine neural responses during anticipation of negative and positive emotional images. The Clinician-Administered PTSD Scale was used to characterize PTSD symptom severity. The Wechsler Adult Intelligence Scale, Third Edition, Digit Symbol Test, Delis-Kaplan Executive Function System Color-Word Interference Test, and Wisconsin Card Sorting Test were used to characterize neuropsychological performance. Women with PTSD performed worse on complex visuomotor processing speed (Digit Symbol Test) and executive function (Color-Word Interference Inhibition/Switching subtest) measures compared with control subjects. Posttraumatic stress disorder was associated with greater anterior insula and attenuated lateral prefrontal cortex (PFC) activation during emotional anticipation. Greater dorsolateral PFC activation (anticipation of negative images minus anticipation of positive images) was associated with lower PTSD symptom severity and better visuomotor processing speed and executive functioning. Greater medial PFC and amygdala activation related to slower visuomotor processing speed. During emotional anticipation, women with PTSD show exaggerated activation in the anterior insula, a region important for monitoring internal bodily state. Greater dorsolateral PFC response

Cannabinoid modulation of prefrontal-limbic activation during fear extinction learning and recall in humans

PubMed Central

Rabinak, Christine A.; Angstadt, Mike; Lyons, Maryssa; Mori, Shoko; Milad, Mohammed R.; Liberzon, Israel; Phan, K. Luan

2013-01-01

Pre-extinction administration of ∆9-tetrahydrocannibinol (THC) facilitates recall of extinction in healthy humans, and evidence from animal studies suggest that this likely involves via enhancement of the cannabinoid system within the ventromedial prefrontal cortex (vmPFC) and hippocampus (HIPP), brain structures critical to fear extinction. However, the effect of cannabinoids on the underlying neural circuitry of extinction memory recall in humans has not been demonstrated. We conducted a functional magnetic resonance imaging (fMRI) study using a randomized, double-blind, placebo-controlled, between-subjects design (N=14/group) coupled with a standard Pavlovian fear extinction paradigm and an acute pharmacological challenge with oral dronabinol (synthetic THC) in healthy adult volunteers. We examined the effects of THC on vmPFC and HIPP activation when tested for recall of extinction learning 24 hours after extinction learning. Compared to subjects who received placebo, participants who received THC showed increased vmPFC and HIPP activation to a previously extinguished conditioned stimulus (CS+E) during extinction memory recall. This study provides the first evidence that pre-extinction administration of THC modulates prefrontal-limbic circuits during fear extinction in humans and prompts future investigation to test if cannabinoid agonists can rescue or correct the impaired behavioral and neural function during extinction recall in patients with PTSD. Ultimately, the cannabinoid system may serve as a promising target for innovative intervention strategies (e.g. pharmacological enhancement of exposure-based therapy) in PTSD and other fear learning-related disorders. PMID:24055595

The Influence of Televised Food Commercials on Children's Food Choices: Evidence from Ventromedial Prefrontal Cortex Activations.

PubMed

Bruce, Amanda S; Pruitt, Stephen W; Ha, Oh-Ryeong; Cherry, J Bradley C; Smith, Timothy R; Bruce, Jared M; Lim, Seung-Lark

2016-10-01

To investigate how food commercials influence children's food choices. Twenty-three children ages 8-14 years provided taste and health ratings for 60 food items. Subsequently, these children were scanned with the use of functional magnetic resonance imaging while making food choices (ie, "eat" or "not eat") after watching food and nonfood television commercials. Our results show that watching food commercials changes the way children consider the importance of taste when making food choices. Children did not use health values for their food choices, indicating children's decisions were largely driven by hedonic, immediate rewards (ie, "tastiness"); however, children placed significantly more importance on taste after watching food commercials compared with nonfood commercials. This change was accompanied by faster decision times during food commercial trials. The ventromedial prefrontal cortex, a reward valuation brain region, showed increased activity during food choices after watching food commercials compared with after watching nonfood commercials. Overall, our results suggest watching food commercials before making food choices may bias children's decisions based solely on taste, and that food marketing may systematically alter the psychological and neurobiologic mechanisms of children's food decisions. Copyright © 2016 Elsevier Inc. All rights reserved.

The Influence of Televised Food Commercials on Children's Food Choices: Evidence from Ventromedial Prefrontal Cortex Activations

PubMed Central

Bruce, Amanda S.; Pruitt, Stephen W.; Ha, Oh-Ryeong; Cherry, J. Bradley C.; Smith, Timothy R.; Bruce, Jared M.; Lim, Seung-Lark

2016-01-01

Objective To investigate how food commercials influence children's food choices. Study design Twenty-three children ages 8-14 years provided taste and health ratings for 60 food items. Subsequently, these children were scanned with the use of functional magnetic resonance imaging while making food choices (ie, “eat” or “not eat”) after watching food and nonfood television commercials. Results Our results show that watching food commercials changes the way children consider the importance of taste when making food choices. Children did not use health values for their food choices, indicating children's decisions were largely driven by hedonic, immediate rewards (ie, “tastiness”); however, children placed significantly more importance on taste after watching food commercials compared with nonfood commercials. This change was accompanied by faster decision times during food commercial trials. The ventromedial prefrontal cortex, a reward valuation brain region, showed increased activity during food choices after watching food commercials compared with after watching nonfood commercials. Conclusion Overall, our results suggest watching food commercials before making food choices may bias children's decisions based solely on taste, and that food marketing may systematically alter the psychological and neurobiologic mechanisms of children's food decisions. PMID:27526621

Cognitive and behavioural deficits associated with the orbitomedial prefrontal cortex in amyotrophic lateral sclerosis.

PubMed

Meier, Sandra L; Charleston, Alison J; Tippett, Lynette J

2010-11-01

Amyotrophic lateral sclerosis, a progressive disease affecting motor neurons, may variably affect cognition and behaviour. We tested the hypothesis that functions associated with orbitomedial prefrontal cortex are affected by evaluating the behavioural and cognitive performance of 18 participants with amyotrophic lateral sclerosis without dementia and 18 healthy, matched controls. We measured Theory of Mind (Faux Pas Task), emotional prosody recognition (Aprosodia Battery), reversal of behaviour in response to changes in reward (Probabilistic Reversal Learning Task), decision making without risk (Holiday Apartment Task) and aberrant behaviour (Neuropsychiatric Inventory). We also assessed dorsolateral prefrontal function, using verbal and written fluency and planning (One-touch Stockings of Cambridge), to determine whether impairments in tasks sensitive to these two prefrontal regions co-occur. The patient group was significantly impaired at identifying social faux pas, recognizing emotions and decision-making, indicating mild, but consistent impairment on most measures sensitive to orbitomedial prefrontal cortex. Significant levels of aberrant behaviour were present in 50% of patients. Patients were also impaired on verbal fluency and planning. Individual subject analyses involved computing classical dissociations between tasks sensitive to different prefrontal regions. These revealed heterogeneous patterns of impaired and spared cognitive abilities: 33% of participants had classical dissociations involving orbitomedial prefrontal tasks, 17% had classical dissociations involving dorsolateral prefrontal tasks, 22% had classical dissociations between tasks of both regions, and 28% had no classical dissociations. These data indicate subtle changes in behaviour, emotional processing, decision-making and altered social awareness, associated with orbitomedial prefrontal cortex, may be present in a significant proportion of individuals with amyotrophic lateral sclerosis

Serotonin 1B Receptors Regulate Prefrontal Function by Gating Callosal and Hippocampal Inputs.

PubMed

Kjaerby, Celia; Athilingam, Jegath; Robinson, Sarah E; Iafrati, Jillian; Sohal, Vikaas S

2016-12-13

Both medial prefrontal cortex (mPFC) and serotonin play key roles in anxiety; however, specific mechanisms through which serotonin might act on the mPFC to modulate anxiety-related behavior remain unknown. Here, we use a combination of optogenetics and synaptic physiology to show that serotonin acts presynaptically via 5-HT1B receptors to selectively suppress inputs from the contralateral mPFC and ventral hippocampus (vHPC), while sparing those from mediodorsal thalamus. To elucidate how these actions could potentially regulate prefrontal circuit function, we infused a 5-HT1B agonist into the mPFC of freely behaving mice. Consistent with previous studies that have optogenetically inhibited vHPC-mPFC projections, activating prefrontal 5-HT1B receptors suppressed theta-frequency mPFC activity (4-12 Hz), and reduced avoidance of anxiogenic regions in the elevated plus maze. These findings suggest a potential mechanism, linking specific receptors, synapses, patterns of circuit activity, and behavior, through which serotonin may regulate prefrontal circuit function, including anxiety-related behaviors. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Collaborative activity between parietal and dorso-lateral prefrontal cortex in dynamic spatial working memory revealed by fMRI.

PubMed

Diwadkar, V A; Carpenter, P A; Just, M A

2000-07-01

Functional MRI was used to determine how the constituents of the cortical network subserving dynamic spatial working memory respond to two types of increases in task complexity. Participants mentally maintained the most recent location of either one or three objects as the three objects moved discretely in either a two- or three-dimensional array. Cortical activation in the dorsolateral prefrontal (DLPFC) and the parietal cortex increased as a function of the number of object locations to be maintained and the dimensionality of the display. An analysis of the response characteristics of the individual voxels showed that a large proportion were activated only when both the variables imposed the higher level of demand. A smaller proportion were activated specifically in response to increases in task demand associated with each of the independent variables. A second experiment revealed the same effect of dimensionality in the parietal cortex when the movement of objects was signaled auditorily rather than visually, indicating that the additional representational demands induced by 3-D space are independent of input modality. The comodulation of activation in the prefrontal and parietal areas by the amount of computational demand suggests that the collaboration between areas is a basic feature underlying much of the functionality of spatial working memory. Copyright 2000 Academic Press.

The change of the brain activation patterns as children learn algebra equation solving

NASA Astrophysics Data System (ADS)

Qin, Yulin; Carter, Cameron S.; Silk, Eli M.; Stenger, V. Andrew; Fissell, Kate; Goode, Adam; Anderson, John R.

2004-04-01

In a brain imaging study of children learning algebra, it is shown that the same regions are active in children solving equations as are active in experienced adults solving equations. As with adults, practice in symbol manipulation produces a reduced activation in prefrontal cortex area. However, unlike adults, practice seems also to produce a decrease in a parietal area that is holding an image of the equation. This finding suggests that adolescents' brain responses are more plastic and change more with practice. These results are integrated in a cognitive model that predicts both the behavioral and brain imaging results.

Abnormal prefrontal and parietal activity linked to deficient active binding in working memory in schizophrenia.

PubMed

Grot, Stéphanie; Légaré, Virginie Petel; Lipp, Olivier; Soulières, Isabelle; Dolcos, Florin; Luck, David

2017-10-01

Working memory deficits have been widely reported in schizophrenia, and may result from inefficient binding processes. These processes, and their neural correlates, remain understudied in schizophrenia. Thus, we designed an FMRI study aimed at investigating the neural correlates of both passive and active binding in working memory in schizophrenia. Nineteen patients with schizophrenia and 23 matched controls were recruited to perform a working memory binding task, in which they were instructed to memorize three letters and three spatial locations. In the passive binding condition, letters and spatial locations were directly presented as bound. Conversely, in the active binding condition, words and spatial locations were presented as separated, and participants were instructed to intentionally create associations between them. Patients exhibited a similar performance to the controls for the passive binding condition, but a significantly lower performance for the active binding. FMRI analyses revealed that this active binding deficit was related to aberrant activity in the posterior parietal cortex and the ventrolateral prefrontal cortex. This study provides initial evidence of a specific deficit for actively binding information in schizophrenia, which is linked to dysfunctions in the neural networks underlying attention, manipulation of information, and encoding strategies. Together, our results suggest that all these dysfunctions may be targets for neuromodulation interventions known to improve cognitive deficits in schizophrenia. Copyright © 2017 Elsevier B.V. All rights reserved.

Predicting Treatment Outcomes from Prefrontal Cortex Activation for Self-Harming Patients with Borderline Personality Disorder: A Preliminary Study

PubMed Central

Ruocco, Anthony C.; Rodrigo, Achala H.; McMain, Shelley F.; Page-Gould, Elizabeth; Ayaz, Hasan; Links, Paul S.

2016-01-01

Self-harm is a potentially lethal symptom of borderline personality disorder (BPD) that often improves with dialectical behavior therapy (DBT). While DBT is effective for reducing self-harm in many patients with BPD, a small but significant number of patients either does not improve in treatment or ends treatment prematurely. Accordingly, it is crucial to identify factors that may prospectively predict which patients are most likely to benefit from and remain in treatment. In the present preliminary study, 29 actively self-harming patients with BPD completed brain-imaging procedures probing activation of the prefrontal cortex (PFC) during impulse control prior to beginning DBT and after 7 months of treatment. Patients that reduced their frequency of self-harm the most over treatment displayed lower levels of neural activation in the bilateral dorsolateral prefrontal cortex (DLPFC) prior to beginning treatment, and they showed the greatest increases in activity within this region after 7 months of treatment. Prior to starting DBT, treatment non-completers demonstrated greater activation than treatment-completers in the medial PFC and right inferior frontal gyrus. Reductions in self-harm over the treatment period were associated with increases in activity in right DLPFC even after accounting for improvements in depression, mania, and BPD symptom severity. These findings suggest that pre-treatment patterns of activation in the PFC underlying impulse control may be prospectively associated with improvements in self-harm and treatment attrition for patients with BPD treated with DBT. PMID:27242484

Predicting Treatment Outcomes from Prefrontal Cortex Activation for Self-Harming Patients with Borderline Personality Disorder: A Preliminary Study.

PubMed

Ruocco, Anthony C; Rodrigo, Achala H; McMain, Shelley F; Page-Gould, Elizabeth; Ayaz, Hasan; Links, Paul S

2016-01-01

Self-harm is a potentially lethal symptom of borderline personality disorder (BPD) that often improves with dialectical behavior therapy (DBT). While DBT is effective for reducing self-harm in many patients with BPD, a small but significant number of patients either does not improve in treatment or ends treatment prematurely. Accordingly, it is crucial to identify factors that may prospectively predict which patients are most likely to benefit from and remain in treatment. In the present preliminary study, 29 actively self-harming patients with BPD completed brain-imaging procedures probing activation of the prefrontal cortex (PFC) during impulse control prior to beginning DBT and after 7 months of treatment. Patients that reduced their frequency of self-harm the most over treatment displayed lower levels of neural activation in the bilateral dorsolateral prefrontal cortex (DLPFC) prior to beginning treatment, and they showed the greatest increases in activity within this region after 7 months of treatment. Prior to starting DBT, treatment non-completers demonstrated greater activation than treatment-completers in the medial PFC and right inferior frontal gyrus. Reductions in self-harm over the treatment period were associated with increases in activity in right DLPFC even after accounting for improvements in depression, mania, and BPD symptom severity. These findings suggest that pre-treatment patterns of activation in the PFC underlying impulse control may be prospectively associated with improvements in self-harm and treatment attrition for patients with BPD treated with DBT.

Acetylcholine Release in Prefrontal Cortex Promotes Gamma Oscillations and Theta-Gamma Coupling during Cue Detection.

PubMed

Howe, William M; Gritton, Howard J; Lusk, Nicholas A; Roberts, Erik A; Hetrick, Vaughn L; Berke, Joshua D; Sarter, Martin

2017-03-22

The capacity for using external cues to guide behavior ("cue detection") constitutes an essential aspect of attention and goal-directed behavior. The cortical cholinergic input system, via phasic increases in prefrontal acetylcholine release, plays an essential role in attention by mediating such cue detection. However, the relationship between cholinergic signaling during cue detection and neural activity dynamics in prefrontal networks remains unclear. Here we combined subsecond measures of cholinergic signaling, neurophysiological recordings, and cholinergic receptor blockade to delineate the cholinergic contributions to prefrontal oscillations during cue detection in rats. We first confirmed that detected cues evoke phasic acetylcholine release. These cholinergic signals were coincident with increased neuronal synchrony across several frequency bands and the emergence of theta-gamma coupling. Muscarinic and nicotinic cholinergic receptors both contributed specifically to gamma synchrony evoked by detected cues, but the effects of blocking the two receptor subtypes were dissociable. Blocking nicotinic receptors primarily attenuated high-gamma oscillations occurring during the earliest phases of the cue detection process, while muscarinic (M1) receptor activity was preferentially involved in the transition from high to low gamma power that followed and corresponded to the mobilization of networks involved in cue-guided decision making. Detected cues also promoted coupling between gamma and theta oscillations, and both nicotinic and muscarinic receptor activity contributed to this process. These results indicate that acetylcholine release coordinates neural oscillations during the process of cue detection. SIGNIFICANCE STATEMENT The capacity of learned cues to direct attention and guide responding ("cue detection") is a key component of goal-directed behavior. Rhythmic neural activity and increases in acetylcholine release in the prefrontal cortex contribute to

Acetylcholine Release in Prefrontal Cortex Promotes Gamma Oscillations and Theta–Gamma Coupling during Cue Detection

PubMed Central

Hetrick, Vaughn L.; Berke, Joshua D.

2017-01-01

The capacity for using external cues to guide behavior (“cue detection”) constitutes an essential aspect of attention and goal-directed behavior. The cortical cholinergic input system, via phasic increases in prefrontal acetylcholine release, plays an essential role in attention by mediating such cue detection. However, the relationship between cholinergic signaling during cue detection and neural activity dynamics in prefrontal networks remains unclear. Here we combined subsecond measures of cholinergic signaling, neurophysiological recordings, and cholinergic receptor blockade to delineate the cholinergic contributions to prefrontal oscillations during cue detection in rats. We first confirmed that detected cues evoke phasic acetylcholine release. These cholinergic signals were coincident with increased neuronal synchrony across several frequency bands and the emergence of theta–gamma coupling. Muscarinic and nicotinic cholinergic receptors both contributed specifically to gamma synchrony evoked by detected cues, but the effects of blocking the two receptor subtypes were dissociable. Blocking nicotinic receptors primarily attenuated high-gamma oscillations occurring during the earliest phases of the cue detection process, while muscarinic (M1) receptor activity was preferentially involved in the transition from high to low gamma power that followed and corresponded to the mobilization of networks involved in cue-guided decision making. Detected cues also promoted coupling between gamma and theta oscillations, and both nicotinic and muscarinic receptor activity contributed to this process. These results indicate that acetylcholine release coordinates neural oscillations during the process of cue detection. SIGNIFICANCE STATEMENT The capacity of learned cues to direct attention and guide responding (“cue detection”) is a key component of goal-directed behavior. Rhythmic neural activity and increases in acetylcholine release in the prefrontal cortex

Developmental changes in real life decision making: performance on a gambling task previously shown to depend on the ventromedial prefrontal cortex.

PubMed

Crone, Eveline A; van der Molen, Maurits W

2004-01-01

Patients with bilateral lesions of the ventromedial prefrontal cortex, when performing gambling tasks modeling real-life decision-making, opt for choices that yield high immediate gains in spite of higher future losses. Under the hypothesis that the prefrontal cortex is the last brain region to mature, it was examined whether young children would show a similar preference for immediate prospects. In Experiment 1, 4 age groups (6-9, 10-12, 13-15 and 18-25 years olds) performed 2 versions of a computerized variant of the original Iowa gambling task under 3 different feedback conditions (no feedback, global feedback, and option-specific feedback) and completed the Raven Standard Progressive Matrices as an index of inductive reasoning ability. In Experiment 2, 3 age groups (7-8, 11-12, and 15-16 year olds) performed both task versions in addition to a working memory task ("Digit Span Backwards"). Results showed a developmental increase in the sensitivity to future consequences, positive or negative, that could not be explained by developmental changes in working memory capacity or inductive reasoning. It was concluded that young children share with ventromedial prefrontal patients the failure to anticipate on future outcomes.

Subchronic glucocorticoids, glutathione depletion and a postpartum model elevate monoamine oxidase a activity in the prefrontal cortex of rats.

PubMed

Raitsin, Sofia; Tong, Junchao; Kish, Stephen; Xu, Xin; Magomedova, Lilia; Cummins, Carolyn; Andreazza, Ana C; Scola, Gustavo; Baker, Glen; Meyer, Jeffrey H

2017-07-01

Recent human brain imaging studies implicate dysregulation of monoamine oxidase-A (MAO-A), in particular in the prefrontal cortex (PFC) and anterior cingulate cortex (ACC), in the development of major depressive disorder (MDD). This study investigates the influence of four alterations underlying important pathologies of MDD, namely, chronic elevation of glucocorticoid levels, glutathione depletion, changes in female gonadal sex hormones and serotonin concentration fluctuation, on MAO-A and MAO-B activities in rats. Young adult rats exposed chronically to the synthetic glucocorticoid dexamethasone at 0, 0.05, 0.5, and 2.0mg/kg/day (osmotic minipumps) for eight days showed significant dose-dependent increases in activities of MAO-A in PFC (+17%, p<0.001) and ACC (+9%, p<0.01) and MAO-B in PFC (+14%, p<0.001) and increased serotonin turnover in the PFC (+31%, p<0.01), not accounted for by dexamethasone-induced changes in serotonin levels, since neither serotonin depletion nor supplementation affected MAO-A activity. Sub-acute depletion of the major antioxidant glutathione by diethyl maleate (5mmol/kg, i.p.) for three days, which resulted in a 36% loss of glutathione in PFC (p=0.0005), modestly, but significantly, elevated activities of MAO-A in PFC and MAO-B in PFC, ACC and hippocampus (+6-9%, p<0.05). Changes in estrogen and progesterone representing pseudopregnancy were associated with significantly elevated MAO-A activity in the ACC day 4-7 postpartum (10-18%, p<0.05 to p<0.0001) but not the PFC or hippocampus. Hence, our study provides data in support of strategies targeting glucocorticoid and glutathione systems, as well as changes in female sex hormones for normalization of MAO-A activities and thus treatment of mood disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

Juvenile social experience and differential age-related changes in the dendritic morphologies of subareas of the prefrontal cortex in rats.

PubMed

Himmler, Brett T; Mychasiuk, Richelle; Nakahashi, Ayuno; Himmler, Stephanie M; Pellis, Sergio M; Kolb, Bryan

2018-04-01

Juvenile social interactions have been shown to influence the dendritic complexity of neurons in the prefrontal cortex (PFC). In particular, social play induces pruning of the cells in the medial prefrontal cortex (mPFC), whereas interacting with multiple partners, whether those interactions involve play or not, increases the complexity of cells in the orbital frontal cortex (OFC). Previous studies suggest that these changes differ in their stability during adulthood. In the present study, rats were reared in groups of either four (quads) or two (pairs) and the brains of the rats from each rearing condition were then harvested at 60 days (i.e., shortly after sexual maturity) and 100 days (i.e., fully adult). The rats housed with multiple partners had more complex neurons of the OFC at 60 days and this complexity declined to a comparable level to that of pair housed rats by 100 days. In contrast, the play-induced changes of the mPFC remained similar at both ages. These findings suggest that the changes in the PFC induced by different social experiences in the juvenile period differ in how long they are maintained in adulthood. Differences in the functions regulated by the OFC and the mPFC are considered with regard to these differences in the stability of juvenile-induced neural changes. © 2017 Wiley Periodicals, Inc.

In patients suffering from major depressive disorders, quantitative EEG showed favorable changes in left and right prefrontal cortex.

PubMed

Haghighi, Mohammad; Ludyga, Sebastian; Rahimi, Boshra; Jahangard, Leila; Ahmadpanah, Mohammad; Torabian, Saadat; Esnaashari, Farzaneh; Nazaribadie, Marzieh; Bajoghli, Hafez; Sadeghi Bahmani, Dena; Holsboer-Trachsler, Edith; Brand, Serge

2017-05-01

Patients suffering from major depressive disorders (MDD) report anhedonia, low concentration and lack of goal-oriented behavior. Data from imaging and quantitative EEG (QEEG) studies show an asymmetry in the prefrontal cortex (PFC), with lower left as compared to right PFC-activity, associated with specific depression-related behavior. Cordance is a QEEG measurement, which combines absolute and relative power of EEG-spectra with strong correlations with regional perfusion. The aim of the present study was to investigate to what extent a four weeks lasting treatment with a standard SSRI had an influence on neuronal activation and MDD-related symptoms. Twenty patients suffering from severe MDD were treated with citalopram (40mg) for four consecutive weeks. At baseline and at the end of the treatment, patients underwent QEEG. Experts rated the degree of depression with the Hamilton Depression Rating Scale (HDRS). Over time, theta cordance increased over right ventromedial and left dorsolateral PFC, whereas alpha cordance decreased over dorsolateral PFC. Improvement in MDD-related symptoms was higher in patients showing decreased EEG theta cordance over right dorsal PFC and increased EEG alpha cordance over left dorsolateral PFC. In patients suffering from MDD, treatment response was associated with favorable changes in neuronal activity. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Subtle Alterations in Brain Anatomy May Change an Individual’s Personality in Chronic Pain

PubMed Central

Gustin, Sylvia M.; McKay, Jamie G.; Petersen, Esben T.; Peck, Chris C.; Murray, Greg M.; Henderson, Luke A.

