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.

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

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.

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

PubMed

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

2014-09-01

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

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

NASA Astrophysics Data System (ADS)

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

2003-12-01

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

The development of the ventral prefrontal cortex and social flexibility.

PubMed

Nelson, Eric E; Guyer, Amanda E

2011-07-01

Over the last several years a number of studies in both humans and animals have suggested that the orbitofrontal and ventrolateral prefrontal cortices play an important role in generating flexible behavior. We suggest that input from these brain regions contribute to three functions involved in generating flexible behavior within social contexts: valuation, inhibition, and rule use. Recent studies have also demonstrated that the prefrontal cortex undergoes a prolonged course of maturation that extends well after puberty. Here, we review evidence that the prolonged development of these prefrontal regions parallels a slowly emerging ability for flexible social behavior. We also speculate on the possibility that sensitive periods for organizing social behavior may be embedded within this developmental time-fame. Finally, we discuss the role of prefrontal cortex in adolescent mood and anxiety disorders, particularly as orbitofrontal and ventrolateral prefrontal cortices are engaged in a social context.

The Development of the Ventral Prefrontal Cortex and Social Flexibility

PubMed Central

Nelson, Eric E.; Guyer, Amanda E.

2011-01-01

Over the last several years a number of studies in both humans and animals have suggested that the orbitofrontal and ventrolateral prefrontal cortices play an important role in generating flexible behavior. We suggest that input from these brain regions contribute to three functions involved in generating flexible behavior within social contexts: valuation, inhibition, and rule use. Recent studies have also demonstrated that the prefrontal cortex undergoes a prolonged course of maturation that extends well after puberty. Here, we review evidence that the prolonged development of these prefrontal regions parallels a slowly emerging ability for flexible social behavior. We also speculate on the possibility that sensitive periods for organizing social behavior may be embedded within this developmental time-fame. Finally, we discuss the role of prefrontal cortex in adolescent mood and anxiety disorders, particularly as orbitofrontal and ventrolateral prefrontal cortices are engaged in a social context. PMID:21804907

Listening to a baby crying induces higher electroencephalographic synchronization among prefrontal, temporal and parietal cortices in adoptive mothers.

PubMed

Pérez-Hernández, M; Hernández-González, M; Hidalgo-Aguirre, R M; Amezcua-Gutiérrez, C; Guevara, M A

2017-05-01

Women who adopt babies show caring behaviors and respond to stimuli from their infants just as biological mothers do, but several studies have shown that the cerebral functionality of biological mothers (BM) and adoptive mothers (AM) changes in relation to the type and emotional mean of the stimuli they receive from their babies. The complex perception and processing of different stimuli with emotional content (such as those emitted by babies) require functional synchronization among different cortical and subcortical brain areas. To determine whether the degree of functional synchronization between cortices varies when they perceive such stimuli, this study characterized the degree of cortical electroencephalographic (EEG) synchronization (correlation) among prefrontal, temporal and parietal areas in BM, AM and non-mothers while listening to a recording of a baby crying. BM showed a decreased EEG synchronization between the prefrontal and temporal cortices that may indicate a decrease in the modulatory control that the former exerts on the posterior cortices, and could be associated with deeper emotional involvement and increased sensitivity to the baby crying. The AM, in contrast, had higher degree of EEG synchronization between cortical areas in both hemispheres, likely associated with a greater modulation of the affective information of the crying baby, which allowed them to perceive it as less unpleasant. These data enrich our knowledge of the neurofunctional changes involved in motherhood, and of the neural processes that allow mothers (biological and adoptive) to be sensitive to their infants' cues and respond appropriately. Copyright © 2017 Elsevier Inc. All rights reserved.

Bipolar disorder type I and II show distinct relationships between cortical thickness and executive function.

PubMed

Abé, C; Rolstad, S; Petrovic, P; Ekman, C-J; Sparding, T; Ingvar, M; Landén, M

2018-06-15

Frontal cortical abnormalities and executive function impairment co-occur in bipolar disorder. Recent studies have shown that bipolar subtypes differ in the degree of structural and functional impairments. The relationships between cognitive performance and cortical integrity have not been clarified and might differ across patients with bipolar disorder type I, II, and healthy subjects. Using a vertex-wise whole-brain analysis, we investigated how cortical integrity, as measured by cortical thickness, correlates with executive performance in patients with bipolar disorder type I, II, and controls (N = 160). We found focal associations between executive function and cortical thickness in the medial prefrontal cortex in bipolar II patients and controls, but not in bipolar I disorder. In bipolar II patients, we observed additional correlations in lateral prefrontal and occipital regions. Our findings suggest that bipolar disorder patients show altered structure-function relationships, and importantly that those relationships may differ between bipolar subtypes. The findings are line with studies suggesting subtype-specific neurobiological and cognitive profiles. This study contributes to a better understanding of brain structure-function relationships in bipolar disorder and gives important insights into the neuropathophysiology of diagnostic subtypes. © 2018 The Authors Acta Psychiatrica Scandinavica Published by John Wiley & Sons Ltd.

Advancing functional dysconnectivity and atrophy in progressive supranuclear palsy.

PubMed

Brown, Jesse A; Hua, Alice Y; Trujllo, Andrew; Attygalle, Suneth; Binney, Richard J; Spina, Salvatore; Lee, Suzee E; Kramer, Joel H; Miller, Bruce L; Rosen, Howard J; Boxer, Adam L; Seeley, William W

2017-01-01

Progressive supranuclear palsy syndrome (PSP-S) results from neurodegeneration within a network of brainstem, subcortical, frontal and parietal cortical brain regions. It is unclear how network dysfunction progresses and relates to longitudinal atrophy and clinical decline. In this study, we evaluated patients with PSP-S (n = 12) and healthy control subjects (n = 20) at baseline and 6 months later. Subjects underwent structural MRI and task-free functional MRI (tf-fMRI) scans and clinical evaluations at both time points. At baseline, voxel based morphometry (VBM) revealed that patients with mild-to-moderate clinical symptoms showed structural atrophy in subcortex and brainstem, prefrontal cortex (PFC; supplementary motor area, paracingulate, dorsal and ventral medial PFC), and parietal cortex (precuneus). Tf-fMRI functional connectivity (FC) was examined in a rostral midbrain tegmentum (rMT)-anchored intrinsic connectivity network that is compromised in PSP-S. In healthy controls, this network contained a medial parietal module, a prefrontal-paralimbic module, and a subcortical-brainstem module. Baseline FC deficits in PSP-S were most severe in rMT network integrative hubs in the prefrontal-paralimbic and subcortical-brainstem modules. Longitudinally, patients with PSP-S had declining intermodular FC between the subcortical-brainstem and parietal modules, while progressive atrophy was observed in subcortical-brainstem regions (midbrain, pallidum) and posterior frontal (perirolandic) cortex. This suggested that later-stage subcortical-posterior cortical change may follow an earlier-stage subcortical-anterior cortical disease process. Clinically, patients with more severe baseline impairment showed greater subsequent prefrontal-parietal cortical FC declines and posterior frontal atrophy rates, while patients with more rapid longitudinal clinical decline showed coupled prefrontal-paralimbic FC decline. VBM and FC can augment disease monitoring in PSP-S by tracking the disease through stages while detecting changes that accompany heterogeneous clinical progression.

Amygdala functional disconnection with the prefrontal-cingulate-temporal circuit in chronic tinnitus patients with depressive mood.

PubMed

Chen, Yu-Chen; Bo, Fan; Xia, Wenqing; Liu, Shenghua; Wang, Peng; Su, Wen; Xu, Jin-Jing; Xiong, Zhenyu; Yin, Xindao

2017-10-03

Chronic tinnitus is often accompanied with depressive symptom, which may arise from aberrant functional coupling between the amygdala and cerebral cortex. To explore this hypothesis, resting-state functional magnetic resonance imaging (fMRI) was used to investigate the disrupted amygdala-cortical functional connectivity (FC) in chronic tinnitus patients with depressive mood. Chronic tinnitus patients with depressive mood (n=20), without depressive mood (n=20), and well-matched healthy controls (n=23) underwent resting-state fMRI scanning. Amygdala-cortical FC was characterized using a seed-based whole-brain correlation method. The bilateral amygdala FC was compared among the three groups. Compared to non-depressed patients, depressive tinnitus patients showed decreased amygdala FC with the prefrontal cortex and anterior cingulate cortex as well as increased amygdala FC with the postcentral gyrus and lingual gyrus. Relative to healthy controls, depressive tinnitus patients revealed decreased amygdala FC with the superior and middle temporal gyrus, anterior and posterior cingulate cortex, and prefrontal cortex, as well as increased amygdala FC with the postcentral gyrus and lingual gyrus. The current study identified for the first time abnormal resting-state amygdala-cortical FC with the prefrontal-cingulate-temporal circuit in chronic tinnitus patients with depressive mood, which will provide novel insight into the underlying neuropathological mechanisms of tinnitus-induced depressive disorder. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed

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

2016-02-01

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

Age Differences in Prefrontal Surface Area and Thickness in Middle Aged to Older Adults.

PubMed

Dotson, Vonetta M; Szymkowicz, Sarah M; Sozda, Christopher N; Kirton, Joshua W; Green, Mackenzie L; O'Shea, Andrew; McLaren, Molly E; Anton, Stephen D; Manini, Todd M; Woods, Adam J

2015-01-01

Age is associated with reductions in surface area and cortical thickness, particularly in prefrontal regions. There is also evidence of greater thickness in some regions at older ages. Non-linear age effects in some studies suggest that age may continue to impact brain structure in later decades of life, but relatively few studies have examined the impact of age on brain structure within middle-aged to older adults. We investigated age differences in prefrontal surface area and cortical thickness in healthy adults between the ages of 51 and 81 years. Participants received a structural 3-Tesla magnetic resonance imaging scan. Based on a priori hypotheses, primary analyses focused on surface area and cortical thickness in the dorsolateral prefrontal cortex, anterior cingulate cortex, and orbitofrontal cortex. We also performed exploratory vertex-wise analyses of surface area and cortical thickness across the entire cortex. We found that older age was associated with smaller surface area in the dorsolateral prefrontal and orbitofrontal cortices but greater cortical thickness in the dorsolateral prefrontal and anterior cingulate cortices. Vertex-wise analyses revealed smaller surface area in primarily frontal regions at older ages, but no age effects were found for cortical thickness. Results suggest age is associated with reduced surface area but greater cortical thickness in prefrontal regions during later decades of life, and highlight the differential effects age has on regional surface area and cortical thickness.

Evolution of the cerebellar cortex: the selective expansion of prefrontal-projecting cerebellar lobules.

PubMed

Balsters, J H; Cussans, E; Diedrichsen, J; Phillips, K A; Preuss, T M; Rilling, J K; Ramnani, N

2010-02-01

It has been suggested that interconnected brain areas evolve in tandem because evolutionary pressures act on complete functional systems rather than on individual brain areas. The cerebellar cortex has reciprocal connections with both the prefrontal cortex and motor cortex, forming independent loops with each. Specifically, in capuchin monkeys cerebellar cortical lobules Crus I and Crus II connect with prefrontal cortex, whereas the primary motor cortex connects with cerebellar lobules V, VI, VIIb, and VIIIa. Comparisons of extant primate species suggest that the prefrontal cortex has expanded more than cortical motor areas in human evolution. Given the enlargement of the prefrontal cortex relative to motor cortex in humans, our hypothesis would predict corresponding volumetric increases in the parts of the cerebellum connected to the prefrontal cortex, relative to cerebellar lobules connected to the motor cortex. We tested the hypothesis by comparing the volumes of cerebellar lobules in structural MRI scans in capuchins, chimpanzees and humans. The fractions of cerebellar volume occupied by Crus I and Crus II were significantly larger in humans compared to chimpanzees and capuchins. Our results therefore support the hypothesis that in the cortico-cerebellar system, functionally related structures evolve in concert with each other. The evolutionary expansion of these prefrontal-projecting cerebellar territories might contribute to the evolution of the higher cognitive functions of humans. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Emotion regulation ability varies in relation to intrinsic functional brain architecture

PubMed Central

Uchida, Mai; Biederman, Joseph; Gabrieli, John D. E.; Micco, Jamie; de Los Angeles, Carlo; Brown, Ariel; Kenworthy, Tara; Kagan, Elana

2015-01-01

This study investigated the neural basis of individual variation in emotion regulation, specifically the ability to reappraise negative stimuli so as to down-regulate negative affect. Brain functions in young adults were measured with functional Magnetic Resonance Imaging during three conditions: (i) attending to neutral pictures; (ii) attending to negative pictures and (iii) reappraising negative pictures. Resting-state functional connectivity was measured with amygdala and dorsolateral prefrontal cortical (DLPFC) seed regions frequently associated with emotion regulation. Participants reported more negative affect after attending to negative than neutral pictures, and less negative affect following reappraisal. Both attending to negative vs neutral pictures and reappraising vs attending to negative pictures yielded widespread activations that were significantly right-lateralized for attending to negative pictures and left-lateralized for reappraising negative pictures. Across participants, more successful reappraisal correlated with less trait anxiety and more positive daily emotion, greater activation in medial and lateral prefrontal regions, and lesser resting-state functional connectivity between (a) right amygdala and both medial prefrontal and posterior cingulate cortices, and (b) bilateral DLPFC and posterior visual cortices. The ability to regulate emotion, a source of resilience or of risk for distress, appears to vary in relation to differences in intrinsic functional brain architecture. PMID:25999363

Emotion regulation ability varies in relation to intrinsic functional brain architecture.

PubMed

Uchida, Mai; Biederman, Joseph; Gabrieli, John D E; Micco, Jamie; de Los Angeles, Carlo; Brown, Ariel; Kenworthy, Tara; Kagan, Elana; Whitfield-Gabrieli, Susan

2015-12-01

This study investigated the neural basis of individual variation in emotion regulation, specifically the ability to reappraise negative stimuli so as to down-regulate negative affect. Brain functions in young adults were measured with functional Magnetic Resonance Imaging during three conditions: (i) attending to neutral pictures; (ii) attending to negative pictures and (iii) reappraising negative pictures. Resting-state functional connectivity was measured with amygdala and dorsolateral prefrontal cortical (DLPFC) seed regions frequently associated with emotion regulation. Participants reported more negative affect after attending to negative than neutral pictures, and less negative affect following reappraisal. Both attending to negative vs neutral pictures and reappraising vs attending to negative pictures yielded widespread activations that were significantly right-lateralized for attending to negative pictures and left-lateralized for reappraising negative pictures. Across participants, more successful reappraisal correlated with less trait anxiety and more positive daily emotion, greater activation in medial and lateral prefrontal regions, and lesser resting-state functional connectivity between (a) right amygdala and both medial prefrontal and posterior cingulate cortices, and (b) bilateral DLPFC and posterior visual cortices. The ability to regulate emotion, a source of resilience or of risk for distress, appears to vary in relation to differences in intrinsic functional brain architecture. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

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

PubMed Central

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

2016-01-01

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

Alterations of resting state networks and structural connectivity in relation to the prefrontal and anterior cingulate cortices in late prematurity.

PubMed

Degnan, Andrew J; Wisnowski, Jessica L; Choi, SoYoung; Ceschin, Rafael; Bhushan, Chitresh; Leahy, Richard M; Corby, Patricia; Schmithorst, Vincent J; Panigrahy, Ashok

2015-01-07

Late preterm birth is increasingly recognized as a risk factor for cognitive and social deficits. The prefrontal cortex is particularly vulnerable to injury in late prematurity because of its protracted development and extensive cortical connections. Our study examined children born late preterm without access to advanced postnatal care to assess structural and functional connectivity related to the prefrontal cortex. Thirty-eight preadolescents [19 born late preterm (34-36 /7 weeks gestational age) and 19 at term] were recruited from a developing community in Brazil. Participants underwent neuropsychological testing. Individuals underwent three-dimensional T1-weighted, diffusion-weighted, and resting state functional MRI. Probabilistic tractography and functional connectivity analyses were carried out using unilateral seeds combining the medial prefrontal cortex and the anterior cingulate cortex. Late preterm children showed increased functional connectivity within regions of the default mode, salience, and central-executive networks from both right and left frontal cortex seeds. Decreased functional connectivity was observed within the right parahippocampal region from left frontal seeding. Probabilistic tractography showed a pattern of decreased streamlines in frontal white matter pathways and the corpus callosum, but also increased streamlines in the left orbitofrontal white matter and the right frontal white matter when seeded from the right. Late preterm children and term control children scored similarly on neuropsychological testing. Prefrontal cortical connectivity is altered in late prematurity, with hyperconnectivity observed in key resting state networks in the absence of neuropsychological deficits. Abnormal structural connectivity indicated by probabilistic tractography suggests subtle changes in white matter development, implying disruption of normal maturation during the late gestational period.

