Monkey Prefrontal Neurons Reflect Logical Operations for Cognitive Control in a Variant of the AX Continuous Performance Task (AX-CPT)

PubMed Central

Blackman, Rachael K.; Crowe, David A.; DeNicola, Adele L.; Sakellaridi, Sofia; MacDonald, Angus W.

2016-01-01

Cognitive control is the ability to modify the behavioral response to a stimulus based on internal representations of goals or rules. We sought to characterize neural mechanisms in prefrontal cortex associated with cognitive control in a context that would maximize the potential for future translational relevance to human neuropsychiatric disease. To that end, we trained monkeys to perform a dot-pattern variant of the AX continuous performance task that is used to measure cognitive control impairment in patients with schizophrenia (MacDonald, 2008; Jones et al., 2010). Here we describe how information processing for cognitive control in this task is related to neural activity patterns in prefrontal cortex of monkeys, to advance our understanding of how behavioral flexibility is implemented by prefrontal neurons in general, and to model neural signals in the healthy brain that may be disrupted to produce cognitive control deficits in schizophrenia. We found that the neural representation of stimuli in prefrontal cortex is strongly biased toward stimuli that inhibit prepotent or automatic responses. We also found that population signals encoding different stimuli were modulated to overlap in time specifically in the case that information from multiple stimuli had to be integrated to select a conditional response. Finally, population signals relating to the motor response were biased toward less frequent and therefore less automatic actions. These data relate neuronal activity patterns in prefrontal cortex to logical information processing operations required for cognitive control, and they characterize neural events that may be disrupted in schizophrenia. SIGNIFICANCE STATEMENT Functional imaging studies have demonstrated that cognitive control deficits in schizophrenia are associated with reduced activation of the dorsolateral prefrontal cortex (MacDonald et al., 2005). However, these data do not reveal how the disease has disrupted the function of prefrontal neurons to produce the observed deficits in cognitive control. Relating cognitive control to neurophysiological signals at a cellular level in prefrontal cortex is a necessary first step toward understanding how disruption of these signals could lead to cognitive control failure in neuropsychiatric disease. To that end, we translated a task that measures cognitive control deficits in patients with schizophrenia to monkeys and describe here how neural signals in prefrontal cortex relate to performance. PMID:27053213

The BOLD Response during Stroop Task-Like Inhibition Paradigms: Effects of Task Difficulty and Task-Relevant Modality

ERIC Educational Resources Information Center

Mitchell, Rachel L. C.

2005-01-01

Previous studies of the Stroop task propose two key mediators: the prefrontal and cingulate cortices but hints exist of functional specialization within these regions. This study aimed to examine the effect of task modality upon the prefrontal and cingulate response by examining the response to colour, number, and shape Stroop tasks whilst BOLD…

Social cognition and prefrontal hemodynamic responses during a working memory task in schizophrenia.

PubMed

Pu, Shenghong; Nakagome, Kazuyuki; Yamada, Takeshi; Itakura, Masashi; Yamanashi, Takehiko; Yamada, Sayaka; Masai, Mieko; Miura, Akihiko; Yamauchi, Takahira; Satake, Takahiro; Iwata, Masaaki; Nagata, Izumi; Roberts, David L; Kaneko, Koichi

2016-03-01

Social cognition is an important determinant of functional impairment in schizophrenia, but its relationship with the prefrontal functional abnormalities associated with the condition is still unclear. The present study aimed to explore the relationship between social cognition and prefrontal function in patients with schizophrenia using 52-channel near-infrared spectroscopy (NIRS). Twenty-six patients with schizophrenia and 26 age-, gender-, and intelligence quotient-matched healthy controls (HCs) participated in the study. Hemodynamic responses in the prefrontal and superior temporal cortical regions were assessed during a working memory task using NIRS. Social cognition was assessed using the Social Cognition Screening Questionnaire (SCSQ). The observed hemodynamic responses were significantly reduced in the lateral prefrontal cortex (PFC), the frontopolar cortex, and temporal regions in subjects with schizophrenia compared to HCs. Additionally, lateral PFC hemodynamic responses assessed during the working memory task demonstrated a strong positive correlation with the SCSQ theory of mind (ToM) subscale score even after controlling for working memory performance. These results suggest that ToM integrity is closely related to lateral PFC functional abnormalities found in patients with schizophrenia. In addition, this study provides evidence to suggest that NIRS could be used to identify biomarkers of social cognition function in subjects with schizophrenia.

Action control is mediated by prefrontal BDNF and glucocorticoid receptor binding.

PubMed

Gourley, Shannon L; Swanson, Andrew M; Jacobs, Andrea M; Howell, Jessica L; Mo, Michelle; Dileone, Ralph J; Koleske, Anthony J; Taylor, Jane R

2012-12-11

Stressor exposure biases decision-making strategies from those based on the relationship between actions and their consequences to others restricted by stimulus-response associations. Chronic stressor exposure also desensitizes glucocorticoid receptors (GR) and diminishes motivation to acquire food reinforcement, although causal relationships are largely not established. We show that a history of chronic exposure to the GR ligand corticosterone or acute posttraining GR blockade with RU38486 makes rodents less able to perform actions based on their consequences. Thus, optimal GR binding is necessary for the consolidation of new response-outcome learning. In contrast, medial prefrontal (but not striatal) BDNF can account for stress-related amotivation, in that selective medial prefrontal cortical Bdnf knockdown decreases break-point ratios in a progressive-ratio task. Knockdown also increases vulnerability to RU38486. Despite the role of BDNF in dendritic spine reorganization, deep-layer spine remodeling does not obviously parallel progressive-ratio response patterns, but treatment with the Na(+)-channel inhibitor riluzole reverses corticosteroid-induced motivational deficits and restores prefrontal BDNF expression after corticosterone. We argue that when prefrontal neurotrophin systems are compromised, and GR-mediated hypothalamic-pituitary-adrenal axis feedback is desensitized (as in the case of chronic stress hormone exposure), amotivation and inflexible maladaptive response strategies that contribute to stress-related mood disorders result.

Incremental rate of prefrontal oxygenation determines performance speed during cognitive Stroop test: the effect of ageing.

PubMed

Endo, Kana; Liang, Nan; Idesako, Mitsuhiro; Ishii, Kei; Matsukawa, Kanji

2018-02-19

Cognitive function declines with age. The underlying mechanisms responsible for the deterioration of cognitive performance, however, remain poorly understood. We hypothesized that an incremental rate of prefrontal oxygenation during a cognitive Stroop test decreases in progress of ageing, resulting in a slowdown of cognitive performance. To test this hypothesis, we identified, using multichannel near-infrared spectroscopy, the characteristics of the oxygenated-hemoglobin concentration (Oxy-Hb) responses of the prefrontal cortex to both incongruent Stroop and congruent word-reading test. Spatial distributions of the significant changes in the three components (initial slope, peak amplitude, and area under the curve) of the Oxy-Hb response were compared between young and elderly subjects. The Stroop interference time (as a difference in total periods for executing Stroop and word-reading test, respectively) approximately doubled in elderly as compared to young subjects. The Oxy-Hb in the rostrolateral, but not caudal, prefrontal cortex increased during the Stroop test in both age groups. The initial slope of the Oxy-Hb response, rather than the peak and area under the curve, had a strong correlation with cognitive performance speed. Taken together, it is likely that the incremental rate of prefrontal oxygenation may decrease in progress of ageing, resulting in a decline in cognitive performance.

Extinction Circuits for Fear and Addiction Overlap in Prefrontal Cortex

ERIC Educational Resources Information Center

Peters, Jamie; Kalivas, Peter W.; Quirk, Gregory J.

2009-01-01

Extinction is a form of inhibitory learning that suppresses a previously conditioned response. Both fear and drug seeking are conditioned responses that can lead to maladaptive behavior when expressed inappropriately, manifesting as anxiety disorders and addiction, respectively. Recent evidence indicates that the medial prefrontal cortex (mPFC) is…

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.

Single-Trial Regression Elucidates the Role of Prefrontal Theta Oscillations in Response Conflict

PubMed Central

Cohen, Michael X; Cavanagh, James F.

2011-01-01

In most cognitive neuroscience experiments there are many behavioral and experimental dynamics, and many indices of brain activity, that vary from trial to trial. For example, in studies of response conflict, conflict is usually treated as a binary variable (i.e., response conflict exists or does not in any given trial), whereas some evidence and intuition suggests that conflict may vary in intensity from trial to trial. Here we demonstrate that single-trial multiple regression of time–frequency electrophysiological activity reveals neural mechanisms of cognitive control that are not apparent in cross-trial averages. We also introduce a novel extension to oscillation phase coherence and synchronization analyses, based on “weighted” phase modulation, that has advantages over standard coherence measures in terms of linking electrophysiological dynamics to trial-varying behavior and experimental variables. After replicating previous response conflict findings using trial-averaged data, we extend these findings using single-trial analytic methods to provide novel evidence for the role of medial frontal–lateral prefrontal theta-band synchronization in conflict-induced response time dynamics, including a role for lateral prefrontal theta-band activity in biasing response times according to perceptual conflict. Given that these methods shed new light on the prefrontal mechanisms of response conflict, they are also likely to be useful for investigating other neurocognitive processes. PMID:21713190

Operant Conditioning of Primate Prefrontal Neurons

PubMed Central

Schultz, Wolfram; Sakagami, Masamichi

2010-01-01

An operant is a behavioral act that has an impact on the environment to produce an outcome, constituting an important component of voluntary behavior. Because the environment can be volatile, the same action may cause different consequences. Thus to obtain an optimal outcome, it is crucial to detect action–outcome relationships and adapt the behavior accordingly. Although prefrontal neurons are known to change activity depending on expected reward, it remains unknown whether prefrontal activity contributes to obtaining reward. We investigated this issue by setting variable relationships between levels of single-neuron activity and rewarding outcomes. Lateral prefrontal neurons changed their spiking activity according to the specific requirements for gaining reward, without the animals making a motor response. Thus spiking activity constituted an operant response. Data from a control task suggested that these changes were unlikely to reflect simple reward predictions. These data demonstrate a remarkable capacity of prefrontal neurons to adapt to specific operant requirements at the single-neuron level. PMID:20107129

Empirical Evaluation of Visual Fatigue from Display Alignment Errors Using Cerebral Hemodynamic Responses

PubMed Central

Wiyor, Hanniebey D.; Ntuen, Celestine A.

2013-01-01

The purpose of this study was to investigate the effect of stereoscopic display alignment errors on visual fatigue and prefrontal cortical tissue hemodynamic responses. We collected hemodynamic data and perceptual ratings of visual fatigue while participants performed visual display tasks on 8 ft × 6 ft NEC LT silver screen with NEC LT 245 DLP projectors. There was statistical significant difference between subjective measures of visual fatigue before air traffic control task (BATC) and after air traffic control task (ATC 3), (P < 0.05). Statistical significance was observed between left dorsolateral prefrontal cortex oxygenated hemoglobin (l DLPFC-HbO2), left dorsolateral prefrontal cortex deoxygenated hemoglobin (l DLPFC-Hbb), and right dorsolateral prefrontal cortex deoxygenated hemoglobin (r DLPFC-Hbb) on stereoscopic alignment errors (P < 0.05). Thus, cortical tissue oxygenation requirement in the left hemisphere indicates that the effect of visual fatigue is more pronounced in the left dorsolateral prefrontal cortex. PMID:27006917

Reward-Based Learning Drives Rapid Sensory Signals in Medial Prefrontal Cortex and Dorsal Hippocampus Necessary for Goal-Directed Behavior.

PubMed

Le Merre, Pierre; Esmaeili, Vahid; Charrière, Eloïse; Galan, Katia; Salin, Paul-A; Petersen, Carl C H; Crochet, Sylvain

2018-01-03

The neural circuits underlying learning and execution of goal-directed behaviors remain to be determined. Here, through electrophysiological recordings, we investigated fast sensory processing across multiple cortical areas as mice learned to lick a reward spout in response to a brief deflection of a single whisker. Sensory-evoked signals were absent from medial prefrontal cortex and dorsal hippocampus in naive mice, but developed with task learning and correlated with behavioral performance in mice trained in the detection task. The sensory responses in medial prefrontal cortex and dorsal hippocampus occurred with short latencies of less than 50 ms after whisker deflection. Pharmacological and optogenetic inactivation of medial prefrontal cortex or dorsal hippocampus impaired behavioral performance. Neuronal activity in medial prefrontal cortex and dorsal hippocampus thus appears to contribute directly to task performance, perhaps providing top-down control of learned, context-dependent transformation of sensory input into goal-directed motor output. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Shed a light in fatigue detection with near-infrared spectroscopy during long-lasting driving

NASA Astrophysics Data System (ADS)

Gao, Yuan; Pan, Boan; Li, Kai; Li, Ting

2016-03-01

Fatigue driving is one of the leading roles to induce traffic accident and injury, which urgently desires a novel technique to monitor the fatigue level at driving. Functional near infrared spectroscopy (fNIRS) is capable of noninvasive monitoring brain-activities-related hemodynamic responses. Here, we developed a fINRS imager and setup a classic psychological experiment to trigger visual divided attention which varied responding to driving fatigue, and attempted to record the drive-fatigue-level correlated hemodynamic response in the prefrontal cortex. 7 volunteers were recruited to take 7 hours driving and the experimental test was repeated every 1 hour and 8 times in total. The hemodynamic response were extracted and graphed with pseudo image. The analysis on the relationship between the fNIRS-measured hemodynamic response and fatigue level finally displayed that the oxyhemoglobin concentration in one channel of left prefrontal lobe increased with driving duration in significant correlation. And the spatial pattern of hemodynamic response in the prefrontal lobe varied with driving duration as well. The findings indicated the potential of fNIRSmeasured hemodynamic index in some sensitive spot of prefrontal lobe as a driving fatigue indicator and the promising use of fNIRS in traffic safety field.

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.

Task alters category representations in prefrontal but not high-level visual cortex.

PubMed

Bugatus, Lior; Weiner, Kevin S; Grill-Spector, Kalanit

2017-07-15

A central question in neuroscience is how cognitive tasks affect category representations across the human brain. Regions in lateral occipito-temporal cortex (LOTC), ventral temporal cortex (VTC), and ventro-lateral prefrontal cortex (VLFPC) constitute the extended "what" pathway, which is considered instrumental for visual category processing. However, it is unknown (1) whether distributed responses across LOTC, VTC, and VLPFC explicitly represent category, task, or some combination of both, and (2) in what way representations across these subdivisions of the extended 'what' pathway may differ. To fill these gaps in knowledge, we scanned 12 participants using fMRI to test the effect of category and task on distributed responses across LOTC, VTC, and VLPFC. Results reveal that task and category modulate responses in both high-level visual regions, as well as prefrontal cortex. However, we found fundamentally different types of representations across the brain. Distributed responses in high-level visual regions are more strongly driven by category than task, and exhibit task-independent category representations. In contrast, distributed responses in prefrontal cortex are more strongly driven by task than category, and contain task-dependent category representations. Together, these findings of differential representations across the brain support a new idea that LOTC and VTC maintain stable category representations allowing efficient processing of visual information, while prefrontal cortex contains flexible representations in which category information may emerge only when relevant to the task. Copyright © 2017 Elsevier Inc. All rights reserved.

Prefrontal cortex activation during obstacle negotiation: What's the effect size and timing?

PubMed

Maidan, Inbal; Shustak, Shiran; Sharon, Topaz; Bernad-Elazari, Hagar; Geffen, Nimrod; Giladi, Nir; Hausdorff, Jeffrey M; Mirelman, Anat

2018-04-01

Obstacle negotiation is a daily activity that requires the integration of sensorimotor and cognitive information. Recent studies provide evidence for the important role of prefrontal cortex during obstacle negotiation. We aimed to explore the effects of obstacle height and available response time on prefrontal activation. Twenty healthy young adults (age: 30.1 ± 1.0 years; 50% women) walked in an obstacle course while negotiating anticipated and unanticipated obstacles at heights of 50 mm and 100 mm. Prefrontal activation was measured using a functional near-infrared spectroscopy system. Kinect cameras measured the obstacle negotiation strategy. Prefrontal activation was defined based on mean level of HbO 2 before, during and after obstacle negotiation and the HbO 2 slope from gait initiation and throughout the task. Changes between types of obstacles were assessed using linear-mix models and partial correlation analyses evaluated the relationship between prefrontal activation and the distance between the feet as the subjects traversed the obstacles. Different obstacle heights showed similar changes in prefrontal activation measures (p > 0.210). However, during unanticipated obstacles, the slope of the HbO 2 response was steeper (p = 0.048), as compared to anticipated obstacles. These changes in prefrontal activation during negotiation of unanticipated obstacles were correlated with greater distance of the leading foot after the obstacles (r = 0.831, p = 0.041). These findings are the first to show that the pattern of prefrontal activation depends on the nature of the obstacle. More specifically, during unanticipated obstacles the recruitment of the prefrontal cortex is faster and greater than during negotiating anticipated obstacles. These results provide evidence of the important role of the prefrontal cortex and the ability of healthy young adults to tailor the activation pattern to different types of obstacles. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

The role of the prefrontal cortex in controlling gender-stereotypical associations: a TMS investigation.

PubMed

Cattaneo, Zaira; Mattavelli, Giulia; Platania, Elisa; Papagno, Costanza

2011-06-01

Stereotypes associated with gender, race, ethnicity and religion are powerful forces in human social interactions. Previous neuroimaging and neuropsychological studies point to a role of the prefrontal cortex in controlling stereotypical responses. Here we used transcranial magnetic stimulation (TMS) in combination with an Implicit Association Test (IAT) to highlight the possible causal role of the left dorsolateral prefrontal cortex (DLPFC) and the right anterior dorsomedial prefrontal cortex (aDMPFC) in controlling gender-stereotypical responses. Young male and female participants were tested. Our results showed that applying TMS over the left DLPFC and the right aDMPFC increased the gender-stereotypical bias in male participants compared to when TMS was applied to a control site (vertex). This suggests that both the left DLPFC and the right aDMPFC play a direct role in stereotyping. Females did not show a significant gender bias on the IAT; correspondingly their responses were unaffected by TMS. Copyright © 2011 Elsevier Inc. All rights reserved.

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

Effects of electrical stimulation of the lateral aspect of the prefrontal cortex upon attack behavior in cats.

PubMed

Siegel, A; Edinger, H; Dotto, M

1975-08-15

An experiment was performed to determine the role of the lateral aspect of the prefrontal cortex upon quiet biting attack behavior elicited from the hypothalamus in the cat. The results of this experiment indicate that stimulation of 19 of 28 electrode sites sampled in the lateral prefrontal cortex produced a statistically significant inhibition of attack behavior elicited from the hypothalamus of the ipsilateral side. Stimulation of sites in the prefrontal cortex on the side contralateral to the hypothalamus from which attack was elicited had no effect upon this response. No systematic effect of prefrontal stimulation upon flight behavior was observed. Anatomical studies suggest that the lateral prefrontal cortex may inhibit attack behavior by modulating neurons in either the mediodorsal thalamic nucleus or ventral tegmental area.

The Medial Prefrontal Cortex Is Critical for Memory Retrieval and Resolving Interference

ERIC Educational Resources Information Center

Peters, Gregory J.; David, Christopher N.; Marcus, Madison D.; Smith, David M.

2013-01-01

The prefrontal cortex (PFC) is known to be critically involved in strategy switching, attentional set shifting, and inhibition of prepotent responses. A central feature of this kind of behavioral flexibility is the ability to resolve conflicting response tendencies, suggesting a general role of the PFC in resolving interference. If so, the PFC…

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. PMID:25071482

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

Converging evidence for the association of functional genetic variation in the serotonin receptor 2a gene with prefrontal function and olanzapine treatment.

PubMed

Blasi, Giuseppe; De Virgilio, Caterina; Papazacharias, Apostolos; Taurisano, Paolo; Gelao, Barbara; Fazio, Leonardo; Ursini, Gianluca; Sinibaldi, Lorenzo; Andriola, Ileana; Masellis, Rita; Romano, Raffaella; Rampino, Antonio; Di Giorgio, Annabella; Lo Bianco, Luciana; Caforio, Grazia; Piva, Francesco; Popolizio, Teresa; Bellantuono, Cesario; Todarello, Orlando; Kleinman, Joel E; Gadaleta, Gemma; Weinberger, Daniel R; Bertolino, Alessandro

2013-09-01

Serotonin (5-hydroxytryptamine) receptor 2a (5-HT2AR) signaling is important for modulation of corticostriatal pathways and prefrontal activity during cognition. Furthermore, newer antipsychotic drugs target 5-HT2AR. A single-nucleotide polymorphism in the 5-HT2AR gene (HTR2A rs6314, C>T; OMIM 182135) has been weakly associated with differential 5-HT2AR signaling and with physiologic as well as behavioral effects. To use a hierarchical approach to determine the functional effects of this single-nucleotide polymorphism on 5-HT2AR messenger RNA and protein expression, on prefrontal phenotypes linked with genetic risk for schizophrenia, and on treatment with olanzapine. In silico predictions, in vitro, and case-control investigations. Academic and clinical facilities. The postmortem study included 112 brains from healthy individuals; the in vivo investigation included a total sample of 371 healthy individuals and patients with schizophrenia. EXPOSURES Patients received olanzapine monotherapy for 8 weeks. In silico predictions, messenger RNA, and protein expression in postmortem human prefrontal cortex and HeLa cells, functional magnetic resonance imaging prefrontal activity and behavior during working memory and attention in healthy individuals, and response to an 8-week trial of olanzapine treatment in patients with schizophrenia. Bioinformatic analysis predicted that rs6314 alters patterns of splicing, with possible effects on HTR2A expression. Moreover, the T allele was associated with reduced prefrontal messenger RNA expression in postmortem prefrontal cortex, with reduced protein expression in vitro, inefficient prefrontal blood oxygen level-dependent functional magnetic resonance imaging response during working memory and attentional control processing, and impaired working memory and attention behavior, as well as with attenuated improvement in negative symptoms after olanzapine treatment. Our results suggest that HTR2A rs6314 affects 5-HT2AR expression and functionally contributes to genetic modulation of known endophenotypes of schizophrenia-like higher-level cognitive behaviors and related prefrontal activity, as well as response to treatment with olanzapine.

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.

Long-Term Citalopram Treatment Alters the Stress Responses of the Cortical Dopamine and Noradrenaline Systems: the Role of Cortical 5-HT1A Receptors

PubMed Central

Kaneko, Fumi; Kishikawa, Yuki; Hanada, Yuuki; Yamada, Makiko; Kakuma, Tatsuyuki; Kawahara, Hiroshi; Nishi, Akinori

2016-01-01

Background: Cortical dopamine and noradrenaline are involved in the stress response. Citalopram, a selective serotonin reuptake inhibitor, has direct and indirect effects on the serotonergic system. Furthermore, long-term treatment with citalopram affects the dopamine and noradrenaline systems, which could contribute to the therapeutic action of antidepressants. Methods: The effects of long-term treatment with citalopram on the responses of the dopamine and noradrenaline systems in the rat prefrontal cortex to acute handling stress were evaluated using in vivo microdialysis. Results: Acute handling stress increased dopamine and noradrenaline levels in the prefrontal cortex. The dopamine and noradrenaline responses were suppressed by local infusion of a 5-HT1A receptor agonist, 7-(Dipropylamino)-5,6,7,8-tetrahydronaphthalen-1-ol;hydrobromide, into the prefrontal cortex. The dopamine response was abolished by long-term treatment with citalopram, and the abolished dopamine response was reversed by local infusion of a 5-HT1A receptor antagonist, (Z)-but-2-enedioic acid;N-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-pyridin-2-ylcyclohexanecarboxamide into the prefrontal cortex. On the other hand, long-term treatment with citalopram reduced the basal noradrenaline levels (approximately 40% of the controls), but not the basal dopamine levels. The noradrenaline response was maintained despite the low basal noradrenaline levels. Signaling from the 5-HT1A receptors and α2-adrenoceptors was not involved in the decrease in the basal noradrenaline levels but partially affected the noradrenaline response. Conclusions: Chronic citalopram treatment differentially suppresses the dopamine and noradrenaline systems in the prefrontal cortex, and the dopamine stress response was preferentially controlled by upregulating 5-HT1A receptor signaling. Our findings provide insight into how antidepressants modulate the dopamine and noradrenaline systems to overcome acute stress. PMID:27029212

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.

Medial Prefrontal Cortex Is Selectively Involved in Response Selection Using Visual Context in the Background

ERIC Educational Resources Information Center

Lee, Inah; Shin, Ji Yun

2012-01-01

The exact roles of the medial prefrontal cortex (mPFC) in conditional choice behavior are unknown and a visual contextual response selection task was used for examining the issue. Inactivation of the mPFC severely disrupted performance in the task. mPFC inactivations, however, did not disrupt the capability of perceptual discrimination for visual…

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.

Alcohol Attenuates Load-related Activation During a Working Memory Task: Relation to Level of Response to Alcohol

PubMed Central

Paulus, Martin P.; Tapert, Susan F.; Pulido, Carmen; Schuckit, Marc A.

2008-01-01

Background A low level of response to alcohol is a major risk factor for the development of alcohol dependence, but neural correlates of this marker are unclear. Method Ten healthy volunteers were classified by median split on level of response to alcohol and underwent 2 sessions of functional magnetic resonance imaging following ingestion of a moderate dose of alcohol and a placebo. The blood oxygen level–dependent activation to an event-related visual working memory test was examined. Results The subjects exhibited longer response latencies and more errors as a function of increasing working memory load and showed a load-dependent increase in activation in dorsolateral prefrontal cortex, posterior parietal cortex, and visual cortex. Alcohol did not affect performance (errors or response latency), but attenuated the working memory load–dependent activation in the dorsolateral prefrontal cortex. During the placebo condition, individuals with a low level of response to alcohol showed greater activation in dorsolateral prefrontal cortex and posterior parietal cortex than those with a high level of response to alcohol. During the alcohol condition, groups showed similar attenuation of load-dependent brain activation in these regions. Conclusion Low-level responders relative to high-level responders exhibited an increased working memory load–dependent activation in dorsolateral prefrontal cortex and posterior parietal cortex when not exposed to alcohol. This increase in brain response was attenuated in low-level responders after ingesting a moderate dose of alcohol. PMID:16899039

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.

Neurobiological mechanisms underlying the blocking effect in aversive learning.

PubMed

Eippert, Falk; Gamer, Matthias; Büchel, Christian

2012-09-19

Current theories of classical conditioning assume that learning depends on the predictive relationship between events, not just on their temporal contiguity. Here we employ the classic experiment substantiating this reasoning-the blocking paradigm-in combination with functional magnetic resonance imaging (fMRI) to investigate whether human amygdala responses in aversive learning conform to these assumptions. In accordance with blocking, we demonstrate that significantly stronger behavioral and amygdala responses are evoked by conditioned stimuli that are predictive of the unconditioned stimulus than by conditioned stimuli that have received the same pairing with the unconditioned stimulus, yet have no predictive value. When studying the development of this effect, we not only observed that it was related to the strength of previous conditioned responses, but also that predictive compared with nonpredictive conditioned stimuli received more overt attention, as measured by fMRI-concurrent eye tracking, and that this went along with enhanced amygdala responses. We furthermore observed that prefrontal regions play a role in the development of the blocking effect: ventromedial prefrontal cortex (subgenual anterior cingulate) only exhibited responses when conditioned stimuli had to be established as nonpredictive for an outcome, whereas dorsolateral prefrontal cortex also showed responses when conditioned stimuli had to be established as predictive. Most importantly, dorsolateral prefrontal cortex connectivity to amygdala flexibly switched between positive and negative coupling, depending on the requirements posed by predictive relationships. Together, our findings highlight the role of predictive value in explaining amygdala responses and identify mechanisms that shape these responses in human fear conditioning.

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.

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.

Control over Conflict during Movement Preparation: Role of Posterior Parietal Cortex

PubMed Central

Coulthard, Elizabeth J.; Nachev, Parashkev; Husain, Masud

2008-01-01

Summary Flexible behavior in humans often requires that rapid choices be made between conflicting action plans. Although much attention has focused on prefrontal regions, little is understood about the contribution of parietal cortex under situations of response conflict. Here we show that right parietal damage associated with spatial neglect leads to paradoxical facilitation (speeding) of rightward movements in the presence of conflicting leftward response plans. These findings indicate a critical role for parietal regions in action planning when there is response competition. In contrast, patients with prefrontal damage have an augmented cost of conflict for both leftward and rightward movements. The results suggest involvement of two independent systems in situations of response conflict, with right parietal cortex being a crucial site for automatic activation of competing motor plans and prefrontal regions acting independently to inhibit action plans irrelevant to current task goals. PMID:18400170

Risk-dependent reward value signal in human prefrontal cortex

PubMed Central

Tobler, Philippe N.; Christopoulos, George I.; O'Doherty, John P.; Dolan, Raymond J.; Schultz, Wolfram

2009-01-01

When making choices under uncertainty, people usually consider both the expected value and risk of each option, and choose the one with the higher utility. Expected value increases the expected utility of an option for all individuals. Risk increases the utility of an option for risk-seeking individuals, but decreases it for risk averse individuals. In 2 separate experiments, one involving imperative (no-choice), the other choice situations, we investigated how predicted risk and expected value aggregate into a common reward signal in the human brain. Blood oxygen level dependent responses in lateral regions of the prefrontal cortex increased monotonically with increasing reward value in the absence of risk in both experiments. Risk enhanced these responses in risk-seeking participants, but reduced them in risk-averse participants. The aggregate value and risk responses in lateral prefrontal cortex contrasted with pure value signals independent of risk in the striatum. These results demonstrate an aggregate risk and value signal in the prefrontal cortex that would be compatible with basic assumptions underlying the mean-variance approach to utility. PMID:19369207

Changes of the Prefrontal EEG (Electroencephalogram) Activities According to the Repetition of Audio-Visual Learning.

ERIC Educational Resources Information Center

Kim, Yong-Jin; Chang, Nam-Kee

2001-01-01

Investigates the changes of neuronal response according to a four time repetition of audio-visual learning. Obtains EEG data from the prefrontal (Fp1, Fp2) lobe from 20 subjects at the 8th grade level. Concludes that the habituation of neuronal response shows up in repetitive audio-visual learning and brain hemisphericity can be changed by…

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

Striatal dopamine D2 receptor availability predicts the thalamic and medial prefrontal responses to reward in cocaine abusers three years later

DOE Office of Scientific and Technical Information (OSTI.GOV)

Asensio, S.; Goldstein, R.; Asensio, S.

Low levels of dopamine (DA) D2 receptor availability at a resting baseline have been previously reported in drug addicted individuals and have been associated with reduced ventral and dorsal prefrontal metabolism. The reduction in DA D2 receptor availability along with the reduced ventral frontal metabolism is thought to underlie compromised sensitivity to nondrug reward, a core characteristic of drug addiction. We therefore hypothesized that variability in DA D2 receptor availability at baseline will covary with dynamic responses to monetary reward in addicted individuals. Striatal DA D2 receptor availability was measured with [{sup 11}C]raclopride and positron emission tomography and response tomore » monetary reward was measured (an average of three years later) with functional magnetic resonance imaging in seven cocaine-addicted individuals. Results show that low DA D2 receptor availability in the dorsal striatum was associated with decreased thalamic response to monetary reward; while low availability in ventral striatum was associated with increased medial prefrontal (Brodmann Area 6/8/32) response to monetary reward. These preliminary results, that need to be replicated in larger sample sizes and validated with healthy controls, suggest that resting striatal DA D2 receptor availability predicts variability in functional responses to a nondrug reinforcer (money) in prefrontal cortex, implicated in behavioral monitoring, and in thalamus, implicated in conditioned responses and expectation, in cocaine-addicted individuals.« less

Striatal dopamine D2 receptor availability predicts the thalamic and medial prefrontal responses to reward in cocaine abusers three years later

PubMed Central

Asensio, Samuel; Romero, Maria J.; Romero, Francisco J.; Wong, Christopher; Alia-Klein, Nelly; Tomasi, Dardo; Wang, Gene-Jack; Telang, Frank; Volkow, Nora D.; Goldstein, Rita Z.

2009-01-01

Low levels of dopamine (DA) D2 receptor availability at a resting baseline have been previously reported in drug addicted individuals and have been associated with reduced ventral and dorsal prefrontal metabolism. The reduction in DA D2 receptor availability along with the reduced ventral frontal metabolism is thought to underlie compromised sensitivity to non-drug reward, a core characteristic of drug addiction. We therefore hypothesized that variability in DA D2 receptor availability at baseline will covary with dynamic responses to monetary reward in addicted individuals. Striatal DA D2 receptor availability was measured with [11C]raclopride and positron emission tomography and response to monetary reward was measured (an average of 3 years later) with functional magnetic resonance imaging in seven cocaine addicted individuals. Results show that low DA D2 receptor availability in the dorsal striatum was associated with decreased thalamic response to monetary reward; while low availability in ventral striatum was associated with increased medial prefrontal (Brodmann Area 6/8/32) response to monetary reward. These preliminary results, that need to be replicated in larger sample sizes and validated with healthy controls, suggest that resting striatal DA D2 receptor availability predicts variability in functional responses to a non-drug reinforcer (money) in prefrontal cortex, implicated in behavioral monitoring, and in thalamus, implicated in conditioned responses and expectation, in cocaine addicted individuals. PMID:20034014

Affective context interferes with cognitive control in unipolar depression: An fMRI investigation

PubMed Central

Dichter, Gabriel S.; Felder, Jennifer N.; Smoski, Moria J.

2009-01-01

Background Unipolar major depressive disorder (MDD) is characterized by aberrant amygdala responses to sad stimuli and poor cognitive control, but the interactive effects of these impairments are poorly understood. Aim To evaluate brain activation in MDD in response to cognitive control stimuli embedded within sad and neutral contexts. Method Fourteen adults with MDD and fifteen matched controls participated in a mixed block/event-related functional magnetic resonance imaging (fMRI) task that presented oddball target stimuli embedded within blocks of sad or neutral images. Results Target events activated similar prefrontal brain regions in both groups. However, responses to target events embedded within blocks of emotional images revealed a clear group dissociation. During neutral blocks, the control group demonstrated greater activation to targets in the midfrontal gyrus and anterior cingulate relative to the MDD group, replicating previous findings of prefrontal hypo-activation in MDD samples to cognitive control stimuli. However, during sad blocks, the MDD group demonstrated greater activation in a number of prefrontal regions, including the mid-, inferior, and orbito-frontal gyri and the anterior cingulate, suggesting that relatively more prefrontal brain activation was required to disengage from the sad images to respond to the target events. Limitations A larger sample size would have provided greater statistical power, and more standardized stimuli would have increased external validity. Conclusions This double dissociation of prefrontal responses to target events embedded within neutral and sad context suggests that MDD impacts not only responses to affective events, but extends to other cognitive processes carried out in the context of affective engagement. This implies that emotional reactivity to sad events in MDD may impact functioning more broadly than previously understood. PMID:18706701

Differences in executive functioning between violent and non-violent offenders.

PubMed

Meijers, J; Harte, J M; Meynen, G; Cuijpers, P

2017-07-01

A growing body of neuropsychological and neurobiological research shows a relationship between functioning of the prefrontal cortex and criminal and violent behaviour. The prefrontal cortex is crucial for executive functions such as inhibition, attention, working memory, set-shifting and planning. A deficit in these functions - a prefrontal deficit - may result in antisocial, impulsive or even aggressive behaviour. While several meta-analyses show large effect sizes for the relationship between a prefrontal deficit, executive dysfunction and criminality, there are few studies investigating differences in executive functions between violent and non-violent offenders. Considering the relevance of identifying risk factors for violent offending, the current study explores whether a distinction between violent and non-violent offenders can be made using an extensive neuropsychological test battery. Male remand prisoners (N = 130) in Penitentiary Institution Amsterdam Over-Amstel were administered an extensive neuropsychological test battery (Cambridge Automated Neuropsychological Test Battery; CANTAB) measuring response inhibition, planning, attention, set-shifting, working memory and impulsivity/reward sensitivity. Violent offenders performed significantly worse on the stop-signal task (partial correlation r = 0.205, p = 0.024), a task measuring response inhibition. No further differences were found between violent and non-violent offenders. Explorative analyses revealed a significant relationship between recidivism and planning (partial correlation r = -0.209, p = 0.016). Violent offenders show worse response inhibition compared to non-violent offenders, suggesting a more pronounced prefrontal deficit in violent offenders than in non-violent offenders.

Prolonged hemodynamic response during incidental facial emotion processing in inter-episode bipolar I disorder.

PubMed

Rosenfeld, Ethan S; Pearlson, Godfrey D; Sweeney, John A; Tamminga, Carol A; Keshavan, Matcheri S; Nonterah, Camilla; Stevens, Michael C

2014-03-01

This fMRI study examined whether hemodynamic responses to affectively-salient stimuli were abnormally prolonged in remitted bipolar disorder, possibly representing a novel illness biomarker. A group of 18 DSM-IV bipolar I-diagnosed adults in remission and a demographically-matched control group performed an event-related fMRI gender-discrimination task in which face stimuli had task-irrelevant neutral, happy or angry expressions designed to elicit incidental emotional processing. Participants' brain activation was modeled using a "fully informed" SPM5 basis set. Mixed-model ANOVA tested for diagnostic group differences in BOLD response amplitude and shape within brain regions-of-interest selected from ALE meta-analysis of previous comparable fMRI studies. Bipolar-diagnosed patients had a generally longer duration and/or later-peaking hemodynamic response in amygdala and numerous prefrontal cortex brain regions. Data are consistent with existing models of bipolar limbic hyperactivity, but the prolonged frontolimbic response more precisely details abnormalities recognized in previous studies. Prolonged hemodynamic responses were unrelated to stimulus type, task performance, or degree of residual mood symptoms, suggesting an important novel trait vulnerability brain dysfunction in bipolar disorder. Bipolar patients also failed to engage pregenual cingulate and left orbitofrontal cortex-regions important to models of automatic emotion regulation-while engaging a delayed dorsolateral prefrontal cortex response not seen in controls. These results raise questions about whether there are meaningful relationships between bipolar dysfunction of specific ventromedial prefrontal cortex regions believed to automatically regulate emotional reactions and the prolonged responses in more lateral aspects of prefrontal cortex.

Emotional eating and routine restraint scores are associated with activity in brain regions involved in urge and self-control.

PubMed

Wood, Samantha M W; Schembre, Susan M; He, Qinghua; Engelmann, Jeffrey M; Ames, Susan L; Bechara, Antoine

2016-10-15

Researchers have proposed a variety of behavioral traits that may lead to weight gain and obesity; however, little is known about the neurocognitive mechanisms underlying these weight-related eating behaviors. In this study, we measured activation of reward circuitry during a task requiring response and inhibition to food stimuli. We assessed participants' emotional eating, external eating, and two subscales of dietary restraint-routine restraint and compensatory restraint-using the Weight-Related Eating Questionnaire. For routine restraint, we found positive associations with activation in the insula, dorsolateral prefrontal cortex, anterior cingulate cortex, orbitofrontal cortex and ventromedial prefrontal cortex in response to high-calorie versus low-calorie foods. For emotional eating, we found positive associations with insula and dorsolateral prefrontal cortex activation in response to high-calorie versus low-calorie foods. We also found positive associations between emotional eating and dorsolateral prefrontal cortex activation in response to approach versus inhibition towards high-calorie foods. Thus, our results demonstrate an increase in activation across brain regions related to self-control and urges in response to high-calorie food associated with both emotional eating and routine restraint. Overall, these results support the construct validity of both emotional eating and routine restraint and provide preliminary evidence that these subscales have similar neural correlates. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Novelty response of rats determines the effect of prefrontal alpha-2 adrenoceptor modulation on anxiety.

PubMed

Uzsoki, B; Tóth, M; Hernádi, I

2011-07-25

In this study we provide evidence that animals of the same population, although identical in age and sex, have individual reactions to the prefrontal modulation of adrenoceptors. We have examined the dose-dependent action of α(2)-adrenoceptor agents on the anxiety of rats with different response to novelty in the elevated plus maze (EPM) apparatus. Rats were divided into high (HR) and low responder (LR) groups based on their locomotor activity in a novel open field environment. HR rats also showed increased locomotion and low anxiety in the EPM. Prefrontal injection of α(2)-receptor antagonist yohimbine, BRL44408 or imiloxan caused anxiety only in HR rats. The α(2A/D)-receptor agonist guanfacine increased anxiety levels of both groups. However, the effective dose was lower in HR rats. The present results propose different prefrontal adrenoceptor sensitivity of rats showing distinct baseline activity levels. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Integration of faces and vocalizations in ventral prefrontal cortex: Implications for the evolution of audiovisual speech

PubMed Central

Romanski, Lizabeth M.

2012-01-01

The integration of facial gestures and vocal signals is an essential process in human communication and relies on an interconnected circuit of brain regions, including language regions in the inferior frontal gyrus (IFG). Studies have determined that ventral prefrontal cortical regions in macaques [e.g., the ventrolateral prefrontal cortex (VLPFC)] share similar cytoarchitectonic features as cortical areas in the human IFG, suggesting structural homology. Anterograde and retrograde tracing studies show that macaque VLPFC receives afferents from the superior and inferior temporal gyrus, which provide complex auditory and visual information, respectively. Moreover, physiological studies have shown that single neurons in VLPFC integrate species-specific face and vocal stimuli. Although bimodal responses may be found across a wide region of prefrontal cortex, vocalization responsive cells, which also respond to faces, are mainly found in anterior VLPFC. This suggests that VLPFC may be specialized to process and integrate social communication information, just as the IFG is specialized to process and integrate speech and gestures in the human brain. PMID:22723356

Response disengagement on a spatial self-ordered sequencing task: effects of regionally selective excitotoxic lesions and serotonin depletion within the prefrontal cortex.

PubMed

Walker, Susannah C; Robbins, Trevor W; Roberts, Angela C

2009-05-06

Prefrontal cortex (PFC) is critical for self-ordered response sequencing. Patients with frontal lobe damage are impaired on response sequencing tasks, and increased blood flow has been reported in ventrolateral and dorsolateral PFC in subjects performing such tasks. Previously, we have shown that large excitotoxic lesions of the lateral PFC (LPFC) and orbitofrontal cortex FC (OFC), but not global prefrontal dopamine depletion, markedly impaired marmoset performance on a spatial self-ordered sequencing task (SSOST). To determine whether LPFC or OFC was responsible for the previously observed impairments and whether the underlying neural mechanism was modulated by serotonin, the present study compared the effects of selective LPFC and OFC excitotoxic lesions and 5,7-DHT-induced PFC serotonin depletions in marmosets on SSOST performance. Severe and long-lasting impairments in SSOST performance, including robust perseverative responding, followed LPFC but not OFC lesions. The deficit was ameliorated by task manipulations that precluded perseveration. Depletions of serotonin within LPFC and OFC had no effect, despite impairing performance on a visual discrimination reversal task, thus providing further evidence for differential monaminergic regulation of prefrontal function. In the light of the proposed attentional control functions of ventrolateral PFC and the failure of LPFC-lesioned animals to disengage from the immediately preceding response, it is proposed that this deficit may be due to a failure to attend to and register that a response has been made and thus should not be repeated. However, 5-HT does not appear to be implicated in this response inhibitory capacity.

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.

Auditory mismatch impairments are characterized by core neural dysfunctions in schizophrenia

PubMed Central

Gaebler, Arnim Johannes; Mathiak, Klaus; Koten, Jan Willem; König, Andrea Anna; Koush, Yury; Weyer, David; Depner, Conny; Matentzoglu, Simeon; Edgar, James Christopher; Willmes, Klaus; Zvyagintsev, Mikhail

2015-01-01

Major theories on the neural basis of schizophrenic core symptoms highlight aberrant salience network activity (insula and anterior cingulate cortex), prefrontal hypoactivation, sensory processing deficits as well as an impaired connectivity between temporal and prefrontal cortices. The mismatch negativity is a potential biomarker of schizophrenia and its reduction might be a consequence of each of these mechanisms. In contrast to the previous electroencephalographic studies, functional magnetic resonance imaging may disentangle the involved brain networks at high spatial resolution and determine contributions from localized brain responses and functional connectivity to the schizophrenic impairments. Twenty-four patients and 24 matched control subjects underwent functional magnetic resonance imaging during an optimized auditory mismatch task. Haemodynamic responses and functional connectivity were compared between groups. These data sets further entered a diagnostic classification analysis to assess impairments on the individual patient level. In the control group, mismatch responses were detected in the auditory cortex, prefrontal cortex and the salience network (insula and anterior cingulate cortex). Furthermore, mismatch processing was associated with a deactivation of the visual system and the dorsal attention network indicating a shift of resources from the visual to the auditory domain. The patients exhibited reduced activation in all of the respective systems (right auditory cortex, prefrontal cortex, and the salience network) as well as reduced deactivation of the visual system and the dorsal attention network. Group differences were most prominent in the anterior cingulate cortex and adjacent prefrontal areas. The latter regions also exhibited a reduced functional connectivity with the auditory cortex in the patients. In the classification analysis, haemodynamic responses yielded a maximal accuracy of 83% based on four features; functional connectivity data performed similarly or worse for up to about 10 features. However, connectivity data yielded a better performance when including more than 10 features yielding up to 90% accuracy. Among others, the most discriminating features represented functional connections between the auditory cortex and the anterior cingulate cortex as well as adjacent prefrontal areas. Auditory mismatch impairments incorporate major neural dysfunctions in schizophrenia. Our data suggest synergistic effects of sensory processing deficits, aberrant salience attribution, prefrontal hypoactivation as well as a disrupted connectivity between temporal and prefrontal cortices. These deficits are associated with subsequent disturbances in modality-specific resource allocation. Capturing different schizophrenic core dysfunctions, functional magnetic resonance imaging during this optimized mismatch paradigm reveals processing impairments on the individual patient level, rendering it a potential biomarker of schizophrenia. PMID:25743635

The role of the dorsomedial part of the prefrontal cortex serotonergic innervation in rat responses to the aversively conditioned context: behavioral, biochemical and immunocytochemical studies.

PubMed

Lehner, Małgorzata; Taracha, Ewa; Turzyńska, Danuta; Sobolewska, Alicja; Hamed, Adam; Kołomańska, Paulina; Skórzewska, Anna; Maciejak, Piotr; Szyndler, Janusz; Bidziński, Andrzej; Płaźnik, Adam

2008-10-10

In this study we have explored differences in animal reactivity to conditioned aversive stimuli using the conditioned fear test (a contextual fear-freezing response), in rats subjected to the selective lesion of the prefrontal cortex serotonergic innervation, and differing in their response to the acute painful stimulation, a footshock (HS--high sensitivity rats, and LS--low sensitivity rats, selected arbitrarily according to their behavior in the 'flinch-jump' pre-test). Local administration of serotonergic neurotoxin (5,7-dihydroxytryptamine) to the dorsomedial part of the prefrontal cortex caused a very strong, structure and neurotransmitter selective depletion of serotonin concentration. In HS rats, the serotonergic lesion significantly disinhibited rat behavior controlled by fear, enhanced c-Fos expression in the dorsomedial prefrontal area, and increased the concentration of GABA in the basolateral amygdala, measured in vivo after the testing session of the conditioned fear test. The LS animals revealed an opposite pattern of behavioral and biochemical changes after serotonergic lesion: an increase in the duration of a freezing response, and expression of c-Fos in the basolateral and central nuclei of amygdala, and a lower GABA concentration in the basolateral amygdala. In control conditions, c-Fos expression did not differ in LS and HS, naïve, not conditioned and not exposed to the test cage animals. The present study adds more arguments for the controlling role of serotonergic innervation of the dorsomedial part of the prefrontal cortex in processing emotional input by other brain centers. Moreover, it provides experimental data, which may help to better explain the anatomical and biochemical basis of differences in individual reactivity to stressful stimulation, and, possibly, to anxiolytic drugs with serotonergic or GABAergic profiles of action.

The toxic influence of dibromoacetic acid on the hippocampus and pre-frontal cortex of rat: involvement of neuroinflammation response and oxidative stress.

PubMed

Jiang, Wenbo; Li, Bai; Chen, Yingying; Gao, Shuying

2017-12-01

Dibromoacetic acid (DBA) exsits in drinking water as a by-product of disinfection as a result of chlorination or ozonation processes. Hippocampus and pre-frontal cortex are the key structures in memory formation and weanling babies are more sensitive to environmental toxicant than adults, so this study was conducted to evaluate the potential neurotoxicity effects of DBA exposure when administered intragastrically for 4 weeks to weanling Sprague-Dawley rats, at concentration of 0, 20, 50, 125 mg/kg via the neurobehavioral and neurochemical effects. Results indicated that animals weight gain and food consumption were not significantly affected by DBA. However, morris water maze test showed varying degrees of changes between control and high-dose group. Additionally, the level of malondialdehyde (MDA) and generation of reactive oxygen species (ROS) in the hippocampus and pre-frontal cortex of rats increased significantly. The activities of total superoxide dismutase (SOD) and the glutathione (GSH) content in the hippocampus and pre-frontal cortex of rats decreased significantly after treatment with DBA. Treatment with DBA increased the protein and mRNA expression of Iba-1, NF-κB, TNF-α, IL-6, IL-1β and HO-1 in the hippocampus and pre-frontal cortex of rats. These data suggested that DBA had a toxic influence on the hippocampus and pre-frontal cortex of rats, and that the mechanism of toxicity might be associated with the neuroinflammation response and oxidative stress.

An information-processing model of three cortical regions: evidence in episodic memory retrieval.

PubMed

Sohn, Myeong-Ho; Goode, Adam; Stenger, V Andrew; Jung, Kwan-Jin; Carter, Cameron S; Anderson, John R

2005-03-01

ACT-R (Anderson, J.R., et al., 2003. An information-processing model of the BOLD response in symbol manipulation tasks. Psychon. Bull. Rev. 10, 241-261) relates the inferior dorso-lateral prefrontal cortex to a retrieval buffer that holds information retrieved from memory and the posterior parietal cortex to an imaginal buffer that holds problem representations. Because the number of changes in a problem representation is not necessarily correlated with retrieval difficulties, it is possible to dissociate prefrontal-parietal activations. In two fMRI experiments, we examined this dissociation using the fan effect paradigm. Experiment 1 compared a recognition task, in which representation requirement remains the same regardless of retrieval difficulty, with a recall task, in which both representation and retrieval loads increase with retrieval difficulty. In the recognition task, the prefrontal activation revealed a fan effect but not the parietal activation. In the recall task, both regions revealed fan effects. In Experiment 2, we compared visually presented stimuli and aurally presented stimuli using the recognition task. While only the prefrontal region revealed the fan effect, the activation patterns in the prefrontal and the parietal region did not differ by stimulus presentation modality. In general, these results provide support for the prefrontal-parietal dissociation in terms of retrieval and representation and the modality-independent nature of the information processed by these regions. Using ACT-R, we also provide computational models that explain patterns of fMRI responses in these two areas during recognition and recall.

Role of Prefrontal Serotonergic and Dopaminergic Systems in Encounter-Induced Hyperactivity in Methamphetamine-Sensitized Mice.

PubMed

Tanaka, Tatsunori; Ago, Yukio; Umehara, Chiaki; Imoto, Emina; Hasebe, Shigeru; Hashimoto, Hitoshi; Takuma, Kazuhiro; Matsuda, Toshio

2017-05-01

Isolation-reared mice show social encounter-induced hyperactivity with activation of prefrontal serotonergic and dopaminergic systems, but it is not known whether this stress response is observed in other pathological conditions. Here we examined whether the social encounter stimulation induces abnormal behavior during withdrawal in chronic methamphetamine-treated mice. To induce methamphetamine-induced behavioral sensitization, male mice were injected with methamphetamine (1 mg/kg) once daily for 7 days. The encounter with an intruder elicited hyperactivity 24 h after the last injection of methamphetamine in methamphetamine-sensitized mice. This response was observed even as long as 2 weeks after withdrawal of methamphetamine. The encounter increased c-Fos expression in the prefrontal cortex, dorsal raphe nucleus and ventral tegmental area in methamphetamine-sensitized mice, while it did not in control mice. Furthermore, the encounter increased extracellular serotonin (5-HT) and dopamine, but not noradrenaline, levels in the prefrontal cortex in methamphetamine-sensitized mice. Local injection of 5,7-dihydroxytryptamine and 6-hydroxydopamine into the prefrontal cortex attenuated encounter-induced hyperactivity in methamphetamine-sensitized mice and it markedly decreased prefrontal 5-HT and dopamine levels, respectively. Pharmacological analysis showed that the encounter-induced hyperactivity is mediated by dopamine D1 receptors and 5-HT2A receptors and attenuated by anxiolytics and antidepressants such as diazepam, osemozotan and selective 5-HT reuptake inhibitors. The effect of paroxetine was blocked by the 5-HT3 receptor antagonist azasetron. The present study shows that psychological stress elicits hyperactivity with activation of prefrontal 5-HT and dopamine systems in methamphetamine-dependent mice and suggests that the abnormal behavior is associated with anxiety and depression. © The Author 2016. Published by Oxford University Press on behalf of CINP.

Preschool Anxiety Disorders Predict Different Patterns of Amygdala-Prefrontal Connectivity at School-Age

PubMed Central

Carpenter, Kimberly L. H.; Angold, Adrian; Chen, Nan-Kuei; Copeland, William E.; Gaur, Pooja; Pelphrey, Kevin; Song, Allen W.; Egger, Helen L.

2015-01-01

Objective In this prospective, longitudinal study of young children, we examined whether a history of preschool generalized anxiety, separation anxiety, and/or social phobia is associated with amygdala-prefrontal dysregulation at school-age. As an exploratory analysis, we investigated whether distinct anxiety disorders differ in the patterns of this amygdala-prefrontal dysregulation. Methods Participants were children taking part in a 5-year study of early childhood brain development and anxiety disorders. Preschool symptoms of generalized anxiety, separation anxiety, and social phobia were assessed with the Preschool Age Psychiatric Assessment (PAPA) in the first wave of the study when the children were between 2 and 5 years old. The PAPA was repeated at age 6. We conducted functional MRIs when the children were 5.5 to 9.5 year old to assess neural responses to viewing of angry and fearful faces. Results A history of preschool social phobia predicted less school-age functional connectivity between the amygdala and the ventral prefrontal cortices to angry faces. Preschool generalized anxiety predicted less functional connectivity between the amygdala and dorsal prefrontal cortices in response to fearful faces. Finally, a history of preschool separation anxiety predicted less school-age functional connectivity between the amygdala and the ventral prefrontal cortices to angry faces and greater school-age functional connectivity between the amygdala and dorsal prefrontal cortices to angry faces. Conclusions Our results suggest that there are enduring neurobiological effects associated with a history of preschool anxiety, which occur over-and-above the effect of subsequent emotional symptoms. Our results also provide preliminary evidence for the neurobiological differentiation of specific preschool anxiety disorders. PMID:25625285

Applying Neurodevelopmental Theory to School-Based Drug Misuse Prevention during Adolescence

ERIC Educational Resources Information Center

Riggs, Nathaniel R.; Black, David S.; Ritt-Olson, Anamara

2014-01-01

Adolescence is characterized by incredible development in the prefrontal cortex of the brain, which is responsible for behavioral and emotional self-regulation, and higher order cognitive decision-making skills (that is, executive function). Typically late prefrontal cortical development and its integration with limbic areas of the brain…

Impairment of working memory maintenance and response in schizophrenia: functional magnetic resonance imaging evidence.

PubMed

Driesen, Naomi R; Leung, Hoi-Chung; Calhoun, Vincent D; Constable, R Todd; Gueorguieva, Ralitza; Hoffman, Ralph; Skudlarski, Pawel; Goldman-Rakic, Patricia S; Krystal, John H

2008-12-15

Comparing prefrontal cortical activity during particular phases of working memory in healthy subjects and individuals diagnosed with schizophrenia might help to define the phase-specific deficits in cortical function that contribute to cognitive impairments associated with schizophrenia. This study featured a spatial working memory task, similar to that used in nonhuman primates, that was designed to facilitate separating brain activation into encoding, maintenance, and response phases. Fourteen patients with schizophrenia (4 medication-free) and 12 healthy comparison participants completed functional magnetic resonance imaging while performing a spatial working memory task with two levels of memory load. Task accuracy was similar in patients and healthy participants. However, patients showed reductions in brain activation during maintenance and response phases but not during the encoding phase. The reduced prefrontal activity during the maintenance phase of working memory was attributed to a greater rate of decay of prefrontal activity over time in patients. Cortical deficits in patients did not appear to be related to antipsychotic treatment. In patients and in healthy subjects, the time-dependent reduction in prefrontal activity during working memory maintenance correlated with poorer performance on the memory task. Overall, these data highlight that basic research insights into the distinct neurobiologies of the maintenance and response phases of working memory are of potential importance for understanding the neurobiology of cognitive impairment in schizophrenia and advancing its treatment.

Attention to Multiple Objects Facilitates Their Integration in Prefrontal and Parietal Cortex.

PubMed

Kim, Yee-Joon; Tsai, Jeffrey J; Ojemann, Jeffrey; Verghese, Preeti

2017-05-10

Selective attention is known to interact with perceptual organization. In visual scenes, individual objects that are distinct and discriminable may occur on their own, or in groups such as a stack of books. The main objective of this study is to probe the neural interaction that occurs between individual objects when attention is directed toward one or more objects. Here we record steady-state visual evoked potentials via electrocorticography to directly assess the responses to individual stimuli and to their interaction. When human participants attend to two adjacent stimuli, prefrontal and parietal cortex shows a selective enhancement of only the neural interaction between stimuli, but not the responses to individual stimuli. When only one stimulus is attended, the neural response to that stimulus is selectively enhanced in prefrontal and parietal cortex. In contrast, early visual areas generally manifest responses to individual stimuli and to their interaction regardless of attentional task, although a subset of the responses is modulated similarly to prefrontal and parietal cortex. Thus, the neural representation of the visual scene as one progresses up the cortical hierarchy becomes more highly task-specific and represents either individual stimuli or their interaction, depending on the behavioral goal. Attention to multiple objects facilitates an integration of objects akin to perceptual grouping. SIGNIFICANCE STATEMENT Individual objects in a visual scene are seen as distinct entities or as parts of a whole. Here we examine how attention to multiple objects affects their neural representation. Previous studies measured single-cell or fMRI responses and obtained only aggregate measures that combined the activity to individual stimuli as well as their potential interaction. Here, we directly measure electrocorticographic steady-state responses corresponding to individual objects and to their interaction using a frequency-tagging technique. Attention to two stimuli increases the interaction component that is a hallmark for perceptual integration of stimuli. Furthermore, this stimulus-specific interaction is represented in prefrontal and parietal cortex in a task-dependent manner. Copyright © 2017 the authors 0270-6474/17/374942-12$15.00/0.

Auditory inhibitory gating in medial prefrontal cortex: Single unit and local field potential analysis.

PubMed

Mears, R P; Klein, A C; Cromwell, H C

2006-08-11

Medial prefrontal cortex is a crucial region involved in inhibitory processes. Damage to the medial prefrontal cortex can lead to loss of normal inhibitory control over motor, sensory, emotional and cognitive functions. The goal of the present study was to examine the basic properties of inhibitory gating in this brain region in rats. Inhibitory gating has recently been proposed as a neurophysiological assay for sensory filters in higher brain regions that potentially enable or disable information throughput. This perspective has important clinical relevance due to the findings that gating is dramatically impaired in individuals with emotional and cognitive impairments (i.e. schizophrenia). We used the standard inhibitory gating two-tone paradigm with a 500 ms interval between tones and a 10 s interval between tone pairs. We recorded both single unit and local field potentials from chronic microwire arrays implanted in the medial prefrontal cortex. We investigated short-term (within session) and long-term (between session) variability of auditory gating and additionally examined how altering the interval between the tones influenced the potency of the inhibition. The local field potentials displayed greater variability with a reduction in the amplitudes of the tone responses over both the short and long-term time windows. The decrease across sessions was most intense for the second tone response (test tone) leading to a more robust gating (lower T/C ratio). Surprisingly, single unit responses of different varieties retained similar levels of auditory responsiveness and inhibition in both the short and long-term analysis. Neural inhibition decreased monotonically related to the increase in intertone interval. This change in gating was most consistent in the local field potentials. Subsets of single unit responses did not show the lack of inhibition even for the longer intertone intervals tested (4 s interval). These findings support the idea that the medial prefrontal cortex is an important site where early inhibitory functions reside and potentially mediate psychological processes.

Induction of genomic instability in TK6 human lymphoblasts exposed to 137Cs gamma radiation: comparison to the induction by exposure to accelerated 56Fe particles

NASA Technical Reports Server (NTRS)

Evans, Helen H.; Horng, Min-Fen; Ricanati, Marlene; Diaz-Insua, M.; Jordan, Robert; Schwartz, Jeffrey L.

2003-01-01

The induction of genomic instability in TK6 human lymphoblasts by exposure to (137)Cs gamma radiation was investigated by measuring the frequency and characteristics of unstable clones isolated approximately 36 generations after exposure. Clones surviving irradiation and control clones were analyzed for 17 characteristics including chromosomal aberrations, growth defects, alterations in response to a second irradiation, and mutant frequencies at the thymidine kinase and Na(+)/K(+) ATPase loci. Putative unstable clones were defined as those that exhibited a significant alteration in one or more characteristics compared to the controls. The frequency and characteristics of the unstable clones were compared in clones exposed to (137)Cs gamma rays or (56)Fe particles. The majority of the unstable clones isolated after exposure to either gamma rays or (56)Fe particles exhibited chromosomal instability. Alterations in growth characteristics, radiation response and mutant frequencies occurred much less often than cytogenetic alterations in these unstable clones. The frequency and complexity of the unstable clones were greater after exposure to (56)Fe particles than to gamma rays. Unstable clones that survived 36 generations after exposure to gamma rays exhibited increases in the incidence of dicentric chromosomes but not of chromatid breaks, whereas unstable clones that survived 36 generations after exposure to (56)Fe particles exhibited increases in both chromatid and chromosome aberrations.

Projection-free approximate balanced truncation of large unstable systems

NASA Astrophysics Data System (ADS)

Flinois, Thibault L. B.; Morgans, Aimee S.; Schmid, Peter J.

2015-08-01

In this article, we show that the projection-free, snapshot-based, balanced truncation method can be applied directly to unstable systems. We prove that even for unstable systems, the unmodified balanced proper orthogonal decomposition algorithm theoretically yields a converged transformation that balances the Gramians (including the unstable subspace). We then apply the method to a spatially developing unstable system and show that it results in reduced-order models of similar quality to the ones obtained with existing methods. Due to the unbounded growth of unstable modes, a practical restriction on the final impulse response simulation time appears, which can be adjusted depending on the desired order of the reduced-order model. Recommendations are given to further reduce the cost of the method if the system is large and to improve the performance of the method if it does not yield acceptable results in its unmodified form. Finally, the method is applied to the linearized flow around a cylinder at Re = 100 to show that it actually is able to accurately reproduce impulse responses for more realistic unstable large-scale systems in practice. The well-established approximate balanced truncation numerical framework therefore can be safely applied to unstable systems without any modifications. Additionally, balanced reduced-order models can readily be obtained even for large systems, where the computational cost of existing methods is prohibitive.

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.

Neural Correlates of Response Inhibition and Cigarette Smoking in Late Adolescence

PubMed Central

Galván, Adriana; Poldrack, Russell A; Baker, Christine M; McGlennen, Kristine M; London, Edythe D

2011-01-01

Smoking is usually initiated in adolescence, and is the leading preventable cause of death in the United States. Little is known, however, about the links between smoking and neurobiological function in adolescent smokers. This study aimed to probe prefrontal cortical function in late adolescent smokers, using a response inhibition task, and to assess possible relationships between inhibition-related brain activity, clinical features of smoking behavior, and exposure to cigarette smoking. Participants in this study were otherwise healthy late adolescent smokers (15–21 years of age; n=25), who reported daily smoking for at least the 6 months before testing, and age- and education-matched nonsmokers (16–21 years of age; n=25), who each reported smoking fewer than five cigarettes in their lifetimes. The subjects performed the Stop-signal Task, while undergoing functional magnetic resonance imaging. There were no significant group differences in prefrontal cortical activity during response inhibition, but the Heaviness of Smoking Index, a measure of smoking behavior and dependence, was negatively related to neural function in cortical regions of the smokers. These findings suggest that smoking can modulate prefrontal cortical function. Given the late development of the prefrontal cortex, which continues through adolescence, it is possible that smoking may influence the trajectory of brain development during this critical developmental period. PMID:21270772

Test-retest reliability of the prefrontal response to affective pictures based on functional near-infrared spectroscopy

NASA Astrophysics Data System (ADS)

Huang, Yuxia; Mao, Mengchai; Zhang, Zong; Zhou, Hui; Zhao, Yang; Duan, Lian; Kreplin, Ute; Xiao, Xiang; Zhu, Chaozhe

2017-01-01

Functional near-infrared spectroscopy (fNIRS) is being increasingly applied to affective and social neuroscience research; however, the reliability of this method is still unclear. This study aimed to evaluate the test-retest reliability of the fNIRS-based prefrontal response to emotional stimuli. Twenty-six participants viewed unpleasant and neutral pictures, and were simultaneously scanned by fNIRS in two sessions three weeks apart. The reproducibility of the prefrontal activation map was evaluated at three spatial scales (mapwise, clusterwise, and channelwise) at both the group and individual levels. The influence of the time interval was also explored and comparisons were made between longer (intersession) and shorter (intrasession) time intervals. The reliabilities of the activation map at the group level for the mapwise (up to 0.88, the highest value appeared in the intersession assessment) and clusterwise scales (up to 0.91, the highest appeared in the intrasession assessment) were acceptable, indicating that fNIRS may be a reliable tool for emotion studies, especially for a group analysis and under larger spatial scales. However, it should be noted that the individual-level and the channelwise fNIRS prefrontal responses were not sufficiently stable. Future studies should investigate which factors influence reliability, as well as the validity of fNIRS used in emotion studies.

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.

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

Shifting brain inhibitory balance and connectivity of the prefrontal cortex of adults with autism spectrum disorder

PubMed Central

Ajram, L A; Horder, J; Mendez, M A; Galanopoulos, A; Brennan, L P; Wichers, R H; Robertson, D M; Murphy, C M; Zinkstok, J; Ivin, G; Heasman, M; Meek, D; Tricklebank, M D; Barker, G J; Lythgoe, D J; Edden, R A E; Williams, S C; Murphy, D G M; McAlonan, G M

2017-01-01

Currently, there are no effective pharmacologic treatments for the core symptoms of autism spectrum disorder (ASD). There is, nevertheless, potential for progress. For example, recent evidence suggests that the excitatory (E) glutamate and inhibitory (I) GABA systems may be altered in ASD. However, no prior studies of ASD have examined the ‘responsivity’ of the E–I system to pharmacologic challenge; or whether E–I modulation alters abnormalities in functional connectivity of brain regions implicated in the disorder. Therefore, we used magnetic resonance spectroscopy ([1H]MRS) to measure prefrontal E–I flux in response to the glutamate and GABA acting drug riluzole in adult men with and without ASD. We compared the change in prefrontal ‘Inhibitory Index’—the GABA fraction within the pool of glutamate plus GABA metabolites—post riluzole challenge; and the impact of riluzole on differences in resting-state functional connectivity. Despite no baseline differences in E–I balance, there was a significant group difference in response to pharmacologic challenge. Riluzole increased the prefrontal cortex inhibitory index in ASD but decreased it in controls. There was also a significant group difference in prefrontal functional connectivity at baseline, which was abolished by riluzole within the ASD group. Our results also show, for we believe the first time in ASD, that E–I flux can be ‘shifted’ with a pharmacologic challenge, but that responsivity is significantly different from controls. Further, our initial evidence suggests that abnormalities in functional connectivity can be ‘normalised’ by targeting E–I, even in adults. PMID:28534874

Guanfacine Modulates the Emotional Biasing of Amygdala-Prefrontal Connectivity for Cognitive Control

PubMed Central

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

2014-01-01

Functional interactions between amygdala and prefrontal cortex provide a cortical entry point for emotional cues to bias cognitive control. Stimulation of α2 adrenoceptors enhances the prefrontal control functions and blocks the amygdala-dependent encoding of emotional cues. However, the impact of this stimulation on amygdala-prefrontal interactions and the emotional biasing of cognitive control have not been established. We tested the effect of the α2 adrenoceptor agonist guanfacine on psychophysiological interactions of amygdala with prefrontal cortex for the emotional biasing of response execution and inhibition. Fifteen healthy adults were scanned twice with event-related functional magnetic resonance imaging while performing an emotional go/no-go task following administration of oral guanfacine (1 mg) and placebo in a double-blind, counterbalanced design. Happy, sad, and neutral faces served as trial cues. Guanfacine moderated the effect of face emotion on the task-related functional connectivity of left and right amygdala with left inferior frontal gyrus compared to placebo, by selectively reversing the functional co-activation of the two regions for response execution cued by sad faces. This shift from positively to negatively correlated activation for guanfacine was associated with selective improvements in the relatively low accuracy of responses to sad faces seen for placebo. These results demonstrate the importance of functional interactions between amygdala and inferior frontal gyrus to both bottom-up biasing of cognitive control and top-down control of emotional processing, as well as for the α2 adrenoceptor-mediated modulation of these processes. These mechanisms offer a possibile method to address the emotional reactivity that is common to several psychiatric disorders. PMID:25059532

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…

ALCOHOL AND THE PREFRONTAL CORTEX

PubMed Central

Abernathy, Kenneth; Chandler, L. Judson; Woodward, John J.