2014-01-01

It is well established that gross prefrontal cortex damage can affect an individual’s personality. It is also possible that subtle prefrontal cortex changes associated with conditions such as chronic pain, and not detectable until recent advances in human brain imaging, may also result in subtle changes in an individual’s personality. In an animal model of chronic neuropathic pain, subtle prefrontal cortex changes including altered basal dendritic length, resulted in altered decision making ability. Using multiple magnetic resonance imaging techniques, we found in humans, although gray matter volume and on-going activity were unaltered, chronic neuropathic pain was associated with reduced free and bound proton movement, indicators of subtle anatomical changes, in the medial prefrontal cortex, anterior cingulate cortex and mediodorsal thalamus. Furthermore, proton spectroscopy revealed an increase in neural integrity in the medial prefrontal cortex in neuropathic pain patients, the degree of which was significantly correlated to the personality temperament of novelty seeking. These data reveal that even subtle changes in prefrontal cortex anatomy may result in a significant change in an individual’s personality. PMID:25291361

Protective role of curcumin against sulfite-induced structural changes in rats' medial prefrontal cortex.

PubMed

Noorafshan, Ali; Asadi-Golshan, Reza; Abdollahifar, Mohammad-Amin; Karbalay-Doust, Saied

2015-08-01

Sodium metabisulfite as a food preservative can affect the central nervous system. Curcumin, the main ingredient of turmeric has neuroprotective activity. This study was designed to evaluate the effects of sulfite and curcumin on the medial prefrontal cortex (mPFC) using stereological methods. Thirty rats were randomly divided into five groups. The rats in groups I-V received distilled water, olive oil, curcumin (100 mg/kg/day), sodium metabisulfite (25 mg/kg/day), and sulfite + curcumin, respectively, for 8 weeks. The brains were subjected to the stereological methods. Cavalieri and optical disector techniques were used to estimate the total volume of mPFC and the number of neurons and glial cells. Intersections counting were applied on the thick vertical uniform random sections to estimate the dendrites length, and classify the spines. Non-parametric tests were used to analyze the data. The mean mPFC volume, neurons number, glia number, dendritic length, and total spines per neuron were 3.7 mm(3), 365,000, 180,000, 1820 µm, and 1700 in distilled water group, respectively. A reduction was observed in the volume of mPFC (∼8%), number of neurons (∼15%), and number of glia (∼14%) in mPFC of the sulfite group compared to the control groups (P < 0.005). Beside, dendritic length per neuron (∼10%) and the total spines per neuron (mainly mushroom spines) (∼25%) were reduced in the sulfite group (P < 0.005). The sulfite-induced structural changes in mPFC and curcumin had a protective role against the changes in the rats.

Mitigation of sociocommunicational deficits of autism through oxytocin-induced recovery of medial prefrontal activity: a randomized trial.

PubMed

Watanabe, Takamitsu; Abe, Osamu; Kuwabara, Hitoshi; Yahata, Noriaki; Takano, Yosuke; Iwashiro, Norichika; Natsubori, Tatsunobu; Aoki, Yuta; Takao, Hidemasa; Kawakubo, Yuki; Kamio, Yoko; Kato, Nobumasa; Miyashita, Yasushi; Kasai, Kiyoto; Yamasue, Hidenori

2014-02-01

Sociocommunicational deficits make it difficult for individuals with autism spectrum disorders (ASD) to understand communication content with conflicting verbal and nonverbal information. Despite growing prospects for oxytocin as a therapeutic agent for ASD, no direct neurobiological evidence exists for oxytocin's beneficial effects on this core symptom of ASD. This is slowing clinical application of the neuropeptide. To directly examine whether oxytocin has beneficial effects on the sociocommunicational deficits of ASD using both behavioral and neural measures. At the University of Tokyo Hospital, we conducted a randomized, double-blind, placebo-controlled, within-subject-crossover, single-site experimental trial in which intranasal oxytocin and placebo were administered. A total of 40 highly functioning men with ASD participated and were randomized in the trial. Single-dose intranasal administration of oxytocin (24 IU) and placebo. Using functional magnetic resonance imaging, we examined effects of oxytocin on behavioral neural responses of the participants to a social psychological task. In our previous case-control study using the same psychological task, when making decisions about social information with conflicting verbal and nonverbal contents, participants with ASD made judgments based on nonverbal contents less frequently with longer time and could not induce enough activation in the medial prefrontal cortex. Therefore, our main outcomes and measures were the frequency of the nonverbal information-based judgments (NVJs), the response time for NVJs, and brain activity of the medial prefrontal cortex during NVJs. Intranasal oxytocin enabled the participants to make NVJs more frequently (P = .03) with shorter response time (P = .02). During the mitigated behavior, oxytocin increased the originally diminished brain activity in the medial prefrontal cortex (P < .001). Moreover, oxytocin enhanced functional coordination in the area (P < .001), and the

Social defeat stress causes depression-like behavior with metabolite changes in the prefrontal cortex of rats.

PubMed

Liu, Yi-Yun; Zhou, Xin-Yu; Yang, Li-Ning; Wang, Hai-Yang; Zhang, Yu-Qing; Pu, Jun-Cai; Liu, Lan-Xiang; Gui, Si-Wen; Zeng, Li; Chen, Jian-Jun; Zhou, Chan-Juan; Xie, Peng

2017-01-01

Major depressive disorder is a serious mental disorder with high morbidity and mortality. The role of social stress in the development of depression remains unclear. Here, we used the social defeat stress paradigm to induce depression-like behavior in rats, then evaluated the behavior of the rats and measured metabolic changes in the prefrontal cortex using gas chromatography-mass spectrometry. Within the first week after the social defeat procedure, the sucrose preference test (SPT), open field test (OFT), elevated plus maze (EPM) and forced swim test (FST) were conducted to examine the depressive-like and anxiety-like behaviors. For our metabolite analysis, multivariate statistics were applied to observe the distribution of all samples and to differentiate the socially defeated group from the control group. Ingenuity pathway analysis was used to find the potential relationships among the differential metabolites. In the OFT and EPM, there were no significant differences between the two experimental groups. In the SPT and FST, socially defeated rats showed less sucrose intake and longer immobility time compared with control rats. Metabolic profiling identified 25 significant variables with good predictability. Ingenuity pathways analysis revealed that "Hereditary Disorder, Neurological Disease, Lipid Metabolism" was the most significantly altered network. Stress-induced alterations of low molecular weight metabolites were observed in the prefrontal cortex of rats. Particularly, lipid metabolism, amino acid metabolism, and energy metabolism were significantly perturbed. The results of this study suggest that repeated social defeat can lead to metabolic changes and depression-like behavior in rats.

Responses of prefrontal multisensory neurons to mismatching faces and vocalizations.

PubMed

Diehl, Maria M; Romanski, Lizabeth M

2014-08-20

Social communication relies on the integration of auditory and visual information, which are present in faces and vocalizations. Evidence suggests that the integration of information from multiple sources enhances perception compared with the processing of a unimodal stimulus. Our previous studies demonstrated that single neurons in the ventrolateral prefrontal cortex (VLPFC) of the rhesus monkey (Macaca mulatta) respond to and integrate conspecific vocalizations and their accompanying facial gestures. We were therefore interested in how VLPFC neurons respond differentially to matching (congruent) and mismatching (incongruent) faces and vocalizations. We recorded VLPFC neurons during the presentation of movies with congruent or incongruent species-specific facial gestures and vocalizations as well as their unimodal components. Recordings showed that while many VLPFC units are multisensory and respond to faces, vocalizations, or their combination, a subset of neurons showed a significant change in neuronal activity in response to incongruent versus congruent vocalization movies. Among these neurons, we typically observed incongruent suppression during the early stimulus period and incongruent enhancement during the late stimulus period. Incongruent-responsive VLPFC neurons were both bimodal and nonlinear multisensory, fostering their ability to respond to changes in either modality of a face-vocalization stimulus. These results demonstrate that ventral prefrontal neurons respond to changes in either modality of an audiovisual stimulus, which is important in identity processing and for the integration of multisensory communication information. Copyright © 2014 the authors 0270-6474/14/3411233-11$15.00/0.

Medial prefrontal cortex neuronal circuits in fear behavior.

PubMed

Courtin, J; Bienvenu, T C M; Einarsson, E Ö; Herry, C

2013-06-14

The medial prefrontal cortex (mPFC) has emerged as a key structure involved in the modulation of fear behavior over the past few decades. Anatomical, functional and electrophysiological studies have begun to shed light on the precise mechanisms by which different prefrontal regions regulate the expression and inhibition of fear behavior. These studies have established a canonical view of mPFC functions during fear behavior with dorsal regions selectively involved in the expression of fear behavior and ventral regions linked to the inhibition of fear behavior. Although numerous reports support this view, recent data have refined this model and suggested that dorsal prefrontal regions might also play an important role in the encoding of fear behavior itself. The recent development of sophisticated approaches such as large scale neuronal recordings, simultaneous multisite recordings of spiking activity and local field potentials (LFPs) along with optogenetic approaches will facilitate the testing of these new hypotheses in the near future. Here we provide an extensive review of the literature on the role of mPFC in fear behavior and propose further directions to dissect the contribution of specific prefrontal neuronal elements and circuits in the regulation of fear behavior. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Dopamine D2-receptor blockade enhances decoding of prefrontal signals in humans.

PubMed

Kahnt, Thorsten; Weber, Susanna C; Haker, Helene; Robbins, Trevor W; Tobler, Philippe N

2015-03-04

The prefrontal cortex houses representations critical for ongoing and future behavior expressed in the form of patterns of neural activity. Dopamine has long been suggested to play a key role in the integrity of such representations, with D2-receptor activation rendering them flexible but weak. However, it is currently unknown whether and how D2-receptor activation affects prefrontal representations in humans. In the current study, we use dopamine receptor-specific pharmacology and multivoxel pattern-based functional magnetic resonance imaging to test the hypothesis that blocking D2-receptor activation enhances prefrontal representations. Human subjects performed a simple reward prediction task after double-blind and placebo controlled administration of the D2-receptor antagonist amisulpride. Using a whole-brain searchlight decoding approach we show that D2-receptor blockade enhances decoding of reward signals in the medial orbitofrontal cortex. Examination of activity patterns suggests that amisulpride increases the separation of activity patterns related to reward versus no reward. Moreover, consistent with the cortical distribution of D2 receptors, post hoc analyses showed enhanced decoding of motor signals in motor cortex, but not of visual signals in visual cortex. These results suggest that D2-receptor blockade enhances content-specific representations in frontal cortex, presumably by a dopamine-mediated increase in pattern separation. These findings are in line with a dual-state model of prefrontal dopamine, and provide new insights into the potential mechanism of action of dopaminergic drugs. Copyright © 2015 the authors 0270-6474/15/354104-08$15.00/0.

MTHFR 677C --> T genotype disrupts prefrontal function in schizophrenia through an interaction with COMT 158Val --> Met.

PubMed

Roffman, Joshua L; Gollub, Randy L; Calhoun, Vince D; Wassink, Thomas H; Weiss, Anthony P; Ho, Beng C; White, Tonya; Clark, Vincent P; Fries, Jill; Andreasen, Nancy C; Goff, Donald C; Manoach, Dara S

2008-11-11

Understanding how risk genes cumulatively impair brain function in schizophrenia could provide critical insights into its pathophysiology. Working memory impairment in schizophrenia has been associated with abnormal dopamine signaling in the prefrontal cortex, which is likely under complex genetic control. The catechol-O-methyltransferase (COMT) 158Val --> Met polymorphism (rs4680), which affects the availability of prefrontal dopamine signaling, consistently stratifies prefrontal activation during working memory performance. However, the low-dopamine COMT 158Val allele does not confer increased risk for schizophrenia, and its effects on prefrontal function are not specific to the disorder. In the setting of other genetic variants influencing prefrontal dopamine signaling, COMT 158Val --> Met genotype may exert disease-specific effects. A second polymorphism, methylenetetrahydrofolate reductase (MTHFR) 677C --> T (rs1801133), has been associated with overall schizophrenia risk and executive function impairment in patients, and may influence dopamine signaling through mechanisms upstream of COMT effects. We found that the hypofunctional 677T variant was associated with decreased working memory load-dependent activation in the prefrontal and insular cortices in 79 schizophrenia patients, but not in 75 demographically matched healthy controls. Further, significant MTHFR x COMT genotype interactions were observed, which differed by diagnostic group: Reduced prefrontal activation was associated with the 677T and 158Val alleles in patients, but with 677C/C and 158Met/Met genotype in controls. These findings are consistent with epistatic effects of the COMT and MTHFR polymorphisms on prefrontal dopamine signaling, and suggest that in schizophrenia patients, the MTHFR 677T allele exacerbates prefrontal dopamine deficiency. The findings also suggest the importance of weighing COMT effects on prefrontal function within the context of MTHFR genotype.

Spatial Learning and Action Planning in a Prefrontal Cortical Network Model

PubMed Central

Martinet, Louis-Emmanuel; Sheynikhovich, Denis; Benchenane, Karim; Arleo, Angelo

2011-01-01

The interplay between hippocampus and prefrontal cortex (PFC) is fundamental to spatial cognition. Complementing hippocampal place coding, prefrontal representations provide more abstract and hierarchically organized memories suitable for decision making. We model a prefrontal network mediating distributed information processing for spatial learning and action planning. Specific connectivity and synaptic adaptation principles shape the recurrent dynamics of the network arranged in cortical minicolumns. We show how the PFC columnar organization is suitable for learning sparse topological-metrical representations from redundant hippocampal inputs. The recurrent nature of the network supports multilevel spatial processing, allowing structural features of the environment to be encoded. An activation diffusion mechanism spreads the neural activity through the column population leading to trajectory planning. The model provides a functional framework for interpreting the activity of PFC neurons recorded during navigation tasks. We illustrate the link from single unit activity to behavioral responses. The results suggest plausible neural mechanisms subserving the cognitive “insight” capability originally attributed to rodents by Tolman & Honzik. Our time course analysis of neural responses shows how the interaction between hippocampus and PFC can yield the encoding of manifold information pertinent to spatial planning, including prospective coding and distance-to-goal correlates. PMID:21625569

Heat exposure in female rats elicits abnormal fear expression and cellular changes in prefrontal cortex and hippocampus.

PubMed

Gruene, Tina M; Lipps, Jennifer; Rey, Colin D; Bouck, Anna; Shansky, Rebecca M

2014-11-01

Despite a twofold higher prevalence of fear-related disorders in women, the neurobiological factors that modulate and drive fear expression are rarely studied in female animals. Fear conditioning and extinction are useful tools for dissecting these mechanisms, and here we tested the effects of environmental manipulations - four days of exposure to 31°C temperatures in the animal housing facility - on fear learning and memory exclusively in female rats. We found that heat exposure disrupted freezing to tone during fear conditioning, and elicited enhanced freezing during extinction and extinction retrieval. We also performed immunohistochemistry for c-fos expression in the infralimbic (IL) and prelimbic (PL) regions of the prefrontal cortex during extinction retrieval, and found that heat exposure induced a switch from IL-dominated activity to PL-dominated activity. Finally, morphological analysis of spines in hippocampal CA3 neurons revealed an increase in spine head diameter in heat-exposed animals, which may partly underlie the persistent freezing observed in these animals. Together, our data show that heat exposure can induce changes at behavioral, physiological, and structural levels, and add to a woefully lacking body of literature on fear processes in female animals. Copyright © 2014 Elsevier Inc. All rights reserved.

Dynamic changes in prefrontal cortex gene expression following lysergic acid diethylamide administration.

PubMed

Nichols, Charles D; Garcia, Efrain E; Sanders-Bush, Elaine

2003-03-17

Lysergic acid diethylamide (LSD) is a psychoactive drug that transiently alters human perception, behavior, and mood at extremely low doses. Certain aspects of the behavior elicited by acute doses of LSD closely resemble symptoms of mental disorders such as schizophrenia. Characterizing gene expression profiles after LSD will be important for understanding how it alters behavior, and will lead to novel insights into disorders, such as schizophrenia, whose behavioral symptoms resemble the temporary effects of hallucinogenic drugs. We previously identified a small collection of genes within the rat prefrontal cortex that respond to LSD. Many of the products of these genes are involved in the process of synaptic plasticity. In the current report, we present a detailed analysis of the expression of these genes within the brain using RNase protection analysis. We find that the gene response to LSD is quite dynamic. The expression of some genes increases rapidly and decreases rapidly, while other genes change more gradually. Dose-response studies show two classes of expression; gene expression maximally stimulated at lower doses, versus gene expression that continues to rise at the higher doses. The role of the 5-HT(1A) and 5-HT(2A) receptor in mediating the increases in gene expression was examined in a series of experiments using receptor specific antagonists. Most expression increases were due to activation of the 5-HT(2A) receptor, however expression of two genes had neither a 5-HT(1A) nor a 5-HT(2A) receptor component.

Relationship between changes in rat behavior and integral biochemical indexes determined by laser correlation spectroscopy after photothrombosis of the prefrontal cortex.

PubMed

Romanova, G A; Shakova, F M; Kovaleva, O I; Pivovarov, V V; Khlebnikova, N N; Karganov, M Yu

2004-02-01

Experiments on rats showed that Noopept improved retention and retrieval of conditioned passive avoidance response after phototrombosis of the prefrontal cortex (a procedure impairing retention of memory traces). The impairment of mnesic functions was accompanied by changes in integral biochemical indexes of the plasma determined by laser correlation spectroscopy. Treatment of behavioral disorders with Noopepet normalized biochemical indexes.

Increased transient Na+ conductance and action potential output in layer 2/3 prefrontal cortex neurons of the fmr1-/y mouse.

PubMed

Routh, Brandy N; Rathour, Rahul K; Baumgardner, Michael E; Kalmbach, Brian E; Johnston, Daniel; Brager, Darrin H

2017-07-01

Layer 2/3 neurons of the prefrontal cortex display higher gain of somatic excitability, responding with a higher number of action potentials for a given stimulus, in fmr1 -/y mice. In fmr1 -/y L2/3 neurons, action potentials are taller, faster and narrower. Outside-out patch clamp recordings revealed that the maximum Na + conductance density is higher in fmr1 -/y L2/3 neurons. Measurements of three biophysically distinct K + currents revealed a depolarizing shift in the activation of a rapidly inactivating (A-type) K + conductance. Realistic neuronal simulations of the biophysical observations recapitulated the elevated action potential and repetitive firing phenotype. Fragile X syndrome is the most common form of inherited mental impairment and autism. The prefrontal cortex is responsible for higher order cognitive processing, and prefrontal dysfunction is believed to underlie many of the cognitive and behavioural phenotypes associated with fragile X syndrome. We recently demonstrated that somatic and dendritic excitability of layer (L) 5 pyramidal neurons in the prefrontal cortex of the fmr1 -/y mouse is significantly altered due to changes in several voltage-gated ion channels. In addition to L5 pyramidal neurons, L2/3 pyramidal neurons play an important role in prefrontal circuitry, integrating inputs from both lower brain regions and the contralateral cortex. Using whole-cell current clamp recording, we found that L2/3 pyramidal neurons in prefrontal cortex of fmr1 -/y mouse fired more action potentials for a given stimulus compared with wild-type neurons. In addition, action potentials in fmr1 -/y neurons were significantly larger, faster and narrower. Voltage clamp of outside-out patches from L2/3 neurons revealed that the transient Na + current was significantly larger in fmr1 -/y neurons. Furthermore, the activation curve of somatic A-type K + current was depolarized. Realistic conductance-based simulations revealed that these biophysical changes in Na

Cognitive regulation during decision making shifts behavioral control between ventromedial and dorsolateral prefrontal value systems.

PubMed

Hutcherson, Cendri A; Plassmann, Hilke; Gross, James J; Rangel, Antonio

2012-09-26

Cognitive regulation is often used to influence behavioral outcomes. However, the computational and neurobiological mechanisms by which it affects behavior remain unknown. We studied this issue using an fMRI task in which human participants used cognitive regulation to upregulate and downregulate their cravings for foods at the time of choice. We found that activity in both ventromedial prefrontal cortex (vmPFC) and dorsolateral prefrontal cortex (dlPFC) correlated with value. We also found evidence that two distinct regulatory mechanisms were at work: value modulation, which operates by changing the values assigned to foods in vmPFC and dlPFC at the time of choice, and behavioral control modulation, which operates by changing the relative influence of the vmPFC and dlPFC value signals on the action selection process used to make choices. In particular, during downregulation, activation decreased in the value-sensitive region of dlPFC (indicating value modulation) but not in vmPFC, and the relative contribution of the two value signals to behavior shifted toward the dlPFC (indicating behavioral control modulation). The opposite pattern was observed during upregulation: activation increased in vmPFC but not dlPFC, and the relative contribution to behavior shifted toward the vmPFC. Finally, ventrolateral PFC and posterior parietal cortex were more active during both upregulation and downregulation, and were functionally connected with vmPFC and dlPFC during cognitive regulation, which suggests that they help to implement the changes to the decision-making circuitry generated by cognitive regulation.

Cognitive Regulation during Decision Making Shifts Behavioral Control between Ventromedial and Dorsolateral Prefrontal Value Systems

PubMed Central

Plassmann, Hilke; Gross, James J.; Rangel, Antonio

2012-01-01

Cognitive regulation is often used to influence behavioral outcomes. However, the computational and neurobiological mechanisms by which it affects behavior remain unknown. We studied this issue using an fMRI task in which human participants used cognitive regulation to upregulate and downregulate their cravings for foods at the time of choice. We found that activity in both ventromedial prefrontal cortex (vmPFC) and dorsolateral prefrontal cortex (dlPFC) correlated with value. We also found evidence that two distinct regulatory mechanisms were at work: value modulation, which operates by changing the values assigned to foods in vmPFC and dlPFC at the time of choice, and behavioral control modulation, which operates by changing the relative influence of the vmPFC and dlPFC value signals on the action selection process used to make choices. In particular, during downregulation, activation decreased in the value-sensitive region of dlPFC (indicating value modulation) but not in vmPFC, and the relative contribution of the two value signals to behavior shifted toward the dlPFC (indicating behavioral control modulation). The opposite pattern was observed during upregulation: activation increased in vmPFC but not dlPFC, and the relative contribution to behavior shifted toward the vmPFC. Finally, ventrolateral PFC and posterior parietal cortex were more active during both upregulation and downregulation, and were functionally connected with vmPFC and dlPFC during cognitive regulation, which suggests that they help to implement the changes to the decision-making circuitry generated by cognitive regulation. PMID:23015444

Prefrontal brain asymmetry and pre-menstrual dysphoric disorder symptomatology.

PubMed

Accortt, Eynav E; Stewart, Jennifer L; Coan, James A; Manber, Rachel; Allen, John J B

2011-01-01

Pre-menstrual dysphoric disorder (PMDD), a dysphoric form of pre-menstrual syndrome, is included as a diagnosis for further study in the DSM-IV-TR (APA, 2000). The present study investigated whether a marker of risk for major depressive disorder (MDD), prefrontal brain asymmetry, also characterizes women with PMDD. In a sample of 25 college women with PMDD symptomatology and 25 matched controls, resting frontal electroencephalographic (EEG) activity was assessed on four occasions within a two-week span. Across several frontal sites women with PMDD had relatively less left than right prefrontal brain activity, consistent with a diathesis-stress model for menstrual-related dysphoria. The findings suggest an overlap in the risk profile for MDD and PMDD. Published by Elsevier B.V.

ADOLESCENT INTERMITTENT ETHANOL EXPOSURE ENHANCES ETHANOL ACTIVATION OF THE NUCLEUS ACCUMBENS WHILE BLUNTING THE PREFRONTAL CORTEX RESPONSES IN ADULT RAT

PubMed Central

LIU, W.; CREWS, F. T.

2016-01-01

The brain continues to develop through adolescence when excessive alcohol consumption is prevalent in humans. We hypothesized that binge drinking doses of ethanol during adolescence will cause changes in brain ethanol responses that persist into adulthood. To test this hypothesis Wistar rats were treated with an adolescent intermittent ethanol (AIE; 5 g/kg, i.g. 2 days on–2 days off; P25–P54) model of underage drinking followed by 25 days of abstinence during maturation to young adulthood (P80). Using markers of neuronal activation c-Fos, EGR1, and phophorylated extracellar signal regulated kinase (pERK1/2), adult responses to a moderate and binge drinking ethanol challenge, e.g., 2 or 4 g/kg, were determined. Adult rats showed dose dependent increases in neuronal activation markers in multiple brain regions during ethanol challenge. Brain regional responses correlated are consistent with anatomical connections. AIE led to marked decreases in adult ethanol PFC (prefrontal cortex) and blunted responses in the amygdala. Binge drinking doses led to the nucleus accumbens (NAc) activation that correlated with the ventral tegmental area (VTA) activation. In contrast to other brain regions, AIE enhanced the adult NAc response to binge drinking doses. These studies suggest that adolescent alcohol exposure causes long-lasting changes in brain responses to alcohol that persist into adulthood. PMID:25727639

The role of left prefrontal cortex in language and memory

PubMed Central

Gabrieli, John D. E.; Poldrack, Russell A.; Desmond, John E.