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

PubMed

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

2011-08-01

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

Amygdala reactivity in healthy adults is correlated with prefrontal cortical thickness.

PubMed

Foland-Ross, Lara C; Altshuler, Lori L; Bookheimer, Susan Y; Lieberman, Matthew D; Townsend, Jennifer; Penfold, Conor; Moody, Teena; Ahlf, Kyle; Shen, Jim K; Madsen, Sarah K; Rasser, Paul E; Toga, Arthur W; Thompson, Paul M

2010-12-08

Recent evidence suggests that putting feelings into words activates the prefrontal cortex (PFC) and suppresses the response of the amygdala, potentially helping to alleviate emotional distress. To further elucidate the relationship between brain structure and function in these regions, structural and functional magnetic resonance imaging (MRI) data were collected from a sample of 20 healthy human subjects. Structural MRI data were processed using cortical pattern-matching algorithms to produce spatially normalized maps of cortical thickness. During functional scanning, subjects cognitively assessed an emotional target face by choosing one of two linguistic labels (label emotion condition) or matched geometric forms (control condition). Manually prescribed regions of interest for the left amygdala were used to extract percentage signal change in this region occurring during the contrast of label emotion versus match forms. A correlation analysis between left amygdala activation and cortical thickness was then performed along each point of the cortical surface, resulting in a color-coded r value at each cortical point. Correlation analyses revealed that gray matter thickness in left ventromedial PFC was inversely correlated with task-related activation in the amygdala. These data add support to a general role of the ventromedial PFC in regulating activity of the amygdala.

Age-Dependent Brain Gene Expression and Copy Number Anomalies in Autism Suggest Distinct Pathological Processes at Young Versus Mature Ages

PubMed Central

Winn, Mary E.; Barnes, Cynthia Carter; Li, Hai-Ri; Weiss, Lauren; Fan, Jian-Bing; Murray, Sarah; April, Craig; Belinson, Haim; Fu, Xiang-Dong; Wynshaw-Boris, Anthony; Schork, Nicholas J.; Courchesne, Eric

2012-01-01

Autism is a highly heritable neurodevelopmental disorder, yet the genetic underpinnings of the disorder are largely unknown. Aberrant brain overgrowth is a well-replicated observation in the autism literature; but association, linkage, and expression studies have not identified genetic factors that explain this trajectory. Few studies have had sufficient statistical power to investigate whole-genome gene expression and genotypic variation in the autistic brain, especially in regions that display the greatest growth abnormality. Previous functional genomic studies have identified possible alterations in transcript levels of genes related to neurodevelopment and immune function. Thus, there is a need for genetic studies involving key brain regions to replicate these findings and solidify the role of particular functional pathways in autism pathogenesis. We therefore sought to identify abnormal brain gene expression patterns via whole-genome analysis of mRNA levels and copy number variations (CNVs) in autistic and control postmortem brain samples. We focused on prefrontal cortex tissue where excess neuron numbers and cortical overgrowth are pronounced in the majority of autism cases. We found evidence for dysregulation in pathways governing cell number, cortical patterning, and differentiation in young autistic prefrontal cortex. In contrast, adult autistic prefrontal cortex showed dysregulation of signaling and repair pathways. Genes regulating cell cycle also exhibited autism-specific CNVs in DNA derived from prefrontal cortex, and these genes were significantly associated with autism in genome-wide association study datasets. Our results suggest that CNVs and age-dependent gene expression changes in autism may reflect distinct pathological processes in the developing versus the mature autistic prefrontal cortex. Our results raise the hypothesis that genetic dysregulation in the developing brain leads to abnormal regional patterning, excess prefrontal neurons, cortical overgrowth, and neural dysfunction in autism. PMID:22457638

Age-dependent brain gene expression and copy number anomalies in autism suggest distinct pathological processes at young versus mature ages.

PubMed

Chow, Maggie L; Pramparo, Tiziano; Winn, Mary E; Barnes, Cynthia Carter; Li, Hai-Ri; Weiss, Lauren; Fan, Jian-Bing; Murray, Sarah; April, Craig; Belinson, Haim; Fu, Xiang-Dong; Wynshaw-Boris, Anthony; Schork, Nicholas J; Courchesne, Eric

2012-01-01

Autism is a highly heritable neurodevelopmental disorder, yet the genetic underpinnings of the disorder are largely unknown. Aberrant brain overgrowth is a well-replicated observation in the autism literature; but association, linkage, and expression studies have not identified genetic factors that explain this trajectory. Few studies have had sufficient statistical power to investigate whole-genome gene expression and genotypic variation in the autistic brain, especially in regions that display the greatest growth abnormality. Previous functional genomic studies have identified possible alterations in transcript levels of genes related to neurodevelopment and immune function. Thus, there is a need for genetic studies involving key brain regions to replicate these findings and solidify the role of particular functional pathways in autism pathogenesis. We therefore sought to identify abnormal brain gene expression patterns via whole-genome analysis of mRNA levels and copy number variations (CNVs) in autistic and control postmortem brain samples. We focused on prefrontal cortex tissue where excess neuron numbers and cortical overgrowth are pronounced in the majority of autism cases. We found evidence for dysregulation in pathways governing cell number, cortical patterning, and differentiation in young autistic prefrontal cortex. In contrast, adult autistic prefrontal cortex showed dysregulation of signaling and repair pathways. Genes regulating cell cycle also exhibited autism-specific CNVs in DNA derived from prefrontal cortex, and these genes were significantly associated with autism in genome-wide association study datasets. Our results suggest that CNVs and age-dependent gene expression changes in autism may reflect distinct pathological processes in the developing versus the mature autistic prefrontal cortex. Our results raise the hypothesis that genetic dysregulation in the developing brain leads to abnormal regional patterning, excess prefrontal neurons, cortical overgrowth, and neural dysfunction in autism.

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

PubMed

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

2013-08-01

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

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

Regional microstructural organization of the cerebral cortex is affected by preterm birth.

PubMed

Bouyssi-Kobar, Marine; Brossard-Racine, Marie; Jacobs, Marni; Murnick, Jonathan; Chang, Taeun; Limperopoulos, Catherine

2018-01-01

To compare regional cerebral cortical microstructural organization between preterm infants at term-equivalent age (TEA) and healthy full-term newborns, and to examine the impact of clinical risk factors on cerebral cortical micro-organization in the preterm cohort. We prospectively enrolled very preterm infants (gestational age (GA) at birth<32 weeks; birthweight<1500 g) and healthy full-term controls. Using non-invasive 3T diffusion tensor imaging (DTI) metrics, we quantified regional micro-organization in ten cerebral cortical areas: medial/dorsolateral prefrontal cortex, anterior/posterior cingulate cortex, insula, posterior parietal cortex, motor/somatosensory/auditory/visual cortex. ANCOVA analyses were performed controlling for sex and postmenstrual age at MRI. We studied 91 preterm infants at TEA and 69 full-term controls. Preterm infants demonstrated significantly higher diffusivity in the prefrontal, parietal, motor, somatosensory, and visual cortices suggesting delayed maturation of these cortical areas. Additionally, postnatal hydrocortisone treatment was related to accelerated microstructural organization in the prefrontal and somatosensory cortices. Preterm birth alters regional microstructural organization of the cerebral cortex in both neurocognitive brain regions and areas with primary sensory/motor functions. We also report for the first time a potential protective effect of postnatal hydrocortisone administration on cerebral cortical development in preterm infants.

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.

Evidence for a cerebral cortical thickness network anti-correlated with amygdalar volume in healthy youths: implications for the neural substrates of emotion regulation.

PubMed

Albaugh, Matthew D; Ducharme, Simon; Collins, D Louis; Botteron, Kelly N; Althoff, Robert R; Evans, Alan C; Karama, Sherif; Hudziak, James J

2013-05-01

Recent functional connectivity studies have demonstrated that, in resting humans, activity in a dorsally-situated neocortical network is inversely associated with activity in the amygdalae. Similarly, in human neuroimaging studies, aspects of emotion regulation have been associated with increased activity in dorsolateral, dorsomedial, orbital and ventromedial prefrontal regions, as well as concomitant decreases in amygdalar activity. These findings indicate the presence of two countervailing systems in the human brain that are reciprocally related: a dorsally-situated cognitive control network, and a ventrally-situated limbic network. We investigated the extent to which this functional reciprocity between limbic and dorsal neocortical regions is recapitulated from a purely structural standpoint. Specifically, we hypothesized that amygdalar volume would be related to cerebral cortical thickness in cortical regions implicated in aspects of emotion regulation. In 297 typically developing youths (162 females, 135 males; 572 MRIs), the relationship between cortical thickness and amygdalar volume was characterized. Amygdalar volume was found to be inversely associated with thickness in bilateral dorsolateral and dorsomedial prefrontal, inferior parietal, as well as bilateral orbital and ventromedial prefrontal cortices. Our findings are in line with previous work demonstrating that a predominantly dorsally-centered neocortical network is reciprocally related to core limbic structures such as the amygdalae. Future research may benefit from investigating the extent to which such cortical-limbic morphometric relations are qualified by the presence of mood and anxiety psychopathology. Copyright © 2012 Elsevier Inc. All rights reserved.

GABA and glutamate in schizophrenia: a 7 T ¹H-MRS study.

PubMed

Marsman, Anouk; Mandl, René C W; Klomp, Dennis W J; Bohlken, Marc M; Boer, Vincent O; Andreychenko, Anna; Cahn, Wiepke; Kahn, René S; Luijten, Peter R; Hulshoff Pol, Hilleke E

2014-01-01

Schizophrenia is characterized by loss of brain volume, which may represent an ongoing pathophysiological process. This loss of brain volume may be explained by reduced neuropil rather than neuronal loss, suggesting abnormal synaptic plasticity and cortical microcircuitry. A possible mechanism is hypofunction of the NMDA-type of glutamate receptor, which reduces the excitation of inhibitory GABAergic interneurons, resulting in a disinhibition of glutamatergic pyramidal neurons. Disinhibition of pyramidal cells may result in excessive stimulation by glutamate, which in turn could cause neuronal damage or death through excitotoxicity. In this study, GABA/creatine ratios, and glutamate, NAA, creatine and choline concentrations in the prefrontal and parieto-occipital cortices were measured in 17 patients with schizophrenia and 23 healthy controls using proton magnetic resonance spectroscopy at an ultra-high magnetic field strength of 7 T. Significantly lower GABA/Cr ratios were found in patients with schizophrenia in the prefrontal cortex as compared to healthy controls, with GABA/Cr ratios inversely correlated with cognitive functioning in the patients. No significant change in the GABA/Cr ratio was found between patients and controls in the parieto-occipital cortex, nor were levels of glutamate, NAA, creatine, and choline differed in patients and controls in the prefrontal and parieto-occipital cortices. Our findings support a mechanism involving altered GABA levels distinguished from glutamate levels in the medial prefrontal cortex in schizophrenia, particularly in high functioning patients. A (compensatory) role for GABA through altered inhibitory neurotransmission in the prefrontal cortex may be ongoing in (higher functioning) patients with schizophrenia.

Prefrontal cortical-specific differences in behavior and synaptic plasticity between adolescent and adult mice.

PubMed

Konstantoudaki, Xanthippi; Chalkiadaki, Kleanthi; Vasileiou, Elisabeth; Kalemaki, Katerina; Karagogeos, Domna; Sidiropoulou, Kyriaki

2018-03-01

Adolescence is a highly vulnerable period for the emergence of major neuropsychological disorders and is characterized by decreased cognitive control and increased risk-taking behavior and novelty-seeking. The prefrontal cortex (PFC) is involved in the cognitive control of impulsive and risky behavior. Although the PFC is known to reach maturation later than other cortical areas, little information is available regarding the functional changes from adolescence to adulthood in PFC, particularly compared with other primary cortical areas. This study aims to understand the development of PFC-mediated, compared with non-PFC-mediated, cognitive functions. Toward this aim, we performed cognitive behavioral tasks in adolescent and adult mice and subsequently investigated synaptic plasticity in two different cortical areas. Our results showed that adolescent mice exhibit impaired performance in PFC-dependent cognitive tasks compared with adult mice, whereas their performance in non-PFC-dependent tasks is similar to that of adults. Furthermore, adolescent mice exhibited decreased long-term potentiation (LTP) within upper-layer synapses of the PFC but not the barrel cortex. Blocking GABA A receptor function significantly augments LTP in both the adolescent and adult PFC. No change in intrinsic excitability of PFC pyramidal neurons was observed between adolescent and adult mice. Finally, increased expression of the NR2A subunit of the N-methyl-d-aspartate receptors is found only in the adult PFC, a change that could underlie the emergence of LTP. In conclusion, our results demonstrate physiological and behavioral changes during adolescence that are specific to the PFC and could underlie the reduced cognitive control in adolescents. NEW & NOTEWORTHY This study reports that adolescent mice exhibit impaired performance in cognitive functions dependent on the prefrontal cortex but not in cognitive functions dependent on other cortical regions. The current results propose reduced synaptic plasticity in the upper layers of the prefrontal cortex as a cellular correlate of this weakened cognitive function. This decreased synaptic plasticity is due to reduced N-methyl-d-aspartate receptor expression but not due to dampened intrinsic excitability or enhanced GABAergic signaling during adolescence.

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

PubMed

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

2017-11-02

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

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

PubMed

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

2017-03-06

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

Individual mediodorsal thalamic neurons project to multiple areas of the rat prefrontal cortex: A single neuron-tracing study using virus vectors.

PubMed

Kuramoto, Eriko; Pan, Shixiu; Furuta, Takahiro; Tanaka, Yasuhiro R; Iwai, Haruki; Yamanaka, Atsushi; Ohno, Sachi; Kaneko, Takeshi; Goto, Tetsuya; Hioki, Hiroyuki

2017-01-01

The prefrontal cortex has an important role in a variety of cognitive and executive processes, and is generally defined by its reciprocal connections with the mediodorsal thalamic nucleus (MD). The rat MD is mainly subdivided into three segments, the medial (MDm), central (MDc), and lateral (MDl) divisions, on the basis of the cytoarchitecture and chemoarchitecture. The MD segments are known to topographically project to multiple prefrontal areas at the population level: the MDm mainly to the prelimbic, infralimbic, and agranular insular areas; the MDc to the orbital and agranular insular areas; and the MDl to the prelimbic and anterior cingulate areas. However, it is unknown whether individual MD neurons project to single or multiple prefrontal cortical areas. In the present study, we visualized individual MD neurons with Sindbis virus vectors, and reconstructed whole structures of MD neurons. While the main cortical projection targets of MDm, MDc, and MDl neurons were generally consistent with those of previous results, it was found that individual MD neurons sent their axon fibers to multiple prefrontal areas, and displayed various projection patterns in the target areas. Furthermore, the axons of single MD neurons were not homogeneously spread, but were rather distributed to form patchy axon arbors approximately 1 mm in diameter. The multiple-area projections and patchy axon arbors of single MD neurons might be able to coactivate cortical neuron groups in distant prefrontal areas simultaneously. Furthermore, considerable heterogeneity of the projection patterns is likely, to recruit the different sets of cortical neurons, and thus contributes to a variety of prefrontal functions. J. Comp. Neurol. 525:166-185, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The relationship between dispositional empathy and prefrontal cortical functioning in patients with frontal lobe epilepsy.

PubMed

Gul, Amara; Ahmad, Hira

2017-01-01

Rehabilitation focuses brain-behavior relationship which highlights interaction between psychological and neurobiological factors for better patient care. There is a missing link in the literature about socio-cognitive aspects of frontal lobe epilepsy. Our objective was to examine prefrontal cortical functioning (PCF) and empathic abilities in patients with frontal lobe epilepsy (FLE). Further, we analyzed whether any relationship between components of dispositional empathy and PCF exists in patients with FLE. The study was designed in an experimental paradigm. Sixty patients with FLE were recruited from Sheikh Zayed and Jinnah hospital, Pakistan. Sixty healthy individuals in response to an advertisement took part in the study as control subjects. Participants completed interpersonal reactivity index. Following they performed clock drawing test and word-color identification task switching experiment. Patients with FLE demonstrated weaker PCF (i.e., cognitive flexibility and executive function) as compared to healthy control subjects. Patients with FLE scored lesser on cognitive empathy as compared to healthy control subjects. On contrary, there was no significant difference between patient and control group on affective empathy. Cognitive not affective empathy was potential predictor of PCF. Cognitive empathy is a significant marker of prefrontal cortical functioning (PCF) in FLE. Higher cognitive empathy would lead to efficient PCF.

Sequence of information processing for emotions based on the anatomic dialogue between prefrontal cortex and amygdala.