2013-01-01

The prefrontal cortex occupies the anterior portion of the frontal lobes and is thought to be one of the most complex anatomical and functional structures of the mammalian brain. Its major role is to integrate and interpret inputs from cortical and sub-cortical structures and use this information to develop purposeful responses that reflect both present and future circumstances. This includes both action-oriented sequences involved in obtaining rewards and inhibition of behaviors that pose undue risk or harm to the individual. Given the central role in initiating and regulating these often complex cognitive and behavioral responses, it is no surprise that alcohol has profound effects on the function of the prefrontal cortex. In this chapter, we review the basic anatomy and physiology of the prefrontal cortex and discuss what is known about the actions of alcohol on the function of this brain region. This includes a review of both the human and animal literature including information on the electrophysiological and behavioral effects that follow acute and chronic exposure to alcohol. The chapter concludes with a discussion of unanswered questions and areas needing further investigation. PMID:20813246

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.

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.

Brain signatures of moral sensitivity in adolescents with early social deprivation.

PubMed

Escobar, María Josefina; Huepe, David; Decety, Jean; Sedeño, Lucas; Messow, Marie Kristin; Baez, Sandra; Rivera-Rei, Álvaro; Canales-Johnson, Andrés; Morales, Juan Pablo; Gómez, David Maximiliano; Schröeder, Johannes; Manes, Facundo; López, Vladimir; Ibánez, Agustín

2014-06-19

The present study examined neural responses associated with moral sensitivity in adolescents with a background of early social deprivation. Using high-density electroencephalography (hdEEG), brain activity was measured during an intentional inference task, which assesses rapid moral decision-making regarding intentional or unintentional harm to people and objects. We compared the responses to this task in a socially deprived group (DG) with that of a control group (CG). The event-related potentials (ERPs) results showed atypical early and late frontal cortical markers associated with attribution of intentionality during moral decision-making in DG (especially regarding intentional harm to people). The source space of the hdEEG showed reduced activity for DG compared with CG in the right prefrontal cortex, bilaterally in the ventromedial prefrontal cortex (vmPFC), and right insula. Moreover, the reduced response in vmPFC for DG was predicted by higher rates of externalizing problems. These findings demonstrate the importance of the social environment in early moral development, supporting a prefrontal maturation model of social deprivation.

Integration of auditory and visual communication information in the primate ventrolateral prefrontal cortex.

PubMed

Sugihara, Tadashi; Diltz, Mark D; Averbeck, Bruno B; Romanski, Lizabeth M

2006-10-25

The integration of auditory and visual stimuli is crucial for recognizing objects, communicating effectively, and navigating through our complex world. Although the frontal lobes are involved in memory, communication, and language, there has been no evidence that the integration of communication information occurs at the single-cell level in the frontal lobes. Here, we show that neurons in the macaque ventrolateral prefrontal cortex (VLPFC) integrate audiovisual communication stimuli. The multisensory interactions included both enhancement and suppression of a predominantly auditory or a predominantly visual response, although multisensory suppression was the more common mode of response. The multisensory neurons were distributed across the VLPFC and within previously identified unimodal auditory and visual regions (O'Scalaidhe et al., 1997; Romanski and Goldman-Rakic, 2002). Thus, our study demonstrates, for the first time, that single prefrontal neurons integrate communication information from the auditory and visual domains, suggesting that these neurons are an important node in the cortical network responsible for communication.

Integration of Auditory and Visual Communication Information in the Primate Ventrolateral Prefrontal Cortex

PubMed Central

Sugihara, Tadashi; Diltz, Mark D.; Averbeck, Bruno B.; Romanski, Lizabeth M.

2009-01-01

The integration of auditory and visual stimuli is crucial for recognizing objects, communicating effectively, and navigating through our complex world. Although the frontal lobes are involved in memory, communication, and language, there has been no evidence that the integration of communication information occurs at the single-cell level in the frontal lobes. Here, we show that neurons in the macaque ventrolateral prefrontal cortex (VLPFC) integrate audiovisual communication stimuli. The multisensory interactions included both enhancement and suppression of a predominantly auditory or a predominantly visual response, although multisensory suppression was the more common mode of response. The multisensory neurons were distributed across the VLPFC and within previously identified unimodal auditory and visual regions (O’Scalaidhe et al., 1997; Romanski and Goldman-Rakic, 2002). Thus, our study demonstrates, for the first time, that single prefrontal neurons integrate communication information from the auditory and visual domains, suggesting that these neurons are an important node in the cortical network responsible for communication. PMID:17065454

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.

The association between cognitive deficits and prefrontal hemodynamic responses during performance of working memory task in patients with schizophrenia.

PubMed

Pu, Shenghong; Nakagome, Kazuyuki; Itakura, Masashi; Iwata, Masaaki; Nagata, Izumi; Kaneko, Koichi

2016-04-01

Schizophrenia-associated cognitive deficits are resistant to treatment and thus pose a lifelong burden. The Brief Assessment of Cognition in Schizophrenia (BACS) provides reliable and valid assessments across cognitive domains. However, because the prefrontal functional abnormalities specifically associated with the level of cognitive deficits in schizophrenia have not been examined, we explored this relationship. Patients with schizophrenia (N=87) and matched healthy controls (N=50) participated in the study. Using near-infrared spectroscopy (NIRS), we measured the hemodynamic responses in the prefrontal and superior temporal cortical surface areas during a working memory task. Correlation analyses revealed a relationship between the hemodynamics and the BACS composite and domain scores. Hemodynamic responses of the left dorsolateral prefrontal cortex (DLPFC) and left frontopolar cortex (FPC) in the higher-level-of-cognitive-function schizophrenia group were weaker than the responses of the controls but similar to those of the lower-level-of-cognitive-function schizophrenia group. However, hemodynamic responses in the right DLPFC, bilateral ventrolateral PFC (VLPFC), and right temporal regions decreased with increasing cognitive deficits. In addition, the hemodynamic response correlated positively with the level of cognitive function (BACS composite scores) in the right DLPFC, bilateral VLPFC, right FPC, and bilateral temporal regions in schizophrenia. The correlation was driven by all BACS domains. Our results suggest that the linked functional deficits in the right DLPFC, bilateral VLPFC, right FPC, and bilateral temporal regions may be related to BACS-measured cognitive impairments in schizophrenia and show that linking the neurocognitive deficits and brain abnormalities can increase our understanding of schizophrenia pathophysiology. Copyright © 2015 Elsevier B.V. All rights reserved.

Cerebral responses and role of the prefrontal cortex in conditioned pain modulation: an fMRI study in healthy subjects

PubMed Central

Bogdanov, Volodymyr B.; Viganò, Alessandro; Noirhomme, Quentin; Bogdanova, Olena V.; Guy, Nathalie; Laureys, Steven; Renshaw, Perry F.; Dallel, Radhouane; Phillips, Christophe; Schoenen, Jean

2017-01-01

The mechanisms underlying conditioned pain modulation (CPM) are multifaceted. We searched for a link between individual differences in prefrontal cortex activity during multi-trial heterotopic noxious cold conditioning and modulation of the cerebral response to phasic heat pain. In 24 healthy female subjects, we conditioned laser heat stimuli to the left hand by applying alternatively ice-cold or lukewarm compresses to the right foot. We compared pain ratings with cerebral fMRI BOLD responses. We also analyzed the relation between CPM and BOLD changes produced by the heterotopic cold conditioning itself, as well as the impact of anxiety and habituation of cold-pain ratings. Specific cerebral activation was identified in precuneus and left posterior insula/SII, respectively, during early and sustained phases of cold application. During cold conditioning, laser pain decreased (n = 7), increased (n = 10) or stayed unchanged (n = 7). At the individual level, the psychophysical effect was directly proportional to the cold-induced modulation of the laser-induced BOLD response in left posterior insula/SII. The latter correlated with the BOLD response recorded 80 s earlier during the initial 10-s phase of cold application in anterior cingulate, orbitofrontal and lateral prefrontal cortices. High anxiety and habituation of cold pain were associated with greater laser heat-induced pain during heterotopic cold stimulation. The habituation was also linked to the early cold-induced orbitofrontal responses. We conclude that individual differences in conditioned pain modulation are related to different levels of prefrontal cortical activation by the early part of the conditioning stimulus, possibly due to different levels in trait anxiety. PMID:25461267

Gender differences in brain activity generated by unpleasant word stimuli concerning body image: an fMRI study.

PubMed

Shirao, Naoko; Okamoto, Yasumasa; Mantani, Tomoyuki; Okamoto, Yuri; Yamawaki, Shigeto

2005-01-01

We have previously reported that the temporomesial area, including the amygdala, is activated in women when processing unpleasant words concerning body image. To detect gender differences in brain activation during processing of these words. Functional magnetic resonance imaging was used to investigate 13 men and 13 women during an emotional decision task consisting of unpleasant words concerning body image and neutral words. The left medial prefrontal cortex and hippocampus were activated only among men, and the left amygdala was activated only among women during the task; activation in the apical prefrontal region was significantly greater in men than in women. Our data suggest that the prefrontal region is responsible for the gender differences in the processing of words concerning body image, and may also be responsible for gender differences in susceptibility to eating disorders.

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 without dementia, some with no signs of dysfunction in tasks sensitive to other regions of prefrontal cortex. This demonstration of variability in cognitive integrity supports previous research indicating amyotrophic lateral sclerosis is a heterogeneous disease.

Anatomical insights into the interaction of emotion and cognition in the prefrontal cortex

PubMed Central

Ray, Rebecca; Zald, David H.

2011-01-01

Ray, R. and D. Zald. Anatomical insights into the interaction of emotion and cognition in the prefrontal cortex. NEUROSCI BIOBEHAV REV 36(X) XXX-XXX, 2011. -Psychological research increasingly indicates that emotional processes interact with other aspects of cognition. Studies have demonstrated both the ability of emotional stimuli to influence a broad range of cognitive operations, and the ability of humans to use top-down cognitive control mechanisms to regulate emotional responses. Portions of the prefrontal cortex appear to play a significant role in these interactions. However, the manner in which these interactions are implemented remains only partially elucidated. In the present review we describe the anatomical connections between ventral and dorsal prefrontal areas as well as their connections with limbic regions. Only a subset of prefrontal areas are likely to directly influence amygdalar processing, and as such models of prefrontal control of emotions and models of emotional regulation should be constrained to plausible pathways of influence. We also focus on how the specific pattern of feedforward and feedback connections between these regions may dictate the nature of information flow between ventral and dorsal prefrontal areas and the amygdala. These patterns of connections are inconsistent with several commonly expressed assumptions about the nature of communications between emotion and cognition. PMID:21889953

Prefrontal Norepinephrine Determines Attribution of “High” Motivational Salience

PubMed Central

Ventura, Rossella; Latagliata, Emanuele Claudio; Morrone, Cristina; La Mela, Immacolata; Puglisi-Allegra, Stefano

2008-01-01

Intense motivational salience attribution is considered to have a major role in the development of different psychopathologies. Numerous brain areas are involved in “normal” motivational salience attribution processes; however, it is not clear whether common or different neural mechanisms also underlie intense motivational salience attribution. To elucidate this a brain area and a neural system had to be envisaged that were involved only in motivational salience attribution to highly salient stimuli. Using intracerebral microdialysis, we found that natural stimuli induced an increase in norepinephrine release in the medial prefrontal cortex of mice proportional to their salience, and that selective prefrontal norepinephrine depletion abolished the increase of norepinephrine release in the medial prefrontal cortex induced by exposure to appetitive (palatable food) or aversive (light) stimuli independently of salience. However, selective norepinephrine depletion in the medial prefrontal cortex impaired the place conditioning induced exclusively by highly salient stimuli, thus indicating that prefrontal noradrenergic transmission determines approach or avoidance responses to both reward- and aversion-related natural stimuli only when the salience of the unconditioned natural stimulus is high enough to induce sustained norepinephrine outflow. This affirms that prefrontal noradrenergic transmission determines motivational salience attribution selectively when intense motivational salience is processed, as in conditions that characterize psychopathological outcomes. PMID:18725944

Threatening faces induce fear circuitry hypersynchrony in soldiers with post-traumatic stress disorder.

PubMed

Dunkley, Benjamin T; Pang, Elizabeth W; Sedge, Paul A; Jetly, Rakesh; Doesburg, Sam M; Taylor, Margot J

2016-01-01

Post-traumatic stress disorder (PTSD) is associated with atypical responses to emotional face stimuli with preferential processing given to threat-related facial expressions via hyperactive amygdalae disengaged from medial prefrontal modulation. We examined implicit emotional face perception in soldiers with (n = 20) and without (n = 25) PTSD using magnetoencephalography to define spatiotemporal network interactions, and a subsequent region-of-interest analysis to characterize the network role of the right amygdala and medial prefrontal cortex in threatening face perception. Contrasts of network interactions revealed the PTSD group were hyperconnected compared to controls in the phase-locking response in the 2-24 Hz range for angry faces, but not for happy faces when contrasting groups. Hyperconnectivity in PTSD was greatest in the posterior cingulate, right ventromedial prefrontal cortex, right parietal regions and the right temporal pole, as well as the right amygdala. Graph measures of right amygdala and medial prefrontal connectivity revealed increases in node strength and clustering in PTSD, but not inter-node connectivity. Additionally, these measures were found to correlate with anxiety and depression. In line with prior studies, amygdala hyperconnectivity was observed in PTSD in relation to threatening faces, but the medial prefrontal cortex also displayed enhanced connectivity in our network-based approach. Overall, these results support preferential neurophysiological encoding of threat-related facial expressions in those with PTSD.

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

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.

Atypical prefrontal cortical responses to joint/non-joint attention in children with autism spectrum disorder (ASD): A functional near-infrared spectroscopy study

PubMed Central

Zhu, Huilin; Li, Jun; Fan, Yuebo; Li, Xinge; Huang, Dan; He, Sailing

2015-01-01

Autism spectrum disorder (ASD) is a neuro-developmental disorder, characterized by impairments in one’s capacity for joint attention. In this study, functional near-infrared spectroscopy (fNIRS) was applied to study the differences in activation and functional connectivity in the prefrontal cortex between children with autism spectrum disorder (ASD) and typically developing (TD) children. 21 ASD and 20 TD children were recruited to perform joint and non-joint attention tasks. Compared with TD children, children with ASD showed reduced activation and atypical functional connectivity pattern in the prefrontal cortex during joint attention. The atypical development of left prefrontal cortex might play an important role in social cognition defects of children with ASD. PMID:25798296

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.

Tuning the Engine of Cognition: A Focus on NMDA/D1 Receptor Interactions in Prefrontal Cortex

ERIC Educational Resources Information Center

Castner, Stacy A.; Williams, Graham V.

2007-01-01

The prefrontal cortex of the primate frontal lobes provides the capacity for judgment which can constantly adapt behavior in order to optimize its outcome. Adjudicating between long-term memory programs and prepotent responses, this capacity reviews all incoming information and provides an interpretation dependent on the events that have just…

The Ventromedial Prefrontal Cortex in a Model of Traumatic Stress: Fear Inhibition or Contextual Processing?

ERIC Educational Resources Information Center

Pennington, Zachary T.; Anderson, Austin S.; Fanselow, Michael S.

2017-01-01

The ventromedial prefrontal cortex (vmPFC) has consistently appeared altered in post-traumatic stress disorder (PTSD). Although the vmPFC is thought to support the extinction of learned fear responses, several findings support a broader role for this structure in the regulation of fear. To further characterize the relationship between vmPFC…

Cerebellar modulation of frontal cortex dopamine efflux in mice: relevance to autism and schizophrenia.

PubMed

Mittleman, Guy; Goldowitz, Daniel; Heck, Detlef H; Blaha, Charles D

2008-07-01

Cerebellar and frontal cortical pathologies have been commonly reported in schizophrenia, autism, and other developmental disorders. Whether there is a relationship between prefrontal and cerebellar pathologies is unknown. Using fixed potential amperometry, dopamine (DA) efflux evoked by cerebellar or, dentate nucleus electrical stimulation (50 Hz, 200 muA) was recorded in prefrontal cortex of urethane anesthetized lurcher (Lc/+) mice with 100% loss of cerebellar Purkinje cells and wildtype (+/+) control mice. Cerebellar stimulation with 25 and 100 pulses evoked prefrontal cortex DA efflux in +/+ mice that persisted for 12 and 25 s poststimulation, respectively. In contrast, 25 pulse cerebellar stimulation failed to evoke prefrontal cortex DA efflux in Lc/+ mice indicating a dependency on cerebellar Purkinje cell outputs. Dentate nucleus stimulation (25 pulses) evoked a comparable but briefer (baseline recovery within 7 s) increase in prefrontal cortex DA efflux compared to similar cerebellar stimulation in +/+ mice. However, in Lc/+ mice 25 pulse dentate nucleus evoked prefrontal cortex DA efflux was attenuated by 60% with baseline recovery within 4 s suggesting that dentate nucleus outputs to prefrontal cortex remain partially functional. DA reuptake blockade enhanced 100 pulse stimulation evoked prefrontal cortex responses, while serotonin or norepinephrine reuptake blockade were without effect indicating the specificity of the amperometric recordings to DA. Results provide neurochemical evidence that the cerebellum can modulate DA efflux in the prefrontal cortex. Together, these findings may explain why cerebellar and frontal cortical pathologies co-occur, and may provide a mechanism that accounts for the diversity of symptoms common to multiple developmental disorders.

Cerebellar Modulation of Frontal Cortex Dopamine Efflux in Mice: Relevance to Autism and Schizophrenia

PubMed Central

MITTLEMAN, GUY; GOLDOWITZ, DANIEL; HECK, DETLEF H.; BLAHA, CHARLES D.

2013-01-01

Cerebellar and frontal cortical pathologies have been commonly reported in schizophrenia, autism, and other developmental disorders. Whether there is a relationship between prefrontal and cerebellar pathologies is unknown. Using fixed potential amperometry, dopamine (DA) efflux evoked by cerebellar or, dentate nucleus electrical stimulation (50 Hz, 200 μA) was recorded in prefrontal cortex of urethane anesthetized lurcher (Lc/+) mice with 100% loss of cerebellar Purkinje cells and wildtype (+/+) control mice. Cerebellar stimulation with 25 and 100 pulses evoked prefrontal cortex DA efflux in +/+ mice that persisted for 12 and 25 s poststimulation, respectively. In contrast, 25 pulse cerebellar stimulation failed to evoke prefrontal cortex DA efflux in Lc/+ mice indicating a dependency on cerebellar Purkinje cell outputs. Dentate nucleus stimulation (25 pulses) evoked a comparable but briefer (baseline recovery within 7 s) increase in prefrontal cortex DA efflux compared to similar cerebellar stimulation in +/+ mice. However, in Lc/+ mice 25 pulse dentate nucleus evoked prefrontal cortex DA efflux was attenuated by 60% with baseline recovery within 4 s suggesting that dentate nucleus outputs to prefrontal cortex remain partially functional. DA reuptake blockade enhanced 100 pulse stimulation evoked pre-frontal cortex responses, while serotonin or norepinephrine reuptake blockade were without effect indicating the specificity of the amperometric recordings to DA. Results provide neurochemical evidence that the cerebellum can modulate DA efflux in the prefrontal cortex. Together, these findings may explain why cerebellar and frontal cortical pathologies co-occur, and may provide a mechanism that accounts for the diversity of symptoms common to multiple developmental disorders. PMID:18435424

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

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

Unstable slope management program.

DOT National Transportation Integrated Search

2009-08-01

This Rapid Response Project gathered information on existing unstable slope management programs, with a : focus on asset management practices in the United States and overseas. On the basis of this study, the research : team summarized and recommende...

Temperament Type Specific Metabolite Profiles of the Prefrontal Cortex and Serum in Cattle

PubMed Central

Brand, Bodo; Hadlich, Frieder; Brandt, Bettina; Schauer, Nicolas; Graunke, Katharina L.; Langbein, Jan; Repsilber, Dirk; Ponsuksili, Siriluk; Schwerin, Manfred

2015-01-01

In the past decade the number of studies investigating temperament in farm animals has increased greatly because temperament has been shown not only to affect handling but also reproduction, health and economically important production traits. However, molecular pathways underlying temperament and molecular pathways linking temperament to production traits, health and reproduction have yet to be studied in full detail. Here we report the results of metabolite profiling of the prefrontal cortex and serum of cattle with distinct temperament types that were performed to further explore their molecular divergence in the response to the slaughter procedure and to identify new targets for further research of cattle temperament. By performing an untargeted comprehensive metabolite profiling, 627 and 1097 metabolite features comprising 235 and 328 metabolites could be detected in the prefrontal cortex and serum, respectively. In total, 54 prefrontal cortex and 51 serum metabolite features were indicated to have a high relevance in the classification of temperament types by a sparse partial least square discriminant analysis. A clear discrimination between fearful/neophobic-alert, interested-stressed, subdued/uninterested-calm and outgoing/neophilic-alert temperament types could be observed based on the abundance of the identified relevant prefrontal cortex and serum metabolites. Metabolites with high relevance in the classification of temperament types revealed that the main differences between temperament types in the response to the slaughter procedure were related to the abundance of glycerophospholipids, fatty acyls and sterol lipids. Differences in the abundance of metabolites related to C21 steroid metabolism and oxidative stress indicated that the differences in the metabolite profiles of the four extreme temperament types could be the result of a temperament type specific regulation of molecular pathways that are known to be involved in the stress and fear response. PMID:25927228

Temperament type specific metabolite profiles of the prefrontal cortex and serum in cattle.

PubMed

Brand, Bodo; Hadlich, Frieder; Brandt, Bettina; Schauer, Nicolas; Graunke, Katharina L; Langbein, Jan; Repsilber, Dirk; Ponsuksili, Siriluk; Schwerin, Manfred

2015-01-01

In the past decade the number of studies investigating temperament in farm animals has increased greatly because temperament has been shown not only to affect handling but also reproduction, health and economically important production traits. However, molecular pathways underlying temperament and molecular pathways linking temperament to production traits, health and reproduction have yet to be studied in full detail. Here we report the results of metabolite profiling of the prefrontal cortex and serum of cattle with distinct temperament types that were performed to further explore their molecular divergence in the response to the slaughter procedure and to identify new targets for further research of cattle temperament. By performing an untargeted comprehensive metabolite profiling, 627 and 1097 metabolite features comprising 235 and 328 metabolites could be detected in the prefrontal cortex and serum, respectively. In total, 54 prefrontal cortex and 51 serum metabolite features were indicated to have a high relevance in the classification of temperament types by a sparse partial least square discriminant analysis. A clear discrimination between fearful/neophobic-alert, interested-stressed, subdued/uninterested-calm and outgoing/neophilic-alert temperament types could be observed based on the abundance of the identified relevant prefrontal cortex and serum metabolites. Metabolites with high relevance in the classification of temperament types revealed that the main differences between temperament types in the response to the slaughter procedure were related to the abundance of glycerophospholipids, fatty acyls and sterol lipids. Differences in the abundance of metabolites related to C21 steroid metabolism and oxidative stress indicated that the differences in the metabolite profiles of the four extreme temperament types could be the result of a temperament type specific regulation of molecular pathways that are known to be involved in the stress and fear response.

Guanfacine modulates the emotional biasing of amygdala-prefrontal connectivity for cognitive control.

PubMed

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

2014-09-01

Functional interactions between amygdala and prefrontal cortex provide a cortical entry point for emotional cues to bias cognitive control. Stimulation of α2 adrenoceptors enhances the prefrontal control functions and blocks the amygdala-dependent encoding of emotional cues. However, the impact of this stimulation on amygdala-prefrontal interactions and the emotional biasing of cognitive control have not been established. We tested the effect of the α2 adrenoceptor agonist guanfacine on psychophysiological interactions of amygdala with prefrontal cortex for the emotional biasing of response execution and inhibition. Fifteen healthy adults were scanned twice with event-related functional magnetic resonance imaging while performing an emotional go/no-go task following administration of oral guanfacine (1mg) and placebo in a double-blind, counterbalanced design. Happy, sad, and neutral faces served as trial cues. Guanfacine moderated the effect of face emotion on the task-related functional connectivity of left and right amygdala with left inferior frontal gyrus compared to placebo, by selectively reversing the functional co-activation of the two regions for response execution cued by sad faces. This shift from positively to negatively correlated activation for guanfacine was associated with selective improvements in the relatively low accuracy of responses to sad faces seen for placebo. These results demonstrate the importance of functional interactions between amygdala and inferior frontal gyrus to both bottom-up biasing of cognitive control and top-down control of emotional processing, as well as for the α2 adrenoceptor-mediated modulation of these processes. These mechanisms offer a possibile method to address the emotional reactivity that is common to several psychiatric disorders. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Cordance derived from REM sleep EEG as a biomarker for treatment response in depression--a naturalistic study after antidepressant medication.

PubMed

Adamczyk, Marek; Gazea, Mary; Wollweber, Bastian; Holsboer, Florian; Dresler, Martin; Steiger, Axel; Pawlowski, Marcel

2015-04-01

To evaluate whether prefrontal cordance in theta frequency band derived from REM sleep EEG after the first week of antidepressant medication could characterize the treatment response after 4 weeks of therapy in depressed patients. 20 in-patients (15 females, 5 males) with a depressive episode and 20 healthy matched controls were recruited into 4-week, open label, case-control study. Patients were treated with various antidepressants. No significant differences in age (responders (mean ± SD): 45 ± 22) years; non-responders: 49 ± 12 years), medication or Hamilton Depression Rating Scale (HAM-D) score (responders: 23.8 ± 4.5; non-responders 24.5 ± 7.6) at inclusion into the study were found between responders and non-responders. Response to treatment was defined as a ≥50% reduction of HAM-D score at the end of four weeks of active medication. Sleep EEG of patients was recorded after the first and the fourth week of medication. Cordance was computed for prefrontal EEG channels in theta frequency band during tonic REM sleep. The group of 8 responders had significantly higher prefrontal theta cordance in relation to the group of 12 non-responders after the first week of antidepressant medication. This finding was significant also when controlling for age, gender and number of previous depressive episodes (F1,15 = 6.025, P = .027). Furthermore, prefrontal cordance of all patients showed significant positive correlation (r = 0.52; P = .019) with the improvement of HAM-D score between the inclusion week and fourth week of medication. The results suggest that prefrontal cordance derived from REM sleep EEG could provide a biomarker for the response to antidepressant treatment in depressed patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

Modulation of working memory function by motivation through loss-aversion.

PubMed

Krawczyk, Daniel C; D'Esposito, Mark

2013-04-01

Cognitive performance is affected by motivation. Few studies, however, have investigated the neural mechanisms of the influence of motivation through potential monetary punishment on working memory. We employed functional MRI during a delayed recognition task that manipulated top-down control demands with added monetary incentives to some trials in the form of potential losses of bonus money. Behavioral performance on the task was influenced by loss-threatening incentives in the form of faster and more accurate performance. As shown previously, we found enhancement of activity for relevant stimuli occurs throughout all task periods (e.g., stimulus encoding, maintenance, and response) in both prefrontal and visual association cortex. Further, these activation patterns were enhanced for trials with possible monetary loss relative to nonincentive trials. During the incentive cue, the amygdala and striatum showed significantly greater activation when money was at a possible loss on the trial. We also evaluated patterns of functional connectivity between regions responsive to monetary consequences and prefrontal areas responsive to the task. This analysis revealed greater delay period connectivity between and the left insula and prefrontal cortex with possible monetary loss relative to nonincentive trials. Overall, these results reveal that incentive motivation can modulate performance on working memory tasks through top-down signals via amplification of activity within prefrontal and visual association regions selective to processing the perceptual inputs of the stimuli to be remembered. Copyright © 2011 Wiley Periodicals, Inc.

rTMS on left prefrontal cortex contributes to memories for positive emotional cues: a comparison between pictures and words.

PubMed

Balconi, M; Cobelli, C

2015-02-26

The present research explored the cortical correlates of emotional memories in response to words and pictures. Subjects' performance (Accuracy Index, AI; response times, RTs; RTs/AI) was considered when a repetitive Transcranial Magnetic Stimulation (rTMS) was applied on the left dorsolateral prefrontal cortex (LDLPFC). Specifically, the role of LDLPFC was tested by performing a memory task, in which old (previously encoded targets) and new (previously not encoded distractors) emotional pictures/words had to be recognized. Valence (positive vs. negative) and arousing power (high vs. low) of stimuli were also modulated. Moreover, subjective evaluation of emotional stimuli in terms of valence/arousal was explored. We found significant performance improving (higher AI, reduced RTs, improved general performance) in response to rTMS. This "better recognition effect" was only related to specific emotional features, that is positive high arousal pictures or words. Moreover no significant differences were found between stimulus categories. A direct relationship was also observed between subjective evaluation of emotional cues and memory performance when rTMS was applied to LDLPFC. Supported by valence and approach model of emotions, we supposed that a left lateralized prefrontal system may induce a better recognition of positive high arousal words, and that evaluation of emotional cue is related to prefrontal activation, affecting the recognition memories of emotions. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Modulation of working memory function by motivation through loss-aversion

PubMed Central

Krawczyk, Daniel C.; D’Esposito, Mark

2012-01-01

Cognitive performance is affected by motivation. Few studies, however, have investigated the neural mechanisms of the influence of motivation through potential monetary punishment on working memory. We employed functional MRI during a delayed recognition task that manipulated top-down control demands with added monetary incentives to some trials in the form of potential losses of bonus money. Behavioral performance on the task was influenced by loss-threatening incentives in the form of faster and more accurate performance. As shown previously, we found enhancement of activity for relevant stimuli occurs throughout all task periods (e.g. stimulus encoding, maintenance, and response) in both prefrontal and visual association cortex. Further, these activation patterns were enhanced for trials with possible monetary loss relative to non-incentive trials. During the incentive cue, the amygdala and striatum showed significantly greater activation when money was at a possible loss on the trial. We also evaluated patterns of functional connectivity between regions responsive to monetary consequences and prefrontal areas responsive to the task. This analysis revealed greater delay period connectivity between and the left insula and prefrontal cortex with possible monetary loss relative to non-incentive trials. Overall, these results reveal that incentive motivation can modulate performance on working memory tasks through top-down signals via amplification of activity within prefrontal and visual association regions selective to processing the perceptual inputs of the stimuli to be remembered. PMID:22113962

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.

Homeostatic Regulation of Memory Systems and Adaptive Decisions

PubMed Central

Mizumori, Sheri JY; Jo, Yong Sang

2013-01-01

While it is clear that many brain areas process mnemonic information, understanding how their interactions result in continuously adaptive behaviors has been a challenge. A homeostatic-regulated prediction model of memory is presented that considers the existence of a single memory system that is based on a multilevel coordinated and integrated network (from cells to neural systems) that determines the extent to which events and outcomes occur as predicted. The “multiple memory systems of the brain” have in common output that signals errors in the prediction of events and/or their outcomes, although these signals differ in terms of what the error signal represents (e.g., hippocampus: context prediction errors vs. midbrain/striatum: reward prediction errors). The prefrontal cortex likely plays a pivotal role in the coordination of prediction analysis within and across prediction brain areas. By virtue of its widespread control and influence, and intrinsic working memory mechanisms. Thus, the prefrontal cortex supports the flexible processing needed to generate adaptive behaviors and predict future outcomes. It is proposed that prefrontal cortex continually and automatically produces adaptive responses according to homeostatic regulatory principles: prefrontal cortex may serve as a controller that is intrinsically driven to maintain in prediction areas an experience-dependent firing rate set point that ensures adaptive temporally and spatially resolved neural responses to future prediction errors. This same drive by prefrontal cortex may also restore set point firing rates after deviations (i.e. prediction errors) are detected. In this way, prefrontal cortex contributes to reducing uncertainty in prediction systems. An emergent outcome of this homeostatic view may be the flexible and adaptive control that prefrontal cortex is known to implement (i.e. working memory) in the most challenging of situations. Compromise to any of the prediction circuits should result in rigid and suboptimal decision making and memory as seen in addiction and neurological disease. © 2013 The Authors. Hippocampus Published by Wiley Periodicals, Inc. PMID:23929788

Homeostatic regulation of memory systems and adaptive decisions.

PubMed

Mizumori, Sheri J Y; Jo, Yong Sang

2013-11-01

While it is clear that many brain areas process mnemonic information, understanding how their interactions result in continuously adaptive behaviors has been a challenge. A homeostatic-regulated prediction model of memory is presented that considers the existence of a single memory system that is based on a multilevel coordinated and integrated network (from cells to neural systems) that determines the extent to which events and outcomes occur as predicted. The "multiple memory systems of the brain" have in common output that signals errors in the prediction of events and/or their outcomes, although these signals differ in terms of what the error signal represents (e.g., hippocampus: context prediction errors vs. midbrain/striatum: reward prediction errors). The prefrontal cortex likely plays a pivotal role in the coordination of prediction analysis within and across prediction brain areas. By virtue of its widespread control and influence, and intrinsic working memory mechanisms. Thus, the prefrontal cortex supports the flexible processing needed to generate adaptive behaviors and predict future outcomes. It is proposed that prefrontal cortex continually and automatically produces adaptive responses according to homeostatic regulatory principles: prefrontal cortex may serve as a controller that is intrinsically driven to maintain in prediction areas an experience-dependent firing rate set point that ensures adaptive temporally and spatially resolved neural responses to future prediction errors. This same drive by prefrontal cortex may also restore set point firing rates after deviations (i.e. prediction errors) are detected. In this way, prefrontal cortex contributes to reducing uncertainty in prediction systems. An emergent outcome of this homeostatic view may be the flexible and adaptive control that prefrontal cortex is known to implement (i.e. working memory) in the most challenging of situations. Compromise to any of the prediction circuits should result in rigid and suboptimal decision making and memory as seen in addiction and neurological disease. Copyright © 2013 Wiley Periodicals, Inc.

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.

Moral transgressions corrupt neural representations of value.

PubMed

Crockett, Molly J; Siegel, Jenifer Z; Kurth-Nelson, Zeb; Dayan, Peter; Dolan, Raymond J

2017-06-01

Moral systems universally prohibit harming others for personal gain. However, we know little about how such principles guide moral behavior. Using a task that assesses the financial cost participants ascribe to harming others versus themselves, we probed the relationship between moral behavior and neural representations of profit and pain. Most participants displayed moral preferences, placing a higher cost on harming others than themselves. Moral preferences correlated with neural responses to profit, where participants with stronger moral preferences had lower dorsal striatal responses to profit gained from harming others. Lateral prefrontal cortex encoded profit gained from harming others, but not self, and tracked the blameworthiness of harmful choices. Moral decisions also modulated functional connectivity between lateral prefrontal cortex and the profit-sensitive region of dorsal striatum. The findings suggest moral behavior in our task is linked to a neural devaluation of reward realized by a prefrontal modulation of striatal value representations.

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

Attentional impulsivity in binge eating disorder modulates response inhibition performance and frontal brain networks.

PubMed

Hege, M A; Stingl, K T; Kullmann, S; Schag, K; Giel, K E; Zipfel, S; Preissl, H

2015-02-01

A subgroup of overweight and obese people is characterized by binge eating disorder (BED). Increased impulsivity has been suggested to cause binge eating and subsequent weight gain. In the current study, neuronal correlates of increased impulsivity in binge eating disorder during behavioral response inhibition were investigated. Magnetic brain activity and behavioral responses of 37 overweight and obese individuals with and without diagnosed BED were recorded while performing a food-related visual go-nogo task. Trait impulsivity was assessed with the Barratt Impulsiveness Scale (BIS-11). Specifically, increased attentional impulsiveness (a subscale of the BIS-11) in BED was related to decreased response inhibition performance and hypoactivity in the prefrontal control network, which was activated when response inhibition was required. Furthermore, participants with BED showed a trend for a food-specific inhibition performance decline. This was possibly related to the absence of a food-specific activity increase in the prefrontal control network in BED, as observed in the control group. In addition, an increase in activity related to the actual button press during prepotent responses and alterations in visual processing were observed. Our results suggest an attentional impulsiveness-related attenuation in response inhibition performance in individuals with BED. This might have been related to increased reward responsiveness and limited resources to activate the prefrontal control network involved in response inhibition. Our results substantiate the importance of neuronal markers for investigating prevention and treatment of obesity, especially in specific subgroups at risk such as BED.

Unemotional on all counts: Evidence of reduced affective responses in individuals with high callous-unemotional traits across emotion systems and valences.

PubMed

Fanti, Kostas A; Panayiotou, Georgia; Lombardo, Michael V; Kyranides, Melina Nicole

2016-01-01

The current study aimed to identify atypical neurophysiological activity associated with deficient affective processing in individuals with high callous-unemotional traits (CU). Fifty-six participants (M age = 20.52; 46% male) divided in two groups, differentiated on levels of CU traits, were invited to participate in the experimental phase of the study. Medial prefrontal cortex activity, measured with functional Near-Infrared Spectroscopy, and facial electro-myography activity were recorded during videos depicting violent, comedy and neutral scenes. Individuals high on CU traits showed similar medial prefrontal cortex oxygenated hemoglobin (HbO(2)) activity to positive and negative films, while the pre-frontal cortical responses of low CU individuals were more pronounced to positive than negative materials. High CU participants also showed reduced facial electromyography at the corrugator muscle in response to violent films, which was not differentiated from their responses to comedy films. These findings suggest that individuals high on CU traits show reduced but not absent (i.e., flat) affect to emotional material. Deficits in processing positive and negative valent material, measured with different neuro-physiological modalities, might be essential to understand CU traits.

Variation in Dopamine D2 and Serotonin 5-HT2A Receptor Genes is Associated with Working Memory Processing and Response to Treatment with Antipsychotics

PubMed Central

Blasi, Giuseppe; Selvaggi, Pierluigi; Fazio, Leonardo; Antonucci, Linda Antonella; Taurisano, Paolo; Masellis, Rita; Romano, Raffaella; Mancini, Marina; Zhang, Fengyu; Caforio, Grazia; Popolizio, Teresa; Apud, Jose; Weinberger, Daniel R; Bertolino, Alessandro

2015-01-01

Dopamine D2 and serotonin 5-HT2A receptors contribute to modulate prefrontal cortical physiology and response to treatment with antipsychotics in schizophrenia. Similarly, functional variation in the genes encoding these receptors is also associated with these phenotypes. In particular, the DRD2 rs1076560 T allele predicts a lower ratio of expression of D2 short/long isoforms, suboptimal working memory processing, and better response to antipsychotic treatment compared with the G allele. Furthermore, the HTR2A T allele is associated with lower 5-HT2A expression, impaired working memory processing, and poorer response to antipsychotics compared with the C allele. Here, we investigated in healthy subjects whether these functional polymorphisms have a combined effect on prefrontal cortical physiology and related cognitive behavior linked to schizophrenia as well as on response to treatment with second-generation antipsychotics in patients with schizophrenia. In a total sample of 620 healthy subjects, we found that subjects with the rs1076560 T and rs6314 T alleles have greater fMRI prefrontal activity during working memory. Similar results were obtained within the attentional domain. Also, the concomitant presence of the rs1076560 T/rs6314 T alleles also predicted lower behavioral accuracy during working memory. Moreover, we found that rs1076560 T carrier/rs6314 CC individuals had better responses to antipsychotic treatment in two independent samples of patients with schizophrenia (n=63 and n=54, respectively), consistent with the previously reported separate effects of these genotypes. These results indicate that DRD2 and HTR2A genetic variants together modulate physiological prefrontal efficiency during working memory and also modulate the response to antipsychotics. Therefore, these results suggest that further exploration is needed to better understand the clinical consequences of these genotype–phenotype relationships. PMID:25563748

Variation in Dopamine D2 and Serotonin 5-HT2A Receptor Genes is Associated with Working Memory Processing and Response to Treatment with Antipsychotics.

PubMed

Blasi, Giuseppe; Selvaggi, Pierluigi; Fazio, Leonardo; Antonucci, Linda Antonella; Taurisano, Paolo; Masellis, Rita; Romano, Raffaella; Mancini, Marina; Zhang, Fengyu; Caforio, Grazia; Popolizio, Teresa; Apud, Jose; Weinberger, Daniel R; Bertolino, Alessandro

2015-06-01

Dopamine D2 and serotonin 5-HT2A receptors contribute to modulate prefrontal cortical physiology and response to treatment with antipsychotics in schizophrenia. Similarly, functional variation in the genes encoding these receptors is also associated with these phenotypes. In particular, the DRD2 rs1076560 T allele predicts a lower ratio of expression of D2 short/long isoforms, suboptimal working memory processing, and better response to antipsychotic treatment compared with the G allele. Furthermore, the HTR2A T allele is associated with lower 5-HT2A expression, impaired working memory processing, and poorer response to antipsychotics compared with the C allele. Here, we investigated in healthy subjects whether these functional polymorphisms have a combined effect on prefrontal cortical physiology and related cognitive behavior linked to schizophrenia as well as on response to treatment with second-generation antipsychotics in patients with schizophrenia. In a total sample of 620 healthy subjects, we found that subjects with the rs1076560 T and rs6314 T alleles have greater fMRI prefrontal activity during working memory. Similar results were obtained within the attentional domain. Also, the concomitant presence of the rs1076560 T/rs6314 T alleles also predicted lower behavioral accuracy during working memory. Moreover, we found that rs1076560 T carrier/rs6314 CC individuals had better responses to antipsychotic treatment in two independent samples of patients with schizophrenia (n=63 and n=54, respectively), consistent with the previously reported separate effects of these genotypes. These results indicate that DRD2 and HTR2A genetic variants together modulate physiological prefrontal efficiency during working memory and also modulate the response to antipsychotics. Therefore, these results suggest that further exploration is needed to better understand the clinical consequences of these genotype-phenotype relationships.

Locus coeruleus phasic discharge is essential for stimulus-induced gamma oscillations in the prefrontal cortex.

PubMed

Neves, Ricardo M; van Keulen, Silvia; Yang, Mingyu; Logothetis, Nikos K; Eschenko, Oxana

2018-03-01

The locus coeruleus (LC) noradrenergic (NE) neuromodulatory system is critically involved in regulation of neural excitability via its diffuse ascending projections. Tonic NE release in the forebrain is essential for maintenance of vigilant states and increases the signal-to-noise ratio of cortical sensory responses. The impact of phasic NE release on cortical activity and sensory processing is less explored. We previously reported that LC microstimulation caused a transient desynchronization of population activity in the medial prefrontal cortex (mPFC), similar to noxious somatosensory stimuli. The LC receives nociceptive information from the medulla and therefore may mediate sensory signaling to its forebrain targets. Here we performed extracellular recordings in LC and mPFC while presenting noxious stimuli in urethane-anesthetized rats. A brief train of foot shocks produced a robust phasic response in the LC and a transient change in the mPFC power spectrum, with the strongest modulation in the gamma (30-90 Hz) range. The LC phasic response preceded prefrontal gamma power increase, and cortical modulation was proportional to the LC excitation. We also quantitatively characterized distinct cortical states and showed that sensory responses in both LC and mPFC depend on the ongoing cortical state. Finally, cessation of the LC firing by bilateral local iontophoretic injection of clonidine, an α 2 -adrenoreceptor agonist, completely eliminated sensory responses in the mPFC without shifting cortex to a less excitable state. Together, our results suggest that the LC phasic response induces gamma power increase in the PFC and is essential for mediating sensory information along an ascending noxious pathway. NEW & NOTEWORTHY Our study shows linear relationships between locus coeruleus phasic excitation and the amplitude of gamma oscillations in the prefrontal cortex. Results suggest that the locus coeruleus phasic response is essential for mediating sensory information along an ascending noxious pathway.

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.

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.

Brain responses mediating idiom comprehension: gender and hemispheric differences.

PubMed

Kana, Rajesh K; Murdaugh, Donna L; Wolfe, Kelly R; Kumar, Sandhya L

2012-07-27

Processing figurative language, such as idioms, is unique in that it requires one to make associations between words and non-literal meanings that are contextually appropriate. At the neural level, processing idiomatic phrases has been linked to recruitment of bilateral dorsolateral prefrontal cortices (DLPFC), the left temporal cortex, superior medial prefrontal gyrus (MPFC), and the left inferior frontal gyrus (LIFG). This functional MRI study examined the brain responses associated with processing idiomatic compared to literal sentences. In addition, gender differences in neural responses associated with language comprehension were also explored. In an fMRI scanner, thirty-six healthy adult volunteers viewed sentences that were either literal or idiomatic in nature, and answered subsequent comprehension questions. This sentence comprehension tasks activated mainly prefrontal language areas (LIFG, LSFG, and RMFG). Consistent with previous findings, idiomatic sentences showed increased response in LIFG. These results are discussed in the backdrop of the graded salience hypothesis. Furthermore, we found gender differences in brain activation and functional connectivity during this task. Women showed greater overall activation than men when comprehending literal and idiomatic sentences; whereas men had significantly greater functional connectivity between LIFG and LMTG than women across tasks. Overall, the findings of this study highlight the gender differences in neural responses associated with figurative language comprehension. Published by Elsevier B.V.

Socioeconomic disadvantages and neural sensitivity to infant cry: role of maternal distress.

PubMed

Kim, Pilyoung; Capistrano, Christian; Congleton, Christina

2016-10-01

Socioeconomic disadvantage such as poverty can increase distress levels, which may further make low-income mothers more vulnerable to difficulties in the transition to parenthood. However, little is known about the neurobiological processes by which poverty and maternal distress are associated with risks for adaptations to motherhood. Thus, the current study examined the associations between income and neural responses to infant cry sounds among first-time new mothers (N = 28) during the early postpartum period. Lower income was associated with reduced responses to infant cry in the medial prefrontal gyrus (involved in evaluating emotional values of stimuli), middle prefrontal gyrus (involved in affective regulation) and superior temporal gyrus (involved in sensory information processing). When examining the role of maternal distress, we found a mediating role of perceived stress, but not depressive symptoms, in the links between income and prefrontal responses to infant cry. Reduced neural responses to infant cry in the right middle frontal gyrus and superior temporal gyrus were further associated with less positive perceptions of parenting. The results demonstrate that perceived stress associated with socioeconomic disadvantages may contribute to reduced neural responses to infant cry, which is further associated with less positive perceptions of motherhood. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

A novel double loop control model design for chemical unstable processes.

PubMed

Cong, Er-Ding; Hu, Ming-Hui; Tu, Shan-Tung; Xuan, Fu-Zhen; Shao, Hui-He

2014-03-01

In this manuscript, based on Smith predictor control scheme for unstable process in industry, an improved double loop control model is proposed for chemical unstable processes. Inner loop is to stabilize integrating the unstable process and transform the original process to first-order plus pure dead-time dynamic stable process. Outer loop is to enhance the performance of set point response. Disturbance controller is designed to enhance the performance of disturbance response. The improved control system is simple with exact physical meaning. The characteristic equation is easy to realize stabilization. Three controllers are separately design in the improved scheme. It is easy to design each controller and good control performance for the respective closed-loop transfer function separately. The robust stability of the proposed control scheme is analyzed. Finally, case studies illustrate that the improved method can give better system performance than existing design methods. © 2013 ISA Published by ISA All rights reserved.

Using functional near-infrared spectroscopy (fNIRS) to detect the prefrontal cortical responses to deception under different motivations

PubMed Central

Li, Fang; Zhu, Huilin; Gao, Qianqian; Xu, Guixiong; Li, Xinge; Hu, Ziqiang; He, Sailing

2015-01-01

In this study, functional near-infrared spectroscopy (fNIRS) was adopted to investigate the prefrontal cortical responses to deception under different motivations. By using a feigned memory impairment paradigm, 19 healthy adults were asked to deceive under the two different motivations: to obtain rewards and to avoid punishments. Results indicated that when deceiving for obtaining rewards, there was greater neural activation in the right inferior frontal gyrus (IFG) than the control condition. When deceiving for avoiding punishments, there was greater activation in the right inferior frontal gyrus (IFG) and the left middle frontal gyrus (MFG) than the control condition. In addition, deceiving for avoiding punishments led to greater neural activation in the left MFG than when deceiving for obtaining rewards. Furthermore, the results showed a moderate hit rate in detecting deception under either motivation. These results demonstrated that deception with different motivations led to distinct responses in the prefrontal cortex. fNIRS could provide a useful technique for the detection of deception with strategy of feigning memory impairment under different motivations. PMID:26417519

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.

Impairment of social and moral behavior related to early damage in human prefrontal cortex.

PubMed

Anderson, S W; Bechara, A; Damasio, H; Tranel, D; Damasio, A R

1999-11-01

The long-term consequences of early prefrontal cortex lesions occurring before 16 months were investigated in two adults. As is the case when such damage occurs in adulthood, the two early-onset patients had severely impaired social behavior despite normal basic cognitive abilities, and showed insensitivity to future consequences of decisions, defective autonomic responses to punishment contingencies and failure to respond to behavioral interventions. Unlike adult-onset patients, however, the two patients had defective social and moral reasoning, suggesting that the acquisition of complex social conventions and moral rules had been impaired. Thus early-onset prefrontal damage resulted in a syndrome resembling psychopathy.

The Role of Left Hemispheric Structures for Emotional Processing as a Monitor of Bodily Reaction and Felt Chill - a Case-Control Functional Imaging Study.

PubMed

Grunkina, Viktoria; Holtz, Katharina; Klepzig, Kai; Neubert, Jörg; Horn, Ulrike; Domin, Martin; Hamm, Alfons O; Lotze, Martin

2016-01-01

Background: The particular function of the left anterior human insula on emotional arousal has been illustrated with several case studies. Only after left hemispheric insula lesions, patients lose their pleasure in habits such as listening to joyful music. In functional magnetic resonance imaging studies (fMRI) activation in the left anterior insula has been associated with both processing of emotional valence and arousal. Tight interactions with different areas of the prefrontal cortex are involved in bodily response monitoring and cognitive appraisal of a given stimulus. Therefore, a large left hemispheric lesion including the left insula should impair the bodily response of chill experience (objective chill response) but leave the cognitive aspects of chill processing (subjective chill response) unaffected. Methods: We investigated a patient (MC) with a complete left hemispheric media cerebral artery stroke, testing fMRI representation of pleasant (music) and unpleasant (harsh sounds) chill response. Results: Although chill response to both pleasant and unpleasant rated sounds was confirmed verbally at passages also rated as chilling by healthy participants, skin conductance response was almost absent in MC. For a healthy control (HC) objective and subjective chill response was positively associated. Bilateral prefrontal fMRI-response to chill stimuli was sustained in MC whereas insula activation restricted to the right hemisphere. Diffusion imaging together with lesion maps revealed that left lateral tracts were completely damaged but medial prefrontal structures were intact. Conclusion: With this case study we demonstrate how bodily response and cognitive appraisal are differentially participating in the internal monitor of chill response.

Investigating the Usability and Acute Effects of a Bedside Video Console to Prefrontal Cortical Activity Alterations: A Preclinical Study in Healthy Elderly.

PubMed

Knols, Ruud H; Swanenburg, Jaap; De Bon, Dino; Gennaro, Federico; Wolf, Martin; Krüger, Bernard; Bettex, Dominique; de Bruin, Eling D

2017-01-01

Elderly people at risk of developing cognitive decline; e.g., following surgery, may benefit from structured, challenging, and repetitive cognitive video training. This study assessed usability and acute effects of a newly developed bedside console (COPHYCON). Fifteen healthy elderly individuals performed a one-time 80-min intervention, including cognitive video games aimed at improving awareness and selective attention. Perceived usefulness and perceived ease of use (Technology Acceptance Model) were assessed together with measures of the achieved game level, reaction times, (in-) correct responses during ALERT and SELECT game play. Further, prefrontal cortical involvement of the regional cerebral hemoglobin saturation (rS02%) assessed with functional near infrared spectroscopy (fNIRS) ( n = 5) and EEG power ( n = 10) was analyzed. All participants completed the study without any adverse events. Perceived usefulness and perceived ease of use (TAM scores range 1-7) of the system varied between 3.9 and 6.3. The game levels reached for awareness varied between 9 and 11 (initial score 8-10), for reaction speed between 439 and 469 ms, and for correct responses between 74.1 and 78.8%. The highest level for the selective attention games was 2 (initial score 1), where reaction speed varied between 439 and 469 ms, correct responses between 96.2 and 98.5%, respectively. The decrease of rS02% in the right prefrontal cortex during gameplay was significantly ( p < 0.001) lower, compared to the left prefrontal cortex. Four participants yielded significant lower rS02% measures after exergaming with the ALERT games ( p < 0.000), but not with the SELECT games. EEG recordings of theta power significantly decreased in the averaged ~0.25-0.75 time interval for the left prefrontal cortex sensor across the cognitive game levels between the ALERT 1 and SELECT 1, as well as between SELECT 1 and 2 games. Participants rated the usability of the COPHYCON training positively. Further results indicate that video gaming may be an effective measure to affect prefrontal cortical functioning in elderly. The results warrant a clinical explorative study investigating the feasibility of the COPHYCON in a clinical setting.

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 contributes to clinically relevant cognitive deficits, and we consider pharmacological strategies for ameliorating cognitive deficits by rebalancing disinhibition-induced aberrant neural activity. Linked Articles This article is part of a themed section on Pharmacology of Cognition: a Panacea for Neuropsychiatric Disease? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.19/issuetoc. © 2017 The British Pharmacological Society.

Impairment of learning and memory after photothrombosis of the prefrontal cortex in rat brain: effects of Noopept.

PubMed

Romanova, G A; Shakova, F M; Gudasheva, T A; Ostrovskaya, R U

2002-12-01

Experiments were performed on rats trained conditioned passive avoidance response. Acquisition and retention of memory traces were impaired after photothrombosis of the prefrontal cortex. The acyl-prolyl-containing dipeptide Noopept facilitated retention and retrieval of a conditioned passive avoidance response, normalized learning capacity in animals with ischemic damage to the cerebral cortex, and promoted finish training in rats with hereditary learning deficit. These results show that Noopept improves all three stages of memory. It should be emphasized that the effect of Noopept was most pronounced in animals with impaired mnesic function.

Asymmetric and persistent responses in price volatility of fertilizers through stable and unstable periods

NASA Astrophysics Data System (ADS)

Lahmiri, Salim

2017-01-01

Fertilizers are important to improve agricultural productivity growth. The purpose of this study is to investigate asymmetry, leverage, and persistence of shocks on price volatility of five fertilizers using EGARCH model during stable and unstable time periods, corresponding to before and after 2007 international financial crisis, respectively. Using price data of rock phosphate, triple super phosphate, diammonium phosphate (DAP), urea, and potassium chloride, it is found that fertilizers price volatilities display an apparent asymmetric response to shocks which have much pronounced and permanent effect during unstable period than in during stable period. Such effects should be taken into account whenever volatility modeling of fertilizers is considered, particularly during periods of volatile price.

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.

The actions of metabolic inhibition on human detrusor smooth muscle contractility from stable and unstable bladders.

PubMed

Hockey, J S; Wu, C; Fry, C H

2000-09-01

To determine the important cellular site(s) of action of a brief exposure to NaCN (chosen to reduce mitochondrial respiration and hence mimic cellular hypoxia) on the mechanical properties and regulation of intracellular [Ca2+] in human detrusor smooth muscle. Using muscle samples obtained from patients with stable and unstable bladders, to determine whether the unstable bladder is associated with changes in the functional properties of detrusor muscle under these circumstances. Materials and methods Experiments were conducted in vitro on muscle strips or isolated cells. Isometric tension was recorded in muscle strips during electrical stimulation or exposure to agonists. Intracellular [Ca2+] and [H+] were measured by epifluorescence microscopy, and cell autofluorescence measured as an index of mitochondrial function. There were no differences in the responses to electrical stimulation and varying concentrations of carbachol in muscle strips from stable and unstable bladders. NaCN (2 mmol/L) reduced the contraction induced by carbachol (10 micromol/L) by a mean (SD) of 43 (16)% and 56 (15)% in the two groups; the reduction in the unstable was significantly less than in the stable group. NaCN similarly reduced the response to 10 mmol/L caffeine, but had no effect on the KCl-induced contraction. NaCN significantly increased the resting sarcoplasmic [Ca2+] and attenuated the calcium transients evoked by carbachol and caffeine, but again had no effect on the KCl-induced transient. The reduction of the carbachol calcium transient was also less in cells from unstable bladders than in those from stable bladders. There was no effect of NaCN on intracellular pH, except for a brief, transient alkalosis. NaCN reduces both the contraction and Ca-transient to carbachol by reducing Ca2+ accumulation by intracellular stores, because the carbachol- and caffeine-evoked responses were similar. Any effect on transmembrane Ca2+ flux was minimal because there was no effect on KCl-induced responses. The greater resilience of tissue from unstable bladders to acute cellular hypoxia may reflect some adaptation acquired in vivo.

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.

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 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.

Dynamic encoding of responses and outcomes by neurons in medial prefrontal cortex

PubMed Central

Luk, Chung-Hay; Wallis, Jonathan D.

2009-01-01

Medial prefrontal cortex (MPFC) and lateral prefrontal cortex (LPFC) both contribute to goal-directed behavior, but their precise role remains unclear. Several lines of evidence suggest that MPFC is more important than LPFC for outcome-guided response selection. To examine this, we trained two subjects to perform a task that required them to monitor the specific outcome associated with a specific response on a trial-by-trial basis. While the subjects performed this task, we recorded the electrical activity of single neurons simultaneously from MPFC and LPFC. There were marked differences in the neuronal properties of these two areas. Neurons encoding the response were present in both areas, but in MPFC, there were also neurons that encoded the outcome. In particular, neurons encoded the subject’s intended response and how preferable the received outcome was. Thus, only in MPFC was all the information necessary to solve the task encoded. In addition, largely separate populations of MPFC neurons encoded the response and the outcome. Neurons encoding the outcome were in the anterior parts of MPFC: posterior to the corpus callosum there was a marked drop in their incidence. Our results suggest differences in the contribution of MPFC and LPFC to action control. MPFC neurons encode the desirability of the outcome produced by a specific response on a trial-by-trial basis. This capability may contribute to several of the functions of MPFC, such as action valuation, error detection and decision-making. PMID:19515921

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

Control of acceleration during sudden ankle supination in people with unstable ankles.

PubMed

Vaes, P; Van Gheluwe, B; Duquet, W

2001-12-01

Comparative study of differences in functional control during ankle supination in the standing position in matched stable and unstable ankles (ex post facto design). To document acceleration and deceleration during ankle supination in the standing position and to determine differences in control of supination perturbation between stable and unstable ankles. Repetitive ankle sprain can be explained by mechanical instability only in a minority of cases. Exercise therapy for ankle instability is based on clinical experience. Joint stability has not yet been measured in dynamic situations that are similar to the situations leading to a traumatic sprain. The process of motor control during accelerating ankle supination has not been adequately addressed in the literature. Patients with complaints of ankle instability (16 unstable ankles) and nonimpaired controls (18 stable ankles) were examined (N = 17 subjects, 10 women and 7 men). The average age was 23.7 +/- 5.0 years (range, 20-41 y). Control of supination speed was studied during 50 degrees of ankle supination in the standing position using accelerometry (total supination time and deceleration times) and electromyography (latency time). Timing of motor response was estimated by measuring electromechanical delay. The presence of an early, sudden, and presumably passive slowdown of ankle supination in the standing position was observed. Peroneal muscle motor response was detected before the end of the supination. Unstable ankles showed significantly shorter total supination time (109.3 ms versus 124.1 ms) and significantly longer latency time (58.9 ms versus 47.7 ms). Functional control in unstable ankles is less efficient in decelerating the ankle during the supination test procedures used in our study. Our conclusions are based on significantly faster total supination and significantly slower electromyogram response in unstable ankles. The results support the hypothesis that both decelerating the total supination movement during balance disturbance and enhancing the speed of evertor activation through exercise can be specific therapy goals.

Network Mechanisms of Clinical Response to Transcranial Magnetic Stimulation in Posttraumatic Stress Disorder and Major Depressive Disorder.

PubMed

Philip, Noah S; Barredo, Jennifer; van 't Wout-Frank, Mascha; Tyrka, Audrey R; Price, Lawrence H; Carpenter, Linda L

2018-02-01

Repetitive transcranial magnetic stimulation (TMS) therapy can modulate pathological neural network functional connectivity in major depressive disorder (MDD). Posttraumatic stress disorder is often comorbid with MDD, and symptoms of both disorders can be alleviated with TMS therapy. This is the first study to evaluate TMS-associated changes in connectivity in patients with comorbid posttraumatic stress disorder and MDD. Resting-state functional connectivity magnetic resonance imaging was acquired before and after TMS therapy in 33 adult outpatients in a prospective open trial. TMS at 5 Hz was delivered, in up to 40 daily sessions, to the left dorsolateral prefrontal cortex. Analyses used a priori seeds relevant to TMS, posttraumatic stress disorder, or MDD (subgenual anterior cingulate cortex [sgACC], left dorsolateral prefrontal cortex, hippocampus, and basolateral amygdala) to identify imaging predictors of response and to evaluate clinically relevant changes in connectivity after TMS, followed by leave-one-out cross-validation. Imaging results were explored using data-driven multivoxel pattern activation. More negative pretreatment connectivity between the sgACC and the default mode network predicted clinical improvement, as did more positive amygdala-to-ventromedial prefrontal cortex connectivity. After TMS, symptom reduction was associated with reduced connectivity between the sgACC and the default mode network, left dorsolateral prefrontal cortex, and insula, and reduced connectivity between the hippocampus and the salience network. Multivoxel pattern activation confirmed seed-based predictors and correlates of treatment outcomes. These results highlight the central role of the sgACC, default mode network, and salience network as predictors of TMS response and suggest their involvement in mechanisms of action. Furthermore, this work indicates that there may be network-based biomarkers of clinical response relevant to these commonly comorbid disorders. Published by Elsevier Inc.

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.

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.

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.

Traumatic stress: effects on the brain

PubMed Central

Bremner, J. Douglas

2006-01-01

Brain areas implicated in the stress response include the amygdala, hippocampus, and prefrontal cortex. Traumatic stress can be associated with lasting changes in these brain areas. Traumatic stress is associated with increased cortisol and norepinephrine responses to subsequent stressors. Antidepressants have effets on the hippocampus that counteract the effects of stress. Findings from animal studies have been extended to patients with post-traumatic stress disorder (PTSD) showing smaller hippocampal and anterior cingulate volumes, increased amygdala function, and decreased medial prefrontal/anterior cingulate function. In addition, patients with PTSD show increased cortisol and norepinephrine responses to stress. Treatments that are efficacious for PTSD show a promotion of neurogenesis in animal studies, as well as promotion of memory and increased hippocampal volume in PTSD. PMID:17290802

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

Switch-task performance in rats is disturbed by 12 h of sleep deprivation but not by 12 h of sleep fragmentation.

PubMed

Leenaars, Cathalijn H C; Joosten, Ruud N J M A; Zwart, Allard; Sandberg, Hans; Ruimschotel, Emma; Hanegraaf, Maaike A J; Dematteis, Maurice; Feenstra, Matthijs G P; van Someren, Eus J W

2012-02-01

Task-switching is an executive function involving the prefrontal cortex. Switching temporarily attenuates the speed and/or accuracy of performance, phenomena referred to as switch costs. In accordance with the idea that prefrontal function is particularly sensitive to sleep loss, switch-costs increase during prolonged waking in humans. It has been difficult to investigate the underlying neurobiological mechanisms because of the lack of a suitable animal model. Here, we introduce the first switch-task for rats and report the effects of sleep deprivation and inactivation of the medial prefrontal cortex. Rats were trained to repeatedly switch between 2 stimulus-response associations, indicated by the presentation of a visual or an auditory stimulus. These stimulus-response associations were offered in blocks, and performance was compared for the first and fifth trials of each block. Performance was tested after exposure to 12 h of total sleep deprivation, sleep fragmentation, and their respective movement control conditions. Finally, it was tested after pharmacological inactivation of the medial prefrontal cortex. Controlled laboratory settings. 15 male Wistar rats. Both accuracy and latency showed switch-costs at baseline. Twelve hours of total sleep deprivation, but not sleep fragmentation, impaired accuracy selectively on the switch-trials. Inactivation of the medial prefrontal cortex by local neuronal inactivation resulted in an overall decrease in accuracy. We developed and validated a switch-task that is sensitive to sleep deprivation. This introduces the possibility for in-depth investigations on the neurobiological mechanisms underlying executive impairments after sleep disturbance in a rat model.

Activation of the mesocortical dopamine system by feeding: lack of a selective response to stress.

PubMed

Taber, M T; Fibiger, H C

1997-03-01

There is wide agreement that catecholamine systems in the prefrontal cortex are activated by stressful stimuli. To date, however, the extent to which other stimuli can increase the activity of these systems has received little attention. In the present study, the effects of tail pinch stress and feeding on dopamine and noradrenaline release in the prefrontal cortex of rats were examined using in vivo brain microdialysis. Both stimuli increased dopamine release, with peak effects reaching 212% above baseline for tail pinch and 165% above baseline for feeding. The effects of the two stimuli on peak dopamine release were not significantly different. Both stimuli also significantly increased noradrenaline release, with peak effects reaching 128% above baseline for tail pinch and 98% above baseline for feeding. The effects of the two stimuli on peak noradrenaline release were not significantly different. These results indicate that activation of catecholaminergic afferents to the prefrontal cortex is not specific to stress, but also occurs in response to non-stressors with positive motivational valence.

Increased oxygen load in the prefrontal cortex from mouth breathing: a vector-based near-infrared spectroscopy study.

PubMed

Sano, Masahiro; Sano, Sayaka; Oka, Noriyuki; Yoshino, Kayoko; Kato, Toshinori

2013-12-04

Individuals who habitually breathe through the mouth are more likely than nasal breathers to have sleep disorders and attention deficit hyperactive disorder. We hypothesized that brain hemodynamic responses in the prefrontal cortex might be different for mouth and nasal breathing. To test this hypothesis, we measured changes in oxyhemoglobin and deoxyhemoglobin in the prefrontal cortex during mouth breathing and nasal breathing in healthy adults (n=9) using vector-based near-infrared spectroscopy. The angle k, calculated from changes in oxyhemoglobin and deoxyhemoglobin and indicating the degree of oxygen exchange, was significantly higher during mouth breathing (P<0.05), indicating an increased oxygen load. Mouth breathing also caused a significant increase in deoxyhemoglobin, but oxyhemoglobin did not increase. This difference in oxygen load in the brain arising from different breathing routes can be evaluated quantitatively using vector-based near-infrared spectroscopy. Phase responses could help to provide an earlier and more reliable diagnosis of a patient's habitual breathing route than a patient interview.

Increased oxygen load in the prefrontal cortex from mouth breathing: a vector-based near-infrared spectroscopy study

PubMed Central

Sano, Sayaka; Oka, Noriyuki; Yoshino, Kayoko; Kato, Toshinori

2013-01-01

Individuals who habitually breathe through the mouth are more likely than nasal breathers to have sleep disorders and attention deficit hyperactive disorder. We hypothesized that brain hemodynamic responses in the prefrontal cortex might be different for mouth and nasal breathing. To test this hypothesis, we measured changes in oxyhemoglobin and deoxyhemoglobin in the prefrontal cortex during mouth breathing and nasal breathing in healthy adults (n=9) using vector-based near-infrared spectroscopy. The angle k, calculated from changes in oxyhemoglobin and deoxyhemoglobin and indicating the degree of oxygen exchange, was significantly higher during mouth breathing (P<0.05), indicating an increased oxygen load. Mouth breathing also caused a significant increase in deoxyhemoglobin, but oxyhemoglobin did not increase. This difference in oxygen load in the brain arising from different breathing routes can be evaluated quantitatively using vector-based near-infrared spectroscopy. Phase responses could help to provide an earlier and more reliable diagnosis of a patient’s habitual breathing route than a patient interview. PMID:24169579

Rule-Selection and Action-Selection have a Shared Neuroanatomical Basis in the Human Prefrontal and Parietal Cortex

PubMed Central

Hughes, L.; Eckstein, D.; Owen, A.M.

2008-01-01

The human capacity for voluntary action is one of the major contributors to our success as a species. In addition to choosing actions themselves, we can also voluntarily choose behavioral codes or sets of rules that can guide future responses to events. Such rules have been proposed to be superordinate to actions in a cognitive hierarchy and mediated by distinct brain regions. We used event-related functional magnetic resonance imaging to study novel tasks of rule-based and voluntary action. We show that the voluntary selection of rules to govern future responses to events is associated with activation of similar regions of prefrontal and parietal cortex as the voluntary selection of an action itself. The results are discussed in terms of hierarchical models and the adaptive coding potential of prefrontal neurons and their contribution to a global workspace for nonautomatic tasks. These tasks include the choices we make about our behavior. PMID:18234684

Neuronal correlates of reward and loss in Cluster B personality disorders: a functional magnetic resonance imaging study.

PubMed

Völlm, Birgit; Richardson, Paul; McKie, Shane; Elliott, Rebecca; Dolan, Mairead; Deakin, Bill

2007-11-15

Decision making is guided by the likely consequences of behavioural choices. Neuronal correlates of financial reward have been described in a number of functional imaging studies in humans. Areas implicated in reward include ventral striatum, dopaminergic midbrain, amygdala and orbitofrontal cortex. Response to loss has not been as extensively studied but may involve prefrontal and medial temporal cortices. It has been proposed that increased sensitivity to reward and reduced sensitivity to punishment underlie some of the psychopathology in impulsive personality disordered individuals. However, few imaging studies using reinforcement tasks have been conducted in this group. In this fMRI study, we investigate the effects of positive (monetary reward) and negative (monetary loss) outcomes on BOLD responses in two target selection tasks. The experimental group comprised eight people with Cluster B (antisocial and borderline) personality disorder, whilst the control group contained fourteen healthy participants. A key finding was the absence of prefrontal responses and reduced BOLD signal in the subcortical reward system in the PD group during positive reinforcement. Impulsivity scores correlated negatively with prefrontal responses in the PD but not the control group during both, reward and loss. Our results suggest dysfunctional responses to rewarding and aversive stimuli in Cluster B personality disordered individuals but do not support the notion of hypersensitivity to reward and hyposensitivity to loss.

Prefrontocortical dopamine loss in rats delays long-term extinction of contextual conditioned fear, and reduces social interaction without affecting short-term social interaction memory.