1998-01-01

This article reviews attempts to characterize the mental operations mediated by left inferior prefrontal cortex, especially the anterior and inferior portion of the gyrus, with the functional neuroimaging techniques of positron emission tomography and functional magnetic resonance imaging. Activations in this region occur during semantic, relative to nonsemantic, tasks for the generation of words to semantic cues or the classification of words or pictures into semantic categories. This activation appears in the right prefrontal cortex of people known to be atypically right-hemisphere dominant for language. In this region, activations are associated with meaningful encoding that leads to superior explicit memory for stimuli and deactivations with implicit semantic memory (repetition priming) for words and pictures. New findings are reported showing that patients with global amnesia show deactivations in the same region associated with repetition priming, that activation in this region reflects selection of a response from among numerous relative to few alternatives, and that activations in a portion of this region are associated specifically with semantic relative to phonological processing. It is hypothesized that activations in left inferior prefrontal cortex reflect a domain-specific semantic working memory capacity that is invoked more for semantic than nonsemantic analyses regardless of stimulus modality, more for initial than for repeated semantic analysis of a word or picture, more when a response must be selected from among many than few legitimate alternatives, and that yields superior later explicit memory for experiences. PMID:9448258

Activation of dorsolateral prefrontal cortex in a dual neuropsychological screening test: an fMRI approach.

PubMed

Tachibana, Atsumichi; Noah, J Adam; Bronner, Shaw; Ono, Yumie; Hirano, Yoshiyuki; Niwa, Masami; Watanabe, Kazuko; Onozuka, Minoru

2012-05-28

The Kana Pick-out Test (KPT), which uses Kana or Japanese symbols that represent syllables, requires parallel processing of discrete (pick-out) and continuous (reading) dual tasks. As a dual task, the KPT is thought to test working memory and executive function, particularly in the prefrontal cortex (PFC), and is widely used in Japan as a clinical screen for dementia. Nevertheless, there has been little neurological investigation into PFC activity during this test. We used functional magnetic resonance imaging (fMRI) to evaluate changes in the blood oxygenation level-dependent (BOLD) signal in young healthy adults during performance of a computerized KPT dual task (comprised of reading comprehension and picking out vowels) and compared it to its single task components (reading or vowel pick-out alone). Behavioral performance of the KPT degraded compared to its single task components. Performance of the KPT markedly increased BOLD signal intensity in the PFC, and also activated sensorimotor, parietal association, and visual cortex areas. In conjunction analyses, bilateral BOLD signal in the dorsolateral PFC (Brodmann's areas 45, 46) was present only in the KPT. Our results support the central bottleneck theory and suggest that the dorsolateral PFC is an important mediator of neural activity for both short-term storage and executive processes. Quantitative evaluation of the KPT with fMRI in healthy adults is the first step towards understanding the effects of aging or cognitive impairment on KPT performance.

Optical mapping of prefrontal brain connectivity and activation during emotion anticipation.

PubMed

Wang, Meng-Yun; Lu, Feng-Mei; Hu, Zhishan; Zhang, Juan; Yuan, Zhen

2018-09-17

Accumulated neuroimaging evidence shows that the dorsal lateral prefrontal cortex (dlPFC) is activated during emotion anticipation. The aim of this work is to examine the brain connectivity and activation differences in dlPFC between the positive, neutral and negative emotion anticipation by using functional near-infrared spectroscopy (fNIRS). The hemodynamic responses were first assessed for all subjects during the performance of various emotion anticipation tasks. And then small-world analysis was performed, in which the small-world network indicators including the clustering coefficient, average path length, average node degree, and measure of small-world index were calculated for the functional brain networks associated with the positive, neutral and negative emotion anticipation, respectively. We discovered that compared to negative and neutral emotion anticipation, the positive one exhibited enhanced brain activation in the left dlPFC. Although the functional brain networks for the three emotion anticipation cases manifested the small-world properties regarding the clustering coefficient, average path length, average node degree, and measure of small-world index, the positive one showed significantly higher clustering coefficient and shorter average path length than those from the neutral and negative cases. Consequently, the small-world network indicators and brain activation in dlPPC were able to distinguish well between the positive, neutral and negative emotion anticipation. Copyright © 2018 Elsevier B.V. All rights reserved.

Near-infrared imaging of the effects of glucose ingestion and regulation on prefrontal activation during dual-task execution in healthy fasting older adults.

PubMed

Gagnon, Christine; Desjardins-Crépeau, Laurence; Tournier, Isabelle; Desjardins, Michèle; Lesage, Frédéric; Greenwood, Carol E; Bherer, Louis

2012-06-15

Glucose enhancing effects in older adults have mostly been observed for episodic memory, but have recently been found for attentional control performance. Yet, brain activation patterns underlying these effects are still unknown. The present study examined the acute effects of glucose ingestion on prefrontal brain activation during the execution of a divided attention task in fasting non-diabetic older adults. Twenty older adults (60 years and older) took part in the study that included two experimental sessions. After an overnight fast, participants received either a glucose drink (50 g) or a placebo (saccharin) drink, following which they completed a dual-task. During task execution, prefrontal activation was recorded with functional near-infrared spectroscopy (fNIRS). A repeated-measures design was used such that each participant served as his or her own control. The two experimental sessions were counterbalanced among participants and were performed two weeks apart. When participants were in the glucose condition, they showed similar dual-task costs for both tasks, whereas in the placebo condition they prioritized one task over the other, with a significantly larger dual-task cost for the non-prioritized task (p<0.01). Differential brain activation was also observed in right ventral-lateral prefrontal regions for oxygenated hemoglobin and deoxygenated hemoglobin, with more activation apparent in the glucose condition (p<0.05). Furthermore, behavioral and activation data were influenced by individual differences in glucose regulation. Glucose ingestion appears to momentarily enhance fasting seniors' capacity to coordinate more equally two concurrent tasks and this is reflected in brain activation patterns. Copyright © 2012 Elsevier B.V. All rights reserved.

A key role of the prefrontal cortex in the maintenance of chronic tinnitus: An fMRI study using a Stroop task.

PubMed

Araneda, Rodrigo; Renier, Laurent; Dricot, Laurence; Decat, Monique; Ebner-Karestinos, Daniela; Deggouj, Naïma; De Volder, Anne G

2018-01-01

Since we recently showed in behavioural tasks that the top-down cognitive control was specifically altered in tinnitus sufferers, here we wanted to establish the link between this impaired executive function and brain alterations in the frontal cortex in tinnitus patients. Using functional magnetic resonance imaging (fMRI), we monitored the brain activity changes in sixteen tinnitus patients (TP) and their control subjects (CS) while they were performing a spatial Stroop task, both in audition and vision. We observed that TP differed from CS in their functional recruitment of the dorsolateral prefrontal cortex (dlPFC, BA46), the cingulate gyrus and the ventromedial prefrontal cortex (vmPFC, BA10). This recruitment was higher during interference conditions in tinnitus participants than in controls, whatever the sensory modality. Furthermore, the brain activity level in the right dlPFC and vmPFC correlated with the performance in the Stroop task in TP. Due to the direct link between poor executive functions and prefrontal cortex alterations in TP, we postulate that a lack of inhibitory modulation following an impaired top-down cognitive control may maintain tinnitus by hampering habituation mechanisms. This deficit in executive functions caused by prefrontal cortex alterations would be a key-factor in the generation and persistence of tinnitus.

Dynamic Changes in Amygdala Activation and Functional Connectivity in Children and Adolescents with Anxiety Disorders

PubMed Central

Swartz, Johnna R.; Phan, K. Luan; Angstadt, Mike; Fitzgerald, Kate D.; Monk, Christopher S.

2015-01-01

Anxiety disorders are associated with abnormalities in amygdala function and prefrontal cortex-amygdala connectivity. The majority of fMRI studies have examined mean group differences in amygdala activation or connectivity in children and adolescents with anxiety disorders relative to controls, but emerging evidence suggests that abnormalities in amygdala function are dependent on the timing of the task and may vary across the course of a scanning session. The goal of the present study was to extend our knowledge of the dynamics of amygdala dysfunction by examining whether changes in amygdala activation and connectivity over scanning differ in pediatric anxiety disorder patients relative to typically developing controls during an emotion processing task. Examining changes in activation over time allows for a comparison of how brain function differs during initial exposure to novel stimuli versus more prolonged exposure. Participants included 34 anxiety disorder patients and 19 controls 7 to 19 years old. Participants performed an emotional face matching task during fMRI scanning and the task was divided into thirds in order to examine change in activation over time. Results demonstrated that patients exhibited an abnormal pattern of amygdala activation characterized by an initially heightened amygdala response relative to controls at the beginning of scanning, followed by significant decreases in activation over time. In addition, controls evidenced greater prefrontal cortex-amygdala connectivity during the beginning of scanning relative to patients. These results indicate that differences in emotion processing between the groups vary from initial exposure to novel stimuli relative to more prolonged exposure. Implications are discussed regarding how this pattern of neural activation may relate to altered early-occurring or anticipatory emotion-regulation strategies and maladaptive later-occurring strategies in children and adolescents with anxiety disorders. PMID

Nonlinear responses within the medial prefrontal cortex reveal when specific implicit information influences economic decision making.

PubMed

Deppe, Michael; Schwindt, Wolfram; Kugel, Harald; Plassmann, Hilke; Kenning, Peter

2005-04-01

The authors used functional magnetic resonance imaging (fMRI) to investigate how individual economic decisions are influenced by implicit memory contributions. Twenty-two participants were asked to make binary decisions between different brands of sensorily nearly undistinguishable consumer goods. Changes of brain activity comparing decisions in the presence or absence of a specific target brand were detected by fMRI. Only when the tar get brand was the participant's favorite one did the authors find reduced activation in the dorsolateral prefrontal, posterior parietal, and occipital cortices and the left premotor area (Brodmann areas [BA] 9, 46, 7/19, and 6). Simultaneously, activity was increased in the inferior precuneus and posterior cingulate (BA 7), right superior frontal gyrus (BA 10), right supramarginal gyrus (BA 40), and, most pronounced, in the ventromedial prefrontal cortex (BA 10). For products mainly distinguishable by brand information, the authors revealed a nonlinear winner-take-all effect for a participant's favorite brand characterized, on one hand, by reduced activation in brain areas associated with working memory and reasoning and, on the other hand, increased activation in areas involved in processing of emotions and self-reflections during decision making.

Metabotropic glutamate receptor 3 activation is required for long-term depression in medial prefrontal cortex and fear extinction

PubMed Central

Walker, Adam G.; Wenthur, Cody J.; Xiang, Zixiu; Rook, Jerri M.; Emmitte, Kyle A.; Niswender, Colleen M.; Lindsley, Craig W.; Conn, P. Jeffrey

2015-01-01

Clinical studies have revealed that genetic variations in metabotropic glutamate receptor 3 (mGlu3) affect performance on cognitive tasks dependent upon the prefrontal cortex (PFC) and may be linked to psychiatric conditions such as schizophrenia, bipolar disorder, and addiction. We have performed a series of studies aimed at understanding how mGlu3 influences PFC function and cognitive behaviors. In the present study, we found that activation of mGlu3 can induce long-term depression in the mouse medial PFC (mPFC) in vitro. Furthermore, in vivo administration of a selective mGlu3 negative allosteric modulator impaired learning in the mPFC-dependent fear extinction task. The results of these studies implicate mGlu3 as a major regulator of PFC function and cognition. Additionally, potentiators of mGlu3 may be useful in alleviating prefrontal impairments associated with several CNS disorders. PMID:25583490

Dorsomedial prefrontal cortex mediates rapid evaluations predicting the outcome of romantic interactions

PubMed Central

Cooper, Jeffrey C.; Dunne, Simon; Furey, Teresa; O’Doherty, John P.

2012-01-01

Humans frequently make real-world decisions based on rapid evaluations of minimal information – for example, should we talk to an attractive stranger at a party? Little is known, however, about how the brain makes rapid evaluations with real and immediate social consequences. To address this question, we scanned participants with FMRI while they viewed photos of individuals that they subsequently met at real-life “speed-dating” events. Neural activity in two areas of dorsomedial prefrontal cortex, paracingulate cortex and rostromedial prefrontal cortex (RMPFC), was predictive of whether each individual would be ultimately pursued for a romantic relationship or rejected. Activity in these areas was attributable to two distinct components of romantic evaluation: either consensus judgments about physical beauty (paracingulate cortex) or individualized preferences based on a partner’s perceived personality (RMPFC). These data identify novel computational roles for these regions of the dorsomedial prefrontal cortex in even very rapid social evaluations. Even a first glance, then, can accurately predict romantic desire, but that glance involves a mix of physical and psychological judgments that depend on specific regions of dorsomedial prefrontal cortex. PMID:23136406

Cholinergic Overstimulation Attenuates Rule Selectivity in Macaque Prefrontal Cortex.

PubMed

Major, Alex J; Vijayraghavan, Susheel; Everling, Stefan

2018-01-31

Acetylcholine is released in the prefrontal cortex (PFC) and is a key modulator of cognitive performance in primates. Cholinergic stimulation has been shown to have beneficial effects on performance of cognitive tasks, and cholinergic receptors are being actively explored as promising targets for ameliorating cognitive deficits in Alzheimer's disease. We hypothesized that cholinergic stimulation of PFC during performance of a cognitive task would augment neuronal activity and neuronal coding of task attributes. We iontophoretically applied the general cholinergic receptor agonist carbachol onto neurons in dorsolateral PFC (DLPFC) of male rhesus macaques performing rule-guided prosaccades and antisaccades, a well established oculomotor task for testing cognitive control. Carbachol application had heterogeneous effects on neuronal excitability, with both excitation and suppression observed in significant proportions. Contrary to our prediction, neurons with rule-selective activity exhibited a reduction in selectivity during carbachol application. Cholinergic stimulation disrupted rule selectivity regardless of whether it had suppressive or excitatory effects on these neurons. In addition, cholinergic stimulation excited putative pyramidal neurons, whereas the activity of putative interneurons remained unchanged. Moreover, cholinergic stimulation attenuated saccade direction selectivity in putative pyramidal neurons due to nonspecific increases in activity. Our results suggest excessive cholinergic stimulation has detrimental effects on DLPFC representations of task attributes. These findings delineate the complexity and heterogeneity of neuromodulation of cerebral cortex by cholinergic stimulation, an area of active exploration with respect to the development of cognitive enhancers. SIGNIFICANCE STATEMENT The neurotransmitter acetylcholine is known to be important for cognitive processes in the prefrontal cortex. Removal of acetylcholine from prefrontal cortex can

Genetic predictor of working memory and prefrontal function in women with HIV.

PubMed

Sundermann, Erin E; Bishop, Jeffrey R; Rubin, Leah H; Little, Deborah M; Meyer, Vanessa J; Martin, Eileen; Weber, Kathleen; Cohen, Mardge; Maki, Pauline M

2015-02-01

The Val158Met (rs4680) single-nucleotide polymorphism (SNP) of the catechol-O-methyltransferase gene (COMT) influences executive function and prefrontal function through its effect on dopamine (DA) metabolism. Both HIV and the Val allele of the Val158Met SNP are associated with compromised executive function and inefficient prefrontal function. The present study used behavioral and neuroimaging techniques to determine independent and interactive associations between HIV serostatus and COMT genotype on working memory and prefrontal function in women. For the behavioral study, 54 HIV-infected and 33 HIV-uninfected women completed the 0-, 1-, and 2-back conditions of the verbal N-back, a working memory test. For the imaging study, 36 women (23 HIV-infected, 13 HIV-uninfected) underwent functional magnetic resonance imaging (fMRI) assessments while completing the N-back task. HIV-infected women demonstrated significantly worse N-back performance compared with HIV-uninfected women (p < 0.05). A significant serostatus by genotype interaction (p < 0.01) revealed that, among Val/Val, but not Met allele carriers, HIV-infected women performed significantly worse than HIV-uninfected controls across N-back conditions (p < 0.01). Analogous to behavioral findings, a serostatus by genotype interaction revealed that HIV-infected Val/Val carriers showed significantly greater prefrontal activation compared with HIV-uninfected Val/Val carriers (p < 0.01). Conversely, HIV-uninfected Met allele carriers demonstrated significantly greater prefrontal activation compared with HIV-infected Met allele carriers. Findings suggest that the combination of HIV infection and the Val/Val COMT genotype leads to working memory deficits and altered prefrontal function in HIV-infected individuals.

Active avoidance requires inhibitory signaling in the rodent prelimbic prefrontal cortex

PubMed Central

Bravo-Rivera, Christian; Rodriguez-Romaguera, Jose; Pagan-Rivera, Pablo A; Burgos-Robles, Anthony; Roman-Ortiz, Ciorana; Quirk, Gregory J

2018-01-01

Much is known about the neural circuits of conditioned fear and its relevance to understanding anxiety disorders, but less is known about other anxiety-related behaviors such as active avoidance. Using a tone-signaled, platform-mediated avoidance task, we observed that pharmacological inactivation of the prelimbic prefrontal cortex (PL) delayed avoidance. Surprisingly, optogenetic silencing of PL glutamatergic neurons did not delay avoidance. Consistent with this, inhibitory but not excitatory responses of rostral PL neurons were associated with avoidance training. To test the importance of these inhibitory responses, we optogenetically stimulated PL neurons to counteract the tone-elicited reduction in firing rate. Photoactivation of rostral (but not caudal) PL neurons at 4 Hz impaired avoidance. These findings suggest that inhibitory responses of rostral PL neurons signal the avoidability of a potential threat and underscore the importance of designing behavioral optogenetic studies based on neuronal firing responses. PMID:29851381

Repetitive transcranial magnetic stimulation over the right dorsolateral prefrontal cortex affects strategic decision-making.

PubMed

van 't Wout, Mascha; Kahn, René S; Sanfey, Alan G; Aleman, André

2005-11-07

Although decision-making is typically seen as a rational process, emotions play a role in tasks that include unfairness. Recently, activation in the right dorsolateral prefrontal cortex during offers experienced as unfair in the Ultimatum Game was suggested to subserve goal maintenance in this task. This is restricted to correlational evidence, however, and it remains unclear whether the dorsolateral prefrontal cortex is crucial for strategic decision-making. The present study used repetitive transcranial magnetic stimulation in order to investigate the causal role of the dorsolateral prefrontal cortex in strategic decision-making in the Ultimatum Game. The results showed that repetitive transcranial magnetic stimulation over the right dorsolateral prefrontal cortex resulted in an altered decision-making strategy compared with sham stimulation. We conclude that the dorsolateral prefrontal cortex is causally implicated in strategic decision-making in healthy human study participants.

Brain Activity in Self- and Value-Related Regions in Response to Online Antismoking Messages Predicts Behavior Change

PubMed Central

Cooper, Nicole; Tompson, Steve; O’Donnell, Matthew Brook; Falk, Emily B.

2017-01-01

In this study, we combined approaches from media psychology and neuroscience to ask whether brain activity in response to online antismoking messages can predict smoking behavior change. In particular, we examined activity in subregions of the medial prefrontal cortex linked to self- and value-related processing, to test whether these neurocognitive processes play a role in message-consistent behavior change. We observed significant relationships between activity in both brain regions of interest and behavior change (such that higher activity predicted a larger reduction in smoking). Furthermore, activity in these brain regions predicted variance independent of traditional, theory-driven self-report metrics such as intention, self-efficacy, and risk perceptions. We propose that valuation is an additional cognitive process that should be investigated further as we search for a mechanistic explanation of the relationship between brain activity and media effects relevant to health behavior change. PMID:29057013

Effect of stimulation by foliage plant display images on prefrontal cortex activity: a comparison with stimulation using actual foliage plants.

PubMed

Igarashi, Miho; Song, Chorong; Ikei, Harumi; Miyazaki, Yoshifumi

2015-01-01

Natural scenes like forests and flowers evoke neurophysiological responses that can suppress anxiety and relieve stress. We examined whether images of natural objects can elicit neural responses similar to those evoked by real objects by comparing the activation of the prefrontal cortex during presentation of real foliage plants with a projected image of the same foliage plants. Oxy-hemoglobin concentrations in the prefrontal cortex were measured using time-resolved near-infrared spectroscopy while the subjects viewed the real plants or a projected image of the same plants. Compared with a projected image of foliage plants, viewing the actual foliage plants significantly increased oxy-hemoglobin concentrations in the prefrontal cortex. However, using the modified semantic differential method, subjective emotional response ratings ("comfortable vs. uncomfortable" and "relaxed vs. awakening") were similar for both stimuli. The frontal cortex responded differently to presentation of actual plants compared with images of these plants even when the subjective emotional response was similar. These results may help explain the physical and mental health benefits of urban, domestic, and workplace foliage. © 2014 The Authors. Journal of Neuroimaging published by the American Society of Neuroimaging.

The medial prefrontal and orbitofrontal cortices differentially regulate dopamine system function.

PubMed

Lodge, Daniel J

2011-05-01

The prefrontal cortex (PFC) is essential for top-down control over higher-order executive function. In this study we demonstrate that the medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC) differentially regulate VTA dopamine neuron activity, and furthermore, the pattern of activity in the PFC drastically alters the dopamine neuron response. Thus, although single-pulse activation of the mPFC either excites or inhibits equivalent numbers of dopamine neurons, activation of the OFC induces a primarily inhibitory response. Moreover, activation of the PFC with a pattern that mimics spontaneous burst firing of pyramidal neurons produces a strikingly different response. Specifically, burst-like activation of the mPFC induces a massive increase in dopamine neuron firing, whereas a similar pattern of OFC activation largely inhibits dopamine activity. Taken together, these data demonstrate that the mPFC and OFC differentially regulate dopamine neuron activity, and that the pattern of cortical activation is critical for determining dopamine system output.

Selective memory retrieval of auditory what and auditory where involves the ventrolateral prefrontal cortex.

PubMed

Kostopoulos, Penelope; Petrides, Michael

2016-02-16

There is evidence from the visual, verbal, and tactile memory domains that the midventrolateral prefrontal cortex plays a critical role in the top-down modulation of activity within posterior cortical areas for the selective retrieval of specific aspects of a memorized experience, a functional process often referred to as active controlled retrieval. In the present functional neuroimaging study, we explore the neural bases of active retrieval for auditory nonverbal information, about which almost nothing is known. Human participants were scanned with functional magnetic resonance imaging (fMRI) in a task in which they were presented with short melodies from different locations in a simulated virtual acoustic environment within the scanner and were then instructed to retrieve selectively either the particular melody presented or its location. There were significant activity increases specifically within the midventrolateral prefrontal region during the selective retrieval of nonverbal auditory information. During the selective retrieval of information from auditory memory, the right midventrolateral prefrontal region increased its interaction with the auditory temporal region and the inferior parietal lobule in the right hemisphere. These findings provide evidence that the midventrolateral prefrontal cortical region interacts with specific posterior cortical areas in the human cerebral cortex for the selective retrieval of object and location features of an auditory memory experience.

Lateral Orbitofrontal Cortical Modulation on the Medial Prefrontal Cortex-Amygdala Pathway: Differential Regulation of Intra-Amygdala GABAA and GABAB Receptors.

PubMed

Chang, Chun-Hui

2017-07-01

The basolateral complex of the amygdala receives inputs from neocortical areas, including the medial prefrontal cortex and lateral orbitofrontal cortex. Earlier studies have shown that lateral orbitofrontal cortex activation exerts an inhibitory gating on medial prefrontal cortex-amygdala information flow. Here we examined the individual role of GABAA and GABAB receptors in this process. In vivo extracellular single-unit recordings were done in anesthetized rats. We searched amygdala neurons that fire in response to medial prefrontal cortex activation, tested lateral orbitofrontal cortex gating at different delays (lateral orbitofrontal cortex-medial prefrontal cortex delays: 25, 50, 100, 250, 500, and 1000 milliseconds), and examined differential contribution of GABAA and GABAB receptors with iontophoresis. Relative to baseline, lateral orbitofrontal cortex stimulation exerted an inhibitory modulatory gating on the medial prefrontal cortex-amygdala pathway and was effective up to a long delay of 500 ms (long-delay latencies at 100, 250, and 500 milliseconds). Moreover, blockade of intra-amygdala GABAA receptors with bicuculline abolished the lateral orbitofrontal cortex inhibitory gating at both short- (25 milliseconds) and long-delay (100 milliseconds) intervals, while blockade of GABAB receptors with saclofen reversed the inhibitory gating at long delay (100 milliseconds) only. Among the majority of the neurons examined (8 of 9), inactivation of either GABAA or GABAB receptors during baseline did not change evoked probability per se, suggesting that local feed-forward inhibitory mechanism is pathway specific. Our results suggest that the effect of lateral orbitofrontal cortex inhibitory modulatory gating was effective up to 500 milliseconds and that intra-amygdala GABAA and GABAB receptors differentially modulate the short- and long-delay lateral orbitofrontal cortex inhibitory gating on the medial prefrontal cortex-amygdala pathway. © The Author 2017

Emotion regulation in spider phobia: role of the medial prefrontal cortex

PubMed Central

Schäfer, Axel; Walter, Bertram; Stark, Rudolf; Vaitl, Dieter; Schienle, Anne

2009-01-01

Phobic responses are strong emotional reactions towards phobic objects, which can be described as a deficit in the automatic regulation of emotions. Difficulties in the voluntary cognitive control of these emotions suggest a further phobia-specific deficit in effortful emotion regulation mechanisms. The actual study is based on this emotion regulation conceptualization of specific phobias. The aim is to investigate the neural correlates of these two emotion regulation deficits in spider phobics. Sixteen spider phobic females participated in a functional magnetic resonance imaging (fMRI) study in which they were asked to voluntarily up- and down-regulate their emotions elicited by spider and generally aversive pictures with a reappraisal strategy. In line with the hypothesis concerning an automatic emotion regulation deficit, increased activity in the insula and reduced activity in the ventromedial prefrontal cortex was observed. Furthermore, phobia-specific effortful regulation within phobics was associated with altered activity in medial prefrontal cortex areas. Altogether, these results suggest that spider phobic subjects are indeed characterized by a deficit in the automatic as well as the effortful regulation of emotions elicited by phobic compared with aversive stimuli. These two forms of phobic emotion regulation deficits are associated with altered activity in different medial prefrontal cortex subregions. PMID:19398537

Effect of trait anxiety on prefrontal control mechanisms during emotional conflict.