PubMed

Ghashghaei, H T; Hilgetag, C C; Barbas, H

2007-02-01

The prefrontal cortex and the amygdala have synergistic roles in regulating purposive behavior, effected through bidirectional pathways. Here we investigated the largely unknown extent and laminar relationship of prefrontal input-output zones linked with the amygdala using neural tracers injected in the amygdala in rhesus monkeys. Prefrontal areas varied vastly in their connections with the amygdala, with the densest connections found in posterior orbitofrontal and posterior medial cortices, and the sparsest in anterior lateral prefrontal areas, especially area 10. Prefrontal projection neurons directed to the amygdala originated in layer 5, but significant numbers were also found in layers 2 and 3 in posterior medial and orbitofrontal cortices. Amygdalar axonal terminations in prefrontal cortex were most frequently distributed in bilaminar bands in the superficial and deep layers, by columns spanning the entire cortical depth, and less frequently as small patches centered in the superficial or deep layers. Heavy terminations in layers 1-2 overlapped with calbindin-positive inhibitory neurons. A comparison of the relationship of input to output projections revealed that among the most heavily connected cortices, cingulate areas 25 and 24 issued comparatively more projections to the amygdala than they received, whereas caudal orbitofrontal areas were more receivers than senders. Further, there was a significant relationship between the proportion of 'feedforward' cortical projections from layers 2-3 to 'feedback' terminations innervating the superficial layers of prefrontal cortices. These findings indicate that the connections between prefrontal cortices and the amygdala follow similar patterns as corticocortical connections, and by analogy suggest pathways underlying the sequence of information processing for emotions.

The functional anatomical distinction between truth telling and deception is preserved among people with schizophrenia.

PubMed

Kaylor-Hughes, Catherine J; Lankappa, Sudheer T; Fung, Robert; Hope-Urwin, Alexandra E; Wilkinson, Iain D; Spence, Sean A

2011-02-01

A recently emergent functional neuroimaging literature has described the functional anatomical correlates of deception among healthy volunteers, most often implicating the ventrolateral prefrontal and anterior cingulate cortices. To date, there have been no such imaging studies of people with severe mental illness. To discover whether the brains of people with schizophrenia would manifest a similar functional anatomical distinction between the states of truthfulness and deceit. It is hypothesised that, as with healthy people, persons with schizophrenia will show activation in the ventrolateral prefrontal and anterior cingulate cortices when lying. Fifty-two people satisfying Diagnostic and Statistical Manual of Mental Disorder-IV criteria for schizophrenia or schizoaffective disorder underwent functional magnetic resonance imaging at 3 T while responding truthfully or with lies to questions concerning their recent actions. Half the sample was concurrently experiencing delusions. As hypothesised, patients exhibited greater activity in ventrolateral prefrontal cortices while lying. Truthful responses were not associated with any areas of relatively increased activation. The presence or absence of delusions did not substantially affect these findings, although subtle laterality effects were discernible upon post hoc analyses. As in healthy cohorts, the brains of people with schizophrenia exhibit a functional anatomical distinction between the states of truthfulness and deceit. Furthermore, this distinction pertains even in the presence of delusions. Copyright © 2010 John Wiley & Sons, Ltd.

Efficiency of the Prefrontal Cortex during Working Memory in Attention-Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Sheridan, Margaret A.; Hinshaw, Stephen; D'Esposito, Mark

2007-01-01

Objective: Previous research has demonstrated that during task conditions requiring an increase in inhibitory function or working memory, children and adults with attention-deficit/hyperactivity disorder (ADHD) exhibit greater and more varied prefrontal cortical(PFC) activation compared to age-matched control participants. This pattern may reflect…

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…

Estimates of projection overlap and zones of convergence within frontal-striatal circuits.

PubMed

Averbeck, Bruno B; Lehman, Julia; Jacobson, Moriah; Haber, Suzanne N

2014-07-16

Frontal-striatal circuits underlie important decision processes, and pathology in these circuits is implicated in many psychiatric disorders. Studies have shown a topographic organization of cortical projections into the striatum. However, work has also shown that there is considerable overlap in the striatal projection zones of nearby cortical regions. To characterize this in detail, we quantified the complete striatal projection zones from 34 cortical injection locations in rhesus monkeys. We first fit a statistical model that showed that the projection zone of a cortical injection site could be predicted with considerable accuracy using a cross-validated model estimated on only the other injection sites. We then examined the fraction of overlap in striatal projection zones as a function of distance between cortical injection sites, and found that there was a highly regular relationship. Specifically, nearby cortical locations had as much as 80% overlap, and the amount of overlap decayed exponentially as a function of distance between the cortical injection sites. Finally, we found that some portions of the striatum received inputs from all the prefrontal regions, making these striatal zones candidates as information-processing hubs. Thus, the striatum is a site of convergence that allows integration of information spread across diverse prefrontal cortical areas. Copyright © 2014 the authors 0270-6474/14/339497-09$15.00/0.

Differential Motor and Prefrontal Cerebello-Cortical Network Development: Evidence from Multimodal Neuroimaging

PubMed Central

Bernard, Jessica A.; Orr, Joseph M.; Mittal, Vijay A.

2015-01-01

While our understanding of cerebellar structural development through adolescence and young adulthood has expanded, we still lack knowledge of the developmental patterns of cerebellar networks during this critical portion of the lifespan. Volume in lateral posterior cerebellar regions associated with cognition and the prefrontal cortex develops more slowly, reaching their peak volume in adulthood, particularly as compared to motor Lobule V. We predicted that resting state functional connectivity of the lateral posterior regions would show a similar pattern of development during adolescence and young adulthood. That is, we expected to see changes over time in Crus I and Crus II connectivity with the cortex, but no changes in Lobule V connectivity. Additionally, we were interested in how structural connectivity changes in cerebello-thalamo-cortical white matter are related to changes in functional connectivity. A sample of 23 individuals between 12 and 21 years old underwent neuroimaging scans at baseline and 12-months later. Functional networks of Crus I and Crus II showed significant connectivity decreases over 12-months, though there were no differences in Lobule V. Furthermore, these functional connectivity changes were correlated with increases in white matter structural integrity in the corresponding cerebello-thalamo-cortical white matter tract. We suggest that these functional network changes are due to both later pruning in the prefrontal cortex as well as further development of the white matter tracts linking these brain regions. PMID:26391125

Cognitive impact of social stress and coping strategy throughout development.

PubMed

Snyder, Kevin P; Barry, Mark; Valentino, Rita J

2015-01-01

Stress experience during adolescence has been linked to the development of psychiatric disorders in adulthood, many of which are associated with impairments in prefrontal cortex function. The current study was designed to determine the immediate and enduring effects of repeated social stress on a prefrontal cortex-dependent cognitive task. Early adolescent (P28), mid-adolescent (P42), and adult (P70) rats were exposed to resident-intruder stress for 5 days and tested in an operant strategy-shifting task (OSST) during the following week or several weeks later during adulthood. Engagement of prefrontal cortical neurons during the task was assessed by expression of the immediate early gene, c-fos. Social stress during adolescence had no immediate effects on task performance, but impaired strategy-shifting in adulthood, whereas social stress that occurred during adulthood had no effect. The cognitive impairment produced by adolescent social stress was most pronounced in rats with a passive coping strategy. Notably, strategy-shifting performance was positively correlated with medial prefrontal cortical c-fos in adulthood but not in adolescence, suggesting that the task engages different brain regions in adolescents compared to adults. Adolescent social stress produces a protracted impairment in prefrontal cortex-mediated cognition that is related to coping strategy. This impairment may be selectively expressed in adulthood because prefrontal cortical activity is integral to task performance at this age but not during adolescence.

Cadherin-8 expression, synaptic localization, and molecular control of neuronal form in prefrontal corticostriatal circuits.

PubMed

Friedman, Lauren G; Riemslagh, Fréderike W; Sullivan, Josefa M; Mesias, Roxana; Williams, Frances M; Huntley, George W; Benson, Deanna L

2015-01-01

Neocortical interactions with the dorsal striatum support many motor and executive functions, and such underlying functional networks are particularly vulnerable to a variety of developmental, neurological, and psychiatric brain disorders, including autism spectrum disorders, Parkinson's disease, and Huntington's disease. Relatively little is known about the development of functional corticostriatal interactions, and in particular, virtually nothing is known of the molecular mechanisms that control generation of prefrontal cortex-striatal circuits. Here, we used regional and cellular in situ hybridization techniques coupled with neuronal tract tracing to show that Cadherin-8 (Cdh8), a homophilic adhesion protein encoded by a gene associated with autism spectrum disorders and learning disability susceptibility, is enriched within striatal projection neurons in the medial prefrontal cortex and in striatal medium spiny neurons forming the direct or indirect pathways. Developmental analysis of quantitative real-time polymerase chain reaction and western blot data show that Cdh8 expression peaks in the prefrontal cortex and striatum at P10, when cortical projections start to form synapses in the striatum. High-resolution immunoelectron microscopy shows that Cdh8 is concentrated at excitatory synapses in the dorsal striatum, and Cdh8 knockdown in cortical neurons impairs dendritic arborization and dendrite self-avoidance. Taken together, our findings indicate that Cdh8 delineates developing corticostriatal circuits where it is a strong candidate for regulating the generation of normal cortical projections, neuronal morphology, and corticostriatal synapses. © 2014 Wiley Periodicals, Inc.

Abnormal functional connectivity density in children with anisometropic amblyopia at resting-state.

PubMed

Wang, Tianyue; Li, Qian; Guo, Mingxia; Peng, Yanmin; Li, Qingji; Qin, Wen; Yu, Chunshui

2014-05-14

Amblyopia is a developmental disorder resulting from anomalous binocular visual input in early life. Task-based neuroimaging studies have widely investigated cortical functional impairments in amblyopia, but changes in spontaneous neuronal functional activities in amblyopia remain largely unknown. In the present study, functional connectivity density (FCD) mapping, an ultrafast data-driven method based on fMRI, was applied for the first time to investigate changes in cortical functional connectivities in amblyopia during the resting-state. We quantified and compared both short- and long-range FCD in both the brains of children with anisometropic amblyopia (AAC) and normal sighted children (NSC). In contrast to the NSC, the AAC showed significantly decreased short-range FCD in the inferior temporal/fusiform gyri, parieto-occipital and rostrolateral prefrontal cortices, as well as decreased long-range FCD in the premotor cortex, dorsal inferior parietal lobule, frontal-insular and dorsal prefrontal cortices. Furthermore, most regions with reduced long-range FCD in the AAC showed decreased functional connectivity with occipital and posterior parietal cortices in the AAC. The results suggest that chronically poor visual input in amblyopia not only impairs the brain's short-range functional connections in visual pathways and in the frontal cortex, which is important for cognitive control, but also affects long-range functional connections among the visual areas, posterior parietal and frontal cortices that subserve visuomotor and visual-guided actions, visuospatial attention modulation and the integration of salient information. This study provides evidence for abnormal spontaneous brain activities in amblyopia. Copyright © 2014 Elsevier B.V. All rights reserved.

Computational Cognitive Neuroscience of Early Memory Development

ERIC Educational Resources Information Center

Munakata, Yuko

2004-01-01

Numerous brain areas work in concert to subserve memory, with distinct memory functions relying differentially on distinct brain areas. For example, semantic memory relies heavily on posterior cortical regions, episodic memory on hippocampal regions, and working memory on prefrontal cortical regions. This article reviews relevant findings from…

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

Connecting to create: expertise in musical improvisation is associated with increased functional connectivity between premotor and prefrontal areas.

PubMed

Pinho, Ana Luísa; de Manzano, Örjan; Fransson, Peter; Eriksson, Helene; Ullén, Fredrik

2014-04-30

Musicians have been used extensively to study neural correlates of long-term practice, but no studies have investigated the specific effects of training musical creativity. Here, we used human functional MRI to measure brain activity during improvisation in a sample of 39 professional pianists with varying backgrounds in classical and jazz piano playing. We found total hours of improvisation experience to be negatively associated with activity in frontoparietal executive cortical areas. In contrast, improvisation training was positively associated with functional connectivity of the bilateral dorsolateral prefrontal cortices, dorsal premotor cortices, and presupplementary areas. The effects were significant when controlling for hours of classical piano practice and age. These results indicate that even neural mechanisms involved in creative behaviors, which require a flexible online generation of novel and meaningful output, can be automated by training. Second, improvisational musical training can influence functional brain properties at a network level. We show that the greater functional connectivity seen in experienced improvisers may reflect a more efficient exchange of information within associative networks of importance for musical creativity.

Connecting to Create: Expertise in Musical Improvisation Is Associated with Increased Functional Connectivity between Premotor and Prefrontal Areas

PubMed Central

Pinho, Ana Luísa; de Manzano, Örjan; Fransson, Peter; Eriksson, Helene

2014-01-01

Musicians have been used extensively to study neural correlates of long-term practice, but no studies have investigated the specific effects of training musical creativity. Here, we used human functional MRI to measure brain activity during improvisation in a sample of 39 professional pianists with varying backgrounds in classical and jazz piano playing. We found total hours of improvisation experience to be negatively associated with activity in frontoparietal executive cortical areas. In contrast, improvisation training was positively associated with functional connectivity of the bilateral dorsolateral prefrontal cortices, dorsal premotor cortices, and presupplementary areas. The effects were significant when controlling for hours of classical piano practice and age. These results indicate that even neural mechanisms involved in creative behaviors, which require a flexible online generation of novel and meaningful output, can be automated by training. Second, improvisational musical training can influence functional brain properties at a network level. We show that the greater functional connectivity seen in experienced improvisers may reflect a more efficient exchange of information within associative networks of importance for musical creativity. PMID:24790186

Developmental effects of androgens in the human brain.

PubMed

Nguyen, T-V

2018-02-01

Neuroendocrine theories of brain development posit that androgens play a crucial role in sex-specific cortical growth, although little is known about the differential effects of testosterone and dehydroepiandrosterone (DHEA) on cortico-limbic development and cognition during adolescence. In this context, the National Institutes of Health Study of Normal Brain Development, a longitudinal study of typically developing children and adolescents aged 4-24 years (n=433), offers a unique opportunity to examine the developmental effects of androgens on cortico-limbic maturation and cognition. Using data from this sample, our group found that higher testosterone levels were associated with left-sided decreases in cortical thickness (CTh) in post-pubertal boys, particularly in the prefrontal cortex, compared to right-sided increases in CTh in somatosensory areas in pre-pubertal girls. Prefrontal-amygdala and prefrontal-hippocampal structural covariance (considered to reflect structural connectivity) also varied according to testosterone levels, with the testosterone-related brain phenotype predicting higher aggression levels and lower executive function, particularly in boys. By contrast, DHEA was associated with a pre-pubertal increase in CTh of several regions involved in cognitive control in both boys and girls. Covariance within several cortico-amygdalar structural networks also varied as a function of DHEA levels, with the DHEA-related brain phenotype predicting improvements in visual attention in both boys and girls. DHEA-related cortico-hippocampal structural covariance, on the other hand, predicted higher scores on a test of working memory. Interestingly, there were significant interactions between testosterone and DHEA, such that DHEA tended to mitigate the anti-proliferative effects of testosterone on brain structure. In sum, testosterone-related effects on the developing brain may lead to detrimental effects on cortical functions (ie, higher aggression and lower executive function), whereas DHEA-related effects may optimise cortical functions (ie, better attention and working memory), perhaps by decreasing the influence of amygdalar and hippocampal afferents on cortical functions. © 2017 British Society for Neuroendocrinology.

Repeated exposure to delta 9-tetrahydrocannabinol reduces prefrontal cortical dopamine metabolism in the rat.

PubMed

Jentsch, J D; Verrico, C D; Le, D; Roth, R H

1998-05-01

Long-term abuse of marijuana by humans can induce profound behavioral deficits characterized by cognitive and memory impairments. In particular, deficits on tasks dependent on frontal lobe function have been reported in cannabis abusers. In the current study, we examined whether long-term exposure to delta9-tetrahydrocannabinol, the active ingredient in marijuana, altered the neurochemistry of the frontal cortex in rats. Two weeks administration of delta9-tetrahydrocannabinol reduced dopamine transmission in the medial prefrontal cortex, while dopamine metabolism in striatal regions was unaffected. These data are consistent with earlier findings of dopaminergic regulation of frontal cortical cognition. Thus, cognitive deficits in heavy abusers of cannabis may be subserved by drug-induced alterations in frontal cortical dopamine transmission.

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

PubMed

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

2009-11-01

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

MRI morphometry of mamillary bodies, caudate nuclei, and prefrontal cortices after chemotherapy for childhood leukemia: multivariate models of early and late developing memory subsystems.