PubMed

Fernandez Espejo, Emilio

2003-03-01

Prefrontal dopamine loss delays extinction of cued fear conditioning responses, but its role in contextual fear conditioning has not been explored. Medial prefrontal lesions also enhance social interaction in rats, but the role of prefrontal dopamine loss on social interaction memory is not known. Besides, a role for subcortical accumbal dopamine on mnesic changes after prefrontal dopamine manipulation has been proposed but not explored. The objective was to study the involvement of dopaminergic neurotransmission in the medial prefrontal cortex (mPFC) and nucleus accumbens in two mnesic tasks: contextual fear conditioning and social interaction memory. For contextual fear conditioning, short- and long-term freezing responses after an electric shock were studied, as well as extinction retention. Regarding social interaction memory, the recognition of a juvenile, a very sensitive short-term memory test, was used. Dopamine loss was carried out by injection of 6-hydroxydopamine, and postmortem catecholamine levels were analyzed by high-performance liquid chromatography. Prefrontocortical dopamine loss (>76%) led to a reactive enhancement of accumbal dopamine content (p<0.01), supporting the hypothesis that a hyperdopaminergic tone emerges in the nucleus accumbens after prefrontocortical dopamine loss. In lesioned rats, long-term extinction of contextual fear conditioning was significantly delayed and extinction retention was impaired without changes in acquisition and short-term contextual fear conditioning and, on the other hand, acquisition and short-term social interaction memory were not affected, although time spent on social interaction was significantly reduced. Added dopamine loss in the nucleus accumbens (>76%) did not alter these behavioral changes. In summary, the results of the present study indicate that the dopaminergic network in the mPFC (but not in the nucleus accumbens) coordinates the normal long-term extinction of contextual fear conditioning responses without affecting their acquisition, and it is involved in time spent on social interaction, but not acquisition and short-term social interaction memory.

[Cognitive Functions in the Prefrontal Association Cortex; Transitive Inference and the Lateral Prefrontal Cortex].

PubMed

Tanaka, Shingo; Oguchi, Mineki; Sakagami, Masamichi

2016-11-01

To behave appropriately in a complex and uncertain world, the brain makes use of several distinct learning systems. One such system is called the "model-free process", via which conditioning allows the association between a stimulus or response and a given reward to be learned. Another system is called the "model-based process". Via this process, the state transition between a stimulus and a response is learned so that the brain is able to plan actions prior to their execution. Several studies have tried to relate the difference between model-based and model-free processes to the difference in functions of the lateral prefrontal cortex (LPFC) and the striatum. Here, we describe a series of studies that demonstrate the ability of LPFC neurons to categorize visual stimuli by their associated behavioral responses and to generate abstract information. If LPFC neurons utilize abstract code to associate a stimulus with a reward, they should be able to infer similar relationships between other stimuli of the same category and their rewards without direct experience of these stimulus-reward contingencies. We propose that this ability of LPFC neurons to utilize abstract information can contribute to the model-based learning process.

Cerebral responses to local and global auditory novelty under general anesthesia

PubMed Central

Uhrig, Lynn; Janssen, David; Dehaene, Stanislas; Jarraya, Béchir

2017-01-01

Primate brains can detect a variety of unexpected deviations in auditory sequences. The local-global paradigm dissociates two hierarchical levels of auditory predictive coding by examining the brain responses to first-order (local) and second-order (global) sequence violations. Using the macaque model, we previously demonstrated that, in the awake state, local violations cause focal auditory responses while global violations activate a brain circuit comprising prefrontal, parietal and cingulate cortices. Here we used the same local-global auditory paradigm to clarify the encoding of the hierarchical auditory regularities in anesthetized monkeys and compared their brain responses to those obtained in the awake state as measured with fMRI. Both, propofol, a GABAA-agonist, and ketamine, an NMDA-antagonist, left intact or even enhanced the cortical response to auditory inputs. The local effect vanished during propofol anesthesia and shifted spatially during ketamine anesthesia compared with wakefulness. Under increasing levels of propofol, we observed a progressive disorganization of the global effect in prefrontal, parietal and cingulate cortices and its complete suppression under ketamine anesthesia. Anesthesia also suppressed thalamic activations to the global effect. These results suggest that anesthesia preserves initial auditory processing, but disturbs both short-term and long-term auditory predictive coding mechanisms. The disorganization of auditory novelty processing under anesthesia relates to a loss of thalamic responses to novelty and to a disruption of higher-order functional cortical networks in parietal, prefrontal and cingular cortices. PMID:27502046

Task-dependent response conflict monitoring and cognitive control in anterior cingulate and dorsolateral prefrontal cortices.

PubMed

Kim, Chobok; Chung, Chongwook; Kim, Jeounghoon

2013-11-06

Previous experience affects our behavior in terms of adjustments. It has been suggested that the conflict monitor-controller system implemented in the prefrontal cortex plays a critical role in such adjustments. Previous studies suggested that there exists multiple conflict monitor-controller systems associated with the level of information (i.e., stimulus and response levels). In this study, we sought to test whether different types of conflicts occur at the same information processing level (i.e., response level) are independently processed. For this purpose, we designed a task paradigm to measure two different types of response conflicts using color-based and location-based conflict stimuli and measured the conflict adaptation effects associated with the two types of conflicts either independently (i.e., single conflict conditions) or simultaneously (i.e., a double-conflict condition). The behavioral results demonstrated that performance on current incongruent trials was faster only when the preceding trial was the same type of response conflict regardless of whether they included a single- or double-conflict. Imaging data also showed that anterior cingulate and dorsolateral prefrontal cortices operate in a task-specific manner. These findings suggest that there may be multiple monitor-controller loops for color-based and location-based conflicts even at the same response level. Importantly, our results suggest that double-conflict processing is qualitatively different from single-conflict processing although double-conflict shares the same sources of conflict with two single-conflict conditions. © 2013 Published by Elsevier B.V.

Response to learned threat: An FMRI study in adolescent and adult anxiety.

PubMed

Britton, Jennifer C; Grillon, Christian; Lissek, Shmuel; Norcross, Maxine A; Szuhany, Kristin L; Chen, Gang; Ernst, Monique; Nelson, Eric E; Leibenluft, Ellen; Shechner, Tomer; Pine, Daniel S

2013-10-01

Poor threat-safety discrimination reflects prefrontal cortex dysfunction in adult anxiety disorders. While adolescent anxiety disorders are impairing and predict high risk for adult anxiety disorders, the neural correlates of threat-safety discrimination have not been investigated in this population. The authors compared prefrontal cortex function in anxious and healthy adolescents and adults following conditioning and extinction, processes requiring threat-safety learning. Anxious and healthy adolescents and adults (N=114) completed fear conditioning and extinction in the clinic. The conditioned stimuli (CS+) were neutral faces, paired with an aversive scream. Physiological and subjective data were acquired. Three weeks later, 82 participants viewed the CS+ and morphed images resembling the CS+ in an MRI scanner. During scanning, participants made difficult threat-safety discriminations while appraising threat and explicit memory of the CS+. During conditioning and extinction, the anxious groups reported more fear than the healthy groups, but the anxious adolescent and adult groups did not differ on physiological measures. During imaging, both anxious adolescents and adults exhibited lower activation in the subgenual anterior cingulate cortex than their healthy counterparts, specifically when appraising threat. Compared with their age-matched counterpart groups, anxious adults exhibited reduced activation in the ventromedial prefrontal cortex when appraising threat, whereas anxious adolescents exhibited a U-shaped pattern of activation, with greater activation in response to the most extreme CS+ and CS-. Two regions of the prefrontal cortex are involved in anxiety disorders. Reduced subgenual anterior cingulate cortex engagement is a shared feature in adult and adolescent anxiety disorders, but ventromedial prefrontal cortex dysfunction is age-specific. The unique U-shaped pattern of activation in the ventromedial prefrontal cortex in many anxious adolescents may reflect heightened sensitivity to threat and safety conditions. How variations in the pattern relate to later risk for adult illness remains to be determined.

Medial prefrontal cortex involvement in the expression of extinction and ABA renewal of instrumental behavior for a food reinforcer.

PubMed

Eddy, Meghan C; Todd, Travis P; Bouton, Mark E; Green, John T

2016-02-01

Instrumental renewal, the return of extinguished instrumental responding after removal from the extinction context, is an important model of behavioral relapse that is poorly understood at the neural level. In two experiments, we examined the role of the dorsomedial prefrontal cortex (dmPFC) and the ventromedial prefrontal cortex (vmPFC) in extinction and ABA renewal of instrumental responding for a sucrose reinforcer. Previous work, exclusively using drug reinforcers, has suggested that the roles of the dmPFC and vmPFC in expression of extinction and ABA renewal may depend at least in part on the type of drug reinforcer used. The current experiments used a food reinforcer because the behavioral mechanisms underlying the extinction and renewal of instrumental responding are especially well worked out in this paradigm. After instrumental conditioning in context A and extinction in context B, we inactivated dmPFC, vmPFC, or a more ventral medial prefrontal cortex region by infusing baclofen/muscimol (B/M) just prior to testing in both contexts. In rats with inactivated dmPFC, ABA renewal was still present (i.e., responding increased when returned to context A); however responding was lower (less renewal) than controls. Inactivation of vmPFC increased responding in context B (the extinction context) and decreased responding in context A, indicating no renewal in these animals. There was no effect of B/M infusion on rats with cannula placements ventral to the vmPFC. Fluorophore-conjugated muscimol was infused in a subset of rats following test to visualize infusion spread. Imaging suggested that the infusion spread was minimal and mainly constrained to the targeted area. Together, these experiments suggest that there is a region of medial prefrontal cortex encompassing both dmPFC and vmPFC that is important for ABA renewal of extinguished instrumental responding for a food reinforcer. In addition, vmPFC, but not dmPFC, is important for expression of extinction of responding for a food reinforcer. The role of the medial prefrontal cortex in renewal in the original conditioning context may depend in part on control over excitatory context-response or context-(response-outcome) relations that might be learned in acquisition. The role of the vmPFC in expression of extinction may depend on its control over inhibitory context-response or context-(response-outcome) relations that are learned in extinction. Copyright © 2015 Elsevier Inc. All rights reserved.

NMDA Receptor-Dependent Processes in the Medial Prefrontal Cortex Are Important for Acquisition and the Early Stage of Consolidation during Trace, but Not Delay Eyeblink Conditioning

ERIC Educational Resources Information Center

Takehara-Nishiuchi, Kaori; Kawahara, Shigenori; Kirino, Yutaka

2005-01-01

Permanent lesions in the medial prefrontal cortex (mPFC) affect acquisition of conditioned responses (CRs) during trace eyeblink conditioning and retention of remotely acquired CRs. To clarify further roles of the mPFC in this type of learning, we investigated the participation of the mPFC in mnemonic processes both during and after daily…

Selection, integration, and conflict monitoring; assessing the nature and generality of prefrontal cognitive control mechanisms.

PubMed

Badre, David; Wagner, Anthony D

2004-02-05

Prefrontal cortex (PFC) supports flexible behavior by mediating cognitive control, though the elemental forms of control supported by PFC remain a central debate. Dorsolateral PFC (DLPFC) is thought to guide response selection under conditions of response conflict or, alternatively, may refresh recently active representations within working memory. Lateral frontopolar cortex (FPC) may also adjudicate response conflict, though others propose that FPC supports higher order control processes such as subgoaling and integration. Anterior cingulate cortex (ACC) is hypothesized to upregulate response selection by detecting response conflict; it remains unclear whether ACC functions generalize beyond monitoring response conflict. The present fMRI experiment directly tested these competing theories regarding the functional roles of DLPFC, FPC, and ACC. Results reveal dissociable control processes in PFC, with mid-DLPFC selectively mediating resolution of response conflict and FPC further mediating subgoaling/integration. ACC demonstrated a broad sensitivity to control demands, suggesting a generalized role in modulating cognitive control.

Coding of vocalizations by single neurons in ventrolateral prefrontal cortex.

PubMed

Plakke, Bethany; Diltz, Mark D; Romanski, Lizabeth M

2013-11-01

Neuronal activity in single prefrontal neurons has been correlated with behavioral responses, rules, task variables and stimulus features. In the non-human primate, neurons recorded in ventrolateral prefrontal cortex (VLPFC) have been found to respond to species-specific vocalizations. Previous studies have found multisensory neurons which respond to simultaneously presented faces and vocalizations in this region. Behavioral data suggests that face and vocal information are inextricably linked in animals and humans and therefore may also be tightly linked in the coding of communication calls in prefrontal neurons. In this study we therefore examined the role of VLPFC in encoding vocalization call type information. Specifically, we examined previously recorded single unit responses from the VLPFC in awake, behaving rhesus macaques in response to 3 types of species-specific vocalizations made by 3 individual callers. Analysis of responses by vocalization call type and caller identity showed that ∼19% of cells had a main effect of call type with fewer cells encoding caller. Classification performance of VLPFC neurons was ∼42% averaged across the population. When assessed at discrete time bins, classification performance reached 70 percent for coos in the first 300 ms and remained above chance for the duration of the response period, though performance was lower for other call types. In light of the sub-optimal classification performance of the majority of VLPFC neurons when only vocal information is present, and the recent evidence that most VLPFC neurons are multisensory, the potential enhancement of classification with the addition of accompanying face information is discussed and additional studies recommended. Behavioral and neuronal evidence has shown a considerable benefit in recognition and memory performance when faces and voices are presented simultaneously. In the natural environment both facial and vocalization information is present simultaneously and neural systems no doubt evolved to integrate multisensory stimuli during recognition. This article is part of a Special Issue entitled "Communication Sounds and the Brain: New Directions and Perspectives". Copyright © 2013 Elsevier B.V. All rights reserved.

Automatic detection of a prefrontal cortical response to emotionally rated music using multi-channel near-infrared spectroscopy

NASA Astrophysics Data System (ADS)

Moghimi, Saba; Kushki, Azadeh; Power, Sarah; Guerguerian, Anne Marie; Chau, Tom

2012-04-01

Emotional responses can be induced by external sensory stimuli. For severely disabled nonverbal individuals who have no means of communication, the decoding of emotion may offer insight into an individual’s state of mind and his/her response to events taking place in the surrounding environment. Near-infrared spectroscopy (NIRS) provides an opportunity for bed-side monitoring of emotions via measurement of hemodynamic activity in the prefrontal cortex, a brain region known to be involved in emotion processing. In this paper, prefrontal cortex activity of ten able-bodied participants was monitored using NIRS as they listened to 78 music excerpts with different emotional content and a control acoustic stimuli consisting of the Brown noise. The participants rated their emotional state after listening to each excerpt along the dimensions of valence (positive versus negative) and arousal (intense versus neutral). These ratings were used to label the NIRS trial data. Using a linear discriminant analysis-based classifier and a two-dimensional time-domain feature set, trials with positive and negative emotions were discriminated with an average accuracy of 71.94% ± 8.19%. Trials with audible Brown noise representing a neutral response were differentiated from high arousal trials with an average accuracy of 71.93% ± 9.09% using a two-dimensional feature set. In nine out of the ten participants, response to the neutral Brown noise was differentiated from high arousal trials with accuracies exceeding chance level, and positive versus negative emotional differentiation accuracies exceeded the chance level in seven out of the ten participants. These results illustrate that NIRS recordings of the prefrontal cortex during presentation of music with emotional content can be automatically decoded in terms of both valence and arousal encouraging future investigation of NIRS-based emotion detection in individuals with severe disabilities.

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 suggest that the executive functions resolving interference at least partially differ between the groups. PMID:27014044

Enhanced prefrontal function with pharmacotherapy on a response inhibition task in adolescent bipolar disorder.

PubMed

Pavuluri, Mani N; Passarotti, Alessandra M; Harral, Erin M; Sweeney, John A

2010-11-01

The aim of the current study is to determine whether pharmacotherapy normalizes cognitive circuitry function supporting voluntary behavioral inhibition in adolescent bipolar disorder. Healthy controls and unmedicated patients with DSM-IV adolescent bipolar disorder in manic, mixed, or hypomanic episodes were matched on demographics and IQ (n = 13 per group; mean age = 14.4 ± 2.4 years). Functional magnetic resonance imaging studies were performed at baseline and after 14 weeks, during which time patients with adolescent bipolar disorder were treated initially with second-generation antipsychotics (SGAs) followed by lamotrigine monotherapy. The primary outcome measure was a Response Inhibition Task, which involved a planned motor response, already "on the way" to execution, that had to be voluntarily inhibited by the subjects in the trials in which a stop signal was presented. There were 6 blocks, each with a predominant rate of either "go" or "stop" trials. The study was conducted from June 2006 through July 2009. All patients showed significant improvement (P < .001) in both the manic and depressive symptoms from baseline. Behavioral data showed that accuracy improved over 14 weeks in patients and healthy controls. Significant time by group interaction effects for the difference between stop versus go blocks showed greater increases of activation in prefrontal (left inferior and middle frontal gyri and medial frontal gyrus bilaterally) and temporal (left superior temporal gyrus and right middle temporal gyrus) regions and greater decreases in activation in right putamen and bilateral thalamus at follow-up in the adolescent bipolar disorder group than in healthy controls. Increased ventrolateral prefrontal cortex function was related to clinical treatment response. Treatment with SGAs followed by lamotrigine monotherapy enhanced prefrontal and temporal lobe activity during a Response Inhibition Task demonstrating the reversal of disorder-relevant neural circuitry dysfunction in patients with adolescent bipolar disorder. Patient performance was not slowed down with this treatment regimen. clinicaltrials.gov Identifier: NCT00176228. © Copyright 2010 Physicians Postgraduate Press, Inc.

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.

Arrested development: early prefrontal lesions impair the maturation of moral judgement.

PubMed

Taber-Thomas, Bradley C; Asp, Erik W; Koenigs, Michael; Sutterer, Matthew; Anderson, Steven W; Tranel, Daniel

2014-04-01

Learning to make moral judgements based on considerations beyond self-interest is a fundamental aspect of moral development. A deficit in such learning is associated with poor socialization and criminal behaviour. The neural systems required for the acquisition and maturation of moral competency are not well understood. Here we show in a unique sample of neurological patients that focal lesions involving ventromedial prefrontal cortex, acquired during development, result in an abnormally egocentric pattern of moral judgement. In response to simple hypothetical moral scenarios, the patients were more likely than comparison participants to endorse self-interested actions that involved breaking moral rules or physically harming others in order to benefit themselves. This pattern (which we also found in subjects with psychopathy) differs from that of patients with adult-onset ventromedial prefrontal cortex lesions--the latter group showed normal rejection of egocentric rule violations. This novel contrast of patients with ventromedial prefrontal cortex lesions acquired during development versus during adulthood yields new evidence suggesting that the ventromedial prefrontal cortex is a critical neural substrate for the acquisition and maturation of moral competency that goes beyond self-interest to consider the welfare of others. Disruption to this affective neural system early in life interrupts moral development.

Soleus and lateral gastrocnemius H-reflexes during standing with unstable footwear.

PubMed

Friesenbichler, Bernd; Lepers, Romuald; Maffiuletti, Nicola A

2015-05-01

Unstable footwear has been shown to increase lower extremity muscle activity, but the reflex response to perturbations induced by this intervention is unknown. Twenty healthy subjects stood in stable and unstable footwear conditions (presented randomly) while H-reflex amplitude and background muscle activity were measured in the soleus and lateral gastrocnemius (LG) muscles. Wearing unstable footwear resulted in larger H-reflexes (normalized to the maximal M-wave) for the LG (+12%; P = 0.025), but not for the soleus (+4%; P > 0.05). Background activity of both muscles was significantly higher in the unstable condition. The H-reflex facilitation observed with unstable footwear was unexpected, as challenging postural conditions usually result in reflex depression. Increased muscle activity, decreased presynaptic inhibition, and/or more forward postural position may have (over-)compensated the expected reflex depression. Differences between LG and soleus H-reflex modulation may be due to diverging motor unit recruitment thresholds. © 2015 Wiley Periodicals, Inc.

Investigating the Usability and Acute Effects of a Bedside Video Console to Prefrontal Cortical Activity Alterations: A Preclinical Study in Healthy Elderly

PubMed Central

Knols, Ruud H.; Swanenburg, Jaap; De Bon, Dino; Gennaro, Federico; Wolf, Martin; Krüger, Bernard; Bettex, Dominique; de Bruin, Eling D.

2017-01-01

Elderly people at risk of developing cognitive decline; e.g., following surgery, may benefit from structured, challenging, and repetitive cognitive video training. This study assessed usability and acute effects of a newly developed bedside console (COPHYCON). Fifteen healthy elderly individuals performed a one-time 80-min intervention, including cognitive video games aimed at improving awareness and selective attention. Perceived usefulness and perceived ease of use (Technology Acceptance Model) were assessed together with measures of the achieved game level, reaction times, (in-) correct responses during ALERT and SELECT game play. Further, prefrontal cortical involvement of the regional cerebral hemoglobin saturation (rS02%) assessed with functional near infrared spectroscopy (fNIRS) (n = 5) and EEG power (n = 10) was analyzed. All participants completed the study without any adverse events. Perceived usefulness and perceived ease of use (TAM scores range 1–7) of the system varied between 3.9 and 6.3. The game levels reached for awareness varied between 9 and 11 (initial score 8–10), for reaction speed between 439 and 469 ms, and for correct responses between 74.1 and 78.8%. The highest level for the selective attention games was 2 (initial score 1), where reaction speed varied between 439 and 469 ms, correct responses between 96.2 and 98.5%, respectively. The decrease of rS02% in the right prefrontal cortex during gameplay was significantly (p < 0.001) lower, compared to the left prefrontal cortex. Four participants yielded significant lower rS02% measures after exergaming with the ALERT games (p < 0.000), but not with the SELECT games. EEG recordings of theta power significantly decreased in the averaged ~0.25–0.75 time interval for the left prefrontal cortex sensor across the cognitive game levels between the ALERT 1 and SELECT 1, as well as between SELECT 1 and 2 games. Participants rated the usability of the COPHYCON training positively. Further results indicate that video gaming may be an effective measure to affect prefrontal cortical functioning in elderly. The results warrant a clinical explorative study investigating the feasibility of the COPHYCON in a clinical setting. PMID:29234277

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

Distinct Neural Circuits Support Transient and Sustained Processes in Prospective Memory and Working Memory

PubMed Central

West, Robert; Braver, Todd

2009-01-01

Current theories are divided as to whether prospective memory (PM) involves primarily sustained processes such as strategic monitoring, or transient processes such as the retrieval of intentions from memory when a relevant cue is encountered. The current study examined the neural correlates of PM using a functional magnetic resonance imaging design that allows for the decomposition of brain activity into sustained and transient components. Performance of the PM task was primarily associated with sustained responses in a network including anterior prefrontal cortex (lateral Brodmann area 10), and these responses were dissociable from sustained responses associated with active maintenance in working memory. Additionally, the sustained responses in anterior prefrontal cortex correlated with faster response times for prospective responses. Prospective cues also elicited selective transient activity in a region of interest along the right middle temporal gyrus. The results support the conclusion that both sustained and transient processes contribute to efficient PM and provide novel constraints on the functional role of anterior PFC in higher-order cognition. PMID:18854581

Theta dynamics reveal domain-specific control over stimulus and response conflict.

PubMed

Nigbur, Roland; Cohen, Michael X; Ridderinkhof, K Richard; Stürmer, Birgit

2012-05-01

Cognitive control allows us to adjust to environmental changes. The medial frontal cortex (MFC) is thought to detect conflicts and recruit additional resources from other brain areas including the lateral prefrontal cortices. Here we investigated how the MFC acts in concert with visual, motor, and lateral prefrontal cortices to support adaptations of goal-directed behavior. Physiologically, these interactions may occur through local and long-range synchronized oscillation dynamics, particularly in the theta range (4-8 Hz). A speeded flanker task allowed us to investigate conflict-type-specific control networks for perceptual and response conflicts. Theta power over MFC was sensitive to both perceptual and response conflict. Interareal theta phase synchrony, however, indicated a selective enhancement specific for response conflicts between MFC and left frontal cortex as well as between MFC and the presumed motor cortex contralateral to the response hand. These findings suggest that MFC theta-band activity is both generally involved in conflict processing and specifically involved in linking a neural network controlling response conflict.

A General Role for Medial Prefrontal Cortex in Event Prediction

DTIC Science & Technology

2014-07-11

anterior cingulate cortex modulates attentional response: combined fMRI and ERP evidence. J. Cogn . Neurosci . 18, 766–780. doi: 10.1162/jocn.2006.18.5.766...losses in the anterior cingulate cortex. Cogn . Affect. Behav. Neurosci . 7, 327–336. doi: 10.3758/cabn.7.4.327 Shima, K., and Tanji, J. (1998). Role of...COMPUTATIONAL NEUROSCIENCE ORIGINAL RESEARCH ARTICLE published: 11 July 2014 doi: 10.3389/fncom.2014.00069 A general role for medial prefrontal

Amygdala-prefrontal cortical functional connectivity during implicit emotion processing differentiates youth with bipolar spectrum from youth with externalizing disorders.

PubMed

Hafeman, Danella; Bebko, Genna; Bertocci, Michele A; Fournier, Jay C; Chase, Henry W; Bonar, Lisa; Perlman, Susan B; Travis, Michael; Gill, Mary Kay; Diwadkar, Vaibhav A; Sunshine, Jeffrey L; Holland, Scott K; Kowatch, Robert A; Birmaher, Boris; Axelson, David; Horwitz, Sarah M; Arnold, L Eugene; Fristad, Mary A; Frazier, Thomas W; Youngstrom, Eric A; Findling, Robert L; Phillips, Mary L

2017-01-15

Both bipolar spectrum disorders (BPSD) and attention deficit hyperactivity disorder (ADHD) present with emotion-regulation deficits, but require different clinical management. We examined how the neurobiological underpinnings of emotion regulation might differentiate youth with BPSD versus ADHD (and healthy controls, HCs), specifically assessing functional connectivity (FxC) of amygdala-prefrontal circuitry during an implicit emotion processing task. We scanned a subset of the Longitudinal Assessment of Manic Symptoms (LAMS) sample, a clinically recruited cohort with elevated behavioral and emotional dysregulation, and age/sex-ratio matched HCs. Our sample consisted of 22 youth with BPSD, 30 youth with ADHD/no BPSD, and 26 HCs. We used generalized psychophysiological interaction (gPPI) to calculate group differences to emerging emotional faces vs. morphing shapes in FxC between bilateral amygdala and ventral prefrontal cortex/anterior cingulate cortex. FxC between amygdala and left ventrolateral prefrontal cortex (VLPFC) in response to emotions vs. shapes differed by group (p=.05): while BPSD showed positive FxC (emotions>shapes), HC and ADHD showed inverse FxC (emotions

Cocaine. Selective regional effects on central monoamines.

PubMed

Hadfield, M G

1995-01-01

Cocaine HCl (0, 10, or 50 mg/kg) was injected into adult male ICR mice ip. Thirty minutes later, the brains were removed, and nine regions were isolated: olfactory bulbs, olfactory tubercles, prefrontal cortex, septum, striatum, amygdala, hypothalamus, hippocampus, and thalamus. Using high-performance liquid chromatography, concentrations of norepinephrine, dopamine, serotonin, and their major metabolites and the metabolite/neurotransmitter ratios were determined as an indicator of utilization. Serotonergic systems responded most dramatically. 5HIAA/5-HT decreases were seen in all the brain regions, except the septum, hippocampus, and olfactory bulbs. In most instances, the alterations were dose-dependent. The most profound changes were seen in the amygdala, prefrontal cortex, hypothalamus, and thalamus. For noradrenergic systems, significant responses were seen only in the amygdala, prefrontal cortex, and hypothalamus, but then only at the lower dose. The dopaminergic responses were more complex and not always dose-dependent. The DOPAC/DA ratio was decreased only in the amygdala and striatum at the lower dose, and the olfactory tubercles at the higher dose. It was increased in the septum. The HVA/DA ratios were decreased in the amygdala, prefrontal cortex, and hypothalamus, but only at the lower dose (like MHPG/NE). The 3MT/DA ratio was decreased in the thalamus at the lower dose and in the olfactory tubercles at the higher dose, whereas it was increased in the prefrontal cortex at the lower dose. The HVA and DOPAC routes of degradation were both utilized only by the amygdala. Thus, cocaine produced its most comprehensive effects in this nucleus, as well as the greatest absolute percentage changes for all three of the monoamine systems studied.

Effect of gender and hand laterality on pain processing in human neonates.

PubMed

Ozawa, Mio; Kanda, Katsuya; Hirata, Michio; Kusakawa, Isao; Suzuki, Chieko

2011-01-01

Previous studies in adults have reported that handedness and gender can affect pain perception. However, it is currently unclear when these differences emerge in human development. Therefore, we examined prefrontal responses to pain stimulation among newborns during their first acute pain experience after birth. Forty newborns at 4-6 days postnatal age were observed during clinically required blood sampling while prefrontal activation was measured with near infrared spectroscopy. Blood sampling in this study was the first experience of a procedure involving skin breaking for these infants. We divided subjects into a right-hand stimulation group (n=21) and a left-hand stimulation group (n=19), depending on whether blood was sampled from the right or the left hand. A three-way analysis of variance (ANOVA) was conducted to examine the effects of several variables on the magnitude of the oxy-Hb value in response to pain stimulus, including stimulus side (right hand or left hand), gender (male or female), recording side (right prefrontal area or left prefrontal area) and interactions between these variables. The data revealed a significant effect of stimulus side (F (1, 72)=9.892, P=0.002), showing that the right-hand stimulation induced a greater prefrontal activation than the left-hand stimulation. No significant gender difference or interactions were found. Our findings suggest that hand laterality affects pain perception even in neonates. However, gender differences in pain perception did not appear to occur during the neonatal period. Further investigations using brain-imaging techniques are required to identify laterality- or gender-related differences in pain processing in humans. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

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.

Memory retrieval in response to partial cues requires NMDA receptor-dependent neurotransmission in the medial prefrontal cortex.

PubMed

Jo, Yong Sang; Choi, June-Seek

2014-03-01

The medial prefrontal cortex (mPFC) has been suggested to play a crucial role in retrieving detailed contextual information about a previous learning episode in response to a single retrieval cue. However, few studies investigated the neurochemical mechanisms that mediate the prefrontal retrieval process. In the current study, we examined whether N-methyl-D-aspartate receptors (NMDARs) in the mPFC were necessary for retrieval of a well-learned spatial location on the basis of partial or degraded spatial cues. Rats were initially trained to find a hidden platform in the Morris water maze using four extramaze cues in the surrounding environment. Their retrieval performance was subsequently tested under different cue conditions. Infusions of DL-2-amino-5-phosphonovaleric acid (APV), a NMDAR antagonist, significantly disrupted memory retrieval when three of the original cues were removed. By contrast, APV injections into the mPFC did not affect animals' retrieval performance when the original cues were presented or when three novels landmarks were added alongside the original cues. These results indicate that prefrontal NMDARs are required for memory retrieval when allocentric spatial information is degraded. NMDAR-dependent neurotransmission in the mPFC may facilitate an active retrieval process to reactivate complete contextual representations associated with partial retrieval cues. Copyright © 2013 Elsevier Inc. All rights reserved.

Resolving response, decision, and strategic control: evidence for a functional topography in dorsomedial prefrontal cortex.

PubMed

Venkatraman, Vinod; Rosati, Alexandra G; Taren, Adrienne A; Huettel, Scott A

2009-10-21

The dorsomedial prefrontal cortex (DMPFC) plays a central role in aspects of cognitive control and decision making. Here, we provide evidence for an anterior-to-posterior topography within the DMPFC using tasks that evoke three distinct forms of control demands--response, decision, and strategic--each of which could be mapped onto independent behavioral data. Specifically, we identify three spatially distinct regions within the DMPFC: a posterior region associated with control demands evoked by multiple incompatible responses, a middle region associated with control demands evoked by the relative desirability of decision options, and an anterior region that predicts control demands related to deviations from an individual's preferred decision-making strategy. These results provide new insight into the functional organization of DMPFC and suggest how recent controversies about its role in complex decision making and response mapping can be reconciled.

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

Resolving Response, Decision, and Strategic Control: Evidence for a Functional Topography in Dorsomedial Prefrontal Cortex

PubMed Central

Venkatraman, Vinod; Rosati, Alexandra G.; Taren, Adrienne A.; Huettel, Scott A.

2009-01-01

The dorsomedial prefrontal cortex (DMPFC) plays a central role in aspects of cognitive control and decision making. Here, we provide evidence for an anterior-to-posterior topography within the DMPFC using tasks that evoke three distinct forms of control demands – response, decision, and strategic – each of which could be mapped on to independent behavioral data. Specifically, we identify three spatially distinct regions within the DMPFC: a posterior region associated with control demands evoked by multiple incompatible responses, a middle region associated with control demands evoked by the relative desirability of decision options, and an anterior region that predicts control demands related to deviations from an individual's preferred decision-making strategy. These results provide new insight into the functional organization of DMPFC, and suggest how recent controversies about its role in complex decision making and response mapping can be reconciled. PMID:19846703

Clinically Anxious Individuals Show Disrupted Feedback between Inferior Frontal Gyrus and Prefrontal-Limbic Control Circuit.

PubMed

Cha, Jiook; DeDora, Daniel; Nedic, Sanja; Ide, Jaime; Greenberg, Tsafrir; Hajcak, Greg; Mujica-Parodi, Lilianne Rivka

2016-04-27

Clinical anxiety is associated with generalization of conditioned fear, in which innocuous stimuli elicit alarm. Using Pavlovian fear conditioning (electric shock), we quantify generalization as the degree to which subjects' neurobiological responses track perceptual similarity gradients to a conditioned stimulus. Previous studies show that the ventromedial prefrontal cortex (vmPFC) inversely and ventral tegmental area directly track the gradient of perceptual similarity to the conditioned stimulus in healthy individuals, whereas clinically anxious individuals fail to discriminate. Here, we extend this work by identifying specific functional roles within the prefrontal-limbic circuit. We analyzed fMRI time-series acquired from 57 human subjects during a fear generalization task using entropic measures of circuit-wide regulation and feedback (power spectrum scale invariance/autocorrelation), in combination with structural (diffusion MRI-probabilistic tractography) and functional (stochastic dynamic causal modeling) measures of prefrontal-limbic connectivity within the circuit. Group comparison and correlations with anxiety severity across 57 subjects revealed dysregulatory dynamic signatures within the inferior frontal gyrus (IFG), which our prior work has linked to impaired feedback within the circuit. Bayesian model selection then identified a fully connected prefrontal-limbic model comprising the IFG, vmPFC, and amygdala. Dysregulatory IFG dynamics were associated with weaker reciprocal excitatory connectivity between the IFG and the vmPFC. The vmPFC exhibited inhibitory influence on the amygdala. Our current results, combined with our previous work across a threat-perception spectrum of 137 subjects and a meta-analysis of 366 fMRI studies, dissociate distinct roles for three prefrontal-limbic regions, wherein the IFG provides evaluation of stimulus meaning, which then informs the vmPFC in inhibiting the amygdala. Affective neuroscience has generally treated prefrontal regions (orbitofrontal cortex, dorsolateral prefrontal cortex, inferior frontal gyrus, ventromedial prefrontal cortex) equivalently as inhibitory components of the prefrontal-limbic system. Yet research across the anxiety spectrum suggests that the inferior frontal gyrus may have a more complex role in emotion regulation, as this region shows abnormal function in disorders of both hyperarousal and hypoarousal. Using entropic measures of circuit-wide regulation and feedback, in combination with measures of structural and functional connectivity, we dissociate distinct roles for three prefrontal-limbic regions, wherein the inferior frontal gyrus provides evaluation of stimulus meaning, which then informs the ventromedial prefrontal cortex in inhibiting the amygdala. This reconfiguration coheres with studies of conceptual disambiguation also implicating the inferior frontal gyrus. Copyright © 2016 the authors 0270-6474/16/364708-11$15.00/0.

Amodal processing in human prefrontal cortex.

PubMed

Tamber-Rosenau, Benjamin J; Dux, Paul E; Tombu, Michael N; Asplund, Christopher L; Marois, René

2013-07-10

Information enters the cortex via modality-specific sensory regions, whereas actions are produced by modality-specific motor regions. Intervening central stages of information processing map sensation to behavior. Humans perform this central processing in a flexible, abstract manner such that sensory information in any modality can lead to response via any motor system. Cognitive theories account for such flexible behavior by positing amodal central information processing (e.g., "central executive," Baddeley and Hitch, 1974; "supervisory attentional system," Norman and Shallice, 1986; "response selection bottleneck," Pashler, 1994). However, the extent to which brain regions embodying central mechanisms of information processing are amodal remains unclear. Here we apply multivariate pattern analysis to functional magnetic resonance imaging (fMRI) data to compare response selection, a cognitive process widely believed to recruit an amodal central resource across sensory and motor modalities. We show that most frontal and parietal cortical areas known to activate across a wide variety of tasks code modality, casting doubt on the notion that these regions embody a central processor devoid of modality representation. Importantly, regions of anterior insula and dorsolateral prefrontal cortex consistently failed to code modality across four experiments. However, these areas code at least one other task dimension, process (instantiated as response selection vs response execution), ensuring that failure to find coding of modality is not driven by insensitivity of multivariate pattern analysis in these regions. We conclude that abstract encoding of information modality is primarily a property of subregions of the prefrontal cortex.

Prefrontal Electrical Stimulation in Non-depressed Reduces Levels of Reported Negative Affects from Daily Stressors

PubMed Central

Austin, Adelaide; Jiga-Boy, Gabriela M.; Rea, Sara; Newstead, Simon A.; Roderick, Sian; Davis, Nick J.; Clement, R. Marc; Boy, Frédéric

2016-01-01

Negative emotional responses to the daily life stresses have cumulative effects which, in turn, impose wide-ranging negative constraints on emotional well being and neurocognitive performance (Kalueff and Nutt, 2007; Nadler et al., 2010; Charles et al., 2013). Crucial cognitive functions such as memory and problem solving, as well more short term emotional responses (e.g., anticipation of- and response to- monetary rewards or losses) are influenced by mood. The negative impact of these behavioral responses is felt at the individual level, but it also imposes major economic burden on modern healthcare systems. Although much research has been undertaken to understand the underlying mechanisms of depressed mood and design efficient treatment pathways, comparatively little was done to characterize mood modulations that remain within the boundaries of a healthy mental functioning. In one placebo-controlled experiment, we applied daily prefrontal transcranial Direct Current Stimulation (tDCS) at five points in time, and found reliable improvements on self-reported mood evaluation. Using a new team of experimenters, we replicated this finding in an independent double-blinded placebo-controlled experiment and showed that stimulation over a shorter period of time (3 days) is sufficient to create detectable mood improvements. Taken together, our data show that repeated bilateral prefrontal tDCS can reduce psychological distress in non-depressed individuals. PMID:26973591

'Just can't hide it': a behavioral and lesion study on emotional response modulation after right prefrontal damage.

PubMed

Salas, Christian E; Castro, Osvaldo; Yuen, Kenneth Sl; Radovic, Darinka; d'Avossa, Giovanni; Turnbull, Oliver H

2016-10-01

Historically, emotion regulation problems have been reported as a common consequence of right prefrontal cortex (rPFC) damage. It has been proposed that the rPFC, particularly the rIFG, has a key role inhibiting prepotent reflexive actions, thus contributing to emotion regulation and self-regulation. This study is the first to directly explore this hypothesis, by testing whether damage to the rIFG compromises the voluntary modulation of emotional responses, and whether performance on inhibition tasks is associated with emotion regulation. 10 individuals with unilateral right prefrontal damage and 15 matched healthy controls were compared on a well-known response modulation task. During the task participants had to amplify and suppress their facial emotional expressions, while watching film clips eliciting amusement. Measures of executive control, emotion regulation strategies usage and symptomatology were also collected. As a group, individuals with rPFC damage presented a significantly reduced range of response modulation compared with controls. In addition, performance in the suppression task was associated with measures of cognitive inhibition and suppression usage. Interestingly, these effects were driven primarily by a subgroup of individuals with rPFC damage, all of whom also had damage to the right posterior insula, and who presented a marked impairment in suppressing facial emotional expressions. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Prosocial attitudes and empathic behavior in emotional positive versus negative situations: brain response (ERPs) and source localization (LORETA) analysis.

PubMed

Balconi, Michela; Canavesio, Ylenia

2013-03-01

The present research firstly investigated the neural correlates (ERPs, event-related potentials) of attitudes to engage in prosocial-helping behaviors, and secondly, it analyzed the relation between these brain-based potentials and personal profile (high vs. low empathic profile). It was considered the subjects' behavior in response to specific emotional situations (positive vs. negative) in case it was required a possible prosocial intervention. Thirty-one subjects were invited to empathize with the emotional contexts (videotapes that reproduced two person's exchanges) and to decide whether to intervene or not to support these persons. BEES questionnaire for empathic behavior was submitted to the subjects after the experimental session. ERP acquisition and LORETA source analysis revealed a negative ongoing deflection (N200 effect) more prefrontally distributed (dorsolateral prefrontal cortex) in response to prosocial intervention options mainly for negative and positive contexts. Moreover, a significant positive correlation was found between high-empathic profiles, intervention behaviors (higher frequency of interventions) and N200 amplitude (higher peak). These results highlight the role of emotions in prosocial behavior, since the N200 effect was considered a marker of the emotional significance of the interpersonal situation. Secondly, the empathic trait may explain the prosocial decisional processes: Higher empathic trait contributes to induce subject's intervention behavior which in turn appears to be directly related to the cortical responsiveness within the prefrontal areas.

‘Just can’t hide it’: a behavioral and lesion study on emotional response modulation after right prefrontal damage

PubMed Central

Castro, Osvaldo; Yuen, Kenneth SL; Radovic, Darinka; d’Avossa, Giovanni; Turnbull, Oliver H.

2016-01-01

Introduction: Historically, emotion regulation problems have been reported as a common consequence of right prefrontal cortex (rPFC) damage. It has been proposed that the rPFC, particularly the rIFG, has a key role inhibiting prepotent reflexive actions, thus contributing to emotion regulation and self-regulation. This study is the first to directly explore this hypothesis, by testing whether damage to the rIFG compromises the voluntary modulation of emotional responses, and whether performance on inhibition tasks is associated with emotion regulation. Method: 10 individuals with unilateral right prefrontal damage and 15 matched healthy controls were compared on a well-known response modulation task. During the task participants had to amplify and suppress their facial emotional expressions, while watching film clips eliciting amusement. Measures of executive control, emotion regulation strategies usage and symptomatology were also collected. Results: As a group, individuals with rPFC damage presented a significantly reduced range of response modulation compared with controls. In addition, performance in the suppression task was associated with measures of cognitive inhibition and suppression usage. Interestingly, these effects were driven primarily by a subgroup of individuals with rPFC damage, all of whom also had damage to the right posterior insula, and who presented a marked impairment in suppressing facial emotional expressions PMID:27317928

Hierarchy stability moderates the effect of status on stress and performance in humans

PubMed Central

Knight, Erik L.; Mehta, Pranjal H.

2017-01-01

High social status reduces stress responses in numerous species, but the stress-buffering effect of status may dissipate or even reverse during times of hierarchical instability. In an experimental test of this hypothesis, 118 participants (57.3% female) were randomly assigned to a high- or low-status position in a stable or unstable hierarchy and were then exposed to a social-evaluative stressor (a mock job interview). High status in a stable hierarchy buffered stress responses and improved interview performance, but high status in an unstable hierarchy boosted stress responses and did not lead to better performance. This general pattern of effects was observed across endocrine (cortisol and testosterone), psychological (feeling in control), and behavioral (competence, dominance, and warmth) responses to the stressor. The joint influence of status and hierarchy stability on interview performance was explained by feelings of control and testosterone reactivity. Greater feelings of control predicted enhanced interview performance, whereas increased testosterone reactivity predicted worse performance. These results provide direct causal evidence that high status confers adaptive benefits for stress reduction and performance only when the social hierarchy is stable. When the hierarchy is unstable, high status actually exacerbates stress responses. PMID:27994160

Hierarchy stability moderates the effect of status on stress and performance in humans.

PubMed

Knight, Erik L; Mehta, Pranjal H

2017-01-03

High social status reduces stress responses in numerous species, but the stress-buffering effect of status may dissipate or even reverse during times of hierarchical instability. In an experimental test of this hypothesis, 118 participants (57.3% female) were randomly assigned to a high- or low-status position in a stable or unstable hierarchy and were then exposed to a social-evaluative stressor (a mock job interview). High status in a stable hierarchy buffered stress responses and improved interview performance, but high status in an unstable hierarchy boosted stress responses and did not lead to better performance. This general pattern of effects was observed across endocrine (cortisol and testosterone), psychological (feeling in control), and behavioral (competence, dominance, and warmth) responses to the stressor. The joint influence of status and hierarchy stability on interview performance was explained by feelings of control and testosterone reactivity. Greater feelings of control predicted enhanced interview performance, whereas increased testosterone reactivity predicted worse performance. These results provide direct causal evidence that high status confers adaptive benefits for stress reduction and performance only when the social hierarchy is stable. When the hierarchy is unstable, high status actually exacerbates stress responses.

Recognition memory of newly learned faces.

PubMed

Ishai, Alumit; Yago, Elena

2006-12-11

We used event-related fMRI to study recognition memory of newly learned faces. Caucasian subjects memorized unfamiliar, neutral and happy South Korean faces and 4 days later performed a memory retrieval task in the MR scanner. We predicted that previously seen faces would be recognized faster and more accurately and would elicit stronger neural activation than novel faces. Consistent with our hypothesis, novel faces were recognized more slowly and less accurately than previously seen faces. We found activation in a distributed cortical network that included face-responsive regions in the visual cortex, parietal and prefrontal regions, and the hippocampus. Within all regions, correctly recognized, previously seen faces evoked stronger activation than novel faces. Additionally, in parietal and prefrontal cortices, stronger activation was observed during correct than incorrect trials. Finally, in the hippocampus, false alarms to happy faces elicited stronger responses than false alarms to neutral faces. Our findings suggest that face recognition memory is mediated by stimulus-specific representations stored in extrastriate regions; parietal and prefrontal regions where old and new items are classified; and the hippocampus where veridical memory traces are recovered.

Frontal Brain Asymmetry and Willingness to Pay.

PubMed

Ramsøy, Thomas Z; Skov, Martin; Christensen, Maiken K; Stahlhut, Carsten

2018-01-01

Consumers frequently make decisions about how much they are willing to pay (WTP) for specific products and services, but little is known about the neural mechanisms underlying such calculations. In this study, we were interested in testing whether specific brain activation-the asymmetry in engagement of the prefrontal cortex-would be related to consumer choice. Subjects saw products and subsequently decided how much they were willing to pay for each product, while undergoing neuroimaging using electroencephalography. Our results demonstrate that prefrontal asymmetry in the gamma frequency band, and a trend in the beta frequency band that was recorded during product viewing was significantly related to subsequent WTP responses. Frontal asymmetry in the alpha band was not related to WTP decisions. Besides suggesting separate neuropsychological mechanisms of consumer choice, we find that one specific measure-the prefrontal gamma asymmetry-was most strongly related to WTP responses, and was most coupled to the actual decision phase. These findings are discussed in light of the psychology of WTP calculations, and in relation to the recent emergence of consumer neuroscience and neuromarketing.

Frontal Brain Asymmetry and Willingness to Pay

PubMed Central

Ramsøy, Thomas Z.; Skov, Martin; Christensen, Maiken K.; Stahlhut, Carsten

2018-01-01

Consumers frequently make decisions about how much they are willing to pay (WTP) for specific products and services, but little is known about the neural mechanisms underlying such calculations. In this study, we were interested in testing whether specific brain activation—the asymmetry in engagement of the prefrontal cortex—would be related to consumer choice. Subjects saw products and subsequently decided how much they were willing to pay for each product, while undergoing neuroimaging using electroencephalography. Our results demonstrate that prefrontal asymmetry in the gamma frequency band, and a trend in the beta frequency band that was recorded during product viewing was significantly related to subsequent WTP responses. Frontal asymmetry in the alpha band was not related to WTP decisions. Besides suggesting separate neuropsychological mechanisms of consumer choice, we find that one specific measure—the prefrontal gamma asymmetry—was most strongly related to WTP responses, and was most coupled to the actual decision phase. These findings are discussed in light of the psychology of WTP calculations, and in relation to the recent emergence of consumer neuroscience and neuromarketing. PMID:29662432

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. Published by Oxford University Press on behalf of CINP.

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 Physiological Society.

Electroconvulsive Therapy Response in Major Depressive Disorder: A Pilot Functional Network Connectivity Resting State fMRI Investigation

PubMed Central

Abbott, Christopher C.; Lemke, Nicholas T.; Gopal, Shruti; Thoma, Robert J.; Bustillo, Juan; Calhoun, Vince D.; Turner, Jessica A.

2013-01-01

Major depressive disorder (MDD) is associated with increased functional connectivity in specific neural networks. Electroconvulsive therapy (ECT), the gold-standard treatment for acute, treatment-resistant MDD, but temporal dependencies between networks associated with ECT response have yet to be investigated. In the present longitudinal, case–control investigation, we used independent component analysis to identify distinct networks of brain regions with temporally coherent hemodynamic signal change and functional network connectivity (FNC) to assess component time course correlations across these networks. MDD subjects completed imaging and clinical assessments immediately prior to the ECT series and a minimum of 5 days after the last ECT treatment. We focused our analysis on four networks affected in MDD: the subcallosal cingulate gyrus, default mode, dorsal lateral prefrontal cortex, and dorsal medial prefrontal cortex (DMPFC). In an older sample of ECT subjects (n = 12) with MDD, remission associated with the ECT series reverses the relationship from negative to positive between the posterior default mode (p_DM) and two other networks: the DMPFC and left dorsal lateral prefrontal cortex (l_DLPFC). Relative to demographically healthy subjects (n = 12), the FNC between the p_DM areas and the DMPFC normalizes with ECT response. The FNC changes following treatment did not correlate with symptom improvement; however, a direct comparison between ECT remitters and non-remitters showed the pattern of increased FNC between the p_DM and l_DLPFC following ECT to be specific to those who responded to the treatment. The differences between ECT remitters and non-remitters suggest that this increased FNC between p_DM areas and the left dorsolateral prefrontal cortex is a neural correlate and potential biomarker of recovery from a depressed episode. PMID:23459749

Electroconvulsive therapy response in major depressive disorder: a pilot functional network connectivity resting state FMRI investigation.

PubMed

Abbott, Christopher C; Lemke, Nicholas T; Gopal, Shruti; Thoma, Robert J; Bustillo, Juan; Calhoun, Vince D; Turner, Jessica A

2013-01-01

Major depressive disorder (MDD) is associated with increased functional connectivity in specific neural networks. Electroconvulsive therapy (ECT), the gold-standard treatment for acute, treatment-resistant MDD, but temporal dependencies between networks associated with ECT response have yet to be investigated. In the present longitudinal, case-control investigation, we used independent component analysis to identify distinct networks of brain regions with temporally coherent hemodynamic signal change and functional network connectivity (FNC) to assess component time course correlations across these networks. MDD subjects completed imaging and clinical assessments immediately prior to the ECT series and a minimum of 5 days after the last ECT treatment. We focused our analysis on four networks affected in MDD: the subcallosal cingulate gyrus, default mode, dorsal lateral prefrontal cortex, and dorsal medial prefrontal cortex (DMPFC). In an older sample of ECT subjects (n = 12) with MDD, remission associated with the ECT series reverses the relationship from negative to positive between the posterior default mode (p_DM) and two other networks: the DMPFC and left dorsal lateral prefrontal cortex (l_DLPFC). Relative to demographically healthy subjects (n = 12), the FNC between the p_DM areas and the DMPFC normalizes with ECT response. The FNC changes following treatment did not correlate with symptom improvement; however, a direct comparison between ECT remitters and non-remitters showed the pattern of increased FNC between the p_DM and l_DLPFC following ECT to be specific to those who responded to the treatment. The differences between ECT remitters and non-remitters suggest that this increased FNC between p_DM areas and the left dorsolateral prefrontal cortex is a neural correlate and potential biomarker of recovery from a depressed episode.

Testing assumptions on prefrontal transcranial direct current stimulation: Comparison of electrode montages using multimodal fMRI.

PubMed

Wörsching, Jana; Padberg, Frank; Goerigk, Stephan; Heinz, Irmgard; Bauer, Christine; Plewnia, Christian; Hasan, Alkomiet; Ertl-Wagner, Birgit; Keeser, Daniel

2018-05-04

Transcranial direct current stimulation (tDCS) of the prefrontal cortex (PFC) has been widely applied in cognitive neurosciences and advocated as a therapeutic intervention, e.g. in major depressive disorder. Although several targets and protocols have been suggested, comparative studies of tDCS parameters, particularly electrode montages and their cortical targets, are still lacking. This study investigated a priori hypotheses on specific effects of prefrontal-tDCS montages by using multimodal functional magnetic resonance imaging (fMRI) in healthy participants. 28 healthy male participants underwent three common active-tDCS montages and sham tDCS in a pseudo-randomized order, comprising a total of 112 tDCS-fMRI sessions. Active tDCS was applied at 2 mA for 20 min. Before and after tDCS, a resting-state fMRI (RS fMRI) was recorded, followed by a task fMRI with a delayed-response working-memory (DWM) task for assessing cognitive control over emotionally negative or neutral distractors. After tDCS with a cathode-F3/anode-F4 montage, RS-fMRI connectivity decreased in a medial part of the left PFC. Also, after the same stimulation condition, regional brain activity during DWM retrieval decreased more in this area after negative than after neutral distraction, and responses to the DWM task were faster, independent of distractor type. The current study does not confirm our a priori hypotheses on direction and localization of polarity-dependent tDCS effects using common bipolar electrode montages over PFC regions, but it provides evidence for montage-specific effects on multimodal neurophysiological and behavioral outcome measures. Systematic research on the actual targets and the respective dose-response relationships of prefrontal tDCS is warranted. Copyright © 2018 Elsevier Inc. All rights reserved.

Implicit sequence-specific motor learning after sub-cortical stroke is associated with increased prefrontal brain activations: An fMRI study

PubMed Central

Meehan, Sean K.; Randhawa, Bubblepreet; Wessel, Brenda; Boyd, Lara A.

2010-01-01

Implicit motor learning is preserved after stroke, but how the brain compensates for damage to facilitate learning is unclear. We used a random effects analysis to determine how stroke alters patterns of brain activity during implicit sequence-specific motor learning as compared to general improvements in motor control. Nine healthy participants and 9 individuals with chronic, right focal sub-cortical stroke performed a continuous joystick-based tracking task during an initial fMRI session, over 5 days of practice, and a retention test during a separate fMRI session. Sequence-specific implicit motor learning was differentiated from general improvements in motor control by comparing tracking performance on a novel, repeated tracking sequences during early practice and again at the retention test. Both groups demonstrated implicit sequence-specific motor learning at the retention test, yet substantial differences were apparent. At retention, healthy control participants demonstrated increased BOLD response in left dorsal premotor cortex (BA 6) but decreased BOLD response left dorsolateral prefrontal cortex (DLPFC; BA 9) during repeated sequence tracking. In contrast, at retention individuals with stroke did not show this reduction in DLPFC during repeated tracking. Instead implicit sequence-specific motor learning and general improvements in motor control were associated with increased BOLD response in the left middle frontal gyrus BA 8, regardless of sequence type after stroke. These data emphasize the potential importance of a prefrontal-based attentional network for implicit motor learning after stroke. The present study is the first to highlight the importance of the prefrontal cortex for implicit sequence-specific motor learning after stroke. PMID:20725908

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.

Prefrontal responses to Stroop tasks in subjects with post-traumatic stress disorder assessed by functional near infrared spectroscopy.

PubMed

Yennu, Amarnath; Tian, Fenghua; Smith-Osborne, Alexa; J Gatchel, Robert; Woon, Fu Lye; Liu, Hanli

2016-07-25

Studies on posttraumatic stress disorder (PTSD) showing attentional deficits have implicated abnormal activities in the frontal lobe. In this study, we utilized multichannel functional near-infrared spectroscopy (fNIRS) to investigate selective attention-related hemodynamic activity in the prefrontal cortex among 15 combat-exposed war-zone veterans with PTSD and 13 age- and gender-matched healthy controls. While performing the incongruent Stroop task, healthy controls showed significant activations in the left lateral prefrontal cortex (LPFC) compared to baseline readings. This observation is consistent with previously reported results. In comparison, subjects with PTSD failed to activate left LPFC during the same Stroop task. Our observations may implicate that subjects with PTSD experienced difficulty in overcoming Stroop interference. We also observed significant negative correlation between task reaction times and hemodynamic responses from left LPFC during the incongruent Stroop task in the PTSD group. Regarding the methodology used in this study, we have learned that an appropriate design of Stroop paradigms is important for meeting an optimal cognitive load which can lead to better brain image contrasts in response to Stroop interference between healthy versus PTSD subjects. Overall, the feasibility of fNIRS for studying and mapping neural correlates of selective attention and interference in subjects with PTSD is reported.

Prefrontal responses to Stroop tasks in subjects with post-traumatic stress disorder assessed by functional near infrared spectroscopy

PubMed Central

Yennu, Amarnath; Tian, Fenghua; Smith-Osborne, Alexa; J. Gatchel, Robert; Woon, Fu Lye; Liu, Hanli

2016-01-01

Studies on posttraumatic stress disorder (PTSD) showing attentional deficits have implicated abnormal activities in the frontal lobe. In this study, we utilized multichannel functional near-infrared spectroscopy (fNIRS) to investigate selective attention-related hemodynamic activity in the prefrontal cortex among 15 combat-exposed war-zone veterans with PTSD and 13 age- and gender-matched healthy controls. While performing the incongruent Stroop task, healthy controls showed significant activations in the left lateral prefrontal cortex (LPFC) compared to baseline readings. This observation is consistent with previously reported results. In comparison, subjects with PTSD failed to activate left LPFC during the same Stroop task. Our observations may implicate that subjects with PTSD experienced difficulty in overcoming Stroop interference. We also observed significant negative correlation between task reaction times and hemodynamic responses from left LPFC during the incongruent Stroop task in the PTSD group. Regarding the methodology used in this study, we have learned that an appropriate design of Stroop paradigms is important for meeting an optimal cognitive load which can lead to better brain image contrasts in response to Stroop interference between healthy versus PTSD subjects. Overall, the feasibility of fNIRS for studying and mapping neural correlates of selective attention and interference in subjects with PTSD is reported. PMID:27452397

Prefrontal responses to Stroop tasks in subjects with post-traumatic stress disorder assessed by functional near infrared spectroscopy

NASA Astrophysics Data System (ADS)

Yennu, Amarnath; Tian, Fenghua; Smith-Osborne, Alexa; J. Gatchel, Robert; Woon, Fu Lye; Liu, Hanli

2016-07-01

Studies on posttraumatic stress disorder (PTSD) showing attentional deficits have implicated abnormal activities in the frontal lobe. In this study, we utilized multichannel functional near-infrared spectroscopy (fNIRS) to investigate selective attention-related hemodynamic activity in the prefrontal cortex among 15 combat-exposed war-zone veterans with PTSD and 13 age- and gender-matched healthy controls. While performing the incongruent Stroop task, healthy controls showed significant activations in the left lateral prefrontal cortex (LPFC) compared to baseline readings. This observation is consistent with previously reported results. In comparison, subjects with PTSD failed to activate left LPFC during the same Stroop task. Our observations may implicate that subjects with PTSD experienced difficulty in overcoming Stroop interference. We also observed significant negative correlation between task reaction times and hemodynamic responses from left LPFC during the incongruent Stroop task in the PTSD group. Regarding the methodology used in this study, we have learned that an appropriate design of Stroop paradigms is important for meeting an optimal cognitive load which can lead to better brain image contrasts in response to Stroop interference between healthy versus PTSD subjects. Overall, the feasibility of fNIRS for studying and mapping neural correlates of selective attention and interference in subjects with PTSD is reported.

Positive and Negative Affect and Adolescent Adjustment: Moderation Effects of Prefrontal Functioning.

PubMed

Brieant, Alexis; Holmes, Christopher J; Maciejewski, Dominique; Lee, Jacob; Deater-Deckard, Kirby; King-Casas, Brooks; Kim-Spoon, Jungmeen

2018-03-01

We examined whether cognitive control moderates the effects of emotion on adolescent internalizing and externalizing symptomatology in a longitudinal study of 138 adolescents. Self-reported positive affect (PA) and negative affect and behavioral and neural indicators of cognitive control, indexed by performance and prefrontal hemodynamic response during a cognitive interference task, were collected at Time 1. Self-reported internalizing and externalizing symptomatology were collected at Time 1 and Time 2 (1 year later). Results indicated that higher PA predicted decreases in externalizing symptomatology, but only for adolescents with poor neural cognitive control. No moderation effects were found for behavioral cognitive control. Findings imply the beneficial effects of PA on the development of externalizing problems among adolescents with poor prefrontal functioning. © 2018 Society for Research on Adolescence.

Differential mesocorticolimbic responses to palatable food in binge eating prone and binge eating resistant female rats.

PubMed

Sinclair, Elaine B; Culbert, Kristen M; Gradl, Dana R; Richardson, Kimberlei A; Klump, Kelly L; Sisk, Cheryl L

2015-12-01

Binge eating is a key symptom of many eating disorders (e.g. binge eating disorder, bulimia nervosa, anorexia nervosa binge/purge type), yet the neurobiological underpinnings of binge eating are poorly understood. The mesocorticolimbic reward circuit, including the nucleus accumbens and the medial prefrontal cortex, is likely involved because this circuit mediates the hedonic value and incentive salience of palatable foods (PF). Here we tested the hypothesis that higher propensity for binge eating is associated with a heightened response (i.e., Fos induction) of the nucleus accumbens and medial prefrontal cortex to PF, using an animal model that identifies binge eating prone (BEP) and binge eating resistant (BER) rats. Forty adult female Sprague-Dawley rats were given intermittent access to PF (high fat pellets) 3×/week for 3 weeks. Based on a pattern of either consistently high or consistently low PF consumption across these feeding tests, 8 rats met criteria for categorization as BEP, and 11 rats met criteria for categorization as BER. One week after the final feeding test, BEP and BER rats were either exposed to PF in their home cages or were given no PF in their home cages for 1h prior to perfusion, leading to three experimental groups for the Fos analysis: BEPs given PF, BERs given PF, and a No PF control group. The total number of Fos-immunoreactive (Fos-ir) cells in the nucleus accumbens core and shell, and the cingulate, prelimbic, and infralimbic regions of the medial prefrontal cortex was estimated by stereological analysis. PF induced higher Fos expression in the nucleus accumbens shell and core and in the prelimbic and infralimbic cortex of BEP rats compared to No PF controls. Throughout the nucleus accumbens and medial prefrontal cortex, PF induced higher Fos expression in BEP than in BER rats, even after adjusting for differences in PF intake. Differences in the neural activation pattern between BEP and BER rats were more robust in prefrontal cortex than in nucleus accumbens. These data confirm that PF activates brain regions responsible for encoding the incentive salience and hedonic properties of PF, and suggest that binge eating proneness is associated with enhanced responses to PF in brain regions that exert executive control over food reward. Copyright © 2015 Elsevier Inc. All rights reserved.

Differential mesocorticolimbic responses to palatable food in binge eating prone and binge eating resistant female rats

PubMed Central

Sinclair, Elaine B.; Culbert, Kristen M.; Gradl, Dana R.; Richardson, Kimberlei A.; Klump, Kelly L.; Sisk, Cheryl L.

2017-01-01

Binge eating is a key symptom of many eating disorders (e.g. binge eating disorder, bulimia nervosa, anorexia nervosa binge/purge type), yet the neurobiological underpinnings of binge eating are poorly understood. The mesocorticolimbic reward circuit, including the nucleus accumbens and the medial prefrontal cortex, is likely involved because this circuit mediates the hedonic value and incentive salience of palatable foods (PF). Here we tested the hypothesis that higher propensity for binge eating is associated with a heightened response (i.e., Fos induction) of the nucleus accumbens and medial prefrontal cortex to PF, using an animal model that identifies binge eating prone (BEP) and binge eating resistant (BER) rats. Forty adult female Sprague–Dawley rats were given intermittent access to PF (high fat pellets) 3×/week for 3 weeks. Based on a pattern of either consistently high or consistently low PF consumption across these feeding tests, 8 rats met criteria for categorization as BEP, and 11 rats met criteria for categorization as BER. One week after the final feeding test, BEP and BER rats were either exposed to PF in their home cages or were given no PF in their home cages for 1 h prior to perfusion, leading to three experimental groups for the Fos analysis: BEPs given PF, BERs given PF, and a No PF control group. The total number of Fos-immunoreactive (Fos-ir) cells in the nucleus accumbens core and shell, and the cingulate, prelimbic, and infralimbic regions of the medial prefrontal cortex was estimated by stereological analysis. PF induced higher Fos expression in the nucleus accumbens shell and core and in the prelimbic and infralimbic cortex of BEP rats compared to No PF controls. Throughout the nucleus accumbens and medial pre-frontal cortex, PF induced higher Fos expression in BEP than in BER rats, even after adjusting for differences in PF intake. Differences in the neural activation pattern between BEP and BER rats were more robust in prefrontal cortex than in nucleus accumbens. These data confirm that PF activates brain regions responsible for encoding the incentive salience and hedonic properties of PF, and suggest that binge eating proneness is associated with enhanced responses to PF in brain regions that exert executive control over food reward. PMID:26459117

Dynamic representation of partially occluded objects in primate prefrontal and visual cortex

PubMed Central

Choi, Hannah; Shea-Brown, Eric

2017-01-01

Successful recognition of partially occluded objects is presumed to involve dynamic interactions between brain areas responsible for vision and cognition, but neurophysiological evidence for the involvement of feedback signals is lacking. Here, we demonstrate that neurons in the ventrolateral prefrontal cortex (vlPFC) of monkeys performing a shape discrimination task respond more strongly to occluded than unoccluded stimuli. In contrast, neurons in visual area V4 respond more strongly to unoccluded stimuli. Analyses of V4 response dynamics reveal that many neurons exhibit two transient response peaks, the second of which emerges after vlPFC response onset and displays stronger selectivity for occluded shapes. We replicate these findings using a model of V4/vlPFC interactions in which occlusion-sensitive vlPFC neurons feed back to shape-selective V4 neurons, thereby enhancing V4 responses and selectivity to occluded shapes. These results reveal how signals from frontal and visual cortex could interact to facilitate object recognition under occlusion. PMID:28925354

Blunted ventral striatal responses to anticipated rewards foreshadow problematic drug use in novelty-seeking adolescents

PubMed Central

Büchel, Christian; Peters, Jan; Banaschewski, Tobias; Bokde, Arun L. W.; Bromberg, Uli; Conrod, Patricia J.; Flor, Herta; Papadopoulos, Dimitri; Garavan, Hugh; Gowland, Penny; Heinz, Andreas; Walter, Henrik; Ittermann, Bernd; Mann, Karl; Martinot, Jean-Luc; Paillère-Martinot, Marie-Laure; Nees, Frauke; Paus, Tomas; Pausova, Zdenka; Poustka, Luise; Rietschel, Marcella; Robbins, Trevor W.; Smolka, Michael N.; Gallinat, Juergen; Schumann, Gunter; Knutson, Brian; Arroyo, Mercedes; Artiges, Eric; Aydin, Semiha; Bach, Christine; Barbot, Alexis; Barker, Gareth; Bruehl, Ruediger; Cattrell, Anna; Constant, Patrick; Crombag, Hans; Czech, Katharina; Dalley, Jeffrey; Decideur, Benjamin; Desrivieres, Sylvane; Fadai, Tahmine; Fauth-Buhler, Mira; Feng, Jianfeng; Filippi, Irinia; Frouin, Vincent; Fuchs, Birgit; Gemmeke, Isabel; Genauck, Alexander; Hanratty, Eanna; Heinrichs, Bert; Heym, Nadja; Hubner, Thomas; Ihlenfeld, Albrecht; Ing, Alex; Ireland, James; Jia, Tianye; Jones, Jennifer; Jurk, Sarah; Kaviani, Mehri; Klaassen, Arno; Kruschwitz, Johann; Lalanne, Christophe; Lanzerath, Dirk; Lathrop, Mark; Lawrence, Claire; Lemaitre, Hervé; Macare, Christine; Mallik, Catherine; Mar, Adam; Martinez-Medina, Lourdes; Mennigen, Eva; de Carvahlo, Fabiana Mesquita; Mignon, Xavier; Millenet, Sabina; Miranda, Ruben; Müller, Kathrin; Nymberg, Charlotte; Parchetka, Caroline; Pena-Oliver, Yolanda; Pentilla, Jani; Poline, Jean-Baptiste; Quinlan, Erin Burke; Rapp, Michael; Ripke, Stephan; Ripley, Tamzin; Robert, Gabriel; Rogers, John; Romanowski, Alexander; Ruggeri, Barbara; Schmäl, Christine; Schmidt, Dirk; Schneider, Sophia; Schubert, Florian; Schwartz, Yannick; Sommer, Wolfgang; Spanagel, Rainer; Speiser, Claudia; Spranger, Tade; Stedman, Alicia; Stephens, Dai; Strache, Nicole; Ströhle, Andreas; Struve, Maren; Subramaniam, Naresh; Theobald, David; Vetter, Nora; Vulser, Helene; Weiss, Katharina; Whelan, Robert; Williams, Steve; Xu, Bing; Yacubian, Juliana; Yu, Tao; Ziesch, Veronika

2017-01-01

Novelty-seeking tendencies in adolescents may promote innovation as well as problematic impulsive behaviour, including drug abuse. Previous research has not clarified whether neural hyper- or hypo-responsiveness to anticipated rewards promotes vulnerability in these individuals. Here we use a longitudinal design to track 144 novelty-seeking adolescents at age 14 and 16 to determine whether neural activity in response to anticipated rewards predicts problematic drug use. We find that diminished BOLD activity in mesolimbic (ventral striatal and midbrain) and prefrontal cortical (dorsolateral prefrontal cortex) regions during reward anticipation at age 14 predicts problematic drug use at age 16. Lower psychometric conscientiousness and steeper discounting of future rewards at age 14 also predicts problematic drug use at age 16, but the neural responses independently predict more variance than psychometric measures. Together, these findings suggest that diminished neural responses to anticipated rewards in novelty-seeking adolescents may increase vulnerability to future problematic drug use. PMID:28221370

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.