PubMed

Comte, Magali; Cancel, Aïda; Coull, Jennifer T; Schön, Daniele; Reynaud, Emmanuelle; Boukezzi, Sarah; Rousseau, Pierre-François; Robert, Gabriel; Khalfa, Stéphanie; Guedj, Eric; Blin, Olivier; Weinberger, Daniel R; Fakra, Eric

2015-06-01

Converging evidence points to a link between anxiety proneness and altered emotional functioning, including threat-related biases in selective attention and higher susceptibility to emotionally ambiguous stimuli. However, during these complex emotional situations, it remains unclear how trait anxiety affects the engagement of the prefrontal emotional control system and particularly the anterior cingulate cortex (ACC), a core region at the intersection of the limbic and prefrontal systems. Using an emotional conflict task and functional magnetic resonance imaging (fMRI), we investigated in healthy subjects the relations between trait anxiety and both regional activity and functional connectivity (psychophysiological interaction) of the ACC. Higher levels of anxiety were associated with stronger task-related activation in ACC but with reduced functional connectivity between ACC and lateral prefrontal cortex (LPFC). These results support the hypothesis that when one is faced with emotionally incompatible information, anxiety leads to inefficient high-order control, characterized by insufficient ACC-LPFC functional coupling and increases, possibly compensatory, in activation of ACC. Our findings provide a deeper understanding of the pathophysiology of the neural circuitry underlying anxiety and may offer potential treatment markers for anxiety disorders. © 2015 Wiley Periodicals, Inc.

Prefrontal activity and diagnostic monitoring of memory retrieval: FMRI of the criterial recollection task.

PubMed

Gallo, David A; Kensinger, Elizabeth A; Schacter, Daniel L

2006-01-01

According to the distinctiveness heuristic, subjects rely more on detailed recollections (and less on familiarity) when memory is tested for pictures relative to words, leading to reduced false recognition. If so, then neural regions that have been implicated in effortful postretrieval monitoring (e.g., dorsolateral prefrontal cortex) might be recruited less heavily when trying to remember pictures. We tested this prediction with the criterial recollection task. Subjects studied black words, paired with either the same word in red font or a corresponding colored picture. Red words were repeated at study to equate recognition hits for red words and pictures. During fMRI scanning, alternating red word memory tests and picture memory tests were given, using only white words as test stimuli (say "yes" only if you recollect a corresponding red word or picture, respectively). These tests were designed so that subjects had to rely on memory for the criterial information. Replicating prior behavioral work, we found enhanced rejection of lures on the picture test compared to the red word test, indicating that subjects had used a distinctiveness heuristic. Critically, dorsolateral prefrontal activity was reduced when rejecting familiar lures on the picture test, relative to the red word test. These findings indicate that reducing false recognition via the distinctiveness heuristic is not heavily dependent on frontally mediated postretrieval monitoring processes.

Increasing contextual demand modulates anterior and lateral prefrontal brain regions associated with proactive interference.

PubMed

Wolf, Robert Christian; Walter, Henrik; Vasic, Nenad

2010-01-01

Using a parametric version of a modified item-recognition paradigm with three different load levels and by means of event-related functional magnetic resonance imaging, this study tested the hypothesis that cerebral activation associated with intratrial proactive interference (PI) during working memory retrieval is influenced by increased context processing. We found activation of left BA 45 during interference trials across all levels of cognitive processing, and left lateralized activation of the dorsolateral prefrontal cortex (DLPFC, BA 9/46) and the frontopolar cortex (FPC, BA 10) with increasing contextual load. Compared with high susceptibility to PI, low susceptibility was associated with activation of the left DLPFC. These results suggest that an intratrial PI effect can be modulated by increasing context processing of a transiently relevant stimulus set. Moreover, PI resolution associated with increasing context load involves multiple prefrontal regions including the ventro- and dorsolateral prefrontal cortex as well as frontopolar brain areas. Furthermore, low susceptibility to PI might be influenced by increased executive control exerted by the DLPFC.

Noradrenaline and acetylcholine responsiveness of glucose-monitoring and glucose-insensitive neurons in the mediodorsal prefrontal cortex.

PubMed

Nagy, Bernadett; Szabó, István; Csetényi, Bettina; Hormay, Edina; Papp, Szilárd; Keresztes, Dóra; Karádi, Zoltán

2014-01-16

The mediodorsal prefrontal cortex (mdPFC), as part of the forebrain glucose-monitoring (GM) system, plays important role in several regulatory processes to control the internal state of the organism and to initiate behavioral outputs accordingly. Little is known, however, about the neurochemical sensitivity of neurons located in this area. Substantial evidence indicates that the locus ceruleus - noradrenaline (NA) projection system and the nucleus basalis magnocellularis - cholinergic projection system regulate behavioral state and state dependent processing of sensory information, various cognitive functions already associated with the mdPFC. The main goal of the present study was to examine noradrenergic and cholinergic responsiveness of glucose-monitoring and glucose-insensitive (GIS) neurons in the mediodorsal prefrontal cortex. One fifth of the neurons tested changed in firing rate to microelectrophoretically applied NA. Responsiveness of the GM cells to this catecholamine proved to be significantly higher than that of the GIS units. Microiontophoretic application of acetylcholine (Ach) resulted in activity changes (predominantly facilitation) of more than 40% of the mdPFC neurons. Proportion of Ach sensitive units among the GM and the GIS neurons was found to be similar. The glucose-monitoring neurons of the mdPFC and their distinct NA and remarkable Ach sensitivity are suggested to be of particular significance in prefrontal control of adaptive behaviors. © 2013 Published by Elsevier B.V.

Ventral Midline Thalamus Is Critical for Hippocampal–Prefrontal Synchrony and Spatial Working Memory

PubMed Central

Hallock, Henry L.; Wang, Arick

2016-01-01

Maintaining behaviorally relevant information in spatial working memory (SWM) requires functional synchrony between the dorsal hippocampus and medial prefrontal cortex (mPFC). However, the mechanism that regulates synchrony between these structures remains unknown. Here, we used a unique dual-task approach to compare hippocampal–prefrontal synchrony while rats switched between an SWM-dependent task and an SWM-independent task within a single behavioral session. We show that task-specific representations in mPFC neuronal populations are accompanied by SWM-specific oscillatory synchrony and directionality between the dorsal hippocampus and mPFC. We then demonstrate that transient inactivation of the reuniens and rhomboid (Re/Rh) nuclei of the ventral midline thalamus abolished only the SWM-specific activity patterns that were seen during dual-task sessions within the hippocampal–prefrontal circuit. These findings demonstrate that Re/Rh facilitate bidirectional communication between the dorsal hippocampus and mPFC during SWM, providing evidence for a causal role of Re/Rh in regulating hippocampal–prefrontal synchrony and SWM-directed behavior. SIGNIFICANCE STATEMENT Hippocampal–prefrontal synchrony has long been thought to be critical for spatial working memory (SWM) and the ventral midline thalamic reuniens and rhomboid nuclei (Re/Rh) have long been considered a potential site for synchronizing the hippocampus and medial prefrontal cortex. However, the hypothesis that Re/Rh are critical for hippocampal–prefrontal synchrony and SWM has not been tested. We first used a dual-task approach to identify SWM-specific patterns of hippocampal–prefrontal synchrony. We then demonstrated that Re/Rh inactivation concurrently disrupted SWM-specific behavior and the SWM-specific patterns of hippocampal–prefrontal synchrony seen during dual-task performance. These results provide the first direct evidence that Re/Rh contribute to SWM by modulating hippocampal–prefrontal

Longitudinal relationships among activity in attention redirection neural circuitry and symptom severity in youth.

PubMed

Bertocci, Michele A; Bebko, Genna; Dwojak, Amanda; Iyengar, Satish; Ladouceur, Cecile D; Fournier, Jay C; Versace, Amelia; Perlman, Susan B; Almeida, Jorge R C; Travis, Michael J; Gill, Mary Kay; Bonar, Lisa; Schirda, Claudiu; Diwadkar, Vaibhav A; Sunshine, Jeffrey L; Holland, Scott K; Kowatch, Robert A; Birmaher, Boris; Axelson, David; Horwitz, Sarah M; Frazier, Thomas; Arnold, L Eugene; Fristad, Mary A; Youngstrom, Eric A; Findling, Robert L; Phillips, Mary L

2017-05-01

Changes in neural circuitry function may be associated with longitudinal changes in psychiatric symptom severity. Identification of these relationships may aid in elucidating the neural basis of psychiatric symptom evolution over time. We aimed to distinguish these relationships using data from the Longitudinal Assessment of Manic Symptoms (LAMS) cohort. Forty-one youth completed two study visits (mean=21.3 months). Elastic-net regression (Multiple response Gaussian family) identified emotional regulation neural circuitry that changed in association with changes in depression, mania, anxiety, affect lability, and positive mood and energy dysregulation, accounting for clinical and demographic variables. Non-zero coefficients between change in the above symptom measures and change in activity over the inter-scan interval were identified in right amygdala and left ventrolateral prefrontal cortex. Differing patterns of neural activity change were associated with changes in each of the above symptoms over time. Specifically, from Scan1 to Scan2, worsening affective lability and depression severity were associated with increased right amygdala and left ventrolateral prefrontal cortical activity. Worsening anxiety and positive mood and energy dysregulation were associated with decreased right amygdala and increased left ventrolateral prefrontal cortical activity. Worsening mania was associated with increased right amygdala and decreased left ventrolateral prefrontal cortical activity. These changes in neural activity between scans accounted for 13.6% of the variance; that is 25% of the total explained variance (39.6%) in these measures. Distinct neural mechanisms underlie changes in different mood and anxiety symptoms overtime.

Removing the effect of response time on brain activity reveals developmental differences in conflict processing in the posterior medial prefrontal cortex.

PubMed

Carp, Joshua; Fitzgerald, Kate Dimond; Taylor, Stephan F; Weissman, Daniel H

2012-01-02

In functional magnetic resonance imaging (fMRI) studies, researchers often attempt to ensure that group differences in brain activity are not confounded with group differences in mean reaction time (RT). However, even when groups are matched for performance, they may differ in terms of the RT-BOLD relationship: the degree to which brain activity varies with RT on a trial-by-trial basis. Group activation differences might therefore be influenced by group differences in the relationship between brain activity and time on task. Here, we investigated whether correcting for this potential confound alters group differences in brain activity. Specifically, we reanalyzed data from a functional MRI study of response conflict in children and adults, in which conventional analyses indicated that conflict-related activity did not differ between groups. We found that the RT-BOLD relationship was weaker in children than in adults. Consequently, after removing the effect of RT on brain activity, children exhibited greater conflict-related activity than adults in both the posterior medial prefrontal cortex and the right dorsolateral prefrontal cortex. These results identify the RT-BOLD relationship as an important potential confound in fMRI studies of group differences. They also suggest that the magnitude of the RT-BOLD relationship may be a useful biomarker of brain maturity. Copyright © 2011 Elsevier Inc. All rights reserved.

Differential contribution of left and right prefrontal cortex to associative cued-recall memory: a parametric PET study.

PubMed

Lepage, Martin

2004-03-01

Several brain imaging studies have implicated prefrontal regions bilaterally during cued-recall memory tasks and yet the functional significance of these regions remains poorly understood. Using PET, we examined the neural activity in prefrontal regions of 15 subjects while they performed three cued-recall tasks differing in pre-experimental semantic associations between cues and targets. This manipulation produced varying levels of retrieval performance when one member (a semantic category name) of the triad was used as a cue for the retrieval of the other two members. The percentage of items correctly recalled was 10, 46, and 70 in the low, medium, and high cued-recall conditions, respectively. Linear contrast analyses of the PET data identified brain regions where neural activity varied with the number of items retrieved from memory. A left lateral prefrontal region showed maximal activity during the high cued-recall condition, which likely reflects processes involved in retrieval success and possibly in the generation of memory responses. Three right prefrontal regions (anterior and dorsolateral) showed maximal activity during the low cued-recall condition, which likely reflects processes involved in memory search/monitoring. These findings add further support for a bilateral prefrontal contribution to memory cued-recall tasks and point to differential roles of the two hemispheres.

A face to remember: emotional expression modulates prefrontal activity during memory formation.

PubMed

Sergerie, Karine; Lepage, Martin; Armony, Jorge L

2005-01-15

Emotion can exert a modulatory role on episodic memory. Several studies have shown that negative stimuli (e.g., words, pictures) are better remembered than neutral ones. Although facial expressions are powerful emotional stimuli and have been shown to influence perception and attention processes, little is known about their effect on memory. We used functional magnetic resonance imaging (fMRI) in humans to investigate the effects of expression (happy, neutral, and fearful) on prefrontal cortex (PFC) activity during the encoding of faces, using a subsequent memory effect paradigm. Our results show that activity in right PFC predicted memory for faces, regardless of expression, while a homotopic region in the left hemisphere was associated with successful encoding only for faces with an emotional expression. These findings are consistent with the proposed role of right dorsolateral PFC in successful encoding of nonverbal material, but also suggest that left DLPFC may be a site where integration of memory and emotional processes occurs. This study sheds new light on the current controversy regarding the hemispheric lateralization of PFC in memory encoding.

Dopamine modulates an intrinsic mGluR5-mediated depolarization underlying prefrontal persistent activity

PubMed Central

Sidiropoulou, Kyriaki; Lu, Fang-Min; Fowler, Melissa A.; Xiao, Rui; Phillips, Christopher; Ozkan, Emin D.; Zhu, Michael X.; White, Francis J.; Cooper, Donald C.

2009-01-01

Intrinsic properties of neurons that enable them to maintain depolarized, persistently activated states in the absence of sustained input are poorly understood. In short-term memory tasks, individual prefrontal cortical (PFC) neurons are capable of maintaining persistent action potential output during delay periods between informative cues and behavioral responses. Dopamine and drugs of abuse alter PFC function and working memory possibly by modulating intrinsic neuronal properties. Here we use patch-clamp recording of layer 5 PFC pyramidal neurons to identify an action potential burst-evoked intrinsic mGluR5-mediated postsynaptic depolarization that initiates an activated state. Depolarization occurs in the absence of recurrent synaptic activity and is reduced by a postsynaptic dopamine D1/5 receptor pathway. The depolarization is substantially diminished following behavioral sensitization to cocaine; moreover the D1/5 receptor modulation is lost. We propose the burst-evoked intrinsic depolarization to be a novel form of short-term cellular memory that is modulated by dopamine and cocaine experience. PMID:19169252

Prefrontal cortex haemodynamics and affective responses during exercise: a multi-channel near infrared spectroscopy study.

PubMed

Tempest, Gavin D; Eston, Roger G; Parfitt, Gaynor

2014-01-01

The dose-response effects of the intensity of exercise upon the potential regulation (through top-down processes) of affective (pleasure-displeasure) responses in the prefrontal cortex during an incremental exercise protocol have not been explored. This study examined the functional capacity of the prefrontal cortex (reflected by haemodynamics using near infrared spectroscopy) and affective responses during exercise at different intensities. Participants completed an incremental cycling exercise test to exhaustion. Changes (Δ) in oxygenation (O2Hb), deoxygenation (HHb), blood volume (tHb) and haemoglobin difference (HbDiff) were measured from bilateral dorsal and ventral prefrontal areas. Affective responses were measured every minute during exercise. Data were extracted at intensities standardised to: below ventilatory threshold, at ventilatory threshold, respiratory compensation point and the end of exercise. During exercise at intensities from ventilatory threshold to respiratory compensation point, ΔO2Hb, ΔHbDiff and ΔtHb were greater in mostly ventral than dorsal regions. From the respiratory compensation point to the end of exercise, ΔO2Hb remained stable and ΔHbDiff declined in dorsal regions. As the intensity increased above the ventilatory threshold, inverse associations between affective responses and oxygenation in (a) all regions of the left hemisphere and (b) lateral (dorsal and ventral) regions followed by the midline (ventral) region in the right hemisphere were observed. Differential activation patterns occur within the prefrontal cortex and are associated with affective responses during cycling exercise.

Prefrontal Cortex Haemodynamics and Affective Responses during Exercise: A Multi-Channel Near Infrared Spectroscopy Study

PubMed Central

Tempest, Gavin D.; Eston, Roger G.; Parfitt, Gaynor

2014-01-01

The dose-response effects of the intensity of exercise upon the potential regulation (through top-down processes) of affective (pleasure-displeasure) responses in the prefrontal cortex during an incremental exercise protocol have not been explored. This study examined the functional capacity of the prefrontal cortex (reflected by haemodynamics using near infrared spectroscopy) and affective responses during exercise at different intensities. Participants completed an incremental cycling exercise test to exhaustion. Changes (Δ) in oxygenation (O2Hb), deoxygenation (HHb), blood volume (tHb) and haemoglobin difference (HbDiff) were measured from bilateral dorsal and ventral prefrontal areas. Affective responses were measured every minute during exercise. Data were extracted at intensities standardised to: below ventilatory threshold, at ventilatory threshold, respiratory compensation point and the end of exercise. During exercise at intensities from ventilatory threshold to respiratory compensation point, ΔO2Hb, ΔHbDiff and ΔtHb were greater in mostly ventral than dorsal regions. From the respiratory compensation point to the end of exercise, ΔO2Hb remained stable and ΔHbDiff declined in dorsal regions. As the intensity increased above the ventilatory threshold, inverse associations between affective responses and oxygenation in (a) all regions of the left hemisphere and (b) lateral (dorsal and ventral) regions followed by the midline (ventral) region in the right hemisphere were observed. Differential activation patterns occur within the prefrontal cortex and are associated with affective responses during cycling exercise. PMID:24788166

Motor learning and modulation of prefrontal cortex: an fNIRS assessment

NASA Astrophysics Data System (ADS)

Ono, Yumie; Noah, Jack Adam; Zhang, Xian; Nomoto, Yasunori; Suzuki, Tatsuya; Shimada, Sotaro; Tachibana, Atsumichi; Bronner, Shaw; Hirsch, Joy

2015-12-01

Objective. Prefrontal hemodynamic responses are observed during performance of motor tasks. Using a dance video game (DVG), a complex motor task that requires temporally accurate footsteps with given visual and auditory cues, we investigated whether 20 h of DVG training modified hemodynamic responses of the prefrontal cortex in six healthy young adults. Approach. Fronto-temporal activity during actual DVG play was measured using functional near-infrared spectroscopy (fNIRS) pre- and post-training. To evaluate the training-induced changes in the time-courses of fNIRS signals, we employed a regression analysis using the task-specific template fNIRS signals that were generated from alternate well-trained and/or novice DVG players. The HRF was also separately incorporated as a template to construct an alternate regression model. Change in coefficients for template functions at pre- and post- training were determined and compared among different models. Main results. Training significantly increased the motor performance using the number of temporally accurate steps in the DVG as criteria. The mean oxygenated hemoglobin (ΔoxyHb) waveform changed from an activation above baseline pattern to that of a below baseline pattern. Participants showed significantly decreased coefficients for regressors of the ΔoxyHb response of novice players and HRF. The model using ΔoxyHb responses from both well-trained and novice players of DVG as templates showed the best fit for the ΔoxyHb responses of the participants at both pre- and post-training when analyzed with Akaike information criteria. Significance. These results suggest that the coefficients for the template ΔoxyHb responses of the novice players are sensitive indicators of motor learning during the initial stage of training and thus clinically useful to determine the improvement in motor performance when patients are engaged in a specific rehabilitation program.

Distributed value representation in the medial prefrontal cortex during intertemporal choices.

PubMed

Wang, Qiang; Luo, Shan; Monterosso, John; Zhang, Jintao; Fang, Xiaoyi; Dong, Qi; Xue, Gui

2014-05-28

The ability to resist current temptations in favor of long-term benefits is a critical human capacity. Despite the extensive studies on the neural mechanisms of intertemporal choices, how the subjective value of immediate and delayed rewards is represented and compared in the brain remains to be elucidated. The present fMRI study addressed this question by simultaneously and independently manipulating the magnitude of immediate and delayed rewards in an intertemporal decision task, combined with univariate analysis and multiple voxel pattern analysis. We found that activities in the posterior portion of the dorsal medial prefrontal cortex (DmPFC) were modulated by the value of immediate options, whereas activities in the adjacent anterior DmPFC were modulated by the subjective value of delayed options. Brain signal change in the ventral mPFC was positively correlated with the "relative value" (the absolute difference of subjective value between two intertemporal alternatives). In contrast, the dorsal anterior cingulate cortex activity was negatively correlated with the relative value. These results suggest that immediate and delayed rewards are separately represented in the dorsal mPFC and compared in the ventral mPFC to guide decisions. The functional dissociation of posterior and anterior DmPFC in representing immediate and delayed reward is consistent with the general structural and functional architecture of the prefrontal cortex and may provide a neural basis for human's unique capacity to delayed gratification. Copyright © 2014 the authors 0270-6474/14/347522-09$15.00/0.

A common profile of prefrontal cortical activation following exposure to nicotine- or chocolate-associated contextual cues.

PubMed

Schroeder, B E; Binzak, J M; Kelley, A E

2001-01-01

Conditioning and learning factors are likely to play key roles in the process of addiction and in relapse to drug use. In nicotine addiction, for example, contextual cues associated with smoking can be powerful determinants of craving and relapse, even after considerable periods of abstinence. Using the detection of the immediate-early gene product, Fos, we examined which regions of the brain are activated by environmental cues associated with nicotine administration, and compared this profile to the pattern induced by cues associated with a natural reward, chocolate. In the first experiment, rats were treated with either nicotine (0.4 mg/ml/kg) or saline once per day for 10 days in a test environment distinct from their home cages. In the second experiment, rats were given access to either a bowl of chocolate chips or an empty bowl in the distinct environment for 10 days. After a 4-day interval, rats were re-introduced to the environment where they previously received either nicotine treatment or chocolate access. Nicotine-associated sensory cues elicited marked and specific activation of Fos expression in prefrontal cortical and limbic regions. Moreover, exposure to cues associated with the natural reward, chocolate, induced a pattern of gene expression that showed many similarities with that elicited by drug cues, particularly in prefrontal regions. These observations support the hypothesis that addictive drugs induce long-term neuroadaptations in brain regions subserving normal learning and memory for motivationally salient stimuli.

CHANGES IN APICAL DENDRITIC STRUCTURE CORRELATE WITH SUSTAINED ERK1/2 PHOSPHORYLATION IN MEDIAL PREFRONTAL CORTEX OF A RAT MODEL OF DOPAMINE D1 RECEPTOR AGONIST SENSITIZATION

PubMed Central

Papadeas, Sophia T.; Halloran, Christopher; McCown, Thomas J.; Breese, George R.; Blake, Bonita L.

2008-01-01

Rats lesioned with 6-hydroxydopamine (6-OHDA) as neonates exhibit behavioral and neurochemical abnormalities in adulthood that mimic Lesch-Nyhan disease, schizophrenia and other developmental disorders of frontostriatal circuit dysfunction. In these animals, a latent sensitivity to D1 agonists is maximally exposed by repeated administration of dopamine agonists in the post-pubertal period (D1 priming). In neonate-lesioned, adult rats primed with SKF-38393, we found selective, persistent alterations in the morphology of pyramidal neuron apical dendrites in the prelimbic area of the medial prefrontal cortex (mPFC). In these animals, dendrite bundling patterns and the typically straight trajectories of primary dendritic shafts were disrupted, whereas the diameter of higher-order oblique branches was increased. Although not present in neonate-lesioned rats treated with saline, these morphological changes persisted at least 21 days after repeated dosing with SKF-38393, and were not accompanied by markers of neurodegenerative change. A sustained increase in phospho-ERK immunoreactivity in wavy dendritic shafts over the same period suggested a relationship between prolonged ERK phosphorylation and dendritic remodeling in D1-primed rats. In support of this hypothesis, pretreatment with the MEK1/2-ERK1/2 pathway inhibitors PD98059 or SL327, prior to each priming dose of SKF-38393, prevented the morphological changes associated with D1 priming. Together, these findings demonstrate that repeated stimulation of D1 receptors in adulthood interacts with the developmental loss of dopamine to profoundly and persistently modify neuronal signaling and dendrite morphology in the mature prefrontal cortex. Furthermore, sustained elevation of ERK activity in mPFC pyramidal neurons may play a role in guiding these morphological changes in vivo. PMID:18785628

Activation of the prefrontal cortex by unilateral transcranial direct current stimulation leads to an asymmetrical effect on risk preference in frames of gain and loss.