PubMed

Ciesielski, K T; Lesnik, P G; Benzel, E C; Hart, B L; Sanders, J A

1999-06-01

Neurotoxic intrathecal chemotherapy for childhood acute lymphoblastic leukemia (ALL) affects developing structures and functions of memory and learning subsystems selectively. Results show significant reductions in magnetic resonance imaging morphometry of mamillary bodies, components of the corticolimbic-diencephalic subsystem subserving functionally later developing, single-trial memory, nonsignificant changes in bilateral heads of the caudate nuclei, components of the corticostriatal subsystem subserving functionally earlier developing, multitrial learning, significant reductions in prefrontal cortical volume, visual and verbal single-trial memory deficits, and visuospatial, but not verbal, multitrial learning deficits. Multiple regression models provide evidence for partial dissociation and connectivity between the subsystems, and suggest that greater involvement of caudate may compensate for inefficient corticolimbic-diencephalic components.

Functional Neuroanatomical Correlates of The Frontal Assessment Battery Performance in Alzheimer Disease: A FDG-PET Study.

PubMed

Lee, Jun Ho; Byun, Min Soo; Sohn, Bo Kyung; Choe, Young Min; Yi, Dahyun; Han, Ji Young; Choi, Hyo Jung; Baek, Hyewon; Woo, Jong Inn; Lee, Dong Young

2015-09-01

We aimed to elucidate the functional neuroanatomical correlates of Frontal Assessment Battery (FAB) performances by applying [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) to a large population of patients with Alzheimer disease (AD). The FAB was administered to 177 patients with AD, and regional cerebral glucose metabolism (rCMglc) was measured by FDG-PET scan. Correlations between FAB scores and rCMglc were explored using both region-of-interest-based (ROI-based) and voxel-based approaches. The ROI-based analysis showed that FAB scores correlated with the rCMglc of the dorsolateral prefrontal cortices. Voxel-based approach revealed significant positive correlations between FAB scores and rCMglc which were in various cortical regions including the temporal and parietal cortices as well as frontal regions, independent of age, gender, and education. After controlling the effect of global disease severity with Mini-Mental State Examination score, significant positive correlation was found only in the bilateral prefrontal regions. Although FAB scores are influenced by temporoparietal dysfunction due to the overall progression of AD, it likely reflects prefrontal dysfunction specifically regardless of global cognitive state or disease severity in patients with AD. © The Author(s) 2015.

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

PubMed

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

2016-12-13

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

Centrality of prefrontal and motor preparation cortices to Tourette Syndrome revealed by meta-analysis of task-based neuroimaging studies.

PubMed

Polyanska, Liliana; Critchley, Hugo D; Rae, Charlotte L

2017-01-01

Tourette Syndrome (TS) is a neurodevelopmental condition characterized by chronic multiple tics, which are experienced as compulsive and 'unwilled'. Patients with TS can differ markedly in the frequency, severity, and bodily distribution of tics. Moreover, there are high comorbidity rates with attention deficit hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD), anxiety disorders, and depression. This complex clinical profile may account for apparent variability of findings across neuroimaging studies that connect neural function to cognitive and motor behavior in TS. Here we crystalized information from neuroimaging regarding the functional circuitry of TS, and furthermore, tested specifically for neural determinants of tic severity, by applying activation likelihood estimation (ALE) meta-analyses to neuroimaging (activation) studies of TS. Fourteen task-based studies (13 fMRI and one H2O-PET) met rigorous inclusion criteria. These studies, encompassing 25 experiments and 651 participants, tested for differences between TS participants and healthy controls across cognitive, motor, perceptual and somatosensory domains. Relative to controls, TS participants showed distributed differences in the activation of prefrontal (inferior, middle, and superior frontal gyri), anterior cingulate, and motor preparation cortices (lateral premotor cortex and supplementary motor area; SMA). Differences also extended into sensory (somatosensory cortex and the lingual gyrus; V4); and temporo-parietal association cortices (posterior superior temporal sulcus, supramarginal gyrus, and retrosplenial cortex). Within TS participants, tic severity (reported using the Yale Global Tic Severity Scale; YGTSS) selectively correlated with engagement of SMA, precentral gyrus, and middle frontal gyrus across tasks. The dispersed involvement of multiple cortical regions with differences in functional reactivity may account for heterogeneity in the symptomatic expression of TS and its comorbidities. More specifically for tics and tic severity, the findings reinforce previously proposed contributions of premotor and lateral prefrontal cortices to tic expression.

Prefrontal contributions to visual selective attention.

PubMed

Squire, Ryan F; Noudoost, Behrad; Schafer, Robert J; Moore, Tirin

2013-07-08

The faculty of attention endows us with the capacity to process important sensory information selectively while disregarding information that is potentially distracting. Much of our understanding of the neural circuitry underlying this fundamental cognitive function comes from neurophysiological studies within the visual modality. Past evidence suggests that a principal function of the prefrontal cortex (PFC) is selective attention and that this function involves the modulation of sensory signals within posterior cortices. In this review, we discuss recent progress in identifying the specific prefrontal circuits controlling visual attention and its neural correlates within the primate visual system. In addition, we examine the persisting challenge of precisely defining how behavior should be affected when attentional function is lost.

Executive Functions and Prefrontal Cortex: A Matter of Persistence?

PubMed Central

Ball, Gareth; Stokes, Paul R.; Rhodes, Rebecca A.; Bose, Subrata K.; Rezek, Iead; Wink, Alle-Meije; Lord, Louis-David; Mehta, Mitul A.; Grasby, Paul M.; Turkheimer, Federico E.

2011-01-01

Executive function is thought to originates from the dynamics of frontal cortical networks. We examined the dynamic properties of the blood oxygen level dependent time-series measured with functional MRI (fMRI) within the prefrontal cortex (PFC) to test the hypothesis that temporally persistent neural activity underlies performance in three tasks of executive function. A numerical estimate of signal persistence, the Hurst exponent, postulated to represent the coherent firing of cortical networks, was determined and correlated with task performance. Increasing persistence in the lateral PFC was shown to correlate with improved performance during an n-back task. Conversely, we observed a correlation between persistence and increasing commission error – indicating a failure to inhibit a prepotent response – during a Go/No-Go task. We propose that persistence within the PFC reflects dynamic network formation and these findings underline the importance of frequency analysis of fMRI time-series in the study of executive functions. PMID:21286223

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2014-01-01

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

Stimulant Medication and Prefrontal Functional Connectivity during Working Memory in ADHD: A Preliminary Report

ERIC Educational Resources Information Center

Sheridan, Margaret A.; Hinshaw, Stephen; D'Esposito, Mark

2010-01-01

Objective: Recent theoretical and empirical work suggests that while unmedicated, children with ADHD have a deficit in subcortical processing that leads to greater and more varied prefrontal cortical (PFC) activation, compared to (a) age-matched control participants and (b) their own brain activity while on stimulant medication. This pattern has…

Prenatal cocaine exposure decreases parvalbumin-immunoreactive neurons and GABA-to-projection neuron ratio in the medial prefrontal cortex.

PubMed

McCarthy, Deirdre M; Bhide, Pradeep G

2012-01-01

Cocaine abuse during pregnancy produces harmful effects not only on the mother but also on the unborn child. The neurotransmitters dopamine and serotonin are known as the principal targets of the action of cocaine in the fetal and postnatal brain. However, recent evidence suggests that cocaine can impair cerebral cortical GABA neuron development and function. We sought to analyze the effects of prenatal cocaine exposure on the number and distribution of GABA and projection neurons (inhibitory interneurons and excitatory output neurons, respectively) in the mouse cerebral cortex. We found that the prenatal cocaine exposure decreased GABA neuron numbers and GABA-to-projection neuron ratio in the medial prefrontal cortex of 60-day-old mice. The neighboring prefrontal cortex did not show significant changes in either of these measures. However, there was a significant increase in projection neuron numbers in the prefrontal cortex but not in the medial prefrontal cortex. Thus, the effects of cocaine on GABA and projection neurons appear to be cortical region specific. The population of parvalbumin-immunoreactive GABA neurons was decreased in the medial prefrontal cortex following the prenatal cocaine exposure. The cocaine exposure also delayed the developmental decline in the volume of the medial prefrontal cortex. Thus, prenatal cocaine exposure produced persisting and region-specific effects on cortical cytoarchitecture and impaired the physiological balance between excitatory and inhibitory neurotransmission. These structural changes may underlie the electrophysiological and behavioral effects of prenatal cocaine exposure observed in animal models and human subjects. Copyright © 2012 S. Karger AG, Basel.

Differentiating a network of executive attention: LORETA neurofeedback in anterior cingulate and dorsolateral prefrontal cortices.

PubMed

Cannon, Rex; Congedo, Marco; Lubar, Joel; Hutchens, Teresa

2009-01-01

This study examines the differential effects of space-specific neuro-operant learning, utilizing low-resolution electromagnetic tomographic (LORETA) neurofeedback in three regions of training (ROTs), namely, the anterior cingulate gyrus (AC) and right and left dorsolateral prefrontal cortices (RPFC and LPFC respectively). This study was conducted with 14 nonclinical students with a mean age of 22. We utilized electrophysiological measurements and subtests of the WAIS-III for premeasures and postmeasures. The data indicate that the AC shares a significant association with the RPFC and LPFC; however, each of the ROTs exhibits different cortical effects in all frequencies when trained exclusively. LORETA neurofeedback (LNFB) appears to enhance the functioning and strengthening of networks of cortical units physiologically related to each ROT; moreover, significant changes are mapped for each frequency domain, showing the associations within this possible attentional network.

The relationship between level of processing and hippocampal-cortical functional connectivity during episodic memory formation in humans.

PubMed

Schott, Björn H; Wüstenberg, Torsten; Wimber, Maria; Fenker, Daniela B; Zierhut, Kathrin C; Seidenbecher, Constanze I; Heinze, Hans-Jochen; Walter, Henrik; Düzel, Emrah; Richardson-Klavehn, Alan

2013-02-01

New episodic memory traces represent a record of the ongoing neocortical processing engaged during memory formation (encoding). Thus, during encoding, deep (semantic) processing typically establishes more distinctive and retrievable memory traces than does shallow (perceptual) processing, as assessed by later episodic memory tests. By contrast, the hippocampus appears to play a processing-independent role in encoding, because hippocampal lesions impair encoding regardless of level of processing. Here, we clarified the neural relationship between processing and encoding by examining hippocampal-cortical connectivity during deep and shallow encoding. Participants studied words during functional magnetic resonance imaging and freely recalled these words after distraction. Deep study processing led to better recall than shallow study processing. For both levels of processing, successful encoding elicited activations of bilateral hippocampus and left prefrontal cortex, and increased functional connectivity between left hippocampus and bilateral medial prefrontal, cingulate and extrastriate cortices. Successful encoding during deep processing was additionally associated with increased functional connectivity between left hippocampus and bilateral ventrolateral prefrontal cortex and right temporoparietal junction. In the shallow encoding condition, on the other hand, pronounced functional connectivity increases were observed between the right hippocampus and the frontoparietal attention network activated during shallow study processing. Our results further specify how the hippocampus coordinates recording of ongoing neocortical activity into long-term memory, and begin to provide a neural explanation for the typical advantage of deep over shallow study processing for later episodic memory. Copyright © 2011 Wiley Periodicals, Inc.

The prefrontal landscape: implications of functional architecture for understanding human mentation and the central executive.

PubMed

Goldman-Rakic, P S

1996-10-29

The functional architecture of prefrontal cortex is central to our understanding of human mentation and cognitive prowess. This region of the brain is often treated as an undifferentiated structure, on the one hand, or as a mosaic of psychological faculties, on the other. This paper focuses on the working memory processor as a specialization of prefrontal cortex and argues that the different areas within prefrontal cortex represent iterations of this function for different information domains, including spatial cognition, object cognition and additionally, in humans, semantic processing. According to this parallel processing architecture, the 'central executive' could be considered an emergent property of multiple domain-specific processors operating interactively. These processors are specializations of different prefrontal cortical areas, each interconnected both with the domain-relevant long-term storage sites in posterior regions of the cortex and with appropriate output pathways.

Development of cortical asymmetry in typically developing children and its disruption in attention-deficit/hyperactivity disorder.

PubMed

Shaw, Philip; Lalonde, Francois; Lepage, Claude; Rabin, Cara; Eckstrand, Kristen; Sharp, Wendy; Greenstein, Deanna; Evans, Alan; Giedd, J N; Rapoport, Judith

2009-08-01

Just as typical development of anatomical asymmetries in the human brain has been linked with normal lateralization of motor and cognitive functions, disruption of asymmetry has been implicated in the pathogenesis of neurodevelopmental disorders such as attention-deficit/hyperactivity disorder (ADHD). No study has examined the development of cortical asymmetry using longitudinal neuroanatomical data. To delineate the development of cortical asymmetry in children with and without ADHD. Longitudinal study. Government Clinical Research Institute. A total of 218 children with ADHD and 358 typically developing children, from whom 1133 neuroanatomical magnetic resonance images were acquired prospectively. Cortical thickness was estimated at 40 962 homologous points in the left and right hemispheres, and the trajectory of change in asymmetry was defined using mixed-model regression. In right-handed typically developing individuals, a mean (SE) increase in the relative thickness of the right orbitofrontal and inferior frontal cortex with age of 0.011 (0.0018) mm per year (t(337) = 6.2, P < .001) was balanced against a relative left-hemispheric increase in the occipital cortical regions of 0.013 (0.0015) mm per year (t(337) = 8.1, P < .001). Age-related change in asymmetry in non-right-handed typically developing individuals was less extensive and was localized to different cortical regions. In ADHD, the posterior component of this evolving asymmetry was intact, but the prefrontal component was lost. These findings explain the way that, in typical development, the increased dimensions of the right frontal and left occipital cortical regions emerge in adulthood from the reversed pattern of childhood cortical asymmetries. Loss of the prefrontal component of this evolving asymmetry in ADHD is compatible with disruption of prefrontal function in the disorder and demonstrates the way that disruption of typical processes of asymmetry can inform our understanding of neurodevelopmental disorders.

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

PubMed

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

1998-08-01

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

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.

Expression of β1- and β2-adrenoceptors in different subtypes of interneurons in the medial prefrontal cortex of mice.

PubMed

Liu, Y; Liang, X; Ren, W-W; Li, B-M

2014-01-17

Noradrenaline acting via β-adrenoceptors (β-ARs) in the CNS plays an important role in learning/memory and cognitive functions. β-ARs have been shown to be expressed in cortical pyramidal and subcortical principal cells. However, little is known about β-AR expression in different subtypes of GABAergic neurons. Here, we report that both β1- and β2-ARs are expressed in a majority of GABAergic interneurons in the medial prefrontal cortex of mice, including parvalbumin (PV)-, calretinin (CR)-, calbindin D-28k (CB)-, somatostatin (SST)- and Reelin-immunoreactive (ir) interneurons. Relative to PV-, CB-, SST- and Reelin-ir interneurons, CR-ir interneurons are less likely to express β1- and β2-ARs. SST-ir interneurons are more likely to express β2-AR compared with the other subtypes of interneurons. The present results are of significance for understanding the role of β-ARs in prefrontal cortical functions. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Morphological abnormalities in prefrontal surface area and thalamic volume in attention deficit/hyperactivity disorder.

PubMed

Batty, Martin J; Palaniyappan, Lena; Scerif, Gaia; Groom, Madeleine J; Liddle, Elizabeth B; Liddle, Peter F; Hollis, Chris

2015-08-30

Although previous morphological studies have demonstrated abnormalities in prefrontal cortical thickness in children with attention deficit/hyperactivity disorder (ADHD), studies investigating cortical surface area are lacking. As the development of cortical surface is closely linked to the establishment of thalam-ocortical connections, any abnormalities in the structure of the thalamus are likely to relate to altered cortical surface area. Using a clinically well-defined sample of children with ADHD (n = 25, 1 female) and typically developing controls (n = 24, 1 female), we studied surface area across the cortex to determine whether children with ADHD had reduced thalamic volume that related to prefrontal cortical surface area. Relative to controls, children with ADHD had a significant reduction in thalamic volume and dorsolateral prefrontal cortical area in both hemispheres. Furthermore, children with ADHD with smaller thalamic volumes were found to have greater reductions in surface area, a pattern not evident in the control children. Our results are further evidence of reduced lateral prefrontal cortical area in ADHD. Moreover, for the first time, we have also shown a direct association between thalamic anatomy and frontal anatomy in ADHD, suggesting the pathophysiological process that alters surface area maturation is likely to be linked to the development of the thalamus. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Pyramidal Cells in Prefrontal Cortex of Primates: Marked Differences in Neuronal Structure Among Species

PubMed Central

Elston, Guy N.; Benavides-Piccione, Ruth; Elston, Alejandra; Manger, Paul R.; DeFelipe, Javier

2010-01-01

The most ubiquitous neuron in the cerebral cortex, the pyramidal cell, is characterized by markedly different dendritic structure among different cortical areas. The complex pyramidal cell phenotype in granular prefrontal cortex (gPFC) of higher primates endows specific biophysical properties and patterns of connectivity, which differ from those in other cortical regions. However, within the gPFC, data have been sampled from only a select few cortical areas. The gPFC of species such as human and macaque monkey includes more than 10 cortical areas. It remains unknown as to what degree pyramidal cell structure may vary among these cortical areas. Here we undertook a survey of pyramidal cells in the dorsolateral, medial, and orbital gPFC of cercopithecid primates. We found marked heterogeneity in pyramidal cell structure within and between these regions. Moreover, trends for gradients in neuronal complexity varied among species. As the structure of neurons determines their computational abilities, memory storage capacity and connectivity, we propose that these specializations in the pyramidal cell phenotype are an important determinant of species-specific executive cortical functions in primates. PMID:21347276

A cerebellar thalamic cortical circuit for error-related cognitive control.