A comparison of head motion and prefrontal haemodynamics during upright and recumbent cycling exercise.

PubMed

Tempest, Gavin D; Eston, Roger G; Parfitt, Gaynor

2017-11-01

The aim of this observational study was to compare head motion and prefrontal haemodynamics during exercise using three commercial cycling ergometers. Participants (n = 12) completed an incremental exercise test to exhaustion during upright, recumbent and semi-recumbent cycling. Head motion (using accelerometry), physiological data (oxygen uptake, end-tidal carbon dioxide [P ET CO 2 ] and heart rate) and changes in prefrontal haemodynamics (oxygenation, deoxygenation and blood volume using near infrared spectroscopy [NIRS]) were recorded. Despite no difference in oxygen uptake and heart rate, head motion was higher and P ET CO 2 was lower during upright cycling at maximal exercise (P<0·05). Analyses of covariance (covariates: head motion P>0·05; P ET CO 2 , P<0·01) revealed that prefrontal oxygenation was higher during semi-recumbent than recumbent cycling and deoxygenation and blood volume were higher during upright than recumbent and semi-recumbent cycling (respectively; P<0·05). This work highlights the robustness of the utility of NIRS to head motion and describes the potential postural effects upon the prefrontal haemodynamic response during upright and recumbent cycling exercise. © 2016 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

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.

Getting Over It: Long-Lasting Effects of Emotion Regulation on Amygdala Response.

PubMed

Denny, Bryan T; Inhoff, Marika C; Zerubavel, Noam; Davachi, Lila; Ochsner, Kevin N

2015-09-01

Little is known about whether emotion regulation can have lasting effects on the ability of a stimulus to continue eliciting affective responses in the future. We addressed this issue in this study. Participants cognitively reappraised negative images once or four times, and then 1 week later, they passively viewed old and new images, so that we could identify lasting effects of prior reappraisal. As in prior work, active reappraisal increased prefrontal responses but decreased amygdala responses and self-reported emotion. At 1 week, amygdala responses remained attenuated for images that had been repeatedly reappraised compared with images that had been reappraised once, new control images, and control images that had been seen as many times as reappraised images but had never been reappraised. Prefrontal activation was not selectively elevated for repeatedly reappraised images and was not related to long-term attenuation of amygdala responses. These results suggest that reappraisal can exert long-lasting "dose-dependent" effects on amygdala response that may cause lasting changes in the neural representation of an unpleasant event's emotional value. © The Author(s) 2015.

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

Prefrontal hemodynamic responses and the degree of flow experience among occupational therapy students during their performance of a cognitive task.

PubMed

Hirao, Kazuki

2014-01-01

Although flow experience is positively associated with motivation to learn, the biological basis of flow experience is poorly understood. Accumulation of evidence on the underlying brain mechanisms related to flow is necessary for a deeper understanding of the motivation to learn. The purpose of this study is to investigate the relationship between flow experience and brain function using near-infrared spectroscopy (NIRS) during the performance of a cognitive task. Sixty right-handed occupational therapy (OT) students participated in this study. These students performed a verbal fluency test (VFT) while 2-channel NIRS was used to assess changes in oxygenated hemoglobin concentration (oxygenated hemoglobin [oxy-Hb]) in the prefrontal cortex. Soon after that, the OT students answered the flow questionnaire (FQ) to assess the degree of flow experience during the VFT. Average oxy-Hb in the prefrontal cortex had a significant negative correlation with the satisfaction scores on the FQ. Satisfaction during the flow experience correlated with prefrontal hemodynamic suppression. This finding may assist in understanding motivation to learn and related flow experience.

Effect of transmission intensity and age on subclass antibody responses to Plasmodium falciparum pre-erythrocytic and blood-stage antigens.

PubMed

Noland, Gregory S; Jansen, Paul; Vulule, John M; Park, Gregory S; Ondigo, Bartholomew N; Kazura, James W; Moormann, Ann M; John, Chandy C

2015-02-01

Cytophilic immunoglobulin (IgG) subclass responses (IgG1 and IgG3) to Plasmodium falciparum antigens have been associated with protection from malaria, yet the relative importance of transmission intensity and age in generation of subclass responses to pre-erythrocytic and blood-stage antigens have not been clearly defined. We analyzed IgG subclass responses to the pre-erythrocytic antigens CSP, LSA-1, and TRAP and the blood-stage antigens AMA-1, EBA-175, and MSP-1 in asymptomatic residents age 2 years or older in stable (n=116) and unstable (n=96) transmission areas in Western Kenya. In the area of stable malaria transmission, a high prevalence of cytophilic (IgG1 and IgG3) antibodies to each antigen was seen in all age groups. Prevalence and levels of cytophilic antibodies to pre-erythrocytic and blood-stage P. falciparum antigens increased with age in the unstable transmission area, yet IgG1 and IgG3 responses to most antigens for all ages in the unstable transmission area were less prevalent and lower in magnitude than even the youngest age group from the stable transmission area. The dominance of cytophilic responses over non-cytophilic (IgG2 and IgG4) was more pronounced in the stable transmission area, and the ratio of IgG3 over IgG1 generally increased with age. In the unstable transmission area, the ratio of cytophilic to non-cytophilic antibodies did not increase with age, and tended to be IgG3-biased for pre-erythrocytic antigens yet IgG1-biased for blood-stage antigens. The differences between areas could not be attributed to active parasitemia status, as there were minimal differences in antibody responses between those positive and negative for Plasmodium infection by microscopy in the stable transmission area. Individuals in areas of unstable transmission have low cytophilic to non-cytophilic IgG subclass ratios and low IgG3:IgG1 ratios to P. falciparum antigens. These imbalances could contribute to the persistent risk of clinical malaria in these areas and serve as population-level, age-specific biomarkers of transmission. Copyright © 2014 Elsevier B.V. All rights reserved.

Depressed Immune Responses and Accelerated Splenic Apoptosis due to Experience of Food Deprivation and Inequality but not Unstable Social Status in Balb/c Mice.

PubMed

Aghajani, Marjan; Vaez Mahdavi, Mohammad Reza; Najafabadi, Mohsen Khalili; Ghazanfari, Tooba; Moradi, Fatemeh; Golchoobian, Ravieh; Askari, Hasan; Sanadgol, Nima; Moghaddam, Ehsan Kazemi

2017-01-01

We aimed to show that the immune system is sensitive to the detrimental effects of inequality and social injustice, and splenic vulnerability to apoptosis may also increase. In order of better determination of immune responses to chronic social stress, we implemented food deprivation, food intake inequality, and unstable social status (a change of cage-mate every 3 days) for a period of 14 days in 60 male Balb/c mice. At the end of this stress period, nitric oxide (NO) production by peritoneal adherent cells and the serum concentration of corticosterone were measured. Moreover, the viability of peritoneal adherent cells and spleen lymphocytes was evaluated by MTT assay. The terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay was done to reveal the TUNEL-reactive apoptotic bodies in the spleen. Our results showed that food deprivation and inequality caused significant changes in the apoptosis of splenic cells in comparison with the control group (p < 0.05). Moreover, the vital activities of lymphocytes and peritoneal adherent cells, as well as NO production by the latter, increased significantly (p < 0.05). However, the experience of unstable social status did not cause a further increase in the viability of lymphocytes and peritoneal adherent cells, or NO production in animals that were food-deprived or experienced inequality. Serum concentration of corticosterone in all experimental groups, except for animals that experienced unstable social status only, significantly decreased versus the control group (p < 0.05). The results suggest that poverty and social inequality, but not unstable social status, affect immune responses and are likely involved in the induction of splenic apoptosis in mice. © 2017 S. Karger AG, Basel.

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.

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 transition from childhood to adolescence is marked by a general decrease in amygdala reactivity and an affect-specific ventral-to-dorsal shift in medial prefrontal recruitment.

PubMed

Silvers, Jennifer A; Insel, Catherine; Powers, Alisa; Franz, Peter; Helion, Chelsea; Martin, Rebecca; Weber, Jochen; Mischel, Walter; Casey, B J; Ochsner, Kevin N

2017-06-01

Understanding how and why affective responses change with age is central to characterizing typical and atypical emotional development. Prior work has emphasized the role of the amygdala and prefrontal cortex (PFC), which show age-related changes in function and connectivity. However, developmental neuroimaging research has only recently begun to unpack whether age effects in the amygdala and PFC are specific to affective stimuli or may be found for neutral stimuli as well, a possibility that would support a general, rather than affect-specific, account of amygdala-PFC development. To examine this, 112 individuals ranging from 6 to 23 years of age viewed aversive and neutral images while undergoing fMRI scanning. Across age, participants reported more negative affect and showed greater amygdala responses for aversive than neutral stimuli. However, children were generally more sensitive to both neutral and aversive stimuli, as indexed by affective reports and amygdala responses. At the same time, the transition from childhood to adolescence was marked by a ventral-to-dorsal shift in medial prefrontal responses to aversive, but not neutral, stimuli. Given the role that dmPFC plays in executive control and higher-level representations of emotion, these results suggest that adolescence is characterized by a shift towards representing emotional events in increasingly cognitive terms. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Prefrontal and Parietal Correlates of Cognitive Control Related to the Adult Outcome of Attention-Deficit/Hyperactivity Disorder Diagnosed in Childhood

PubMed Central

Schulz, Kurt P.; Li, Xiaobo; Clerkin, Suzanne M.; Fan, Jin; Berwid, Olga G.; Newcorn, Jeffrey H.; Halperin, Jeffrey M.

2017-01-01

The protracted and highly variable development of prefrontal cortex regions that support cognitive control has been purported to shape the adult outcome of attention-deficit/hyperactivity disorder (ADHD). This neurodevelopmental model was tested in a prospectively followed sample of 27 adult probands who were diagnosed with ADHD in childhood and 28 carefully matched comparison subjects aged 21 – 28 years. Probands were classified with persistent ADHD or remitted ADHD. Behavioral and neural responses to the stimulus and response conflict task performed during functional magnetic resonance imaging were compared in probands and comparison subjects and in probands with persistent and remitted ADHD. Response speed and accuracy for stimulus, response, and combined conflicts did not differ across groups. Orbitofrontal, inferior frontal and parietal activation was lower in probands than comparison subjects, but only for combined conflicts, when demand for cognitive control was highest. Reduced activation for combined conflicts in probands was almost wholly attributable to the persistence of ADHD; orbitofrontal, inferior frontal, anterior cingulate and parietal activation was lower in probands with persistent ADHD than both probands with remitted ADHD and comparison subjects, but did not differ between probands with remitted ADHD and comparison subjects. These data provide the first evidence that prefrontal and parietal activation during cognitive control parallels the adult outcome of ADHD diagnosed in childhood, with persistence of symptoms linked to reduced activation and symptom recovery associated with activation indistinguishable from adults with no history of ADHD. PMID:28292705

Altered emotional interference processing in affective and cognitive-control brain circuitry in major depression

PubMed Central

Fales, Christina L.; Barch, Deanna M.; Rundle, Melissa M.; Mintun, Mark A.; Snyder, Abraham Z.; Cohen, Jonathan D.; Mathews, Jose; Sheline, Yvette I.

2008-01-01

Background Major depression is characterized by a negativity bias: an enhanced responsiveness to, and memory for, affectively negative stimuli. However it is not yet clear whether this bias represents (1) impaired top-down cognitive control over affective responses, potentially linked to deficits in dorsolateral prefrontal cortex function; or (2) enhanced bottom-up responses to affectively-laden stimuli that dysregulate cognitive control mechanisms, potentially linked to deficits in amygdala and anterior cingulate function. Methods We used an attentional interference task using emotional distracters to test for top-down versus bottom-up dysfunction in the interaction of cognitive-control circuitry and emotion-processing circuitry. A total of 27 patients with major depression and 24 controls were tested. Event-related functional magnetic resonance imaging was carried out as participants directly attended to, or attempted to ignore, fear-related stimuli. Results Compared to controls, patients with depression showed an enhanced amygdala response to unattended fear-related stimuli (relative to unattended neutral). By contrast, control participants showed increased activity in right dorsolateral prefrontal cortex (Brodmann areas 46/9) when ignoring fear stimuli (relative to neutral), which the patients with depression did not. In addition, the depressed participants failed to show evidence of error-related cognitive adjustments (increased activity in bilateral dorsolateral prefrontal cortex on post-error trials), but the control group did show them. Conclusions These results suggest multiple sources of dysregulation in emotional and cognitive control circuitry in depression, implicating both top-down and bottom-up dysfunction. PMID:17719567

Bladder control, urgency, and urge incontinence: evidence from functional brain imaging.

PubMed

Griffiths, Derek; Tadic, Stasa D

2008-01-01

To review brain imaging studies of bladder control in subjects with normal control and urge incontinence; to define a simple model of supraspinal bladder control; and to propose a neural correlate of urgency and possible origins of urge incontinence. Review of published reports of brain imaging relevant to urine storage, and secondary analyses of our own recent observations. In a simple model of normal urine storage, bladder and urethral afferents received in the periaqueductal gray (PAG) are mapped in the insula, forming the basis of sensation; the anterior cingulate gyrus (ACG) provides monitoring and control; the prefrontal cortex makes voiding decisions. The net result, as the bladder fills, is inhibition of the pontine micturition center (PMC) and of voiding, together with gradual increase in insular response, corresponding to increasing desire to void. In urge-incontinent subjects, brain responses differ. At large bladder volumes and strong sensation, but without detrusor overactivity (DO), most cortical responses become exaggerated, especially in ACG. This may be both a learned reaction to previous incontinence episodes and the neural correlate of urgency. The neural signature of DO itself seems to be prefrontal deactivation. Possible causes of urge incontinence include dysfunction of prefrontal cortex or limbic system, suggested by weak responses and/or deactivation, as well as abnormal afferent signals or re-emergence of infantile reflexes. Bladder control depends on an extensive network of brain regions. Dysfunction in various parts may contribute to urge incontinence, suggesting that there are different phenotypes requiring different treatments. (c) 2007 Wiley-Liss, Inc.

Ventromedial prefrontal cortex response to concentrated sucrose reflects liking rather than sweet quality coding.

PubMed

Rudenga, Kristin J; Small, Dana M

2013-09-01

The perception of the pleasantness of sweet tastes varies widely across individuals. Here, we exploit these differences to isolate brain response to sweet-taste pleasantness while controlling for intensity, quality, and physiological significance. Thirty subjects participated in functional MRI scanning while consuming individually calibrated weak and strong sucrose solutions. All subjects found the weak sweet taste to be neutral in pleasantness, but half of the subjects found strong sweet taste pleasant (likers), whereas half found strong sweet taste unpleasant (dislikers). Greater response was observed in the ventromedial prefrontal cortex (vmPFC) to the sucrose when it was rated pleasant versus neutral compared with unpleasant versus neutral. This suggests that response in the vmPFC underlies sweet-taste preference, this region is preferentially sensitive to affectively positive tastes, and it is the positive value rather than physiological significance, quality, or intensity that drives responses here. Likers versus dislikers did not differ in their diet, alcohol use, body weight, gender, or taq1A allele status, but likers were more likely to report emotional eating. None of these factors influenced response in the vmPFC.

COMT Val158Met Genotype Selectively Alters Prefrontal [18F]Fallypride Displacement and Subjective Feelings of Stress in Response to a Psychosocial Stress Challenge

PubMed Central

Lataster, Johan; Ceccarini, Jenny; Kenis, Gunther; Booij, Linda; Pruessner, Jens; Van Laere, Koen; van Winkel, Ruud; van Os, Jim; Myin-Germeys, Inez

2013-01-01

Catechol-O-methyltransferase (COMT) plays an essential role in degradation of extracellular dopamine in prefrontal regions of the brain. Although a polymorphism in this gene, COMT Val158Met, affects human behavior in response to stress little is known about its effect on dopaminergic activity associated with the human stress response, which may be of interest for stress-related psychiatric disorders such as psychosis. We aimed to investigate the effect of variations in COMT genotype on in vivo measures of stress-induced prefrontal cortex (PFC) dopaminergic processing and subjective stress responses. A combined sample of healthy controls and healthy first-degree relatives of psychosis patients (n = 26) were subjected to an [18F]fallypride Positron Emission Tomography scan. Psychosocial stress during the scan was induced using the Montreal Imaging Stress Task and subjective stress was assessed every 12 minutes. Parametric t-maps, generated using the linear extension of the simplified reference region model, revealed an effect of COMT genotype on the spatial extent of [18F]fallypride displacement. Detected effects of exposure to psychosocial stress were unilateral and remained restricted to the left superior and right inferior frontal gyrus, with Met-hetero- and homozygotes showing less [18F]fallypride displacement than Val-homozygotes. Additionally, Met-hetero- and homozygotes experienced larger subjective stress responses than Val-homozygotes. The direction of the effects remained the same when the data was analyzed separately for controls and first-degree relatives. The human stress response may be mediated in part by COMT-dependent dopaminergic PFC activity, providing speculation for the neurobiology underlying COMT-dependent differences in human behaviour following stress. Implications of these results for stress-related psychopathology and models of dopaminergic functioning are discussed. PMID:23799032

COMT Val158Met genotype selectively alters prefrontal [18F]fallypride displacement and subjective feelings of stress in response to a psychosocial stress challenge.

PubMed

Hernaus, Dennis; Collip, Dina; Lataster, Johan; Ceccarini, Jenny; Kenis, Gunther; Booij, Linda; Pruessner, Jens; Van Laere, Koen; van Winkel, Ruud; van Os, Jim; Myin-Germeys, Inez

2013-01-01

Catechol-O-methyltransferase (COMT) plays an essential role in degradation of extracellular dopamine in prefrontal regions of the brain. Although a polymorphism in this gene, COMT Val(158)Met, affects human behavior in response to stress little is known about its effect on dopaminergic activity associated with the human stress response, which may be of interest for stress-related psychiatric disorders such as psychosis. We aimed to investigate the effect of variations in COMT genotype on in vivo measures of stress-induced prefrontal cortex (PFC) dopaminergic processing and subjective stress responses. A combined sample of healthy controls and healthy first-degree relatives of psychosis patients (n = 26) were subjected to an [(18)F]fallypride Positron Emission Tomography scan. Psychosocial stress during the scan was induced using the Montreal Imaging Stress Task and subjective stress was assessed every 12 minutes. Parametric t-maps, generated using the linear extension of the simplified reference region model, revealed an effect of COMT genotype on the spatial extent of [(18)F]fallypride displacement. Detected effects of exposure to psychosocial stress were unilateral and remained restricted to the left superior and right inferior frontal gyrus, with Met-hetero- and homozygotes showing less [(18)F]fallypride displacement than Val-homozygotes. Additionally, Met-hetero- and homozygotes experienced larger subjective stress responses than Val-homozygotes. The direction of the effects remained the same when the data was analyzed separately for controls and first-degree relatives. The human stress response may be mediated in part by COMT-dependent dopaminergic PFC activity, providing speculation for the neurobiology underlying COMT-dependent differences in human behaviour following stress. Implications of these results for stress-related psychopathology and models of dopaminergic functioning are discussed.

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.

Representation of aversive prediction errors in the human periaqueductal gray

PubMed Central

Roy, Mathieu; Shohamy, Daphna; Daw, Nathaniel; Jepma, Marieke; Wimmer, Elliott; Wager, Tor D.

2014-01-01

Pain is a primary driver of learning and motivated action. It is also a target of learning, as nociceptive brain responses are shaped by learning processes. We combined an instrumental pain avoidance task with an axiomatic approach to assessing fMRI signals related to prediction errors (PEs), which drive reinforcement-based learning. We found that pain PEs were encoded in the periaqueductal gray (PAG), an important structure for pain control and learning in animal models. Axiomatic tests combined with dynamic causal modeling suggested that ventromedial prefrontal cortex, supported by putamen, provides an expected value-related input to the PAG, which then conveys PE signals to prefrontal regions important for behavioral regulation, including orbitofrontal, anterior mid-cingulate, and dorsomedial prefrontal cortices. Thus, pain-related learning involves distinct neural circuitry, with implications for behavior and pain dynamics. PMID:25282614

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

Frontal dysfunctions of impulse control - a systematic review in borderline personality disorder and attention-deficit/hyperactivity disorder.

PubMed

Sebastian, Alexandra; Jung, Patrick; Krause-Utz, Annegret; Lieb, Klaus; Schmahl, Christian; Tüscher, Oliver

2014-01-01

Disorders such as borderline personality disorder (BPD) or attention-deficit/hyperactivity disorder (ADHD) are characterized by impulsive behaviors. Impulsivity as used in clinical terms is very broadly defined and entails different categories including personality traits as well as different cognitive functions such as emotion regulation or interference resolution and impulse control. Impulse control as an executive function, however, is neither cognitively nor neurobehaviorally a unitary function. Recent findings from behavioral and cognitive neuroscience studies suggest related but dissociable components of impulse control along functional domains like selective attention, response selection, motivational control, and behavioral inhibition. In addition, behavioral and neural dissociations are seen for proactive vs. reactive inhibitory motor control. The prefrontal cortex with its sub-regions is the central structure in executing these impulse control functions. Based on these concepts of impulse control, neurobehavioral findings of studies in BPD and ADHD were reviewed and systematically compared. Overall, patients with BPD exhibited prefrontal dysfunctions across impulse control components rather in orbitofrontal, dorsomedial, and dorsolateral prefrontal regions, whereas patients with ADHD displayed disturbed activity mainly in ventrolateral and medial prefrontal regions. Prefrontal dysfunctions, however, varied depending on the impulse control component and from disorder to disorder. This suggests a dissociation of impulse control related frontal dysfunctions in BPD and ADHD, although only few studies are hitherto available to assess frontal dysfunctions along different impulse control components in direct comparison of these disorders. Yet, these findings might serve as a hypothesis for the future systematic assessment of impulse control components to understand differences and commonalities of prefrontal cortex dysfunction in impulsive disorders.

Can neural activation in dorsolateral prefrontal cortex predict responsiveness to information? An application to egg production systems and campaign advertising.

PubMed

McFadden, Brandon R; Lusk, Jayson L; Crespi, John M; Cherry, J Bradley C; Martin, Laura E; Aupperle, Robin L; Bruce, Amanda S

2015-01-01

Consumers prefer to pay low prices and increase animal welfare; however consumers are typically forced to make tradeoffs between price and animal welfare. Campaign advertising (i.e., advertising used during the 2008 vote on Proposition 2 in California) may affect how consumers make tradeoffs between price and animal welfare. Neuroimaging data was used to determine the effects of brain activation in dorsolateral prefrontal cortex (dlPFC) on choices making a tradeoff between price and animal welfare and responsiveness to campaign advertising. Results indicated that activation in the dlPFC was greater when making choices that forced a tradeoff between price and animal welfare, compared to choices that varied only by price or animal welfare. Furthermore, greater activation differences in right dlPFC between choices that forced a tradeoff and choices that did not, indicated greater responsiveness to campaign advertising.

Can Neural Activation in Dorsolateral Prefrontal Cortex Predict Responsiveness to Information? An Application to Egg Production Systems and Campaign Advertising

PubMed Central

McFadden, Brandon R.; Lusk, Jayson L.; Crespi, John M.; Cherry, J. Bradley C.; Martin, Laura E.; Aupperle, Robin L.; Bruce, Amanda S.

2015-01-01

Consumers prefer to pay low prices and increase animal welfare; however consumers are typically forced to make tradeoffs between price and animal welfare. Campaign advertising (i.e., advertising used during the 2008 vote on Proposition 2 in California) may affect how consumers make tradeoffs between price and animal welfare. Neuroimaging data was used to determine the effects of brain activation in dorsolateral prefrontal cortex (dlPFC) on choices making a tradeoff between price and animal welfare and responsiveness to campaign advertising. Results indicated that activation in the dlPFC was greater when making choices that forced a tradeoff between price and animal welfare, compared to choices that varied only by price or animal welfare. Furthermore, greater activation differences in right dlPFC between choices that forced a tradeoff and choices that did not, indicated greater responsiveness to campaign advertising. PMID:26018592

Impaired Functional Connectivity in the Prefrontal Cortex: A Mechanism for Chronic Stress-Induced Neuropsychiatric Disorders

PubMed Central

Negrón-Oyarzo, Ignacio; Aboitiz, Francisco; Fuentealba, Pablo

2016-01-01

Chronic stress-related psychiatric diseases, such as major depression, posttraumatic stress disorder, and schizophrenia, are characterized by a maladaptive organization of behavioral responses that strongly affect the well-being of patients. Current evidence suggests that a functional impairment of the prefrontal cortex (PFC) is implicated in the pathophysiology of these diseases. Therefore, chronic stress may impair PFC functions required for the adaptive orchestration of behavioral responses. In the present review, we integrate evidence obtained from cognitive neuroscience with neurophysiological research with animal models, to put forward a hypothesis that addresses stress-induced behavioral dysfunctions observed in stress-related neuropsychiatric disorders. We propose that chronic stress impairs mechanisms involved in neuronal functional connectivity in the PFC that are required for the formation of adaptive representations for the execution of adaptive behavioral responses. These considerations could be particularly relevant for understanding the pathophysiology of chronic stress-related neuropsychiatric disorders. PMID:26904302

Prefrontal Consolidation Supports the Attainment of Fear Memory Accuracy

ERIC Educational Resources Information Center

Vieira, Philip A.; Lovelace, Jonathan W.; Corches, Alex; Rashid, Asim J.; Josselyn, Sheena A.; Korzus, Edward

2014-01-01

The neural mechanisms underlying the attainment of fear memory accuracy for appropriate discriminative responses to aversive and nonaversive stimuli are unclear. Considerable evidence indicates that coactivator of transcription and histone acetyltransferase cAMP response element binding protein (CREB) binding protein (CBP) is critically required…

Amygdala inputs to prefrontal cortex guide behavior amid conflicting cues of reward and punishment

PubMed Central

Burgos-Robles, Anthony; Kimchi, Eyal Y.; Izadmehr, Ehsan M.; Porzenheim, Mary Jane; Ramos-Guasp, William A.; Nieh, Edward H.; Felix-Ortiz, Ada C.; Namburi, Praneeth; Leppla, Christopher A.; Presbrey, Kara N.; Anandalingam, Kavitha K.; Pagan-Rivera, Pablo A.; Anahtar, Melodi; Beyeler, Anna; Tye, Kay M.

2017-01-01

Orchestrating appropriate behavioral responses in the face of competing signals that predict either rewards or threats in the environment is crucial for survival. The basolateral amygdala (BLA) and prelimbic (PL) medial prefrontal cortex (mPFC) have been implicated in reward-seeking and fear-related responses, but how information flows between these reciprocally-connected structures to coordinate behavior is unknown. We recorded neuronal activity from the BLA and PL while rats performed a task where in shock- and sucrose-predictive cues were simultaneously presented to induce competition. The correlated firing primarily displayed a BLA→PL directionality during the shock-associated cue. Furthermore, the majority of optogenetically-identified PL-projecting BLA neurons recorded encoded the shock-associated cue, and more accurately predicted behavioral responses during competition than unidentified BLA neurons. Finally, BLA→PL photostimulation increased freezing, whereas both chemogenetic and optogenetic inhibition reduced freezing. The BLA→PL circuit plays a critical role in governing the selection of behavioral responses in the face of competing signals. PMID:28436980

Dorsomedial Prefrontal Cortex Contribution to Behavioral and Nucleus Accumbens Neuronal Responses to Incentive Cues

PubMed Central

Ishikawa, Akinori; Ambroggi, Frederic; Nicola, Saleem M.; Fields, Howard L.

2008-01-01

Cue-elicited phasic changes in firing of nucleus accumbens (NAc) neurons can facilitate reward-seeking behavior. Here, we test the hypothesis that the medial prefrontal cortex (mPFC), which sends a dense glutamatergic projection to the NAc core, contributes to NAc neuronal firing responses to reward-predictive cues. Rats trained to perform an operant response to a cue for sucrose were implanted with recording electrodes in the core of the NAc and microinjection cannulas in the dorsal mPFC (dmPFC). The cue-evoked firing of NAc neurons was reduced by bilateral injection of GABAA and GABAB agonists into the dmPFC concomitant with loss of behavioral responding to the cue. In addition, unilateral dmPFC inactivation reduced ipsilateral cue excitations and contralateral cue inhibitions. These findings indicate that cue-evoked excitations and inhibitions of NAc core neurons depend on dmPFC projections to the NAc and that these phasic changes contribute to the behavioral response to reward-predictive cues. PMID:18463262

Prefrontal cortex activity during response selection predicts processing speed impairment in schizophrenia

PubMed Central

Woodward, Neil D.; Duffy-Alberto, Brittney; Karbasforoushan, Haleh

2014-01-01

Processing speed is the most impaired neuropsychological domain in schizophrenia and a robust predictor of functional outcome. Determining the specific cognitive operations underlying processing speed dysfunction and indentifying their neural correlates may assist in developing pro-cognitive interventions. Response selection, the process of mapping stimuli onto motor responses, correlates with neuropsychological tests of processing speed and may contribute to processing speed impairment in schizophrenia. This study investigated the relationship between behavioral and neural measures of response selection, and a neuropsychological index of processing speed in schizophrenia. 26 patients with schizophrenia and 21 healthy subjects underwent fMRI scanning during performance of 2 and 4-choice-reaction time (RT) tasks and completed the Wechsler Adult Intelligence Scale-III (WAIS) Processing Speed Index (PSI). Response selection, defined as RT slowing between 2 and 4-choice RT, was impaired in schizophrenia and correlated with psychometric processing speed. Greater activation of the dorsolateral prefrontal cortex (PFC) was observed in schizophrenia and correlated with poorer WAIS PSI scores. Deficient response selection and abnormal recruitment of the dorsolateral PFC during response selection contribute to processing speed impairment in schizophrenia. Interventions that improve response selection and normalize dorsolateral PFC function may improve processing speed in schizophrenia. PMID:23816240

Wind tunnel experiments on unstable self-excited vibration of sectional girders

NASA Astrophysics Data System (ADS)

Král, Radomil; Pospíšil, Stanislav; Náprstek, Jiří

2014-01-01

In this paper, a wind tunnel analysis of two degrees-of-freedom system represented by sectional girders is carried out. Besides an evaluation of the aeroelastic coefficients, the analysis is focused on the influence of the natural frequency ratio on the initiation of unstable vibration, which can be of practical interest. On the phenomenological level, the paper also discusses experimentally ascertained response regimes, with an emphasis on their stability character. The attention is paid to the memory effect in the response described by the hysteresis loop together with the separation curves determining the stability boundaries. The influence of initial disturbance on the stability is examined. Two types of cross-sections were investigated: (i) rectangular one with the aspect ratio 1:5, and (ii) bridge-like cross-section with comparable principal dimensions. For both types of cross-sections, the limits of the stability are significantly affected by an intentionally introduced initial disturbance. This holds especially with regard to the rectangular profile where the separation curves create very narrow sub-domains between a stable and an unstable response, while the bridge-like cross-section demonstrates much stable behaviour.

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.

Mapping Compulsivity in the DSM-5 Obsessive Compulsive and Related Disorders: Cognitive Domains, Neural Circuitry, and Treatment

PubMed Central

Apergis-Schoute, Annemieke M; Vaghi, Matilde M; Banca, Paula; Gillan, Claire M; Voon, Valerie; Chamberlain, Samuel R; Cinosi, Eduardo; Reid, Jemma; Shahper, Sonia; Bullmore, Edward T; Sahakian, Barbara J; Robbins, Trevor W

2018-01-01

Abstract Compulsions are repetitive, stereotyped thoughts and behaviors designed to reduce harm. Growing evidence suggests that the neurocognitive mechanisms mediating behavioral inhibition (motor inhibition, cognitive inflexibility) reversal learning and habit formation (shift from goal-directed to habitual responding) contribute toward compulsive activity in a broad range of disorders. In obsessive compulsive disorder, distributed network perturbation appears focused around the prefrontal cortex, caudate, putamen, and associated neuro-circuitry. Obsessive compulsive disorder-related attentional set-shifting deficits correlated with reduced resting state functional connectivity between the dorsal caudate and the ventrolateral prefrontal cortex on neuroimaging. In contrast, experimental provocation of obsessive compulsive disorder symptoms reduced neural activation in brain regions implicated in goal-directed behavioral control (ventromedial prefrontal cortex, caudate) with concordant increased activation in regions implicated in habit learning (presupplementary motor area, putamen). The ventromedial prefrontal cortex plays a multifaceted role, integrating affective evaluative processes, flexible behavior, and fear learning. Findings from a neuroimaging study of Pavlovian fear reversal, in which obsessive compulsive disorder patients failed to flexibly update fear responses despite normal initial fear conditioning, suggest there is an absence of ventromedial prefrontal cortex safety signaling in obsessive compulsive disorder, which potentially undermines explicit contingency knowledge and may help to explain the link between cognitive inflexibility, fear, and anxiety processing in compulsive disorders such as obsessive compulsive disorder. PMID:29036632

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.

Prefrontal cortical minicolumn: from executive control to disrupted cognitive processing

PubMed Central

Casanova, Manuel F.

2014-01-01

The prefrontal cortex of the primate brain has a modular architecture based on the aggregation of neurons in minicolumnar arrangements having afferent and efferent connections distributed across many brain regions to represent, select and/or maintain behavioural goals and executive commands. Prefrontal cortical microcircuits are assumed to play a key role in the perception to action cycle that integrates relevant information about environment, and then selects and enacts behavioural responses. Thus, neurons within the interlaminar microcircuits participate in various functional states requiring the integration of signals across cortical layers and the selection of executive variables. Recent research suggests that executive abilities emerge from cortico-cortical interactions between interlaminar prefrontal cortical microcircuits, whereas their disruption is involved in a broad spectrum of neurologic and psychiatric disorders such as autism, schizophrenia, Alzheimer’s and drug addiction. The focus of this review is on the structural, functional and pathological approaches involving cortical minicolumns. Based on recent technological progress it has been demonstrated that microstimulation of infragranular cortical layers with patterns of microcurrents derived from supragranular layers led to an increase in cognitive performance. This suggests that interlaminar prefrontal cortical microcircuits are playing a causal role in improving cognitive performance. An important reason for the new interest in cortical modularity comes from both the impressive progress in understanding anatomical, physiological and pathological facets of cortical microcircuits and the promise of neural prosthetics for patients with neurological and psychiatric disorders. PMID:24531625

Effect of acute psychological stress on prefrontal GABA concentration determined by proton magnetic resonance spectroscopy.

PubMed

Hasler, Gregor; van der Veen, Jan Willem; Grillon, Christian; Drevets, Wayne C; Shen, Jun

2010-10-01

Impaired function of the central gamma-aminobutyric acid (GABA) system, which provides the brain's major inhibitory pathways, is thought to play an important role in the pathophysiology of anxiety disorders. The effect of acute psychological stress on the human GABA-ergic system is still unknown, however. The purpose of this study was to determine the effect of acute stress on prefrontal GABA levels. A recently developed noninvasive magnetic resonance spectroscopy method was used to measure changes in the GABA concentration of the prefrontal cortex in 10 healthy human subjects during a threat-of-shock condition and during a safe condition (two sessions on different days). The main outcome measure was the mean GABA concentration within a 3×3×2-cm(3) voxel selected from the medial prefrontal cortex. Prefrontal GABA decreased by approximately 18% in the threat-of-shock condition relative to the safe condition. This reduction was specific to GABA, since the concentrations of N-acetyl-aspartate, choline-containing compounds, and glutamate/glutamine levels obtained in the same spectra did not change significantly. This result appeared compatible with evidence from preclinical studies in rodents, which showed rapid presynaptic down-regulation of GABA-ergic neurotransmission in response to acute psychological stress. The molecular mechanism and functional significance of this reduced inhibitory effect of acute psychological stress in relation to impaired GABA-ergic function in anxiety disorders merit further investigation.

Working-memory capacity protects model-based learning from stress.

PubMed

Otto, A Ross; Raio, Candace M; Chiang, Alice; Phelps, Elizabeth A; Daw, Nathaniel D

2013-12-24

Accounts of decision-making have long posited the operation of separate, competing valuation systems in the control of choice behavior. Recent theoretical and experimental advances suggest that this classic distinction between habitual and goal-directed (or more generally, automatic and controlled) choice may arise from two computational strategies for reinforcement learning, called model-free and model-based learning. Popular neurocomputational accounts of reward processing emphasize the involvement of the dopaminergic system in model-free learning and prefrontal, central executive-dependent control systems in model-based choice. Here we hypothesized that the hypothalamic-pituitary-adrenal (HPA) axis stress response--believed to have detrimental effects on prefrontal cortex function--should selectively attenuate model-based contributions to behavior. To test this, we paired an acute stressor with a sequential decision-making task that affords distinguishing the relative contributions of the two learning strategies. We assessed baseline working-memory (WM) capacity and used salivary cortisol levels to measure HPA axis stress response. We found that stress response attenuates the contribution of model-based, but not model-free, contributions to behavior. Moreover, stress-induced behavioral changes were modulated by individual WM capacity, such that low-WM-capacity individuals were more susceptible to detrimental stress effects than high-WM-capacity individuals. These results enrich existing accounts of the interplay between acute stress, working memory, and prefrontal function and suggest that executive function may be protective against the deleterious effects of acute stress.

Neural mechanisms underlying ecstasy-related attentional bias.

PubMed

Roberts, Gloria M P; Garavan, Hugh

2013-08-30

Conditioned responses to cues associated with drug taking play a pivotal role in a number of theories of drug addiction. This study examined whether attentional biases towards drug-related cues exist in recreational drug users who predominantly used ecstasy (3,4-methylenedioxymethamphetamine). Experiment 1 compared 30 ecstasy users, 25 cannabis users, and 30 controls in an attentional distraction task in which neutral, evocative, and ecstasy-related pictures were presented within a coloured border, requiring participants to respond as quickly as possible to the border colour. Experiment 2 employed functional magnetic resonance imaging (fMRI) and the attentional distraction task and tested 20 ecstasy users and 20 controls. Experiment 1 revealed significant response speed interference by the ecstasy-related pictures in the ecstasy users only. Experiment 2 revealed increased prefrontal and occipital activity in ecstasy users in all conditions. Activations in response to the ecstasy stimuli in these regions showed an apparent antagonism whereby ecstasy users, relative to controls, showed increased occipital but decreased right prefrontal activation. These results are interpreted to reflect increased visual processing of, and decreased prefrontal control over, the irrelevant but salient ecstasy-related stimuli. These results suggest that right inferior frontal cortex may play an important role in controlling drug-related attentional biases and may thus play an important role in mediating control over drug usage. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The effects of acute foot shock stress on empathy levels in rats.

PubMed

Karakilic, Aslı; Kizildag, Servet; Kandis, Sevim; Guvendi, Guven; Koc, Basar; Camsari, Gamze B; Camsari, Ulas M; Ates, Mehmet; Arda, Sevil Gonenc; Uysal, Nazan

2018-09-03

Empathy defined as the ability to understand and the share the feelings, thoughts, and attitudes of another, is an important skill in survival and reproduction. Among many factors that affect empathy include psychological stress, anxiety states. The aim of this study was to investigate the impact of acute psychological stress on empathic behavior and its association with oxytocin and vasopressin levels in amygdala and prefrontal cortex. Rats were subjected to 0.2 mA (low) and 1.6 mA (high) intensity of foot shock stress for duration of 20 min. Empathic behavior was found to be improved as a response to low intensity stress, but not to high intensity stress. As a response to lower intensity stress, vasopressin was increased in prefrontal cortex and amygdala; oxytocin was increased in only prefrontal cortex, and corticosterone levels increased in general. Anxiety indicators did not change in low intensity stress group yet; high intensity stress group demonstrated a lesser degree of anxiety response. High intensity stress group stayed unexpectedly more active in middle area of elevated plus maze test equipment, which may support impaired executive decision making abilities in the setting of high anxiety states. Further research is needed to investigate gender effects, the role of dopaminergic system and other stress related pathways in acute stress. Copyright © 2018 Elsevier B.V. All rights reserved.

Functional mapping of the neural circuitry of rat maternal motivation: effects of site-specific transient neural inactivation

PubMed Central

Pereira, Mariana; Morrell, Joan I.

2011-01-01

The present review focuses on recent studies from our laboratory examining the neural circuitry subserving rat maternal motivation across postpartum. We employed a site-specific neural inactivation method by infusion of bupivacaine to map the maternal motivation circuitry using two complementary behavioral approaches: unconditioned maternal responsiveness and choice of pup- over cocaine-conditioned incentives in a concurrent pup/cocaine choice conditioned place preference task. Our findings revealed that during the early postpartum period, distinct brain structures, including the medial preoptic area, ventral tegmental area and medial prefrontal cortex infralimbic and anterior cingulate subregions, contribute a pup-specific bias to the motivational circuitry. As the postpartum period progresses and the pups grow older, our findings further revealed that maternal responsiveness becomes progressively less dependent on medial preoptic area and medial prefrontal cortex infralimbic activity, and more distributed in the maternal circuitry, such that additional network components, including the medial prefrontal cortex prelimbic subregion, are recruited with maternal experience, and contribute to the expression of late postpartum maternal behavior. Collectively, our findings provide strong evidence that the remarkable ability of postpartum females to successfully care for their developing infants is subserved by a distributed neural network that carries out efficient and dynamic processing of complex, constantly changing incoming environmental and pup-related stimuli, ultimately allowing the progression of appropriate expression and waning of maternal responsiveness across the postpartum period. PMID:21815954

How Do Negative Emotions Impair Self-Control? A Neural Model of Negative Urgency

PubMed Central

Chester, David S.; Lynam, Donald R.; Milich, Richard; Powell, David K.; Andersen, Anders H.; DeWall, C. Nathan

2016-01-01

Self-control often fails when people experience negative emotions. Negative urgency represents the dispositional tendency to experience such self-control failure in response to negative affect. The neural underpinnings of negative urgency are not fully understood, nor is the more general phenomenon of self-control failure in response to negative emotions. Previous theorizing suggests that an insufficient, inhibitory response from the prefrontal cortex may be the culprit behind such self-control failure. However, we entertained an alternative hypothesis: negative emotions lead to self-control failure because they excessively tax inhibitory regions of the prefrontal cortex. Using fMRI, we compared the neural activity of people high in negative urgency with controls on an emotional, inhibitory Go/No-Go task. While experiencing negative (but not positive or neutral) emotions, participants high in negative urgency showed greater recruitment of inhibitory brain regions than controls. Suggesting a compensatory function, inhibitory accuracy among participants high in negative urgency was associated with greater prefrontal recruitment. Greater activity in the anterior insula on negatively-valenced, inhibitory trials predicted greater substance abuse one month and one year after the MRI scan among individuals high in negative urgency. These results suggest that, among people whose negative emotions often lead to self-control failure, excessive reactivity of the brain’s regulatory resources may be the culprit. PMID:26892861

Effect of bupropion treatment on brain activation induced by cigarette-related cues in smokers.

PubMed

Culbertson, Christopher S; Bramen, Jennifer; Cohen, Mark S; London, Edythe D; Olmstead, Richard E; Gan, Joanna J; Costello, Matthew R; Shulenberger, Stephanie; Mandelkern, Mark A; Brody, Arthur L

2011-05-01

Nicotine-dependent smokers exhibit craving and brain activation in the prefrontal and limbic regions when presented with cigarette-related cues. Bupropion hydrochloride treatment reduces cue-induced craving in cigarette smokers; however, the mechanism by which bupropion exerts this effect has not yet been described. To assess changes in regional brain activation in response to cigarette-related cues from before to after treatment with bupropion (vs placebo). Randomized, double-blind, before-after controlled trial. Academic brain imaging center. Thirty nicotine-dependent smokers (paid volunteers). Participants were randomly assigned to receive 8 weeks of treatment with either bupropion or a matching placebo pill (double-blind). Subjective cigarette craving ratings and regional brain activations (blood oxygen level-dependent response) in response to viewing cue videos. Bupropion-treated participants reported less craving and exhibited reduced activation in the left ventral striatum, right medial orbitofrontal cortex, and bilateral anterior cingulate cortex from before to after treatment when actively resisting craving compared with placebo-treated participants. When resisting craving, reduction in self-reported craving correlated with reduced regional brain activation in the bilateral medial orbitofrontal and left anterior cingulate cortices in all participants. Treatment with bupropion is associated with improved ability to resist cue-induced craving and a reduction in cue-induced activation of limbic and prefrontal brain regions, while a reduction in craving, regardless of treatment type, is associated with reduced activation in prefrontal brain regions.

Hope, coping skills, and the prefrontal cortex in alcohol use disorder recovery.

PubMed

Bradshaw, Spencer D; Shumway, Sterling T; Dsauza, Cynthia M; Morris, Neli; Hayes, Nicholas D

2017-09-01

Alcohol use disorders adversely affect individual and societal health. These disorders are a chronic brain disease, and protective factors against relapse should be studied. Prefrontal cortex (PFC) dysfunction is evident in alcohol use disorders, and research that explores recovery of the PFC in alcohol use disorders is needed, specifically in regard to how psychological and behavioral factors can augment medicalized treatments and protect against relapse. For example, hope or a belief that recovery is possible is an important cognitive construct-thought to precede behavioral action-that has been associated with relapse. In this study, associations between healthy coping skills and hope (psychological/behavioral factors) and PFC regional activation in response to alcohol cue exposure were examined. It was also examined whether such associations were unique to alcohol cues. Forty-two participants, 32 males and nine females in recovery from an alcohol use disorder (AUD), were administered a subjective hope and coping in recovery measure. They also viewed alcohol, positive, negative, and neutral cues during functional near-infrared spectroscopy (fNIR) PFC assessment. Levels of healthy coping skills positively correlated with activation in the right dorsomedial prefrontal cortex (DMPFC) in response to alcohol cues. This finding was unique to alcohol cues. The association between coping skills and activation of the right DMPFC in response to alcohol cues may reflect greater action restraint and top-down PFC control processing that may protect against relapse.

Role of Prefrontal Cortex Glucocorticoid Receptors in Stress and Emotion

PubMed Central

McKlveen, Jessica M.; Myers, Brent; Flak, Jonathan N.; Bundzikova, Jana; Solomon, Matia B.; Seroogy, Kim B.; Herman, James P.

2013-01-01

Background Stress-related disorders (e.g., depression) are associated with hypothalamic-pituitary-adrenocortical axis dysregulation and prefrontal cortex (PFC) dysfunction, suggesting a functional link between aberrant prefrontal corticosteroid signaling and mood regulation. Methods We used a virally mediated knockdown strategy (short hairpin RNA targeting the glucocorticoid receptor [GR]) to attenuate PFC GR signaling in the rat PFC. Adult male rats received bilateral microinjections of vector control or short hairpin RNA targeting the GR into the prelimbic (n = 44) or infralimbic (n = 52) cortices. Half of the animals from each injection group underwent chronic variable stress, and all were subjected to novel restraint. The first 2 days of chronic variable stress were used to assess depression- and anxiety-like behavior in the forced swim test and open field. Results The GR knockdown confined to the infralimbic PFC caused acute stress hyper-responsiveness, sensitization of stress responses after chronic variable stress, and induced depression-like behavior (increased immobility in the forced swim test). Knockdown of GR in the neighboring prelimbic PFC increased hypothalamic-pituitary-adrenocortical axis responses to acute stress and caused hyper-locomotion in the open field, but did not affect stress sensitization or helplessness behavior. Conclusions The data indicate a marked functional heterogeneity of glucocorticoid action in the PFC and highlight a prominent role for the infralimbic GR in appropriate stress adaptation, emotional control, and mood regulation. PMID:23683655

Modulation of financial deprivation on deception and its neural correlates.

PubMed

Sun, Peng; Ling, Xiaoli; Zheng, Li; Chen, Jia; Li, Lin; Liu, Zhiyuan; Cheng, Xuemei; Guo, Xiuyan

2017-11-01

Deception is a universal phenomenon in human society and plays an important role in everyday life. Previous studies have revealed that people might have an internalized moral norm of keeping honest and the deceptive behavior was reliably correlated with activation in executive brain regions of prefrontal cortices to over-ride intuitive honest responses. Using functional magnetic resonance imaging, this study sought to investigate how financial position modulated the neural responses during deceptive decision. Twenty-one participants were scanned when they played a series of adapted Dictator Game with different partners after a ball-guess game. Specifically, participants gained or lost money in the ball-guess game, and had opportunities to get more financial gains through cheating in the following adapted Dictator Game. Behavioral results indicated that participants did not cheat to the full extent; instead they were more likely to lie after losing money compared with gaining money. At the neural level, weaker activities in the dorsolateral prefrontal cortices were observed when participants lied after losing money than gaining money. Together, our data indicated that, people really had an internalized norm of keeping honest, but it would be lenient when people feel financial deprivation. And suppressing the truthful response originating from moral norm of keeping honest was associated with increased level of activation in the dorsolateral prefrontal cortices, but this association became weaker when people were under financial deprivation.

Functional Neuroimaging in Psychopathy.

PubMed

Del Casale, Antonio; Kotzalidis, Georgios D; Rapinesi, Chiara; Di Pietro, Simone; Alessi, Maria Chiara; Di Cesare, Gianluigi; Criscuolo, Silvia; De Rossi, Pietro; Tatarelli, Roberto; Girardi, Paolo; Ferracuti, Stefano

2015-01-01

Psychopathy is associated with cognitive and affective deficits causing disruptive, harmful and selfish behaviour. These have considerable societal costs due to recurrent crime and property damage. A better understanding of the neurobiological bases of psychopathy could improve therapeutic interventions, reducing the related social costs. To analyse the major functional neural correlates of psychopathy, we reviewed functional neuroimaging studies conducted on persons with this condition. We searched the PubMed database for papers dealing with functional neuroimaging and psychopathy, with a specific focus on how neural functional changes may correlate with task performances and human behaviour. Psychopathy-related behavioural disorders consistently correlated with dysfunctions in brain areas of the orbitofrontal-limbic (emotional processing and somatic reaction to emotions; behavioural planning and responsibility taking), anterior cingulate-orbitofrontal (correct assignment of emotional valence to social stimuli; violent/aggressive behaviour and challenging attitude) and prefrontal-temporal-limbic (emotional stimuli processing/response) networks. Dysfunctional areas more consistently included the inferior frontal, orbitofrontal, dorsolateral prefrontal, ventromedial prefrontal, temporal (mainly the superior temporal sulcus) and cingulated cortices, the insula, amygdala, ventral striatum and other basal ganglia. Emotional processing and learning, and several social and affective decision-making functions are impaired in psychopathy, which correlates with specific changes in neural functions. © 2015 S. Karger AG, Basel.

Switch-Task Performance in Rats Is Disturbed by 12 h of Sleep Deprivation But Not by 12 h of Sleep Fragmentation

PubMed Central

Leenaars, Cathalijn H.C.; Joosten, Ruud N.J.M.A.; Zwart, Allard; Sandberg, Hans; Ruimschotel, Emma; Hanegraaf, Maaike A.J.; Dematteis, Maurice; Feenstra, Matthijs G.P.; van Someren, Eus J.W.

2012-01-01

Study Objectives: Task-switching is an executive function involving the prefrontal cortex. Switching temporarily attenuates the speed and/or accuracy of performance, phenomena referred to as switch costs. In accordance with the idea that prefrontal function is particularly sensitive to sleep loss, switch-costs increase during prolonged waking in humans. It has been difficult to investigate the underlying neurobiological mechanisms because of the lack of a suitable animal model. Here, we introduce the first switch-task for rats and report the effects of sleep deprivation and inactivation of the medial prefrontal cortex. Design: Rats were trained to repeatedly switch between 2 stimulus-response associations, indicated by the presentation of a visual or an auditory stimulus. These stimulus-response associations were offered in blocks, and performance was compared for the first and fifth trials of each block. Performance was tested after exposure to 12 h of total sleep deprivation, sleep fragmentation, and their respective movement control conditions. Finally, it was tested after pharmacological inactivation of the medial prefrontal cortex. Settings: Controlled laboratory settings. Participants: 15 male Wistar rats. Measurements & Results: Both accuracy and latency showed switch-costs at baseline. Twelve hours of total sleep deprivation, but not sleep fragmentation, impaired accuracy selectively on the switch-trials. Inactivation of the medial prefrontal cortex by local neuronal inactivation resulted in an overall decrease in accuracy. Conclusions: We developed and validated a switch-task that is sensitive to sleep deprivation. This introduces the possibility for in-depth investigations on the neurobiological mechanisms underlying executive impairments after sleep disturbance in a rat model. Citation: Leenaars CHC; Joosten RNJMA; Zwart A; Sandberg H; Ruimschotel E; Hanegraaf MAJ; Dematteis M; Feenstra MGP; van Someren EJW. Switch-task performance in rats is disturbed by 12 h of sleep deprivation but not by 12 h of sleep fragmentation. SLEEP 2012;35(2):211-221. PMID:22294811

Self-reported tolerance influences prefrontal cortex hemodynamics and affective responses.

PubMed

Tempest, Gavin; Parfitt, Gaynor

2016-02-01

The relationship between cognitive and sensory processes in the brain contributes to the regulation of affective responses (pleasure-displeasure). Exercise can be used to manipulate sensory processes (by increasing physiological demand) in order to examine the role of dispositional traits that may influence an individual's ability to cognitively regulate these responses. With the use of near infrared spectroscopy, in this study we examined the influence of self-reported tolerance upon prefrontal cortex (PFC) hemodynamics and affective responses. The hemodynamic response was measured in individuals with high or low tolerance during an incremental exercise test. Sensory manipulation was standardized against metabolic processes (ventilatory threshold [VT] and respiratory compensation point [RCP]), and affective responses were recorded. The results showed that the high-tolerance group displayed a larger hemodynamic response within the right PFC above VT (which increased above RCP). The low-tolerance group showed a larger hemodynamic response within the left PFC above VT. The high-tolerance group reported a more positive/less negative affective response above VT. These findings provide direct neurophysiological evidence of differential hemodynamic responses within the PFC that are associated with tolerance in the presence of increased physiological demands. This study supports the role of dispositional traits and previous theorizing into the underlying mechanisms (cognitive vs. sensory processes) of affective responses.

Chronic spatial working memory deficit associated with the superior longitudinal fasciculus: a study using voxel-based lesion-symptom mapping and intraoperative direct stimulation in right prefrontal glioma surgery.

PubMed

Kinoshita, Masashi; Nakajima, Riho; Shinohara, Harumichi; Miyashita, Katsuyoshi; Tanaka, Shingo; Okita, Hirokazu; Nakada, Mitsutoshi; Hayashi, Yutaka

2016-10-01

OBJECTIVE Although the right prefrontal region is regarded as a silent area, chronic deficits of the executive function, including working memory (WM), could occur after resection of a right prefrontal glioma. This may be overlooked by postoperative standard examinations, and the disabilities could affect the patient's professional life. The right prefrontal region is a part of the frontoparietal network and is subserved by the superior longitudinal fasciculus (SLF); however, the role of the SLF in spatial WM is unclear. This study investigated a persistent spatial WM deficit in patients who underwent right prefrontal glioma resection, and evaluated the relationship between the spatial WM deficit and the SLF. METHODS Spatial WM was examined in 24 patients who underwent prefrontal glioma resection (right, n = 14; left, n = 10) and in 14 healthy volunteers using a spatial 2-back task during the long-term postoperative period. The neural correlates of spatial WM were evaluated using lesion mapping and voxel-based lesion-symptom mapping. In addition, the spatial 2-back task was performed during surgery under direct subcortical electrical stimulation in 2 patients with right prefrontal gliomas. RESULTS Patients with a right prefrontal lesion had a significant chronic spatial WM deficit. Voxel-based lesion-symptom mapping analysis revealed a significant correlation between spatial WM deficit and the region that overlapped the first and second segments of the SLF (SLF I and SLF II). Two patients underwent awake surgery and had difficulties providing the correct responses in the spatial 2-back task with direct subcortical electrical stimulation on the SLF I, which was preserved and confirmed by postoperative diffusion tensor imaging tractography. These patients exhibited no spatial WM deficits during the postoperative immediate and long-term periods. CONCLUSIONS Spatial WM deficits may persist in patients who undergo resection of the tumor located in the right prefrontal brain parenchyma. Injury to the dorsal frontoparietal subcortical white matter pathway, i.e., the SLF I or SLF I and II, could play a causal role in this chronic deficit. A persistent spatial WM deficit, without motor and language deficits, could affect the professional life of the patient. In such cases, awake surgery would be useful to detect the spatial WM network with appropriate task during tumor exploration.

Neural and Behavioral Responses during Self-Evaluative Processes Differ in Youth with and without Autism

ERIC Educational Resources Information Center

Pfeifer, Jennifer H.; Merchant, Junaid S.; Colich, Natalie L.; Hernandez, Leanna M.; Rudie, Jeff D.; Dapretto, Mirella

2013-01-01

This fMRI study investigated neural responses while making appraisals of self and other, across the social and academic domains, in children and adolescents with and without autism spectrum disorders (ASD). Compared to neurotypical youth, those with ASD exhibited hypoactivation of ventromedial prefrontal cortex during self-appraisals. Responses in…

Flexibility in the face of fear: Hippocampal-prefrontal regulation of fear and avoidance.

PubMed

Moscarello, Justin M; Maren, Stephen

2018-02-01

Generating appropriate defensive behaviors in the face of threat is essential to survival. Although many of these behaviors are 'hard-wired', they are also flexible. For example, Pavlovian fear conditioning generates learned defensive responses, such as conditioned freezing, that can be suppressed through extinction. The expression of extinguished responses is highly context-dependent, allowing animals to engage behavioral responses appropriate to the contexts in which threats are encountered. Likewise, animals and humans will avoid noxious outcomes if given the opportunity. In instrumental avoidance learning, for example, animals overcome conditioned defensive responses, including freezing, in order to actively avoid aversive stimuli. Recent work has greatly advanced understanding of the neural basis of these phenomena and has revealed common circuits involved in the regulation of fear. Specifically, the hippocampus and medial prefrontal cortex play pivotal roles in gating fear reactions and instrumental actions, mediated by the amygdala and nucleus accumbens, respectively. Because an inability to adaptively regulate fear and defensive behavior is a central component of many anxiety disorders, the brain circuits that promote flexible responses to threat are of great clinical significance.

Eyelid Opening with Trigeminal Proprioceptive Activation Regulates a Brainstem Arousal Mechanism.

PubMed

Matsuo, Kiyoshi; Ban, Ryokuya; Hama, Yuki; Yuzuriha, Shunsuke

2015-01-01

Eyelid opening stretches mechanoreceptors in the supratarsal Müller muscle to activate the proprioceptive fiber supplied by the trigeminal mesencephalic nucleus. This proprioception induces reflex contractions of the slow-twitch fibers in the levator palpebrae superioris and frontalis muscles to sustain eyelid and eyebrow positions against gravity. The cell bodies of the trigeminal proprioceptive neurons in the mesencephalon potentially make gap-junctional connections with the locus coeruleus neurons. The locus coeruleus is implicated in arousal and autonomic function. Due to the relationship between arousal, ventromedial prefrontal cortex, and skin conductance, we assessed whether upgaze with trigeminal proprioceptive evocation activates sympathetically innervated sweat glands and the ventromedial prefrontal cortex. Specifically, we examined whether 60° upgaze induces palmar sweating and hemodynamic changes in the prefrontal cortex in 16 subjects. Sweating was monitored using a thumb-mounted perspiration meter, and prefrontal cortex activity was measured with 45-channel, functional near-infrared spectroscopy (fNIRS) and 2-channel NIRS at Fp1 and Fp2. In 16 subjects, palmar sweating was induced by upgaze and decreased in response to downgaze. Upgaze activated the ventromedial prefrontal cortex with an accumulation of integrated concentration changes in deoxyhemoglobin, oxyhemoglobin, and total hemoglobin levels in 12 subjects. Upgaze phasically and degree-dependently increased deoxyhemoglobin level at Fp1 and Fp2, whereas downgaze phasically decreased it in 16 subjects. Unilateral anesthetization of mechanoreceptors in the supratarsal Müller muscle used to significantly reduce trigeminal proprioceptive evocation ipsilaterally impaired the increased deoxyhemoglobin level by 60° upgaze at Fp1 or Fp2 in 6 subjects. We concluded that upgaze with strong trigeminal proprioceptive evocation was sufficient to phasically activate sympathetically innervated sweat glands and appeared to induce rapid oxygen consumption in the ventromedial prefrontal cortex and to rapidly produce deoxyhemoglobin to regulate physiological arousal. Thus, eyelid opening with trigeminal proprioceptive evocation may activate the ventromedial prefrontal cortex via the mesencephalic trigeminal nucleus and locus coeruleus.

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 represent a compensatory response to the absence of affective feedback during the planning and execution of behavior. Increased reliance upon prefrontal processes in isolation from subcortical structures appears to be maladaptive and may drive behavioral withdrawal that is commonly observed in later phases of neurodegeneration. Copyright © 2012 Elsevier Ltd. All rights reserved.

Eyelid Opening with Trigeminal Proprioceptive Activation Regulates a Brainstem Arousal Mechanism

PubMed Central

Matsuo, Kiyoshi; Ban, Ryokuya; Hama, Yuki; Yuzuriha, Shunsuke

2015-01-01

Eyelid opening stretches mechanoreceptors in the supratarsal Müller muscle to activate the proprioceptive fiber supplied by the trigeminal mesencephalic nucleus. This proprioception induces reflex contractions of the slow-twitch fibers in the levator palpebrae superioris and frontalis muscles to sustain eyelid and eyebrow positions against gravity. The cell bodies of the trigeminal proprioceptive neurons in the mesencephalon potentially make gap-junctional connections with the locus coeruleus neurons. The locus coeruleus is implicated in arousal and autonomic function. Due to the relationship between arousal, ventromedial prefrontal cortex, and skin conductance, we assessed whether upgaze with trigeminal proprioceptive evocation activates sympathetically innervated sweat glands and the ventromedial prefrontal cortex. Specifically, we examined whether 60° upgaze induces palmar sweating and hemodynamic changes in the prefrontal cortex in 16 subjects. Sweating was monitored using a thumb-mounted perspiration meter, and prefrontal cortex activity was measured with 45-channel, functional near-infrared spectroscopy (fNIRS) and 2-channel NIRS at Fp1 and Fp2. In 16 subjects, palmar sweating was induced by upgaze and decreased in response to downgaze. Upgaze activated the ventromedial prefrontal cortex with an accumulation of integrated concentration changes in deoxyhemoglobin, oxyhemoglobin, and total hemoglobin levels in 12 subjects. Upgaze phasically and degree-dependently increased deoxyhemoglobin level at Fp1 and Fp2, whereas downgaze phasically decreased it in 16 subjects. Unilateral anesthetization of mechanoreceptors in the supratarsal Müller muscle used to significantly reduce trigeminal proprioceptive evocation ipsilaterally impaired the increased deoxyhemoglobin level by 60° upgaze at Fp1 or Fp2 in 6 subjects. We concluded that upgaze with strong trigeminal proprioceptive evocation was sufficient to phasically activate sympathetically innervated sweat glands and appeared to induce rapid oxygen consumption in the ventromedial prefrontal cortex and to rapidly produce deoxyhemoglobin to regulate physiological arousal. Thus, eyelid opening with trigeminal proprioceptive evocation may activate the ventromedial prefrontal cortex via the mesencephalic trigeminal nucleus and locus coeruleus. PMID:26244675

Differential induction of FosB isoforms throughout the brain by fluoxetine and chronic stress.

PubMed

Vialou, Vincent; Thibault, Mackenzie; Kaska, Sophia; Cooper, Sarah; Gajewski, Paula; Eagle, Andrew; Mazei-Robison, Michelle; Nestler, Eric J; Robison, A J

2015-12-01

Major depressive disorder is thought to arise in part from dysfunction of the brain's "reward circuitry", consisting of the mesolimbic dopamine system and the glutamatergic and neuromodulatory inputs onto this system. Both chronic stress and antidepressant treatment regulate gene transcription in many of the brain regions that make up these circuits, but the exact nature of the transcription factors and target genes involved in these processes remain unclear. Here, we demonstrate induction of the FosB family of transcription factors in ∼25 distinct regions of adult mouse brain, including many parts of the reward circuitry, by chronic exposure to the antidepressant fluoxetine. We further uncover specific patterns of FosB gene product expression (i.e., differential expression of full-length FosB, ΔFosB, and Δ2ΔFosB) in brain regions associated with depression--the nucleus accumbens (NAc), prefrontal cortex (PFC), and hippocampus--in response to chronic fluoxetine treatment, and contrast these patterns with differential induction of FosB isoforms in the chronic social defeat stress model of depression with and without fluoxetine treatment. We find that chronic fluoxetine, in contrast to stress, causes induction of the unstable full-length FosB isoform in the NAc, PFC, and hippocampus even 24 h following the final injection, indicating that these brain regions may undergo chronic activation when fluoxetine is on board, even in the absence of stress. We also find that only the stable ΔFosB isoform correlates with behavioral responses to stress. These data suggest that NAc, PFC, and hippocampus may present useful targets for directed intervention in mood disorders (ie, brain stimulation or gene therapy), and that determining the gene targets of FosB-mediated transcription in these brain regions in response to fluoxetine may yield novel inroads for pharmaceutical intervention in depressive disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

Distinct and overlapping fMRI activation networks for processing of novel identities and locations of objects.

PubMed

Pihlajamäki, Maija; Tanila, Heikki; Könönen, Mervi; Hänninen, Tuomo; Aronen, Hannu J; Soininen, Hilkka

2005-10-01

The ventral visual stream processes information about the identity of objects ('what'), whereas the dorsal stream processes the spatial locations of objects ('where'). There is a corresponding, although disputed, distinction for the ventrolateral and dorsolateral prefrontal areas. Furthermore, there seems to be a distinction between the anterior and posterior medial temporal lobe (MTL) structures in the processing of novel items and new spatial arrangements, respectively. Functional differentiation of the intermediary mid-line cortical and temporal neocortical structures that communicate with the occipitotemporal, occipitoparietal, prefrontal, and MTL structures, however, is unclear. Therefore, in the present functional magnetic resonance imaging (fMRI) study, we examined whether the distinction among the MTL structures extends to these closely connected cortical areas. The most striking difference in the fMRI responses during visual presentation of changes in either items or their locations was the bilateral activation of the temporal lobe and ventrolateral prefrontal cortical areas for novel object identification in contrast to wide parietal and dorsolateral prefrontal activation for the novel locations of objects. An anterior-posterior distinction of fMRI responses similar to the MTL was observed in the cingulate/retrosplenial, and superior and middle temporal cortices. In addition to the distinct areas of activation, certain frontal, parietal, and temporo-occipital areas responded to both object and spatial novelty, suggesting a common attentional network for both types of changes in the visual environment. These findings offer new insights to the functional roles and intrinsic specialization of the cingulate/retrosplenial, and lateral temporal cortical areas in visuospatial cognition.

Age-related differences in striatal, medial temporal, and frontal involvement during value-based decision processing.

PubMed

Su, Yu-Shiang; Chen, Jheng-Ting; Tang, Yong-Jheng; Yuan, Shu-Yun; McCarrey, Anna C; Goh, Joshua Oon Soo

2018-05-21

Appropriate neural representation of value and application of decision strategies are necessary to make optimal investment choices in real life. Normative human aging alters neural selectivity and control processing in brain regions implicated in value-based decision processing including striatal, medial temporal, and frontal areas. However, the specific neural mechanisms of how these age-related functional brain changes modulate value processing in older adults remain unclear. Here, young and older adults performed a lottery-choice functional magnetic resonance imaging experiment in which probabilities of winning different magnitudes of points constituted expected values of stakes. Increasing probability of winning modulated striatal responses in young adults, but modulated medial temporal and ventromedial prefrontal areas instead in older adults. Older adults additionally engaged higher responses in dorso-medio-lateral prefrontal cortices to more unfavorable stakes. Such extrastriatal involvement mediated age-related increase in risk-taking decisions. Furthermore, lower resting-state functional connectivity between lateral prefrontal and striatal areas also predicted lottery-choice task risk-taking that was mediated by higher functional connectivity between prefrontal and medial temporal areas during the task, with this mediation relationship being stronger in older than younger adults. Overall, we report evidence of a systemic neural mechanistic change in processing of probability in mixed-lottery values with age that increases risk-taking of unfavorable stakes in older adults. Moreover, individual differences in age-related effects on baseline frontostriatal communication may be a central determinant of such subsequent age differences in value-based decision neural processing and resulting behaviors. Copyright © 2018 Elsevier Inc. All rights reserved.

Mechanistic comparisons of functional domains across pediatric and adult bipolar disorder highlight similarities, as well as differences, influenced by the developing brain.