PubMed

Ye, Hang; Huang, Daqiang; Wang, Siqi; Zheng, Haoli; Luo, Jun; Chen, Shu

2016-10-01

Previous brain imaging and brain stimulation studies have suggested that the dorsolateral prefrontal cortex may be critical in regulating risk-taking behavior, although its specific causal effect on people's risk preference remains controversial. This paper studied the independent modulation of the activity of the right and left dorsolateral prefrontal cortex using various configurations of transcranial direct current stimulation. We designed a risk-measurement table and adopted a within-subject design to compare the same participant's risk preference before and after unilateral stimulation when presented with different frames of gain and loss. The results confirmed a hemispheric asymmetry and indicated that the right dorsolateral prefrontal cortex has an asymmetric effect on risk preference regarding frames of gain and loss. Enhancing the activity of the right dorsolateral prefrontal cortex significantly decreased the participants' degree of risk aversion in the gain frame, whereas it increased the participants' degree of risk aversion in the loss frame. Our findings provide important information regarding the impact of transcranial direct current stimulation on the risk preference of healthy participants. The effects observed in our experiment compared with those of previous studies provide further evidence of the effects of hemispheric and frame-dependent asymmetry. These findings may be helpful in understanding the neural basis of risk preference in humans, especially when faced with decisions involving possible gain or loss relative to the status quo. Copyright © 2016 Elsevier B.V. All rights reserved.

Role of activity-dependent BDNF expression in hippocampal–prefrontal cortical regulation of behavioral perseverance

PubMed Central

Sakata, Kazuko; Martinowich, Keri; Woo, Newton H.; Schloesser, Robert J.; Jimenez, Dennisse V.; Ji, Yuanyuan; Shen, Liya; Lu, Bai

2013-01-01

Activity-dependent gene transcription, including that of the brain-derived neurotrophic factor (Bdnf) gene, has been implicated in various cognitive functions. We previously demonstrated that mutant mice with selective disruption of activity-dependent BDNF expression (BDNF-KIV mice) exhibit deficits in GABA-mediated inhibition in the prefrontal cortex (PFC). Here, we show that disruption of activity-dependent BDNF expression impairs BDNF-dependent late-phase long-term potentiation (L-LTP) in CA1, a site of hippocampal output to the PFC. Interestingly, early-phase LTP and conventional L-LTP induced by strong tetanic stimulation were completely normal in BDNF-KIV mice. In parallel, attenuation of activity-dependent BDNF expression significantly impairs spatial memory reversal and contextual memory extinction, two executive functions that require intact hippocampal–PFC circuitry. In contrast, spatial and contextual memory per se were not affected. Thus, activity-dependent BDNF expression in the hippocampus and PFC may contribute to cognitive and behavioral flexibility. These results suggest distinct roles for different forms of L-LTP and provide a link between activity-dependent BDNF expression and behavioral perseverance, a hallmark of several psychiatric disorders. PMID:23980178

Disruption of hippocampal–prefrontal cortex activity by dopamine D2R-dependent LTD of NMDAR transmission

PubMed Central

Banks, Paul James; Burroughs, Amelia Caroline; Barker, Gareth Robert Isaac; Brown, Jon Thomas; Warburton, Elizabeth Clea; Bashir, Zafar Iqbal

2015-01-01

Functional connectivity between the hippocampus and prefrontal cortex (PFC) is essential for associative recognition memory and working memory. Disruption of hippocampal–PFC synchrony occurs in schizophrenia, which is characterized by hypofunction of NMDA receptor (NMDAR)-mediated transmission. We demonstrate that activity of dopamine D2-like receptors (D2Rs) leads selectively to long-term depression (LTD) of hippocampal–PFC NMDAR-mediated synaptic transmission. We show that dopamine-dependent LTD of NMDAR-mediated transmission profoundly disrupts normal synaptic transmission between hippocampus and PFC. These results show how dopaminergic activation induces long-term hypofunction of NMDARs, which can contribute to disordered functional connectivity, a characteristic that is a hallmark of psychiatric disorders such as schizophrenia. PMID:26286993

Altered fatty acid concentrations in prefrontal cortex of schizophrenic patients

PubMed Central

Taha, Ameer Y.; Cheon, Yewon; Ma, Kaizong; Rapoport, Stanley I.; Rao, Jagadeesh S.

2013-01-01

Background Disturbances in prefrontal cortex phospholipid and fatty acid composition have been reported in schizophrenic (SCZ) patients, often as percent of total lipid concentration or incomplete lipid profile. In this study, we quantified absolute concentrations (nmol/g wet weight) of several lipid classes and their constituent fatty acids in postmortem prefrontal cortex of SCZ patients (n = 10) and age-matched controls (n = 10). Methods Lipids were extracted, fractionated with thin layer chromatography and assayed. Results Mean total lipid, phospholipid, individual phospholipids, plasmalogen, triglyceride and cholesteryl ester concentrations did not differ significantly between the groups. Compared to controls, SCZ brains showed significant increases in several monounsaturated and polyunsaturated fatty acids in cholesteryl ester. Significant increases or decreases occurred in palmitoleic, linoleic, γ-linolenic and n-3 docosapentaenoic acid in total lipids, triglycerides or phospholipids. Conclusion These changes suggest disturbed prefrontal cortex fatty acid concentrations, particularly within cholesteryl esters, as a pathological aspect of schizophrenia. PMID:23428160

Reward sensitivity modulates brain activity in the prefrontal cortex, ACC and striatum during task switching.

PubMed

Fuentes-Claramonte, Paola; Ávila, César; Rodríguez-Pujadas, Aina; Ventura-Campos, Noelia; Bustamante, Juan C; Costumero, Víctor; Rosell-Negre, Patricia; Barrós-Loscertales, Alfonso

2015-01-01

Current perspectives on cognitive control acknowledge that individual differences in motivational dispositions may modulate cognitive processes in the absence of reward contingencies. This work aimed to study the relationship between individual differences in Behavioral Activation System (BAS) sensitivity and the neural underpinnings involved in processing a switching cue in a task-switching paradigm. BAS sensitivity was hypothesized to modulate brain activity in frontal regions, ACC and the striatum. Twenty-eight healthy participants underwent fMRI while performing a switching task, which elicited activity in fronto-striatal regions during the processing of the switch cue. BAS sensitivity was negatively associated with activity in the lateral prefrontal cortex, anterior cingulate cortex and the ventral striatum. Combined with previous results, our data indicate that BAS sensitivity modulates the neurocognitive processes involved in task switching in a complex manner depending on task demands. Therefore, individual differences in motivational dispositions may influence cognitive processing in the absence of reward contingencies.

Reward Sensitivity Modulates Brain Activity in the Prefrontal Cortex, ACC and Striatum during Task Switching

PubMed Central

Fuentes-Claramonte, Paola; Ávila, César; Rodríguez-Pujadas, Aina; Ventura-Campos, Noelia; Bustamante, Juan C.; Costumero, Víctor; Rosell-Negre, Patricia; Barrós-Loscertales, Alfonso

2015-01-01

Current perspectives on cognitive control acknowledge that individual differences in motivational dispositions may modulate cognitive processes in the absence of reward contingencies. This work aimed to study the relationship between individual differences in Behavioral Activation System (BAS) sensitivity and the neural underpinnings involved in processing a switching cue in a task-switching paradigm. BAS sensitivity was hypothesized to modulate brain activity in frontal regions, ACC and the striatum. Twenty-eight healthy participants underwent fMRI while performing a switching task, which elicited activity in fronto-striatal regions during the processing of the switch cue. BAS sensitivity was negatively associated with activity in the lateral prefrontal cortex, anterior cingulate cortex and the ventral striatum. Combined with previous results, our data indicate that BAS sensitivity modulates the neurocognitive processes involved in task switching in a complex manner depending on task demands. Therefore, individual differences in motivational dispositions may influence cognitive processing in the absence of reward contingencies. PMID:25875640

Reduced NAA levels in the dorsolateral prefrontal cortex of young bipolar patients.

PubMed

Sassi, Roberto B; Stanley, Jeffrey A; Axelson, David; Brambilla, Paolo; Nicoletti, Mark A; Keshavan, Matcheri S; Ramos, Renato T; Ryan, Neal; Birmaher, Boris; Soares, Jair C

2005-11-01

Converging evidence implicates prefrontal circuits in the pathophysiology of bipolar disorder. Proton spectroscopy studies performed in adult bipolar patients assessing prefrontal regions have suggested decreased levels of N-acetylaspartate (NAA), a putative marker of neuronal integrity. In order to examine whether such abnormalities would also be found in younger patients, a 1H spectroscopy study was conducted that focused on the dorsolateral prefrontal cortex of children and adolescents with bipolar disorder. The authors examined the levels of NAA, creatine plus phosphocreatine, and choline-containing molecules in the left dorsolateral prefrontal cortex of 14 bipolar disorder patients (mean age=15.5 years, SD=3, eight female) and 18 healthy comparison subjects (mean age=17.3, SD=3.7, seven female) using short echo time, single-voxel in vivo 1H spectroscopy. Absolute metabolite levels were determined using the water signal as an internal reference. Bipolar patients presented significantly lower NAA levels and a significant inverse correlation between choline-containing molecules and number of previous affective episodes. No differences were found for other metabolites. These findings suggest that young bipolar patients have decreased NAA levels in the dorsolateral prefrontal cortex, similar to what was previously reported in adult patients. Such changes may reflect an underdevelopment of dendritic arborizations and synaptic connections. These neuronal abnormalities in the dorsolateral prefrontal cortex of bipolar disorder youth are unlikely to represent long-term degenerative processes, at least in the subgroup of patients where the illness had relatively early onset.

NOS1 ex1f-VNTR polymorphism influences prefrontal brain oxygenation during a working memory task.

PubMed

Kopf, Juliane; Schecklmann, Martin; Hahn, Tim; Dresler, Thomas; Dieler, Alica C; Herrmann, Martin J; Fallgatter, Andreas J; Reif, Andreas

2011-08-15

Nitric oxide (NO) synthase produces NO, which serves as first and second messenger in neurons, where the protein is encoded by the NOS1 gene. A functional variable number of tandem repeats (VNTR) polymorphism in the promoter region of the alternative first exon 1f of NOS1 is associated with various functions of human behavior, for example increased impulsivity, while another, non-functional variant was linked to decreased verbal working memory and a heightened risk for schizophrenia. We therefore investigated the influence of NOS1 ex 1f-VNTR on working memory function as reflected by both behavioral measures and prefrontal oxygenation. We hypothesized that homozygous short allele carriers exhibit altered brain oxygenation in task-related areas, namely the dorsolateral and ventrolateral prefrontal cortex and the parietal cortex. To this end, 56 healthy subjects were stratified into a homozygous long allele group and a homozygous short allele group comparable for age, sex and intelligence. All subjects completed a letter n-back task (one-, two-, and three-back), while concentration changes of oxygenated (O(2)Hb) hemoglobin in the prefrontal cortex were measured with functional near-infrared spectroscopy (fNIRS). We found load-associated O(2)Hb increases in the prefrontal and parts of the parietal cortex. Significant load-associated oxygenation differences between the two genotype groups could be shown for the dorsolateral prefrontal cortex and the parietal cortex. Specifically, short allele carriers showed a significantly larger increase in oxygenation in all three n-back tasks. This suggests a potential compensatory mechanism, with task-related brain regions being more active in short allele carriers to compensate for reduced NOS1 expression. Copyright © 2011 Elsevier Inc. All rights reserved.

Medial prefrontal cortex activity during the extinction of conditioned fear: an investigation using functional near-infrared spectroscopy.

PubMed

Guhn, Anne; Dresler, Thomas; Hahn, Tim; Mühlberger, Andreas; Ströhle, Andreas; Deckert, Jürgen; Herrmann, Martin J

2012-06-01

The majority of fear conditioning studies in humans have focused on fear acquisition rather than fear extinction. For this reason only a few functional imaging studies on fear extinction are available. A large number of animal studies indicate the medial prefrontal cortex (mPFC) as neuronal substrate of extinction. We therefore determined mPFC contribution during extinction learning after a discriminative fear conditioning in 34 healthy human subjects by using functional near-infrared spectroscopy. During the extinction training, a previously conditioned neutral face (conditioned stimulus, CS+) no longer predicted an aversive scream (unconditioned stimulus, UCS). Considering differential valence and arousal ratings as well as skin conductance responses during the acquisition phase, we found a CS+ related increase in oxygenated haemoglobin concentration changes within the mPFC over the time course of extinction. Late CS+ trials further revealed higher activation than CS- trials in a cluster of probe set channels covering the mPFC. These results are in line with previous findings on extinction and further emphasize the mPFC as significant for associative learning processes. During extinction, the diminished fear association between a former CS+ and a UCS is inversely correlated with mPFC activity--a process presumably dysfunctional in anxiety disorders. Copyright © 2012 S. Karger AG, Basel.

Individual Differences in Typical Reappraisal Use Predict Amygdala and Prefrontal Responses

PubMed Central

Drabant, Emily M.; McRae, Kateri; Manuck, Stephen B.; Hariri, Ahmad R.; Gross, James J.

2010-01-01

Background Participants who are instructed to use reappraisal to downregulate negative emotion show decreased amygdala responses and increased prefrontal responses. However, it is not known whether individual differences in the tendency to use reappraisal manifests in similar neural responses when individuals are spontaneously confronted with negative situations. Such spontaneous emotion regulation might play an important role in normal and pathological responses to the emotional challenges of everyday life. Methods Fifty-six healthy women completed a blood oxygenation-level dependent functional magnetic resonance imaging challenge paradigm involving the perceptual processing of emotionally negative facial expressions. Participants also completed measures of typical emotion regulation use, trait anxiety, and neuroticism. Results Greater use of reappraisal in everyday life was related to decreased amygdala activity and increased prefrontal and parietal activity during the processing of negative emotional facial expressions. These associations were not attributable to variation in trait anxiety, neuroticism, or the use of another common form of emotion regulation, namely suppression. Conclusions These findings suggest that, like instructed reappraisal, individual differences in reappraisal use are associated with decreased activation in ventral emotion generative regions and increased activation in prefrontal control regions in response to negative stimuli. Such individual differences in emotion regulation might predict successful coping with emotional challenges as well as the onset of affective disorders. PMID:18930182

Reciprocal neural response within lateral and ventral medial prefrontal cortex during hot and cold reasoning.

PubMed

Goel, Vinod; Dolan, Raymond J

2003-12-01

Logic is widely considered the basis of rationality. Logical choices, however, are often influenced by emotional responses, sometimes to our detriment, sometimes to our advantage. To understand the neural basis of emotionally neutral ("cold") and emotionally salient ("hot") reasoning we studied 19 volunteers using event-related fMRI, as they made logical judgments about arguments that varied in emotional saliency. Despite identical logical form and content categories across "hot" and "cold" reasoning conditions, lateral and ventral medial prefrontal cortex showed reciprocal response patterns as a function of emotional saliency of content. "Cold" reasoning trials resulted in enhanced activity in lateral/dorsal lateral prefrontal cortex (L/DLPFC) and suppression of activity in ventral medial prefrontal cortex (VMPFC). By contrast, "hot" reasoning trials resulted in enhanced activation in VMPFC and suppression of activation in L/DLPFC. This reciprocal engagement of L/DLPFC and VMPFC provides evidence for a dynamic neural system for reasoning, the configuration of which is strongly influenced by emotional saliency.

Does ventrolateral prefrontal cortex help in searching for the lost key? Evidence from an fNIRS study.

PubMed

Carrieri, Marika; Lancia, Stefania; Bocchi, Alessia; Ferrari, Marco; Piccardi, Laura; Quaresima, Valentina

2018-06-01

The Key Search Task (KST) is a neuropsychological test that requires strategies for searching a lost key in an imaginary field. This request may involve different cognitive processes as mental imagery and navigation planning. This study was aimed at investigating, by a twenty-channel functional near-infrared spectroscopy (fNIRS) system, the hemodynamic response (i.e., oxygenated-hemoglobin (O 2 Hb) and deoxygenated-hemoglobin (HHb) changes) of the prefrontal cortex in navigation planning. A right ventrolateral prefrontal cortex (rVLPFC) activation during the KST was hypothesized. Thirty-eight volunteers performed the KST and a Control Task (CT), the latter requiring the volunteers to mark the X letter. An activation (i.e., increase/decrease in O 2 Hb/HHb) of: 1) rVLPFC during the KST execution, and 2) bilateral dorsolateral prefrontal cortex (DLPFC) during the CT execution was found. The present study provides a contribution in localizing the rVLPFC as the critically active region, within the frontal lobes, that was found maximally activated during mental navigation in the mind's eye of healthy participants while performing the KST. Considering the contribution of rVLPFC in spatial navigation, its activation suggests that the KST could be adopted in the clinical routine for investigating navigation planning. Compared to other neuroimaging techniques, fNIRS (with its relatively low physical constraints) contributes to better clarifying the role of rVLPFC in some aspects of human navigation. Therefore, the combined use of the fNIRS and the KST could be considered as an innovative and valid tool to evaluate fundamental functions for everyday life, such as spatial navigation planning.

Prefrontal Neuronal Responses during Audiovisual Mnemonic Processing

PubMed Central

Hwang, Jaewon

2015-01-01

During communication we combine auditory and visual information. Neurophysiological research in nonhuman primates has shown that single neurons in ventrolateral prefrontal cortex (VLPFC) exhibit multisensory responses to faces and vocalizations presented simultaneously. However, whether VLPFC is also involved in maintaining those communication stimuli in working memory or combining stored information across different modalities is unknown, although its human homolog, the inferior frontal gyrus, is known to be important in integrating verbal information from auditory and visual working memory. To address this question, we recorded from VLPFC while rhesus macaques (Macaca mulatta) performed an audiovisual working memory task. Unlike traditional match-to-sample/nonmatch-to-sample paradigms, which use unimodal memoranda, our nonmatch-to-sample task used dynamic movies consisting of both facial gestures and the accompanying vocalizations. For the nonmatch conditions, a change in the auditory component (vocalization), the visual component (face), or both components was detected. Our results show that VLPFC neurons are activated by stimulus and task factors: while some neurons simply responded to a particular face or a vocalization regardless of the task period, others exhibited activity patterns typically related to working memory such as sustained delay activity and match enhancement/suppression. In addition, we found neurons that detected the component change during the nonmatch period. Interestingly, some of these neurons were sensitive to the change of both components and therefore combined information from auditory and visual working memory. These results suggest that VLPFC is not only involved in the perceptual processing of faces and vocalizations but also in their mnemonic processing. PMID:25609614

Prefrontal Reactivity to Social Signals of Threat as a Predictor of Treatment Response in Anxious Youth

PubMed Central

Kujawa, Autumn; Swain, James E; Hanna, Gregory L; Koschmann, Elizabeth; Simpson, David; Connolly, Sucheta; Fitzgerald, Kate D; Monk, Christopher S; Phan, K Luan

2016-01-01

Neuroimaging has shown promise as a tool to predict likelihood of treatment response in adult anxiety disorders, with potential implications for clinical decision-making. Despite the relatively high prevalence and emergence of anxiety disorders in youth, very little work has evaluated neural predictors of response to treatment. The goal of the current study was to examine brain function during emotional face processing as a predictor of response to treatment in children and adolescents (age 7–19 years; N=41) with generalized, social, and/or separation anxiety disorder. Prior to beginning treatment with the selective serotonin reuptake inhibitor (SSRI) sertraline or cognitive behavior therapy (CBT), participants completed an emotional faces matching task during functional magnetic resonance imaging (fMRI). Whole brain responses to threatening (ie, angry and fearful) and happy faces were examined as predictors of change in anxiety severity following treatment. Greater activation in inferior and superior frontal gyri, including dorsolateral prefrontal cortex and ventrolateral prefrontal cortex, as well as precentral/postcentral gyri during processing of threatening faces predicted greater response to CBT and SSRI treatment. For processing of happy faces, activation in postcentral gyrus was a significant predictor of treatment response. Post-hoc analyses indicated that effects were not significantly moderated by type of treatment. Findings suggest that greater activation in prefrontal regions involved in appraising and regulating responses to social signals of threat predict better response to SSRI and CBT treatment in anxious youth and that neuroimaging may be a useful tool for predicting how youth will respond to treatment. PMID:26708107

Spike-timing-dependent plasticity in the human dorso-lateral prefrontal cortex.

PubMed

Casula, Elias Paolo; Pellicciari, Maria Concetta; Picazio, Silvia; Caltagirone, Carlo; Koch, Giacomo

2016-12-01

Changes in the synaptic strength of neural connections are induced by repeated coupling of activity of interconnected neurons with precise timing, a phenomenon known as spike-timing-dependent plasticity (STDP). It is debated if this mechanism exists in large-scale cortical networks in humans. We combined transcranial magnetic stimulation (TMS) with concurrent electroencephalography (EEG) to directly investigate the effects of two paired associative stimulation (PAS) protocols (fronto-parietal and parieto-frontal) of pre and post-synaptic inputs within the human fronto-parietal network. We found evidence that the dorsolateral prefrontal cortex (DLPFC) has the potential to form robust STDP. Long-term potentiation/depression of TMS-evoked cortical activity is prompted after that DLPFC stimulation is followed/preceded by posterior parietal stimulation. Such bidirectional changes are paralleled by sustained increase/decrease of high-frequency oscillatory activity, likely reflecting STDP responsivity. The current findings could be important to drive plasticity of damaged cortical circuits in patients with cognitive or psychiatric disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

Distorted images of one's own body activates the prefrontal cortex and limbic/paralimbic system in young women: a functional magnetic resonance imaging study.

PubMed

Kurosaki, Mitsuhaya; Shirao, Naoko; Yamashita, Hidehisa; Okamoto, Yasumasa; Yamawaki, Shigeto

2006-02-15

Our aim was to study the gender differences in brain activation upon viewing visual stimuli of distorted images of one's own body. We performed functional magnetic resonance imaging on 11 healthy young men and 11 healthy young women using the "body image tasks" which consisted of fat, real, and thin shapes of the subject's own body. Comparison of the brain activation upon performing the fat-image task versus real-image task showed significant activation of the bilateral prefrontal cortex and left parahippocampal area including the amygdala in the women, and significant activation of the right occipital lobe including the primary and secondary visual cortices in the men. Comparison of brain activation upon performing the thin-image task versus real-image task showed significant activation of the left prefrontal cortex, left limbic area including the cingulate gyrus and paralimbic area including the insula in women, and significant activation of the occipital lobe including the left primary and secondary visual cortices in men. These results suggest that women tend to perceive distorted images of their own bodies by complex cognitive processing of emotion, whereas men tend to perceive distorted images of their own bodies by object visual processing and spatial visual processing.

Decoding the Dopamine Signal in Macaque Prefrontal Cortex: A Simulation Study Using the Cx3Dp Simulator

PubMed Central

Spühler, Isabelle Ayumi; Hauri, Andreas

2013-01-01

Dopamine transmission in the prefrontal cortex plays an important role in reward based learning, working memory and attention. Dopamine is thought to be released non-synaptically into the extracellular space and to reach distant receptors through diffusion. This simulation study examines how the dopamine signal might be decoded by the recipient neuron. The simulation was based on parameters from the literature and on our own quantified, structural data from macaque prefrontal area 10. The change in extracellular dopamine concentration was estimated at different distances from release sites and related to the affinity of the dopamine receptors. Due to the sparse and random distribution of release sites, a transient heterogeneous pattern of dopamine concentration emerges. Our simulation predicts, however, that at any point in the simulation volume there is sufficient dopamine to bind and activate high-affinity dopamine receptors. We propose that dopamine is broadcast to its distant receptors and any change from the local baseline concentration might be decoded by a transient change in the binding probability of dopamine receptors. Dopamine could thus provide a graduated ‘teaching’ signal to reinforce concurrently active synapses and cell assemblies. In conditions of highly reduced or highly elevated dopamine levels the simulations predict that relative changes in the dopamine signal can no longer be decoded, which might explain why cognitive deficits are observed in patients with Parkinson’s disease, or induced through drugs blocking dopamine reuptake. PMID:23951205

Prefrontal responses to digit span memory phases in patients with post-traumatic stress disorder (PTSD): a functional near infrared spectroscopy study.