PubMed

Ide, Jaime S; Li, Chiang-shan R

2011-01-01

Error detection and behavioral adjustment are core components of cognitive control. Numerous studies have focused on the anterior cingulate cortex (ACC) as a critical locus of this executive function. Our previous work showed greater activation in the dorsal ACC and subcortical structures during error detection, and activation in the ventrolateral prefrontal cortex (VLPFC) during post-error slowing (PES) in a stop signal task (SST). However, the extent of error-related cortical or subcortical activation across subjects was not correlated with VLPFC activity during PES. So then, what causes VLPFC activation during PES? To address this question, we employed Granger causality mapping (GCM) and identified regions that Granger caused VLPFC activation in 54 adults performing the SST during fMRI. These brain regions, including the supplementary motor area (SMA), cerebellum, a pontine region, and medial thalamus, represent potential targets responding to errors in a way that could influence VLPFC activation. In confirmation of this hypothesis, the error-related activity of these regions correlated with VLPFC activation during PES, with the cerebellum showing the strongest association. The finding that cerebellar activation Granger causes prefrontal activity during behavioral adjustment supports a cerebellar function in cognitive control. Furthermore, multivariate GCA described the "flow of information" across these brain regions. Through connectivity with the thalamus and SMA, the cerebellum mediates error and post-error processing in accord with known anatomical projections. Taken together, these new findings highlight the role of the cerebello-thalamo-cortical pathway in an executive function that has heretofore largely been ascribed to the anterior cingulate-prefrontal cortical circuit. Copyright © 2010 Elsevier Inc. All rights reserved.

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…

Prefrontal gray matter volume recovery in treatment-seeking cocaine-addicted individuals: a longitudinal study.

PubMed

Parvaz, Muhammad A; Moeller, Scott J; d'Oleire Uquillas, Federico; Pflumm, Amanda; Maloney, Tom; Alia-Klein, Nelly; Goldstein, Rita Z

2017-09-01

Deficits in prefrontal cortical (PFC) function have been consistently reported in individuals with cocaine use disorders (iCUD), and have separately been shown to improve with longer-term abstinence. However, it is less clear whether the PFC structural integrity possibly underlying these deficits is also modulated by sustained reduction in drug use in iCUD. Here, T1-weighted magnetic resonance imaging scans were acquired, and performance on a neuropsychological test battery was assessed, in 19 initially abstinent treatment-seeking iCUD, first at baseline and then after six months of significantly reduced or no drug use (follow-up). A comparison cohort of 12 healthy controls was also scanned twice with a similar inter-scan interval. The iCUD showed increased gray matter volume in the left inferior frontal gyrus and bilaterally in the ventromedial prefrontal cortex at follow-up compared to baseline; healthy controls, as expected, showed no changes over this same time period. The iCUD also showed improved decision making and cognitive flexibility, with the latter correlated significantly with the gray matter volume increases in the inferior frontal gyrus. Given its association with improved cognitive function, the longitudinal recovery in cortical gray matter volume, particularly in regions where structure and function are adversely affected by chronic drug use, reflects a quantifiable positive impact of significantly reduced drug use on cortical structural integrity. © 2016 Society for the Study of Addiction.

Disrupted neural processing of emotional faces in psychopathy.

PubMed

Contreras-Rodríguez, Oren; Pujol, Jesus; Batalla, Iolanda; Harrison, Ben J; Bosque, Javier; Ibern-Regàs, Immaculada; Hernández-Ribas, Rosa; Soriano-Mas, Carles; Deus, Joan; López-Solà, Marina; Pifarré, Josep; Menchón, José M; Cardoner, Narcís

2014-04-01

Psychopaths show a reduced ability to recognize emotion facial expressions, which may disturb the interpersonal relationship development and successful social adaptation. Behavioral hypotheses point toward an association between emotion recognition deficits in psychopathy and amygdala dysfunction. Our prediction was that amygdala dysfunction would combine deficient activation with disturbances in functional connectivity with cortical regions of the face-processing network. Twenty-two psychopaths and 22 control subjects were assessed and functional magnetic resonance maps were generated to identify both brain activation and task-induced functional connectivity using psychophysiological interaction analysis during an emotional face-matching task. Results showed significant amygdala activation in control subjects only, but differences between study groups did not reach statistical significance. In contrast, psychopaths showed significantly increased activation in visual and prefrontal areas, with this latest activation being associated with psychopaths' affective-interpersonal disturbances. Psychophysiological interaction analyses revealed a reciprocal reduction in functional connectivity between the left amygdala and visual and prefrontal cortices. Our results suggest that emotional stimulation may evoke a relevant cortical response in psychopaths, but a disruption in the processing of emotional faces exists involving the reciprocal functional interaction between the amygdala and neocortex, consistent with the notion of a failure to integrate emotion into cognition in psychopathic individuals.

Greater Risk-Sensitivity of Dorsolateral Prefrontal Cortex in Young Smokers than in Nonsmokers

PubMed Central

Galván, Adriana; Schonberg, Tom; Mumford, Jeanette; Kohno, Milky; Poldrack, Russell A.; London, Edythe D.

2013-01-01

Rationale Despite a national reduction in the prevalence of cigarette smoking, ~19% of the adult U.S. population persists in this behavior, with the highest prevalence among 18–25-year-olds. Given that the choice to smoke imposes a known health risk, clarification of brain function related to decision-making, particularly involving risk-taking, in smokers may inform prevention and smoking cessation strategies. Objectives This study aimed to compare brain function related to decision-making in young smokers and nonsmokers. Methods The Balloon Analogue Risk Task (BART) is a computerized risky decision-making task in which participants pump virtual balloons, each pump associated with an incremental increase in potential payoff on a given trial but also with greater risk of balloon explosion and loss of payoff. We used this task to compare brain activation associated with risky decision-making in smokers (n=18) and nonsmokers (n=25) while they performed the BART during functional magnetic resonance imaging (fMRI). The participants were young men and women, 17–21 years of age. Results Risk level (number of pumps) modulated brain activation in the right dorsolateral and ventrolateral prefrontal cortices more in smokers than in nonsmokers; and smoking severity (Heaviness of Smoking Index) was positively related to this modulation in an adjacent frontal region. Conclusions Given evidence for involvement of the right dorsolateral and ventrolateral prefrontal cortices in inhibitory control, these findings suggest that young smokers have a different contribution of prefrontal cortical substrates to risky decision-making than nonsmokers. Future studies are warranted to determine whether the observed neurobiological differences precede or result from smoking. PMID:23644912

Quinolinic acid injection in mouse medial prefrontal cortex affects reversal learning abilities, cortical connectivity and hippocampal synaptic plasticity

PubMed Central

Latif-Hernandez, Amira; Shah, Disha; Ahmed, Tariq; Lo, Adrian C.; Callaerts-Vegh, Zsuzsanna; Van der Linden, Annemie; Balschun, Detlef; D’Hooge, Rudi

2016-01-01

Intracerebral injection of the excitotoxic, endogenous tryptophan metabolite, quinolinic acid (QA), constitutes a chemical model of neurodegenerative brain disease. Complementary techniques were combined to examine the consequences of QA injection into medial prefrontal cortex (mPFC) of C57BL6 mice. In accordance with the NMDAR-mediated synapto- and neurotoxic action of QA, we found an initial increase in excitability and an augmentation of hippocampal long-term potentiation, converting within two weeks into a reduction and impairment, respectively, of these processes. QA-induced mPFC excitotoxicity impaired behavioral flexibility in a reversal variant of the hidden-platform Morris water maze (MWM), whereas regular, extended MWM training was unaffected. QA-induced mPFC damage specifically affected the spatial-cognitive strategies that mice use to locate the platform during reversal learning. These behavioral and cognitive defects coincided with changes in cortical functional connectivity (FC) and hippocampal neuroplasticity. FC between various cortical regions was assessed by resting-state fMRI (rsfMRI) methodology, and mice that had received QA injection into mPFC showed increased FC between various cortical regions. mPFC and hippocampus (HC) are anatomically as well as functionally linked as part of a cortical network that controls higher-order cognitive functions. Together, these observations demonstrate the central functional importance of rodent mPFC as well as the validity of QA-induced mPFC damage as a preclinical rodent model of the early stages of neurodegeneration. PMID:27819338

What Is the Evidence for Inter-laminar Integration in a Prefrontal Cortical Minicolumn?

PubMed

Opris, Ioan; Chang, Stephano; Noga, Brian R

2017-01-01

The objective of this perspective article is to examine columnar inter-laminar integration during the executive control of behavior. The integration hypothesis posits that perceptual and behavioral signals are integrated within the prefrontal cortical inter-laminar microcircuits. Inter-laminar minicolumnar activity previously recorded from the dorsolateral prefrontal cortex (dlPFC) of nonhuman primates, trained in a visual delay match-to-sample (DMS) task, was re-assessed from an integrative perspective. Biomorphic multielectrode arrays (MEAs) played a unique role in the in vivo recording of columnar cell firing in the dlPFC layers 2/3 and 5/6. Several integrative aspects stem from these experiments: 1. Functional integration of perceptual and behavioral signals across cortical layers during executive control. The integrative effect of dlPFC minicolumns was shown by: (i) increased correlated firing on correct vs. error trials; (ii) decreased correlated firing when the number of non-matching images increased; and (iii) similar spatial firing preference across cortical-striatal cells during spatial-trials, and less on object-trials. 2. Causal relations to integration of cognitive signals by the minicolumnar turbo-engines. The inter-laminar integration between the perceptual and executive circuits was facilitated by stimulating the infra-granular layers with firing patterns obtained from supra-granular layers that enhanced spatial preference of percent correct performance on spatial trials. 3. Integration across hierarchical levels of the brain. The integration of intention signals (visual spatial, direction) with movement preparation (timing, velocity) in striatum and with the motor command and posture in midbrain is also discussed. These findings provide evidence for inter-laminar integration of executive control signals within brain's prefrontal cortical microcircuits.

Surface-based morphometry reveals the neuroanatomical basis of the five-factor model of personality

PubMed Central

Riccelli, Roberta; Toschi, Nicola; Nigro, Salvatore; Terracciano, Antonio

2017-01-01

Abstract The five-factor model (FFM) is a widely used taxonomy of human personality; yet its neuro anatomical basis remains unclear. This is partly because past associations between gray-matter volume and FFM were driven by different surface-based morphometry (SBM) indices (i.e. cortical thickness, surface area, cortical folding or any combination of them). To overcome this limitation, we used Free-Surfer to study how variability in SBM measures was related to the FFM in n = 507 participants from the Human Connectome Project. Neuroticism was associated with thicker cortex and smaller area and folding in prefrontal–temporal regions. Extraversion was linked to thicker pre-cuneus and smaller superior temporal cortex area. Openness was linked to thinner cortex and greater area and folding in prefrontal–parietal regions. Agreeableness was correlated to thinner prefrontal cortex and smaller fusiform gyrus area. Conscientiousness was associated with thicker cortex and smaller area and folding in prefrontal regions. These findings demonstrate that anatomical variability in prefrontal cortices is linked to individual differences in the socio-cognitive dispositions described by the FFM. Cortical thickness and surface area/folding were inversely related each others as a function of different FFM traits (neuroticism, extraversion and consciousness vs openness), which may reflect brain maturational effects that predispose or protect against psychiatric disorders. PMID:28122961

Normalization of Cortical Gray Matter Deficits in Nonpsychotic Siblings of Patients with Childhood-Onset Schizophrenia

ERIC Educational Resources Information Center

Mattai, Anand A.; Weisinger, Brian; Greenstein, Deanna; Stidd, Reva; Clasen, Liv; Miller, Rachel; Tossell, Julia W.; Rapoport, Judith L.; Gogtay, Nitin

2011-01-01

Objective: Cortical gray matter (GM) abnormalities in patients with childhood-onset schizophrenia (COS) progress during adolescence ultimately localizing to prefrontal and temporal cortices by early adult age. A previous study of 52 nonpsychotic siblings of COS probands had significant prefrontal and temporal GM deficits that appeared to…

A dorsolateral prefrontal cortex semi-automatic segmenter

NASA Astrophysics Data System (ADS)

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

2006-03-01

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

Trade-off of cerebello-cortical and cortico-cortical functional networks for planning in 6-year-old children.

PubMed

Kipping, Judy A; Margulies, Daniel S; Eickhoff, Simon B; Lee, Annie; Qiu, Anqi

2018-08-01

Childhood is a critical period for the development of cognitive planning. There is a lack of knowledge on its neural mechanisms in children. This study aimed to examine cerebello-cortical and cortico-cortical functional connectivity in association with planning skills in 6-year-olds (n = 76). We identified the cerebello-cortical and cortico-cortical functional networks related to cognitive planning using activation likelihood estimation (ALE) meta-analysis on existing functional imaging studies on spatial planning, and data-driven independent component analysis (ICA) of children's resting-state functional MRI (rs-fMRI). We investigated associations of cerebello-cortical and cortico-cortical functional connectivity with planning ability in 6-year-olds, as assessed using the Stockings of Cambridge task. Long-range functional connectivity of two cerebellar networks (lobules VI and lateral VIIa) with the prefrontal and premotor cortex were greater in children with poorer planning ability. In contrast, cortico-cortical association networks were not associated with the performance of planning in children. These results highlighted the key contribution of the lateral cerebello-frontal functional connectivity, but not cortico-cortical association functional connectivity, for planning ability in 6-year-olds. Our results suggested that brain adaptation to the acquisition of planning ability during childhood is partially achieved through the engagement of the cerebello-cortical functional connectivity. Copyright © 2018 Elsevier Inc. All rights reserved.

Prefrontal Hemodynamic Changes Associated with Subjective Sense of Occlusal Discomfort

PubMed Central

Kobayashi, Goh; Hayama, Rika; Ikuta, Ryuhei; Onozouka, Minoru; Wake, Hiroyuki; Shimada, Atsushi; Shibuya, Tomoaki; Tamaki, Katsushi

2015-01-01

We used functional near-infrared spectroscopy to measure prefrontal brain activity accompanying the physical sensation of oral discomfort that arose when healthy young-adult volunteers performed a grinding motion with mild occlusal elevation (96 μm). We simultaneously evaluated various forms of occlusal discomfort using the visual analogue scale (VAS) and hemodynamic responses to identify the specific prefrontal activity that occurs with increased occlusal discomfort. The Oxy-Hb responses of selected channels in the bilateral frontopolar and dorsolateral prefrontal cortices increased in participants who reported increased severity of occlusal discomfort, while they decreased in those who reported no change or decreased occlusal discomfort during grinding. Moreover, the cumulative values of Oxy-Hb response in some of these channels were statistically significant predictive factors for the VAS scores. A generalized linear model analysis of Oxy-Hb signals in a group of participants who reported increased discomfort further indicated significant cerebral activation in the right frontopolar and dorsolateral prefrontal cortices that overlapped with the results of correlation analyses. Our results suggest that the increased hemodynamic responses in the prefrontal area reflect the top-down control of attention and/or self-regulation against the uncomfortable somatosensory input, which could be a possible marker to detect the subjective sense of occlusal discomfort. PMID:26090407

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.