PubMed

Wegbreit, Ezra; Pavuluri, Mani

2012-01-01

Recent neuroimaging studies have uncovered much about the specific neural deficits in adult bipolar disorder (ABD), but despite promising results, neuroimaging research for pediatric bipolar disorder (PBD) is still developing. The neuroimaging literature is highly heterogeneous, varying in the paradigms used and in participants' mood states and medication status. Despite this variability, several dominant patterns emerge. In response to emotional stimuli, both ABD and PBD show limbic hyperactivity coupled with hypoactivity in ventral prefrontal emotion regulation systems. This pattern occurred most robustly in response to negative incidental stimuli and was especially apparent in manic PBD. ABD showed more variability in ventral prefrontal activity, possibly due to maturational and medication factors. On numerous cognitive paradigms, PBD showed dorsal prefrontal hypoactivity linked to ventral dysfunction, whereas ABD showed compensatory frontal, parietal, and temporal activity with paradigm-specific variations. In emotion-cognition interaction paradigms, patients show dysregulation in regions interfacing between cognitive and emotional brain systems (e.g., ventral prefrontal and cingulate cortices), which expend extra effort to process emotional stimuli effectively and recruit additional posterior attention systems to cope with affective instability. In addition, novel functional connectivity techniques have uncovered connectivity deficits between frontal and limbic regions in ABD and PBD at rest and during active emotional and cognitive tasks. Finally, the neuroimaging literature currently lacks cross-sectional studies comparing PBD with ABD and longitudinal studies following children and adolescents with BD into adulthood. Such studies would provide important insights into patients' prognosis and would determine targets for early interventions in the evolving illness diathesis.

Low-level light therapy improves cortical metabolic capacity and memory retention.

PubMed

Rojas, Julio C; Bruchey, Aleksandra K; Gonzalez-Lima, Francisco

2012-01-01

Cerebral hypometabolism characterizes mild cognitive impairment and Alzheimer's disease. Low-level light therapy (LLLT) enhances the metabolic capacity of neurons in culture through photostimulation of cytochrome oxidase, the mitochondrial enzyme that catalyzes oxygen consumption in cellular respiration. Growing evidence supports that neuronal metabolic enhancement by LLLT positively impacts neuronal function in vitro and in vivo. Based on its effects on energy metabolism, it is proposed that LLLT will also affect the cerebral cortex in vivo and modulate higher-order cognitive functions such as memory. In vivo effects of LLLT on brain and behavior are poorly characterized. We tested the hypothesis that in vivo LLLT facilitates cortical oxygenation and metabolic energy capacity and thereby improves memory retention. Specifically, we tested this hypothesis in rats using fear extinction memory, a form of memory modulated by prefrontal cortex activation. Effects of LLLT on brain metabolism were determined through measurement of prefrontal cortex oxygen concentration with fluorescent quenching oximetry and by quantitative cytochrome oxidase histochemistry. Experiment 1 verified that LLLT increased the rate of oxygen consumption in the prefrontal cortex in vivo. Experiment 2 showed that LLLT-treated rats had an enhanced extinction memory as compared to controls. Experiment 3 showed that LLLT reduced fear renewal and prevented the reemergence of extinguished conditioned fear responses. Experiment 4 showed that LLLT induced hormetic dose-response effects on the metabolic capacity of the prefrontal cortex. These data suggest that LLLT can enhance cortical metabolic capacity and retention of extinction memories, and implicate LLLT as a novel intervention to improve memory.

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.

Domain expertise insulates against judgment bias by monetary favors through a modulation of ventromedial prefrontal cortex

PubMed Central

Kirk, Ulrich; Harvey, Ann; Montague, P. Read

2011-01-01

Recent work using an art-viewing paradigm shows that monetary sponsorship of the experiment by a company (a favor) increases the valuation of paintings placed next to the sponsoring corporate logo, an effect that correlates with modulation of the ventromedial prefrontal cortex (VMPFC). We used the same art-viewing paradigm to test a prevailing idea in the domain of conflict-of-interest: that expertise in a domain insulates against judgment bias even in the presence of a monetary favor. Using a cohort of art experts, we show that monetary favors do not bias the experts’ valuation of art, an effect that correlates with a lack of modulation of the VMPFC across sponsorship conditions. The lack of sponsorship effect in the VMPFC suggests the hypothesis that their brains remove the behavioral sponsorship effect by censoring sponsorship-dependent modulation of VMPFC activity. We tested the hypothesis that prefrontal regions play a regulatory role in mediating the sponsorship effect. We show that the dorsolateral prefrontal cortex (DLPFC) is recruited in the expert group. Furthermore, we tested the hypothesis in nonexpert controls by contrasting brain responses in controls who did not show a sponsorship effect to controls who did. Changes in effective connectivity between the DLPFC and VMPFC were greater in nonexpert controls, with an absence of the sponsorship effect relative to those with a presence of the sponsorship effect. The role of the DLPFC in cognitive control and emotion regulation suggests that it removes the influence of a monetary favor by controlling responses in known valuation regions of the brain including the the VMPFC. PMID:21646526

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

Cortical influences on brainstem circuitry responsible for conditioned pain modulation in humans.

PubMed

Youssef, Andrew M; Macefield, Vaughan G; Henderson, Luke A

2016-07-01

Conditioned pain modulation (CPM) is a powerful endogenous analgesic mechanism which can completely inhibit incoming nociceptor signals at the primary synapse. The circuitry responsible for CPM lies within the brainstem and involves the subnucleus reticularis dorsalis (SRD). While the brainstem is critical for CPM, the cortex can significantly modulate its expression, likely via the brainstem circuitry critical for CPM. Since higher cortical regions such as the anterior, mid-cingulate, and dorsolateral prefrontal cortices are activated by noxious stimuli and show reduced activations during other analgesic responses, we hypothesized that these regions would display reduced responses during CPM analgesia. Furthermore, we hypothesized that functional connectivity strength between these cortical regions and the SRD would be stronger in those that express CPM analgesia compared with those that do not. We used functional magnetic resonance imaging to determine sites recruited during CPM expression and their influence on the SRD. A lack of CPM analgesia was associated with greater signal intensity increases during each test stimulus in the presence of the conditioning stimulus compared to test stimuli alone in the mid-cingulate and dorsolateral prefrontal cortices and increased functional connectivity with the SRD. In contrast, those subjects exhibiting CPM analgesia showed no change in the magnitude of signal intensity increases in these cortical regions or strength of functional connectivity with the SRD. These data suggest that during multiple or widespread painful stimuli, engagement of the prefrontal and cingulate cortices prevents the generation of CPM analgesia, raising the possibility altered responsiveness in these cortical regions underlie the reduced CPM observed in individuals with chronic pain. Hum Brain Mapp 37:2630-2644, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Maternal Neural Responses to Infant Cries and Faces: Relationships with Substance Use

PubMed Central

Landi, Nicole; Montoya, Jessica; Kober, Hedy; Rutherford, Helena J. V.; Mencl, W. Einar; Worhunsky, Patrick D.; Potenza, Marc N.; Mayes, Linda C.

2011-01-01

Substance abuse in pregnant and recently post-partum women is a major public health concern because of effects on the infant and on the ability of the adult to care for the infant. In addition to the negative health effects of teratogenic substances on fetal development, substance use can contribute to difficulties associated with the social and behavioral aspects of parenting. Neural circuits associated with parenting behavior overlap with circuits involved in addiction (e.g., frontal, striatal, and limbic systems) and thus may be co-opted for the craving/reward cycle associated with substance use and abuse and be less available for parenting. The current study investigates the degree to which neural circuits associated with parenting are disrupted in mothers who are substance-using. Specifically, we used functional magnetic resonance imaging to examine the neural response to emotional infant cues (faces and cries) in substance-using compared to non-using mothers. In response to both faces (of varying emotional valence) and cries (of varying distress levels), substance-using mothers evidenced reduced neural activation in regions that have been previously implicated in reward and motivation as well as regions involved in cognitive control. Specifically, in response to faces, substance users showed reduced activation in prefrontal regions, including the dorsolateral and ventromedial prefrontal cortices, as well as visual processing (occipital lobes) and limbic regions (parahippocampus and amygdala). Similarly, in response to infant cries, substance-using mothers showed reduced activation relative to non-using mothers in prefrontal regions, auditory sensory processing regions, insula and limbic regions (parahippocampus and amygdala). These findings suggest that infant stimuli may be less salient for substance-using mothers, and such reduced saliency may impair developing infant-caregiver attachment and the ability of mothers to respond appropriately to their infants. PMID:21720537

Frontal Dysfunctions of Impulse Control – A Systematic Review in Borderline Personality Disorder and Attention-Deficit/Hyperactivity Disorder

PubMed Central

Sebastian, Alexandra; Jung, Patrick; Krause-Utz, Annegret; Lieb, Klaus; Schmahl, Christian; Tüscher, Oliver

2014-01-01

Disorders such as borderline personality disorder (BPD) or attention-deficit/hyperactivity disorder (ADHD) are characterized by impulsive behaviors. Impulsivity as used in clinical terms is very broadly defined and entails different categories including personality traits as well as different cognitive functions such as emotion regulation or interference resolution and impulse control. Impulse control as an executive function, however, is neither cognitively nor neurobehaviorally a unitary function. Recent findings from behavioral and cognitive neuroscience studies suggest related but dissociable components of impulse control along functional domains like selective attention, response selection, motivational control, and behavioral inhibition. In addition, behavioral and neural dissociations are seen for proactive vs. reactive inhibitory motor control. The prefrontal cortex with its sub-regions is the central structure in executing these impulse control functions. Based on these concepts of impulse control, neurobehavioral findings of studies in BPD and ADHD were reviewed and systematically compared. Overall, patients with BPD exhibited prefrontal dysfunctions across impulse control components rather in orbitofrontal, dorsomedial, and dorsolateral prefrontal regions, whereas patients with ADHD displayed disturbed activity mainly in ventrolateral and medial prefrontal regions. Prefrontal dysfunctions, however, varied depending on the impulse control component and from disorder to disorder. This suggests a dissociation of impulse control related frontal dysfunctions in BPD and ADHD, although only few studies are hitherto available to assess frontal dysfunctions along different impulse control components in direct comparison of these disorders. Yet, these findings might serve as a hypothesis for the future systematic assessment of impulse control components to understand differences and commonalities of prefrontal cortex dysfunction in impulsive disorders. PMID:25232313

Prefrontal Neurons Encode a Solution to the Credit-Assignment Problem

PubMed Central

Perge, János A.; Eskandar, Emad N.

2017-01-01

To adapt successfully to our environments, we must use the outcomes of our choices to guide future behavior. Critically, we must be able to correctly assign credit for any particular outcome to the causal features which preceded it. In some cases, the causal features may be immediately evident, whereas in others they may be separated in time or intermingled with irrelevant environmental stimuli, creating a potentially nontrivial credit-assignment problem. We examined the neuronal representation of information relevant for credit assignment in the dorsolateral prefrontal cortex (dlPFC) of two male rhesus macaques performing a task that elicited key aspects of this problem. We found that neurons conveyed the information necessary for credit assignment. Specifically, neuronal activity reflected both the relevant cues and outcomes at the time of feedback and did so in a manner that was stable over time, in contrast to prior reports of representational instability in the dlPFC. Furthermore, these representations were most stable early in learning, when credit assignment was most needed. When the same features were not needed for credit assignment, these neuronal representations were much weaker or absent. These results demonstrate that the activity of dlPFC neurons conforms to the basic requirements of a system that performs credit assignment, and that spiking activity can serve as a stable mechanism that links causes and effects. SIGNIFICANCE STATEMENT Credit assignment is the process by which we infer the causes of our successes and failures. We found that neuronal activity in the dorsolateral prefrontal cortex conveyed the necessary information for performing credit assignment. Importantly, while there are various potential mechanisms to retain a “trace” of the causal events over time, we observed that spiking activity was sufficiently stable to act as the link between causes and effects, in contrast to prior reports that suggested spiking representations were unstable over time. In addition, we observed that this stability varied as a function of learning, such that the neural code was more reliable over time during early learning, when it was most needed. PMID:28634307

BDNF mRNA expression in rat hippocampus and prefrontal cortex: effects of neonatal ventral hippocampal damage and antipsychotic drugs.

PubMed

Lipska, B K; Khaing, Z Z; Weickert, C S; Weinberger, D R

2001-07-01

Brain-derived neurotrophic factor (BDNF) plays an important role in development, synapse remodelling and responses to stress and injury. Its abnormal expression has been implicated in schizophrenia, a neuropsychiatric disorder in which abnormal neural development of the hippocampus and prefrontal cortex has been postulated. To clarify the effects of antipsychotic drugs used in the therapy of schizophrenia on BDNF mRNA, we studied its expression in rats treated with clozapine and haloperidol and in rats with neonatal lesions of the ventral hippocampus, used as an animal model of schizophrenia. Both antipsychotic drugs reduced BDNF expression in the hippocampus of control rats, but did not significantly lower its expression in the prefrontal cortex. The neonatal hippocampal lesion itself suppressed BDNF mRNA expression in the dentate gyrus and tended to reduce its expression in the prefrontal cortex. These results indicate that, unlike antidepressants, antipsychotics down-regulate BDNF mRNA, and suggest that their therapeutic properties are not mediated by stimulation of this neurotrophin. To the extent that the lesioned rat models some pathophysiological aspects of schizophrenia, our data suggest that a neurodevelopmental insult might suppress expression of the neurotrophin in certain brain regions.

Dynamic neural activity during stress signals resilient coping

PubMed Central

Sinha, Rajita; Lacadie, Cheryl M.; Constable, R. Todd; Seo, Dongju

2016-01-01

Active coping underlies a healthy stress response, but neural processes supporting such resilient coping are not well-known. Using a brief, sustained exposure paradigm contrasting highly stressful, threatening, and violent stimuli versus nonaversive neutral visual stimuli in a functional magnetic resonance imaging (fMRI) study, we show significant subjective, physiologic, and endocrine increases and temporally related dynamically distinct patterns of neural activation in brain circuits underlying the stress response. First, stress-specific sustained increases in the amygdala, striatum, hypothalamus, midbrain, right insula, and right dorsolateral prefrontal cortex (DLPFC) regions supported the stress processing and reactivity circuit. Second, dynamic neural activation during stress versus neutral runs, showing early increases followed by later reduced activation in the ventrolateral prefrontal cortex (VLPFC), dorsal anterior cingulate cortex (dACC), left DLPFC, hippocampus, and left insula, suggested a stress adaptation response network. Finally, dynamic stress-specific mobilization of the ventromedial prefrontal cortex (VmPFC), marked by initial hypoactivity followed by increased VmPFC activation, pointed to the VmPFC as a key locus of the emotional and behavioral control network. Consistent with this finding, greater neural flexibility signals in the VmPFC during stress correlated with active coping ratings whereas lower dynamic activity in the VmPFC also predicted a higher level of maladaptive coping behaviors in real life, including binge alcohol intake, emotional eating, and frequency of arguments and fights. These findings demonstrate acute functional neuroplasticity during stress, with distinct and separable brain networks that underlie critical components of the stress response, and a specific role for VmPFC neuroflexibility in stress-resilient coping. PMID:27432990

The Microbiome-Gut-Behavior Axis: Crosstalk Between the Gut Microbiome and Oligodendrocytes Modulates Behavioral Responses.

PubMed

Ntranos, Achilles; Casaccia, Patrizia

2018-01-01

Environmental and dietary stimuli have always been implicated in brain development and behavioral responses. The gut, being the major portal of communication with the external environment, has recently been brought to the forefront of this interaction with the establishment of a gut-brain axis in health and disease. Moreover, recent breakthroughs in germ-free and antibiotic-treated mice have demonstrated the significant impact of the microbiome in modulating behavioral responses in mice and have established a more specific microbiome-gut-behavior axis. One of the mechanisms by which this axis affects social behavior is by regulating myelination at the prefrontal cortex, an important site for complex cognitive behavior planning and decision-making. The prefrontal cortex exhibits late myelination of its axonal projections that could extend into the third decade of life in humans, which make it susceptible to external influences, such as microbial metabolites. Changes in the gut microbiome were shown to alter the composition of the microbial metabolome affecting highly permeable bioactive compounds, such as p-cresol, which could impair oligodendrocyte differentiation. Dysregulated myelination in the prefrontal cortex is then able to affect behavioral responses in mice, shifting them towards social isolation. The reduced social interactions could then limit microbial exchange, which could otherwise pose a threat to the survival of the existing microbial community in the host and, thus, provide an evolutionary advantage to the specific microbial community. In this review, we will analyze the microbiome-gut-behavior axis, describe the interactions between the gut microbiome and oligodendrocytes and highlight their role in the modulation of social behavior.

Prefrontal and parietal correlates of cognitive control related to the adult outcome of attention-deficit/hyperactivity disorder diagnosed in childhood.

PubMed

Schulz, Kurt P; Li, Xiaobo; Clerkin, Suzanne M; Fan, Jin; Berwid, Olga G; Newcorn, Jeffrey H; Halperin, Jeffrey M

2017-05-01

The protracted and highly variable development of prefrontal cortex regions that support cognitive control has been purported to shape the adult outcome of attention-deficit/hyperactivity disorder (ADHD). This neurodevelopmental model was tested in a prospectively followed sample of 27 adult probands who were diagnosed with ADHD in childhood and 28 carefully matched comparison subjects aged 21-28 years. Probands were classified with persistent ADHD or remitted ADHD. Behavioral and neural responses to the Stimulus and Response Conflict Task (SRCT) performed during functional magnetic resonance imaging (fMRI) were compared in probands and comparison subjects and in probands with persistent and remitted ADHD. Response speed and accuracy for stimulus, response, and combined conflicts did not differ across groups. Orbitofrontal, inferior frontal and parietal activation was lower in probands than comparison subjects, but only for combined conflicts, when demand for cognitive control was highest. Reduced activation for combined conflicts in probands was almost wholly attributable to the persistence of ADHD; orbitofrontal, inferior frontal, anterior cingulate and parietal activation was lower in probands with persistent ADHD than both probands with remitted ADHD and comparison subjects, but did not differ between probands with remitted ADHD and comparison subjects. These data provide the first evidence that prefrontal and parietal activation during cognitive control parallels the adult outcome of ADHD diagnosed in childhood, with persistence of symptoms linked to reduced activation and symptom recovery associated with activation indistinguishable from adults with no history of ADHD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Neural mechanisms of symptom improvements in generalized anxiety disorder following mindfulness training☆☆☆

PubMed Central

Hölzel, Britta K.; Hoge, Elizabeth A.; Greve, Douglas N.; Gard, Tim; Creswell, J. David; Brown, Kirk Warren; Barrett, Lisa Feldman; Schwartz, Carl; Vaitl, Dieter; Lazar, Sara W.

2013-01-01

Mindfulness training aims to impact emotion regulation. Generalized anxiety disorder (GAD) symptoms can be successfully addressed through mindfulness-based interventions. This preliminary study is the first to investigate neural mechanisms of symptom improvements in GAD following mindfulness training. Furthermore, we compared brain activation between GAD patients and healthy participants at baseline. 26 patients with a current DSM-IV GAD diagnosis were randomized to an 8-week Mindfulness Based Stress Reduction (MBSR, N = 15) or a stress management education (SME, N = 11) active control program. 26 healthy participants were included for baseline comparisons. BOLD response was assessed with fMRI during affect labeling of angry and neutral facial expressions. At baseline, GAD patients showed higher amygdala activation than healthy participants in response to neutral, but not angry faces, suggesting that ambiguous stimuli reveal stronger reactivity in GAD patients. In patients, amygdala activation in response to neutral faces decreased following both interventions. BOLD response in ventrolateral prefrontal regions (VLPFC) showed greater increase in MBSR than SME participants. Functional connectivity between amygdala and PFC regions increased significantly pre- to post-intervention within the MBSR, but not SME group. Both, change in VLPFC activation and amygdala–prefrontal connectivity were correlated with change in Beck Anxiety Inventory (BAI) scores, suggesting clinical relevance of these changes. Amygdala–prefrontal connectivity turned from negative coupling (typically seen in down-regulation of emotions), to positive coupling; potentially suggesting a unique mechanism of mindfulness. Findings suggest that in GAD, mindfulness training leads to changes in fronto-limbic areas crucial for the regulation of emotion; these changes correspond with reported symptom improvements. PMID:24179799

Blunted neural response to anticipation, effort and consummation of reward and aversion in adolescents with depression symptomatology.

PubMed

Rzepa, Ewelina; Fisk, Jennifer; McCabe, Ciara

2017-03-01

Neural reward function has been proposed as a possible biomarker for depression. However, how the neural response to reward and aversion might differ in young adolescents with current symptoms of depression is as yet unclear. Thirty-three adolescents were recruited, 17 scoring low on the Mood and Feelings Questionnaire (low risk group) and 16 scoring high (high risk group). Our functional magnetic resonance imaging task measured; anticipation (pleasant/unpleasant cue), effort (achieve a pleasant taste or avoid an unpleasant taste) and consummation (pleasant/unpleasant tastes) in regions of interest; ventral medial prefrontal cortex, pregenual cingulate cortex, the insula and ventral striatum. We also examined whole brain group differences. In the regions of interest analysis we found reduced activity in the high risk group in the pregenual cingulate cortex during anticipation and reduced pregenual cingulate cortex and ventral medial prefrontal cortex during effort and consummation. In the whole brain analysis we also found reduced activity in the high risk group in the prefrontal cortex and the precuneus during anticipation. We found reduced activity in the hippocampus during the effort phase and in the anterior cingulate/frontal pole during consummation in the high risk group. Increased anhedonia measures correlated with decreased pregenual cingulate cortex activity during consummation in the high risk group only. Our results are the first to show that adolescents with depression symptoms have blunted neural responses during the anticipation, effort and consummation of rewarding and aversive stimuli. This study suggests that interventions in young people at risk of depression, that can reverse blunted responses, might be beneficial as preventative strategies.

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

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 different phenomenal experiences of affect, depending on the depth of cortical processing. They are in line with a model in which the left ventrolateral prefrontal cortex is a relay station that integrates information about subcortically triggered somatic responses and information resulting from in-depth cortical stimulus processing. Tentatively, we suggest that the observed decoupling of somatic responses and experienced affect, and the reduction of negative phenomenal experience, can be explained by a left ventrolateral prefrontal cortex-mediated inhibition of affect-related somatosensory activity.

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 different phenomenal experiences of affect, depending on the depth of cortical processing. They are in line with a model in which the left ventrolateral prefrontal cortex is a relay station that integrates information about subcortically triggered somatic responses and information resulting from in-depth cortical stimulus processing. Tentatively, we suggest that the observed decoupling of somatic responses and experienced affect, and the reduction of negative phenomenal experience, can be explained by a left ventrolateral prefrontal cortex-mediated inhibition of affect-related somatosensory activity. PMID:19767414

Sex differences in prefrontal hemodynamic response to mental arithmetic as assessed by near-infrared spectroscopy.

PubMed

Yang, Hongyu; Wang, Ying; Zhou, Zhenyu; Gong, Hui; Luo, Qingming; Wang, Yiwen; Lu, Zuhong

2009-12-01

Sex differences in cognitive tasks have been widely investigated. With brain-imaging techniques, the functions of the brain during the performance of tasks can be examined. Mental arithmetic and near-infrared spectroscopy (NIRS) were used to assess sex differences in prefrontal area activation in a functional brain study. Healthy college students were recruited to perform 2 mental arithmetic tasks. In the first (easy) task, students had to subtract a 1-digit number from a 3-digit number. In the second (difficult) task, they had to subtract a 2-digit number from a 3-digit number. Changes in the concentration of oxygenated hemoglobin (oxy-Hgb) in the prefrontal area during the tasks were measured with NIRS. Thirty students (15 men, 15 women; mean [SD] age: 24.9 [2.2] and 24.3 [2.6] years, respectively) were recruited from Southeast University, Nanjing, China, to participate in the study. The concentration of oxy-Hgb increased during both mental arithmetic tasks (difficult task vs easy task, mean [SD] % arbitrary units: 4.36 [4.38] vs 2.26 [2.82]; F(1,28) = 222.80; P < 0.01). Significant interactions of task x sex (F(1,28) = 82.95), time x sex (F(1,28) = 34.48), task x time (F(1,28) = 222.57), and task x time x sex (F(1,28) = 83.09) were obtained (all, P < 0.01). However, for the 2 tasks, no significant differences between men and women were observed in the mean (SD) response time (men vs women, sec: 3.60 [0.74] vs 3.56 [0.49] for the easy task, 6.55 [0.77] vs 6.44 [0.75] for the difficult task; F(1,28) = 0.67; P = NS) or accuracy rate (men vs women, %: 95.33 [7.40] vs 92.77 [8.80] for the easy task, 62.67 [28.56] vs 54.67 [18.75] for the difficult task; F(1,28) = 0.54; P = NS). Male students showed neural efficiency (less prefrontal activation in subjects with better performance) during the difficult task. In these subjects, sex differences in prefrontal response when performing mental arithmetic were associated with the intensity of the task. Compared with men, women had greater efficiency in task performance (ie, less activation or oxygen consumption for equal performance). Copyright 2009 Excerpta Medica Inc. All rights reserved.

Frontostriatal and behavioral adaptations to daily sugar-sweetened beverage intake: a randomized controlled trial.

PubMed

Burger, Kyle S

2017-03-01

Background: Current obesity theories suggest that the repeated intake of highly palatable high-sugar foods causes adaptions in the striatum, parietal lobe, and prefrontal and visual cortices in the brain that may serve to perpetuate consumption in a feed-forward manner. However, the data for humans are cross-sectional and observational, leaving little ability to determine the temporal precedence of repeated consumption on brain response. Objective: We tested the impact of regular sugar-sweetened beverage intake on brain and behavioral responses to beverage stimuli. Design: We performed an experiment with 20 healthy-weight individuals who were randomly assigned to consume 1 of 2 sugar-sweetened beverages daily for 21 d, underwent 2 functional MRI sessions, and completed behavioral and explicit hedonic assessments. Results: Consistent with preclinical experiments, daily beverage consumption resulted in decreases in dorsal striatal response during receipt of the consumed beverage ( r = -0.46) and decreased ventromedial prefrontal response during logo-elicited anticipation ( r = -0.44). This decrease in the prefrontal response correlated with increases in behavioral disinhibition toward the logo of the consumed beverage ( r = 0.54; P = 0.02). Daily beverage consumption also increased precuneus response to both juice logos compared with a tasteless control ( r = 0.45), suggesting a more generalized effect toward beverage cues. Last, the repeated consumption of 1 beverage resulted in an explicit hedonic devaluation of a similar nonconsumed beverage ( P < 0.001). Conclusions: Analogous to previous reports, these initial results provide convergent data for a role of regular sugar-sweetened beverage intake in altering neurobehavioral responses to the regularly consumed beverage that may also extend to other beverage stimuli. Future research is required to provide evidence of replication in a larger sample and to establish whether the neurobehavioral adaptations observed herein are specific to high-sugar and/or nonnutritive-sweetened beverages or more generally related to the repeated consumption of any type of food. This trial was registered at clinicaltrials.gov as NCT02624206. © 2017 American Society for Nutrition.

Differences in Visuo-Motor Control in Skilled vs. Novice Martial Arts Athletes during Sustained and Transient Attention Tasks: A Motor-Related Cortical Potential Study

PubMed Central

Sanchez-Lopez, Javier; Fernandez, Thalia; Silva-Pereyra, Juan; Martinez Mesa, Juan A.; Di Russo, Francesco

2014-01-01

Cognitive and motor processes are essential for optimal athletic performance. Individuals trained in different skills and sports may have specialized cognitive abilities and motor strategies related to the characteristics of the activity and the effects of training and expertise. Most studies have investigated differences in motor-related cortical potential (MRCP) during self-paced tasks in athletes but not in stimulus-related tasks. The aim of the present study was to identify the differences in performance and MRCP between skilled and novice martial arts athletes during two different types of tasks: a sustained attention task and a transient attention task. Behavioral and electrophysiological data from twenty-two martial arts athletes were obtained while they performed a continuous performance task (CPT) to measure sustained attention and a cued continuous performance task (c-CPT) to measure transient attention. MRCP components were analyzed and compared between groups. Electrophysiological data in the CPT task indicated larger prefrontal positive activity and greater posterior negativity distribution prior to a motor response in the skilled athletes, while novices showed a significantly larger response-related P3 after a motor response in centro-parietal areas. A different effect occurred in the c-CPT task in which the novice athletes showed strong prefrontal positive activity before a motor response and a large response-related P3, while in skilled athletes, the prefrontal activity was absent. We propose that during the CPT, skilled athletes were able to allocate two different but related processes simultaneously according to CPT demand, which requires controlled attention and controlled motor responses. On the other hand, in the c-CPT, skilled athletes showed better cue facilitation, which permitted a major economy of resources and “automatic” or less controlled responses to relevant stimuli. In conclusion, the present data suggest that motor expertise enhances neural flexibility and allows better adaptation of cognitive control to the requested task. PMID:24621480

Differences in visuo-motor control in skilled vs. novice martial arts athletes during sustained and transient attention tasks: a motor-related cortical potential study.

PubMed

Sanchez-Lopez, Javier; Fernandez, Thalia; Silva-Pereyra, Juan; Martinez Mesa, Juan A; Di Russo, Francesco

2014-01-01

Cognitive and motor processes are essential for optimal athletic performance. Individuals trained in different skills and sports may have specialized cognitive abilities and motor strategies related to the characteristics of the activity and the effects of training and expertise. Most studies have investigated differences in motor-related cortical potential (MRCP) during self-paced tasks in athletes but not in stimulus-related tasks. The aim of the present study was to identify the differences in performance and MRCP between skilled and novice martial arts athletes during two different types of tasks: a sustained attention task and a transient attention task. Behavioral and electrophysiological data from twenty-two martial arts athletes were obtained while they performed a continuous performance task (CPT) to measure sustained attention and a cued continuous performance task (c-CPT) to measure transient attention. MRCP components were analyzed and compared between groups. Electrophysiological data in the CPT task indicated larger prefrontal positive activity and greater posterior negativity distribution prior to a motor response in the skilled athletes, while novices showed a significantly larger response-related P3 after a motor response in centro-parietal areas. A different effect occurred in the c-CPT task in which the novice athletes showed strong prefrontal positive activity before a motor response and a large response-related P3, while in skilled athletes, the prefrontal activity was absent. We propose that during the CPT, skilled athletes were able to allocate two different but related processes simultaneously according to CPT demand, which requires controlled attention and controlled motor responses. On the other hand, in the c-CPT, skilled athletes showed better cue facilitation, which permitted a major economy of resources and "automatic" or less controlled responses to relevant stimuli. In conclusion, the present data suggest that motor expertise enhances neural flexibility and allows better adaptation of cognitive control to the requested task.

Frontostriatal and behavioral adaptations to daily sugar-sweetened beverage intake: a randomized controlled trial123

PubMed Central

2017-01-01

Background: Current obesity theories suggest that the repeated intake of highly palatable high-sugar foods causes adaptions in the striatum, parietal lobe, and prefrontal and visual cortices in the brain that may serve to perpetuate consumption in a feed-forward manner. However, the data for humans are cross-sectional and observational, leaving little ability to determine the temporal precedence of repeated consumption on brain response. Objective: We tested the impact of regular sugar-sweetened beverage intake on brain and behavioral responses to beverage stimuli. Design: We performed an experiment with 20 healthy-weight individuals who were randomly assigned to consume 1 of 2 sugar-sweetened beverages daily for 21 d, underwent 2 functional MRI sessions, and completed behavioral and explicit hedonic assessments. Results: Consistent with preclinical experiments, daily beverage consumption resulted in decreases in dorsal striatal response during receipt of the consumed beverage (r = −0.46) and decreased ventromedial prefrontal response during logo-elicited anticipation (r = −0.44). This decrease in the prefrontal response correlated with increases in behavioral disinhibition toward the logo of the consumed beverage (r = 0.54; P = 0.02). Daily beverage consumption also increased precuneus response to both juice logos compared with a tasteless control (r = 0.45), suggesting a more generalized effect toward beverage cues. Last, the repeated consumption of 1 beverage resulted in an explicit hedonic devaluation of a similar nonconsumed beverage (P < 0.001). Conclusions: Analogous to previous reports, these initial results provide convergent data for a role of regular sugar-sweetened beverage intake in altering neurobehavioral responses to the regularly consumed beverage that may also extend to other beverage stimuli. Future research is required to provide evidence of replication in a larger sample and to establish whether the neurobehavioral adaptations observed herein are specific to high-sugar and/or nonnutritive-sweetened beverages or more generally related to the repeated consumption of any type of food. This trial was registered at clinicaltrials.gov as NCT02624206. PMID:28179221

Characteristics of genomic instability in clones of TK6 human lymphoblasts surviving exposure to 56Fe ions

NASA Technical Reports Server (NTRS)

Evans, Helen H.; Horng, Min-Fen; Ricanati, Marlene; Diaz-Insua, Mireya; Jordan, Robert; Schwartz, Jeffrey L.

2002-01-01

Genomic instability in the human lymphoblast cell line TK6 was studied in clones surviving 36 generations after exposure to accelerated 56Fe ions. Clones were assayed for 20 characteristics, including chromosome aberrations, plating efficiency, apoptosis, cell cycle distribution, response to a second irradiation, and mutant frequency at two loci. The primary effect of the 56Fe-ion exposure on the surviving clones was a significant increase in the frequency of unstable chromosome aberrations compared to the very low spontaneous frequency, along with an increase in the phenotypic complexity of the unstable clones. The radiation-induced increase in the frequency of unstable chromosome aberrations was much greater than that observed previously in clones of the related cell line, WTK1, which in comparison to the TK6 cell line expresses an increased radiation resistance, a mutant TP53 protein, and an increased frequency of spontaneous unstable chromosome aberrations. The characteristics of the unstable clones of the two cell lines also differed. Most of the TK6 clones surviving exposure to 56Fe ions showed unstable cytogenetic abnormalities, while the phenotype of the WTK1 clones was more diverse. The results underscore the importance of genotype in the characteristics of instability after radiation exposure.

Impaired mixed emotion processing in the right ventrolateral prefrontal cortex in schizophrenia: an fMRI study.

PubMed

Szabó, Ádám György; Farkas, Kinga; Marosi, Csilla; Kozák, Lajos R; Rudas, Gábor; Réthelyi, János; Csukly, Gábor

2017-12-08

Schizophrenia has a negative effect on the activity of the temporal and prefrontal cortices in the processing of emotional facial expressions. However no previous research focused on the evaluation of mixed emotions in schizophrenia, albeit they are frequently expressed in everyday situations and negative emotions are frequently expressed by mixed facial expressions. Altogether 37 subjects, 19 patients with schizophrenia and 18 healthy control subjects were enrolled in the study. The two study groups did not differ in age and education. The stimulus set consisted of 10 fearful (100%), 10 happy (100%), 10 mixed fear (70% fear and 30% happy) and 10 mixed happy facial expressions. During the fMRI acquisition pictures were presented in a randomized order and subjects had to categorize expressions by button press. A decreased activation was found in the patient group during fear, mixed fear and mixed happy processing in the right ventrolateral prefrontal cortex (VLPFC) and the right anterior insula (RAI) at voxel and cluster level after familywise error correction. No difference was found between study groups in activations to happy facial condition. Patients with schizophrenia did not show a differential activation between mixed happy and happy facial expression similar to controls in the right dorsolateral prefrontal cortex (DLPFC). Patients with schizophrenia showed decreased functioning in right prefrontal regions responsible for salience signaling and valence evaluation during emotion recognition. Our results indicate that fear and mixed happy/fear processing are impaired in schizophrenia, while happy facial expression processing is relatively intact.

Developmental trajectories of abuse--an hypothesis for the effects of early childhood maltreatment on dorsolateral prefrontal cortical development.

PubMed

Burrus, Caley

2013-11-01

The United States has a high rate of child maltreatment, with nearly 12 in 1000 children being victims of abuse or neglect. Child abuse strongly predicts negative life outcomes, especially in areas of emotional and mental health. Abused children are also more likely than their peers to engage in violence and enter the juvenile justice system, as well as to become abusive parents themselves. Research has shown that child abuse and trauma can lead to decreased hippocampal volume, which could be indicative of abnormal hippocampal development. Hippocampal development appears to directly affect the development of the dorsolateral prefrontal cortex, a brain area responsible for emotion regulation, cognitive reappraisal, and general executive function. Therefore, I hypothesize that if child abuse results in abnormal hippocampal development, which leads to abnormal dorsolateral prefrontal cortex development, many of the correlated risk factors of child abuse, such as emotionally-laden parenting and unfavorable cognitive distortions regarding children's behaviors, may be in part caused by underdevelopment or abnormal functioning of the dorsolateral prefrontal cortex, as a function of the individual's own experiences with abuse during childhood. If this hypothesis is supported with future research, more targeted, successful, and cost-effective prevention and treatment protocols could ensue. For instance, programs that have been empirically shown to increase the activity of the dorsolateral prefrontal cortex, such as cognitive behavioral therapy, could be effective in decreasing the incidence of intergenerational transfer of abuse. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effect of Acute Psychological Stress on Prefrontal GABA Concentration Determined by Proton Magnetic Resonance Spectroscopy

PubMed Central

Hasler, Gregor; van der Veen, Jan Willem; Grillon, Christian; Drevets, Wayne C.; Shen, Jun

2011-01-01

Objective Impaired function of the central gamma-aminobutyric acid (GABA) system, which provides the brain’s major inhibitory pathways, is thought to play an important role in the pathophysiology of anxiety disorders. The effect of acute psychological stress on the human GABA-ergic system is still unknown, however. The purpose of this study was to determine the effect of acute stress on prefrontal GABA levels. Method A recently developed noninvasive magnetic resonance spectroscopy method was used to measure changes in the GABA concentration of the prefrontal cortex in 10 healthy human subjects during a threat-of-shock condition and during a safe condition (two sessions on different days). The main outcome measure was the mean GABA concentration within a 3×3×2-cm3 voxel selected from the medial prefrontal cortex. Results Prefrontal GABA decreased by approximately 18% in the threat-of-shock condition relative to the safe condition. This reduction was specific to GABA, since the concentrations of N-acetyl-aspartate, choline-containing compounds, and glutamate/glutamine levels obtained in the same spectra did not change significantly. Conclusions This result appeared compatible with evidence from preclinical studies in rodents, which showed rapid presynaptic down-regulation of GABA-ergic neurotransmission in response to acute psychological stress. The molecular mechanism and functional significance of this reduced inhibitory effect of acute psychological stress in relation to impaired GABA-ergic function in anxiety disorders merit further investigation. PMID:20634372

Trunk muscle activity increases with unstable squat movements.

PubMed

Anderson, Kenneth; Behm, David G

2005-02-01

The objective of this study was to determine differences in electromyographic (EMG) activity of the soleus (SOL), vastus lateralis (VL), biceps femoris (BF), abdominal stabilizers (AS), upper lumbar erector spinae (ULES), and lumbo-sacral erector spinae (LSES) muscles while performing squats of varied stability and resistance. Stability was altered by doing the squat movement on a Smith machine, a free squat, and while standing on two balance discs. Fourteen male subjects performed the movements. Activities of the SOL, AS, ULES, and LSES were highest during the unstable squat and lowest with the Smith machine protocol (p < 0.05). Increased EMG activity of these muscles may be attributed to their postural and stabilization role. Furthermore, EMG activity was higher during concentric contractions compared to eccentric contractions. Performing squats on unstable surfaces may permit a training adaptation of the trunk muscles responsible for supporting the spinal column (i.e., erector spinae) as well as the muscles most responsible for maintaining posture (i.e., SOL).

Maternal buffering beyond glucocorticoids: impact of early life stress on corticolimbic circuits that control infant responses to novelty

PubMed Central

Howell, Brittany R.; McMurray, Matthew S.; Guzman, Dora B.; Nair, Govind; Shi, Yundi; McCormack, Kai M.; Hu, Xiaoping; Styner, Martin A.; Sanchez, Mar M.

2017-01-01

Maternal presence has a potent buffering effect on infant fear and stress responses in primates. We previously reported that maternal presence is not effective in buffering the endocrine stress response in infant rhesus monkeys reared by maltreating mothers. We have also reported that maltreating mothers show low maternal responsiveness and permissiveness/secure-base behavior. Although still not understood, it is possible that this maternal buffering effect is mediated, at least partially, through deactivation of amygdala response circuits when mothers are present. Here we studied rhesus monkey infants that differed in the quality of early maternal care to investigate how this early experience modulated maternal buffering effects on behavioral responses to novelty during the weaning period. We also examined the relationship between these behavioral responses and structural connectivity in one of the underlying regulatory neural circuits: amygdala-prefrontal pathways. Our findings suggest that infant exploration in a novel situation is predicted by maternal responsiveness and structural integrity of amygdala-prefrontal white matter depending on maternal presence (positive relationships when mother is absent). These results provide evidence that maternal buffering of infant behavioral inhibition is dependent on the quality of maternal care and structural connectivity of neural pathways that are sensitive to early life stress. PMID:27295326

On the seismic response of instable rock slopes based on ambient vibration recordings

NASA Astrophysics Data System (ADS)

Kleinbrod, Ulrike; Burjánek, Jan; Fäh, Donat

2017-09-01

Rock slope failures can lead to huge human and economic loss depending on their size and exact location. Reasonable hazard mitigation requires thorough understanding of the underlying slope driving mechanisms and its rock mass properties. Measurements of seismic ambient vibrations could improve the characterization and detection of rock instabilities since there is a link between seismic response and internal structure of the unstable rock mass. An unstable slope near the village Gondo has been investigated. The unstable part shows strongly amplified ground motion with respect to the stable part of the rock slope. The amplification values reach maximum factors of 70. The seismic response on the instable part is highly directional and polarized. Re-measurements have been taken 1 year later showing exactly the same results as the original measurements. Neither the amplified frequencies nor the amplification values have changed. Therefore, ambient vibration measurements are repeatable and stay the same, if the rock mass has not undergone any significant change in structure or volume, respectively. Additionally, four new points have been measured during the re-measuring campaign in order to better map the border of the instability.[Figure not available: see fulltext.

Prefrontal control of cerebellum-dependent associative motor learning.

PubMed

Chen, Hao; Yang, Li; Xu, Yan; Wu, Guang-yan; Yao, Juan; Zhang, Jun; Zhu, Zhi-ru; Hu, Zhi-an; Sui, Jian-feng; Hu, Bo

2014-02-01

Behavioral studies have demonstrated that both medial prefrontal cortex (mPFC) and cerebellum play critical roles in trace eyeblink conditioning. However, little is known regarding the mechanism by which the two brain regions interact. By use of electrical stimulation of the caudal mPFC as a conditioned stimulus, we show evidence that persistent outputs from the mPFC to cerebellum are necessary and sufficient for the acquisition and expression of a trace conditioned response (CR)-like response. Specifically, the persistent outputs of caudal mPFC are relayed to the cerebellum via the rostral part of lateral pontine nuclei. Moreover, interfering with persistent activity by blockade of the muscarinic Ach receptor in the caudal mPFC impairs the expression of learned trace CRs. These results suggest an important way for the caudal mPFC to interact with the cerebellum during associative motor learning.

Effect of Bupropion Treatment on Brain Activation Induced by Cigarette-Related Cues in Smokers

PubMed Central

Culbertson, Christopher S.; Bramen, Jennifer; Cohen, Mark S.; London, Edythe D.; Olmstead, Richard E.; Gan, Joanna J.; Costello, Matthew R.; Shulenberger, Stephanie; Mandelkern, Mark A.; Brody, Arthur L.

2011-01-01

Context Nicotine-dependent smokers exhibit craving and brain activation in the prefrontal and limbic regions when presented with cigarette-related cues. Bupropion hydrochloride treatment reduces cue-induced craving in cigarette smokers; however, the mechanism by which bupropion exerts this effect has not yet been described. Objective To assess changes in regional brain activation in response to cigarette-related cues from before to after treatment with bupropion (vs placebo). Design Randomized, double-blind, before-after controlled trial. Setting Academic brain imaging center. Participants Thirty nicotine-dependent smokers (paid volunteers). Interventions Participants were randomly assigned to receive 8 weeks of treatment with either bupropion or a matching placebo pill (double-blind). Main Outcome Measures Subjective cigarette craving ratings and regional brain activations (blood oxygen level-dependent response) in response to viewing cue videos. Results Bupropion-treated participants reported less craving and exhibited reduced activation in the left ventral striatum, right medial orbitofrontal cortex, and bilateral anterior cingulate cortex from before to after treatment when actively resisting craving compared with placebo-treated participants. When resisting craving, reduction in self-reported craving correlated with reduced regional brain activation in the bilateral medial orbitofrontal and left anterior cingulate cortices in all participants. Conclusions Treatment with bupropion is associated with improved ability to resist cue-induced craving and a reduction in cue-induced activation of limbic and prefrontal brain regions, while a reduction in craving, regardless of treatment type, is associated with reduced activation in prefrontal brain regions. PMID:21199957

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.

Common neural substrates for visual working memory and attention.

PubMed

Mayer, Jutta S; Bittner, Robert A; Nikolić, Danko; Bledowski, Christoph; Goebel, Rainer; Linden, David E J

2007-06-01

Humans are severely limited in their ability to memorize visual information over short periods of time. Selective attention has been implicated as a limiting factor. Here we used functional magnetic resonance imaging to test the hypothesis that this limitation is due to common neural resources shared by visual working memory (WM) and selective attention. We combined visual search and delayed discrimination of complex objects and independently modulated the demands on selective attention and WM encoding. Participants were presented with a search array and performed easy or difficult visual search in order to encode one or three complex objects into visual WM. Overlapping activation for attention-demanding visual search and WM encoding was observed in distributed posterior and frontal regions. In the right prefrontal cortex and bilateral insula blood oxygen-level-dependent activation additively increased with increased WM load and attentional demand. Conversely, several visual, parietal and premotor areas showed overlapping activation for the two task components and were severely reduced in their WM load response under the condition with high attentional demand. Regions in the left prefrontal cortex were selectively responsive to WM load. Areas selectively responsive to high attentional demand were found within the right prefrontal and bilateral occipital cortex. These results indicate that encoding into visual WM and visual selective attention require to a high degree access to common neural resources. We propose that competition for resources shared by visual attention and WM encoding can limit processing capabilities in distributed posterior brain regions.

Tasting calories differentially affects brain activation during hunger and satiety.

PubMed

van Rijn, Inge; de Graaf, Cees; Smeets, Paul A M

2015-02-15

An important function of eating is ingesting energy. Our objectives were to assess whether oral exposure to caloric and non-caloric stimuli elicits discriminable responses in the brain and to determine in how far these responses are modulated by hunger state and sweetness. Thirty women tasted three stimuli in two motivational states (hunger and satiety) while their brain responses were measured using functional magnetic resonance imaging in a randomized crossover design. Stimuli were solutions of sucralose (sweet, no energy), maltodextrin (non-sweet, energy) and sucralose+maltodextrin (sweet, energy). We found no main effect of energy content and no interaction between energy content and sweetness. However, there was an interaction between hunger state and energy content in the median cingulate (bilaterally), ventrolateral prefrontal cortex, anterior insula and thalamus. This indicates that the anterior insula and thalamus, areas in which hunger state and taste of a stimulus are integrated, also integrate hunger state with caloric content of a taste stimulus. Furthermore, in the median cingulate and ventrolateral prefrontal cortex, tasting energy resulted in more activation during satiety compared to hunger. This finding indicates that these areas, which are known to be involved in processes that require approach and avoidance, are also involved in guiding ingestive behavior. In conclusion, our results suggest that energy sensing is a hunger state dependent process, in which the median cingulate, ventrolateral prefrontal cortex, anterior insula and thalamus play a central role by integrating hunger state with stimulus relevance. Copyright © 2014 Elsevier B.V. All rights reserved.

Developmental Ethanol Exposure Leads to Long-Term Deficits in Attention and Its Underlying Prefrontal Circuitry

PubMed Central

Bignell, Warren

2016-01-01

Abstract Chronic prenatal exposure to ethanol can lead to a spectrum of teratogenic outcomes that are classified in humans as fetal alcohol spectrum disorders (FASD). One of the most prevalent and persistent neurocognitive components of FASD is attention deficits, and it is now thought that these attention deficits differ from traditional attention deficit hyperactivity disorder (ADHD) in their quality and response to medication. However, the neuronal mechanisms underlying attention deficits in FASD are not well understood. We show here that after developmental binge-pattern ethanol exposure, adult mice exhibit impaired performance on the five-choice serial reaction time test for visual attention, with lower accuracy during initial training and a higher rate of omissions under challenging conditions of high attention demand. Whole-cell electrophysiology experiments in these same mice find dysregulated pyramidal neurons in layer VI of the medial prefrontal cortex, which are critical for normal attention performance. Layer VI neurons show decreased intrinsic excitability and increased responses to stimulation of both nicotinic acetylcholine receptors and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors. Moreover, although nicotinic acetylcholine responses correlate with performance on the five-choice task in control mice, these relationships are completely disrupted in mice exposed to ethanol during development. These findings demonstrate a novel outcome of developmental binge-pattern ethanol exposure and suggest that persistent alterations to the function of prefrontal layer VI neurons play an important mechanistic role in attention deficits associated with FASD. PMID:27844059

Testosterone Modulates Altered Prefrontal Control of Emotional Actions in Psychopathic Offenders(1,2,3).

PubMed

Volman, Inge; von Borries, Anna Katinka Louise; Bulten, Berend Hendrik; Verkes, Robbert Jan; Toni, Ivan; Roelofs, Karin

2016-01-01

Psychopathic individuals are notorious for their controlled goal-directed aggressive behavior. Yet, during social challenges, they often show uncontrolled emotional behavior. Healthy individuals can control their social emotional behavior through anterior prefrontal cortex (aPFC) downregulation of neural activity in the amygdala, with testosterone modulating aPFC-amygdala coupling. This study tests whether individual differences in this neuroendocrine system relate to the paradoxical lack of emotional control observed in human psychopathic offenders. Emotional control was operationalized with an fMRI-adapted approach-avoidance task requiring rule-driven control over rapid emotional responses. Fifteen psychopathic offenders and 19 matched healthy control subjects made approaching and avoiding movements in response to emotional faces. Control of social emotional behavior was required during affect-incongruent trials, when participants had to override affect-congruent, automatic action tendencies and select the opposite response. Psychopathic offenders showed less control-related aPFC activity and aPFC-amygdala coupling during trials requiring control of emotional actions, when compared with healthy control subjects. This pattern was particularly pronounced in psychopathic individuals with high endogenous testosterone levels. These findings suggest that reduced prefrontal coordination underlies reduced behavioral control in psychopathic offenders during emotionally provoking situations. Even though the modest sample size warrants replication, the modulatory role of endogenous testosterone on the aPFC-amygdala circuit suggests a neurobiological substrate of individual differences that is relevant for the advancement of treatment and the reduction of recidivism.

Electromyographic analysis of the serratus anterior and trapezius muscles during push-ups on stable and unstable bases in subjects with scapular dyskinesis.

PubMed

Pirauá, André Luiz Torres; Pitangui, Ana Carolina Rodarti; Silva, Juliana Pereira; Pereira dos Passos, Muana Hiandra; Alves de Oliveira, Valéria Mayaly; Batista, Laísla da Silva Paixão; Cappato de Araújo, Rodrigo

2014-10-01

The present study was performed to assess the electromyographic activity of the scapular muscles during push-ups on a stable and unstable surface, in subjects with scapular dyskinesis. Muscle activation (upper trapezius [UT]; lower trapezius [LT]; upper serratus anterior [SA_5th]; lower serratus anterior [SA_7th]) and ratios (UT/LT; UT/SA_5th; UT/ SA_7th) levels were determined by surface EMG in 30 asymptomatic men with scapular dyskinesis, during push-up performed on a stable and unstable surface. Multivariate analysis of variance with repeated measures was used for statistical analyses. The unstable surface caused a decrease in the EMG activity of the serratus anterior and an increase in EMG activity of the trapezius (p=0.001). UT/SA_5th and UT/ SA_7th ratios were higher during unstable push-ups (p=0.001). The results suggest that, in individuals with scapular dyskinesis, there is increased EMG activity of the trapezius and decreased EMG activity of the serratus anterior in response to an unstable surface. These results suggest that the performance of the push up exercise on an unstable surface may be more favorable to produce higher levels of trapezius activation and lower levels of serratus anterior activation. However, if the goal of the exercise program is the strengthening of the SA muscle, it is suggested to perform the push up on a stable surface. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Cerebellum and Emotional Experience

PubMed Central

Turner, Beth M.; Paradiso, Sergio; Marvel, Cherie L.; Pierson, Ronald; Boles Ponto, Laura L.; Hichwa, Richard D.; Robinson, Robert G.

2007-01-01

Summary While the role of the cerebellum in motor coordination is widely accepted, the notion that it is involved in emotion has only recently gained popularity. To date, functional neuroimaging has not been used in combination with lesion studies to elucidate the role of the cerebellum in the processing of emotional material. We examined six participants with cerebellar stroke and nine age and education matched healthy volunteers. In addition to a complete neuropsychological, neurologic, and psychiatric examination, participants underwent [15O]water positron emission tomography (PET) while responding to emotion-evoking visual stimuli. Cerebellar lesions were associated with reduced pleasant experience in response to happiness-evoking stimuli. Stroke patients reported an unpleasant experience to frightening stimuli similar to healthy controls, yet showed significantly lower activity in the right ventral lateral and left dorsolateral prefrontal cortex, amygdala, thalamus, and retrosplenial cingulate gyrus. Frightening stimuli led to increased activity in the ventral medial prefrontal, anterior cingulate, pulvinar, and insular cortex. This suggests that alternate neural circuitry became responsible for maintaining the evolutionarily critical fear response after cerebellar damage. PMID:17123557

The role of medial prefrontal cortex in memory and decision making.

PubMed

Euston, David R; Gruber, Aaron J; McNaughton, Bruce L

2012-12-20

Some have claimed that the medial prefrontal cortex (mPFC) mediates decision making. Others suggest mPFC is selectively involved in the retrieval of remote long-term memory. Yet others suggests mPFC supports memory and consolidation on time scales ranging from seconds to days. How can all these roles be reconciled? We propose that the function of the mPFC is to learn associations between context, locations, events, and corresponding adaptive responses, particularly emotional responses. Thus, the ubiquitous involvement of mPFC in both memory and decision making may be due to the fact that almost all such tasks entail the ability to recall the best action or emotional response to specific events in a particular place and time. An interaction between multiple memory systems may explain the changing importance of mPFC to different types of memories over time. In particular, mPFC likely relies on the hippocampus to support rapid learning and memory consolidation. Copyright © 2012 Elsevier Inc. All rights reserved.

Differential brain responses to social exclusion by one's own versus opposite-gender peers.

PubMed

Bolling, Danielle Z; Pelphrey, Kevin A; Vander Wyk, Brent C

2012-07-01

Human peer relations provide tangible benefits, including food and protection, as well as emotional benefits. While social exclusion poses a threat to all of these benefits, the psychological threat is particularly susceptible to modulation by the relation of the excluders to the excluded person. The current study used functional magnetic resonance imaging to explore the effects of manipulating the gender relation of participants to their excluders during an interactive ball-toss game. Ventral anterior cingulate cortex activation was higher during exclusion by same-gender peers, while right ventrolateral prefrontal cortex activation negatively correlated with self-reported distress in other-gender exclusion. Results imply that exclusion by one's own gender is fundamentally different from exclusion by the opposite gender, and suggest a regulatory role for ventrolateral prefrontal cortex in response to out-group exclusion. Individual differences in implicit gender attitudes modulated neural responses to exclusion. The importance of these findings to investigations of social cognition is discussed.

Differential brain responses to social exclusion by one’s own versus opposite gender peers

PubMed Central

Bolling, Danielle Z.; Pelphrey, Kevin A.; Wyk, Brent C. Vander

2015-01-01

Human peer relations provide tangible benefits including food and protection, as well as emotional benefits. While social exclusion poses a threat to all of these benefits, the psychological threat is particularly susceptible to modulation by the relation of the excluders to the excluded person. The current study used functional magnetic resonance imaging to explore the effects of manipulating the gender relation of participants to their excluders during an interactive ball toss game. Ventral anterior cingulate cortex activation was higher during exclusion by same-gender peers, while right ventrolateral prefrontal cortex activation negatively correlated with self-reported distress in other-gender exclusion. Results imply that exclusion by one’s own gender is fundamentally different from exclusion by the opposite gender, and suggest a regulatory role for ventrolateral prefrontal cortex in response to out-group exclusion. Individual differences in implicit gender attitudes modulated neural responses to exclusion. The importance of these findings to investigations of social cognition is discussed. PMID:21981758

Response Inhibition in Adults and Teenagers: Spatiotemporal Differences in the Prefrontal Cortex

ERIC Educational Resources Information Center

Vidal, Julie; Mills, Travis; Pang, Elizabeth W.; Taylor, Margot J.

2012-01-01

Inhibition is a core executive function reliant on the frontal lobes that shows protracted maturation through to adulthood. We investigated the spatiotemporal characteristics of response inhibition during a visual go/no-go task in 14 teenagers and 14 adults using magnetoencephalography (MEG) and a contrast between two no-go experimental conditions…

Threat-Detection and Attentional Bias to Threat in Women Recovered from Anorexia Nervosa: Neural Alterations in Extrastriate and Medial Prefrontal Cortices.

PubMed

Bang, Lasse; Rø, Øyvind; Endestad, Tor

2017-03-01

Behavioral studies have shown that anorexia nervosa (AN) is associated with attentional bias to general threat cues. The neurobiological underpinnings of attentional bias to threat in AN are unknown. This study investigated the neural responses associated with threat-detection and attentional bias to threat in AN. We measured neural responses to a dot-probe task, involving pairs of angry and neutral face stimuli, in 22 adult women recovered from AN and 21 comparison women. Recovered AN women did not exhibit a behavioral attentional bias to threat. In response to angry faces, recovered women showed significant hypoactivation in the extrastriate cortex. During attentional bias to angry faces, recovered women showed significant hyperactivation in the medial prefrontal cortex. This was because of significant deactivation in comparison women, which was absent in recovered AN women. Women recovered from AN are characterized by altered neural responses to threat cues. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

Noradrenaline transporter blockade increases fronto-parietal functional connectivity relevant for working memory.

PubMed

Hernaus, Dennis; Casales Santa, Marta Ma; Offermann, Jan Stefan; Van Amelsvoort, Thérèse

2017-04-01

Experimental animal work has demonstrated that dopamine and noradrenaline play an essential role in modulating prefrontal cortex-mediated networks underlying working memory performance. Studies of functional connectivity have been instrumental in extending such notions to humans but, so far, have almost exclusively focussed on pharmacological agents with a predominant dopaminergic mechanism of action. Here, we investigate the effect of a single dose of atomoxetine 60mg, a noradrenaline transporter inhibitor, on working memory performance and associated functional connectivity during an n-back task in 19 healthy male volunteers. Atomoxetine increased functional connectivity between right anterior insula and dorsolateral prefrontal cortex, precentral gyrus, posterior parietal cortex and precuneus during the high-working memory load condition of the n-back task. Increased atomoxetine-induced insula-dorsolateral prefrontal cortex functional connectivity during this condition correlated with decreased reaction time variability and was furthermore predicted by working memory capacity. These results show for the first time that noradrenaline transporter blockade-induced increases in cortical catecholamines accentuate fronto-parietal working memory-related network integrity. The observation of significant inter-subject variability in response to atomoxetine has implications for inverted-U frameworks of dopamine and noradrenaline function, which could be useful to predict drug effects in clinical disorders with variable treatment response. Copyright © 2017 Elsevier B.V. and ECNP. 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.

Changes in cerebral metabolism in patients with a minimally conscious state responding to zolpidem

PubMed Central

Chatelle, Camille; Thibaut, Aurore; Gosseries, Olivia; Bruno, Marie-Aurélie; Demertzi, Athena; Bernard, Claire; Hustinx, Roland; Tshibanda, Luaba; Bahri, Mohamed A.; Laureys, Steven

2014-01-01

Background: Zolpidem, a short-acting non-benzodiazepine GABA agonist hypnotic, has been shown to induce paradoxical responses in some patients with disorders of consciousness (DOC), leading to recovery of arousal and cognitive abilities. We here assessed zolpidem-induced changes in regional brain metabolism in three patients with known zolpidem response in chronic post-anoxic minimally conscious state (MCS). Methods: [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) and standardized clinical assessments using the Coma Recovery Scale-Revised were performed after administration of 10 mg zolpidem or placebo in a randomized double blind 2-day protocol. PET data preprocessing and comparison with a healthy age-matched control group were performed using statistical parametric mapping (SPM8). Results: Behaviorally, all patients recovered functional communication after administration of zolpidem (i.e., emergence from the MCS). FDG-PET showed increased metabolism in dorsolateral prefrontal and mesiofrontal cortices after zolpidem but not after placebo administration. Conclusion: Our data show a metabolic activation of prefrontal areas, corroborating the proposed mesocircuit hypothesis to explain the paradoxical effect of zolpidem observed in some patients with DOC. It also suggests the key role of the prefrontal cortices in the recovery of functional communication and object use in hypoxic patients with chronic MCS. PMID:25520636

Responses of medial and ventrolateral prefrontal cortex to interpersonal conflict for resources.

PubMed

Koban, Leonie; Pichon, Swann; Vuilleumier, Patrik

2014-05-01

Little is known about brain mechanisms recruited during the monitoring and appraisal of social conflicts--for instance, when individuals compete with each other for the same resources. We designed a novel experimental task inducing resource conflicts between two individuals. In an event-related functional magnetic resonance imaging (fMRI) design, participants played with another human participant or against a computer, who across trials chose either different (no-conflict) or the same tokens (conflict trials) in order to obtain monetary gains. In conflict trials, the participants could decide whether they would share the token, and the resulting gain, with the other person or instead keep all points for themselves. Behaviorally, participants shared much more often when playing with a human partner than with a computer. fMRI results demonstrated that the dorsal mediofrontal cortex was selectively activated during human conflicts. This region might play a key role in detecting situations in which self- and social interest are incompatible and require behavioral adjustment. In addition, we found a conflict-related response in the right ventrolateral prefrontal cortex that correlated with measures of social relationship and individual sharing behavior. Taken together, these findings reveal a key role of these prefrontal areas for the appraisal and resolution of interpersonal resource conflicts.

The neural basis for establishing a focal point in pure coordination games

PubMed Central

Rascovsky, Katya; Khella, M. Catherine; Clark, Robin; Grossman, Murray

2012-01-01

When making a decision, humans often have to ‘coordinate’—reach the same conclusion—as another individual without explicitly communicating. Relatively, little is known about the neural basis for coordination. Moreover, previous fMRI investigations have supported conflicting hypotheses. One account proposes that individuals coordinate using a ‘gut feeling’ and that this is supported by insula recruitment. Another account proposes that individuals recruit strategic decision-making mechanisms in prefrontal cortex in order to coordinate. We investigate the neural basis for coordination in individuals with behavioral-variant frontotemporal dementia (bvFTD) who have limitations in social decision-making associated with disease in prefrontal cortex. We demonstrate that bvFTD are impaired at establishing a focal point in a semantic task (e.g. ‘Tell me any boy's name’) that requires coordination relative to a similar, control semantic task that does not. Additionally, coordination limitations in bvFTD are related to cortical thinning in prefrontal cortex. These findings are consistent with behavioral economic models proposing that, beyond a ‘gut feeling’, strategic decision-making contributes to the coordination process, including a probabilistic mechanism that evaluates the salience of a response (e.g. is ‘John’ a frequent boy's name), a hierarchical mechanism that iteratively models an opponent's likely response and a mechanism involved in social perspective taking. PMID:22009019

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.

Imitating expressions: emotion-specific neural substrates in facial mimicry.

PubMed

Lee, Tien-Wen; Josephs, Oliver; Dolan, Raymond J; Critchley, Hugo D

2006-09-01

Intentionally adopting a discrete emotional facial expression can modulate the subjective feelings corresponding to that emotion; however, the underlying neural mechanism is poorly understood. We therefore used functional brain imaging (functional magnetic resonance imaging) to examine brain activity during intentional mimicry of emotional and non-emotional facial expressions and relate regional responses to the magnitude of expression-induced facial movement. Eighteen healthy subjects were scanned while imitating video clips depicting three emotional (sad, angry, happy), and two 'ingestive' (chewing and licking) facial expressions. Simultaneously, facial movement was monitored from displacement of fiducial markers (highly reflective dots) on each subject's face. Imitating emotional expressions enhanced activity within right inferior prefrontal cortex. This pattern was absent during passive viewing conditions. Moreover, the magnitude of facial movement during emotion-imitation predicted responses within right insula and motor/premotor cortices. Enhanced activity in ventromedial prefrontal cortex and frontal pole was observed during imitation of anger, in ventromedial prefrontal and rostral anterior cingulate during imitation of sadness and in striatal, amygdala and occipitotemporal during imitation of happiness. Our findings suggest a central role for right inferior frontal gyrus in the intentional imitation of emotional expressions. Further, by entering metrics for facial muscular change into analysis of brain imaging data, we highlight shared and discrete neural substrates supporting affective, action and social consequences of somatomotor emotional expression.

Responses of medial and ventrolateral prefrontal cortex to interpersonal conflict for resources

PubMed Central

Koban, Leonie; Pichon, Swann; Vuilleumier, Patrik

2014-01-01

Little is known about brain mechanisms recruited during the monitoring and appraisal of social conflicts—for instance, when individuals compete with each other for the same resources. We designed a novel experimental task inducing resource conflicts between two individuals. In an event-related functional magnetic resonance imaging (fMRI) design, participants played with another human participant or against a computer, who across trials chose either different (no-conflict) or the same tokens (conflict trials) in order to obtain monetary gains. In conflict trials, the participants could decide whether they would share the token, and the resulting gain, with the other person or instead keep all points for themselves. Behaviorally, participants shared much more often when playing with a human partner than with a computer. fMRI results demonstrated that the dorsal mediofrontal cortex was selectively activated during human conflicts. This region might play a key role in detecting situations in which self- and social interest are incompatible and require behavioral adjustment. In addition, we found a conflict-related response in the right ventrolateral prefrontal cortex that correlated with measures of social relationship and individual sharing behavior. Taken together, these findings reveal a key role of these prefrontal areas for the appraisal and resolution of interpersonal resource conflicts. PMID:23460073

THC and endocannabinoids differentially regulate neuronal activity in the prefrontal cortex and hippocampus in the sub-chronic PCP model of schizophrenia

PubMed Central

Aguilar, David D; Giuffrida, Andrea; Lodge, Daniel J

2017-01-01

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 CSF 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 to 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. PMID:26510449

Happier People Show Greater Neural Connectivity during Negative Self-Referential Processing.

PubMed

Kim, Eun Joo; Kyeong, Sunghyon; Cho, Sang Woo; Chun, Ji-Won; Park, Hae-Jeong; Kim, Jihye; Kim, Joohan; Dolan, Raymond J; Kim, Jae-Jin

2016-01-01

Life satisfaction is an essential component of subjective well-being and provides a fundamental resource for optimal everyday functioning. The goal of the present study was to examine how life satisfaction influences self-referential processing of emotionally valenced stimuli. Nineteen individuals with high life satisfaction (HLS) and 21 individuals with low life satisfaction (LLS) were scanned using functional MRI while performing a face-word relevance rating task, which consisted of 3 types of face stimuli (self, public other, and unfamiliar other) and 3 types of word stimuli (positive, negative, and neutral). We found a significant group x word valence interaction effect, most strikingly in the dorsal medial prefrontal cortex. In the positive word condition dorsal medial prefrontal cortex activity was significantly higher in the LLS group, whereas in the negative word condition it was significantly higher in the HLS group. The two groups showed distinct functional connectivity of the dorsal medial prefrontal cortex with emotional processing-related regions. The findings suggest that, in response to emotional stimuli, individuals with HLS may successfully recruit emotion regulation-related regions in contrast to individuals with LLS. The difference in functional connectivity during self-referential processing may lead to an influence of life satisfaction on responses to emotion-eliciting stimuli.

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 + and K + channel function could reliably reproduce the observed increase in action potential firing and altered action potential waveform. These results, in conjunction with our prior findings on L5 neurons, suggest that principal neurons in the circuitry of the medial prefrontal cortex are altered in distinct ways in the fmr1 -/y mouse and may contribute to dysfunctional prefrontal cortex processing in fragile X syndrome. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

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.

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.

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.

Functional variation of the dopamine D2 receptor gene is associated with emotional control as well as brain activity and connectivity during emotion processing in humans

PubMed Central

Blasi, Giuseppe; Bianco, Luciana Lo; Taurisano, Paolo; Gelao, Barbara; Romano, Raffaella; Fazio, Leonardo; Papazacharias, Apostolos; Di Giorgio, Annabella; Caforio, Grazia; Rampino, Antonio; Masellis, Rita; Papp, Audrey; Ursini, Gianluca; Sinibaldi, Lorenzo; Popolizio, Teresa; Sadee, Wolfgang; Bertolino, Alessandro

2010-01-01

Personality traits related to emotion processing are, at least in part, heritable and genetically determined. Dopamine D2 receptor signaling is involved in modulation of emotional behavior and activity of associated brain regions such as the amygdala and the prefrontal cortex. An intronic single nucleotide polymorphism within the D2 receptor gene (DRD2, rs1076560, guanine>thymine - G>T) shifts splicing of the two protein isoforms (D2 short, D2S, mainly presynaptic, and D2 long, D2L) and has been associated with modulation of memory performance and brain activity. Here, our aim was to investigate the association of DRD2 rs1076560 genotype with personality traits of emotional stability and with brain physiology during processing of emotionally relevant stimuli. DRD2 genotype and Big Five Questionnaire scores were evaluated in 134 healthy subjects demonstrating that GG subjects have reduced ‘emotion control’ compared with GT subjects. fMRI in a sample of 24 individuals indicated greater amygdala activity during implicit processing and greater dorsolateral prefrontal cortex (DLPFC) response during explicit processing of facial emotional stimuli in GG subjects compared with GT. Other results also demonstrate an interaction between DRD2 genotype and facial emotional expression on functional connectivity of both amygdala and dorsolateral prefrontal regions with overlapping medial prefrontal areas. Moreover, rs1076560 genotype is associated with differential relationships between amygdala/DLPFC functional connectivity and emotion control scores. These results suggest that genetically determined D2 signaling may explain part of personality traits related to emotion processing and individual variability in specific brain responses to emotionally relevant inputs. PMID:19940176

Functional variation of the dopamine D2 receptor gene is associated with emotional control as well as brain activity and connectivity during emotion processing in humans.