PubMed

Tian, Fenghua; Yennu, Amarnath; Smith-Osborne, Alexa; Gonzalez-Lima, F; North, Carol S; Liu, Hanli

2014-01-01

Neuroimaging studies of post-traumatic stress disorder (PTSD)-related memory impairments have consistently implicated abnormal activities in the frontal and parietal lobes. However, most studies have used block designs and could not dissociate the multiple phases of working memory. In this study, the involvement of the prefrontal cortex in working memory phases was assessed among veterans with PTSD and age-/gender-matched healthy controls. Multichannel functional near infrared spectroscopy (fNIRS) was utilized to measure prefrontal cortex hemodynamic activations during memory of neutral (i.e., not trauma-related) forward and backward digit span tasks. An event-related experimental design was utilized to dissociate the different phases (i.e., encoding, maintenance and retrieval) of working memory. The healthy controls showed robust hemodynamic activations during the encoding and retrieval processes. In contrast, the veterans with PTSD were found to have activations during the encoding process, but followed by distinct deactivations during the retrieval process. The PTSD participants, but not the controls, appeared to suppress prefrontal activity during memory retrieval. This deactivation was more pronounced in the right dorsolateral prefrontal cortex during the retrieval phase. These deactivations in PTSD patients might implicate an active inhibition of dorsolateral prefrontal neural activity during retrieval of working memory.

The effects of physical activity on functional MRI activation associated with cognitive control in children: a randomized controlled intervention

PubMed Central

Chaddock-Heyman, Laura; Erickson, Kirk I.; Voss, Michelle W.; Knecht, Anya M.; Pontifex, Matthew B.; Castelli, Darla M.; Hillman, Charles H.; Kramer, Arthur F.

2013-01-01

This study used functional magnetic resonance imaging (fMRI) to examine the influence of a 9-month physical activity program on task-evoked brain activation during childhood. The results demonstrated that 8- to 9-year-old children who participated in 60+ min of physical activity, 5 days per week, for 9 months, showed decreases in fMRI brain activation in the right anterior prefrontal cortex coupled with within-group improvements in performance on a task of attentional and interference control. Children assigned to a wait-list control group did not show changes in brain function. Furthermore, at post-test, children in the physical activity group showed similar anterior frontal brain patterns and incongruent accuracy rates to a group of college-aged young adults. Children in the wait-list control group still differed from the young adults in terms of anterior prefrontal activation and performance at post-test. There were no significant changes in fMRI activation in the anterior cingulate cortex (ACC) for either group. These results suggest that physical activity during childhood may enhance specific elements of prefrontal cortex function involved in cognitive control. PMID:23487583

Chronic smoking and alcoholism change expression of selective genes in the human prefrontal cortex.

PubMed

Flatscher-Bader, Traute; Wilce, Peter A

2006-05-01

Alcoholism is commonly associated with chronic smoking. A number of gene expression profiles of regions within the human mesocorticolimbic system have identified potential alcohol-sensitive genes; however, the influence of smoking on these changes was not taken into account. This study addressed the impact of alcohol and smoking on the expression of 4 genes, previously identified as alcoholism-sensitive, in the human prefrontal cortex (PFC). mRNA expression of apolipoprotein D, tissue inhibitor of the metalloproteinase 3, high-affinity glial glutamate transporter and midkine, was measured in the PFC of alcoholic subjects and controls with and without smoking comorbidity using real-time polymerase chain reaction. The results show that alcohol affects transcription of some of these genes. Additionally, smoking has a marked influence on gene expression. This study emphasizes the need for careful case selection in future gene expression studies to delineate the adaptive molecular process associated with smoking and alcohol.

Prefrontal-Hippocampal Pathways Underlying Inhibitory Control Over Memory

PubMed Central

Anderson, Michael C.; Bunce, Jamie G.; Barbas, Helen

2016-01-01

A key function of the prefrontal cortex is to support inhibitory control over behavior. It is widely believed that this function extends to stopping cognitive processes as well. Consistent with this, mounting evidence establishes the role of the right lateral prefrontal cortex in a clear case of cognitive control: retrieval suppression. Retrieval suppression refers to the ability to intentionally stop the retrieval process that arises when a reminder to a memory appears. Functional imaging data indicates that retrieval suppression involves top-down modulation of hippocampal activity by the dorsolateral prefrontal cortex, but the anatomical pathways supporting this inhibitory modulation remain unclear. Here we bridge this gap by integrating key findings about retrieval suppression observed through functional imaging with a detailed consideration of relevant anatomical pathways observed in non-human primates. Focusing selectively on the potential role of the anterior cingulate cortex, we develop two hypotheses about the pathways mediating interactions between lateral prefrontal cortex and the medial temporal lobes during suppression, and their cellular targets: the entorhinal gating hypothesis, and thalamo-hippocampal modulation via the nucleus reuniens. We hypothesize that whereas entorhinal gating is well situated to stop retrieval proactively, thalamo-hippocampal modulation may interrupt an ongoing act of retrieval reactively. Isolating the pathways that underlie retrieval suppression holds the potential to advance our understanding of a range of psychiatric disorders characterized by persistent intrusive thoughts. More broadly, an anatomical account of retrieval suppression would provide a key model system for understanding inhibitory control over cognition. PMID:26642918

Increasing generosity by disrupting prefrontal cortex

PubMed Central

Sugiyama, Taisei; Grigaityte, Kristina; Iacoboni, Marco

2017-01-01

Recent research suggests that prosocial outcomes in sharing games arise from prefrontal control of self-maximizing impulses. We used continuous Theta Burst Stimulation (cTBS) to disrupt the functioning of two prefrontal areas, the right dorsolateral prefrontal cortex (DLPFC) and dorsomedial prefrontal cortex (DMPFC). We used cTBS in the right MT/V5, as a control area. We then tested subjects’ prosocial inclinations with an unsupervised Dictator Game in which they allocated real money anonymously between themselves and low and high socioeconomic status (SES) players. cTBS over the two prefrontal sites made subjects more generous compared to MT/V5. More specifically, cTBS over DLPFC increased offers to high SES players, while cTBS over DMPFC caused increased offers to low SES players. These data, the first to demonstrate an effect of disruptive neuromodulation on costly sharing, suggest that DLPFC and MPFC exert inhibitory control over prosocial inclinations during costly sharing, though they may do so in different ways. DLPFC may implement contextual control, while DMPFC may implement a tonic form of control. This study demonstrates that humans’ prepotent inclination is toward prosocial outcomes when cognitive control is reduced, even when prosocial decisions carry no strategic benefit and concerns for reputation are minimized. PMID:26942832

Nonlinear response of the anterior cingulate and prefrontal cortex in schizophrenia as a function of variable attentional control.

PubMed

Blasi, Giuseppe; Taurisano, Paolo; Papazacharias, Apostolos; Caforio, Grazia; Romano, Raffaella; Lobianco, Luciana; Fazio, Leonardo; Di Giorgio, Annabella; Latorre, Valeria; Sambataro, Fabio; Popolizio, Teresa; Nardini, Marcello; Mattay, Venkata S; Weinberger, Daniel R; Bertolino, Alessandro

2010-04-01

Previous studies have reported abnormal prefrontal and cingulate activity during attentional control processing in schizophrenia. However, it is not clear how variation in attentional control load modulates activity within these brain regions in this brain disorder. The aim of this study in schizophrenia is to investigate the impact of increasing levels of attentional control processing on prefrontal and cingulate activity. Blood oxygen level-dependent (BOLD) responses of 16 outpatients with schizophrenia were compared with those of 21 healthy subjects while performing a task eliciting increasing levels of attentional control during event-related functional magnetic resonance imaging at 3 T. Results showed reduced behavioral performance in patients at greater attentional control levels. Imaging data indicated greater prefrontal activity at intermediate attentional control levels in patients but greater prefrontal and cingulate responses at high attentional control demands in controls. The BOLD activity profile of these regions in controls increased linearly with increasing cognitive loads, whereas in patients, it was nonlinear. Correlation analysis consistently showed differential region and load-specific relationships between brain activity and behavior in the 2 groups. These results indicate that varying attentional control load is associated in schizophrenia with load- and region-specific modification of the relationship between behavior and brain activity, possibly suggesting earlier saturation of cognitive capacity.

Equivalent brain SPECT perfusion changes underlying therapeutic efficiency in pharmacoresistant depression using either high-frequency left or low-frequency right prefrontal rTMS.

PubMed

Richieri, Raphaëlle; Boyer, Laurent; Padovani, Romain; Adida, Marc; Colavolpe, Cécile; Mundler, Olivier; Lançon, Christophe; Guedj, Eric

2012-12-03

Functional neuroimaging studies have suggested similar mechanisms underlying antidepressant effects of distinct therapeutics. This study aimed to determine and compare functional brain patterns underlying the antidepressant response of 2 distinct protocols of repetitive transcranial magnetic stimulation (rTMS). 99mTc-ECD SPECT was performed before and after rTMS of dorsolateral prefrontal cortex in 61 drug-resistant right-handed patients with major depression, using high frequency (10Hz) left-side stimulation in 33 patients, and low frequency (1Hz) right-side stimulation in 28 patients. Efficiency of rTMS response was defined as at least 50% reduction of the baseline Beck Depression Inventory score. We compared the whole-brain voxel-based brain SPECT changes in perfusion after rTMS, between responders and non-responders in the whole sample (p<0.005, uncorrected), and separately in the subgroup of patients with left- and right-stimulation. Before rTMS, the left- and right-prefrontal stimulation groups did not differ from clinical data and brain SPECT perfusion. rTMS efficiency (evaluated on % of responders) was statistically equivalent in the two groups of patients. In the whole-group of responder patients, a perfusion decrease was found after rTMS, in comparison to non-responders, within the left perirhinal cortex (BA35, BA36). This result was secondarily confirmed separately in the two subgroups, i.e. after either left stimulation (p=0.017) or right stimulation (p<0.001), without significant perfusion differences between these two subgroups. These data show that distinct successful rTMS protocols induce equivalent brain functional changes associated to antidepressive efficiency, consisting to a remote brain limbic activity decrease within the left perirhinal cortex. However, these results will have to be confirmed in a double-blind randomized trial using a sham control group. Copyright © 2012 Elsevier Inc. All rights reserved.

Neural Correlates of Attitude Change Following Positive and Negative Advertisements

PubMed Central

Kato, Junko; Ide, Hiroko; Kabashima, Ikuo; Kadota, Hiroshi; Takano, Kouji; Kansaku, Kenji

2009-01-01

Understanding changes in attitudes towards others is critical to understanding human behaviour. Neuropolitical studies have found that the activation of emotion-related areas in the brain is linked to resilient political preferences, and neuroeconomic research has analysed the neural correlates of social preferences that favour or oppose consideration of intrinsic rewards. This study aims to identify the neural correlates in the prefrontal cortices of changes in political attitudes toward others that are linked to social cognition. Functional magnetic resonance imaging (fMRI) experiments have presented videos from previous electoral campaigns and television commercials for major cola brands and then used the subjects' self-rated affinity toward political candidates as behavioural indicators. After viewing negative campaign videos, subjects showing stronger fMRI activation in the dorsolateral prefrontal cortex lowered their ratings of the candidate they originally supported more than did those with smaller fMRI signal changes in the same region. Subjects showing stronger activation in the medial prefrontal cortex tended to increase their ratings more than did those with less activation. The same regions were not activated by viewing negative advertisements for cola. Correlations between the self-rated values and the neural signal changes underscore the metric representation of observed decisions (i.e., whether to support or not) in the brain. This indicates that neurometric analysis may contribute to the exploration of the neural correlates of daily social behaviour. PMID:19503749

Non-invasive detection of language-related prefrontal high gamma band activity with beamforming MEG.

PubMed

Hashimoto, Hiroaki; Hasegawa, Yuka; Araki, Toshihiko; Sugata, Hisato; Yanagisawa, Takufumi; Yorifuji, Shiro; Hirata, Masayuki

2017-10-27

High gamma band (>50 Hz) activity is a key oscillatory phenomenon of brain activation. However, there has not been a non-invasive method established to detect language-related high gamma band activity. We used a 160-channel whole-head magnetoencephalography (MEG) system equipped with superconducting quantum interference device (SQUID) gradiometers to non-invasively investigate neuromagnetic activities during silent reading and verb generation tasks in 15 healthy participants. Individual data were divided into alpha (8-13 Hz), beta (13-25 Hz), low gamma (25-50 Hz), and high gamma (50-100 Hz) bands and analysed with the beamformer method. The time window was consecutively moved. Group analysis was performed to delineate common areas of brain activation. In the verb generation task, transient power increases in the high gamma band appeared in the left middle frontal gyrus (MFG) at the 550-750 ms post-stimulus window. We set a virtual sensor on the left MFG for time-frequency analysis, and high gamma event-related synchronization (ERS) induced by a verb generation task was demonstrated at 650 ms. In contrast, ERS in the high gamma band was not detected in the silent reading task. Thus, our study successfully non-invasively measured language-related prefrontal high gamma band activity.

Left prefrontal cortex control of novel occurrences during recollection: a psychopharmacological study using scopolamine and event-related fMRI.

PubMed

Bozzali, M; MacPherson, S E; Dolan, R J; Shallice, T

2006-10-15

Recollection and familiarity represent two processes involved in episodic memory retrieval. We investigated how scopolamine (an antagonist of acetylcholine muscarinic receptors) influenced brain activity during memory retrieval, using a paradigm that separated recollection and familiarity. Eighteen healthy volunteers were recruited in a randomized, placebo-controlled, double-blind design using event-related fMRI. Participants were required to perform a verbal recognition memory task within the scanner, either under placebo or scopolamine conditions. Depending on the subcondition, participants were required to make a simple recognition decision (old/new items) or base their decision on more specific information related to prior experience (target/non-target/new items). We show a drug modulation in left prefrontal and perirhinal cortex during recollection. Such an effect was specifically driven by novelty and showed an inverse correlation with accuracy performance. Additionally, we show a direct correlation between drug-related signal change in left prefrontal and perirhinal cortices. We discuss the findings in terms of acetylcholine mediation of the familiarity/novelty signal through perirhinal cortex and the control of the relative signal strength through prefrontal cortex.

Comparison of Physiological and Psychological Relaxation Using Measurements of Heart Rate Variability, Prefrontal Cortex Activity, and Subjective Indexes after Completing Tasks with and without Foliage Plants.

PubMed

Park, Sin-Ae; Song, Chorong; Oh, Yun-Ah; Miyazaki, Yoshifumi; Son, Ki-Cheol

2017-09-20

The objective of this study was to compare physiological and psychological relaxation by assessing heart rate variability (HRV), prefrontal cortex activity, and subjective indexes while subjects performed a task with and without foliage plants. In a crossover experimental design, 24 university students performed a task transferring pots with and without a foliage plant for 3 min. HRV and oxyhemoglobin (oxy-Hb) concentration in the prefrontal cortex were continuously measured. Immediately thereafter, subjective evaluation of emotions was performed using a modified semantic differential (SD) method and a profile of mood state questionnaire (POMS). Results showed that the natural logarithmic (ln) ratio of low frequency/high frequency, as an estimate of sympathetic nerve activity, was significantly lower while performing the task with foliage plants for the average 3 min measurement interval. Oxy-Hb concentration in the left prefrontal cortex showed a tendency to decrease in the 2-3 min interval in the task with foliage plants compared to the task without plants. Moreover, significant psychological relaxation according to POMS score and SD was demonstrated when the task involved foliage plants. In conclusion, the task involving foliage plants led to more physiological and psychological relaxation compared with the task without foliage plants.

Consequences of Variations in Genes that affect Dopamine in Prefrontal Cortex

PubMed Central

Diamond, Adele

2008-01-01

Patricia Goldman-Rakic played a groundbreaking role in investigating the cognitive functions subserved by dorsolateral prefrontal cortex and the key role of dopamine in that. The work discussed here builds on that including: 1) Studies of children predicted to have lower levels of prefrontal dopamine but otherwise basically normal brains (children treated for phenylketonuria [PKU]). Those studies changed medical guidelines, improving the children’s lives. 2) Studies of visual impairments (in contrast sensitivity and motion perception) in PKU children due to reduced retinal dopamine and due to excessive phenylalanine during the first postnatal weeks. Those studies, too, changed medical guidelines. 3) Studies of working memory and inhibitory control differences in typically developing children due to differences in catechol-O-methyltransferase (COMT) genotype, which selectively affect prefrontal dopamine levels. 4) Studies of gender differences in the effect of COMT genotype on cognitive performance in older adults. 5) A hypothesis about fundamental differences between attention deficit hyperactivity disorder (ADHD) that includes hyperactivity and ADHD of the inattentive type. Those disorders are hypothesized to differ in the affected neural system, underlying genetics, responsiveness to medication, comorbidities, and cognitive and behavioral profiles. These sound quite disparate but they all grew systematically out the base laid down by Patricia Goldman-Rakic. PMID:17725999

The brain of opera singers: experience-dependent changes in functional activation.

PubMed

Kleber, B; Veit, R; Birbaumer, N; Gruzelier, J; Lotze, M

2010-05-01

Several studies have shown that motor-skill training over extended time periods results in reorganization of neural networks and changes in brain morphology. Yet, little is known about training-induced adaptive changes in the vocal system, which is largely subserved by intrinsic reflex mechanisms. We investigated highly accomplished opera singers, conservatory level vocal students, and laymen during overt singing of an Italian aria in a neuroimaging experiment. We provide the first evidence that the training of vocal skills is accompanied by increased functional activation of bilateral primary somatosensory cortex representing articulators and larynx. Opera singers showed additional activation in right primary sensorimotor cortex. Further training-related activation comprised the inferior parietal lobe and bilateral dorsolateral prefrontal cortex. At the subcortical level, expert singers showed increased activation in the basal ganglia, the thalamus, and the cerebellum. A regression analysis of functional activation with accumulated singing practice confirmed that vocal skills training correlates with increased activity of a cortical network for enhanced kinesthetic motor control and sensorimotor guidance together with increased involvement of implicit motor memory areas at the subcortical and cerebellar level. Our findings may have ramifications for both voice rehabilitation and deliberate practice of other implicit motor skills that require interoception.

Spatiotemporal dynamics of brain activity during the transition from visually guided to memory-guided force control

PubMed Central

Poon, Cynthia; Chin-Cottongim, Lisa G.; Coombes, Stephen A.; Corcos, Daniel M.

2012-01-01

It is well established that the prefrontal cortex is involved during memory-guided tasks whereas visually guided tasks are controlled in part by a frontal-parietal network. However, the nature of the transition from visually guided to memory-guided force control is not as well established. As such, this study examines the spatiotemporal pattern of brain activity that occurs during the transition from visually guided to memory-guided force control. We measured 128-channel scalp electroencephalography (EEG) in healthy individuals while they performed a grip force task. After visual feedback was removed, the first significant change in event-related activity occurred in the left central region by 300 ms, followed by changes in prefrontal cortex by 400 ms. Low-resolution electromagnetic tomography (LORETA) was used to localize the strongest activity to the left ventral premotor cortex and ventral prefrontal cortex. A second experiment altered visual feedback gain but did not require memory. In contrast to memory-guided force control, altering visual feedback gain did not lead to early changes in the left central and midline prefrontal regions. Decreasing the spatial amplitude of visual feedback did lead to changes in the midline central region by 300 ms, followed by changes in occipital activity by 400 ms. The findings show that subjects rely on sensorimotor memory processes involving left ventral premotor cortex and ventral prefrontal cortex after the immediate transition from visually guided to memory-guided force control. PMID:22696535

Neonatal status epilepticus alters prefrontal-striatal circuitry and enhances methamphetamine-induced behavioral sensitization in adolescence.

PubMed

Lin, Tzu-Chao; Huang, Li-Tung; Huang, Ya-Ni; Chen, Gunng-Shinng; Wang, Jia-Yi

2009-02-01

Neonatal seizures may alter the developing neurocircuitry and cause behavioral abnormalities in adulthood. We found that rats previously subjected to lithium-pilocarpine (LiPC)-induced neonatal status epilepticus (NeoSE) exhibited enhanced behavioral sensitization to methamphetamine (MA) in adolescence. Neurochemically, dopamine (DA) and metabolites were markedly decreased in prefrontal cortex (PFC) and insignificantly changed in striatum by NeoSE, but were increased in both PFC and striatum by NeoSE+MA. Glutamate levels were increased in both PFC and striatum in the NeoSE+MA group. DA turnover, an index of utilization and activity, was increased by NeoSE but reversed by MA in PFC. Gene expression of the regulator of G-protein signaling 4 (RGS4) was downregulated in PFC and striatum by NeoSE and further suppressed by MA. These findings suggest NeoSE affects both dopaminergic and glutamatergic systems in the prefrontal-striatal circuitry that manifests as enhanced behavioral sensitization to MA in adolescence.

Abnormal functional activation and maturation of ventromedial prefrontal cortex and cerebellum during temporal discounting in autism spectrum disorder.

PubMed

Murphy, Clodagh M; Christakou, Anastasia; Giampietro, Vincent; Brammer, Michael; Daly, Eileen M; Ecker, Christine; Johnston, Patrick; Spain, Debbie; Robertson, Dene M; Murphy, Declan G; Rubia, Katya

2017-11-01

People with autism spectrum disorder (ASD) have poor decision-making and temporal foresight. This may adversely impact on their everyday life, mental health, and productivity. However, the neural substrates underlying poor choice behavior in people with ASD, or its' neurofunctional development from childhood to adulthood, are unknown. Despite evidence of atypical structural brain development in ASD, investigation of functional brain maturation in people with ASD is lacking. This cross-sectional developmental fMRI study investigated the neural substrates underlying performance on a temporal discounting (TD) task in 38 healthy (11-35 years old) male adolescents and adults with ASD and 40 age, sex, and IQ-matched typically developing healthy controls. Most importantly, we assessed group differences in the neurofunctional maturation of TD across childhood and adulthood. Males with ASD had significantly poorer task performance and significantly lower brain activation in typical regions that mediate TD for delayed choices, in predominantly right hemispheric regions of ventrolateral/dorsolateral prefrontal cortices, ventromedial prefrontal cortex, striatolimbic regions, and cerebellum. Importantly, differential activation in ventromedial frontal cortex and cerebellum was associated with abnormal functional brain maturation; controls, in contrast to people with ASD, showed progressively increasing activation with increasing age in these regions; which furthermore was associated with performance measures and clinical ASD measures (stereotyped/restricted interests). Findings provide first cross-sectional evidence that reduced activation of TD mediating brain regions in people with ASD during TD is associated with abnormal functional brain development in these regions between childhood and adulthood, and this is related to poor task performance and clinical measures of ASD. Hum Brain Mapp 38:5343-5355, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Acute and chronic changes in brain activity with deep brain stimulation for refractory depression.

PubMed

Conen, Silke; Matthews, Julian C; Patel, Nikunj K; Anton-Rodriguez, José; Talbot, Peter S

2018-04-01

Deep brain stimulation is a potential option for patients with treatment-refractory depression. Deep brain stimulation benefits have been reported when targeting either the subgenual cingulate or ventral anterior capsule/nucleus accumbens. However, not all patients respond and optimum stimulation-site is uncertain. We compared deep brain stimulation of the subgenual cingulate and ventral anterior capsule/nucleus accumbens separately and combined in the same seven treatment-refractory depression patients, and investigated regional cerebral blood flow changes associated with acute and chronic deep brain stimulation. Deep brain stimulation-response was defined as reduction in Montgomery-Asberg Depression Rating Scale score from baseline of ≥50%, and remission as a Montgomery-Asberg Depression Rating Scale score ≤8. Changes in regional cerebral blood flow were assessed using [ 15 O]water positron emission tomography. Remitters had higher relative regional cerebral blood flow in the prefrontal cortex at baseline and all subsequent time-points compared to non-remitters and non-responders, with prefrontal cortex regional cerebral blood flow generally increasing with chronic deep brain stimulation. These effects were consistent regardless of stimulation-site. Overall, no significant regional cerebral blood flow changes were apparent when deep brain stimulation was acutely interrupted. Deep brain stimulation improved treatment-refractory depression severity in the majority of patients, with consistent changes in local and distant brain regions regardless of target stimulation. Remission of depression was reached in patients with higher baseline prefrontal regional cerebral blood flow. Because of the small sample size these results are preliminary and further evaluation is necessary to determine whether prefrontal cortex regional cerebral blood flow could be a predictive biomarker of treatment response.

Lithium modulates the muscarinic facilitation of synaptic plasticity and theta-gamma coupling in the hippocampal-prefrontal pathway.

PubMed

Ruggiero, Rafael N; Rossignoli, Matheus T; Lopes-Aguiar, Cleiton; Leite, João P; Bueno-Junior, Lezio S; Romcy-Pereira, Rodrigo N

2018-06-01

Mood disorders are associated to functional unbalance in mesolimbic and frontal cortical circuits. As a commonly used mood stabilizer, lithium acts through multiple biochemical pathways, including those activated by muscarinic cholinergic receptors crucial for hippocampal-prefrontal communication. Therefore, here we investigated the effects of lithium on prefrontal cortex responses under cholinergic drive. Lithium-treated rats were anesthetized with urethane and implanted with a ventricular cannula for muscarinic activation, a recording electrode in the medial prefrontal cortex (mPFC), and a stimulating electrode in the intermediate hippocampal CA1. Either of two forms of synaptic plasticity, long-term potentiation (LTP) or depression (LTD), were induced during pilocarpine effects, which were monitored in real time through local field potentials. We found that lithium attenuates the muscarinic potentiation of cortical LTP (<20 min) but enhances the muscarinic potentiation of LTD maintenance (>80 min). Moreover, lithium treatment promoted significant cross-frequency coupling between CA1 theta (3-5 Hz) and mPFC low-gamma (30-55 Hz) oscillations. Interestingly, lithium by itself did not affect any of these measures. Thus, lithium pretreatment and muscarinic activation synergistically modulate the hippocampal-prefrontal connectivity. Because these alterations varied with time, oscillatory parameters, and type of synaptic plasticity, our study suggests that lithium influences prefrontal-related circuits through intricate dynamics, informing future experiments on mood disorders. Copyright © 2018. Published by Elsevier Inc.