Experience and the developing prefrontal cortex

PubMed Central

Kolb, Bryan; Mychasiuk, Richelle; Muhammad, Arif; Li, Yilin; Frost, Douglas O.; Gibb, Robbin

2012-01-01

The prefrontal cortex (PFC) receives input from all other cortical regions and functions to plan and direct motor, cognitive, affective, and social behavior across time. It has a prolonged development, which allows the acquisition of complex cognitive abilities through experience but makes it susceptible to factors that can lead to abnormal functioning, which is often manifested in neuropsychiatric disorders. When the PFC is exposed to different environmental events during development, such as sensory stimuli, stress, drugs, hormones, and social experiences (including both parental and peer interactions), the developing PFC may develop in different ways. The goal of the current review is to illustrate how the circuitry of the developing PFC can be sculpted by a wide range of pre- and postnatal factors. We begin with an overview of prefrontal functioning and development, and we conclude with a consideration of how early experiences influence prefrontal development and behavior. PMID:23045653

Effects of Aging on the Neural Correlates of Successful Item and Source Memory Encoding

PubMed Central

Dennis, Nancy A.; Hayes, Scott M.; Prince, Steven E.; Madden, David J.; Huettel, Scott A.; Cabeza, Roberto

2009-01-01

To investigate the neural basis of age-related source memory (SM) deficits, young and older adults were scanned with fMRI while encoding faces, scenes, and face-scene pairs. Successful encoding activity was identified by comparing encoding activity for subsequently remembered versus forgotten items or pairs. Age deficits in successful encoding activity in hippocampal and prefrontal regions were more pronounced for SM (pairs) compared to item memory (faces and scenes). Age-related reductions were also found in regions specialized in processing faces (fusiform face area) and scenes (parahippocampal place area), but these reductions were similar for item and SM. Functional connectivity between the hippocampus and the rest of the brain was also affected by aging; whereas connections with posterior cortices were weaker in older adults, connections with anterior cortices including prefrontal regions were stronger in older adults. Taken together, the results provide a link between SM deficits in older adults and reduced recruitment of hippocampal and prefrontal regions during encoding. The functional connectivity findings are consistent with a posterior-anterior shift with aging (PASA), previously reported in several cognitive domains and linked to functional compensation. PMID:18605869

Looking for truth and finding lies: the prospects for a nascent neuroimaging of deception.

PubMed

Spence, Sean A; Kaylor-Hughes, Catherine J

2008-01-01

Lying is ubiquitous and has acquired many names. In 'natural experiments', both pathological lying and truthfulness implicate prefrontal cortices. Recently, the advent of functional neuroimaging has allowed investigators to study deception in the non-pathological state. Prefrontal cortices are again implicated, although the regions identified vary across experiments. Forensic application of such technology (to the detection of deceit) requires the solution of tractable technical problems. Whether we 'should' detect deception remains an ethical problem: one for societies to resolve. However, such a procedure would only appear to be ethical when subjects volunteer to participate, as might occur during the investigation of alleged miscarriages of justice. We demonstrate how this might be approached.

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

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

PubMed

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

2002-11-30

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

Extensive video-game experience alters cortical networks for complex visuomotor transformations.

PubMed

Granek, Joshua A; Gorbet, Diana J; Sergio, Lauren E

2010-10-01

Using event-related functional magnetic resonance imaging (fMRI), we examined the effect of video-game experience on the neural control of increasingly complex visuomotor tasks. Previously, skilled individuals have demonstrated the use of a more efficient movement control brain network, including the prefrontal, premotor, primary sensorimotor and parietal cortices. Our results extend and generalize this finding by documenting additional prefrontal cortex activity in experienced video gamers planning for complex eye-hand coordination tasks that are distinct from actual video-game play. These changes in activation between non-gamers and extensive gamers are putatively related to the increased online control and spatial attention required for complex visually guided reaching. These data suggest that the basic cortical network for processing complex visually guided reaching is altered by extensive video-game play. Crown Copyright © 2009. Published by Elsevier Srl. All rights reserved.

Age-Related Impairments in Object-Place Associations Are Not Due to Hippocampal Dysfunction

PubMed Central

Hernandez, Abigail R.; Maurer, Andrew P.; Reasor, Jordan E.; Turner, Sean M.; Barthle, Sarah E.; Johnson, Sarah A.; Burke, Sara N.

2016-01-01

Age-associated cognitive decline can reduce an individual’s quality of life. As no single neurobiological deficit can account for the wide spectrum of behavioral impairments observed in old age, it is critical to develop an understanding of how interactions between different brain regions change over the life span. The performance of young and aged animals on behaviors that require the hippocampus and cortical regions to interact, however, has not been well characterized. Specifically, the ability to link a spatial location with specific features of a stimulus, such as object identity, relies on the hippocampus, perirhinal and prefrontal cortices. Although aging is associated with dysfunction in each of these brain regions, behavioral measures of functional change within the hippocampus, perirhinal and prefrontal cortices in individual animals are often not correlated. Thus, how dysfunction of a single brain region within this circuit, such as the hippocampus, impacts behaviors that require communication with the perirhinal and prefrontal cortices remains unknown. To address this question, young and aged rats were tested on the interregion dependent object-place paired association task, as well as a hippocampal-dependent test of spatial reference memory. This particular cohort of aged rats did not show deficits on the hippocampal-dependent task, but were significantly impaired at acquiring object-place associations relative to young. These data suggest that behaviors requiring functional connectivity across different regions of the memory network may be particularly sensitive to aging, and can be used to develop models that will clarify the impact of systems-level dysfunction in the elderly. PMID:26413723

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

Enriched encoding: reward motivation organizes cortical networks for hippocampal detection of unexpected events.

PubMed

Murty, Vishnu P; Adcock, R Alison

2014-08-01

Learning how to obtain rewards requires learning about their contexts and likely causes. How do long-term memory mechanisms balance the need to represent potential determinants of reward outcomes with the computational burden of an over-inclusive memory? One solution would be to enhance memory for salient events that occur during reward anticipation, because all such events are potential determinants of reward. We tested whether reward motivation enhances encoding of salient events like expectancy violations. During functional magnetic resonance imaging, participants performed a reaction-time task in which goal-irrelevant expectancy violations were encountered during states of high- or low-reward motivation. Motivation amplified hippocampal activation to and declarative memory for expectancy violations. Connectivity of the ventral tegmental area (VTA) with medial prefrontal, ventrolateral prefrontal, and visual cortices preceded and predicted this increase in hippocampal sensitivity. These findings elucidate a novel mechanism whereby reward motivation can enhance hippocampus-dependent memory: anticipatory VTA-cortical-hippocampal interactions. Further, the findings integrate literatures on dopaminergic neuromodulation of prefrontal function and hippocampus-dependent memory. We conclude that during reward motivation, VTA modulation induces distributed neural changes that amplify hippocampal signals and records of expectancy violations to improve predictions-a potentially unique contribution of the hippocampus to reward learning. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Electrophysiological Mapping of Novel Prefrontal – Cerebellar Pathways

PubMed Central

Watson, Thomas C.; Jones, Matthew W.; Apps, Richard

2009-01-01

Whilst the cerebellum is predominantly considered a sensorimotor control structure, accumulating evidence suggests that it may also subserve non-motor functions during cognition. However, this possibility is not universally accepted, not least because the nature and pattern of links between higher cortical structures and the cerebellum are poorly characterized. We have therefore used in vivo electrophysiological methods in anaesthetized rats to directly investigate connectivity between the medial prefrontal cortex (prelimbic subdivision, PrL) and the cerebellum. Stimulation of deep layers of PrL evoked distinct field potentials in the cerebellar cortex with a mean latency to peak of approximately 35 ms. These responses showed a well-defined topography, and were maximal in lobule VII of the contralateral vermis (a known oculomotor centre); they were not attenuated by local anaesthesia of the overlying M2 motor cortex, though M2 stimulation did evoke field potentials in lobule VII with a shorter latency (approximately 30 ms). Single unit recordings showed that prelimbic cortical stimulation elicits complex spikes in lobule VII Purkinje cells, indicating transmission via a previously undescribed cerebro-olivocerebellar pathway. Our results therefore establish a physiological basis for communication between PrL and the cerebellum. The role(s) of this pathway remain to be resolved, but presumably relate to control of eye movements and/or distributed networks associated with integrated prefrontal cortical functions. PMID:19738932

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

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

PubMed

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

2003-04-01

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

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.

Thinning of the lateral prefrontal cortex during adolescence predicts emotion regulation in females.

PubMed

Vijayakumar, Nandita; Whittle, Sarah; Yücel, Murat; Dennison, Meg; Simmons, Julian; Allen, Nicholas B

2014-11-01

Adolescence is a crucial period for the development of adaptive emotion regulation strategies. Despite the fact that structural maturation of the prefrontal cortex during adolescence is often assumed to underlie the maturation of emotion regulation strategies, no longitudinal studies have directly assessed this relationship. This study examined whether use of cognitive reappraisal strategies during late adolescence was predicted by (i) absolute prefrontal cortical thickness during early adolescence and (ii) structural maturation of the prefrontal cortex between early and mid-adolescence. Ninety-two adolescents underwent baseline and follow-up magnetic resonance imaging scans when they were aged approximately 12 and 16 years, respectively. FreeSurfer software was used to obtain cortical thickness estimates for three prefrontal regions [anterior cingulate cortex; dorsolateral prefrontal cortex (dlPFC); ventrolateral prefrontal cortex (vlPFC)]. The Emotion Regulation Questionnaire was completed when adolescents were aged approximately 19 years. Results showed that greater cortical thinning of the left dlPFC and left vlPFC during adolescence was significantly associated with greater use of cognitive reappraisal in females, though no such relationship was evident in males. Furthermore, baseline left dlPFC thickness predicted cognitive reappraisal at trend level. These findings suggest that cortical maturation may play a role in the development of adaptive emotion regulation strategies during adolescence. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Cortical activation pattern during shoulder simple versus vibration exercises: a functional near infrared spectroscopy study.

PubMed

Jang, Sung Ho; Yeo, Sang Seok; Lee, Seung Hyun; Jin, Sang Hyun; Lee, Mi Young

2017-08-01

To date, the cortical effect of exercise has not been fully elucidated. Using the functional near infrared spectroscopy, we attempted to compare the cortical effect between shoulder vibration exercise and shoulder simple exercise. Eight healthy subjects were recruited for this study. Two different exercise tasks (shoulder vibration exercise using the flexible pole and shoulder simple exercise) were performed using a block paradigm. We measured the values of oxygenated hemoglobin in the four regions of interest: the primary sensory-motor cortex (SM1 total, arm somatotopy, and leg and trunk somatotopy), the premotor cortex, the supplementary motor area, and the prefrontal cortex. During shoulder vibration exercise and shoulder simple exercise, cortical activation was observed in SM1 (total, arm somatotopy, and leg and trunk somatotopy), premotor cortex, supplementary motor area, and prefrontal cortex. Higher oxygenated hemoglobin values were also observed in the areas of arm somatotopy of SM1 compared with those of other regions of interest. However, no significant difference in the arm somatotopy of SM1 was observed between the two exercises. By contrast, in the leg and trunk somatotopy of SM1, shoulder vibration exercise led to a significantly higher oxy-hemoglobin value than shoulder simple exercise. These two exercises may result in cortical activation effects for the motor areas relevant to the shoulder exercise, especially in the arm somatotopy of SM1. However, shoulder vibration exercise has an additional cortical activation effect for the leg and trunk somatotopy of SM1.

No Effects of Bilateral tDCS over Inferior Frontal Gyrus on Response Inhibition and Aggression

PubMed Central

Lobbestael, Jill; Arntz, Arnoud; Brugman, Suzanne; Sack, Alexander T.

2015-01-01

Response inhibition is defined as the capacity to adequately withdraw pre-planned responses. It has been shown that individuals with deficits in inhibiting pre-planned responses tend to display more aggressive behaviour. The prefrontal cortex is involved in both, response inhibition and aggression. While response inhibition is mostly associated with predominantly right prefrontal activity, the neural components underlying aggression seem to be left-lateralized. These differences in hemispheric dominance are conceptualized in cortical asymmetry theories on motivational direction, which assign avoidance motivation (relevant to inhibit responses) to the right and approach motivation (relevant for aggressive actions) to the left prefrontal cortex. The current study aimed to directly address the inverse relationship between response inhibition and aggression by assessing them within one experiment. Sixty-nine healthy participants underwent bilateral transcranial Direct Current Stimulation (tDCS) to the inferior frontal cortex. In one group we induced right-hemispheric fronto-cortical dominance by means of a combined right prefrontal anodal and left prefrontal cathodal tDCS montage. In a second group we induced left-hemispheric fronto-cortical dominance by means of a combined left prefrontal anodal and right prefrontal cathodal tDCS montage. A control group received sham stimulation. Response inhibition was assessed with a go/no-go task (GNGT) and aggression with the Taylor Aggression Paradigm (TAP). We revealed that participants with poorer performance in the GNGT displayed more aggression during the TAP. No effects of bilateral prefrontal tDCS on either response inhibition or aggression were observed. This is at odds with previous brain stimulation studies applying unilateral protocols. Our results failed to provide evidence in support of the prefrontal cortical asymmetry model in the domain of response inhibition and aggression. The absence of tDCS effects might also indicate that the methodological approach of shifting cortical asymmetry by means of bilateral tDCS protocols has failed. PMID:26161664

Basal Forebrain Gating by Somatostatin Neurons Drives Prefrontal Cortical Activity.

PubMed

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

2017-11-17

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

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

Neural Correlates of Lyrical Improvisation: An fMRI Study of Freestyle Rap

PubMed Central

Liu, Siyuan; Chow, Ho Ming; Xu, Yisheng; Erkkinen, Michael G.; Swett, Katherine E.; Eagle, Michael W.; Rizik-Baer, Daniel A.; Braun, Allen R.

2012-01-01

The neural correlates of creativity are poorly understood. Freestyle rap provides a unique opportunity to study spontaneous lyrical improvisation, a multidimensional form of creativity at the interface of music and language. Here we use functional magnetic resonance imaging to characterize this process. Task contrast analyses indicate that improvised performance is characterized by dissociated activity in medial and dorsolateral prefrontal cortices, providing a context in which stimulus-independent behaviors may unfold in the absence of conscious monitoring and volitional control. Connectivity analyses reveal widespread improvisation-related correlations between medial prefrontal, cingulate motor, perisylvian cortices and amygdala, suggesting the emergence of a network linking motivation, language, affect and movement. Lyrical improvisation appears to be characterized by altered relationships between regions coupling intention and action, in which conventional executive control may be bypassed and motor control directed by cingulate motor mechanisms. These functional reorganizations may facilitate the initial improvisatory phase of creative behavior. PMID:23155479

Neural correlates of lyrical improvisation: an FMRI study of freestyle rap.

PubMed

Liu, Siyuan; Chow, Ho Ming; Xu, Yisheng; Erkkinen, Michael G; Swett, Katherine E; Eagle, Michael W; Rizik-Baer, Daniel A; Braun, Allen R

2012-01-01

The neural correlates of creativity are poorly understood. Freestyle rap provides a unique opportunity to study spontaneous lyrical improvisation, a multidimensional form of creativity at the interface of music and language. Here we use functional magnetic resonance imaging to characterize this process. Task contrast analyses indicate that improvised performance is characterized by dissociated activity in medial and dorsolateral prefrontal cortices, providing a context in which stimulus-independent behaviors may unfold in the absence of conscious monitoring and volitional control. Connectivity analyses reveal widespread improvisation-related correlations between medial prefrontal, cingulate motor, perisylvian cortices and amygdala, suggesting the emergence of a network linking motivation, language, affect and movement. Lyrical improvisation appears to be characterized by altered relationships between regions coupling intention and action, in which conventional executive control may be bypassed and motor control directed by cingulate motor mechanisms. These functional reorganizations may facilitate the initial improvisatory phase of creative behavior.

Abdominal Pain, the Adolescent and Altered Brain Structure and Function

PubMed Central

Becerra, Lino; Heinz, Nicole; Ludwick, Allison; Rasooly, Tali; Wu, Rina; Johnson, Adriana; Schechter, Neil L.; Borsook, David; Nurko, Samuel

2016-01-01

Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disorder of unknown etiology. Although relatively common in children, how this condition affects brain structure and function in a pediatric population remains unclear. Here, we investigate brain changes in adolescents with IBS and healthy controls. Imaging was performed with a Siemens 3 Tesla Trio Tim MRI scanner equipped with a 32-channel head coil. A high-resolution T1-weighted anatomical scan was acquired followed by a T2-weighted functional scan. We used a surface-based morphometric approach along with a seed-based resting-state functional connectivity (RS-FC) analysis to determine if groups differed in cortical thickness and whether areas showing structural differences also showed abnormal RS-FC patterns. Patients completed the Abdominal Pain Index and the GI Module of the Pediatric Quality of Life Inventory to assess abdominal pain severity and impact of GI symptoms on health-related quality of life (HRQOL). Disease duration and pain intensity were also assessed. Pediatric IBS patients, relative to controls, showed cortical thickening in the posterior cingulate (PCC), whereas cortical thinning in posterior parietal and prefrontal areas were found, including the dorsolateral prefrontal cortex (DLPFC). In patients, abdominal pain severity was related to cortical thickening in the intra-abdominal area of the primary somatosensory cortex (SI), whereas HRQOL was associated with insular cortical thinning. Disease severity measures correlated with cortical thickness in bilateral DLPFC and orbitofrontal cortex. Patients also showed reduced anti-correlations between PCC and DLPFC compared to controls, a finding that may reflect aberrant connectivity between default mode and cognitive control networks. We are the first to demonstrate concomitant structural and functional brain changes associated with abdominal pain severity, HRQOL related to GI-specific symptoms, and disease-specific measures in adolescents with IBS. It is possible such changes will be responsive to therapeutic intervention and may be useful as potential markers of disease progression or reversal. PMID:27244227

Abdominal Pain, the Adolescent and Altered Brain Structure and Function.