PubMed

Blasi, Giuseppe; Lo Bianco, Luciana; Taurisano, Paolo; Gelao, Barbara; Romano, Raffaella; Fazio, Leonardo; Papazacharias, Apostolos; Di Giorgio, Annabella; Caforio, Grazia; Rampino, Antonio; Masellis, Rita; Papp, Audrey; Ursini, Gianluca; Sinibaldi, Lorenzo; Popolizio, Teresa; Sadee, Wolfgang; Bertolino, Alessandro

2009-11-25

Personality traits related to emotion processing are, at least in part, heritable and genetically determined. Dopamine D(2) receptor signaling is involved in modulation of emotional behavior and activity of associated brain regions such as the amygdala and the prefrontal cortex. An intronic single nucleotide polymorphism within the D(2) receptor gene (DRD2) (rs1076560, guanine > thymine or G > T) shifts splicing of the two protein isoforms (D(2) short, mainly presynaptic, and D(2) long) and has been associated with modulation of memory performance and brain activity. Here, our aim was to investigate the association of DRD2 rs1076560 genotype with personality traits of emotional stability and with brain physiology during processing of emotionally relevant stimuli. DRD2 genotype and Big Five Questionnaire scores were evaluated in 134 healthy subjects demonstrating that GG subjects have reduced "emotion control" compared with GT subjects. Functional magnetic resonance imaging in a sample of 24 individuals indicated greater amygdala activity during implicit processing and greater dorsolateral prefrontal cortex (DLPFC) response during explicit processing of facial emotional stimuli in GG subjects compared with GT. Other results also demonstrate an interaction between DRD2 genotype and facial emotional expression on functional connectivity of both amygdala and dorsolateral prefrontal regions with overlapping medial prefrontal areas. Moreover, rs1076560 genotype is associated with differential relationships between amygdala/DLPFC functional connectivity and emotion control scores. These results suggest that genetically determined D(2) signaling may explain part of personality traits related to emotion processing and individual variability in specific brain responses to emotionally relevant inputs.

Cocaine addiction is associated with abnormal prefrontal function, increased striatal connectivity and sensitivity to monetary incentives, and decreased connectivity outside the human reward circuit.

PubMed

Vaquero, Lucía; Cámara, Estela; Sampedro, Frederic; Pérez de Los Cobos, José; Batlle, Francesca; Fabregas, Josep Maria; Sales, Joan Artur; Cervantes, Mercè; Ferrer, Xavier; Lazcano, Gerardo; Rodríguez-Fornells, Antoni; Riba, Jordi

2017-05-01

Cocaine addiction has been associated with increased sensitivity of the human reward circuit to drug-related stimuli. However, the capacity of non-drug incentives to engage this network is poorly understood. Here, we characterized the functional sensitivity to monetary incentives and the structural integrity of the human reward circuit in abstinent cocaine-dependent (CD) patients and their matched controls. We assessed the BOLD response to monetary gains and losses in 30 CD patients and 30 healthy controls performing a lottery task in a magnetic resonance imaging scanner. We measured brain gray matter volume (GMV) using voxel-based morphometry and white matter microstructure using voxel-based fractional anisotropy (FA). Functional data showed that, after monetary incentives, CD patients exhibited higher activation in the ventral striatum than controls. Furthermore, we observed an inverted BOLD response pattern in the prefrontal cortex, with activity being highest after unexpected high gains and lowest after losses. Patients showed increased GMV in the caudate and the orbitofrontal cortex, increased white matter FA in the orbito-striatal pathway but decreased FA in antero-posterior association bundles. Abnormal activation in the prefrontal cortex correlated with GMV and FA increases in the orbitofrontal cortex. While functional abnormalities in the ventral striatum were inversely correlated with abstinence duration, structural alterations were not. In conclusion, results suggest abnormal incentive processing in CD patients with high salience for rewards and punishments in subcortical structures but diminished prefrontal control after adverse outcomes. They further suggest that hypertrophy and hyper-connectivity within the reward circuit, to the expense of connectivity outside this network, characterize cocaine addiction. © 2016 Society for the Study of Addiction.

Early Adolescent MK-801 Exposure Impairs the Maturation of Ventral Hippocampal Control of Basolateral Amygdala Drive in the Adult Prefrontal Cortex

PubMed Central

Thomases, Daniel R.; Cass, Daryn K.; Meyer, Jacqueline D.; Caballero, Adriana

2014-01-01

The adolescent susceptibility to the onset of psychiatric disorders is only beginning to be understood when factoring in the development of the prefrontal cortex (PFC). The functional maturation of the PFC is dependent upon proper integration of glutamatergic inputs from the ventral hippocampus (vHipp) and the basolateral amygdala (BLA). Here we assessed how transient NMDAR blockade during adolescence alters the functional interaction of vHipp–BLA inputs in regulating PFC plasticity. Local field potential recordings were used to determine changes in long-term depression (LTD) and long-term potentiation (LTP) of PFC responses resulting from vHipp and BLA high-frequency stimulation in adult rats that received repeated injections of saline or the NMDAR antagonist MK-801 from postnatal day 35 (P35) to P40. We found that early adolescent MK-801 exposure elicited an age- and input-specific dysregulation of vHipp–PFC plasticity, characterized by a shift from LTD to LTP without altering the BLA-induced LTP. Data also showed that the vHipp normally resets the LTP state of BLA transmission; however, this inhibitory regulation is absent following early adolescent MK-801 treatment. This deficit was reminiscent of PFC responses seen in drug-naive juveniles. Notably, local prefrontal upregulation of GABAAα1 function completely restored vHipp functionality and its regulation of BLA plasticity in MK-801-treated rats. Thus, NMDAR signaling is critical for the periadolescent acquisition of a GABA-dependent hippocampal control of PFC plasticity, which enables the inhibitory control of the prefrontal output by the vHipp. A dysregulation of this pathway can alter PFC processing of other converging afferents such as those from the BLA. PMID:24990926

Induction of psychosis by Δ9-tetrahydrocannabinol reflects modulation of prefrontal and striatal function during attentional salience processing.

PubMed

Bhattacharyya, Sagnik; Crippa, José Alexandre; Allen, Paul; Martin-Santos, Rocio; Borgwardt, Stefan; Fusar-Poli, Paolo; Rubia, Katya; Kambeitz, Joseph; O'Carroll, Colin; Seal, Marc L; Giampietro, Vincent; Brammer, Michael; Zuardi, Antonio Waldo; Atakan, Zerrin; McGuire, Philip K

2012-01-01

The aberrant processing of salience is thought to be a fundamental factor underlying psychosis. Cannabis can induce acute psychotic symptoms, and its chronic use may increase the risk of schizophrenia. We investigated whether its psychotic effects are mediated through an influence on attentional salience processing. To examine the effects of Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) on regional brain function during salience processing. Volunteers were studied using event-related functional magnetic resonance imaging on 3 occasions after administration of Δ9-THC, CBD, or placebo while performing a visual oddball detection paradigm that involved allocation of attention to infrequent (oddball) stimuli within a string of frequent (standard) stimuli. University center. Fifteen healthy men with minimal previous cannabis use. Symptom ratings, task performance, and regional brain activation. During the processing of oddball stimuli, relative to placebo, Δ9-THC attenuated activation in the right caudate but augmented it in the right prefrontal cortex. Δ9-Tetrahydrocannabinol also reduced the response latency to standard relative to oddball stimuli. The effect of Δ9-THC in the right caudate was negatively correlated with the severity of the psychotic symptoms it induced and its effect on response latency. The effects of CBD on task-related activation were in the opposite direction of those of Δ9-THC; relative to placebo, CBD augmented left caudate and hippocampal activation but attenuated right prefrontal activation. Δ9-Tetrahydrocannabinol and CBD differentially modulate prefrontal, striatal, and hippocampal function during attentional salience processing. These effects may contribute to the effects of cannabis on psychotic symptoms and on the risk of psychotic disorders.

Neural mechanisms mediating the effects of expectation in visceral placebo analgesia: an fMRI study in healthy placebo responders and nonresponders.

PubMed

Elsenbruch, Sigrid; Kotsis, Vassilios; Benson, Sven; Rosenberger, Christina; Reidick, Daniel; Schedlowski, Manfred; Bingel, Ulrike; Theysohn, Nina; Forsting, Michael; Gizewski, Elke R

2012-02-01

This functional magnetic resonance imaging study analysed the behavioural and neural responses during expectation-mediated placebo analgesia in a rectal pain model in healthy subjects. In N=36 healthy subjects, the blood oxygen level-dependent (BOLD) response during cued anticipation and painful rectal stimulation was measured. Using a within-subject design, placebo analgesia was induced by changing expectations regarding the probability of receiving an analgesic drug to 0%, 50%, and 100%. Placebo responders were identified by median split based on pain reduction (0% to 100% conditions), and changes in neural activation correlating with pain reduction in the 0% and 100% conditions were assessed in a regions-of-interest analysis. Expectation of pain relief resulted in overall reductions in pain and urge to defecate, and this response was significantly more pronounced in responders. Within responders, pain reduction correlated with reduced activation of dorsolateral and ventrolateral prefrontal cortices, somatosensory cortex, and thalamus during cued anticipation (paired t tests on the contrast 0%>100%); during painful stimulation, pain reduction correlated with reduced activation of the thalamus. Compared with nonresponders, responders demonstrated greater placebo-induced decreases in activation of dorsolateral prefrontal cortex during anticipation and in somatosensory cortex, posterior cingulate cortex, and thalamus during pain. In conclusion, the expectation of pain relief can substantially change perceived painfulness of visceral stimuli, which is associated with activity changes in the thalamus, prefrontal, and somatosensory cortices. Placebo analgesia constitutes a paradigm to elucidate psychological components of the pain response relevant to the pathophysiology and treatment of chronic abdominal pain. Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Quantitative representations of an exaggerated anxiety response in the brain of female spider phobics-a parametric fMRI study.

PubMed

Zilverstand, Anna; Sorger, Bettina; Kaemingk, Anita; Goebel, Rainer

2017-06-01

We employed a novel parametric spider picture set in the context of a parametric fMRI anxiety provocation study, designed to tease apart brain regions involved in threat monitoring from regions representing an exaggerated anxiety response in spider phobics. For the stimulus set, we systematically manipulated perceived proximity of threat by varying a depicted spider's context, size, and posture. All stimuli were validated in a behavioral rating study (phobics n = 20; controls n = 20; all female). An independent group participated in a subsequent fMRI anxiety provocation study (phobics n = 7; controls n = 7; all female), in which we compared a whole-brain categorical to a whole-brain parametric analysis. Results demonstrated that the parametric analysis provided a richer characterization of the functional role of the involved brain networks. In three brain regions-the mid insula, the dorsal anterior cingulate, and the ventrolateral prefrontal cortex-activation was linearly modulated by perceived proximity specifically in the spider phobia group, indicating a quantitative representation of an exaggerated anxiety response. In other regions (e.g., the amygdala), activation was linearly modulated in both groups, suggesting a functional role in threat monitoring. Prefrontal regions, such as dorsolateral prefrontal cortex, were activated during anxiety provocation but did not show a stimulus-dependent linear modulation in either group. The results confirm that brain regions involved in anxiety processing hold a quantitative representation of a pathological anxiety response and more generally suggest that parametric fMRI designs may be a very powerful tool for clinical research in the future, particularly when developing novel brain-based interventions (e.g., neurofeedback training). Hum Brain Mapp 38:3025-3038, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Methylphenidate and Atomoxetine-Responsive Prefrontal Cortical Genetic Overlaps in "Impulsive" SHR/NCrl and Wistar Rats.

PubMed

Dela Peña, Ike; Dela Peña, Irene Joy; de la Peña, June Bryan; Kim, Hee Jin; Shin, Chan Young; Han, Doug Hyun; Kim, Bung-Nyun; Ryu, Jong Hoon; Cheong, Jae Hoon

2017-09-01

Impulsivity, the predisposition to act prematurely without foresight, is associated with a number of neuropsychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD). Identifying genetic underpinnings of impulsive behavior may help decipher the complex etiology and neurobiological factors of disorders marked by impulsivity. To identify potential genetic factors of impulsivity, we examined common differentially expressed genes (DEGs) in the prefrontal cortex (PFC) of adolescent SHR/NCrl and Wistar rats, which showed marked decrease in preference for the large but delayed reward, compared with WKY/NCrl rats, in the delay discounting task. Of these DEGs, we examined drug-responsive transcripts whose mRNA levels were altered following treatment (in SHR/NCrl and Wistar rats) with drugs that alleviate impulsivity, namely, the ADHD medications methylphenidate and atomoxetine. Prefrontal cortical genetic overlaps between SHR/NCrl and Wistar rats in comparison with WKY/NCrl included genes associated with transcription (e.g., Btg2, Fos, Nr4a2), synaptic plasticity (e.g., Arc, Homer2), and neuron apoptosis (Grik2, Nmnat1). Treatment with methylphenidate and/or atomoxetine increased choice of the large, delayed reward in SHR/NCrl and Wistar rats and changed, in varying degrees, mRNA levels of Nr4a2, Btg2, and Homer2, genes with previously described roles in neuropsychiatric disorders characterized by impulsivity. While further studies are required, we dissected potential genetic factors that may influence impulsivity by identifying genetic overlaps in the PFC of "impulsive" SHR/NCrl and Wistar rats. Notably, these are also drug-responsive transcripts which may be studied further as biomarkers to predict response to ADHD drugs, and as potential targets for the development of treatments to improve impulsivity.

Possible evidence for re-regulation of HPA axis and brain reward systems over time in treatment in prescription opioid-dependent patients.

PubMed

Bunce, Scott C; Harris, Jonathan D; Bixler, Edward O; Taylor, Megan; Muelly, Emilie; Deneke, Erin; Thompson, Kenneth W; Meyer, Roger E

2015-01-01

There is growing evidence for a neuroadaptive model underlying vulnerability to relapse in opioid dependence. The purpose of this study was to evaluate clinical measures hypothesized to mirror elements of allostatic dysregulation in patients dependent on prescription opioids at 2 time points after withdrawal, compared with healthy control participants. Recently withdrawn (n = 7) prescription opioid-dependent patients were compared with the patients in supervised residential care for 2 to 3 months (extended care; n = 7) and healthy controls (n = 7) using drug cue reactivity, affect-modulated startle response tasks, salivary cortisol, and 8 days of sleep actigraphy. Prefrontal cortex was monitored with functional near-infrared spectroscopy during the cue reactivity task. Startle response results indicated reduced hedonic response to natural rewards among patients recently withdrawn from opioids relative to extended care patients. The recently withdrawn patients showed increased activation to pill stimuli in right dorsolateral prefrontal cortex relative to extended care patients. Cortisol levels were elevated among recently withdrawn patients and intermediate for extended care relative to healthy controls. Actigraphy indicated disturbed sleep between recently withdrawn patients and extended care patients; extended care patients were similar to controls. Dorsolateral prefrontal cortex activation to drug and natural reward cues, startle responses to natural reward cues, day-time cortisol levels, time in bed, and total time spent sleeping were all correlated with the number of days since last drug use (ie, time in supervised residential treatment). These results suggest possible re-regulation of dysregulated hypothalamic-pituitary-adrenal axis and brain reward systems in prescription opioid-dependent patients over the drug-free period in residential treatment.

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.

Impaired "affective theory of mind" is associated with right ventromedial prefrontal damage.

PubMed

Shamay-Tsoory, S G; Tomer, R; Berger, B D; Goldsher, D; Aharon-Peretz, J

2005-03-01

To examine the hypothesis that patients with ventromedial (VM) frontal lesions are impaired in the affective rather than cognitive facets of theory of mind (ToM). Prefrontal brain damage may result in impaired social behavior, especially when the damage involves the orbitofrontal/VM prefrontal cortex (PFC). It has been previously suggested that deficits in ToM may account for such aberrant behavior. However, inconsistent results have been reported, and different regions within the frontal cortex have been associated with ToM impairment. The performance of 26 patients with localized lesions in the PFC was compared with responses of 13 patients with posterior lesions and 13 normal control subjects. Three ToM tasks differing in the level of emotional processing involved were used: second-order false belief task, understanding ironic utterances, and identifying social faux pas. The results indicated that patients with VM (but not dorsolateral) prefrontal lesions were significantly impaired in irony and faux pas but not in second-order false belief as compared with patients with posterior lesions and normal control subjects. Lesions in the right VM area were associated with the most severe ToM deficit. These results are discussed in terms of the cognitive and affective facets of "mind-reading" processes mediated by the VM cortex.

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 Use of Bright and Dark Types of Humour is Rooted in the Brain

PubMed Central

Papousek, Ilona; Ruch, Willibald; Rominger, Christian; Kindermann, Elisabeth; Scheidl, Katharina; Schulter, Günter; Fink, Andreas; Weiss, Elisabeth M.

2017-01-01

The ways in which humour can be used are related to the manifold interpersonal functions humour can serve, some of which are positive, and some negative. In the present study, phasic changes in the functional coupling of prefrontal and posterior cortex (EEG coherence) during other people’s auditory displays of happy and sad mood were recorded to predict people’s typical use of humour in social interactions. Greater use of benevolent humour, the intentions of which are in keeping with the characteristics of “laughing-with” humour, was associated with greater decreases of prefrontal-posterior coupling during the processing of happy laughter. More loose prefrontal-posterior coupling indicates loosening of control of the prefrontal cortex over the incoming perceptual information, thereby opening up the perceptual gate and allowing the brain to become more affected by the social-emotional signals. Greater use of humour styles linked to malicious intentions of “laughing-at” humour was associated with responses indicating a wider opened perceptual gate during the processing of other people’s crying. The findings are consistent with the idea that typical humour styles develop in line with the rewarding values of their outcomes (e.g., interaction partners are happy or hurt), which in turn are defined through the individuals’ latent interpersonal goals. PMID:28211496

Cortical oxygenation suggests increased effort during cognitive inhibition in ecstasy polydrug users.

PubMed

Roberts, C A; Montgomery, Catharine

2015-11-01

It is understood that 3,4-methylenedioxymethamphetamine (ecstasy) causes serotonin dysfunction and deficits in executive functioning. When investigating executive function, functional neuroimaging allows the physiological changes underlying these deficits to be investigated. The present study investigated behavioural and brain indices of inhibition in ecstasy-polydrug users. Twenty ecstasy-polydrug users and 20 drug-naïve participants completed an inhibitory control task (Random Letter Generation (RLG)) while prefrontal haemodynamic response was assessed using functional near infrared spectroscopy (fNIRS). There were no group differences on background measures including sleep quality and mood state. There were also no behavioural differences between the two groups. However, ecstasy-polydrug users displayed significant increases in oxygenated haemoglobin (oxy-Hb) from baseline compared to controls at several voxels relating to areas of the inferior right medial prefrontal cortex, as well the right and left dorsolateral prefrontal cortex. Regression analysis revealed that recency of ecstasy use was a significant predictor of oxy-Hb increase at two voxels over the right hemisphere after controlling for alcohol and cannabis use indices. Ecstasy-polydrug users show increased neuronal activation in the prefrontal cortex compared to non-users. This is taken to be compensatory activation/recruitment of additional resources to attain similar performance levels on the task, which may be reversible with prolonged abstinence. © The Author(s) 2015.

Posterior and prefrontal contributions to the development posttraumatic stress disorder symptom severity: an fMRI study of symptom provocation in acute stress disorder.

PubMed

Cwik, Jan C; Sartory, Gudrun; Nuyken, Malte; Schürholt, Benjamin; Seitz, Rüdiger J

2017-09-01

Acute stress disorder (ASD) is predictive of the development of posttraumatic stress disorder (PTSD). In response to symptom provocation, the exposure to trauma-related pictures, ASD patients showed increased activation of the medial posterior areas of precuneus and posterior cingulate cortex as well as of superior prefrontal cortex in a previous study. The current study aimed at investigating which activated areas are predictive of the development of PTSD. Nineteen ASD patients took part in an fMRI study in which they were shown personalized trauma-related and neutral pictures within 4 weeks of the traumatic event. They were assessed for severity of PTSD 4 weeks later. Activation contrasts between trauma-related and neutral pictures were correlated with subsequent PTSD symptom severity. Greater activation in, among others, right medial precuneus, left retrosplenial cortex, precentral and right superior temporal gyrus as well as less activation in lateral, superior prefrontal and left fusiform gyrus was related to subsequently increased PTSD severity. The results are broadly in line with neural areas related to etiological models of PTSD, namely multisensory associative learning recruiting posterior regions on the one hand and failure to reappraise maladaptive cognitions, thought to involve prefrontal areas, on the other.

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

[Review of the effects of mindfulness meditation on mental and physical health and its mechanisms of action].

PubMed

Ngô, Thanh-Lan

2013-01-01

Interventions based on mindfulness have become increasingly popular. This article reviews the empirical literature on its effects on mental and physical health, discusses presumed mechanisms of action as well as its proposed neurobiological underpinning. Mindfulness is associated with increased well-being as well as reduced cognitive reactivity and behavioral avoidance. It seems to contribute to enhance immune functions, diminish inflammation, diminish the reactivity of the autonomic nervous system, increase telomerase activity, lead to higher levels of plasmatic melatonin and serotonin. It enhances the quality of life for patients suffering from chronic pain, fibromylagia and HIV infection. It facilitates adaptation to the diagnosis of cancer and diabetes. It seems to lead to symptomatic improvement in irritable bowel syndrome, chronic fatigue syndrome, hot flashes, insomnia, stress related hyperphagia. It diminishes craving in substance abuse. The proposed mechanism of action are enhanced metacognitive conscience, interoceptive exposure, experiential acceptance, self-management, attention control, memory, relaxation. Six mechanism of actions for which neurological underpinnings have been published are: attention regulation (anterior cingulate cortex), body awareness (insula, temporoparietal junction), emotion regulation (modulation of the amygdala by the lateral prefrontal cortex), cognitive re-evaluation (activation of the dorsal medial prefrontal cortex or diminished activity in prefrontal regions), exposure/extinction/reconsolidation (ventromedial prefrontal cortex, hippocampus, amygdala) and flexible self-concept (prefrontal median cortex, posterior cingulated cortex, insula, temporoparietal junction). The neurobiological effects of meditation are described. These are: (1) the deactivation of the default mode network that generates spontaneous thoughts, contributes to the maintenance of the autobiographical self and is associated with anxiety and depression; (2) the anterior cingulate cortex that underpins attention functions; (3) the anterior insula associated with the perception of visceral sensation, the detection of heartbeat and respiratory rate, and the affective response to pain; (4) the posterior cingulate cortex which helps to understand the context from which a stimulus emerges; (5) the temporoparietal junction which assumes a central role in empathy and compassion; (6) the amygdala implicated in fear responses. The article ends with a short review of the empirical basis supporting the efficacy for mindfulness based intervention and suggested directions for future research.

Neuroelectrical imaging investigation of cortical activity during listening to music in prelingually deaf children with cochlear implants.

PubMed

Marsella, Pasquale; Scorpecci, Alessandro; Vecchiato, Giovanni; Maglione, Anton Giulio; Colosimo, Alfredo; Babiloni, Fabio

2014-05-01

To date, no objective measure of the pleasantness of music perception by children with cochlear implants has been reported. The EEG alpha asymmetries of pre-frontal cortex activation are known to relate to emotional/affective engagement in a perceived stimulus. More specifically, according to the "withdrawal/approach" model, an unbalanced de-synchronization of the alpha activity in the left prefrontal cortex has been associated with a positive affective state/approach toward a stimulus, and an unbalanced de-synchronization of the same activity in the right prefrontal cortex with a negative affective state/withdrawal from a stimulus. In the present study, High-Resolution EEG with Source Reconstruction was used to compare the music-induced alpha asymmetries of the prefrontal cortex in a group of prelingually deaf implanted children and in a control group of normal-hearing children. Six normal-hearing and six age-matched deaf children using a unilateral cochlear implants underwent High-Resolution EEG recordings as they were listening to a musical cartoon. Musical stimuli were delivered in three versions: Normal, Distort (reverse audio flow) and Mute. The EEG alpha rhythm asymmetry was analyzed: Power Spectral Density was calculated for each Region of Interest, together with a right-left imbalance index. A map of cortical activation was then reconstructed on a realistic cortical model. Asymmetries of EEG alpha rhythm in the prefrontal cortices were observed in both groups. In the normal-hearing children, the asymmetries were consistent with the withdrawal/approach model, whereas in cochlear implant users they were not. Moreover, in implanted children a different pattern of alpha asymmetries in extrafrontal cortical areas was noticed as compared to normal-hearing subjects. The peculiar pattern of alpha asymmetries in implanted children's prefrontal cortex in response to musical stimuli suggests an inability by these subjects to discriminate normal from dissonant music and to appreciate the pleasantness of normal music. High-Resolution EEG may prove to be a promising tool for objectively measuring prefrontal cortex alpha asymmetries in child cochlear implant users. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Dorsolateral prefrontal lesions do not impair tests of scene learning and decision-making that require frontal–temporal interaction

PubMed Central

Baxter, Mark G; Gaffan, David; Kyriazis, Diana A; Mitchell, Anna S

2008-01-01

Theories of dorsolateral prefrontal cortex (DLPFC) involvement in cognitive function variously emphasize its involvement in rule implementation, cognitive control, or working and/or spatial memory. These theories predict broad effects of DLPFC lesions on tests of visual learning and memory. We evaluated the effects of DLPFC lesions (including both banks of the principal sulcus) in rhesus monkeys on tests of scene learning and strategy implementation that are severely impaired following crossed unilateral lesions of frontal cortex and inferotemporal cortex. Dorsolateral lesions had no effect on learning of new scene problems postoperatively, or on the implementation of preoperatively acquired strategies. They were also without effect on the ability to adjust choice behaviour in response to a change in reinforcer value, a capacity that requires interaction between the amygdala and frontal lobe. These intact abilities following DLPFC damage support specialization of function within the prefrontal cortex, and suggest that many aspects of memory and strategic and goal-directed behaviour can survive ablation of this structure. PMID:18702721

Physical activity, fitness, and gray matter volume

PubMed Central

Erickson, Kirk I.; Leckie, Regina L.; Weinstein, Andrea M.

2014-01-01

In this review we explore the association between physical activity, cardiorespiratory fitness, and exercise on gray matter volume in older adults. We conclude that higher cardiorespiratory fitness levels are routinely associated with greater gray matter volume in the prefrontal cortex and hippocampus, and less consistently in other regions. We also conclude that physical activity is associated with greater gray matter volume in the same regions that are associated with cardiorespiratory fitness including the prefrontal cortex and hippocampus. Some heterogeneity in the literature may be explained by effect moderation by age, stress, or other factors. Finally, we report promising results from randomized exercise interventions that suggest that the volume of the hippocampus and prefrontal cortex remain pliable and responsive to moderate intensity exercise for 6-months to 1-year. Physical activity appears to be a propitious method for influencing gray matter volume in late adulthood, but additional well-controlled studies are necessary to inform public policies about the potential protective or therapeutic effects of exercise on brain volume. PMID:24952993

Prefrontal cortical response to conflict during semantic and phonological tasks.

PubMed

Snyder, Hannah R; Feigenson, Keith; Thompson-Schill, Sharon L

2007-05-01

Debates about the function of the prefrontal cortex are as old as the field of neuropsychology--often dated to Paul Broca's seminal work. Theories of the functional organization of the prefrontal cortex can be roughly divided into those that describe organization by process and those that describe organization by material. Recent studies of the function of the posterior, left inferior frontal gyrus (pLIFG) have yielded two quite different interpretations: One hypothesis holds that the pLIFG plays a domain-specific role in phonological processing, whereas another hypothesis describes a more general function of the pLIFG in cognitive control. In the current study, we distinguish effects of increasing cognitive control demands from effects of phonological processing. The results support the hypothesized role for the pLIFG in cognitive control, and more task-specific roles for posterior areas in phonology and semantics. Thus, these results suggest an alternative explanation of previously reported phonology-specific effects in the pLIFG.

Architecture of PFC supports analogy, but PFC is not an analogy machine.

PubMed

Speed, Ann

2010-06-01

In the preceding discussion paper, I proposed a theory of prefrontal cortical organization that was fundamentally intended to address the question: How does prefrontal cortex (PFC) support the various functions for which it seems to be selectively recruited? In so doing, I chose to focus on a particular function, analogy, that seems to have been largely ignored in the theoretical treatments of PFC, but that does underlie many other cognitive functions (Hofstadter, 2001 ; Holyoak & Thagard, 1997 ). At its core, this paper was intended to use analogy as a foundation for exploring one possibility for prefrontal function in general, although it is easy to see how the analogy-specific interpretation arises (as in the comment by Ibáñez). In an attempt to address this more foundational question, this response will step away from analogy as a focus, and will address first the various comments from the perspective of the initial motivation for developing this theory, and then specific issues raised by the commentators.

Awareness of Emotional Stimuli Determines the Behavioral Consequences of Amygdala Activation and Amygdala-Prefrontal Connectivity

PubMed Central

Lapate, R. C.; Rokers, B.; Tromp, D. P. M.; Orfali, N. S.; Oler, J. A.; Doran, S. T.; Adluru, N.; Alexander, A. L.; Davidson, R. J.

2016-01-01

Conscious awareness of negative cues is thought to enhance emotion-regulatory capacity, but the neural mechanisms underlying this effect are unknown. Using continuous flash suppression (CFS) in the MRI scanner, we manipulated visual awareness of fearful faces during an affect misattribution paradigm, in which preferences for neutral objects can be biased by the valence of a previously presented stimulus. The amygdala responded to fearful faces independently of awareness. However, when awareness of fearful faces was prevented, individuals with greater amygdala responses displayed a negative bias toward unrelated novel neutral faces. In contrast, during the aware condition, inverse coupling between the amygdala and prefrontal cortex reduced this bias, particularly among individuals with higher structural connectivity in the major white matter pathway connecting the prefrontal cortex and amygdala. Collectively, these results indicate that awareness promotes the function of a critical emotion-regulatory network targeting the amygdala, providing a mechanistic account for the role of awareness in emotion regulation. PMID:27181344

Different hemodynamic response of prefontal area for men and women to mental arithmetic: a near-infrared spectroscopy study

NASA Astrophysics Data System (ADS)

Yang, Hongyu; Zhou, Zhenyu; Liu, Yun; Ruan, Zongcai; Gong, Hui; Luo, Qingming; Lu, Zuhong

2007-05-01

A 16-channel near-infrared spectroscopy (NIRS) was used to measure concentration changes of oxygenated and deoxygenated hemoglobin (oxy-HB and deoxy-HB) in prefrontal area while the subjects were performing mental works. Thirty healthy college participants were administered two mental arithmetic tasks while the changes of concentration on oxy-HB and deoxy-HB were measured. Oxy-HB increased during the mental works, and the increases of oxy-HB were greater in male subjects than in female subjects during the difficult task. These results suggest that NIRS is sensitive to evaluate the oxy-HB activity of prefrontal cortex during mental works.

Recruitment of prefrontal-striatal circuit in response to skilled motor challenge.

PubMed

Guo, Yumei; Wang, Zhuo; Prathap, Sandhya; Holschneider, Daniel P

2017-12-13

A variety of physical fitness regimens have been shown to improve cognition, including executive function, yet our understanding of which parameters of motor training are important in optimizing outcomes remains limited. We used functional brain mapping to compare the ability of two motor challenges to acutely recruit the prefrontal-striatal circuit. The two motor tasks - walking in a complex running wheel with irregularly spaced rungs or walking in a running wheel with a smooth internal surface - differed only in the extent of skill required for their execution. Cerebral perfusion was mapped in rats by intravenous injection of [C]-iodoantipyrine during walking in either a motorized complex wheel or in a simple wheel. Regional cerebral blood flow (rCBF) was quantified by whole-brain autoradiography and analyzed in three-dimensional reconstructed brains by statistical parametric mapping and seed-based functional connectivity. Skilled or simple walking compared with rest, increased rCBF in regions of the motor circuit, somatosensory and visual cortex, as well as the hippocampus. Significantly greater rCBF increases were noted during skilled walking than for simple walking. Skilled walking, unlike simple walking or the resting condition, was associated with a significant positive functional connectivity in the prefrontal-striatal circuit (prelimbic cortex-dorsomedial striatum) and greater negative functional connectivity in the prefrontal-hippocampal circuit. Our findings suggest that the level of skill of a motor training task determines the extent of functional recruitment of the prefrontal-corticostriatal circuit, with implications for a new approach in neurorehabilitation that uses circuit-specific neuroplasticity to improve motor and cognitive functions.

Prefrontal NMDA receptors expressed in excitatory neurons control fear discrimination and fear extinction.

PubMed

Vieira, Philip A; Corches, Alex; Lovelace, Jonathan W; Westbrook, Kevin B; Mendoza, Michael; Korzus, Edward

2015-03-01

N-methyl-D-aspartate receptors (NMDARs) are critically involved in various learning mechanisms including modulation of fear memory, brain development and brain disorders. While NMDARs mediate opposite effects on medial prefrontal cortex (mPFC) interneurons and excitatory neurons, NMDAR antagonists trigger profound cortical activation. The objectives of the present study were to determine the involvement of NMDARs expressed specifically in excitatory neurons in mPFC-dependent adaptive behaviors, specifically fear discrimination and fear extinction. To achieve this, we tested mice with locally deleted Grin1 gene encoding the obligatory NR1 subunit of the NMDAR from prefrontal CamKIIα positive neurons for their ability to distinguish frequency modulated (FM) tones in fear discrimination test. We demonstrated that NMDAR-dependent signaling in the mPFC is critical for effective fear discrimination following initial generalization of conditioned fear. While mice with deficient NMDARs in prefrontal excitatory neurons maintain normal responses to a dangerous fear-conditioned stimulus, they exhibit abnormal generalization decrement. These studies provide evidence that NMDAR-dependent neural signaling in the mPFC is a component of a neural mechanism for disambiguating the meaning of fear signals and supports discriminative fear learning by retaining proper gating information, viz. both dangerous and harmless cues. We also found that selective deletion of NMDARs from excitatory neurons in the mPFC leads to a deficit in fear extinction of auditory conditioned stimuli. These studies suggest that prefrontal NMDARs expressed in excitatory neurons are involved in adaptive behavior. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

Exercise-induced stress resistance is independent of exercise controllability and the medial prefrontal cortex

PubMed Central

Greenwood, Benjamin N.; Spence, Katie G.; Crevling, Danielle M.; Clark, Peter J.; Craig, Wendy C.; Fleshner, Monika

2014-01-01

Exercise increases resistance against stress-related disorders such as anxiety and depression. Similarly, the perception of control is a powerful predictor of neurochemical and behavioral responses to stress, but whether the experience of choosing to exercise, and exerting control over that exercise, is a critical factor in producing exercise-induced stress resistance is unknown. The current studies investigated whether the protective effects of exercise against the anxiety- and depression-like consequences of stress are dependent on exercise controllability and a brain region implicated in the protective effects of controllable experiences, the medial prefrontal cortex. Adult male Fischer 344 rats remained sedentary, were forced to run on treadmills or motorised running wheels, or had voluntary access to wheels for 6 weeks. Three weeks after exercise onset, rats received sham surgery or excitotoxic lesions of the medial prefrontal cortex. Rats were exposed to home cage or uncontrollable tail shock treatment three weeks later. Shock-elicited fear conditioning and shuttle box escape testing occurred the next day. Both forced and voluntary wheel running, but not treadmill training, prevented the exaggerated fear conditioning and interference with escape learning produced by uncontrollable stress. Lesions of the medial prefrontal cortex failed to eliminate the protective effects of forced or voluntary wheel running. These data suggest that exercise controllability and the medial prefrontal cortex are not critical factors in conferring the protective effects of exercise against the affective consequences of stressor exposure, and imply that exercise perceived as forced may still benefit affect and mental health. PMID:23121339

Decreased prefrontal cortical sensitivity to monetary reward is associated with impaired motivation and self-control in cocaine addiction

PubMed Central

Goldstein, Rita Z.; Alia-Klein, Nelly; Tomasi, Dardo; Zhang, Lei; Cottone, Lisa A.; Maloney, Thomas; Telang, Frank; Caparelli, Elisabeth C.; Chang, Linda; Ernst, Thomas; Samaras, Dimitris; Squires, Nancy K.; Volkow, Nora D.

2008-01-01

Objective To examine the brain’s sensitivity to monetary rewards of different magnitudes in cocaine abusers and to study its association with motivation and self-control. Method Sixteen cocaine abusers and 13 matched healthy comparison subjects performed a forced-choice task under three monetary value conditions while brain activation was measured with functional magnetic resonance imaging. Objective measures of state motivation were assessed by reaction time and accuracy, and subjective measures were assessed by self-reports of task engagement. Measures of trait motivation and self-control were assessed with the Multidimensional Personality Questionnaire. Results The cocaine abusers demonstrated an overall reduced regional brain responsivity to differences between the monetary value conditions. Also, in comparison subjects but not in cocaine abusers reward-induced improvements in performance were associated with self-reports of task engagement, and money-induced activations in the lateral prefrontal cortex were associated with activations in the orbitofrontal cortex. For cocaine subjects, prefrontal cortex sensitivity to money was instead associated with motivation and self-control. Conclusions These findings suggest that in cocaine addiction (1) activation of the corticolimbic reward circuit to gradations of money is altered; (2) lack of a correlation between objective and subjective measures of state motivation may be indicative of disrupted perception of motivational drive, which could contribute to impairments in self-control; and (3) the lateral prefrontal cortex modulates trait motivation and deficits in self-control, and a possible underlying mechanism may encompass a breakdown in prefrontal-orbitofrontal cortical communication. PMID:17202543

Minocycline restores cognitive-relative altered proteins in young bile duct-ligated rat prefrontal cortex.

PubMed

Li, Shih-Wen; Chen, Yu-Chieh; Sheen, Jiunn-Ming; Hsu, Mei-Hsin; Tain, You-Lin; Chang, Kow-Aung; Huang, Li-Tung

2017-07-01

Bile duct ligation (BDL) model is used to study hepatic encephalopathy accompanied by cognitive impairment. We employed the proteomic analysis approach to evaluate cognition-related proteins in the prefrontal cortex of young BDL rats and analyzed the effect of minocycline on these proteins and spatial memory. BDL was induced in young rats at postnatal day 17. Minocycline as a slow-release pellet was implanted into the peritoneum. Morris water maze test and two-dimensional liquid chromatography-tandem mass spectrometry were used to evaluate spatial memory and prefrontal cortex protein expression, respectively. We used 2D/LC-MS/MS to analyze for affected proteins in the prefrontal cortex of young BDL rats. Results were verified with Western blotting, immunohistochemistry, and quantitative real-time PCR. The effect of minocycline in BDL rats was assessed. BDL induced spatial deficits, while minocycline rescued it. Collapsin response mediator protein 2 (CRMP2) and manganese-dependent superoxide dismutase (MnSOD) were upregulated and nucleoside diphosphate kinase B (NME2) was downregulated in young BDL rats. BDL rats exhibited decreased levels of brain-derived neurotrophic factor (BDNF) mRNA as compared with those by the control. However, minocycline treatment restored CRMP2 and NME2 protein expression, BDNF mRNA level, and MnSOD activity to control levels. We demonstrated that BDL altered the expression of CRMP2, NME2, MnSOD, and BDNF in the prefrontal cortex of young BDL rats. However, minocycline treatment restored the expression of the affected mediators that are implicated in cognition. Copyright © 2017 Elsevier Inc. All rights reserved.

Damage to ventromedial prefrontal cortex impairs judgment of harmful intent.

PubMed

Young, Liane; Bechara, Antoine; Tranel, Daniel; Damasio, Hanna; Hauser, Marc; Damasio, Antonio

2010-03-25

Moral judgments, whether delivered in ordinary experience or in the courtroom, depend on our ability to infer intentions. We forgive unintentional or accidental harms and condemn failed attempts to harm. Prior work demonstrates that patients with damage to the ventromedial prefrontal cortex (VMPC) deliver abnormal judgments in response to moral dilemmas and that these patients are especially impaired in triggering emotional responses to inferred or abstract events (e.g., intentions), as opposed to real or actual outcomes. We therefore predicted that VMPC patients would deliver abnormal moral judgments of harmful intentions in the absence of harmful outcomes, as in failed attempts to harm. This prediction was confirmed in the current study: VMPC patients judged attempted harms, including attempted murder, as more morally permissible relative to controls. These results highlight the critical role of the VMPC in processing harmful intent for moral judgment. (c) 2010 Elsevier Inc. All rights reserved.

The neural basis of episodic memory: evidence from functional neuroimaging.

PubMed Central

Rugg, Michael D; Otten, Leun J; Henson, Richard N A

2002-01-01

We review some of our recent research using functional neuroimaging to investigate neural activity supporting the encoding and retrieval of episodic memories, that is, memories for unique events. Findings from studies of encoding indicate that, at the cortical level, the regions responsible for the effective encoding of a stimulus event as an episodic memory include some of the regions that are also engaged to process the event 'online'. Thus, it appears that there is no single cortical site or circuit responsible for episodic encoding. The results of retrieval studies indicate that successful recollection of episodic information is associated with activation of lateral parietal cortex, along with more variable patterns of activity in dorsolateral and anterior prefrontal cortex. Whereas parietal regions may play a part in the representation of retrieved information, prefrontal areas appear to support processes that act on the products of retrieval to align behaviour with the demands of the retrieval task. PMID:12217177

Corticomotor Responses to Attentionally Demanding Motor Performance: A Mini-Review

PubMed Central

Corp, Daniel  T.; Drury, Hannah G. K.; Young, Kayleigh; Do, Michael; Perkins, Tom; Pearce, Alan J.

2013-01-01

Increased attentional demand has been shown to reduce motor performance, leading to increases in accidents, particularly in elderly populations. While these deficits have been well documented behaviorally, their cortical correlates are less well known. Increased attention has been shown to affect activity in prefrontal regions of the cortex. However there have been varying results within past research investigating corticomotor regions, mediating motor performance. This mini-review initially discusses past behavioral research, before moving to studies investigating corticomotor areas in response to changes in attention. Recent dual task studies have revealed a possible decline in the ability of older, but not younger, adults to activate inhibitory processes within the motor cortex, which may be correlated with poor motor performance, and thus accidents. A reduction in cortical inhibition may be caused by neurodegeneration within prefrontal regions of the cortex with age, rendering older adults less able to allocate attention to corticomotor regions. PMID:23579267

Prefrontal cortical regulation of brainwide circuit dynamics and reward-related behavior

PubMed Central

Grosenick, Logan; Warden, Melissa R.; Amatya, Debha; Katovich, Kiefer; Mehta, Hershel; Patenaude, Brian; Ramakrishnan, Charu; Kalanithi, Paul; Etkin, Amit; Knutson, Brian; Glover, Gary H.; Deisseroth, Karl

2016-01-01

Motivation for reward drives adaptive behaviors, whereas impairment of reward perception and experience (anhedonia) can contribute to psychiatric diseases, including depression and schizophrenia. We sought to test the hypothesis that the medial prefrontal cortex (mPFC) controls interactions among specific subcortical regions that govern hedonic responses. By using optogenetic functional magnetic resonance imaging to locally manipulate but globally visualize neural activity in rats, we found that dopamine neuron stimulation drives striatal activity, whereas locally increased mPFC excitability reduces this striatal response and inhibits the behavioral drive for dopaminergic stimulation. This chronic mPFC overactivity also stably suppresses natural reward-motivated behaviors and induces specific new brainwide functional interactions, which predict the degree of anhedonia in individuals. These findings describe a mechanism by which mPFC modulates expression of reward-seeking behavior, by regulating the dynamical interactions between specific distant subcortical regions. PMID:26722001

Moral transgressions corrupt neural representations of value

PubMed Central

Crockett, Molly J.; Siegel, Jenifer Z.; Kurth-Nelson, Zeb; Dayan, Peter; Dolan, Raymond J.

2017-01-01

Moral systems universally prohibit harming others for personal gain. However, we know little about how such principles guide moral behavior. Using a task that assesses the financial cost participants ascribe to harming others versus themselves, we probed the relationship between moral behavior and neural representations of profit and pain. Most participants displayed moral preferences, placing a higher cost on harming others than themselves. Moral preferences correlated with neural responses to profit, where participants with stronger moral preferences had lower dorsal striatal (DS) responses to profit gained from harming others. Lateral prefrontal cortex (LPFC) encoded profits gained from harming others, but not self, and tracked the blameworthiness of harmful choices. Moral decisions also modulated functional connectivity between LPFC and the profit-sensitive region of DS. The findings suggest moral behavior in our task is linked to a neural devaluation of reward realized by a prefrontal modulation of striatal value representations. PMID:28459442

Neural priming in human frontal cortex: multiple forms of learning reduce demands on the prefrontal executive system.

PubMed

Race, Elizabeth A; Shanker, Shanti; Wagner, Anthony D

2009-09-01

Past experience is hypothesized to reduce computational demands in PFC by providing bottom-up predictive information that informs subsequent stimulus-action mapping. The present fMRI study measured cortical activity reductions ("neural priming"/"repetition suppression") during repeated stimulus classification to investigate the mechanisms through which learning from the past decreases demands on the prefrontal executive system. Manipulation of learning at three levels of representation-stimulus, decision, and response-revealed dissociable neural priming effects in distinct frontotemporal regions, supporting a multiprocess model of neural priming. Critically, three distinct patterns of neural priming were identified in lateral frontal cortex, indicating that frontal computational demands are reduced by three forms of learning: (a) cortical tuning of stimulus-specific representations, (b) retrieval of learned stimulus-decision mappings, and (c) retrieval of learned stimulus-response mappings. The topographic distribution of these neural priming effects suggests a rostrocaudal organization of executive function in lateral frontal cortex.

Neural basis of economic bubble behavior.

PubMed

Ogawa, A; Onozaki, T; Mizuno, T; Asamizuya, T; Ueno, K; Cheng, K; Iriki, A

2014-04-18

Throughout human history, economic bubbles have formed and burst. As a bubble grows, microeconomic behavior ceases to be constrained by realistic predictions. This contradicts the basic assumption of economics that agents have rational expectations. To examine the neural basis of behavior during bubbles, we performed functional magnetic resonance imaging while participants traded shares in a virtual stock exchange with two non-bubble stocks and one bubble stock. The price was largely deflected from the fair price in one of the non-bubble stocks, but not in the other. Their fair prices were specified. The price of the bubble stock showed a large increase and battering, as based on a real stock-market bust. The imaging results revealed modulation of the brain circuits that regulate trade behavior under different market conditions. The premotor cortex was activated only under a market condition in which the price was largely deflected from the fair price specified. During the bubble, brain regions associated with the cognitive processing that supports order decisions were identified. The asset preference that might bias the decision was associated with the ventrolateral prefrontal cortex and the dorsolateral prefrontal cortex (DLPFC). The activity of the inferior parietal lobule (IPL) was correlated with the score of future time perspective, which would bias the estimation of future price. These regions were deemed to form a distinctive network during the bubble. A functional connectivity analysis showed that the connectivity between the DLPFC and the IPL was predominant compared with other connectivities only during the bubble. These findings indicate that uncertain and unstable market conditions changed brain modes in traders. These brain mechanisms might lead to a loss of control caused by wishful thinking, and to microeconomic bubbles that expand, on the macroscopic scale, toward bust. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Working memory and prefrontal/temporal hemodynamic responses during post-task period in patients with schizophrenia: A multi-channel near-infrared spectroscopy study.

PubMed

Noda, Takamasa; Nakagome, Kazuyuki; Setoyama, Shiori; Matsushima, Eisuke

2017-12-01

The relationship between cognitive impairments and social dysfunction in schizophrenia is widely accepted. Neuroimaging studies in patients with schizophrenia have demonstrated abnormal function in the prefrontal region during various neurocognitive tasks. However, studies exploring the neural basis of these cognitive impairments are still limited. Multi-channel near-infrared spectroscopy (NIRS) is a non-invasive functional neuroimaging technique used to detect the spatiotemporal characteristics of brain activity. Previous NIRS studies indicated oxy-hemoglobin (oxy-Hb) increase in patients with schizophrenia during the verbal fluency task (VFT), but to a lesser extent than in healthy participants. Furthermore, aberrant re-increase in the prefrontal region was observed during the post-task period. We hypothesized that prefrontal/temporal oxy-Hb aberrant re-increase during the post-task period was associated with cognitive impairment because oxy-Hb aberrant re-increase represent inadequate suppression of neural activity in the post-task period. We recruited 30 patients with schizophrenia and 30 healthy participants in this study. All participants underwent 52-channel NIRS measurement using the VFT. The patients with schizophrenia showed oxy-Hb aberrant re-increase in prefrontal and temporal regions during the post-task period. Although there was no significant relationship between changes in the oxy-Hb during the task and the scores of the Brief Assessment of Cognition in Schizophrenia (BACS), a significant negative correlation was observed between the oxy-Hb during the post-task period and BACS working memory z-scores (in DLPFC and temporal regions). These results suggest that oxy-Hb re-increase during the post-task period in prefrontal and temporal regions is associated with WM deficits in patients with schizophrenia and NIRS may be a potential biomarker of working memory in chronic schizophrenia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dissociations of cognitive inhibition, response inhibition, and emotional interference: Voxelwise ALE meta-analyses of fMRI studies.

PubMed

Hung, Yuwen; Gaillard, Schuyler L; Yarmak, Pavel; Arsalidou, Marie

2018-06-19

Inhibitory control is the stopping of a mental process with or without intention, conceptualized as mental suppression of competing information because of limited cognitive capacity. Inhibitory control dysfunction is a core characteristic of many major psychiatric disorders. Inhibition is generally thought to involve the prefrontal cortex; however, a single inhibitory mechanism is insufficient for interpreting the heterogeneous nature of human cognition. It remains unclear whether different dimensions of inhibitory processes-specifically cognitive inhibition, response inhibition, and emotional interference-rely on dissociated neural systems. We conducted systematic meta-analyses of fMRI studies in the BrainMap database supplemented by PubMed using whole-brain activation likelihood estimation. A total of 66 study experiments including 1,447 participants and 987 foci revealed that while the left anterior insula was concordant in all inhibitory dimensions, cognitive inhibition reliably activated specific dorsal frontal inhibitory system, engaging dorsal anterior cingulate, dorsolateral prefrontal cortex, and parietal areas, whereas emotional interference reliably implicated a ventral inhibitory system, involving the ventral surface of the inferior frontal gyrus and the amygdala. Response inhibition showed concordant clusters in the fronto-striatal system, including the dorsal anterior cingulate region and extended supplementary motor areas, the dorsal and ventral lateral prefrontal cortex, basal ganglia, midbrain regions, and parietal regions. We provide an empirically derived dimensional model of inhibition characterizing neural systems underlying different aspects of inhibitory mechanisms. This study offers a fundamental framework to advance current understanding of inhibition and provides new insights for future clinical research into disorders with different types of inhibition-related dysfunctions. © 2018 Wiley Periodicals, Inc.

Compensatory processing during rule-based category learning in older adults.

PubMed

Bharani, Krishna L; Paller, Ken A; Reber, Paul J; Weintraub, Sandra; Yanar, Jorge; Morrison, Robert G

2016-01-01

Healthy older adults typically perform worse than younger adults at rule-based category learning, but better than patients with Alzheimer's or Parkinson's disease. To further investigate aging's effect on rule-based category learning, we monitored event-related potentials (ERPs) while younger and neuropsychologically typical older adults performed a visual category-learning task with a rule-based category structure and trial-by-trial feedback. Using these procedures, we previously identified ERPs sensitive to categorization strategy and accuracy in young participants. In addition, previous studies have demonstrated the importance of neural processing in the prefrontal cortex and the medial temporal lobe for this task. In this study, older adults showed lower accuracy and longer response times than younger adults, but there were two distinct subgroups of older adults. One subgroup showed near-chance performance throughout the procedure, never categorizing accurately. The other subgroup reached asymptotic accuracy that was equivalent to that in younger adults, although they categorized more slowly. These two subgroups were further distinguished via ERPs. Consistent with the compensation theory of cognitive aging, older adults who successfully learned showed larger frontal ERPs when compared with younger adults. Recruitment of prefrontal resources may have improved performance while slowing response times. Additionally, correlations of feedback-locked P300 amplitudes with category-learning accuracy differentiated successful younger and older adults. Overall, the results suggest that the ability to adapt one's behavior in response to feedback during learning varies across older individuals, and that the failure of some to adapt their behavior may reflect inadequate engagement of prefrontal cortex.

Hemispheric asymmetry in stress processing in rat prefrontal cortex and the role of mesocortical dopamine.

PubMed

Sullivan, R M

2004-06-01

The prefrontal cortex (PFC) is known to play an important role not only in the regulation of emotion, but in the integration of affective states with appropriate modulation of autonomic and neuroendocrine stress regulatory systems. The present review highlights findings in the rat which helps to elucidate the complex nature of prefrontal involvement in emotion and stress regulation. The medial PFC is particularly important in this regard and while dorsomedial regions appear to play a suppressive role in such regulation, the ventromedial (particularly infralimbic) region appears to activate behavioral, neuroendocrine and sympathetic autonomic systems in response to stressful situations. This may be especially true of spontaneous stress-related behavior or physiological responses to relatively acute stressors. The role of the medial PFC is somewhat more complex in conditions involving learned adjustments to stressful situations, such as the extinction of conditioned fear responses, but it is clear that the medial PFC is important in incorporating stressful experience for future adaptive behavior. It is also suggested that mesocortical dopamine plays an important adaptive role in this region by preventing excessive behavioral and physiological stress reactivity. The rat brain shows substantial hemispheric specialization in many respects, and while the right PFC is normally dominant in the activation of stress-related systems, the left may play a role in countering this activation through processes of interhemispheric inhibition. This proposed basic template for the lateralization of stress regulatory systems is suggested to be associated with efficient stress and emotional self-regulation, and also to be shaped by both early postnatal experience and gender differences.

Compensatory Processing During Rule-Based Category Learning in Older Adults

PubMed Central

Bharani, Krishna L.; Paller, Ken A.; Reber, Paul J.; Weintraub, Sandra; Yanar, Jorge; Morrison, Robert G.

2016-01-01

Healthy older adults typically perform worse than younger adults at rule-based category learning, but better than patients with Alzheimer's or Parkinson's disease. To further investigate aging's effect on rule-based category learning, we monitored event-related potentials (ERPs) while younger and neuropsychologically typical older adults performed a visual category-learning task with a rule-based category structure and trial-by-trial feedback. Using these procedures, we previously identified ERPs sensitive to categorization strategy and accuracy in young participants. In addition, previous studies have demonstrated the importance of neural processing in the prefrontal cortex and the medial temporal lobe for this task. In this study, older adults showed lower accuracy and longer response times than younger adults, but there were two distinct subgroups of older adults. One subgroup showed near-chance performance throughout the procedure, never categorizing accurately. The other subgroup reached asymptotic accuracy that was equivalent to that in younger adults, although they categorized more slowly. These two subgroups were further distinguished via ERPs. Consistent with the compensation theory of cognitive aging, older adults who successfully learned showed larger frontal ERPs when compared with younger adults. Recruitment of prefrontal resources may have improved performance while slowing response times. Additionally, correlations of feedback-locked P300 amplitudes with category-learning accuracy differentiated successful younger and older adults. Overall, the results suggest that the ability to adapt one's behavior in response to feedback during learning varies across older individuals, and that the failure of some to adapt their behavior may reflect inadequate engagement of prefrontal cortex. PMID:26422522

A machine learning approach to identify functional biomarkers in human prefrontal cortex for individuals with traumatic brain injury using functional near-infrared spectroscopy.

PubMed

Karamzadeh, Nader; Amyot, Franck; Kenney, Kimbra; Anderson, Afrouz; Chowdhry, Fatima; Dashtestani, Hadis; Wassermann, Eric M; Chernomordik, Victor; Boccara, Claude; Wegman, Edward; Diaz-Arrastia, Ramon; Gandjbakhche, Amir H

2016-11-01

We have explored the potential prefrontal hemodynamic biomarkers to characterize subjects with Traumatic Brain Injury (TBI) by employing the multivariate machine learning approach and introducing a novel task-related hemodynamic response detection followed by a heuristic search for optimum set of hemodynamic features. To achieve this goal, the hemodynamic response from a group of 31 healthy controls and 30 chronic TBI subjects were recorded as they performed a complexity task. To determine the optimum hemodynamic features, we considered 11 features and their combinations in characterizing TBI subjects. We investigated the significance of the features by utilizing a machine learning classification algorithm to score all the possible combinations of features according to their predictive power. The identified optimum feature elements resulted in classification accuracy, sensitivity, and specificity of 85%, 85%, and 84%, respectively. Classification improvement was achieved for TBI subject classification through feature combination. It signified the major advantage of the multivariate analysis over the commonly used univariate analysis suggesting that the features that are individually irrelevant in characterizing the data may become relevant when used in combination. We also conducted a spatio-temporal classification to identify regions within the prefrontal cortex (PFC) that contribute in distinguishing between TBI and healthy subjects. As expected, Brodmann areas (BA) 10 within the PFC were isolated as the region that healthy subjects (unlike subjects with TBI), showed major hemodynamic activity in response to the High Complexity task. Overall, our results indicate that identified temporal and spatio-temporal features from PFC's hemodynamic activity are promising biomarkers in classifying subjects with TBI.

A human chemosignal modulates frontolimbic activity and connectivity in response to emotional stimuli.

PubMed

Hummer, Tom A; Phan, K Luan; Kern, David W; McClintock, Martha K

2017-01-01

Evidence suggests the putative human pheromone Δ4,16-androstadien-3-one (androstadienone), a natural component of human sweat, increases attention to emotional information when passively inhaled, even in minute amounts. However, the neural mechanisms underlying androstadienone's impact on the perception of emotional stimuli have not been clarified. To characterize how the compound modifies neural circuitry while attending to emotional information, 22 subjects (11 women) underwent two fMRI scanning sessions, one with an androstadienone solution and one with a carrier control solution alone on their upper lip. During each session, participants viewed blocks of emotionally positive, negative, or neutral images. The BOLD response to emotional images (relative to neutral images) was greater during exposure to androstadienone in right orbitofrontal and lateral prefrontal cortex, particularly during positive image blocks. Androstadienone did not impact the response to social images, compared to nonsocial images, and results were not related to participant sex or olfactory sensitivity. To examine how androstadienone influences effective connectivity of this network, a dynamic causal model was employed with primary visual cortex (V1), amygdala, prefrontal cortex, and orbitofrontal cortex on each side. These models indicated that emotional images increased the drive from V1 to the amygdala during the control session. With androstadienone present, this drive to amygdala was decreased specifically for positive images, which drove downstream increases in orbitofrontal and prefrontal activity. This evidence suggests that androstadienone may act as a chemical signal to increase attention to positively valenced information via modifications to amygdala connectivity. Copyright © 2016. Published by Elsevier Ltd.

Sustained conditioned responses in prelimbic prefrontal neurons are correlated with fear expression and extinction failure.

PubMed

Burgos-Robles, Anthony; Vidal-Gonzalez, Ivan; Quirk, Gregory J

2009-07-01

During auditory fear conditioning, it is well established that lateral amygdala (LA) neurons potentiate their response to the tone conditioned stimulus, and that this potentiation is required for conditioned fear behavior. Conditioned tone responses in LA, however, last only a few hundred milliseconds and cannot be responsible for sustained fear responses to a tone lasting tens of seconds. Recent evidence from inactivation and stimulation studies suggests that the prelimbic (PL) prefrontal cortex is necessary for expression of learned fears, but the timing of PL tone responses and correlations with fear behavior have not been studied. Using multichannel unit recording techniques in behaving rats, we observed sustained conditioned tone responses in PL that were correlated with freezing behavior on a second-to-second basis during the presentation of a 30 s tone. PL tone responses were also correlated with conditioned freezing across different experimental phases (habituation, conditioning, extinction). Moreover, the persistence of PL responses after extinction training was associated with failure to express extinction memory. Together with previous inactivation findings, the present results suggest that PL transforms transient amygdala inputs to a sustained output that drives conditioned fear responses and gates the expression of extinction. Given the relatively long latency of conditioned responses we observed in PL (approximately 100 ms after tone onset), we propose that PL integrates inputs from the amygdala, hippocampus, and other cortical sources to regulate the expression of fear memories.

Longitudinal development of prefrontal function during early childhood.

PubMed

Moriguchi, Yusuke; Hiraki, Kazuo

2011-04-01

This is a longitudinal study on development of prefrontal function in young children. Prefrontal areas have been observed to develop dramatically during early childhood. To elucidate this development, we gave children cognitive shifting tasks related to prefrontal function at 3 years of age (Time 1) and 4 years of age (Time 2). We then monitored developmental changes in behavioral performance and examined prefrontal activation using near infrared spectroscopy. We found that children showed better behavioral performance and significantly stronger inferior prefrontal activation at Time 2 than they did at Time 1. Moreover, we demonstrated individual differences in prefrontal activation for the same behavioral tasks. Children who performed better in tasks at Time 1 showed significant activation of the right inferior prefrontal regions at Time 1 and significant activation of the bilateral inferior prefrontal regions at Time 2. Children who showed poorer performance at Time 1 exhibited no significant inferior prefrontal activation at Time 1 but significant left inferior prefrontal activation at Time 2. These results indicate the importance of the longitudinal method to address the link between cognitive and neural development. Copyright © 2011 Elsevier Ltd. All rights reserved.

Prefrontal activation in response to emotional words in patients with bipolar disorder and major depressive disorder.

PubMed

Matsubara, Toshio; Matsuo, Koji; Nakashima, Mami; Nakano, Masayuki; Harada, Kenichiro; Watanuki, Toshio; Egashira, Kazuteru; Watanabe, Yoshifumi

2014-01-15

Abnormal emotional processing is involved in the pathophysiology of bipolar disorder (BD) and major depressive disorder (MDD). However, whether the neural mechanism underlying this deficit is a trait characteristic of BD and MDD is unclear. The aim of this study was to elucidate the similarities and differences in processing of emotional stimuli between patients with BD and MDD in remission, using functional near-infrared spectroscopy (fNIRS). Thirty-two patients (16 with BD and 16 with MDD) and 20 healthy control subjects matched for age, sex, handedness, and years of education were included. An emotional Stroop task, including happy, sad, and threat words, was used. The relative oxygenated and deoxygenated hemoglobin concentration ([oxy-Hb] and [deoxy-Hb]) changes in the frontal region were measured using 52-channels of NIRS. During the threat task, compared to healthy control subjects, patients with BD showed significantly increased [oxy-Hb] in the left inferior frontal region whereas patients with MDD showed significantly increased [oxy-Hb] in the left middle frontal region. During the happy task, compared to healthy control subjects, patients with BD showed significantly decreased [oxy-Hb] in the middle frontal region in both hemispheres. Moreover, patients with BD exhibited decreased [oxy-Hb] and increased [deoxy-Hb] in the superior frontal and middle frontal regions compared to MDD in response to the happy stimulus. No significant differences in [oxy-Hb] or [deoxy-Hb] were seen between the groups during the sad task. These results suggest that abnormal neural responses to emotional stimuli in patients with mood disorders in remission may be a trait characteristic, that negative emotional stimuli are associated with similar prefrontal responses, and that positive emotional stimuli are associated with different prefrontal responses in patients with BD and MDD. These findings indicate that different neural circuits play a role in emotional processing in BD and MDD; this may aid the elucidation of the pathophysiology of these two disorders. Copyright © 2013 Elsevier Inc. All rights reserved.

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 magnitude of these neural effects was predictive of the behavioral effects (P ≤ .01). These findings provide the first neurobiological evidence for oxytocin's beneficial effects on sociocommunicational deficits of ASD and give us the initial account for neurobiological mechanisms underlying any beneficial effects of the neuropeptide. umin.ac.jp/ctr Identifier: UMIN000002241 and UMIN000004393.

Solving the Credit Assignment Problem With the Prefrontal Cortex

PubMed Central

Stolyarova, Alexandra

2018-01-01

In naturalistic multi-cue and multi-step learning tasks, where outcomes of behavior are delayed in time, discovering which choices are responsible for rewards can present a challenge, known as the credit assignment problem. In this review, I summarize recent work that highlighted a critical role for the prefrontal cortex (PFC) in assigning credit where it is due in tasks where only a few of the multitude of cues or choices are relevant to the final outcome of behavior. Collectively, these investigations have provided compelling support for specialized roles of the orbitofrontal (OFC), anterior cingulate (ACC), and dorsolateral prefrontal (dlPFC) cortices in contingent learning. However, recent work has similarly revealed shared contributions and emphasized rich and heterogeneous response properties of neurons in these brain regions. Such functional overlap is not surprising given the complexity of reciprocal projections spanning the PFC. In the concluding section, I overview the evidence suggesting that the OFC, ACC and dlPFC communicate extensively, sharing the information about presented options, executed decisions and received rewards, which enables them to assign credit for outcomes to choices on which they are contingent. This account suggests that lesion or inactivation/inhibition experiments targeting a localized PFC subregion will be insufficient to gain a fine-grained understanding of credit assignment during learning and instead poses refined questions for future research, shifting the focus from focal manipulations to experimental techniques targeting cortico-cortical projections. PMID:29636659

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.

Investigation of prefrontal cerebral hemodynamics during quantitative autonomic testing using NIRS (Conference Presentation)

NASA Astrophysics Data System (ADS)

Phillips, Zephaniah; Paik, Seung-Ho; Kim, Yoohwan; Kim, Byung-Jo; Choi, Youngwoon; Kim, Beop-Min

2017-02-01

In this work, we analyzed the clinical applicability of NIRS for use during Quantitative Autonomic Testing (QAT). QAT is a protocol consisting of deep breathing, Valsalva maneuver, and tilt table examination. It is used to diagnose a patient with disorders of the autonomic nervous system (ANS). Disorders of ANS includes orthostatic hyper/hypotension, vasovagal syncope, and postural orthostatic tachycardia syndrome. The results of QAT are typically analyzed with the use of blood pressure and heart rate data, however these metrics may be influenced by factors such as arrhythmia, making the data interpretation and diagnosis difficult for clinicians. We tested our custom built 108-channel NIRS probe on 26 elderly patients during the QAT protocol with various ANS disorders. We found that prefrontal cerebral oxygenation correlated well with blood pressure and heart rate changes for all three tasks, making it a clinically feasible tool for observing ANS functionality. During the Valsalva maneuver, we observed a longer delayed and lower amplitude response of cerebral oxygenation to the prefrontal area in orthostatic intolerant patients. During the tilt table examination, we saw a larger response in cerebral oxygenation and less equal transient cerebral oxygenation during tilt up and tilt down in tilt table examinations that were positive (unhealthy), compared to tilt table examinations that were negative (healthy). Overall, our study showcases NIRS as an enhanced tool for understanding ANS disorders.

Working-memory capacity protects model-based learning from stress

PubMed Central

Otto, A. Ross; Raio, Candace M.; Chiang, Alice; Phelps, Elizabeth A.; Daw, Nathaniel D.

2013-01-01

Accounts of decision-making have long posited the operation of separate, competing valuation systems in the control of choice behavior. Recent theoretical and experimental advances suggest that this classic distinction between habitual and goal-directed (or more generally, automatic and controlled) choice may arise from two computational strategies for reinforcement learning, called model-free and model-based learning. Popular neurocomputational accounts of reward processing emphasize the involvement of the dopaminergic system in model-free learning and prefrontal, central executive–dependent control systems in model-based choice. Here we hypothesized that the hypothalamic-pituitary-adrenal (HPA) axis stress response—believed to have detrimental effects on prefrontal cortex function—should selectively attenuate model-based contributions to behavior. To test this, we paired an acute stressor with a sequential decision-making task that affords distinguishing the relative contributions of the two learning strategies. We assessed baseline working-memory (WM) capacity and used salivary cortisol levels to measure HPA axis stress response. We found that stress response attenuates the contribution of model-based, but not model-free, contributions to behavior. Moreover, stress-induced behavioral changes were modulated by individual WM capacity, such that low-WM-capacity individuals were more susceptible to detrimental stress effects than high-WM-capacity individuals. These results enrich existing accounts of the interplay between acute stress, working memory, and prefrontal function and suggest that executive function may be protective against the deleterious effects of acute stress. PMID:24324166

The nexus between decision making and emotion regulation: a review of convergent neurocognitive substrates.

PubMed

Mitchell, Derek G V

2011-02-02

Emotional information, such as reward or punishment, gains rapid and often preferential access to neurocognitive resources. This ability to quickly evaluate and integrate emotion-related information is thought to benefit a range of behaviours critical for survival. Conversely, the improper use of, or preoccupation with, emotional information is associated with disruptions in functioning and psychiatric disorders. Optimally, an organism utilizes emotional information when it is significant, and minimizes its influence when it is not. Recently, similar regions of prefrontal cortex have been identified that are associated with regulating both behavioural conflict (motor response selection or inhibition) and affective conflict (emotional representation and awareness). In this review, data will be examined that concerns this convergence between decision making (modulating what we do) and emotion regulation (modulating how we feel) and an informal model will be proposed linking these processes at a neurocognitive level. The studies reviewed collectively support the conclusion that overlapping areas of prefrontal cortex perform similar computations whether the functional objective is to modulate an operant response, or an emotional one. Specifically, the idea is raised that key aspects of decision making and emotion regulation are bound by a common functional objective in which internal representations of conditioned stimuli and reinforcers are modulated to facilitate optimal behaviour or states. Emphasis is placed on dorsomedial, dorsolateral, ventrolateral, and ventromedial regions of prefrontal cortex. Copyright © 2010 Elsevier B.V. All rights reserved.

Effects of prefrontal rTMS on autonomic reactions to affective pictures.