Reduced prefrontal activation in pediatric patients with obsessive-compulsive disorder during verbal episodic memory encoding.

PubMed

Batistuzzo, Marcelo Camargo; Balardin, Joana Bisol; Martin, Maria da Graça Morais; Hoexter, Marcelo Queiroz; Bernardes, Elisa Teixeira; Borcato, Sonia; Souza, Marina de Marco E; Querido, Cicero Nardini; Morais, Rosa Magaly; de Alvarenga, Pedro Gomes; Lopes, Antonio Carlos; Shavitt, Roseli Gedanke; Savage, Cary R; Amaro, Edson; Miguel, Euripedes C; Polanczyk, Guilherme V; Miotto, Eliane C

2015-10-01

Patients with obsessive-compulsive disorder (OCD) often present with deficits in episodic memory, and there is evidence that these difficulties may be secondary to executive dysfunction, that is, impaired selection and/or application of memory-encoding strategies (mediation hypothesis). Semantic clustering is an effective strategy to enhance encoding of verbal episodic memory (VEM) when word lists are semantically related. Self-initiated mobilization of this strategy has been associated with increased activity in the prefrontal cortex, particularly the orbitofrontal cortex, a key region in the pathophysiology of OCD. We therefore studied children and adolescents with OCD during uncued semantic clustering strategy application in a VEM functional magnetic resonance imaging (fMRI)-encoding paradigm. A total of 25 pediatric patients with OCD (aged 8.1-17.5 years) and 25 healthy controls (HC, aged 8.1-16.9) matched for age, gender, handedness, and IQ were evaluated using a block design VEM paradigm that manipulated semantically related and unrelated words. The semantic clustering strategy score (SCS) predicted VEM performance in HC (p < .001, R(2) = 0.635), but not in patients (p = .099). Children with OCD also presented hypoactivation in the dorsomedial prefrontal cortex (cluster-corrected p < .001). Within-group analysis revealed a negative correlation between Yale-Brown Obsessive Compulsive Scale scores and activation of orbitofrontal cortex in the group with OCD. Finally, a positive correlation between age and SCS was found in HC (p = .001, r = 0.635), but not in patients with OCD (p = .936, r = 0.017). Children with OCD presented altered brain activation during the VEM paradigm and absence of expected correlation between SCS and age, and between SCS and total words recalled. These results suggest that different neural mechanisms underlie self-initiated semantic clustering in OCD. Copyright © 2015 American Academy of Child and Adolescent Psychiatry

Ginkobiloba extract improves working memory performance in middle-aged women: role of asymmetry of prefrontal cortex activity during a working memory task.

PubMed

Sakatani, Kaoru; Tanida, Masahiro; Hirao, Naoyasu; Takemura, Naohiro

2014-01-01

In order to clarify the mechanism through which extract of Ginkgo biloba leaves (EGb) improves cognitive function, we examined the effects of EGb on cerebral blood oxygenation in the prefrontal cortex (PFC) and on performance during a working memory task, using near-infrared spectrometry (NIRS). First, we evaluated differences in behavioral performance of the Sternberg working memory test (ST) and in the activation pattern of the PFC during ST between 15 young and 19 middle-aged healthy women. Then, we examined the effect of EGb (120 mg/day for 6 weeks) on ST performance and PFC activation pattern in the middle-aged group. The middle-aged group exhibited a longer reaction time (RT) in ST than the young group and showed a different PFC activation pattern during ST, i.e., the middle-aged group showed bilateral activation while the young group showed right-dominant activation. In the middle-aged group, administration of EGb for 6 weeks shortened the RT of ST and changed the PFC activation pattern to right-dominant, like that in the young group. The results indicate the PFC plays a role in the physiological cognitive function-enhancing effect of EGb. EGb might improve working memory function in middle-aged individuals by counteracting the occurrence of aging-related hemispheric asymmetry reduction.

Microglial activation, increased TNF and SERT expression in the prefrontal cortex define stress-altered behaviour in mice susceptible to anhedonia.

PubMed

Couch, Yvonne; Anthony, Daniel C; Dolgov, Oleg; Revischin, Alexander; Festoff, Barry; Santos, Ana Isabel; Steinbusch, Harry W; Strekalova, Tatyana

2013-03-01

A chronic stress paradigm comprising exposure to predation, tail suspension and restraint induces a depressive syndrome in C57BL/6J mice that occurs in some, but not all, animals. Here, we sought to extend our behavioural studies to investigate how susceptibility (sucrose preference<65%) or resilience (sucrose preference>65%) to stress-induced anhedonia affects the 5HT system and the expression of inflammation-related genes. All chronically stressed animals, displayed increased level of anxiety, but susceptible mice exhibited an increased propensity to float in the forced swim test and demonstrate hyperactivity under stressful lighting conditions. These changes were not present in resilient or acutely stressed animals. Compared to resilient animals, susceptible mice showed elevated expression of tumour necrosis factor alpha (TNF) and the 5-HT transporter (SERT) in the pre-frontal area. Enhanced expression of 5HT(2A) and COX-1 in the pre-frontal area was observed in all stressed animals. In turn, indoleamine-2,3-dioxygenase (IDO) was significantly unregulated in the raphe of susceptible animals. At the cellular level, increased numbers of Iba-1-positive microglial cells were also present in the prefrontal area of susceptible animals compared to resilient animals. Consequently, the susceptible animals display a unique molecular profile when compared to resilient, but anxious, animals. Unexpectedly, this altered profile provides a rationale for exploring anti-inflammatory, and possibly, TNF-targeted therapy for major depression. Copyright © 2013 Elsevier Inc. All rights reserved.

Reduced prefrontal hemodynamic response in adult attention-deficit hyperactivity disorder as measured by near-infrared spectroscopy.

PubMed

Ueda, Shotaro; Ota, Toyosaku; Iida, Junzo; Yamamuro, Kazuhiko; Yoshino, Hiroki; Kishimoto, Naoko; Kishimoto, Toshifumi

2018-06-01

Recent developments in near-infrared spectroscopy (NIRS) have enabled non-invasive clarification of brain functions in psychiatric disorders. In pediatric attention-deficit hyperactivity disorder (ADHD), reduced prefrontal hemodynamic responses have been observed with NIRS repeatedly. However, there are few studies of adult ADHD by multi-channel NIRS. Therefore, in this study, we used multi-channel NIRS to examine the characteristics of prefrontal hemodynamic responses during the Stroop Color-Word Task (SCWT) in adult ADHD patients and in age- and sex-matched control subjects. Twelve treatment-naïve adults with ADHD and 12 age- and sex-matched healthy control subjects participated in the present study after giving consent. We used 24-channel NIRS to measure the oxygenated hemoglobin (oxy-Hb) changes at the frontal lobes of participants during the SCWT. We compared the oxy-Hb changes between adults with ADHD and control subjects by t-tests with Bonferroni correction. During the SCWT, the oxy-Hb changes observed in the ADHD group were significantly smaller than those in the control group in channels 11, 16, 18, 21, 22, 23, and 24, corresponding to the prefrontal cortex. At channels 16, 21, 23, and 24 of the ADHD group, there were negative correlations between the symptomatic severity and the oxy-Hb changes. The present study suggests that adults with ADHD have reduced prefrontal hemodynamic response as measured by NIRS. © 2018 The Authors. Psychiatry and Clinical Neurosciences © 2018 Japanese Society of Psychiatry and Neurology.

The prefrontal cortex and hybrid learning during iterative competitive games.

PubMed

Abe, Hiroshi; Seo, Hyojung; Lee, Daeyeol

2011-12-01

Behavioral changes driven by reinforcement and punishment are referred to as simple or model-free reinforcement learning. Animals can also change their behaviors by observing events that are neither appetitive nor aversive when these events provide new information about payoffs available from alternative actions. This is an example of model-based reinforcement learning and can be accomplished by incorporating hypothetical reward signals into the value functions for specific actions. Recent neuroimaging and single-neuron recording studies showed that the prefrontal cortex and the striatum are involved not only in reinforcement and punishment, but also in model-based reinforcement learning. We found evidence for both types of learning, and hence hybrid learning, in monkeys during simulated competitive games. In addition, in both the dorsolateral prefrontal cortex and orbitofrontal cortex, individual neurons heterogeneously encoded signals related to actual and hypothetical outcomes from specific actions, suggesting that both areas might contribute to hybrid learning. © 2011 New York Academy of Sciences.

An fMRI study into emotional processing in Parkinson's disease: Does increased medial prefrontal activation compensate for striatal dysfunction?

PubMed

Moonen, Anja J H; Weiss, Peter H; Wiesing, Michael; Weidner, Ralph; Fink, Gereon R; Reijnders, Jennifer S A M; Weber, Wim M; Leentjens, Albert F G

2017-01-01

Apart from a progressive decline of motor functions, Parkinson's disease (PD) is also characterized by non-motor symptoms, including disturbed processing of emotions. This study aims at assessing emotional processing and its neurobiological correlates in PD with the focus on how medicated Parkinson patients may achieve normal emotional responsiveness despite basal ganglia dysfunction. Nineteen medicated patients with mild to moderate PD (without dementia or depression) and 19 matched healthy controls passively viewed positive, negative, and neutral pictures in an event-related blood oxygen level-dependent functional magnetic resonance imaging study (BOLD-fMRI). Individual subjective ratings of valence and arousal levels for these pictures were obtained right after the scanning. Parkinson patients showed similar valence and arousal ratings as controls, denoting intact emotional processing at the behavioral level. Yet, Parkinson patients showed decreased bilateral putaminal activation and increased activation in the right dorsomedial prefrontal cortex (PFC), compared to controls, both most pronounced for highly arousing emotional stimuli. Our findings revealed for the first time a possible compensatory neural mechanism in Parkinson patients during emotional processing. The increased medial PFC activity may have modulated emotional responsiveness in patients via top-down cognitive control, therewith restoring emotional processing at the behavioral level, despite striatal dysfunction. These results may impact upon current treatment strategies of affective disorders in PD as patients may benefit from this intact or even compensatory influence of prefrontal areas when therapeutic strategies are applied that rely on cognitive control to modulate disturbed processing of emotions.

Dyspnea-Related Cues Engage the Prefrontal Cortex

PubMed Central

Herigstad, Mari; Hayen, Anja; Evans, Eleanor; Hardinge, Frances M.; Davies, Robert J.; Wiech, Katja

2015-01-01

BACKGROUND: Dyspnea is the major source of disability in COPD. In COPD, environmental cues (eg, the prospect of having to climb stairs) become associated with dyspnea and may trigger dyspnea even before physical activity commences. We hypothesized that brain activation relating to such cues would be different between patients with COPD and healthy control subjects, reflecting greater engagement of emotional mechanisms in patients. METHODS: Using functional MRI (FMRI), we investigated brain responses to dyspnea-related word cues in 41 patients with COPD and 40 healthy age-matched control subjects. We combined these findings with scores on self-report questionnaires, thus linking the FMRI task with clinically relevant measures. This approach was adapted from studies in pain that enabled identification of brain networks responsible for pain processing despite absence of a physical challenge. RESULTS: Patients with COPD demonstrated activation in the medial prefrontal cortex and anterior cingulate cortex, which correlated with the visual analog scale (VAS) response to word cues. This activity independently correlated with patient responses on questionnaires of depression, fatigue, and dyspnea vigilance. Activation in the anterior insula, lateral prefrontal cortex, and precuneus correlated with the VAS dyspnea scale but not with the questionnaires. CONCLUSIONS: The findings suggest that engagement of the emotional circuitry of the brain is important for interpretation of dyspnea-related cues in COPD and is influenced by depression, fatigue, and vigilance. A heightened response to salient cues is associated with increased symptom perception in chronic pain and asthma, and the findings suggest that such mechanisms may be relevant in COPD. PMID:26134891

The role of prefrontal cortex in psychopathy

PubMed Central

Koenigs, Michael

2014-01-01

Psychopathy is a personality disorder characterized by remorseless and impulsive antisocial behavior. Given the significant societal costs of the recidivistic criminal activity associated with the disorder, there is a pressing need for more effective treatment strategies, and hence, a better understanding of the psychobiological mechanisms underlying the disorder. The prefrontal cortex (PFC) is likely to play an important role in psychopathy. In particular, the ventromedial and anterior cingulate sectors of PFC are theorized to mediate a number of social and affective decision-making functions that appear to be disrupted in psychopathy. This article provides a critical summary of human neuroimaging data implicating prefrontal dysfunction in psychopathy. A growing body of evidence associates psychopathy with structural and functional abnormalities in ventromedial PFC and anterior cingulate cortex. Although this burgeoning field still faces a number of methodological challenges and outstanding questions that will need to be resolved by future studies, the research to date has established a link between psychopathy and PFC. PMID:22752782

Stimulation of D2 receptors in the prefrontal cortex reduces PCP-induced hyperactivity, acetylcholine release and dopamine metabolism in the nucleus accumbens.

PubMed

Del Arco, A; Mora, F; Mohammed, A H; Fuxe, K

2007-02-01

The aim of the present study was to investigate the effects of stimulation of D2 receptors in the prefrontal cortex (PFC) on spontaneous motor activity and the hyperactivity induced by the psychomimetic phencyclidine (PCP). In addition, the effects of prefrontal D2 stimulation under PCP treatment on dialysate concentrations of acetylcholine, choline, dopamine, DOPAC and HVA in the nucleus accumbens were also investigated. Sprague-Dawley male rats were implanted with guide cannulae to perform bilateral injections into the medial PFC of the D2 agonist quinpirole (1.5 and 5 microg/side). Horizontal and vertical spontaneous motor activity and the motor activity induced by systemic injections of the PCP (5 mg/kg i.p.) were monitored in the open field. PFC injections of quinpirole (1.5 and 5 microg/side) significantly decreased horizontal and vertical spontaneous motor activity in a dose-related manner. These effects were blocked by the D2 antagonist raclopride (5 microg/side). Microinjections of quinpirole (1.5 and 5 microg/side) into the PFC also significantly attenuated the hyperactivity produced by PCP (5 mg/kg i.p.). PCP also increased dialysate concentrations of acetylcholine, and dopamine metabolites in the nucleus accumbens. These increases were also reduced by injections of quinpirole (5 microg/side) into the PFC. These results suggest that the stimulation of prefrontal D2 receptors plays an inhibitory role in regulating spontaneous and PCP-induced motor activity and also in the neurochemical changes produced by PCP in the nucleus accumbens.

Sleep restriction in rats leads to changes in operant behaviour indicative of reduced prefrontal cortex function.

PubMed

Kamphuis, Jeanine; Baichel, Swetlana; Lancel, Marike; de Boer, Sietse F; Koolhaas, Jaap M; Meerlo, Peter

2017-02-01

Sleep deprivation has profound effects on cognitive performance, and some of these effects may be mediated by impaired prefrontal cortex function. In search of an animal model to investigate this relationship we studied the influence of restricted sleep on operant conditioning in rats, particularly the performance in a differential reinforcement of low rate responding (DRL) task, which is highly dependent upon an intact prefrontal cortex. Animals were trained to withhold a lever press until an imposed delay of 30 s after the last press had passed in order to achieve a food reward. Once the animals had mastered the task, they were sleep-restricted for 7 days with 20 h of sleep deprivation per day. At the end of each daily sleep deprivation session, performance on the DRL task was assessed. The results show that sleep-restricted animals were less able to time their responses correctly, started pressing the lever more randomly and showed signs of behavioural disinhibition, the latter possibly reflecting enhanced impulsivity. Our data support the hypothesis that a sleep debt has disruptive consequences for the functioning of the prefrontal cortex. This model offers possibilities for future studies investigating the underlying biochemical and molecular mechanisms of this relationship. © 2016 European Sleep Research Society.

Age-related changes in prefrontal norepinephrine transporter density: The basis for improved cognitive flexibility after low doses of atomoxetine in adolescent rats

PubMed Central

Bradshaw, Sarah E.; Agster, Kara L.; Waterhouse, Barry D.; McGaughy, Jill A.

2016-01-01

Adolescence is a period of major behavioral and brain reorganization. As diagnoses and treatment of disorders like attention deficit hyperactivity disorder (ADHD) often occur during adolescence, it is important to understand how the prefrontal cortices change and how these changes may influence the response to drugs during development. The current study uses an adolescent rat model to study the effect of standard ADHD treatments, atomoxetine and methylphenidate on attentional set shifting and reversal learning. While both of these drugs act as norepinephrine reuptake inhibitors, higher doses of atomoxetine and all doses of methylphenidate also block dopamine transporters (DAT). Low doses of atomoxetine, were effective at remediating cognitive rigidity found in adolescents. In contrast, methylphenidate improved performance in rats unable to form an attentional set due to distractibility but was without effect in normal subjects. We also assessed the effects of GBR 12909, a selective DAT inhibitor, but found no effect of any dose on behavior. A second study in adolescent rats investigated changes in norepinephrine transporter (NET) and dopamine beta hydroxylase (DBH) density in five functionally distinct subregions of the prefrontal cortex: infralimbic, prelimbic, anterior cingulate, medial and lateral orbitofrontal cortices. These regions are implicated in impulsivity and distractibility. We found that NET, but not DBH, changed across adolescence in a regionally selective manner. The prelimbic cortex, which is critical to cognitive rigidity, and the lateral orbitofrontal cortex, critical to reversal learning and some forms of response inhibition, showed higher levels of NET at early than mid- to late adolescence. PMID:26774596

Effects of milk casein-derived peptides on absolute oxyhaemoglobin concentrations in the prefrontal area and on work efficiency after mental stress loading in male students.

PubMed

Nakamura, H; Iwamoto, M; Ogata, T; Washida, K; Sekine, K; Takase, M; Park, B J; Morikawa, T; Miyazaki, Y

2008-01-01

This study examined the influence of milk casein-derived peptides on cerebral activity after mental stress loading. In a crossover study, 16 male students were given a drink containing peptides (peptide group), or water (control group) before stress loading. The oxyhaemoglobin (HbO(2)) concentration in the prefrontal area of the brain and work efficiency were measured as indicators of cerebral activity and differences in these parameters were examined according to type A or type B personality. Type A behaviour was defined as: aggression-hostility, hard-driving-time-urgency and speed-power, whereas type B behaviour did not have these characteristics. Peptide intake resulted in a significant increase in both HbO(2) concentration and work efficiency, whilst a similar increase was not seen in the control group. When divided into type A or type B personality, the changes in HbO(2) concentration for the control group differed significantly in the right prefrontal area. Moreover, in type A subjects the HbO(2) concentration in the right prefrontal area following intake was significantly different between the peptide and control groups.

Altered prefrontal cortical function during processing of fear-relevant stimuli in pregnancy.

PubMed

Roos, Annerine; Robertson, Frances; Lochner, Christine; Vythilingum, Bavanisha; Stein, Dan J

2011-09-12

In non-pregnant individuals, the prefrontal cortex (PFC) is involved in the regulation of emotion, and appears to play a role in anxiety. Near-infrared spectroscopy (NIRS) detects cortical neural activation without harmful radiation making it safe for use in pregnancy. The aims of this study were to assess neural circuitry involved in processing fear-relevant stimuli during pregnancy using NIRS, and to determine associations between activation of this circuitry, distress and anxiety symptoms, attention to threat, cortisol, estrogen, progesterone and testosterone levels. There was significant activation of the PFC in response to fearful faces compared to rest in both pregnant and control groups. Within pregnancy, the activation was most pronounced at trimester 2, compared to the other trimesters. In pregnant women only (all trimesters), PFC activation was significantly associated with increased distress and anxiety, but with decreased selective attention to masked fear. PFC activation was also significantly associated with increased levels of cortisol and testosterone in pregnancy. PFC function appears to be altered during processing of fear-relevant stimuli in pregnancy. Changes in hormone levels may lead to changes in PFC function, and in turn to changes in cognitive-affective processing and anxiety. Further work is needed, however, to explore precisely how PFC function is altered in pregnancy; it is possible that certain changes reflect altered processing of threat stimuli, while others reflect attempts to compensate for distressing and anxious symptoms that emerge during pregnancy. Copyright © 2011 Elsevier B.V. All rights reserved.

Auditory connections and functions of prefrontal cortex

PubMed Central

Plakke, Bethany; Romanski, Lizabeth M.

2014-01-01

The functional auditory system extends from the ears to the frontal lobes with successively more complex functions occurring as one ascends the hierarchy of the nervous system. Several areas of the frontal lobe receive afferents from both early and late auditory processing regions within the temporal lobe. Afferents from the early part of the cortical auditory system, the auditory belt cortex, which are presumed to carry information regarding auditory features of sounds, project to only a few prefrontal regions and are most dense in the ventrolateral prefrontal cortex (VLPFC). In contrast, projections from the parabelt and the rostral superior temporal gyrus (STG) most likely convey more complex information and target a larger, widespread region of the prefrontal cortex. Neuronal responses reflect these anatomical projections as some prefrontal neurons exhibit responses to features in acoustic stimuli, while other neurons display task-related responses. For example, recording studies in non-human primates indicate that VLPFC is responsive to complex sounds including vocalizations and that VLPFC neurons in area 12/47 respond to sounds with similar acoustic morphology. In contrast, neuronal responses during auditory working memory involve a wider region of the prefrontal cortex. In humans, the frontal lobe is involved in auditory detection, discrimination, and working memory. Past research suggests that dorsal and ventral subregions of the prefrontal cortex process different types of information with dorsal cortex processing spatial/visual information and ventral cortex processing non-spatial/auditory information. While this is apparent in the non-human primate and in some neuroimaging studies, most research in humans indicates that specific task conditions, stimuli or previous experience may bias the recruitment of specific prefrontal regions, suggesting a more flexible role for the frontal lobe during auditory cognition. PMID:25100931

How stable is activation in the amygdala and prefrontal cortex in adolescence? A study of emotional face processing across three measurements.

PubMed

van den Bulk, Bianca G; Koolschijn, P Cédric M P; Meens, Paul H F; van Lang, Natasja D J; van der Wee, Nic J A; Rombouts, Serge A R B; Vermeiren, Robert R J M; Crone, Eveline A

2013-04-01

Prior developmental functional magnetic resonance imaging (fMRI) studies have demonstrated elevated activation patterns in the amygdala and prefrontal cortex (PFC) in response to viewing emotional faces. As adolescence is a time of substantial variability in mood and emotional responsiveness, the stability of activation patterns could be fluctuating over time. In the current study, 27 healthy adolescents (age: 12-19 years) were scanned three times over a period of six months (mean test-retest interval of three months; final samples N=27, N=22, N=18). At each session, participants performed the same emotional faces task. At first measurement the presentation of emotional faces resulted in heightened activation in bilateral amygdala, bilateral lateral PFC and visual areas including the fusiform face area. Average activation did not differ across test-sessions over time, indicating that at the group level activation patterns in this network do not vary significantly over time. However, using the Intraclass Correlation Coefficient (ICC), fMRI reliability demonstrated only fair reliability for PFC (ICC=0.41-0.59) and poor reliability for the amygdala (ICC<0.4). These findings suggest substantial variability of brain activity over time and may have implications for studies investigating the influence of treatment effects on changes in neural levels in adolescents with psychiatric disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.

Agency Modulates the Lateral and Medial Prefrontal Cortex Responses in Belief-Based Decision Making

PubMed Central

Xue, Gui; He, Qinghua; Lu, Zhong-Lin; Levin, Irwin P.; Dong, Qi; Bechara, Antoine

2013-01-01

Many real-life decisions in complex and changing environments are guided by the decision maker’s beliefs, such as her perceived control over decision outcomes (i.e., agency), leading to phenomena like the “illusion of control”. However, the neural mechanisms underlying the “agency” effect on belief-based decisions are not well understood. Using functional imaging and a card guessing game, we revealed that the agency manipulation (i.e., either asking the subjects (SG) or the computer (CG) to guess the location of the winning card) not only affected the size of subjects’ bets, but also their “world model” regarding the outcome dependency. Functional imaging results revealed that the decision-related activation in the lateral and medial prefrontal cortex (PFC) was significantly modulated by agency and previous outcome. Specifically, these PFC regions showed stronger activation when subjects made decisions after losses than after wins under the CG condition, but the pattern was reversed under the SG condition. Furthermore, subjects with high external attribution of negative events were more affected by agency at the behavioral and neural levels. These results suggest that the prefrontal decision-making system can be modulated by abstract beliefs, and are thus vulnerable to factors such as false agency and attribution. PMID:23762332

Prefrontal Cortex Contributions to Episodic Retrieval Monitoring and Evaluation

ERIC Educational Resources Information Center

Cruse, Damian; Wilding, Edward L.