PubMed

Hubbard, Catherine S; Becerra, Lino; Heinz, Nicole; Ludwick, Allison; Rasooly, Tali; Wu, Rina; Johnson, Adriana; Schechter, Neil L; Borsook, David; Nurko, Samuel

2016-01-01

Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disorder of unknown etiology. Although relatively common in children, how this condition affects brain structure and function in a pediatric population remains unclear. Here, we investigate brain changes in adolescents with IBS and healthy controls. Imaging was performed with a Siemens 3 Tesla Trio Tim MRI scanner equipped with a 32-channel head coil. A high-resolution T1-weighted anatomical scan was acquired followed by a T2-weighted functional scan. We used a surface-based morphometric approach along with a seed-based resting-state functional connectivity (RS-FC) analysis to determine if groups differed in cortical thickness and whether areas showing structural differences also showed abnormal RS-FC patterns. Patients completed the Abdominal Pain Index and the GI Module of the Pediatric Quality of Life Inventory to assess abdominal pain severity and impact of GI symptoms on health-related quality of life (HRQOL). Disease duration and pain intensity were also assessed. Pediatric IBS patients, relative to controls, showed cortical thickening in the posterior cingulate (PCC), whereas cortical thinning in posterior parietal and prefrontal areas were found, including the dorsolateral prefrontal cortex (DLPFC). In patients, abdominal pain severity was related to cortical thickening in the intra-abdominal area of the primary somatosensory cortex (SI), whereas HRQOL was associated with insular cortical thinning. Disease severity measures correlated with cortical thickness in bilateral DLPFC and orbitofrontal cortex. Patients also showed reduced anti-correlations between PCC and DLPFC compared to controls, a finding that may reflect aberrant connectivity between default mode and cognitive control networks. We are the first to demonstrate concomitant structural and functional brain changes associated with abdominal pain severity, HRQOL related to GI-specific symptoms, and disease-specific measures in adolescents with IBS. It is possible such changes will be responsive to therapeutic intervention and may be useful as potential markers of disease progression or reversal.

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

PubMed

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

2008-11-11

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

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

Parsing dimensional vs diagnostic category-related patterns of reward circuitry function in behaviorally and emotionally dysregulated youth in the Longitudinal Assessment of Manic Symptoms study.

PubMed

Bebko, Genna; Bertocci, Michele A; Fournier, Jay C; Hinze, Amanda K; Bonar, Lisa; Almeida, Jorge R C; Perlman, Susan B; Versace, Amelia; Schirda, Claudiu; Travis, Michael; Gill, Mary Kay; Demeter, Christine; Diwadkar, Vaibhav A; Ciuffetelli, Gary; Rodriguez, Eric; Olino, Thomas; Forbes, Erika; Sunshine, Jeffrey L; Holland, Scott K; Kowatch, Robert A; Birmaher, Boris; Axelson, David; Horwitz, Sarah M; Arnold, L Eugene; Fristad, Mary A; Youngstrom, Eric A; Findling, Robert L; Phillips, Mary L

2014-01-01

Pediatric disorders characterized by behavioral and emotional dysregulation pose diagnostic and treatment challenges because of high comorbidity, suggesting that they may be better conceptualized dimensionally rather than categorically. Identifying neuroimaging measures associated with behavioral and emotional dysregulation in youth may inform understanding of underlying dimensional vs disorder-specific pathophysiologic features. To identify, in a large cohort of behaviorally and emotionally dysregulated youth, neuroimaging measures that (1) are associated with behavioral and emotional dysregulation pathologic dimensions (behavioral and emotional dysregulation measured with the Parent General Behavior Inventory 10-Item Mania Scale [PGBI-10M], mania, depression, and anxiety) or (2) differentiate diagnostic categories (bipolar spectrum disorders, attention-deficit/hyperactivity disorder, anxiety, and disruptive behavior disorders). A multisite neuroimaging study was conducted from February 1, 2011, to April 15, 2012, at 3 academic medical centers: University Hospitals Case Medical Center, Cincinnati Children's Hospital Medical Center, and University of Pittsburgh Medical Center. Participants included a referred sample of behaviorally and emotionally dysregulated youth from the Longitudinal Assessment of Manic Symptoms (LAMS) study (n = 85) and healthy youth (n = 20). Region-of-interest analyses examined relationships among prefrontal-ventral striatal reward circuitry during a reward paradigm (win, loss, and control conditions), symptom dimensions, and diagnostic categories. Regardless of diagnosis, higher PGBI-10M scores were associated with greater left middle prefrontal cortical activity (r = 0.28) and anxiety with greater right dorsal anterior cingulate cortical (r = 0.27) activity to win. The 20 highest (t = 2.75) and 20 lowest (t = 2.42) PGBI-10M-scoring youth showed significantly greater left middle prefrontal cortical activity to win compared with 20 healthy youth. Disruptive behavior disorders were associated with lower left ventrolateral prefrontal cortex activity to win (t = 2.68) (all P < .05, corrected). Greater PGBI-10M-related left middle prefrontal cortical activity and anxiety-related right dorsal anterior cingulate cortical activity to win may reflect heightened reward sensitivity and greater attention to reward in behaviorally and emotionally dysregulated youth regardless of diagnosis. Reduced left ventrolateral prefrontal cortex activity to win may reflect reward insensitivity in youth with disruptive behavior disorders. Despite a distinct reward-related neurophysiologic feature in disruptive behavior disorders, findings generally support a dimensional approach to studying neural mechanisms in behaviorally and emotionally dysregulated youth.

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.

Thalamic amplification of cortical connectivity sustains attentional control

PubMed Central

Schmitt, L. Ian; Wimmer, Ralf D.; Nakajima, Miho; Happ, Michael; Mofakham, Sima; Halassa, Michael M.

2017-01-01

While interactions between the thalamus and cortex are critical for cognitive function1–3, the exact contribution of the thalamus to these interactions is often unclear. Recent studies have shown diverse connectivity patterns across the thalamus 4,5, but whether this diversity translates to thalamic functions beyond relaying information to or between cortical regions6 is unknown. Here, by investigating prefrontal cortical (PFC) representation of two rules used to guide attention, we find that the mediodorsal thalamus (MD) sustains these representations without relaying categorical information. Specifically, MD input amplifies local PFC connectivity, enabling rule-specific neural sequences to emerge and thereby maintain rule representations. Consistent with this notion, broadly enhancing PFC excitability diminishes rule specificity and behavioral performance, while enhancing MD excitability improves both. Overall, our results define a previously unknown principle in neuroscience; thalamic control of functional cortical connectivity. This function indicates that the thalamus plays much more central roles in cognition than previously thought. PMID:28467827

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

PubMed

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

2015-10-01

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

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.

Age-dependent changes in prefrontal intrinsic connectivity

PubMed Central

Zhou, Xin; Zhu, Dantong; Katsuki, Fumi; Qi, Xue-Lian; Lees, Cynthia J.; Bennett, Allyson J.; Salinas, Emilio; Stanford, Terrence R.; Constantinidis, Christos

2014-01-01

The prefrontal cortex continues to mature after puberty and into early adulthood, mirroring the time course of maturation of cognitive abilities. However, the way in which prefrontal activity changes during peri- and postpubertal cortical maturation is largely unknown. To address this question, we evaluated the developmental stage of peripubertal rhesus monkeys with a series of morphometric, hormonal, and radiographic measures, and conducted behavioral and neurophysiological tests as the monkeys performed working memory tasks. We compared firing rate and the strength of intrinsic functional connectivity between neurons in peripubertal vs. adult monkeys. Notably, analyses of spike train cross-correlations demonstrated that the average magnitude of functional connections measured between neurons was lower overall in the prefrontal cortex of peripubertal monkeys compared with adults. The difference resulted because negative functional connections (indicative of inhibitory interactions) were stronger and more prevalent in peripubertal compared with adult monkeys, whereas the positive connections showed similar distributions in the two groups. Our results identify changes in the intrinsic connectivity of prefrontal neurons, particularly that mediated by inhibition, as a possible substrate for peri- and postpubertal advances in cognitive capacity. PMID:24567390

P300 and LORETA: comparison of normal subjects and schizophrenic patients.

PubMed

Winterer, G; Mulert, C; Mientus, S; Gallinat, J; Schlattmann, P; Dorn, H; Herrmann, W M

2001-01-01

It was the aim of the present study 1) to investigate how many cortical activity maxima of scalp-recorded P300 are detected by Low Resolution Electromagentic Tomography (LORETA) when analyses are performed with high time-resolution, 2) to see if the resulting LORETA-solution is in accordance with intracortical recordings as reported by others and 3) to compare the given pattern of cortical activation maxima in the P300-timeframe between schizophrenic patients and normal controls. Current density analysis was performed in 3-D Talairach space with high time resolution i.e. in 6 ms steps. This was done during an auditory choice reaction paradigm separately for normal subjects and schizophrenic patients with subsequent group comparisons. In normal subjects, a sequence of at least seven cortical activation maxima was found between 240-420ms poststimulus: the prefrontal cortex, anterior or medial cingulum, posterior cingulum, parietal cortex, temporal lobe, prefrontal cortex, medial or anterior cingulum. Within the given limits of spatial resolution, this sequential maxima distribution largely met the expectations from reports on intracranial recordings and functional neuroimaging studies. However, localization accuracy was higher near the central midline than at lateral aspects of the brain. Schizophrenic patients less activated their cortex in a widespread area mainly in the left hemisphere including the prefrontal cortex, posterior cingulum and the temporal lobe. From these analyses and comparsions with intracranial recordings as reported by others, it is concluded that LORETA correctly localizes P300-related cortical activity maxima on the basis of 19 electrodes except for lateral cortical aspects which is most likely an edge-phenomenon. The data further suggest that the P300-deficit in schizophrenics involves an extended cortical network of the left hemisphere at several steps in time during the information processing stream.

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

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.

Positive Association of Video Game Playing with Left Frontal Cortical Thickness in Adolescents

PubMed Central

Kühn, Simone; Lorenz, Robert; Banaschewski, Tobias; Barker, Gareth J.; Büchel, Christian; Conrod, Patricia J.; Flor, Herta; Garavan, Hugh; Ittermann, Bernd; Loth, Eva; Mann, Karl; Nees, Frauke; Artiges, Eric; Paus, Tomas; Rietschel, Marcella; Smolka, Michael N.; Ströhle, Andreas; Walaszek, Bernadetta; Schumann, Gunter; Heinz, Andreas; Gallinat, Jürgen

2014-01-01

Playing video games is a common recreational activity of adolescents. Recent research associated frequent video game playing with improvements in cognitive functions. Improvements in cognition have been related to grey matter changes in prefrontal cortex. However, a fine-grained analysis of human brain structure in relation to video gaming is lacking. In magnetic resonance imaging scans of 152 14-year old adolescents, FreeSurfer was used to estimate cortical thickness. Cortical thickness across the whole cortical surface was correlated with self-reported duration of video gaming (hours per week). A robust positive association between cortical thickness and video gaming duration was observed in left dorsolateral prefrontal cortex (DLPFC) and left frontal eye fields (FEFs). No regions showed cortical thinning in association with video gaming frequency. DLPFC is the core correlate of executive control and strategic planning which in turn are essential cognitive domains for successful video gaming. The FEFs are a key region involved in visuo-motor integration important for programming and execution of eye movements and allocation of visuo-spatial attention, processes engaged extensively in video games. The results may represent the biological basis of previously reported cognitive improvements due to video game play. Whether or not these results represent a-priori characteristics or consequences of video gaming should be studied in future longitudinal investigations. PMID:24633348

Awake vs. anesthetized: layer-specific sensory processing in visual cortex and functional connectivity between cortical areas

PubMed Central

Sellers, Kristin K.; Bennett, Davis V.; Hutt, Axel; Williams, James H.

2015-01-01

During general anesthesia, global brain activity and behavioral state are profoundly altered. Yet it remains mostly unknown how anesthetics alter sensory processing across cortical layers and modulate functional cortico-cortical connectivity. To address this gap in knowledge of the micro- and mesoscale effects of anesthetics on sensory processing in the cortical microcircuit, we recorded multiunit activity and local field potential in awake and anesthetized ferrets (Mustela putoris furo) during sensory stimulation. To understand how anesthetics alter sensory processing in a primary sensory area and the representation of sensory input in higher-order association areas, we studied the local sensory responses and long-range functional connectivity of primary visual cortex (V1) and prefrontal cortex (PFC). Isoflurane combined with xylazine provided general anesthesia for all anesthetized recordings. We found that anesthetics altered the duration of sensory-evoked responses, disrupted the response dynamics across cortical layers, suppressed both multimodal interactions in V1 and sensory responses in PFC, and reduced functional cortico-cortical connectivity between V1 and PFC. Together, the present findings demonstrate altered sensory responses and impaired functional network connectivity during anesthesia at the level of multiunit activity and local field potential across cortical layers. PMID:25833839

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.

A critical appraisal of neuroimaging studies of bipolar disorder: toward a new conceptualization of underlying neural circuitry and roadmap for future research

PubMed Central

Phillips, Mary L; Swartz, Holly A.

2014-01-01

Objective This critical review appraises neuroimaging findings in bipolar disorder in emotion processing, emotion regulation, and reward processing neural circuitry, to synthesize current knowledge of the neural underpinnings of bipolar disorder, and provide a neuroimaging research “roadmap” for future studies. Method We examined findings from all major studies in bipolar disorder that used fMRI, volumetric analyses, diffusion imaging, and resting state techniques, to inform current conceptual models of larger-scale neural circuitry abnormalities in bipolar disorder Results Bipolar disorder can be conceptualized in neural circuitry terms as parallel dysfunction in bilateral prefrontal cortical (especially ventrolateral prefrontal cortical)-hippocampal-amygdala emotion processing and emotion regulation neural circuitries, together with an “overactive” left-sided ventral striatal-ventrolateral and orbitofrontal cortical reward processing circuitry, that result in characteristic behavioral abnormalities associated with bipolar disorder: emotional lability, emotional dysregulation and heightened reward sensitivity. A potential structural basis for these functional abnormalities are gray matter decreases in prefrontal and temporal cortices, amygdala and hippocampus, and fractional anisotropy decreases in white matter tracts connecting prefrontal and subcortical regions. Conclusion Neuroimaging studies of bipolar disorder clearly demonstrate abnormalities in neural circuitries supporting emotion processing, emotion regulation and reward processing, although there are several limitations to these studies. Future neuroimaging research in bipolar disorder should include studies adopting dimensional approaches; larger studies examining neurodevelopmental trajectories in bipolar disorder and at-risk youth; multimodal neuroimaging studies using integrated systems approaches; and studies using pattern recognition approaches to provide clinically useful, individual-level data. Such studies will help identify clinically-relevant biomarkers to guide diagnosis and treatment decision-making for individuals with bipolar disorder. PMID:24626773

An insula-frontostriatal network mediates flexible cognitive control by adaptively predicting changing control demands

PubMed Central

Jiang, Jiefeng; Beck, Jeffrey; Heller, Katherine; Egner, Tobias

2015-01-01

The anterior cingulate and lateral prefrontal cortices have been implicated in implementing context-appropriate attentional control, but the learning mechanisms underlying our ability to flexibly adapt the control settings to changing environments remain poorly understood. Here we show that human adjustments to varying control demands are captured by a reinforcement learner with a flexible, volatility-driven learning rate. Using model-based functional magnetic resonance imaging, we demonstrate that volatility of control demand is estimated by the anterior insula, which in turn optimizes the prediction of forthcoming demand in the caudate nucleus. The caudate's prediction of control demand subsequently guides the implementation of proactive and reactive attentional control in dorsal anterior cingulate and dorsolateral prefrontal cortices. These data enhance our understanding of the neuro-computational mechanisms of adaptive behaviour by connecting the classic cingulate-prefrontal cognitive control network to a subcortical control-learning mechanism that infers future demands by flexibly integrating remote and recent past experiences. PMID:26391305

Effects of Mandibular Retrusive Deviation on Prefrontal Cortex Activation: A Functional Near-Infrared Spectroscopy Study

PubMed Central

Otsuka, Takero; Yamasaki, Ryuichi; Shimazaki, Tateshi; Sasaguri, Kenichi; Kawata, Toshitsugu

2015-01-01

The objective of this study was to evaluate occlusal condition by assessing brain activity in the prefrontal cortex, which is associated with emotion. Functional near-infrared spectroscopy (fNIRS) was used to detect changes in cerebral blood flow in the prefrontal cortex of 12 healthy volunteers. The malocclusion model was a custom-made splint that forced the mandible into retrusion. A splint with no modification was used as a control. The cortical activation during clenching was compared between the retrusive position condition and the control condition. A visual analog scale score for discomfort was also obtained during clenching and used to evaluate the interaction between fNIRS data and psychiatric changes. Activation of the prefrontal cortex was significantly greater during clenching in the mandibular retrusive condition than during clenching in the control condition. Furthermore, Spearman rank-correlation coefficient revealed a parallel relation between prefrontal cortex activation and visual analog scale score for discomfort. These results indicate that fNIRS can be used to objectively evaluate the occlusal condition by evaluating activity in the prefrontal cortex. PMID:26075235

Effects of mandibular retrusive deviation on prefrontal cortex activation: a functional near-infrared spectroscopy study.