PubMed

Berger, Christoph; Domes, Gregor; Balschat, Johannes; Thome, Johannes; Höppner, Jacqueline

2017-02-01

Repetitive transcranial magnetic stimulation (rTMS) can modulate the excitability of stimulated cortical areas, such as prefrontal areas involved in emotion regulation. Low frequency (LF) rTMS is expected to have inhibitory effects on prefrontal regions, and thereby should disinhibit limbic activity, resulting in enhanced emotional and autonomic reactions. For high frequency (HF) rTMS, the opposite pattern might be assumed. The objective of this study was to determine the effects of different rTMS frequencies applied to the right dlPFC on autonomic functions and on emotional perception. In a crossover design, two groups of 20 healthy young women were either stimulated with one session of LF rTMS (1 Hz) or one session of HF rTMS (10 Hz), compared to sham stimulation. We assessed phasic cardiac responses (PCR), skin conductance reactions (SCR), and emotional appraisal of emotional pictures as well as recognition memory after each rTMS application. After LF rTMS, PCR (heart rate deceleration) during presentation of pictures with negative and neutral valence was significantly increased compared to the presentation of positive pictures. In contrast, the modulatory effect of picture valence and arousal on the cardiac orienting response was absent after HF rTMS. Our results suggest that frontal LF rTMS indirectly activates the ANS via inhibition of the right dlPFC activity, likely by enhancing the sensory processing or attention to aversive and neutral stimuli.

Dissociable Brain States Linked to Common and Creative Object Use

PubMed Central

Chrysikou, Evangelia G.; Thompson-Schill, Sharon L.

2013-01-01

Studies of conceptual processing have revealed that the prefrontal cortex is implicated in close-ended, deliberate memory retrieval, especially the left ventrolateral prefrontal regions. However, much of human thought—particularly that which is characterized as creative—requires more open-ended, spontaneous memory retrieval. To explore the neural systems that support conceptual processing under these two distinct circumstances, we obtained functional magnetic resonance images from 24 participants either while retrieving the common use of an everyday object (e.g., “blowing your nose,” in response to a picture of a tissue) or while generating a creative (i.e., uncommon but plausible) use for it (e.g., “protective padding in a package”). The patterns of activation during open- and closed-ended tasks were reliably different, with regard to the magnitude of anterior versus posterior activation. Specifically, the close-ended task (i.e., Common Use task) reliably activated regions of lateral prefrontal cortex, whereas the open-ended task (i.e., Uncommon Use task) reliably activated regions of occipito-temporal cortex. Furthermore, there was variability across subjects in the types of responses produced on the open-ended task that was associated with the magnitude of activation in the middle occipital gyrus on this task. The present experiment is the first to demonstrate a dynamic tradeoff between anterior frontal and posterior occipitotemporal regions brought about by the close- or open-ended task demands. PMID:20533561

A Pilot Study of the Effects of Mindfulness-Based Stress Reduction on Post-traumatic Stress Disorder Symptoms and Brain Response to Traumatic Reminders of Combat in Operation Enduring Freedom/Operation Iraqi Freedom Combat Veterans with Post-traumatic Stress Disorder.

PubMed

Bremner, James Douglas; Mishra, Sanskriti; Campanella, Carolina; Shah, Majid; Kasher, Nicole; Evans, Sarah; Fani, Negar; Shah, Amit Jasvant; Reiff, Collin; Davis, Lori L; Vaccarino, Viola; Carmody, James

2017-01-01

Brain imaging studies in patients with post-traumatic stress disorder (PTSD) have implicated a circuitry of brain regions including the medial prefrontal cortex, amygdala, hippocampus, parietal cortex, and insula. Pharmacological treatment studies have shown a reversal of medial prefrontal deficits in response to traumatic reminders. Mindfulness-based stress reduction (MBSR) is a promising non-pharmacologic approach to the treatment of anxiety and pain disorders. The purpose of this study was to assess the effects of MBSR on PTSD symptoms and brain response to traumatic reminders measured with positron-emission tomography (PET) in Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) combat veterans with PTSD. We hypothesized that MBSR would show increased prefrontal response to stress and improved PTSD symptoms in veterans with PTSD. Twenty-six OEF/OIF combat veterans with PTSD who had recently returned from a combat zone were block randomized to receive eight sessions of MBSR or present-centered group therapy (PCGT). PTSD patients underwent assessment of PTSD symptoms with the Clinician-Administered PTSD Scale (CAPS), mindfulness with the Five Factor Mindfulness Questionnaire (FFMQ) and brain imaging using PET in conjunction with exposure to neutral and Iraq combat-related slides and sound before and after treatment. Nine patients in the MBSR group and 8 in the PCGT group completed all study procedures. Post-traumatic stress disorder patients treated with MBSR (but not PCGT) had an improvement in PTSD symptoms measured with the CAPS that persisted for 6 months after treatment. MBSR also resulted in an increase in mindfulness measured with the FFMQ. MBSR-treated patients had increased anterior cingulate and inferior parietal lobule and decreased insula and precuneus function in response to traumatic reminders compared to the PCGT group. This study shows that MBSR is a safe and effective treatment for PTSD. Furthermore, MBSR treatment is associated with changes in brain regions that have been implicated in PTSD and are involved in extinction of fear responses to traumatic memories as well as regulation of the stress response.

The Dorsal Medial Prefrontal Cortex Responds Preferentially to Social Interactions during Natural Viewing.

PubMed

Wagner, Dylan D; Kelley, William M; Haxby, James V; Heatherton, Todd F

2016-06-29

Humans display a strong tendency to make spontaneous inferences concerning the thoughts and intentions of others. Although this ability relies upon the concerted effort of multiple brain regions, the dorsal medial prefrontal cortex (DMPFC) is most closely associated with the ability to reason about other people's mental states and form impressions of their character. Here, we investigated this region's putative social category preference using fMRI as 34 participants engaged in uninstructed viewing of a complex naturalistic stimulus. Using a data-driven "reverse correlation" approach, we characterize the DMPFC's stimulus response profile from ongoing neural responses to a dynamic movie stimulus. Results of this analysis demonstrate that the DMPFC's response profile is dominated by the presence of scenes involving social interactions between characters. Subsequent content analysis of video clips created from this response profile confirmed this finding. In contrast, regions of the inferotemporal and parietal cortex were selectively tuned to faces and actions, both features that often covary with social interaction but may be difficult to disentangle using standard event-related approaches. Together, these findings suggest that the DMPFC is finely tuned for processing social interaction above other categories and that this preference is maintained during unrestricted viewing of complex natural stimuli such as movies. Recently, studies have brought into question whether the dorsal medial prefrontal cortex (DMPFC), a region long associated with social cognition, is specialized for the processing of social information. We examine the response profile of this region during natural viewing of a reasonably naturalistic stimulus (i.e., a Hollywood movie) using a data-driven reverse correlation technique. Our findings demonstrate that, during natural viewing, the DMPFC is strongly tuned to the social features of the stimulus above other categories. Moreover, this response differs from other areas with previously well characterized response profiles such as the lateral and medial fusiform gyrus. These findings suggest that this region's dominant function in everyday situations is to support reasoning about the thoughts and intentions of conspecifics. Copyright © 2016 the authors 0270-6474/16/366917-09$15.00/0.

The Dorsal Medial Prefrontal Cortex Responds Preferentially to Social Interactions during Natural Viewing

PubMed Central

Kelley, William M.; Haxby, James V.; Heatherton, Todd F.

2016-01-01

Humans display a strong tendency to make spontaneous inferences concerning the thoughts and intentions of others. Although this ability relies upon the concerted effort of multiple brain regions, the dorsal medial prefrontal cortex (DMPFC) is most closely associated with the ability to reason about other people's mental states and form impressions of their character. Here, we investigated this region's putative social category preference using fMRI as 34 participants engaged in uninstructed viewing of a complex naturalistic stimulus. Using a data-driven “reverse correlation” approach, we characterize the DMPFC's stimulus response profile from ongoing neural responses to a dynamic movie stimulus. Results of this analysis demonstrate that the DMPFC's response profile is dominated by the presence of scenes involving social interactions between characters. Subsequent content analysis of video clips created from this response profile confirmed this finding. In contrast, regions of the inferotemporal and parietal cortex were selectively tuned to faces and actions, both features that often covary with social interaction but may be difficult to disentangle using standard event-related approaches. Together, these findings suggest that the DMPFC is finely tuned for processing social interaction above other categories and that this preference is maintained during unrestricted viewing of complex natural stimuli such as movies. SIGNIFICANCE STATEMENT Recently, studies have brought into question whether the dorsal medial prefrontal cortex (DMPFC), a region long associated with social cognition, is specialized for the processing of social information. We examine the response profile of this region during natural viewing of a reasonably naturalistic stimulus (i.e., a Hollywood movie) using a data-driven reverse correlation technique. Our findings demonstrate that, during natural viewing, the DMPFC is strongly tuned to the social features of the stimulus above other categories. Moreover, this response differs from other areas with previously well characterized response profiles such as the lateral and medial fusiform gyrus. These findings suggest that this region's dominant function in everyday situations is to support reasoning about the thoughts and intentions of conspecifics. PMID:27358450

Modification of persistent responses in medial prefrontal cortex during learning in trace eyeblink conditioning

PubMed Central

2014-01-01

Persistent spiking in response to a discrete stimulus is considered to reflect the active maintenance of a memory for that stimulus until a behavioral response is made. This response pattern has been reported in learning paradigms that impose a temporal gap between stimulus presentation and behavioral response, including trace eyeblink conditioning. However, it is unknown whether persistent responses are acquired as a function of learning or simply represent an already existing category of response type. This fundamental question was addressed by recording single-unit activity in the medial prefrontal cortex (mPFC) of rabbits during the initial learning phase of trace eyeblink conditioning. Persistent responses to the tone conditioned stimulus were observed in the mPFC during the very first training sessions. Further analysis revealed that most cells with persistent responses showed this pattern during the very first training trial, before animals had experienced paired training. However, persistent cells showed reliable decreases in response magnitude over the first training session, which were not observed on the second day of training or for sessions in which learning criterion was met. This modification of response magnitude was specific to persistent responses and was not observed for cells showing phasic tone-evoked responses. The data suggest that persistent responses to discrete stimuli do not require learning but that the ongoing robustness of such responses over the course of training is modified as a result of experience. Putative mechanisms for this modification are discussed, including changes in cellular or network properties, neuromodulatory tone, and/or the synaptic efficacy of tone-associated inputs. PMID:25080570

Insulin sensitivity affects corticolimbic brain responses to visual food cues in polycystic ovary syndrome patients.

PubMed

Alsaadi, Hanin M; Van Vugt, Dean A

2015-11-01

This study examined the effect of insulin sensitivity on the responsiveness of appetite regulatory brain regions to visual food cues. Nineteen participants diagnosed with polycystic ovary syndrome (PCOS) were divided into insulin-sensitive (n=8) and insulin-resistant (n=11) groups based on the homeostatic model assessment of insulin resistance (HOMA2-IR). Subjects underwent functional magnetic resonance imaging (fMRI) while viewing food pictures following water or dextrose consumption. The corticolimbic blood oxygen level dependent (BOLD) responses to high-calorie (HC) or low-calorie (LC) food pictures were compared within and between groups. BOLD responses to food pictures were reduced during a glucose challenge in numerous corticolimbic brain regions in insulin-sensitive but not insulin-resistant subjects. Furthermore, the degree of insulin resistance positively correlated with the corticolimbic BOLD response in the medial prefrontal cortex (mPFC), orbitofrontal cortex (OFC), anterior cingulate and ventral tegmental area (VTA) in response to HC pictures, and in the dorsolateral prefrontal cortex (DLPFC), mPFC, anterior cingulate, and insula in response to LC pictures following a glucose challenge. BOLD signal in the OFC, midbrain, hippocampus, and amygdala following a glucose challenge correlated with HOMA2-IR in response to HC-LC pictures. We conclude that the normal inhibition of corticolimbic brain responses to food pictures during a glucose challenge is compromised in insulin-resistant subjects. The increase in brain responsiveness to food pictures during postprandial hyperinsulinemia may lead to greater non-homeostatic eating and perpetuate obesity in insulin-resistant subjects.

Experience-Dependent Effects of Cocaine Self-Administration/Conditioning on Prefrontal and Accumbens Dopamine Responses

PubMed Central

Ikegami, Aiko; Olsen, Christopher M.; D’Souza, Manoranjan S.; Duvauchelle, Christine L.

2008-01-01

Experiments were performed to examine the effects of cocaine self-administration and conditioning experience on operant behavior, locomotor activity, and nucleus accumbens (NAcc) and prefrontal cortex (PFC) dopamine (DA) responses. Sensory cues were paired with alternating cocaine and nonreinforcement during 12 (limited training) or 40 (long-term training) daily operant sessions. After limited training, NAcc DA responses to cocaine were significantly enhanced in the presence of cocaine-associated cues compared with nonreward cues and significantly depressed after cocaine-paired cues accompanied a nonreinforced lever response. PFC DA levels were generally nonresponsive to cues after the same training duration. However, after long-term training, cocaine-associated cues increased the magnitude of cocaine-stimulated PFC DA levels significantly over levels observed with nonreinforcement cues. Conversely, conditioned cues no longer influenced NAcc DA levels after long-term training. In addition, cocaine-stimulated locomotor activity was enhanced by cocaine-paired cues after long-term, but not after limited, training. Findings demonstrate that cue-induced cocaine expectation exerts a significant impact on dopaminergic and behavioral systems, progressing from mesolimbic to mesocortical regions and from latent to patent behaviors as cocaine and associative experiences escalate. PMID:17469929

Synaptic Modifications in the Medial Prefrontal Cortex in Susceptibility and Resilience to Stress

PubMed Central

Wang, Minghui; Perova, Zinaida; Arenkiel, Benjamin R.

2014-01-01

When facing stress, most individuals are resilient whereas others are prone to developing mood disorders. The brain mechanisms underlying such divergent behavioral responses remain unclear. Here we used the learned helplessness procedure in mice to examine the role of the medial prefrontal cortex (mPFC), a brain region highly implicated in both clinical and animal models of depression, in adaptive and maladaptive behavioral responses to stress. We found that uncontrollable and inescapable stress induced behavioral state-dependent changes in the excitatory synapses onto a subset of mPFC neurons: those that were activated during behavioral responses as indicated by their expression of the activity reporter c-Fos. Whereas synaptic potentiation was linked to learned helplessness, a depression-like behavior, synaptic weakening, was associated with resilience to stress. Notably, enhancing the activity of mPFC neurons using a chemical–genetic method was sufficient to convert the resilient behavior into helplessness. Our results provide direct evidence that mPFC dysfunction is linked to maladaptive behavioral responses to stress, and suggest that enhanced excitatory synaptic drive onto mPFC neurons may underlie the previously reported hyperactivity of this brain region in depression. PMID:24872553

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

Three months of resistance training in overweight and obese individuals improves reactive balance control under unstable conditions.

PubMed

Zemková, Erika; Kyselovičová, Ol'ga; Jeleň, Michal; Kováčiková, Zuzana; Ollé, Gábor; Řtefániková, Gabriela; Vilman, Tomáš; Baláž, Miroslav; Kurdiová, Timea; Ukropec, Jozef; Ukropcová, Barbara

2017-01-01

Contrary to static and dynamic balance, there is a lack of scientific evidence on the training induced changes in reactive balance control in response to unexpected perturbations in overweight and obese individuals. This study evaluates the effect of 3 months of resistance and aerobic training programs on postural responses to unexpected perturbations under stable and unstable conditions in the overweight and obese. A group of 17 overweight and obese subjects, divided into two groups, underwent either resistance or aerobic training for a period of 3 months (3 sessions per week). Prior to and after completing the training, they performed the load release balance test while standing on either a stable or unstable surface, with eyes open and closed. Peak posterior center of pressure (CoP) displacement, and the time to peak posterior CoP displacement during a bipedal stance on a foam surface with eyes open (17.3%, p = 0.019 and 15.4%, p = 0.029) and eyes closed (15.0%, p = 0.027 and 13.2%, p = 0.034), decreased significantly. In addition, the total anterior to posterior CoP displacement, and the time from peak anterior to peak posterior CoP displacement, both with eyes open (18.1%, p = 0.017 and 12.2%, p = 0.040) and eyes closed (16.3%, p = 0.023 and 11.7%, p = 0.044), also significantly decreased. However, after completing the resistance training, the parameters registered while standing on a stable platform, both with eyes open and closed, did not change significantly. The group that underwent an aerobic training also failed to show any significant changes in parameters of the load release balance test. Three months of resistance training in overweight and obese subjects improves reactive balance control in response to unexpected perturbations under unstable conditions, both with and without visual cues. Due to the fact that this unstable load release balance test was found to be sensitive in revealing post-training changes, it would be suitable for implementing in the functional diagnostic for this group, in addition to complementing existing testing methods.

[Decision Making and Electrodermal Activity].

PubMed

Kobayakawa, Mutsutaka

2016-08-01

Decision making is aided by emotions. Bodily responses, such as sweating, heartbeat, and visceral sensation, are used to monitor the emotional state during decision making. Because decision making in dairy life is complicated and cognitively demanding, these bodily signals are thought to facilitate the decision making process by assigning positive or negative values for each of the behavioral options. The sweat response in a decision making task is measured by skin conductance response (SCR). SCR in decision making is divided into two categories: anticipatory SCR is observed before making decisions, and reward/punishment SCR is observed after the outcome of the decision is perceived. Brain lesion studies in human revealed that the amygdala and ventromedial prefrontal cortex are important in decision making. Patients with lesinon in the amygdala exhibit neither the anticipatory nor reward/punishment SCRs, while patients with the ventromedial prefrontal lesions have deficits only in the anticipatory SCRs. Decision making tasks and SCR analysis have contributed to reveal the implicit aspects of decision making. Further research is necessary for clarifying the role of explicit process of decision making and its relationship with the implicit process.

Human Subthalamic Nucleus Theta and Beta Oscillations Entrain Neuronal Firing During Sensorimotor Conflict

PubMed Central

Zavala, Baltazar; Damera, Srikanth; Dong, Jian Wilson; Lungu, Codrin; Brown, Peter; Zaghloul, Kareem A.

2017-01-01

Recent evidence has suggested that prefrontal cortical structures may inhibit impulsive actions during conflict through activation of the subthalamic nucleus (STN). Consistent with this hypothesis, deep brain stimulation to the STN has been associated with altered prefrontal cortical activity and impaired response inhibition. The interactions between oscillatory activity in the STN and its presumably antikinetic neuronal spiking, however, remain poorly understood. Here, we simultaneously recorded intraoperative local field potential and spiking activity from the human STN as participants performed a sensorimotor action selection task involving conflict. We identified several STN neuronal response types that exhibited different temporal dynamics during the task. Some neurons showed early, cue-related firing rate increases that remained elevated longer during high conflict trials, whereas other neurons showed late, movement-related firing rate increases. Notably, the high conflict trials were associated with an entrainment of individual neurons by theta- and beta-band oscillations, both of which have been observed in cortical structures involved in response inhibition. Our data suggest that frequency-specific activity in the beta and theta bands influence STN firing to inhibit impulsivity during conflict. PMID:26494798

Impacts of religious semantic priming on an intertemporal discounting task: Response time effects and neural correlates.

PubMed

Morgan, Jonathan; Clark, Dustin; Tripodis, Yorghos; Halloran, Christopher S; Minsky, April; Wildman, Wesley J; Durso, Raymon; McNamara, Patrick

2016-08-01

The purpose of this study is to test the hypothesis that religious primes would influence intertemporal discounting behaviors in neurotypical older adults, but not in participants with Parkinson's disease (PD). Furthermore, we predicted that this priming effect would be related to functional connectivity within neural networks mediating religious cognition, decision-making, reward valuing, and prospection processes. Contrary to past research with young adults, we found a significant positive relationship between religiosity and discounting rates. Religious semantic primes did not reliably shift individual discounting rates. But religious controls did respond more quickly to intertemporal decisions under the religious priming condition than the neutral condition, compared to response time differences among the participants with PD. Differences in response time were significantly associated with functional connectivity between the nucleus accumbens and various regions, including the left anterior cingulate cortex and Brodmann areas 10 and 46 in the right dorsolateral prefrontal cortex. These results suggest that religious primes influence discounting behavior via dopaminergic meso-limbic and right dorsolateral prefrontal supporting cognitive valuation and prospection processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Self-esteem modulates amygdala-ventrolateral prefrontal cortex connectivity in response to mortality threats.

PubMed

Yanagisawa, Kuniaki; Abe, Nobuhito; Kashima, Emiko S; Nomura, Michio

2016-03-01

Reminders of death often elicit defensive responses in individuals, especially among those with low self-esteem. Although empirical evidence indicates that self-esteem serves as a buffer against mortality threats, the precise neural mechanism underlying this effect remains unknown. We used functional magnetic resonance imaging (fMRI) to test the hypothesis that self-esteem modulates neural responses to death-related stimuli, especially functional connectivity within the limbic-frontal circuitry, thereby affecting subsequent defensive reactions. As predicted, individuals with high self-esteem subjected to a mortality threat exhibited increased amygdala-ventrolateral prefrontal cortex (VLPFC) connectivity during the processing of death-related stimuli compared with individuals who have low self-esteem. Further analysis revealed that stronger functional connectivity between the amygdala and the VLPFC predicted a subsequent decline in responding defensively to those who threaten one's beliefs. These results suggest that the amygdala-VLPFC interaction, which is modulated by self-esteem, can reduce the defensiveness caused by death-related stimuli, thereby providing a neural explanation for why individuals with high self-esteem exhibit less defensive reactions to mortality threats. (c) 2016 APA, all rights reserved).

From rule to response: neuronal processes in the premotor and prefrontal cortex.

PubMed

Wallis, Jonathan D; Miller, Earl K

2003-09-01

The ability to use abstract rules or principles allows behavior to generalize from specific circumstances (e.g., rules learned in a specific restaurant can subsequently be applied to any dining experience). Neurons in the prefrontal cortex (PFC) encode such rules. However, to guide behavior, rules must be linked to motor responses. We investigated the neuronal mechanisms underlying this process by recording from the PFC and the premotor cortex (PMC) of monkeys trained to use two abstract rules: "same" or "different." The monkeys had to either hold or release a lever, depending on whether two successively presented pictures were the same or different, and depending on which rule was in effect. The abstract rules were represented in both regions, although they were more prevalent and were encoded earlier and more strongly in the PMC. There was a perceptual bias in the PFC, relative to the PMC, with more PFC neurons encoding the presented pictures. In contrast, neurons encoding the behavioral response were more prevalent in the PMC, and the selectivity was stronger and appeared earlier in the PMC than in the PFC.

Response contingency directs long-term cocaine-induced neuroplasticity in prefrontal and striatal dopamine terminals.

PubMed

Wiskerke, Joost; Schoffelmeer, Anton N M; De Vries, Taco J

2016-10-01

Exposure to addictive substances such as cocaine is well-known to alter brain organisation. Cocaine-induced neuroadaptations depend on several factors, including drug administration paradigm. To date, studies addressing the consequences of cocaine exposure on dopamine transmission have either not been designed to investigate the role of response contingency or focused only on short-term neuroplasticity. We demonstrate a key role of response contingency in directing long-term cocaine-induced neuroplasticity throughout projection areas of the mesocorticolimbic dopamine system. We found enhanced electrically-evoked [(3)H]dopamine release from superfused brain slices of nucleus accumbens shell and core, dorsal striatum and medial prefrontal cortex three weeks after cessation of cocaine self-administration. In yoked cocaine rats receiving the same amount of cocaine passively, sensitised dopamine terminal reactivity was only observed in the nucleus accumbens core. Control sucrose self-administration experiments demonstrated that the observed neuroadaptations were not the result of instrumental learning per se. Thus, long-term withdrawal from cocaine self-administration is associated with widespread sensitisation of dopamine terminals throughout frontostriatal circuitries. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Object recognition impairment in Fmr1 knockout mice is reversed by amphetamine: involvement of dopamine in the medial prefrontal cortex.

PubMed

Ventura, R; Pascucci, T; Catania, M V; Musumeci, S A; Puglisi-Allegra, S

2004-09-01

Fragile X syndrome is an X-linked form of mental retardation including, among others, symptoms such as stereotypic behaviour, hyperactivity, hyperarousal, and cognitive deficits. We hypothesized that hyperactivity and/or compromised attentional, cognitive functions may lead to impaired performance in cognitive tasks in Fmr1 knockout mice, the most widely used animal model of fragile X syndrome, and suggested that psychostimulant treatment may improve performance by acting on one or both components. Since hyperactivity and cognitive functions have been suggested to depend on striatal and prefrontal cortex dopaminergic dysfunction, we assessed whether amphetamine produced beneficial, positive effects by acting on dopaminergic corticostriatal systems. Our results show that Fmr1 knockout mice are not able to discriminate between a familiar object and a novel one in the object recognition test, thus showing a clear-cut cognitive impairment that, to date, has been difficult to demonstrate in other cognitive tasks. Amphetamine improved performance of Fmr1 knockout mice, leading to enhanced ability to discriminate novel versus familiar objects, without significantly affecting locomotor activity. In agreement with behavioural data, amphetamine produced a greater increase in dopamine release in the prefrontal cortex of Fmr1 knockout compared with the wild-type mice, while a weak striatal dopaminergic response was observed in Fmr1 knockout mice. Our data support the view that the psychostimulant ameliorates performance in Fmr1 knockout mice by improving merely cognitive functions through its action on prefrontal cortical dopamine, irrespective of its action on motor hyperactivity. These results indicate that prefrontal cortical dopamine plays a major role in cognitive impairments characterizing Fmr1 knockout mice, thus pointing to an important aetiological factor in the fragile X syndrome.

White matter integrity between left basal ganglia and left prefrontal cortex is compromised in gambling disorder.

PubMed

van Timmeren, Tim; Jansen, Jochem M; Caan, Matthan W A; Goudriaan, Anna E; van Holst, Ruth J

2017-11-01

Pathological gambling (PG) is a behavioral addiction characterized by an inability to stop gambling despite the negative consequences, which may be mediated by cognitive flexibility deficits. Indeed, impaired cognitive flexibility has previously been linked to PG and also to reduced integrity of white matter connections between the basal ganglia and the prefrontal cortex. It remains unclear, however, how white matter integrity problems relate to cognitive inflexibility seen in PG. We used a cognitive switch paradigm during functional magnetic resonance imaging in pathological gamblers (PGs; n = 26) and healthy controls (HCs; n = 26). Cognitive flexibility performance was measured behaviorally by accuracy and reaction time on the switch task, while brain activity was measured in terms of blood oxygen level-dependent responses. We also used diffusion tensor imaging on a subset of data (PGs = 21; HCs = 21) in combination with tract-based spatial statistics and probabilistic fiber tracking to assess white matter integrity between the basal ganglia and the dorsolateral prefrontal cortex. Although there were no significant group differences in either task performance, related neural activity or tract-based spatial statistics, PGs did show decreased white matter integrity between the left basal ganglia and prefrontal cortex. Our results complement and expand similar findings from a previous study in alcohol-dependent patients. Although we found no association between white matter integrity and task performance here, decreased white matter connections may contribute to a diminished ability to recruit prefrontal networks needed for regulating behavior in PG. Hence, our findings could resonate an underlying risk factor for PG, and we speculate that these findings may extend to addiction in general. © 2016 Society for the Study of Addiction.

Segregated fronto‐cortical and midbrain connections in the mouse and their relation to approach and avoidance orienting behaviors

PubMed Central

Savage, Michael Anthony; McQuade, Richard

2017-01-01

Abstract The orchestration of orienting behaviors requires the interaction of many cortical and subcortical areas, for example the superior colliculus (SC), as well as prefrontal areas responsible for top–down control. Orienting involves different behaviors, such as approach and avoidance. In the rat, these behaviors are at least partially mapped onto different SC subdomains, the lateral (SCl) and medial (SCm), respectively. To delineate the circuitry involved in the two types of orienting behavior in mice, we injected retrograde tracer into the intermediate and deep layers of the SCm and SCl, and thereby determined the main input structures to these subdomains. Overall the SCm receives larger numbers of afferents compared to the SCl. The prefrontal cingulate area (Cg), visual, oculomotor, and auditory areas provide strong input to the SCm, while prefrontal motor area 2 (M2), and somatosensory areas provide strong input to the SCl. The prefrontal areas Cg and M2 in turn connect to different cortical and subcortical areas, as determined by anterograde tract tracing. Even though connectivity pattern often overlap, our labeling approaches identified segregated neural circuits involving SCm, Cg, secondary visual cortices, auditory areas, and the dysgranular retrospenial cortex likely to be involved in avoidance behaviors. Conversely, SCl, M2, somatosensory cortex, and the granular retrospenial cortex comprise a network likely involved in approach/appetitive behaviors. PMID:28177526

Benefits of physical exercise on the aging brain: the role of the prefrontal cortex.

PubMed

Berchicci, Marika; Lucci, Giuliana; Di Russo, Francesco

2013-11-01

Motor planning in older adults likely relies on the overengagement of the prefrontal cortex (PFC) and is associated with slowness of movement and responses. Does a physically active lifestyle counteract the overrecruitment of the PFC during action preparation? This study used high-resolution electroencephalography to measure the effect of physical exercise on the executive functions of the PFC preceding a visuomotor discriminative task. A total of 130 participants aged 15-86 were divided into two groups based on physical exercise participation. The response times and accuracy and the premotor activity of the PFC were separately correlated with age for the two groups. The data were first fit with a linear function and then a higher order polynomial function. We observed that after 35-40 years of age, physically active individuals have faster response times than their less active peers and showed no signs of PFC hyperactivity during motor planning. The present findings show that physical exercise could speed up the response of older people and reveal that also in middle-aged people, moderate-to-high levels of physical exercise benefits the planning/execution of a response and the executive functions mediated by the PFC, counteracting the neural overactivity often observed in the elderly adults.

Cocaine-conditioned odor cues without chronic exposure: Implications for the development of addiction vulnerability.

PubMed

Lowen, Steven B; Rohan, Michael L; Gillis, Timothy E; Thompson, Britta S; Wellons, Clara B W; Andersen, Susan L

2015-01-01

Adolescents are highly vulnerable to addiction and are four times more likely to become addicted at first exposure than at any other age. The dopamine D1 receptor, which is typically overexpressed in the normal adolescent prefrontal cortex, is involved in drug cue responses and is associated with relapse in animal models. In human drug addicts, imaging methods have detected increased activation in response to drug cues in reward- and habit-associated brain regions. These same methods can be applied more quantitatively to rodent models. Here, changes in neuronal activation in response to cocaine-conditioned cues were observed using functional magnetic resonance imaging in juvenile rats that were made to over-express either D1 receptors or green fluorescent protein by viral-mediated transduction. Reduced activation was observed in the amygdala and dopamine cell body regions in the low cue-preferring/control juvenile rats in response to cocaine cues. In contrast, increased activation was observed in the dorsal striatum, nucleus accumbens, prefrontal cortex, and dopamine cell bodies in high cue-preferring/D1 juveniles. The increase in cue salience that is mediated by increased D1 receptor density, rather than excessive cocaine experience, appears to underlie the transition from aversion to reward in cue-induced neural response and may form the basis for habit-forming vulnerability.

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.

Differential contributions of dorso-ventral and rostro-caudal prefrontal white matter tracts to cognitive control in healthy older adults.

PubMed

Strenziok, Maren; Greenwood, Pamela M; Santa Cruz, Sophia A; Thompson, James C; Parasuraman, Raja

2013-01-01

Prefrontal cortex mediates cognitive control by means of circuitry organized along dorso-ventral and rostro-caudal axes. Along the dorso-ventral axis, ventrolateral PFC controls semantic information, whereas dorsolateral PFC encodes task rules. Along the rostro-caudal axis, anterior prefrontal cortex encodes complex rules and relationships between stimuli, whereas posterior prefrontal cortex encodes simple relationships between stimuli and behavior. Evidence of these gradients of prefrontal cortex organization has been well documented in fMRI studies, but their functional correlates have not been examined with regard to integrity of underlying white matter tracts. We hypothesized that (a) the integrity of specific white matter tracts is related to cognitive functioning in a manner consistent with the dorso-ventral and rostro-caudal organization of the prefrontal cortex, and (b) this would be particularly evident in healthy older adults. We assessed three cognitive processes that recruit the prefrontal cortex and can distinguish white matter tracts along the dorso-ventral and rostro-caudal dimensions -episodic memory, working memory, and reasoning. Correlations between cognition and fractional anisotropy as well as fiber tractography revealed: (a) Episodic memory was related to ventral prefrontal cortex-thalamo-hippocampal fiber integrity; (b) Working memory was related to integrity of corpus callosum body fibers subserving dorsolateral prefrontal cortex; and (c) Reasoning was related to integrity of corpus callosum body fibers subserving rostral and caudal dorsolateral prefrontal cortex. These findings confirm the ventrolateral prefrontal cortex's role in semantic control and the dorsolateral prefrontal cortex's role in rule-based processing, in accordance with the dorso-ventral prefrontal cortex gradient. Reasoning-related rostral and caudal superior frontal white matter may facilitate different levels of task rule complexity. This study is the first to demonstrate dorso-ventral and rostro-caudal prefrontal cortex processing gradients in white matter integrity.

Recovery of sediment characteristics in moraine, headwater streams of northern Minnesota after forest harvest

USGS Publications Warehouse

Vondracek, Bruce C.; Merten, Eric C.; Hemstad, Nathaniel A.; Kolka, Randall K.; Newman, Raymond M.; Verry, Elon S.

2010-01-01

We investigated the recovery of sediment characteristics in four moraine, headwater streams in north-central Minnesota after forest harvest. We examined changes in fine sediment levels from 1997 (preharvest) to 2007 (10 years postharvest) at study plots with upland clear felling and riparian thinning, using canopy cover, proportion of unstable banks, surficial fine substrates, residual pool depth, and streambed depth of refusal as response variables. Basin-scale year effects were significant (p < 0.001) for all responses when evaluated by repeated-measures ANOVAs. Throughout the study area, unstable banks increased for several years postharvest, coinciding with an increase in windthrow and fine sediment. Increased unstable banks may have been caused by forest harvest equipment, increased windthrow and exposure of rootwads, or increased discharge and bank scour. Fine sediment in the channels did not recover by summer 2007, even though canopy cover and unstable banks had returned to 1997 levels. After several storm events in fall 2007, 10 years after the initial sediment input, fine sediment was flushed from the channels and returned to 1997 levels. Although our study design did not discern the source of the initial sediment inputs (e.g., forest harvest, road crossings, other natural causes), we have shown that moraine, headwater streams can require an extended period (up to 10 years) and enabling event (e.g., high storm flows) to recover from large inputs of fine sediment.

Recovery of sediment characteristics in moraine, headwater streams of Northern Minnesota after forest harvest

USGS Publications Warehouse

Merten, Eric C.; Hemstad, Nathaniel A.; Kolka, Randall K.; Newman, Raymond M.; Verry, Elon S.; Vondracek, Bruce C.

2010-01-01

We investigated the recovery of sediment characteristics in four moraine, headwater streams in north-central Minnesota after forest harvest. We examined changes in fine sediment levels from 1997 (preharvest) to 2007 (10 years postharvest) at study plots with upland clear felling and riparian thinning, using canopy cover, proportion of unstable banks, surficial fine substrates, residual pool depth, and streambed depth of refusal as response variables. Basin-scale year effects were significant (p < 0.001) for all responses when evaluated by repeated-measures ANOVAs. Throughout the study area, unstable banks increased for several years postharvest, coinciding with an increase in windthrow and fine sediment. Increased unstable banks may have been caused by forest harvest equipment, increased windthrow and exposure of rootwads, or increased discharge and bank scour. Fine sediment in the channels did not recover by summer 2007, even though canopy cover and unstable banks had returned to 1997 levels. After several storm events in fall 2007, 10 years after the initial sediment input, fine sediment was flushed from the channels and returned to 1997 levels. Although our study design did not discern the source of the initial sediment inputs (e.g., forest harvest, road crossings, other natural causes), we have shown that moraine, headwater streams can require an extended period (up to 10 years) and enabling event (e.g., high storm flows) to recover from large inputs of fine sediment.

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

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 cocaine self-administration in rats leads to decrements in medial prefrontal structural and functional plasticity. Notably, these impairments were largely accounted for in rats that self-administered cocaine compared with yoked counterparts. Moreover, we verified previous reports showing that adrenocortical output is augmented by cocaine administration and is more protracted in rats that were permitted to receive the drug contingently instead of passively. These studies suggest that increased adrenocortical activity resulting from cocaine self-administration may contribute to regressive prefrontal structural and functional plasticity. PMID:26311772

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 in WM performance. This suggests that the parasympathetic and sympathetic branches respond differentially due to similar, but distinct neural pathways. Given the ease of HRV data collection, studies of prefrontal tDCS would benefit from collection of this data as it provides unique insight into tDCS effects resulting from propagation through brain networks. PMID:28771509

Chaos in driven Alfvén systems: unstable periodic orbits and chaotic saddles

NASA Astrophysics Data System (ADS)

Chian, A. C.-L.; Santana, W. M.; Rempel, E. L.; Borotto, F. A.; Hada, T.; Kamide, Y.

2007-01-01

The chaotic dynamics of Alfvén waves in space plasmas governed by the derivative nonlinear Schrödinger equation, in the low-dimensional limit described by stationary spatial solutions, is studied. A bifurcation diagram is constructed, by varying the driver amplitude, to identify a number of nonlinear dynamical processes including saddle-node bifurcation, boundary crisis, and interior crisis. The roles played by unstable periodic orbits and chaotic saddles in these transitions are analyzed, and the conversion from a chaotic saddle to a chaotic attractor in these dynamical processes is demonstrated. In particular, the phenomenon of gap-filling in the chaotic transition from weak chaos to strong chaos via an interior crisis is investigated. A coupling unstable periodic orbit created by an explosion, within the gaps of the chaotic saddles embedded in a chaotic attractor following an interior crisis, is found numerically. The gap-filling unstable periodic orbits are responsible for coupling the banded chaotic saddle (BCS) to the surrounding chaotic saddle (SCS), leading to crisis-induced intermittency. The physical relevance of chaos for Alfvén intermittent turbulence observed in the solar wind is discussed.

Lp-stability (1 less than or equal to p less than or equal to infinity) of multivariable nonlinear time-varying feedback systems that are open-loop unstable. [noting unstable convolution subsystem forward control and time varying nonlinear feedback

NASA Technical Reports Server (NTRS)

Callier, F. M.; Desoer, C. A.

1973-01-01

A class of multivariable, nonlinear time-varying feedback systems with an unstable convolution subsystem as feedforward and a time-varying nonlinear gain as feedback was considered. The impulse response of the convolution subsystem is the sum of a finite number of increasing exponentials multiplied by nonnegative powers of the time t, a term that is absolutely integrable and an infinite series of delayed impulses. The main result is a theorem. It essentially states that if the unstable convolution subsystem can be stabilized by a constant feedback gain F and if incremental gain of the difference between the nonlinear gain function and F is sufficiently small, then the nonlinear system is L(p)-stable for any p between one and infinity. Furthermore, the solutions of the nonlinear system depend continuously on the inputs in any L(p)-norm. The fixed point theorem is crucial in deriving the above theorem.

Prefrontal neurons represent winning and losing during competitive video shooting games between monkeys.

PubMed

Hosokawa, Takayuki; Watanabe, Masataka

2012-05-30

Humans and animals must work to support their survival and reproductive needs. Because resources are limited in the natural environment, competition is inevitable, and competing successfully is vitally important. However, the neuronal mechanisms of competitive behavior are poorly studied. We examined whether neurons in the lateral prefrontal cortex (LPFC) showed response sensitivity related to a competitive game. In this study, monkeys played a video shooting game, either competing with another monkey or the computer, or playing alone without a rival. Monkeys performed more quickly and more accurately in the competitive than in the noncompetitive games, indicating that they were more motivated in the competitive than in the noncompetitive games. LPFC neurons showed differential activity between the competitive and noncompetitive games showing winning- and losing-related activity. Furthermore, activities of prefrontal neurons differed depending on whether the competition was between monkeys or between the monkey and the computer. These results indicate that LPFC neurons may play an important role in monitoring the outcome of competition and enabling animals to adapt their behavior to increase their chances of obtaining a reward in a socially interactive environment.

Molecular and Epigenetic Mechanisms for the Complex Effects of Stress on Synaptic Physiology and Cognitive Functions

PubMed Central

Yuen, Eunice Y.; Wei, Jing

2017-01-01

Abstract Evidence over the past decades has found that stress, particularly through the corticosterone stress hormones, produces complex changes in glutamatergic signaling in prefrontal cortex, which leads to the alteration of cognitive processes medicated by this brain region. Interestingly, the effects of stress on glutamatergic transmission appear to be “U-shaped,” depending upon the duration and severity of the stressor. These biphasic effects of acute vs chronic stress represent the adaptive vs maladaptive responses to stressful stimuli. Animal studies suggest that the stress-induced modulation of excitatory synaptic transmission involves changes in presynaptic glutamate release, postsynaptic glutamate receptor membrane trafficking and degradation, spine structure and cytoskeleton network, and epigenetic control of gene expression. This review will discuss current findings on the key molecules involved in the stress-induced regulation of prefrontal cortex synaptic physiology and prefrontal cortex-mediated functions. Understanding the molecular and epigenetic mechanisms that underlie the complex effects of stress will help to develop novel strategies to cope with stress-related mental disorders. PMID:29016816

Molecular and Epigenetic Mechanisms for the Complex Effects of Stress on Synaptic Physiology and Cognitive Functions.

PubMed

Yuen, Eunice Y; Wei, Jing; Yan, Zhen

2017-11-01

Evidence over the past decades has found that stress, particularly through the corticosterone stress hormones, produces complex changes in glutamatergic signaling in prefrontal cortex, which leads to the alteration of cognitive processes medicated by this brain region. Interestingly, the effects of stress on glutamatergic transmission appear to be "U-shaped," depending upon the duration and severity of the stressor. These biphasic effects of acute vs chronic stress represent the adaptive vs maladaptive responses to stressful stimuli. Animal studies suggest that the stress-induced modulation of excitatory synaptic transmission involves changes in presynaptic glutamate release, postsynaptic glutamate receptor membrane trafficking and degradation, spine structure and cytoskeleton network, and epigenetic control of gene expression. This review will discuss current findings on the key molecules involved in the stress-induced regulation of prefrontal cortex synaptic physiology and prefrontal cortex-mediated functions. Understanding the molecular and epigenetic mechanisms that underlie the complex effects of stress will help to develop novel strategies to cope with stress-related mental disorders. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Identifying ADHD children using hemodynamic responses during a working memory task measured by functional near-infrared spectroscopy.

PubMed

Gu, Yue; Miao, Shuo; Han, Junxia; Liang, Zhenhu; Ouyang, Gaoxiang; Yang, Jian; Li, Xiaoli

2018-06-01

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder affecting children and adults. Previous studies found that functional near-infrared spectroscopy (fNIRS) can reveal significant group differences in several brain regions between ADHD children and healthy controls during working memory tasks. This study aimed to use fNIRS activation patterns to identify ADHD children from healthy controls. FNIRS signals from 25 ADHD children and 25 healthy controls performing the n-back task were recorded; then, multivariate pattern analysis was used to discriminate ADHD individuals from healthy controls, and classification performance was evaluated for significance by the permutation test. The results showed that 86.0% ([Formula: see text]) of participants can be correctly classified in leave-one-out cross-validation. The most discriminative brain regions included the bilateral dorsolateral prefrontal cortex, inferior medial prefrontal cortex, right posterior prefrontal cortex, and right temporal cortex. This study demonstrated that, in a small sample, multivariate pattern analysis can effectively identify ADHD children from healthy controls based on fNIRS signals, which argues for the potential utility of fNIRS in future assessments.

Selective representation of task-relevant objects and locations in the monkey prefrontal cortex.

PubMed

Everling, Stefan; Tinsley, Chris J; Gaffan, David; Duncan, John

2006-04-01

In the monkey prefrontal cortex (PFC), task context exerts a strong influence on neural activity. We examined different aspects of task context in a temporal search task. On each trial, the monkey (Macaca mulatta) watched a stream of pictures presented to left or right of fixation. The task was to hold fixation until seeing a particular target, and then to make an immediate saccade to it. Sometimes (unilateral task), the attended pictures appeared alone, with a cue at trial onset indicating whether they would be presented to left or right. Sometimes (bilateral task), the attended picture stream (cued side) was accompanied by an irrelevant stream on the opposite side. In two macaques, we recorded responses from a total of 161 cells in the lateral PFC. Many cells (75/161) showed visual responses. Object-selective responses were strongly shaped by task relevance - with stronger responses to targets than to nontargets, failure to discriminate one nontarget from another, and filtering out of information from an irrelevant stimulus stream. Location selectivity occurred rather independently of object selectivity, and independently in visual responses and delay periods between one stimulus and the next. On error trials, PFC activity followed the correct rules of the task, rather than the incorrect overt behaviour. Together, these results suggest a highly programmable system, with responses strongly determined by the rules and requirements of the task performed.

Altered Brain Response to Drinking Glucose and Fructose in Obese Adolescents

PubMed Central

Sinha, Rajita; Arora, Jagriti; Giannini, Cosimo; Kubat, Jessica; Malik, Saima; Van Name, Michelle A.; Santoro, Nicola; Savoye, Mary; Duran, Elvira J.; Pierpont, Bridget; Cline, Gary; Constable, R. Todd; Sherwin, Robert S.

2016-01-01

Increased sugar-sweetened beverage consumption has been linked to higher rates of obesity. Using functional MRI, we assessed brain perfusion responses to drinking two commonly consumed monosaccharides, glucose and fructose, in obese and lean adolescents. Marked differences were observed. In response to drinking glucose, obese adolescents exhibited decreased brain perfusion in brain regions involved in executive function (prefrontal cortex [PFC]) and increased perfusion in homeostatic appetite regions of the brain (hypothalamus). Conversely, in response to drinking glucose, lean adolescents demonstrated increased PFC brain perfusion and no change in perfusion in the hypothalamus. In addition, obese adolescents demonstrated attenuated suppression of serum acyl-ghrelin and increased circulating insulin level after glucose ingestion; furthermore, the change in acyl-ghrelin and insulin levels after both glucose and fructose ingestion was associated with increased hypothalamic, thalamic, and hippocampal blood flow in obese relative to lean adolescents. Additionally, in all subjects there was greater perfusion in the ventral striatum with fructose relative to glucose ingestion. Finally, reduced connectivity between executive, homeostatic, and hedonic brain regions was observed in obese adolescents. These data demonstrate that obese adolescents have impaired prefrontal executive control responses to drinking glucose and fructose, while their homeostatic and hedonic responses appear to be heightened. Thus, obesity-related brain adaptations to glucose and fructose consumption in obese adolescents may contribute to excessive consumption of glucose and fructose, thereby promoting further weight gain. PMID:27207544

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.

Medial prefrontal pathways for the contextual regulation of extinguished fear in humans

PubMed Central

Åhs, Fredrik; Kragel, Philip A.; Zielinski, David J.; Brady, Rachael; LaBar, Kevin S.

2015-01-01

The maintenance of anxiety disorders is thought to depend, in part, on deficits in extinction memory, possibly due to reduced contextual control of extinction that leads to fear renewal. Animal studies suggest that the neural circuitry responsible fear renewal includes the hippocampus, amygdala, and dorsomedial (dmPFC) and ventromedial (vmPFC) prefrontal cortex. However, the neural mechanisms of context-dependent fear renewal in humans remain poorly understood. We used functional magnetic resonance imaging (fMRI), combined with psychophysiology and immersive virtual reality, to elucidate how the hippocampus, amygdala, and dmPFC and vmPFC interact to drive the context-dependent renewal of extinguished fear. Healthy human participants encountered dynamic fear-relevant conditioned stimuli (CSs) while navigating through 3-D virtual reality environments in the MRI scanner. Conditioning and extinction were performed in two different virtual contexts. Twenty-four hours later, participants were exposed to the CSs without reinforcement while navigating through both contexts in the MRI scanner. Participants showed enhanced skin conductance responses (SCRs) to the previously-reinforced CS+ in the acquisition context on Day 2, consistent with fear renewal, and sustained responses in the dmPFC. In contrast, participants showed low SCRs to the CSs in the extinction context on Day 2, consistent with extinction recall, and enhanced vmPFC activation to the non-reinforced CS−. Structural equation modeling revealed that the dmPFC fully mediated the effect of the hippocampus on right amygdala activity during fear renewal, whereas the vmPFC partially mediated the effect of the hippocampus on right amygdala activity during extinction recall. These results indicate dissociable contextual influences of the hippocampus on prefrontal pathways, which, in turn, determine the level of reactivation of fear associations. PMID:26220745

From cognitive motor preparation to visual processing: The benefits of childhood fitness to brain health.

PubMed

Berchicci, M; Pontifex, M B; Drollette, E S; Pesce, C; Hillman, C H; Di Russo, F

2015-07-09

The association between a fit body and a fit brain in children has led to a rise of behavioral and neuroscientific research. Yet, the relation of cardiorespiratory fitness on premotor neurocognitive preparation with early visual processing has received little attention. Here, 41 healthy, lower and higher fit preadolescent children were administered a modified version of the Eriksen flanker task while electroencephalography (EEG) and behavioral measures were recorded. Event-related potentials (ERPs) locked to the stimulus onset with an earlier than usual baseline (-900/-800 ms) allowed investigation of both the usual post-stimulus (i.e., the P1, N1 and P2) as well as the pre-stimulus ERP components, such as the Bereitschaftspotential (BP) and the prefrontal negativity (pN component). At the behavioral level, aerobic fitness was associated response accuracy, with higher fit children being more accurate than lower fit children. Fitness-related differences selectively emerged at prefrontal brain regions during response preparation, with larger pN amplitude for higher than lower fit children, and at early perceptual stages after stimulus onset, with larger P1 and N1 amplitudes in higher relative to lower fit children. Collectively, the results suggest that the benefits of being aerobically fit appear at the stage of cognitive preparation prior to stimulus presentation and the behavioral response during the performance of a task that challenges cognitive control. Further, it is likely that enhanced activity in prefrontal brain areas may improve cognitive control of visuo-motor tasks, allowing for stronger proactive inhibition and larger early allocation of selective attention resources on relevant external stimuli. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

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.

Negative childhood experiences alter a prefrontal-insular-motor cortical network in healthy adults: A preliminary multimodal rsfMRI-fMRI-MRS-dMRI study

PubMed Central

Duncan, Niall W.; Hayes, Dave J.; Wiebking, Christine; Tiret, Brice; Pietruska, Karin; Chen, David Q.; Rainville, Pierre; Marjańska, Malgorzata; Mohammid, Omar; Doyon, Julien; Hodaie, Mojgan; Northoff, Georg

2016-01-01

Research in humans and animals has shown that negative childhood experiences (NCE) can have long-term effects on the structure and function of the brain. Alterations have been noted in grey and white matter, in the brain’s resting state, on the glutamatergic system, and on neural and behavioural responses to aversive stimuli. These effects can be linked to psychiatric disorder such as depression and anxiety disorders that are influenced by excessive exposure to early life stressors. The aim of the current study was to investigate the effect of NCEs on these systems. Resting state functional MRI (rsfMRI), aversion task fMRI, glutamate magnetic resonance spectroscopy (MRS), and diffusion magnetic resonance imaging (dMRI) were combined with the Childhood Trauma Questionnaire (CTQ) in healthy subjects to examine the impact of NCEs on the brain. Low CTQ scores, a measure of NCEs, were related to higher resting state glutamate levels and higher resting state entropy in the medial prefrontal cortex (mPFC). CTQ scores, mPFC glutamate and entropy, correlated with neural BOLD responses to the anticipation of aversive stimuli in regions throughout the aversion-related network, with strong correlations between all measures in the motor cortex and left insula. Structural connectivity strength, measured using mean fractional anisotropy, between the mPFC and left insula correlated to aversion-related signal changes in the motor cortex. These findings highlight the impact of NCEs on multiple inter-related brain systems. In particular, they highlight the role of a prefrontal-insular-motor cortical network in the processing and responsivity to aversive stimuli and its potential adaptability by NCEs. PMID:26287448

Rasd2 Modulates Prefronto-Striatal Phenotypes in Humans and ‘Schizophrenia-Like Behaviors' in Mice

PubMed Central

Vitucci, Daniela; Di Giorgio, Annabella; Napolitano, Francesco; Pelosi, Barbara; Blasi, Giuseppe; Errico, Francesco; Attrotto, Maria Teresa; Gelao, Barbara; Fazio, Leonardo; Taurisano, Paolo; Di Maio, Anna; Marsili, Valentina; Pasqualetti, Massimo; Bertolino, Alessandro; Usiello, Alessandro

2016-01-01

Rasd2 is a thyroid hormone target gene, which encodes for a GTP-binding protein enriched in the striatum where, among other functions, it modulates dopaminergic neurotransmission. Here we report that human RASD2 mRNA is abundant in putamen, but it also occurs in the cerebral cortex, with a distinctive expression pattern that differs from that present in rodents. Consistent with its localization, we found that a genetic variation in RASD2 (rs6518956) affects postmortem prefrontal mRNA expression in healthy humans and is associated with phenotypes of relevance to schizophrenia, including prefrontal and striatal grey matter volume and physiology during working memory, as measured with magnetic resonance imaging. Interestingly, quantitative real-time PCR analysis indicated that RASD2 mRNA is slightly reduced in postmortem prefrontal cortex of patients with schizophrenia. In the attempt to uncover the neurobiological substrates associated with Rasd2 activity, we used knockout mice to analyze the in vivo influence of this G-protein on the prepulse inhibition of the startle response and psychotomimetic drug-related behavioral response. Data showed that Rasd2 mutants display deficits in basal prepulse inhibition that, in turn, exacerbate gating disruption under psychotomimetic drug challenge. Furthermore, we documented that lack of Rasd2 strikingly enhances the behavioral sensitivity to motor stimulation elicited by amphetamine and phencyclidine. Based on animal model data, along with the finding that RASD2 influences prefronto-striatal phenotypes in healthy humans, we suggest that genetic mutation or reduced levels of this G-protein might have a role in cerebral circuitry dysfunction underpinning exaggerated psychotomimetic drugs responses and development of specific biological phenotypes linked to schizophrenia. PMID:26228524

Rasd2 Modulates Prefronto-Striatal Phenotypes in Humans and 'Schizophrenia-Like Behaviors' in Mice.

PubMed

Vitucci, Daniela; Di Giorgio, Annabella; Napolitano, Francesco; Pelosi, Barbara; Blasi, Giuseppe; Errico, Francesco; Attrotto, Maria Teresa; Gelao, Barbara; Fazio, Leonardo; Taurisano, Paolo; Di Maio, Anna; Marsili, Valentina; Pasqualetti, Massimo; Bertolino, Alessandro; Usiello, Alessandro

2016-02-01

Rasd2 is a thyroid hormone target gene, which encodes for a GTP-binding protein enriched in the striatum where, among other functions, it modulates dopaminergic neurotransmission. Here we report that human RASD2 mRNA is abundant in putamen, but it also occurs in the cerebral cortex, with a distinctive expression pattern that differs from that present in rodents. Consistent with its localization, we found that a genetic variation in RASD2 (rs6518956) affects postmortem prefrontal mRNA expression in healthy humans and is associated with phenotypes of relevance to schizophrenia, including prefrontal and striatal grey matter volume and physiology during working memory, as measured with magnetic resonance imaging. Interestingly, quantitative real-time PCR analysis indicated that RASD2 mRNA is slightly reduced in postmortem prefrontal cortex of patients with schizophrenia. In the attempt to uncover the neurobiological substrates associated with Rasd2 activity, we used knockout mice to analyze the in vivo influence of this G-protein on the prepulse inhibition of the startle response and psychotomimetic drug-related behavioral response. Data showed that Rasd2 mutants display deficits in basal prepulse inhibition that, in turn, exacerbate gating disruption under psychotomimetic drug challenge. Furthermore, we documented that lack of Rasd2 strikingly enhances the behavioral sensitivity to motor stimulation elicited by amphetamine and phencyclidine. Based on animal model data, along with the finding that RASD2 influences prefronto-striatal phenotypes in healthy humans, we suggest that genetic mutation or reduced levels of this G-protein might have a role in cerebral circuitry dysfunction underpinning exaggerated psychotomimetic drugs responses and development of specific biological phenotypes linked to schizophrenia.

Emotion and the Cardiovascular System: Postulated Role of Inputs From the Medial Prefrontal Cortex to the Dorsolateral Periaqueductal Gray.

PubMed

Dampney, Roger

2018-01-01

The midbrain periaqueductal gray (PAG) plays a major role in generating different types of behavioral responses to emotional stressors. This review focuses on the role of the dorsolateral (dl) portion of the PAG, which on the basis of anatomical and functional studies, appears to have a unique and distinctive role in generating behavioral, cardiovascular and respiratory responses to real and perceived emotional stressors. In particular, the dlPAG, but not other parts of the PAG, receives direct inputs from the primary auditory cortex and from the secondary visual cortex. In addition, there are strong direct inputs to the dlPAG, but not other parts of the PAG, from regions within the medial prefrontal cortex that in primates correspond to cortical areas 10 m, 25 and 32. I first summarise the evidence that the inputs to the dlPAG arising from visual, auditory and olfactory signals trigger defensive behavioral responses supported by appropriate cardiovascular and respiratory effects, when such signals indicate the presence of a real external threat, such as the presence of a predator. I then consider the functional roles of the direct inputs from the medial prefrontal cortex, and propose the hypothesis that these inputs are activated by perceived threats, that are generated as a consequence of complex cognitive processes. I further propose that the inputs from areas 10 m, 25 and 32 are activated under different circumstances. The input from cortical area 10 m is of special interest, because this cortical area exists only in primates and is much larger in the brain of humans than in all other primates.

Emotion and the Cardiovascular System: Postulated Role of Inputs From the Medial Prefrontal Cortex to the Dorsolateral Periaqueductal Gray

PubMed Central

Dampney, Roger

2018-01-01

The midbrain periaqueductal gray (PAG) plays a major role in generating different types of behavioral responses to emotional stressors. This review focuses on the role of the dorsolateral (dl) portion of the PAG, which on the basis of anatomical and functional studies, appears to have a unique and distinctive role in generating behavioral, cardiovascular and respiratory responses to real and perceived emotional stressors. In particular, the dlPAG, but not other parts of the PAG, receives direct inputs from the primary auditory cortex and from the secondary visual cortex. In addition, there are strong direct inputs to the dlPAG, but not other parts of the PAG, from regions within the medial prefrontal cortex that in primates correspond to cortical areas 10 m, 25 and 32. I first summarise the evidence that the inputs to the dlPAG arising from visual, auditory and olfactory signals trigger defensive behavioral responses supported by appropriate cardiovascular and respiratory effects, when such signals indicate the presence of a real external threat, such as the presence of a predator. I then consider the functional roles of the direct inputs from the medial prefrontal cortex, and propose the hypothesis that these inputs are activated by perceived threats, that are generated as a consequence of complex cognitive processes. I further propose that the inputs from areas 10 m, 25 and 32 are activated under different circumstances. The input from cortical area 10 m is of special interest, because this cortical area exists only in primates and is much larger in the brain of humans than in all other primates. PMID:29881334

Can functional magnetic resonance imaging studies help with the optimization of health messaging for lifestyle behavior change? A systematic review.

PubMed

Whelan, Maxine E; Morgan, Paul S; Sherar, Lauren B; Orme, Mark W; Esliger, Dale W

2017-06-01

Unhealthy behaviors, including smoking, poor nutrition, excessive alcohol consumption, physical inactivity and sedentary lifestyles, are global risk factors for non-communicable diseases and premature death. Functional magnetic resonance imaging (fMRI) offers a unique approach to optimize health messages by examining how the brain responds to information relating to health. Our aim was to systematically review fMRI studies that have investigated variations in brain activation in response to health messages relating to (i) smoking; (ii) alcohol consumption; (iii) physical activity; (iv) diet; and (v) sedentary behavior. The electronic databases used were Medline/PubMed, Web of Science (Core Collection), PsychINFO, SPORTDiscuss, Cochrane Library and Open Grey. Studies were included if they investigated subjects aged ≥10years and were published before January 2017. Of the 13,836 studies identified in the database search, 18 studies (smoking k=15; diet k=2; physical activity/sedentary behavior k=1) were included in the review. The prefrontal cortex was activated in seven (47%) of the smoking-related studies and the physical activity study. Results suggest that activation of the ventromedial, dorsolateral and medial prefrontal cortex regions were predictive of subsequent behavior change following exposure to aversive anti-smoking stimuli. Studies investigating the neurological responses to anti-smoking material were most abundant. Of note, the prefrontal cortex and amygdala were most commonly activated in response to health messages across lifestyle behaviors. The review highlights an important disparity between research focusing on different lifestyle behaviors. Insights from smoking literature suggest fMRI may help to optimize health messaging in relation to other lifestyle behaviors. Copyright © 2017 Elsevier Inc. All rights reserved.

Functional MRI activation in response to panic-specific, non-panic aversive, and neutral pictures in patients with panic disorder and healthy controls.

PubMed

Engel, K R; Obst, K; Bandelow, B; Dechent, P; Gruber, O; Zerr, I; Ulrich, K; Wedekind, D

2016-09-01

There is evidence that besides limbic brain structures, prefrontal and insular cortical activations and deactivations are involved in the pathophysiology of panic disorder. This study investigated activation response patterns to stimulation with individually selected panic-specific pictures in patients with panic disorder with agoraphobia (PDA) and healthy control subjects using functional magnetic resonance imaging (fMRI). Structures of interest were the prefrontal, cingulate, and insular cortex, and the amygdalo-hippocampal complex. Nineteen PDA subjects (10 females, 9 males) and 21 healthy matched controls were investigated using a Siemens 3-Tesla scanner. First, PDA subjects gave Self-Assessment Manikin (SAM) ratings on 120 pictures showing characteristic panic/agoraphobia situations, of which 20 pictures with the individually highest SAM ratings were selected. Twenty matched pictures showing aversive but not panic-specific stimuli and 80 neutral pictures from the International Affective Picture System were chosen for each subject as controls. Each picture was shown twice in each of four subsequent blocks. Anxiety and depression ratings were recorded before and after the experiment. Group comparisons revealed a significantly greater activation in PDA patients than control subjects in the insular cortices, left inferior frontal gyrus, dorsomedial prefrontal cortex, the left hippocampal formation, and left caudatum, when PA and N responses were compared. Comparisons for stimulation with unspecific aversive pictures showed activation of similar brain regions in both groups. Results indicate region-specific activations to panic-specific picture stimulation in PDA patients. They also imply dysfunctionality in the processing of interoceptive cues in PDA and the regulation of negative emotionality. Therefore, differences in the functional networks between PDA patients and control subjects should be further investigated.

Co-Variation of Peripheral Levels of miR-1202 and Brain Activity and Connectivity During Antidepressant Treatment.

PubMed

Lopez, Juan Pablo; Pereira, Fabricio; Richard-Devantoy, Stéphane; Berlim, Marcelo; Chachamovich, Eduardo; Fiori, Laura M; Niola, Paola; Turecki, Gustavo; Jollant, Fabrice

2017-09-01

MicroRNAs are short non-coding molecules that play a major role in regulating gene expression. Peripheral levels of miR-1202 have been shown to predict and mediate antidepressant response. However, it is not clear to what extent these peripheral measures reflect central neural changes in vivo. We approached this problem with the combined use of peripheral miR-1202 measures and neuroimaging. At baseline and after 8 weeks of desvenlafaxine (50-100 mg die), 20 patients were scanned with 3T magnetic resonance imaging, first at rest then during the Go/NoGo task, a classical test of response inhibition. Blood samples were collected at both time points. During resting state, lower baseline miR-1202 levels were predictive of increased connectivity from T0 to T8 between the posterior cingulate and the prefrontal, parietal, and occipital cortices. Changes in miR-1202 levels following desvenlafaxine treatment were negatively correlated with changes in activity in right precuneus within the default-mode network, and in connectivity between the posterior cingulate and the temporal and prefrontal cortices, and the precuneus. During the Go/NoGo task, baseline miR-1202 levels and changes in these levels were correlated with activity changes in different regions, including bilateral prefrontal, insular, cingulate, and temporal cortices, and left putamen and claustrum. Finally, secondary analyses in a subset of patients showed a trend for a significant correlation between miR-1202 levels and glutamate levels measured by spectroscopy. Changes in peripheral miR-1202 levels were therefore associated with changes in brain activity and connectivity in a network of brain regions associated with depression and antidepressant response. These effects may be mediated by the glutamatergic system.

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.

From blame to punishment: Disrupting prefrontal cortex activity reveals norm enforcement mechanisms

PubMed Central

Buckholtz, Joshua W.; Martin, Justin W.; Treadway, Michael T.; Jan, Katherine; Zald, David H.; Jones, Owen; Marois, René

2017-01-01

Summary Humans maintain a level of cooperation among non-kin that is unrivaled in the animal kingdom. This unique feature of human culture is enabled by our ability to generate, transmit, and follow widely held agreements about morally acceptable and permissible behavior (social norms). However, the social welfare provided by cooperation crucially depends on our ability to enforce these norms by sanctioning those who violate them. Determining moral responsibility and assigning a deserved punishment are two cognitive cornerstones of norm enforcement; together, they form the foundation for modern state-administered systems of justice. Although prior work has implicated the dorsolateral prefrontal cortex (DLPFC) in social norm-based judgments, the relative contribution of this brain region to judgments of moral responsibility and punishment decision-making remains poorly understood. Here, we used repetitive transcranial magnetic stimulation (rTMS) and functional magnetic resonance imaging (fMRI) to determine the specific, causal role of DLPFC function in norm-enforcement behavior. rTMS to DLPFC significantly reduced punishment for wrongful acts without affecting blameworthiness ratings for the same acts, suggesting a neural dissociation between punishment decisions and moral responsibility judgments. We confirmed this dissociation using fMRI: DLPFC is preferentially recruited for punishment decision-making compared to blameworthiness evaluation. Finally, we employed conditional process modeling to show that DLPFC supports punishment decision-making by integrating information about culpability and harm. Together, these findings reveal a selective, causal role for lateral prefrontal cortex in punishment decision-making, and suggest a computational source for this selectivity: the ability of the DLPFC to integrate distinct information processing streams that form the basis of our punishment decisions. PMID:26386518

FRONTO-STRIATAL FUNCTIONAL CONNECTIVITY DURING RESPONSE INHIBITION IN ALCOHOL DEPENDENCE

PubMed Central

Courtney, Kelly E.; Ghahremani, Dara G.; Ray, Lara A.

2013-01-01

Poor response inhibition has been implicated in the development of alcohol dependence, yet little is known about how neural pathways underlying cognitive control are affected in this disorder. Moreover, endogenous opioid levels may impact the functionality of inhibitory control pathways. This study investigated the relationship between alcohol dependence severity and functional connectivity of fronto-striatal networks during response inhibition in an alcohol dependent sample. A secondary aim of this study was to test the moderating effect of a functional polymorphism (A118G) of the µ-opioid receptor (OPRM1) gene. Twenty individuals with alcohol dependence (6 females; 90% Caucasian; mean age = 29.4) who were prospectively genotyped on the OPRM1 gene underwent blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) while performing a Stop Signal Task (SST). The relationship between alcohol dependence severity and functional connectivity within fronto-striatal networks important for response inhibition was assessed using psychophysiological interaction (PPI) analyses. Analyses revealed greater alcohol dependence severity associated with weaker functional connectivity between the putamen and prefrontal regions (e.g., the anterior insula, anterior cingulate, and medial prefrontal cortex) during response inhibition. Further, the OPRM1 genotype was associated with differential response inhibition-related functional connectivity. This study demonstrates that individuals with more severe alcohol dependence exhibit less frontal connectivity with the striatum, a component of cognitive control networks important for response inhibition. These findings suggest that the fronto-striatal pathway underlying response inhibition is weakened as alcoholism progresses. PMID:23240858

Isn’t it ironic? Neural Correlates of Irony Comprehension in Schizophrenia

PubMed Central

Rapp, Alexander M.; Langohr, Karin; Mutschler, Dorothee E.; Klingberg, Stefan; Wild, Barbara; Erb, Michael

2013-01-01

Ironic remarks are frequent in everyday language and represent an important form of social cognition. Increasing evidence indicates a deficit in comprehension in schizophrenia. Several models for defective comprehension have been proposed, including possible roles of the medial prefrontal lobe, default mode network, inferior frontal gyri, mirror neurons, right cerebral hemisphere and a possible mediating role of schizotypal personality traits. We investigated the neural correlates of irony comprehension in schizophrenia by using event-related functional magnetic resonance imaging (fMRI). In a prosody-free reading paradigm, 15 female patients with schizophrenia and 15 healthy female controls silently read ironic and literal text vignettes during fMRI. Each text vignette ended in either an ironic (n = 22) or literal (n = 22) statement. Ironic and literal text vignettes were matched for word frequency, length, grammatical complexity, and syntax. After fMRI, the subjects performed an off-line test to detect error rate. In this test, the subjects indicated by button press whether the target sentence has ironic, literal, or meaningless content. Schizotypal personality traits were assessed using the German version of the schizotypal personality questionnaire (SPQ). Patients with schizophrenia made significantly more errors than did the controls (correct answers, 85.3% vs. 96.3%) on a behavioural level. Patients showed attenuated blood oxygen level-dependent (BOLD) response during irony comprehension mainly in right hemisphere temporal regions (ironic>literal contrast) and in posterior medial prefrontal and left anterior insula regions (for ironic>visual baseline, but not for literal>visual baseline). In patients with schizophrenia, the parahippocampal gyrus showed increased activation. Across all subjects, BOLD response in the medial prefrontal area was negatively correlated with the SPQ score. These results highlight the role of the posterior medial prefrontal and right temporal regions in defective irony comprehension in schizophrenia and the mediating role of schizotypal personality traits. PMID:24040207

Neural and psychophysiological correlates of human performance under stress and high mental workload.