2009-01-01

Although the prefrontal cortex (PFC) plays roles in episodic memory judgments, the specific processes it supports are not understood fully. Event-related potential (ERP) studies of episodic retrieval have revealed an electrophysiological modulation--the right-frontal ERP old/new effect--which is thought to reflect activity in PFC. The functional…

Hemodynamic responses on prefrontal cortex related to meditation and attentional task

PubMed Central

Deepeshwar, Singh; Vinchurkar, Suhas Ashok; Visweswaraiah, Naveen Kalkuni; Nagendra, Hongasandra RamaRao

2015-01-01

Recent neuroimaging studies state that meditation increases regional cerebral blood flow (rCBF) in the prefrontal cortex (PFC). The present study employed functional near infrared spectroscopy (fNIRS) to evaluate the relative hemodynamic changes in PFC during a cognitive task. Twenty-two healthy male volunteers with ages between 18 and 30 years (group mean age ± SD; 22.9 ± 4.6 years) performed a color-word stroop task before and after 20 min of meditation and random thinking. Repeated measures ANOVA was performed followed by a post hoc analysis with Bonferroni adjustment for multiple comparisons between the mean values of “During” and “Post” with “Pre” state. During meditation there was an increased in oxy-hemoglobin (ΔHbO) and total hemoglobin (ΔTHC) concentration with reduced deoxy-hemoglobin (ΔHbR) concentration over the right prefrontal cortex (rPFC), whereas in random thinking there was increased ΔHbR with reduced total hemoglobin concentration on the rPFC. The mean reaction time (RT) was shorter during stroop color word task with concomitant reduction in ΔTHC after meditation, suggestive of improved performance and efficiency in task related to attention. Our findings demonstrated that meditation increased cerebral oxygenation and enhanced performance, which was associated with activation of the PFC. PMID:25741245

Dizocilpine (MK-801) induces distinct changes of N-methyl-D-aspartic acid receptor subunits in parvalbumin-containing interneurons in young adult rat prefrontal cortex.

PubMed

Xi, Dong; Zhang, Wentong; Wang, Huai-Xing; Stradtman, George G; Gao, Wen-Jun

2009-11-01

N-methyl-D-aspartic acid receptor (NMDAR) hypofunction has long been implicated in schizophrenia and NMDARs on gamma-aminobutyric acid (GABA)ergic interneurons are proposed to play an essential role in the pathogenesis. However, controversial results have been reported regarding the regulation of NMDAR expression, and direct evidence of how NMDAR antagonists act on specific subpopulations of prefrontal interneurons is missing. We investigated the effects of the NMDAR antagonist dizocilpine (MK-801) on the expression of NMDAR subtypes in the identified interneurons in young adult rat prefrontal cortex (PFC) by using laser microdissection and real-time polymerase chain reaction, combined with Western blotting and immunofluorescent staining. We found that MK-801 induced distinct changes of NMDAR subunits in the parvalbumin-immunoreactive (PV-ir) interneurons vs. pyramidal neurons in the PFC circuitry. The messenger RNA (mRNA) expression of all NMDAR subtypes, including NR1 and NR2A to 2D, exhibited inverted-U dose-dependent changes in response to MK-801 treatment in the PFC. In contrast, subunit mRNAs of NMDARs in PV-ir interneurons were significantly down-regulated at low doses, unaltered at medium doses, and significantly decreased again at high doses, suggesting a biphasic dose response to MK-801. The differential effects of MK-801 in mRNA expression of NMDAR subunits were consistent with the protein expression of NR2A and NR2B subunits revealed with Western blotting and double immunofluorescent staining. These results suggest that PV-containing interneurons in the PFC exhibit a distinct responsiveness to NMDAR antagonism and that NMDA antagonist can differentially and dose-dependently regulate the functions of pyramidal neurons and GABAergic interneurons in the prefrontal cortical circuitry.

Decreased medial prefrontal cortex activation during self-referential processing in bipolar mania.

PubMed

Herold, Dorrit; Usnich, Tatiana; Spengler, Stephanie; Sajonz, Bastian; Bauer, Michael; Bermpohl, Felix

2017-09-01

Patients with bipolar disorder in mania exhibit symptoms pointing towards altered self-referential processing, such as decreased self-focus, flight of ideas and high distractibility. In depression, the opposite pattern of symptoms has been connected to increased activation of medial prefrontal cortex (mPFC) during self-referential processing. In this study, we hypothesized that (1) patients with mania will exhibit decreased activation in the mPFC during self-referential processing and (2) will be more alexithymic and that levels of alexithymia will correlate negatively with mPFC activation. The neural response to standardized pictures was compared in 14 patients with bipolar I disorder in mania to 14 healthy controls using blood oxygen level dependent contrast magnetic resonance imaging. Participants were asked to indicate with button press during the scanning session for each picture whether the pictures personally related to them or not. Toronto alexithymia scale (TAS) scores were recorded from all participants. In the group analysis, patients with mania exhibited decreased activation in a predefined region of interest in the mPFC during self-referential processing compared to healthy controls. Patients with mania showed significantly higher levels of alexithymia, attributable to difficulties in identifying and describing emotions. Activation in the mPFC correlated negatively with levels of alexithymia. Results presented here should be replicated in a larger group, potentially including unmedicated patients. The finding of decreased mPFC activation during self-referential processing in mania may reflect decreased self-focus and high distractibility. Support for this view comes from the negative correlation between higher alexithymia scores and decreased mPFC activation. These findings represent an opposite clinical and neuroimaging pattern to findings in depression. Copyright © 2017. Published by Elsevier B.V.

Abnormal medial prefrontal cortex activity in heavy cannabis users during conscious emotional evaluation.

PubMed

Wesley, Michael J; Lile, Joshua A; Hanlon, Colleen A; Porrino, Linda J

2016-03-01

Long-term heavy cannabis users (cannabis users) who are not acutely intoxicated have diminished subconscious neural responsiveness to affective stimuli. This study sought to determine if abnormal processing extends to the conscious evaluation of emotional stimuli. Functional magnetic resonance imaging (fMRI) was used to examine brain activity as cannabis users (N = 16) and non-cannabis-using controls (N = 17) evaluated and categorized standardized International Affective Picture System (IAPS) stimuli. Individual judgments were used to isolate activity during the evaluation of emotional (i.e., emotional evaluation) or neutral (i.e., neutral evaluation) stimuli. Within- and between-group analyses were performed. Both groups judged the same stimuli as emotional and had activations in visual, midbrain, and middle cingulate cortices during emotional evaluation, relative to neutral. Within-group analyses also revealed amygdalar and inferior frontal gyrus activations in controls, but not cannabis users, and medial prefrontal cortex (mPFC) deactivations in cannabis users, but not controls, during emotional evaluation, relative to neutral. Between-group comparisons found that mPFC activity during positive and negative evaluation was significantly hypoactive in cannabis users, relative to controls. Abnormal neural processing of affective content extends to the level of consciousness in cannabis users. The hypoactive mPFC responses observed resembles the attenuated mPFC responses found during increased non-affective cognitive load in prior research. These findings suggest that abnormal mPFC singling in cannabis users during emotional evaluation might be associated with increased non-affective cognitive load.

Inhibitory Gating of Basolateral Amygdala Inputs to the Prefrontal Cortex

PubMed Central

McGarry, Laura M.

2016-01-01

Interactions between the prefrontal cortex (PFC) and basolateral amygdala (BLA) regulate emotional behaviors. However, a circuit-level understanding of functional connections between these brain regions remains incomplete. The BLA sends prominent glutamatergic projections to the PFC, but the overall influence of these inputs is predominantly inhibitory. Here we combine targeted recordings and optogenetics to examine the synaptic underpinnings of this inhibition in the mouse infralimbic PFC. We find that BLA inputs preferentially target layer 2 corticoamygdala over neighboring corticostriatal neurons. However, these inputs make even stronger connections onto neighboring parvalbumin and somatostatin expressing interneurons. Inhibitory connections from these two populations of interneurons are also much stronger onto corticoamygdala neurons. Consequently, BLA inputs are able to drive robust feedforward inhibition via two parallel interneuron pathways. Moreover, the contributions of these interneurons shift during repetitive activity, due to differences in short-term synaptic dynamics. Thus, parvalbumin interneurons are activated at the start of stimulus trains, whereas somatostatin interneuron activation builds during these trains. Together, these results reveal how the BLA impacts the PFC through a complex interplay of direct excitation and feedforward inhibition. They also highlight the roles of targeted connections onto multiple projection neurons and interneurons in this cortical circuit. Our findings provide a mechanistic understanding for how the BLA can influence the PFC circuit, with important implications for how this circuit participates in the regulation of emotion. SIGNIFICANCE STATEMENT The prefrontal cortex (PFC) and basolateral amygdala (BLA) interact to control emotional behaviors. Here we show that BLA inputs elicit direct excitation and feedforward inhibition of layer 2 projection neurons in infralimbic PFC. BLA inputs are much stronger at

Comparison of Physiological and Psychological Relaxation Using Measurements of Heart Rate Variability, Prefrontal Cortex Activity, and Subjective Indexes after Completing Tasks with and without Foliage Plants

PubMed Central

Park, Sin-Ae

2017-01-01

The objective of this study was to compare physiological and psychological relaxation by assessing heart rate variability (HRV), prefrontal cortex activity, and subjective indexes while subjects performed a task with and without foliage plants. In a crossover experimental design, 24 university students performed a task transferring pots with and without a foliage plant for 3 min. HRV and oxyhemoglobin (oxy-Hb) concentration in the prefrontal cortex were continuously measured. Immediately thereafter, subjective evaluation of emotions was performed using a modified semantic differential (SD) method and a profile of mood state questionnaire (POMS). Results showed that the natural logarithmic (ln) ratio of low frequency/high frequency, as an estimate of sympathetic nerve activity, was significantly lower while performing the task with foliage plants for the average 3 min measurement interval. Oxy-Hb concentration in the left prefrontal cortex showed a tendency to decrease in the 2–3 min interval in the task with foliage plants compared to the task without plants. Moreover, significant psychological relaxation according to POMS score and SD was demonstrated when the task involved foliage plants. In conclusion, the task involving foliage plants led to more physiological and psychological relaxation compared with the task without foliage plants. PMID:28930169

THC and endocannabinoids differentially regulate neuronal activity in the prefrontal cortex and hippocampus in the subchronic PCP model of schizophrenia.

PubMed

Aguilar, David D; Giuffrida, Andrea; Lodge, Daniel J

2016-02-01

Cannabis use has been associated with an increased risk to develop schizophrenia as well as symptom exacerbation in patients. In contrast, clinical studies have revealed an inverse relationship between the cerebrospinal fluid levels of the endocannabinoid anandamide and symptom severity, suggesting a therapeutic potential for endocannabinoid-enhancing drugs. Indeed, preclinical studies have shown that these drugs can reverse distinct behavioral deficits in a rodent model of schizophrenia. The mechanisms underlying the differences between exogenous and endogenous cannabinoid administration are currently unknown. Using the phencyclidine (PCP) rat model of schizophrenia, we compared the effects on neuronal activity of systematic administration of delta-9-tetrahydrocannabinol (THC) with the fatty acid amide hydrolase inhibitor URB597. Specifically, we found that the inhibitory response in the prefrontal cortex to THC administration was absent in PCP-treated rats. In contrast, an augmented response to endocannabinoid upregulation was observed in the prefrontal cortex of PCP-treated rats. Interestingly, differential effects were also observed at the neuronal population level, as endocannabinoid upregulation induced opposite effects on coordinated activity when compared with THC. Such information is important for understanding why marijuana and synthetic cannabinoid use may be contraindicated in schizophrenia patients while endocannabinoid enhancement may provide a novel therapeutic approach. © The Author(s) 2015.

Morphological alterations in the prefrontal cortex and the amygdala in unsuccessful psychopaths.

PubMed

Yang, Yaling; Raine, Adrian; Colletti, Patrick; Toga, Arthur W; Narr, Katherine L

2010-08-01

Although deficits in several cortical and subcortical structures have been found in psychopaths, it remains unclear whether the neuropathology differs between subgroups of psychopaths (i.e., unsuccessful and successful). Using both traditional and novel image analyses methods, this study aims to reveal gross and subtle morphological changes in the prefrontal cortex and the amygdala in unsuccessful and successful psychopaths. Volumetric segmentation, cortical pattern matching, and surface-based mesh modeling methods were used to examine prefrontal and amygdala structures in 16 unsuccessful psychopaths, 10 successful psychopaths, and 27 controls. Significant reduced gray matter volume and cortical thickness/surface shape in the middle frontal, orbitofrontal cortex and the amygdala were found in unsuccessful psychopaths but not successful psychopaths, compared with controls. This study provides the first evidence of greater prefrontal and amygdala structural deficits in unsuccessful psychopaths, which may predispose them to poor behavioral control and impaired decision-making, thus making them more prone to convictions. Copyright 2010 APA, all rights reserved

Motivational incentives lead to a strong increase in lateral prefrontal activity after self-control exertion

PubMed Central

Luethi, Matthias S.; Binder, Julia; Boesiger, Peter; Luechinger, Roger; Rasch, Björn

2016-01-01

Self-control is key to success in life. Initial acts of self-control temporarily impair subsequent self-control performance. Why such self-control failures occur is unclear, with prominent models postulating a loss of a limited resource vs a loss of motivation, respectively. Here, we used functional magnetic resonance imaging to identify the neural correlates of motivation-induced benefits on self-control. Participants initially exerted or did not exert self-control. In a subsequent Stroop task, participants performed worse after exerting self-control, but not if they were motivated to perform well by monetary incentives. On the neural level, having exerted self-control resulted in decreased activation in the left inferior frontal gyrus. Increasing motivation resulted in a particularly strong activation of this area specifically after exerting self-control. Thus, after self-control exertion participants showed more prefrontal neural activity without improving performance beyond baseline level. These findings suggest that impaired performance after self-control exertion may not exclusively be due to a loss of motivation. PMID:27217108

Ventral medial prefrontal cortex (vmPFC) as a target of the dorsolateral prefrontal modulation by transcranial direct current stimulation (tDCS) in drug addiction.

PubMed

Nakamura-Palacios, Ester Miyuki; Lopes, Isabela Bittencourt Coutinho; Souza, Rodolpho Albuquerque; Klauss, Jaisa; Batista, Edson Kruger; Conti, Catarine Lima; Moscon, Janine Andrade; de Souza, Rodrigo Stênio Moll

2016-10-01

Here, we report some electrophysiologic and imaging effects of the transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (dlPFC) in drug addiction, notably in alcohol and crack-cocaine dependence. The low resolution electromagnetic tomography (LORETA) analysis obtained through event-related potentials (ERPs) under drug-related cues, more specifically in its P3 segment (300-500 ms) in both, alcoholics and crack-cocaine users, showed that the ventral medial prefrontal cortex (vmPFC) was the brain area with the largest change towards increasing activation under drug-related cues in those subjects that kept abstinence during and after the treatment with bilateral tDCS (2 mA, 35 cm(2), cathodal left and anodal right) over dlPFC, applied repetitively (five daily sessions). In an additional study in crack-cocaine, which showed craving decreases after repetitive bilateral tDCS, we examined data originating from diffusion tensor imaging (DTI), and we found increased DTI parameters in the left connection between vmPFC and nucleus accumbens (NAcc), such as the number of voxels, fractional anisotropy (FA) and apparent diffusion coefficient (ADC), in tDCS-treated crack-cocaine users when compared to the sham-tDCS group. This increasing of DTI parameters was significantly correlated with craving decreasing after the repetitive tDCS. The vmPFC relates to the control of drug seeking, possibly by extinguishing this behavior. In our studies, the bilateral dlPFC tDCS reduced relapses and craving to the drug use, and increased the vmPFC activation under drug cues, which may be of a great importance in the control of drug use in drug addiction.

The Cortical Connectivity of the Prefrontal Cortex in the Monkey Brain

PubMed Central

Yeterian, Edward H.; Pandya, Deepak N.; Tomaiuolo, Francesco; Petrides, Michael

2011-01-01

One dimension of understanding the functions of the prefrontal cortex is knowledge of cortical connectivity. We have surveyed three aspects of prefrontal cortical connections: local projections (within the frontal lobe), the termination patterns of long association (post-Rolandic) projections, and the trajectories of major fiber pathways. The local connections appear to be organized in relation to dorsal (hippocampal origin) and ventral (paleocortical origin) architectonic trends. According to the proposal of a dual origin of the cerebral cortex, cortical areas can be traced as originating from archicortex (hippocampus) on the one hand, and paleocortex, on the other hand, in a stepwise manner (e.g., Sanides, 1969; Pandya and Yeterian, 1985). Prefrontal areas within each trend are connected with less architectonically differentiated areas, and, on the other hand, with more differentiated areas. Such organization may allow for the systematic exchange of information within each architectonic trend. The long connections of the prefrontal cortex with post-Rolandic regions seem to be organized preferentially in relation to dorsal and ventral prefrontal architectonic trends. Prefrontal areas are connected with post-Rolandic auditory, visual and somatosensory association areas, and with multimodal and paralimbic regions. This long connectivity likely works in conjunction with local connections to serve prefrontal cortical functions. The afferent and efferent connections of the prefrontal cortex with post-Rolandic regions are conveyed by specific long association pathways. These pathways as well appear to be organized in relation to dorsal and ventral prefrontal architectonic trends. Finally, although prefrontal areas have preferential connections in relation to dual architectonic trends, it is clear that there are interconnections between and among areas in each trend, which may provide a substrate for the overall integrative function of the prefrontal cortex. Prefrontal

An increase in prefrontal oxygenation at the start of voluntary cycling exercise was observed independently of exercise effort and muscle mass.

PubMed

Asahara, Ryota; Endo, Kana; Liang, Nan; Matsukawa, Kanji

2018-05-31

We have reported using near-infrared spectroscopy that an increase in prefrontal oxygenated-hemoglobin concentration (Oxy-Hb) at the start of cycling exercise has relation to central command, defined as a feedforward signal descending from higher brain centers. The final output of central command evokes the exercise effort-dependent cardiovascular responses. If the prefrontal cortex may output the final signal of central command toward the autonomic nervous system, the prefrontal oxygenation should increase depending on exercise effort. To test the hypothesis, we investigated the effects of exercise intensity and muscle mass on prefrontal oxygenation in 13 subjects. The subjects performed one- or two-legged cycling at various relative intensities for 1 min. The prefrontal Oxy-Hb and cardiovascular variables were simultaneously measured during exercise. The increase in cardiac output and the decrease in total peripheral resistance at the start of one- and two-legged cycling were augmented in proportion to exercise intensity and muscle mass recruitment. The prefrontal Oxy-Hb increased at the start of voluntary cycling, while such increase was not developed during passive cycling. Mental imagery of cycling also increased the prefrontal Oxy-Hb, concomitantly with peripheral muscle vasodilatation. However, the increase in prefrontal Oxy-Hb at the start of voluntary cycling seemed independent of exercise intensity and muscle mass recruitment. It is likely that the increased prefrontal activity at the start of cycling exercise is not representative of the final output signal of central command itself toward the autonomic nervous system but may trigger neuronal activity in the caudal brain responsible for the generation of central command.

A novel semi-immersive virtual reality visuo-motor task activates ventrolateral prefrontal cortex: a functional near-infrared spectroscopy study

NASA Astrophysics Data System (ADS)

Basso Moro, Sara; Carrieri, Marika; Avola, Danilo; Brigadoi, Sabrina; Lancia, Stefania; Petracca, Andrea; Spezialetti, Matteo; Ferrari, Marco; Placidi, Giuseppe; Quaresima, Valentina

2016-06-01

Objective. In the last few years, the interest in applying virtual reality systems for neurorehabilitation is increasing. Their compatibility with neuroimaging techniques, such as functional near-infrared spectroscopy (fNIRS), allows for the investigation of brain reorganization with multimodal stimulation and real-time control of the changes occurring in brain activity. The present study was aimed at testing a novel semi-immersive visuo-motor task (VMT), which has the features of being adopted in the field of neurorehabilitation of the upper limb motor function. Approach. A virtual environment was simulated through a three-dimensional hand-sensing device (the LEAP Motion Controller), and the concomitant VMT-related prefrontal cortex (PFC) response was monitored non-invasively by fNIRS. Upon the VMT, performed at three different levels of difficulty, it was hypothesized that the PFC would be activated with an expected greater level of activation in the ventrolateral PFC (VLPFC), given its involvement in the motor action planning and in the allocation of the attentional resources to generate goals from current contexts. Twenty-one subjects were asked to move their right hand/forearm with the purpose of guiding a virtual sphere over a virtual path. A twenty-channel fNIRS system was employed for measuring changes in PFC oxygenated-deoxygenated hemoglobin (O2Hb/HHb, respectively). Main results. A VLPFC O2Hb increase and a concomitant HHb decrease were observed during the VMT performance, without any difference in relation to the task difficulty. Significance. The present study has revealed a particular involvement of the VLPFC in the execution of the novel proposed semi-immersive VMT adoptable in the neurorehabilitation field.

A novel semi-immersive virtual reality visuo-motor task activates ventrolateral prefrontal cortex: a functional near-infrared spectroscopy study.

PubMed

Moro, Sara Basso; Carrieri, Marika; Avola, Danilo; Brigadoi, Sabrina; Lancia, Stefania; Petracca, Andrea; Spezialetti, Matteo; Ferrari, Marco; Placidi, Giuseppe; Quaresima, Valentina

2016-06-01

In the last few years, the interest in applying virtual reality systems for neurorehabilitation is increasing. Their compatibility with neuroimaging techniques, such as functional near-infrared spectroscopy (fNIRS), allows for the investigation of brain reorganization with multimodal stimulation and real-time control of the changes occurring in brain activity. The present study was aimed at testing a novel semi-immersive visuo-motor task (VMT), which has the features of being adopted in the field of neurorehabilitation of the upper limb motor function. A virtual environment was simulated through a three-dimensional hand-sensing device (the LEAP Motion Controller), and the concomitant VMT-related prefrontal cortex (PFC) response was monitored non-invasively by fNIRS. Upon the VMT, performed at three different levels of difficulty, it was hypothesized that the PFC would be activated with an expected greater level of activation in the ventrolateral PFC (VLPFC), given its involvement in the motor action planning and in the allocation of the attentional resources to generate goals from current contexts. Twenty-one subjects were asked to move their right hand/forearm with the purpose of guiding a virtual sphere over a virtual path. A twenty-channel fNIRS system was employed for measuring changes in PFC oxygenated-deoxygenated hemoglobin (O2Hb/HHb, respectively). A VLPFC O2Hb increase and a concomitant HHb decrease were observed during the VMT performance, without any difference in relation to the task difficulty. The present study has revealed a particular involvement of the VLPFC in the execution of the novel proposed semi-immersive VMT adoptable in the neurorehabilitation field.

PSD-Zip70 Deficiency Causes Prefrontal Hypofunction Associated with Glutamatergic Synapse Maturation Defects by Dysregulation of Rap2 Activity.

PubMed

Mayanagi, Taira; Yasuda, Hiroki; Sobue, Kenji

2015-10-21

Dysregulation of synapse formation and plasticity is closely related to the pathophysiology of psychiatric and neurodevelopmental disorders. The prefrontal cortex (PFC) is particularly important for executive functions such as working memory, cognition, and emotional control, which are impaired in the disorders. PSD-Zip70 (Lzts1/FEZ1) is a postsynaptic density (PSD) protein predominantly expressed in the frontal cortex, olfactory bulb, striatum, and hippocampus. Here we found that PSD-Zip70 knock-out (PSD-Zip70KO) mice exhibit working memory and cognitive defects, and enhanced anxiety-like behaviors. These abnormal behaviors are caused by impaired glutamatergic synapse transmission accompanied by tiny-headed immature dendritic spines in the PFC, due to aberrant Rap2 activation, which has roles in synapse formation and plasticity. PSD-Zip70 modulates the Rap2 activity by interacting with SPAR (spine-associated RapGAP) and PDZ-GEF1 (RapGEF) in the postsynapse. Furthermore, suppression of the aberrant Rap2 activation in the PFC rescued the behavioral defects in PSD-Zip70KO mice. Our data demonstrate a critical role for PSD-Zip70 in Rap2-dependent spine synapse development in the PFC and underscore the importance of this regulation in PFC-dependent behaviors. PSD-Zip70 deficiency causes behavioral defects in working memory and cognition, and enhanced anxiety due to prefrontal hypofunction. This study revealed that PSD-Zip70 plays essential roles in glutamatergic synapse maturation via modulation of the Rap2 activity in the PFC. PSD-Zip70 interacts with both SPAR (spine-associated RapGAP) and PDZ-GEF1 (RapGEF) and modulates the Rap2 activity in postsynaptic sites. Our results provide a novel Rap2-specific regulatory mechanism in synaptic maturation involving PSD-Zip70. Copyright © 2015 the authors 0270-6474/15/3514327-14$15.00/0.

Working memory and prefrontal/temporal hemodynamic responses during post-task period in patients with schizophrenia: A multi-channel near-infrared spectroscopy study.