PubMed

Mandrick, Kevin; Peysakhovich, Vsevolod; Rémy, Florence; Lepron, Evelyne; Causse, Mickaël

2016-12-01

In our anxiogenic and stressful world, the maintenance of an optimal cognitive performance is a constant challenge. It is particularly true in complex working environments (e.g. flight deck, air traffic control tower), where individuals have sometimes to cope with a high mental workload and stressful situations. Several models (i.e. processing efficiency theory, cognitive-energetical framework) have attempted to provide a conceptual basis on how human performance is modulated by high workload and stress/anxiety. These models predict that stress can reduce human cognitive efficiency, even in the absence of a visible impact on the task performance. Performance may be protected under stress thanks to compensatory effort, but only at the expense of a cognitive cost. Yet, the psychophysiological cost of this regulation remains unclear. We designed two experiments involving pupil diameter, cardiovascular and prefrontal oxygenation measurements. Participants performed the Toulouse N-back Task that intensively engaged both working memory and mental calculation processes under the threat (or not) of unpredictable aversive sounds. The results revealed that higher task difficulty (higher n level) degraded the performance and induced an increased tonic pupil diameter, heart rate and activity in the lateral prefrontal cortex, and a decreased phasic pupil response and heart rate variability. Importantly, the condition of stress did not impact the performance, but at the expense of a psychophysiological cost as demonstrated by lower phasic pupil response, and greater heart rate and prefrontal activity. Prefrontal cortex seems to be a central region for mitigating the influence of stress because it subserves crucial functions (e.g. inhibition, working memory) that can promote the engagement of coping strategies. Overall, findings confirmed the psychophysiological cost of both mental effort and stress. Stress likely triggered increased motivation and the recruitment of additional cognitive resources that minimize its aversive effects on task performance (effectiveness), but these compensatory efforts consumed resources that caused a loss of cognitive efficiency (ratio between performance effectiveness and mental effort). Copyright © 2016 Elsevier B.V. All rights reserved.

Importance of reward and prefrontal circuitry in hunger and satiety: Prader-Willi syndrome vs simple obesity.

PubMed

Holsen, L M; Savage, C R; Martin, L E; Bruce, A S; Lepping, R J; Ko, E; Brooks, W M; Butler, M G; Zarcone, J R; Goldstein, J M

2012-05-01

The majority of research on obesity (OB) has focused primarily on clinical features (eating behavior, adiposity measures) or peripheral appetite-regulatory peptides (leptin, ghrelin). However, recent functional neuroimaging studies have demonstrated that some reward circuitry regions that are associated with appetite-regulatory hormones are also involved in the development and maintenance of OB. Prader-Willi syndrome (PWS), characterized by hyperphagia and hyperghrelinemia reflecting multi-system dysfunction in inhibitory and satiety mechanisms, serves as an extreme model of genetic OB. Simple (non-PWS) OB represents an OB-control state. This study investigated subcortical food motivation circuitry and prefrontal inhibitory circuitry functioning in response to food stimuli before and after eating in individuals with PWS compared with OB. We hypothesized that groups would differ in limbic regions (that is, hypothalamus, amygdala) and prefrontal regions associated with cognitive control (that is, dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC) after eating. A total of 14 individuals with PWS, 14 BMI- and age-matched individuals with OB, and 15 age-matched healthy-weight controls viewed food and non-food images while undergoing functional MRI before (pre-meal) and after (post-meal) eating. Using SPM8, group contrasts were tested for hypothesized regions: hypothalamus, nucleus accumbens (NAc), amygdala, hippocampus, OFC, medial PFC and DLPFC. Compared with OB and HWC, PWS demonstrated higher activity in reward/limbic regions (NAc, amygdala) and lower activity in the hypothalamus and hippocampus in response to food (vs non-food) images pre-meal. Post meal, PWS exhibited higher subcortical activation (hypothalamus, amygdala, hippocampus) compared with OB and HWC. OB showed significantly higher activity versus PWS and HWC in cortical regions (DLPFC, OFC) associated with inhibitory control. In PWS, compared with OB per se, results suggest hyperactivations in subcortical reward circuitry and hypoactivations in cortical inhibitory regions after eating, which provides evidence of neural substrates associated with variable abnormal food motivation phenotypes in PWS and simple OB.

Importance of Reward and Prefrontal Circuitry in Hunger and Satiety: Prader-Willi Syndrome vs. Simple Obesity

PubMed Central

Holsen, Laura M.; Savage, Cary R.; Martin, Laura E.; Bruce, Amanda S.; Lepping, Rebecca J.; Ko, Eunice; Brooks, William M.; Butler, Merlin G.; Zarcone, Jennifer R.; Goldstein, Jill M.

2011-01-01

Background The majority of research on obesity has focused primarily on clinical features (eating behavior, adiposity measures), or peripheral appetite-regulatory peptides (leptin, ghrelin). However, recent functional neuroimaging studies have demonstrated that some reward circuitry regions which are associated with appetite-regulatory hormones are also involved in the development and maintenance of obesity. Prader-Willi syndrome (PWS), characterized by hyperphagia and hyperghrelinemia reflecting multi-system dysfunction in inhibitory and satiety mechanisms, serves as an extreme model of genetic obesity. Simple (non-PWS) obesity (OB) represents an obesity control state. Objective This study investigated subcortical food motivation circuitry and prefrontal inhibitory circuitry functioning in response to food stimuli before and after eating in individuals with PWS compared with OB. We hypothesized that groups would differ in limbic regions (i.e., hypothalamus, amygdala) and prefrontal regions associated with cognitive control [i.e., dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC)] after eating. Design and Participants Fourteen individuals with PWS, 14 BMI- and age-matched individuals with OB, and 15 age-matched healthy-weight controls (HWC) viewed food and non-food images while undergoing functional MRI before (pre-meal) and after (post-meal) eating. Using SPM8, group contrasts were tested for hypothesized regions: hypothalamus, nucleus accumbens (NAc), amygdala, hippocampus, OFC, medial PFC, and DLPFC. Results Compared with OB and HWC, PWS demonstrated higher activity in reward/limbic regions (NAc, amygdala) and lower activity in hypothalamus and hippocampus, in response to food (vs. non-food) images pre-meal. Post-meal, PWS exhibited higher subcortical activation (hypothalamus, amygdala, hippocampus) compared to OB and HWC. OB showed significantly higher activity versus PWS and HWC in cortical regions (DLPFC, OFC) associated with inhibitory control. Conclusion In PWS compared with obesity per se, results suggest hyperactivations in subcortical reward circuitry and hypoactivations in cortical inhibitory regions after eating, which provides evidence of neural substrates associated with variable abnormal food motivation phenotypes in PWS and simple obesity. PMID:22024642

Unstable power threatens the powerful and challenges the powerless: evidence from cardiovascular markers of motivation.

PubMed

Scheepers, Daan; Röell, Charlotte; Ellemers, Naomi

2015-01-01

Possessing social power has psychological and biological benefits. For example, during task interactions, people high in power are more likely to display a benign cardiovascular (CV) response pattern indicative of "challenge" whereas people low in power are more likely to display a maladaptive CV pattern indicative of "threat" (Scheepers et al., 2012). Challenge is marked by high cardiac output (CO) and low total peripheral resistance (TPR), while threat is marked by low CO and high TPR (Blascovich and Mendes, 2010). In the current work we addressed a possible moderator of the power-threat/challenge relationship, namely the stability of power. We examined the influence of the stability of power (roles could or could not change) on CV responses during a dyadic task where one person was the "chief designer" (high power) and one person was the "assistant" (low power). During the task, different CV-measures were taken [CO, TPR, heart rate, pre-ejection period). Whereas participants in the unstable low power condition showed a stronger tendency toward challenge, participants in the unstable high power condition showed a stronger tendency toward threat. Moreover, participants in the stable low power condition showed CV signs of task disengagement. Results are discussed in terms of the importance of contextual variables in shaping the relationship between power and benign/maladaptive physiological responses.

Unstable power threatens the powerful and challenges the powerless: evidence from cardiovascular markers of motivation

PubMed Central

Scheepers, Daan; Röell, Charlotte; Ellemers, Naomi

2015-01-01

Possessing social power has psychological and biological benefits. For example, during task interactions, people high in power are more likely to display a benign cardiovascular (CV) response pattern indicative of “challenge” whereas people low in power are more likely to display a maladaptive CV pattern indicative of “threat” (Scheepers et al., 2012). Challenge is marked by high cardiac output (CO) and low total peripheral resistance (TPR), while threat is marked by low CO and high TPR (Blascovich and Mendes, 2010). In the current work we addressed a possible moderator of the power-threat/challenge relationship, namely the stability of power. We examined the influence of the stability of power (roles could or could not change) on CV responses during a dyadic task where one person was the “chief designer” (high power) and one person was the “assistant” (low power). During the task, different CV-measures were taken [CO, TPR, heart rate, pre-ejection period). Whereas participants in the unstable low power condition showed a stronger tendency toward challenge, participants in the unstable high power condition showed a stronger tendency toward threat. Moreover, participants in the stable low power condition showed CV signs of task disengagement. Results are discussed in terms of the importance of contextual variables in shaping the relationship between power and benign/maladaptive physiological responses. PMID:26074860

Positive and negative feedback regulatory loops of thiol-oxidative stress response mediated by an unstable isoform of sigmaR in actinomycetes.

PubMed

Kim, Min-Sik; Hahn, Mi-Young; Cho, Yoobok; Cho, Sang-Nae; Roe, Jung-Hye

2009-09-01

Alternate sigma factors provide an effective way of diversifying bacterial gene expression in response to environmental changes. In Streptomyces coelicolor where more than 65 sigma factors are predicted, sigma(R) is the major regulator for response to thiol-oxidative stresses. sigma(R) becomes available when its bound anti-sigma factor RsrA is oxidized at sensitive cysteine thiols to form disulphide bonds. sigma(R) regulon includes genes for itself and multiple thiol-reducing systems, which constitute positive and negative feedback loops respectively. We found that the positive amplification loop involves an isoform of sigma(R) (sigma(R')) with an N-terminal extension of 55 amino acids, produced from an upstream start codon. A major difference between constitutive sigma(R) and inducible sigma(R') is that the latter is markedly unstable (t(1/2) approximately 10 min) compared with the former (> 70 min). The rapid turnover of sigma(R') is partly due to induced ClpP1/P2 proteases from the sigma(R) regulon. This represents a novel way of elaborating positive and negative feedback loops in a control circuit. Similar phenomenon may occur in other actinomycetes that harbour multiple start codons in the sigR homologous gene. We observed that sigH gene, the sigR orthologue in Mycobacterium smegmatis, produces an unstable larger isoform of sigma(H) upon induction by thiol-oxidative stress.

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.

Impulsive-antisocial psychopathic traits linked to increased volume and functional connectivity within prefrontal cortex

PubMed Central

Korponay, Cole; Pujara, Maia; Deming, Philip; Philippi, Carissa; Decety, Jean; Kosson, David S.; Kiehl, Kent A.

2017-01-01

Abstract Psychopathy is a personality disorder characterized by callous lack of empathy, impulsive antisocial behavior, and criminal recidivism. Studies of brain structure and function in psychopathy have frequently identified abnormalities in the prefrontal cortex. However, findings have not yet converged to yield a clear relationship between specific subregions of prefrontal cortex and particular psychopathic traits. We performed a multimodal neuroimaging study of prefrontal cortex volume and functional connectivity in psychopathy, using a sample of adult male prison inmates (N = 124). We conducted volumetric analyses in prefrontal subregions, and subsequently assessed resting-state functional connectivity in areas where volume was related to psychopathy severity. We found that overall psychopathy severity and Factor 2 scores (which index the impulsive/antisocial traits of psychopathy) were associated with larger prefrontal subregion volumes, particularly in the medial orbitofrontal cortex and dorsolateral prefrontal cortex. Furthermore, Factor 2 scores were also positively correlated with functional connectivity between several areas of the prefrontal cortex. The results were not attributable to age, race, IQ, substance use history, or brain volume. Collectively, these findings provide evidence for co-localized increases in prefrontal cortex volume and intra-prefrontal functional connectivity in relation to impulsive/antisocial psychopathic traits. PMID:28402565

Dripping and jetting regimes in co-flowing capillary jets: unforced measurements and response to driving

NASA Astrophysics Data System (ADS)

Baroud, Charles; Cordero, Maria-Luisa; Gallaire, Francois

2011-11-01

We study the breakup of drops in a co-flowing jet, within the confinement of a microfluidic channel. The breakup can occur right after the nozzle (dripping) or through the generation of a liquid jet that breaks up a long distance from the nozzle (jetting). Traditionally, these two regimes have been considered to reflect an absolutely unstable jet or a convectively unstable jet, respectively. We first provide measurements of the frequency of oscillation and breakup of the liquid jet; the dispersion relation thus obtained compares well with existing theories for convective instabilities in the case of the jetting regime. However, the theories in the absolutely unstable mode fail to predict the evolution of the frequency and drop size in the dripping regime. We also test the jet response to an external forcing, using a focused laser to locally heat the jet. The dripping regime is found to be insensitive to the perturbation and the frequency of drop formation remains unaltered. In contrast, the jetting regime locks to the external frequency, which translates into a modification of the drop size in agreement with the dispersion relations. This confirms the convective nature of the jetting regime. Permanent address: Universidad de Chile.

Differential Contributions of Dorso-Ventral and Rostro-Caudal Prefrontal White Matter Tracts to Cognitive Control in Healthy Older Adults

PubMed Central

Strenziok, Maren; Greenwood, Pamela M.; Santa Cruz, Sophia A.; Thompson, James C.; Parasuraman, Raja

2013-01-01

Prefrontal cortex mediates cognitive control by means of circuitry organized along dorso-ventral and rostro-caudal axes. Along the dorso-ventral axis, ventrolateral PFC controls semantic information, whereas dorsolateral PFC encodes task rules. Along the rostro-caudal axis, anterior prefrontal cortex encodes complex rules and relationships between stimuli, whereas posterior prefrontal cortex encodes simple relationships between stimuli and behavior. Evidence of these gradients of prefrontal cortex organization has been well documented in fMRI studies, but their functional correlates have not been examined with regard to integrity of underlying white matter tracts. We hypothesized that (a) the integrity of specific white matter tracts is related to cognitive functioning in a manner consistent with the dorso-ventral and rostro-caudal organization of the prefrontal cortex, and (b) this would be particularly evident in healthy older adults. We assessed three cognitive processes that recruit the prefrontal cortex and can distinguish white matter tracts along the dorso-ventral and rostro-caudal dimensions –episodic memory, working memory, and reasoning. Correlations between cognition and fractional anisotropy as well as fiber tractography revealed: (a) Episodic memory was related to ventral prefrontal cortex-thalamo-hippocampal fiber integrity; (b) Working memory was related to integrity of corpus callosum body fibers subserving dorsolateral prefrontal cortex; and (c) Reasoning was related to integrity of corpus callosum body fibers subserving rostral and caudal dorsolateral prefrontal cortex. These findings confirm the ventrolateral prefrontal cortex's role in semantic control and the dorsolateral prefrontal cortex's role in rule-based processing, in accordance with the dorso-ventral prefrontal cortex gradient. Reasoning-related rostral and caudal superior frontal white matter may facilitate different levels of task rule complexity. This study is the first to demonstrate dorso-ventral and rostro-caudal prefrontal cortex processing gradients in white matter integrity. PMID:24312550

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 corticocortical connectivity may help to elucidate both region-specific and integrative perspectives on the functions of the prefrontal cortex. PMID:21481342

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.

Closing the gate in the limbic striatum: prefrontal suppression of hippocampal and thalamic inputs

PubMed Central

Calhoon, Gwendolyn G.; O’Donnell, Patricio

2013-01-01

SUMMARY Many brain circuits control behavior by integrating information arising from separate inputs onto a common target neuron. Neurons in the ventral striatum (VS) receive converging excitatory afferents from the prefrontal cortex (PFC), hippocampus (HP), and thalamus, among other structures, and the integration of these inputs is critical for shaping goal-directed behaviors. Although HP inputs have been described as gating PFC throughput in the VS, recent data reveal that the VS desynchronizes from the HP during epochs of burst-like PFC activity related to decision-making. It is therefore possible that PFC inputs locally attenuate responses to other glutamatergic inputs to the VS. Here, we found that delivering trains of stimuli to the PFC suppresses HP- and thalamus-evoked synaptic responses in the VS, in part through activation of inhibitory processes. This interaction may enable the PFC to exert influence on basal ganglia loops during decision-making instances with minimal disturbance from ongoing contextual inputs. PMID:23583113

Disrupting the right prefrontal cortex alters moral judgement.

PubMed

Tassy, Sébastien; Oullier, Olivier; Duclos, Yann; Coulon, Olivier; Mancini, Julien; Deruelle, Christine; Attarian, Sharam; Felician, Olivier; Wicker, Bruno

2012-03-01

Humans daily face social situations involving conflicts between competing moral decision. Despite a substantial amount of studies published over the past 10 years, the respective role of emotions and reason, their possible interaction, and their behavioural expression during moral evaluation remains an unresolved issue. A dualistic approach to moral evaluation proposes that the right dorsolateral prefrontal cortex (rDLPFc) controls emotional impulses. However, recent findings raise the possibility that the right DLPFc processes emotional information during moral decision making. We used repetitive transcranial magnetic stimulation (rTMS) to transiently disrupt rDLPFc activity before measuring decision making in the context of moral dilemmas. Results reveal an increase of the probability of utilitarian responses during objective evaluation of moral dilemmas in the rTMS group (compared to a SHAM one). This suggests that the right DLPFc function not only participates to a rational cognitive control process, but also integrates emotions generated by contextual information appraisal, which are decisive for response selection in moral judgements. © The Author (2011). Published by Oxford University Press.

Confidence Leak in Perceptual Decision Making.

PubMed

Rahnev, Dobromir; Koizumi, Ai; McCurdy, Li Yan; D'Esposito, Mark; Lau, Hakwan

2015-11-01

People live in a continuous environment in which the visual scene changes on a slow timescale. It has been shown that to exploit such environmental stability, the brain creates a continuity field in which objects seen seconds ago influence the perception of current objects. What is unknown is whether a similar mechanism exists at the level of metacognitive representations. In three experiments, we demonstrated a robust intertask confidence leak-that is, confidence in one's response on a given task or trial influencing confidence on the following task or trial. This confidence leak could not be explained by response priming or attentional fluctuations. Better ability to modulate confidence leak predicted higher capacity for metacognition as well as greater gray matter volume in the prefrontal cortex. A model based on normative principles from Bayesian inference explained the results by postulating that observers subjectively estimate the perceptual signal strength in a stable environment. These results point to the existence of a novel metacognitive mechanism mediated by regions in the prefrontal cortex. © The Author(s) 2015.

Neuroimaging self-esteem: a fMRI study of individual differences in women

PubMed Central

Lundberg, Erica; Brimson-Théberge, Melanie; Théberge, Jean

2013-01-01

Although neuroimaging studies strongly implicate the medial prefrontal cortex (ventral and dorsal), cingulate gyrus (anterior and posterior), precuneus and temporoparietal cortex in mediating self-referential processing (SRP), little is known about the neural bases mediating individual differences in valenced SRP, that is, processes intrinsic to self-esteem. This study investigated the neural correlates of experimentally engendered valenced SRP via the Visual–Verbal Self-Other Referential Processing Task in 20 women with fMRI. Participants viewed pictures of themselves or unknown other women during separate trials while covertly rehearsing ‘I am’ or ‘She is’, followed by reading valenced trait adjectives, thus variably associating the self/other with positivity/negativity. Response within dorsal and ventral medial prefrontal cortex, cingulate cortex and left temporoparietal cortex varied with individual differences in both pre-task rated self-descriptiveness of the words, as well as task-induced affective responses. Results are discussed as they relate to a social cognitive and affective neuroscience view of self-esteem. PMID:22403154

In the eye of the beholder: individual differences in reward-drive modulate early frontocentral ERPs to angry faces.

PubMed

Bediou, Benoit; Eimer, Martin; d'Amato, Thierry; Hauk, Olaf; Calder, Andrew J

2009-02-01

Individual differences in reward-drive have been associated with increased attention toward facial signals of aggression, heightened experience of anger and vulnerability to display aggressive behaviour. Recent fMRI research suggests that these effects rely on reduced ventromedial prefrontal (and increased amygdala) response to aggressive facial displays compared with neutral and sad expressions in subjects scoring high on reward-drive. However, nothing is known about the timing of this modulation. Using event-related potentials (ERPs), we provide the first evidence that greater proneness to display hostile and aggressive behaviour (measured by high scores on the reward-drive) is associated with a reduced midline frontocentral response to aggressive faces within 200-300ms. In addition to confirming a particular interaction between anger processing and aggression related personality traits in ventromedial prefrontal brain regions, our study brings a first indication of when their interaction occurs in the brain, strengthening results from previous classical as well as functional connectivity fMRI studies.

Emotional modulation of pain: is it the sensation or what we recall?

PubMed

Godinho, Fabio; Magnin, Michel; Frot, Maud; Perchet, Caroline; Garcia-Larrea, Luis

2006-11-01

Emotions modulate pain perception, although the mechanisms underlying this phenomenon remain unclear. In this study, we show that intensity reports significantly increased when painful stimuli were concomitant to images showing human pain, whereas pictures with identical emotional values but without somatic content failed to modulate pain. Early somatosensory responses (<200 ms) remained unmodified by emotions. Conversely, late responses showed a significant enhancement associated with increased pain ratings, localized to the right prefrontal, right temporo-occipital junction, and right temporal pole. In contrast to selective attention, which enhances pain ratings by increasing sensory gain, emotions triggered by seeing other people's pain did not alter processing in SI-SII (primary and second somatosensory areas), but may have biased the transfer to, and the representation of pain in short-term memory buffers (prefrontal), as well as the affective assignment to this representation (temporal pole). Memory encoding and recall, rather than sensory processing, appear to be modulated by empathy with others' physical suffering.

Thinking on luxury or pragmatic brand products: Brain responses to different categories of culturally based brands.

PubMed

Schaefer, Michael; Rotte, Michael

2007-08-24

Culturally based brands have a high impact on people's economic actions. Here we aimed to examine whether socioeconomic information conveyed by certain classes of brands (prestigious versus pragmatic classes) differentially evoke brain response. We presented icons of brands while recording subject's brain activity during a functional magnetic resonance imaging (fMRI) session. After the experiment, we asked subjects to assess the brands according to different characteristics. Results revealed an active network of bilateral superior frontal gyri, hippocampus and posterior cingulate related to familiar brands in general. Brands of the category sports and luxury activated regions in medial prefrontal cortex (MPFC) and precuneus. In contrast, brands rated as value products activated the left superior frontal gyrus and anterior cingulate cortex (ACC). The results suggest an active cortical network related to cognitive control for value brands and a network known to be associated with self-relevant processing for prestigious brands. We discuss the results as differential engagement of the prefrontal cortex depending on the attributed characteristic of a brand.

Disrupting the right prefrontal cortex alters moral judgement

PubMed Central

Tassy, Sébastien; Oullier, Olivier; Duclos, Yann; Coulon, Olivier; Mancini, Julien; Deruelle, Christine; Attarian, Sharam; Felician, Olivier

2012-01-01

Humans daily face social situations involving conflicts between competing moral decision. Despite a substantial amount of studies published over the past 10 years, the respective role of emotions and reason, their possible interaction, and their behavioural expression during moral evaluation remains an unresolved issue. A dualistic approach to moral evaluation proposes that the right dorsolateral prefrontal cortex (rDLPFc) controls emotional impulses. However, recent findings raise the possibility that the right DLPFc processes emotional information during moral decision making. We used repetitive transcranial magnetic stimulation (rTMS) to transiently disrupt rDLPFc activity before measuring decision making in the context of moral dilemmas. Results reveal an increase of the probability of utilitarian responses during objective evaluation of moral dilemmas in the rTMS group (compared to a SHAM one). This suggests that the right DLPFc function not only participates to a rational cognitive control process, but also integrates emotions generated by contextual information appraisal, which are decisive for response selection in moral judgements. PMID:21515641

Bidirectional Control of Anxiety-Related Behaviors in Mice: Role of Inputs Arising from the Ventral Hippocampus to the Lateral Septum and Medial Prefrontal Cortex.

PubMed

Parfitt, Gustavo Morrone; Nguyen, Robin; Bang, Jee Yoon; Aqrabawi, Afif J; Tran, Matthew M; Seo, D Kanghoon; Richards, Blake A; Kim, Jun Chul

2017-07-01

Anxiety is an adaptive response to potentially threatening situations. Exaggerated and uncontrolled anxiety responses become maladaptive and lead to anxiety disorders. Anxiety is shaped by a network of forebrain structures, including the hippocampus, septum, and prefrontal cortex. In particular, neural inputs arising from the ventral hippocampus (vHPC) to the lateral septum (LS) and medial prefrontal cortex (mPFC) are thought to serve as principal components of the anxiety circuit. However, the role of vHPC-to-LS and vHPC-to-mPFC signals in anxiety is unclear, as no study has directly compared their behavioral contribution at circuit level. We targeted LS-projecting vHPC cells and mPFC-projecting vHPC cells by injecting the retrogradely propagating canine adenovirus encoding Cre recombinase into the LS or mPFC, and injecting a Cre-responsive AAV (AAV8-hSyn-FLEX-hM3D or hM4D) into the vHPC. Consequences of manipulating these neurons were examined in well-established tests of anxiety. Chemogenetic manipulation of LS-projecting vHPC cells led to bidirectional changes in anxiety: activation of LS-projecting vHPC cells decreased anxiety whereas inhibition of these cells produced opposite anxiety-promoting effects. The observed anxiety-reducing function of LS-projecting cells was in contrast with the function of mPFC-projecting cells, which promoted anxiety. In addition, double retrograde tracing demonstrated that LS- and mPFC-projecting cells represent two largely anatomically distinct cell groups. Altogether, our findings suggest that the vHPC houses discrete populations of cells that either promote or suppress anxiety through differences in their projection targets. Disruption of the intricate balance in the activity of these two neuron populations may drive inappropriate behavioral responses seen in anxiety disorders.

The selfless mind: How prefrontal involvement in mentalizing with similar and dissimilar others shapes empathy and prosocial behavior.

PubMed

Majdandžić, Jasminka; Amashaufer, Sandra; Hummer, Allan; Windischberger, Christian; Lamm, Claus

2016-12-01

Engaging in mentalizing, i.e., reflecting on others' thoughts, beliefs and feelings, is known to facilitate later empathy and prosocial behavior. Activation in dorsomedial prefrontal (dmPFC) areas during mentalizing has been shown to predict the extent of prosocial behavior. It is unclear, however, what cognitive process drives these effects: a simulation process in which the own mental states are used as a proxy for those of others (self-projection) or an effortful other-enhancement process in which one's own perspective is overridden. In this fMRI study we examined the effects of mentalizing with similar and dissimilar others on behavioral and brain measures of empathy and prosocial behavior, to assess which cognitive process mediates the facilitative effects of mentalizing. Participants had to mentalize with two fictitious target persons, one of whom was manipulated to have similar thoughts and beliefs as the participant, while the other had dissimilar mental states. We then assessed participants' behavioral and neural responses during an empathy for pain task and a prosocial behavior task. Similarity between participant and target person increased empathy and affiliation ratings, and mentalizing with dissimilar persons evoked increased activation in ventrolateral prefrontal cortex, the extent of which was inversely related with bias towards the similar person in empathy. Responses in two dmPFC regions were also predictive of later variations in subsequent empathy and prosocial behavior, either predicting overall prosociality and empathic concern (lateral dmPFC), or predicting reduced empathic bias towards the similar person and a lower response to self-related stressors in pain matrix areas (medial dmPFC). This pattern of results suggests that generating and enhancing other-related representations while overcoming one's own perspective, rather than enhanced recruitment of self-projection processes, is driving the facilitative effects of mentalizing on later empathic and prosocial responses. Copyright © 2016 Elsevier B.V. All rights reserved.

The Impact of Caloric and Non-Caloric Sweeteners on Food Intake and Brain Responses to Food: A Randomized Crossover Controlled Trial in Healthy Humans.

PubMed

Crézé, Camille; Candal, Laura; Cros, Jérémy; Knebel, Jean-François; Seyssel, Kevin; Stefanoni, Nathalie; Schneiter, Philippe; Murray, Micah M; Tappy, Luc; Toepel, Ulrike

2018-05-15

Whether non-nutritive sweetener (NNS) consumption impacts food intake behavior in humans is still unclear. Discrepant sensory and metabolic signals are proposed to mislead brain regulatory centers, in turn promoting maladaptive food choices favoring weight gain. We aimed to assess whether ingestion of sucrose- and NNS-sweetened drinks would differently alter brain responses to food viewing and food intake. Eighteen normal-weight men were studied in a fasted condition and after consumption of a standardized meal accompanied by either a NNS-sweetened (NNS), or a sucrose-sweetened (SUC) drink, or water (WAT). Their brain responses to visual food cues were assessed by means of electroencephalography (EEG) before and 45 min after meal ingestion. Four hours after meal ingestion, spontaneous food intake was monitored during an ad libitum buffet. With WAT, meal intake led to increased neural activity in the dorsal prefrontal cortex and the insula, areas linked to cognitive control and interoception. With SUC, neural activity in the insula increased as well, but decreased in temporal regions linked to food categorization, and remained unchanged in dorsal prefrontal areas. The latter modulations were associated with a significantly lower total energy intake at buffet (mean kcal ± SEM; 791 ± 62) as compared to WAT (942 ± 71) and NNS (917 ± 70). In contrast to WAT and SUC, NNS consumption did not impact activity in the insula, but led to increased neural activity in ventrolateral prefrontal regions linked to the inhibition of reward. Total energy intake at the buffet was not significantly different between WAT and NNS. Our findings highlight the differential impact of caloric and non-caloric sweeteners on subsequent brain responses to visual food cues and energy intake. These variations may reflect an initial stage of adaptation to taste-calorie uncoupling, and could be indicative of longer-term consequences of repeated NNS consumption on food intake behavior.

Neuronal activity during a cued strategy task: Comparison of dorsolateral, orbital and polar prefrontal cortex

PubMed Central

Tsujimoto, Satoshi; Genovesio, Aldo; Wise, Steven P.

2012-01-01

We compared neuronal activity in the dorsolateral (PFdl), orbital (PFo) and polar (PFp) prefrontal cortex as monkeys performed three tasks. In two tasks, a cue instructed one of two strategies: stay with the previous response or shift to the alternative. Visual stimuli served as cues in one of these tasks; in the other, fluid rewards did so. In the third task, visuospatial cues instructed each response. A delay period followed each cue. As reported previously, PFdl encoded strategies (stay or shift) and responses (left or right) during the cue and delay periods, while PFo encoded strategies and PFp encoded neither strategies nor responses; during the feedback period, all three areas encoded responses, not strategies. Four novel findings emerged from the present analysis. (1) The strategy encoded by PFdl and PFo cells during the cue and delay periods was modality specific. (2) The response encoded by PFdl cells was task- and modality specific during the cue period, but during the delay and feedback periods it became task- and modality general. (3) Although some PFdl and PFo cells responded to or anticipated rewards, we could rule out reward effects for most strategy-and response-related activity. (4) Immediately before feedback, only PFp signaled responses that were correct according to the cued strategy; after feedback, only PFo signaled the response that had been made, whether correct or incorrect. These signals support a role in generating responses by PFdl, assigning outcomes to choices by PFo, and assigning outcomes to cognitive processes by PFp. PMID:22875935

Adjoint eigenfunctions of temporally recurrent single-spiral solutions in a simple model of atrial fibrillation.

PubMed

Marcotte, Christopher D; Grigoriev, Roman O

2016-09-01

This paper introduces a numerical method for computing the spectrum of adjoint (left) eigenfunctions of spiral wave solutions to reaction-diffusion systems in arbitrary geometries. The method is illustrated by computing over a hundred eigenfunctions associated with an unstable time-periodic single-spiral solution of the Karma model on a square domain. We show that all leading adjoint eigenfunctions are exponentially localized in the vicinity of the spiral tip, although the marginal modes (response functions) demonstrate the strongest localization. We also discuss the implications of the localization for the dynamics and control of unstable spiral waves. In particular, the interaction with no-flux boundaries leads to a drift of spiral waves which can be understood with the help of the response functions.

Adjoint eigenfunctions of temporally recurrent single-spiral solutions in a simple model of atrial fibrillation

NASA Astrophysics Data System (ADS)

Marcotte, Christopher D.; Grigoriev, Roman O.

2016-09-01

This paper introduces a numerical method for computing the spectrum of adjoint (left) eigenfunctions of spiral wave solutions to reaction-diffusion systems in arbitrary geometries. The method is illustrated by computing over a hundred eigenfunctions associated with an unstable time-periodic single-spiral solution of the Karma model on a square domain. We show that all leading adjoint eigenfunctions are exponentially localized in the vicinity of the spiral tip, although the marginal modes (response functions) demonstrate the strongest localization. We also discuss the implications of the localization for the dynamics and control of unstable spiral waves. In particular, the interaction with no-flux boundaries leads to a drift of spiral waves which can be understood with the help of the response functions.

Sex differences in the neural representation of pain unpleasantness.

PubMed

Girard-Tremblay, Lydia; Auclair, Vincent; Daigle, Kathya; Léonard, Guillaume; Whittingstall, Kevin; Goffaux, Philippe

2014-08-01

Sex differences in pain perception are still poorly understood, but they may be related to the way the brains of men and women respond to the affective dimensions of pain. Using a matched pain intensity paradigm, where pain intensity was kept constant across participants but pain unpleasantness was left free to vary among participants, we studied the relationship between pain unpleasantness and pain-evoked brain activity in healthy men and women separately. Experimental pain was provoked using transcutaneous electrical stimulation of the sural nerve while pain-related brain activity was measured using somatosensory-evoked brain potentials with source localization. Cardiac responses to pain were also measured using electrocardiac recordings. Results revealed that subjective pain unpleasantness was strongly associated with increased perigenual anterior cingulate cortex activity in women, whereas it was strongly associated with decreased ventromedial prefrontal cortex activity in men. Only ventromedial prefrontal cortex deactivations in men were additionally associated with increased autonomic cardiac arousal. These results suggest that in order to deal with pain's objectionable properties, men preferentially deactivate prefrontal suppression regions, leading to the mobilization of threat-control circuits, whereas women recruit well-known emotion-processing areas of the brain. This article presents neuroimaging findings demonstrating that subjective pain unpleasantness ratings are associated with different pain-evoked brain responses in men and women, which has potentially important implications regarding sex differences in the risk of developing chronic pain. Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.

Involvement of the Ventrolateral Prefrontal Cortex in Learning Others' Bad Reputations and Indelible Distrust.

PubMed

Suzuki, Atsunobu; Ito, Yuichi; Kiyama, Sachiko; Kunimi, Mitsunobu; Ohira, Hideki; Kawaguchi, Jun; Tanabe, Hiroki C; Nakai, Toshiharu

2016-01-01

A bad reputation can persistently affect judgments of an individual even when it turns out to be invalid and ought to be disregarded. Such indelible distrust may reflect that the negative evaluation elicited by a bad reputation transfers to a person. Consequently, the person him/herself may come to activate this negative evaluation irrespective of the accuracy of the reputation. If this theoretical model is correct, an evaluation-related brain region will be activated when witnessing a person whose bad reputation one has learned about, regardless of whether the reputation is deemed valid or not. Here, we tested this neural hypothesis with functional magnetic resonance imaging (fMRI). Participants memorized faces paired with either a good or a bad reputation. Next, they viewed the faces alone and inferred whether each person was likely to cooperate, first while retrieving the reputations, and then while trying to disregard them as false. A region of the left ventrolateral prefrontal cortex (vlPFC), which may be involved in negative evaluation, was activated by faces previously paired with bad reputations, irrespective of whether participants attempted to retrieve or disregard these reputations. Furthermore, participants showing greater activity of the left ventrolateral prefrontal region in response to the faces with bad reputations were more likely to infer that these individuals would not cooperate. Thus, once associated with a bad reputation, a person may elicit evaluation-related brain responses on their own, thereby evoking distrust independently of their reputation.

Neural activity associated with self-reflection.

PubMed

Herwig, Uwe; Kaffenberger, Tina; Schell, Caroline; Jäncke, Lutz; Brühl, Annette B

2012-05-24

Self-referential cognitions are important for self-monitoring and self-regulation. Previous studies have addressed the neural correlates of self-referential processes in response to or related to external stimuli. We here investigated brain activity associated with a short, exclusively mental process of self-reflection in the absence of external stimuli or behavioural requirements. Healthy subjects reflected either on themselves, a personally known or an unknown person during functional magnetic resonance imaging (fMRI). The reflection period was initialized by a cue and followed by photographs of the respective persons (perception of pictures of oneself or the other person). Self-reflection, compared with reflecting on the other persons and to a major part also compared with perceiving photographs of one-self, was associated with more prominent dorsomedial and lateral prefrontal, insular, anterior and posterior cingulate activations. Whereas some of these areas showed activity in the "other"-conditions as well, self-selective characteristics were revealed in right dorsolateral prefrontal and posterior cingulate cortex for self-reflection; in anterior cingulate cortex for self-perception and in the left inferior parietal lobe for self-reflection and -perception. Altogether, cingulate, medial and lateral prefrontal, insular and inferior parietal regions show relevance for self-related cognitions, with in part self-specificity in terms of comparison with the known-, unknown- and perception-conditions. Notably, the results are obtained here without behavioural response supporting the reliability of this methodological approach of applying a solely mental intervention. We suggest considering the reported structures when investigating psychopathologically affected self-related processing.

Rhythms of Consciousness: Binocular Rivalry Reveals Large-Scale Oscillatory Network Dynamics Mediating Visual Perception

PubMed Central

Doesburg, Sam M.; Green, Jessica J.; McDonald, John J.; Ward, Lawrence M.

2009-01-01

Consciousness has been proposed to emerge from functionally integrated large-scale ensembles of gamma-synchronous neural populations that form and dissolve at a frequency in the theta band. We propose that discrete moments of perceptual experience are implemented by transient gamma-band synchronization of relevant cortical regions, and that disintegration and reintegration of these assemblies is time-locked to ongoing theta oscillations. In support of this hypothesis we provide evidence that (1) perceptual switching during binocular rivalry is time-locked to gamma-band synchronizations which recur at a theta rate, indicating that the onset of new conscious percepts coincides with the emergence of a new gamma-synchronous assembly that is locked to an ongoing theta rhythm; (2) localization of the generators of these gamma rhythms reveals recurrent prefrontal and parietal sources; (3) theta modulation of gamma-band synchronization is observed between and within the activated brain regions. These results suggest that ongoing theta-modulated-gamma mechanisms periodically reintegrate a large-scale prefrontal-parietal network critical for perceptual experience. Moreover, activation and network inclusion of inferior temporal cortex and motor cortex uniquely occurs on the cycle immediately preceding responses signaling perceptual switching. This suggests that the essential prefrontal-parietal oscillatory network is expanded to include additional cortical regions relevant to tasks and perceptions furnishing consciousness at that moment, in this case image processing and response initiation, and that these activations occur within a time frame consistent with the notion that conscious processes directly affect behaviour. PMID:19582165

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.

Impaired awareness of action-outcome contingency and causality during healthy ageing and following ventromedial prefrontal cortex lesions.

PubMed

O'Callaghan, Claire; Vaghi, Matilde M; Brummerloh, Berit; Cardinal, Rudolf N; Robbins, Trevor W

2018-02-02

Detecting causal relationships between actions and their outcomes is fundamental to guiding goal-directed behaviour. The ventromedial prefrontal cortex (vmPFC) has been extensively implicated in computing these environmental contingencies, via animal lesion models and human neuroimaging. However, whether the vmPFC is critical for contingency learning, and whether it can occur without subjective awareness of those contingencies, has not been established. To address this, we measured response adaption to contingency and subjective awareness of action-outcome relationships in individuals with vmPFC lesions and healthy elderly subjects. We showed that in both vmPFC damage and ageing, successful behavioural adaptation to variations in action-outcome contingencies was maintained, but subjective awareness of these contingencies was reduced. These results highlight two contexts where performance and awareness have been dissociated, and show that learning response-outcome contingencies to guide behaviour can occur without subjective awareness. Preserved responding in the vmPFC group suggests that this region is not critical for computing action-outcome contingencies to guide behaviour. In contrast, our findings highlight a critical role for the vmPFC in supporting awareness, or metacognitive ability, during learning. We further advance the hypothesis that responding to changing environmental contingencies, whilst simultaneously maintaining conscious awareness of those statistical regularities, is a form of dual-tasking that is impaired in ageing due to reduced prefrontal function. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

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 prefrontal resource utilization, particularly during complex walking tasks like obstacle crossing, may approach the ceiling of available resources for people who have walking deficits. Prior cognitive research has revealed that prefrontal over-activation combined with limited prefrontal resources can lead to poor cognitive performance. The present study suggests a similar situation influences walking performance. Future research should further investigate the extent to which prefrontal over-activation during walking is linked to adverse mobility outcomes. Published by Elsevier B.V.

Response of dorsomedial prefrontal cortex predicts altruistic behavior

PubMed Central

Waytz, Adam; Zaki, Jamil; Mitchell, Jason P.

2012-01-01

Human beings have an unusual proclivity for altruistic behavior, and recent commentators have suggested that these prosocial tendencies arise from our unique capacity to understand the minds of others (i.e., to mentalize). The current studies test this hypothesis by examining the relation between altruistic behavior and the reflexive engagement of a neural system reliably associated with mentalizing. Results indicated that activity in the dorsomedial prefrontal cortex (dorsal MPFC)—a region consistently involved in understanding others’ mental states—predicts both monetary donations to others and time spent helping others. These findings address long-standing questions about the proximate source of human altruism by suggesting that prosocial behavior results, in part, from our broader tendency for social-cognitive thought. PMID:22649243

The medial prefrontal cortex and memory of cue location in the rat.

PubMed

Rawson, Tim; O'Kane, Michael; Talk, Andrew

2010-01-01

We developed a single-trial cue-location memory task in which rats experienced an auditory cue while exploring an environment. They then recalled and avoided the sound origination point after the cue was paired with shock in a separate context. Subjects with medial prefrontal cortical (mPFC) lesions made no such avoidance response, but both lesioned and control subjects avoided the cue itself when presented at test. A follow up assessment revealed no spatial learning impairment in either group. These findings suggest that the rodent mPFC is required for incidental learning or recollection of the location at which a discrete cue occurred, but is not required for cue recognition or for allocentric spatial memory. Copyright 2009 Elsevier Inc. All rights reserved.

Reduced dorsolateral prefrontal cortex activation during affective Go/NoGo in violent schizophrenia patients: An fMRI study.

PubMed

Tikàsz, Andràs; Potvin, Stéphane; Richard-Devantoy, Stéphane; Lipp, Olivier; Hodgins, Sheilagh; Lalonde, Pierre; Lungu, Ovidiu; Dumais, Alexandre

2017-11-09

We investigated the influence of anger processing on cognitive control in male schizophrenia patients presenting violent behaviors. We recruited 23 patients without and 24 patients with (SCZ+V) a history of violent behaviors, as well as 22 healthy non-violent men. Participants were administered an affective (angry-neutral faces) Go/NoGo task while undergoing functional magnetic resonance imaging. We found a reduced activation in the dorsolateral prefrontal cortex in SCZ+V patients specifically when inhibiting a response while viewing angry faces. These results show an inability of SCZ+V to recruit a core region of the (inhibitory) cognitive control network in the context of anger. Copyright © 2017 Elsevier B.V. All rights reserved.

Motivation alters response bias and neural activation patterns in a perceptual decision-making task.

PubMed

Reckless, G E; Bolstad, I; Nakstad, P H; Andreassen, O A; Jensen, J

2013-05-15

Motivation has been demonstrated to affect individuals' response strategies in economic decision-making, however, little is known about how motivation influences perceptual decision-making behavior or its related neural activity. Given the important role motivation plays in shaping our behavior, a better understanding of this relationship is needed. A block-design, continuous performance, perceptual decision-making task where participants were asked to detect a picture of an animal among distractors was used during functional magnetic resonance imaging (fMRI). The effect of positive and negative motivation on sustained activity within regions of the brain thought to underlie decision-making was examined by altering the monetary contingency associated with the task. In addition, signal detection theory was used to investigate the effect of motivation on detection sensitivity, response bias and response time. While both positive and negative motivation resulted in increased sustained activation in the ventral striatum, fusiform gyrus, left dorsolateral prefrontal cortex (DLPFC) and ventromedial prefrontal cortex, only negative motivation resulted in the adoption of a more liberal, closer to optimal response bias. This shift toward a liberal response bias correlated with increased activation in the left DLPFC, but did not result in improved task performance. The present findings suggest that motivation alters aspects of the way perceptual decisions are made. Further, this altered response behavior is reflected in a change in left DLPFC activation, a region involved in the computation of perceptual decisions. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

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.

Impulsive-antisocial psychopathic traits linked to increased volume and functional connectivity within prefrontal cortex.

PubMed

Korponay, Cole; Pujara, Maia; Deming, Philip; Philippi, Carissa; Decety, Jean; Kosson, David S; Kiehl, Kent A; Koenigs, Michael

2017-07-01

Psychopathy is a personality disorder characterized by callous lack of empathy, impulsive antisocial behavior, and criminal recidivism. Studies of brain structure and function in psychopathy have frequently identified abnormalities in the prefrontal cortex. However, findings have not yet converged to yield a clear relationship between specific subregions of prefrontal cortex and particular psychopathic traits. We performed a multimodal neuroimaging study of prefrontal cortex volume and functional connectivity in psychopathy, using a sample of adult male prison inmates (N = 124). We conducted volumetric analyses in prefrontal subregions, and subsequently assessed resting-state functional connectivity in areas where volume was related to psychopathy severity. We found that overall psychopathy severity and Factor 2 scores (which index the impulsive/antisocial traits of psychopathy) were associated with larger prefrontal subregion volumes, particularly in the medial orbitofrontal cortex and dorsolateral prefrontal cortex. Furthermore, Factor 2 scores were also positively correlated with functional connectivity between several areas of the prefrontal cortex. The results were not attributable to age, race, IQ, substance use history, or brain volume. Collectively, these findings provide evidence for co-localized increases in prefrontal cortex volume and intra-prefrontal functional connectivity in relation to impulsive/antisocial psychopathic traits. © The Author (2017). Published by Oxford University Press.

The organization of the stress system and its dysregulation in depressive illness.

PubMed

Gold, P W

2015-02-01

Stressors are imminent or perceived challenges to homeostasis. The stress response is an innate, stereotypic, adaptive response to stressors that has evolved in the service of restoring the nonstressed homeostatic set point. It is encoded in specific neuroanatomical sites that activate a specific repertoire of cognitive, behavioral and physiologic phenomena. Adaptive responses, though essential for survival, can become dysregulated and result in disease. A clear example is autoimmune disease. I postulate that depression, like autoimmunity, represents a dysregulated adaptive response: a stress response that has gone awry. The cardinal manifestation of the normal stress response is anxiety. Cognitive programs shift from complex associative operations to rapid retrieval of unconscious emotional memories acquired during prior threatening situations. These emerge automatically to promote survival. To prevent distraction during stressful situations, the capacity to seek and experience pleasure is reduced, food intake is diminished and sexual activity and sleep are held in abeyance. Monoamines, cytokines, glutamate, GABA and other central mediators have key roles in the normal stress response. Many central loci are involved. The subgenual prefrontal cortex restrains the amygdala, the corticotropin-releasing hormone/hypothalamic-pituitary-adrenal (CRH/HPA) axis and the sympathomedullary system. The function of the subgenual prefrontal cortex is moderately diminished during normal stress to disinhibit these loci. This disinhibition promotes anxiety and physiological hyperarousal, while diminishing appetite and sleep. The dorsolateral prefrontal cortex is downregulated, diminishing cognitive regulation of anxiety. The nucleus accumbens is also downregulated, to reduce the propensity for distraction by pleasurable stimuli or the capacity to experience pleasure. Insulin resistance, inflammation and a prothrombotic state acutely emerge. These provide increased glucose for the brain and establish premonitory, proinflammatory and prothrombotic states in anticipation of either injury or hemorrhage during a threatening situation. Essential adaptive intracellular changes include increased neurogenesis, enhancement of neuroplasticity and deployment of a successful endoplasmic reticulum stress response. In melancholic depression, the activities of the central glutamate, norepinephrine and central cytokine systems are significantly and persistently increased. The subgenual prefrontal cortex is functionally impaired, and its size is reduced by as much as 40%. This leads to sustained anxiety and activations of the amygdala, CRH/HPA axis, the sympathomedullary system and their sequella, including early morning awakening and loss of appetite. The sustained activation of the amygdala, in turn, further activates stress system neuroendocrine and autonomic functions. The activity of the nucleus accumbens is further decreased and anhedonia emerges. Concomitantly, neurogenesis and neuroplasticity fall significantly. Antidepressants ameliorate many of these processes. The processes that lead to the behavioral and physiological manifestations of depressive illness produce a significant decrease in lifespan, and a doubling of the incidence of premature coronary artery disease. The incidences of premature diabetes and osteoporosis are also substantially increased. Six physiological processes that occur during stress and that are markedly increased in melancholia set into motion six different mechanisms to produce inflammation, as well as sustained insulin resistance and a prothrombotic state. Clinically, melancholic and atypical depression seem to be antithesis of one another. In melancholia, depressive systems are at their worst in the morning when arousal systems, such as the CRH/HPA axis and the noradrenergic systems, are at their maxima. In atypical depression, depressive symptoms are at their worst in the evening, when these arousal systems are at their minima. Melancholic patients experience anorexia and insomnia, whereas atypical patients experience hyperphagia and hypersomnia. Melancholia seems like an activation and persistence of the normal stress response, whereas atypical depression resembles a stress response that has been excessively inhibited. It is important that we stratify clinical studies of depressed patients to compare melancholic and atypical subtypes and establish their differential pathophysiology. Overall, it is important to note that many of the major mediators of the stress response and melancholic depression, such as the subgenual prefrontal cortex, the amygdala, the noradrenergic system and the CRH/HPA axis participate in multiple reinforcing positive feedback loops. This organization permits the establishment of the markedly exaggerated, persistent elevation of the stress response seen in melancholia. Given their pronounced interrelatedness, it may not matter where in this cascade the first abnormality arises. It will spread to the other loci and initiate each of their activations in a pernicious vicious cycle.

The medial prefrontal cortex: coordinator of autonomic, neuroendocrine and behavioural responses to stress.

PubMed

McKlveen, J M; Myers, B; Herman, J P

2015-06-01

Responding to real or potential threats in the environment requires the coordination of autonomic, neuroendocrine and behavioural processes to promote adaptation and survival. These diverging systems necessitate input from the limbic forebrain to integrate and modulate functional output in accordance with contextual demand. In the present review, we discuss the potential role of the medial prefrontal cortex (mPFC) as a coordinator of behavioural and physiological stress responses across multiple temporal and contextual domains. Furthermore, we highlight converging evidence from rodent and human research indicating the necessity of the mPFC for modulating physiological energetic systems to mobilise or limit energetic resources as needed to ultimately promote behavioural adaptation in the face of stress. We review the literature indicating that glucocorticoids act as one of the primary messengers in the reallocation of energetic resources having profound effects locally within the mPFC, as well as shaping how the mPFC acts within a network of brain structures to modulate responses to stress. Finally, we discuss how both rodent and human studies point toward a critical role of the mPFC in the coordination of anticipatory responses to stress and why this distinction is an important one to make in stress neurobiology. © 2015 British Society for Neuroendocrinology.

Medial prefrontal cortex acetylcholine injection-induced hypotension: the role of hindlimb vasodilation

NASA Technical Reports Server (NTRS)

Crippa, G. E.; Lewis, S. J.; Johnson, A. K.; Correa, F. M.

2000-01-01

The injection of acetylcholine (ACh) into the cingulate region of the medial prefrontal cortex (MPFC) causes a marked fall in arterial blood pressure which is not accompanied by changes in heart rate. The purpose of the present study was to investigate the hemodynamic basis for this stimulus-induced hypotension in Sprague-Dawley rats. The study was designed to determine whether a change in the vascular resistance of hindlimb, renal or mesenteric vascular beds contributes to the fall in arterial pressure in response to ACh injection into the cingulate cortex. Miniature pulsed-Doppler flow probes were used to measure changes in regional blood flow and vascular resistance. The results indicated that the hypotensive response was largely due to a consistent and marked vasodilation in the hindlimb vascular bed. On this basis, an additional experiment was then undertaken to determine the mechanisms that contribute to hindlimb vasodilation. The effect of interrupting the autonomic innervation of one leg on the hindlimb vasodilator response was tested. Unilateral transection of the lumbar sympathetic chain attenuated the cingulate ACh-induced vasodilation in the ipsilateral, but not in the contralateral hindlimb. These results suggest that the hypotensive response to cingulate cortex-ACh injection is caused by skeletal muscle vasodilation mediated by a sympathetic chain-related vasodilator system.

Poor decision-making by chronic marijuana users is associated with decreased functional responsiveness to negative consequences.

PubMed

Wesley, Michael J; Hanlon, Colleen A; Porrino, Linda J

2011-01-30

Chronic marijuana users (MJ Users) perform poorly on the Iowa Gambling Task (IGT), a complex decision-making task in which monetary wins and losses guide strategy development. This functional magnetic resonance imaging (MRI) study sought to determine if the poor performance of MJ Users was related to differences in brain activity while evaluating wins and losses during the strategy development phase of the IGT. MJ Users (16) and Controls (16) performed a modified IGT in an MRI scanner. Performance was tracked and functional activity in response to early wins and losses was examined. While the MJ Users continued to perform poorly at the end of the task, there was no difference in group performance during the initial strategy development phase. During this phase, before the emergence of behavioral differences, Controls exhibited significantly greater activity in response to losses in the anterior cingulate cortex, medial frontal cortex, precuneus, superior parietal lobe, occipital lobe and cerebellum as compared to MJ Users. Furthermore, in Controls, but not MJ Users, the functional response to losses in the anterior cingulate cortex, ventral medial prefrontal cortex and rostral prefrontal cortex positively correlated with performance over time. These data suggest MJ Users are less sensitive to negative feedback during strategy development. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Depression of Excitatory Synapses onto Parvalbumin Interneurons in the Medial Prefrontal Cortex in Susceptibility to Stress

PubMed Central

Delevich, Kristen

2015-01-01

In response to extreme stress, individuals either show resilience or succumb to despair. The prefrontal cortex (PFC) is required for coping with stress, and PFC dysfunction has been implicated in stress-related mental disorders, including depression. Nevertheless, the mechanisms by which the PFC participates in stress responses remain unclear. Here, we investigate the role of parvalbumin (PV) interneurons in the medial PFC (mPFC) in shaping behavioral responses to stress induced by the learned helplessness procedure, in which animals are subjected to an unpredictable and inescapable stressor. PV interneurons in the mPFC were probed and manipulated in knock-in mice expressing the Cre recombinase under the endogenous parvalbumin promoter. Notably, we found that excitatory synaptic transmission onto these neurons was decreased in mice showing helplessness, a behavioral state that is thought to resemble features of human depression. Furthermore, selective suppression of PV interneurons in the mPFC using hM4Di, a DREADD (designer receptor exclusively activated by designer drug), promoted helplessness, indicating that activation of these neurons during stress promotes the establishment of resilient behavior. Our results reveal a cellular mechanism of mPFC dysfunction that may contribute to the emergence of maladaptive behavioral responses in the face of adverse life events. PMID:25698754

A conceptual model of plant responses to climate with implications for monitoring ecosystem change

Treesearch

C. David Bertelsen

2013-01-01

Climate change is affecting natural systems on a global scale and is particularly rapid in the Southwest. It is important to identify impacts of a changing climate before ecosystems become unstable. Recognizing plant responses to climate change requires knowledge of both species present and plant responses to variable climatic conditions. A conceptual model derived...

"Social, technological, and research responses to potential erosion and sediment disasters in the western United States, with examples from California"

Treesearch

R. M. Rice

1985-01-01

Synopsis - Examples from California are used to illustrate typical responses to erosion and debris flow disasters the United States. Political institutions leave virtually all responsibility for disaster prevention to the lowest levels of government or to individuals. Three circumstances in which disasters occur are discussed: urbanized debris cones, urbanized unstable...

Social, technological, and research responses to potential erosion and sediment disasters in the western United States, with examples from California

Treesearch

R. M. Rice

1985-01-01

Examples from California are used to illustrate typical responses to erosion and debris flow disasters in the United States. Political institutions leave virtually all responsibility for disaster prevention to the lowest levels of government or to individuals. Three circumstances in which disasters occur are discussed: urbanized debris cones, urbanized unstable...

Serotonin Transporter Knockout Rats Show Improved Strategy Set-Shifting and Reduced Latent Inhibition

ERIC Educational Resources Information Center

Nonkes, Lourens J. P.; van de Vondervoort, Ilse I. G. M.; de Leeuw, Mark J. C.; Wijlaars, Linda P.; Maes, Joseph H. R.; Homberg, Judith R.

2012-01-01

Behavioral flexibility is a cognitive process depending on prefrontal areas allowing adaptive responses to environmental changes. Serotonin transporter knockout (5-HTT[superscript -/-]) rodents show improved reversal learning in addition to orbitofrontal cortex changes. Another form of behavioral flexibility, extradimensional strategy set-shifting…

Working memory performance and neural activity in prefrontal cortex of peripubertal monkeys

PubMed Central

Zhou, Xin; Zhu, Dantong; Qi, Xue-Lian; Lees, Cynthia J.; Bennett, Allyson J.; Salinas, Emilio; Stanford, Terrence R.

2013-01-01

The dorsolateral prefrontal cortex matures late into adolescence or early adulthood. This pattern of maturation mirrors working memory abilities, which continue to improve into adulthood. However, the nature of the changes that prefrontal neuronal activity undergoes during this process is poorly understood. We investigated behavioral performance and neural activity in working memory tasks around the time of puberty, a developmental event associated with the release of sex hormones and significant neurological change. The developmental stages of male rhesus monkeys were evaluated with a series of morphometric, hormonal, and radiographic measures. Peripubertal monkeys were trained to perform an oculomotor delayed response task and a variation of this task involving a distractor stimulus. We found that the peripubertal monkeys tended to abort a relatively large fraction of trials, and these were associated with low levels of task-related neuronal activity. However, for completed trials, accuracy in the delayed saccade task was high and the appearance of a distractor stimulus did not impact performance significantly. In correct trials delay period activity was robust and was not eliminated by the presentation of a distracting stimulus, whereas in trials that resulted in errors the sustained cue-related activity was significantly weaker. Our results show that in peripubertal monkeys the prefrontal cortex is capable of generating robust persistent activity in the delay periods of working memory tasks, although in general it may be more prone to stochastic failure than in adults. PMID:24047904

Brain nicotinic acetylcholine receptors are involved in stress-induced potentiation of nicotine reward in rats.

PubMed

Javadi, Parastoo; Rezayof, Ameneh; Sardari, Maryam; Ghasemzadeh, Zahra

2017-07-01

The aim of the present study was to examine the possible role of nicotinic acetylcholine receptors of the dorsal hippocampus (CA1 regions), the medial prefrontal cortex or the basolateral amygdala in the effect of acute or sub-chronic stress on nicotine-induced conditioned place preference. Our results indicated that subcutaneous administration of nicotine (0.2 mg/kg) induced significant conditioned place preference. Exposure to acute or sub-chronic elevated platform stress potentiated the response of an ineffective dose of nicotine. Pre-conditioning intra-CA1 (0.5-4 µg/rat) or intra-medial prefrontal cortex (0.2-0.3 µg/rat) microinjection of mecamylamine (a non-selective nicotinic acetylcholine receptor antagonist) reversed acute stress-induced potentiation of nicotine reward as measured in the conditioned place preference paradigm. By contrast, pre-conditioning intra-basolateral amygdala microinjection of mecamylamine (4 µg/rat) potentiated the effects of acute stress on nicotine reward. Our findings also showed that intra-CA1 or intra-medial prefrontal cortex, but not intra-basolateral amygdala, microinjection of mecamylamine (4 µg/rat) prevented the effect of sub-chronic stress on nicotine reward. These findings suggest that exposure to elevated platform stress potentiates the rewarding effect of nicotine which may be associated with the involvement of nicotinic acetylcholine receptors. It seems that there is a different contribution of the basolateral amygdala, the medial prefrontal cortex or the CA1 nicotinic acetylcholine receptors in stress-induced potentiation of nicotine-induced conditioned place preference.

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.

Human ventromedial prefrontal lesions alter incentivisation by reward.

PubMed

Manohar, Sanjay G; Husain, Masud

2016-03-01

Although medial frontal brain regions are implicated in valuation of rewards, evidence from focal lesions to these areas is scant, with many conflicting results regarding motivation and affect, and no human studies specifically examining incentivisation by reward. Here, 19 patients with isolated, focal damage in ventral and medial prefrontal cortex were selected from a database of 453 individuals with subarachnoid haemorrhage. Using a speeded saccadic task based on the oculomotor capture paradigm, we manipulated the maximum reward available on each trial using an auditory incentive cue. Modulation of behaviour by motivation permitted quantification of reward sensitivity. At the group level, medial frontal damage was overall associated with significantly reduced effects of reward on invigorating saccadic velocity and autonomic (pupil) responses compared to age-matched, healthy controls. Crucially, however, some individuals instead showed abnormally strong incentivisation effects for vigour. Increased sensitivity to rewards within the lesion group correlated with damage in subgenual ventromedial prefrontal cortex (vmPFC) areas, which have recently become the target for deep brain stimulation (DBS) in depression. Lesion correlations with clinical apathy suggested that the apathy associated with prefrontal damage is in fact reduced by damage at those coordinates. Reduced reward sensitivity showed a trend to correlate with damage near nucleus accumbens. Lesions did not, on the other hand, influence reward sensitivity of cognitive control, as measured by distractibility. Thus, although medial frontal lesions may generally reduce reward sensitivity, damage to key subregions paradoxically protect from this effect. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Human ventromedial prefrontal lesions alter incentivisation by reward

PubMed Central

Manohar, Sanjay G.; Husain, Masud

2016-01-01

Although medial frontal brain regions are implicated in valuation of rewards, evidence from focal lesions to these areas is scant, with many conflicting results regarding motivation and affect, and no human studies specifically examining incentivisation by reward. Here, 19 patients with isolated, focal damage in ventral and medial prefrontal cortex were selected from a database of 453 individuals with subarachnoid haemorrhage. Using a speeded saccadic task based on the oculomotor capture paradigm, we manipulated the maximum reward available on each trial using an auditory incentive cue. Modulation of behaviour by motivation permitted quantification of reward sensitivity. At the group level, medial frontal damage was overall associated with significantly reduced effects of reward on invigorating saccadic velocity and autonomic (pupil) responses compared to age-matched, healthy controls. Crucially, however, some individuals instead showed abnormally strong incentivisation effects for vigour. Increased sensitivity to rewards within the lesion group correlated with damage in subgenual ventromedial prefrontal cortex (vmPFC) areas, which have recently become the target for deep brain stimulation (DBS) in depression. Lesion correlations with clinical apathy suggested that the apathy associated with prefrontal damage is in fact reduced by damage at those coordinates. Reduced reward sensitivity showed a trend to correlate with damage near nucleus accumbens. Lesions did not, on the other hand, influence reward sensitivity of cognitive control, as measured by distractibility. Thus, although medial frontal lesions may generally reduce reward sensitivity, damage to key subregions paradoxically protect from this effect. PMID:26874940

Structural Covariance of the Prefrontal-Amygdala Pathways Associated with Heart Rate Variability.

PubMed

Wei, Luqing; Chen, Hong; Wu, Guo-Rong

2018-01-01

The neurovisceral integration model has shown a key role of the amygdala in neural circuits underlying heart rate variability (HRV) modulation, and suggested that reciprocal connections from amygdala to brain regions centered on the central autonomic network (CAN) are associated with HRV. To provide neuroanatomical evidence for these theoretical perspectives, the current study used covariance analysis of MRI-based gray matter volume (GMV) to map structural covariance network of the amygdala, and then determined whether the interregional structural correlations related to individual differences in HRV. The results showed that covariance patterns of the amygdala encompassed large portions of cortical (e.g., prefrontal, cingulate, and insula) and subcortical (e.g., striatum, hippocampus, and midbrain) regions, lending evidence from structural covariance analysis to the notion that the amygdala was a pivotal node in neural pathways for HRV modulation. Importantly, participants with higher resting HRV showed increased covariance of amygdala to dorsal medial prefrontal cortex and anterior cingulate cortex (dmPFC/dACC) extending into adjacent medial motor regions [i.e., pre-supplementary motor area (pre-SMA)/SMA], demonstrating structural covariance of the prefrontal-amygdala pathways implicated in HRV, and also implying that resting HRV may reflect the function of neural circuits underlying cognitive regulation of emotion as well as facilitation of adaptive behaviors to emotion. Our results, thus, provide anatomical substrates for the neurovisceral integration model that resting HRV may index an integrative neural network which effectively organizes emotional, cognitive, physiological and behavioral responses in the service of goal-directed behavior and adaptability.

The neural networks of subjectively evaluated emotional conflicts.

PubMed

Rohr, Christiane S; Villringer, Arno; Solms-Baruth, Carolina; van der Meer, Elke; Margulies, Daniel S; Okon-Singer, Hadas

2016-06-01

Previous work on the neural underpinnings of emotional conflict processing has largely focused on designs that instruct participants to ignore a distracter which conflicts with a target. In contrast, this study investigated the noninstructed experience and evaluation of an emotional conflict, where positive or negative cues can be subjectively prioritized. To this end, healthy participants freely watched short film scenes that evoked emotional conflicts while their BOLD responses were measured. Participants' individual ratings of conflict and valence perception during the film scenes were collected immediately afterwards, and the individual ratings were regressed against the BOLD data. Our analyses revealed that (a) amygdala and medial prefrontal cortex were significantly involved in prioritizing positive or negative cues, but not in subjective evaluations of conflict per se, and (b) superior temporal sulcus (STS) and inferior parietal lobule (IPL), which have been implicated in social cognition and emotion control, were involved in both prioritizing positive or negative cues and subjectively evaluating conflict, and may thus constitute "hubs" or "switches" in emotional conflict processing. Psychophysiological interaction (PPI) analyses further revealed stronger functional connectivity between IPL and ventral prefrontal-medial parietal areas in prioritizing negative cues, and stronger connectivity between STS and dorsal-rostral prefrontal-medial parietal areas in prioritizing positive cues. In sum, our results suggest that IPL and STS are important in the subjective evaluation of complex conflicts and influence valence prioritization via prefrontal and parietal control centers. Hum Brain Mapp 37:2234-2246, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Hyperresponsivity and impaired prefrontal control of the mesolimbic reward system in schizophrenia.

PubMed

Richter, Anja; Petrovic, Aleksandra; Diekhof, Esther K; Trost, Sarah; Wolter, Sarah; Gruber, Oliver

2015-12-01

Schizophrenia is characterized by substantial dysfunctions of reward processing, leading to detrimental consequences for decision-making. The neurotransmitter dopamine is responsible for the transmission of reward signals and also known to be involved in the mechanism of psychosis. Using functional magnetic resonance imaging (fMRI), sixteen medicated patients with schizophrenia and sixteen healthy controls performed the 'desire-reason dilemma' (DRD) paradigm. This paradigm allowed us to directly investigate reward-related brain activations depending on the interaction of bottom-up and top-down mechanisms, when a previously conditioned reward stimulus had to be rejected to achieve a superordinate long-term goal. Both patients and controls showed significant activations in the mesolimbic reward system. In patients with schizophrenia, however, we found a significant hyperactivation of the left ventral striatum (vStr) when they were allowed to accept the conditioned reward stimuli, and a reduced top-down regulation of activation in the ventral striatum (vStr) and ventral tegmental area (VTA) while having to reject the immediate reward to pursue the superordinate task-goal. Moreover, while healthy subjects exhibited a negative functional coupling of the vStr with both the anteroventral prefrontal cortex (avPFC) and the ventromedial prefrontal cortex (VMPFC) in the dilemma situation, this functional coupling was significantly impaired in the patient group. These findings provide evidence for an increased ventral striatal activation to reward stimuli and an impaired top-down control of reward signals by prefrontal brain regions in schizophrenia. Copyright © 2015 Elsevier Ltd. All rights reserved.

The neural dynamics of competition resolution for language production in the prefrontal cortex.

PubMed

Bourguignon, Nicolas J; Ohashi, Hiroki; Nguyen, Don; Gracco, Vincent L

2018-03-01

Previous research suggests a pivotal role of the prefrontal cortex (PFC) in word selection during tasks of confrontation naming (CN) and verb generation (VG), both of which feature varying degrees of competition between candidate responses. However, discrepancies in prefrontal activity have also been reported between the two tasks, in particular more widespread and intense activation in VG extending into (left) ventrolateral PFC, the functional significance of which remains unclear. We propose that these variations reflect differences in competition resolution processes tied to distinct underlying lexico-semantic operations: Although CN involves selecting lexical entries out of limited sets of alternatives, VG requires exploration of possible semantic relations not readily evident from the object itself, requiring prefrontal areas previously shown to be recruited in top-down retrieval of information from lexico-semantic memory. We tested this hypothesis through combined independent component analysis of functional imaging data and information-theoretic measurements of variations in selection competition associated with participants' performance in overt CN and VG tasks. Selection competition during CN engaged the anterior insula and surrounding opercular tissue, while competition during VG recruited additional activity of left ventrolateral PFC. These patterns remained after controlling for participants' speech onset latencies indicative of possible task differences in mental effort. These findings have implications for understanding the neural-computational dynamics of cognitive control in language production and how it relates to the functional architecture of adaptive behavior. © 2017 Wiley Periodicals, Inc.