PubMed

Otsuka, Takero; Yamasaki, Ryuichi; Shimazaki, Tateshi; Yoshino, Fumihiko; Sasaguri, Kenichi; Kawata, Toshitsugu

2015-01-01

The objective of this study was to evaluate occlusal condition by assessing brain activity in the prefrontal cortex, which is associated with emotion. Functional near-infrared spectroscopy (fNIRS) was used to detect changes in cerebral blood flow in the prefrontal cortex of 12 healthy volunteers. The malocclusion model was a custom-made splint that forced the mandible into retrusion. A splint with no modification was used as a control. The cortical activation during clenching was compared between the retrusive position condition and the control condition. A visual analog scale score for discomfort was also obtained during clenching and used to evaluate the interaction between fNIRS data and psychiatric changes. Activation of the prefrontal cortex was significantly greater during clenching in the mandibular retrusive condition than during clenching in the control condition. Furthermore, Spearman rank-correlation coefficient revealed a parallel relation between prefrontal cortex activation and visual analog scale score for discomfort. These results indicate that fNIRS can be used to objectively evaluate the occlusal condition by evaluating activity in the prefrontal cortex.

Conserved regional patterns of GABA-related transcript expression in the neocortex of subjects with schizophrenia.

PubMed

Hashimoto, Takanori; Bazmi, H Holly; Mirnics, Karoly; Wu, Qiang; Sampson, Allan R; Lewis, David A

2008-04-01

Individuals with schizophrenia exhibit disturbances in a number of cognitive, affective, sensory, and motor functions that depend on the circuitry of different cortical areas. The cognitive deficits associated with dysfunction of the dorsolateral prefrontal cortex result, at least in part, from abnormalities in GABA neurotransmission, as reflected in a specific pattern of altered expression of GABA-related genes. Consequently, the authors sought to determine whether this pattern of altered gene expression is restricted to the dorsolateral prefrontal cortex or could also contribute to the dysfunction of other cortical areas in subjects with schizophrenia. Real-time quantitative polymerase chain reaction was used to assess the levels of eight GABA-related transcripts in four cortical areas (dorsolateral prefrontal cortex, anterior cingulate cortex, and primary motor and primary visual cortices) of subjects (N=12) with schizophrenia and matched normal comparison subjects. Expression levels of seven transcripts were lower in subjects with schizophrenia, with the magnitude of reduction for each transcript comparable across the four areas. The largest reductions were detected for mRNA encoding somatostatin and parvalbumin, followed by moderate decreases in mRNA expression for the 67-kilodalton isoform of glutamic acid decarboxylase, the GABA membrane transporter GAT-1, and the alpha 1 and delta subunits of GABA(A) receptors. In contrast, the expression of calretinin mRNA did not differ between the subject groups in any of the four areas. Because the areas examined represent the major functional domains (e.g., association, limbic, motor, and sensory) of the cerebral cortex, our findings suggest that a conserved set of molecular alterations affecting GABA neurotransmission contribute to the pathophysiology of different clinical features of schizophrenia.

Task-Rest Modulation of Basal Ganglia Connectivity in Mild to Moderate Parkinson’s Disease

PubMed Central

Müller-Oehring, Eva M.; Sullivan, Edith V.; Pfefferbaum, Adolf; Huang, Neng C.; Poston, Kathleen L.; Bronte-Stewart, Helen M.; Schulte, Tilman

2014-01-01

Parkinson’s disease (PD) is associated with abnormal synchronization in basal ganglia-thalamo-cortical loops. We tested whether early PD patients without demonstrable cognitive impairment exhibit abnormal modulation of functional connectivity at rest, while engaged in a task, or both. PD and healthy controls underwent two functional MRI scans: a resting-state scan and a Stroop Match-to-Sample task scan. Rest-task modulation of basal ganglia (BG) connectivity was tested using seed-to-voxel connectivity analysis with task and rest time series as conditions. Despite substantial overlap of BG–cortical connectivity patterns in both groups, connectivity differences between groups had clinical and behavioral correlates. During rest, stronger putamen–medial parietal and pallidum–occipital connectivity in PD than controls was associated with worse task performance and more severe PD symptoms suggesting that abnormalities in resting-state connectivity denote neural network dedifferentiation. During the executive task, PD patients showed weaker BG-cortical connectivity than controls, i.e., between caudate–supramarginal gyrus and pallidum–inferior prefrontal regions, that was related to more severe PD symptoms and worse task performance. Yet, task processing also evoked stronger striatal–cortical connectivity, specifically between caudate–prefrontal, caudate–precuneus, and putamen–motor/premotor regions in PD relative to controls, which was related to less severe PD symptoms and better performance on the Stroop task. Thus, stronger task-evoked striatal connectivity in PD demonstrated compensatory neural network enhancement to meet task demands and improve performance levels. fMRI-based network analysis revealed that despite resting-state BG network compromise in PD, BG connectivity to prefrontal, premotor, and precuneus regions can be adequately invoked during executive control demands enabling near normal task performance. PMID:25280970

Obsessive Compulsive Disorder Networks: Positron Emission Tomography and Neuropsychology Provide New Insights

PubMed Central

Millet, Bruno; Dondaine, Thibaut; Reymann, Jean-Michel; Bourguignon, Aurélie; Naudet, Florian; Jaafari, Nematollah; Drapier, Dominique; Turmel, Valérie; Mesbah, Habiba; Vérin, Marc; Le Jeune, Florence

2013-01-01

Background Deep brain stimulation has shed new light on the central role of the prefrontal cortex (PFC) in obsessive compulsive disorder (OCD). We explored this structure from a functional perspective, synchronizing neuroimaging and cognitive measures. Methods and Findings This case-control cross-sectional study compared 15 OCD patients without comorbidities and not currently on serotonin reuptake inhibitors or cognitive behavioural therapy with 15 healthy controls (matched for age, sex and education level) on resting-state 18FDG-PET scans and a neuropsychological battery assessing executive functions. We looked for correlations between metabolic modifications and impaired neuropsychological scores. Modifications in glucose metabolism were found in frontal regions (orbitofrontal cortex and dorsolateral cortices), the cingulate gyrus, insula and parietal gyrus. Neuropsychological differences between patients and controls, which were subtle, were correlated with the metabolism of the prefrontal, parietal, and temporal cortices. Conclusion As expected, we confirmed previous reports of a PFC dysfunction in OCD patients, and established a correlation with cognitive deficits. Other regions outside the prefrontal cortex, including the dorsoparietal cortex and the insula, also appeared to be implicated in the pathophysiology of OCD, providing fresh insights on the complexity of OCD syndromes. PMID:23326403

No relative expansion of the number of prefrontal neurons in primate and human evolution.

PubMed

Gabi, Mariana; Neves, Kleber; Masseron, Carolinne; Ribeiro, Pedro F M; Ventura-Antunes, Lissa; Torres, Laila; Mota, Bruno; Kaas, Jon H; Herculano-Houzel, Suzana

2016-08-23

Human evolution is widely thought to have involved a particular expansion of prefrontal cortex. This popular notion has recently been challenged, although controversies remain. Here we show that the prefrontal region of both human and nonhuman primates holds about 8% of cortical neurons, with no clear difference across humans and other primates in the distribution of cortical neurons or white matter cells along the anteroposterior axis. Further, we find that the volumes of human prefrontal gray and white matter match the expected volumes for the number of neurons in the gray matter and for the number of other cells in the white matter compared with other primate species. These results indicate that prefrontal cortical expansion in human evolution happened along the same allometric trajectory as for other primate species, without modification of the distribution of neurons across its surface or of the volume of the underlying white matter. We thus propose that the most distinctive feature of the human prefrontal cortex is its absolute number of neurons, not its relative volume.

"Circadian cortical compensation": a longitudinal study of brain function during technical and cognitive skills in acutely sleep-deprived surgical residents.

PubMed

Leff, Daniel Richard; Orihuela-Espina, Felipe; Athanasiou, Thanos; Karimyan, Vahe; Elwell, Clare; Wong, John; Yang, Guang-Zhong; Darzi, Ara W

2010-12-01

To test the hypothesis that fatigue-induced performance decline in surgical residents is associated with changes in brain function as detected by functional near-infrared spectroscopy. Surgical residents (n = 7) participated in a prospective study involving 2-hourly objective measurements of neurocognitive skill (arithmetic calculations using Nintendo "brain training"), technical performance (surgical knot tying on a trainer, and monitoring time taken, path length and number of movements), and introspective fatigue (questionnaire-based) across 10 hours of acute sleep deprivation (10:00 PM to 8:00 PM. Simultaneously, changes in cortical oxyhemoglobin (HbO₂), deoxyhemoglobin (HHb), and total hemoglobin (HbT), inferring prefrontal function, were recorded by using functional near-infrared spectroscopy. Arithmetic performance remained stable despite increasing levels of subject fatigue (time: P = 0.07, errors: P = 0.70, efficiency: P = 0.58). Technical skill improved between the first (10:00 PM and the second (12:00 AM sessions (P < 0.05) and stabilized thereafter (12:00 AM to 8:00 AM. Greater activation was required to complete cognitive versus technical drills. Stimulus type (0: cognitive, 1: technical) was found to be an independent predictor of changes in cortical excitation (HbO₂: P < 0.01, HHb: P < 0.05, HbT: P < 0.01). Cortical responses to the cognitive task increased over the course of the simulated night shift. In addition, "time interval" was observed to be an independent predictor of cortical hemodynamic change (HbO₂: P < 0.01, HbT: P < 0.01). Neurocognitive tasks may tax the sleep-deprived resident more than well-learned technical skills. Performing cognitive skills at night, such as decision making, may depend upon enhanced prefrontal recruitment indicative of a focused attentional strategy and/or compensation to sleep deprivation. Further work should focus on determining whether errors in performance are associated with attentional lapses and failure of cortical compensation.

Functional Brain Organization of Working Memory in Adolescents Varies in Relation to Family Income and Academic Achievement

ERIC Educational Resources Information Center

Finn, Amy S.; Minas, Jennifer E.; Leonard, Julia A.; Mackey, Allyson P.; Salvatore, John; Goetz, Calvin; West, Martin R.; Gabrieli, Christopher F. O.; Gabrieli, John D. E.

2017-01-01

Working memory (WM) capacity reflects executive functions associated with performance on a wide range of cognitive tasks and education outcomes, including mathematics achievement, and is associated with dorsolateral prefrontal and parietal cortices. Here we asked if family income is associated with variation in the functional brain organization of…

Dynamic Amygdala Influences on the Fronto-Striatal Brain Mechanisms Involved in Self-Control of Impulsive Desires.

PubMed

Krämer, Bernd; Gruber, Oliver

2015-01-01

Human decisions are guided by a variety of motivational factors, such as immediate rewards, long-term goals, and emotions. We used functional magnetic resonance imaging to investigate the dynamic functional interactions between the amygdala, the nucleus accumbens, and the prefrontal cortex that underlie the influences of emotions, desires, and rationality on human decisions. We found that increased functional connectivity between the amygdala and the nucleus accumbens facilitated the approach of an immediate reward in the presence of emotional information. Further, increased functional interactions of the anteroventral prefrontal cortex with the amygdala and the nucleus accumbens were associated with rational decisions in dilemma situations. These findings support previous animal studies by demonstrating that emotional signals from the amygdala and goal-oriented information from prefrontal cortices interface in the nucleus accumbens to guide human decisions and reward-directed actions. © 2015 S. Karger AG, Basel.

The functional neuroanatomy of decision-making.

PubMed

Rosenbloom, Michael H; Schmahmann, Jeremy D; Price, Bruce H

2012-01-01

Decision-making is a complex executive function that draws on past experience, present goals, and anticipation of outcome, and which is influenced by prevailing and predicted emotional tone and cultural context. Functional imaging investigations and focal lesion studies identify the orbitofrontal, anterior cingulate, and dorsolateral prefrontal cortices as critical to decision-making. The authors review the connections of these prefrontal regions with the neocortex, limbic system, basal ganglia, and cerebellum, highlight current ideas regarding the cognitive processes of decision-making that these networks subserve, and present a novel integrated neuroanatomical model for decision-making. Finally, clinical relevance of this circuitry is illustrated through a discussion of frontotemporal dementia, traumatic brain injury, and sociopathy.

Change in cognitive process during dance video game play with different appendages for motor output

NASA Astrophysics Data System (ADS)

Suzuki, Kota; Ono, Yumie; Shimada, Sotaro; Tachibana, Atsumichi; Noah, Jack Adam

2018-02-01

Playing a dance video game (DVG) requires fine temporal control of foot positions based on simultaneous visuoauditory integration. Despite the highly-demanding nature of its cognitive processes, DVG could offer promising exercise opportunities for elderly people to maintain their cognitive abilities due to its strong adherence. Using functional near-infrared spectroscopy, we have previously shown that DVG play with the foot activates prefrontal and temporoparietal cortices. However, it is still in debate whether this brain-stimulatory effect of DVG could also be maintained in case that DVG is played with the hand by people who have difficulty to play DVG in a standing position. We therefore investigated the regional brain activity of 12 healthy, right-handed young-adults when they played DVG with their dominant hand and foot. We found that the DVG-related hemodynamic activity was comparable in the prefrontal area regardless of the appendages while that was significantly smaller in case of playing with the hand related to the foot in the left superior/middle temporal gyrus (S/MTG). A similar trend was also observed in the right S/MTG. These results suggest that the motor preparatory function mediated by the prefrontal cortices is equally employed regardless of appendages while more cognitive load is required in the temporal cortices with foot-played DVG, possibly to integrate visual, auditory, and proprioceptive information. Hand-played DVG may partially substitute foot-played DVG in the sense of cognitive training in the elderly.

Hemispheric encoding/retrieval asymmetry in episodic memory: positron emission tomography findings.

PubMed Central

Tulving, E; Kapur, S; Craik, F I; Moscovitch, M; Houle, S

1994-01-01

Data are reviewed from positron emission tomography studies of encoding and retrieval processes in episodic memory. These data suggest a hemispheric encoding/retrieval asymmetry model of prefrontal involvement in encoding and retrieval of episodic memory. According to this model, the left and right prefrontal lobes are part of an extensive neuronal network that subserves episodic remembering, but the two prefrontal hemispheres play different roles. Left prefrontal cortical regions are differentially more involved in retrieval of information from semantic memory and in simultaneously encoding novel aspects of the retrieved information into episodic memory. Right prefrontal cortical regions, on the other hand, are differentially more involved in episodic memory retrieval. PMID:8134342

Progressive Brain Structural Changes Mapped as Psychosis Develops in ‘At Risk’ Individuals

PubMed Central

Sun, Daqiang; Phillips, Lisa; Velakoulis, Dennis; Yung, Alison; McGorry, Patrick D.; Wood, Stephen J.; van Erp, Theo G. M.; Thompson, Paul M.; Toga, Arthur W.; Cannon, Tyrone D.; Pantelis, Christos

2009-01-01

Background Schizophrenia and related psychoses are associated with brain structural abnormalities. Recent findings in ‘at risk’ populations have identified progressive changes in various brain regions preceding illness onset, while changes especially in prefrontal and superior temporal regions have been demonstrated in first-episode schizophrenia patients. However, the timing of the cortical changes and their regional extent, relative to the emergence of psychosis, has not been clarified. We followed individuals at high-risk for psychosis to determine whether structural changes in the cerebral cortex occur with the onset of psychosis. We hypothesized that progressive volume loss occurs in prefrontal regions during the transition to psychosis. Methods 35 individuals at ultra-high risk (UHR) for developing psychosis, of whom 12 experienced psychotic onset by 1-year follow-up (‘converters’), participated in a longitudinal structural MRI study. Baseline and follow-up T1-weighted MR images were acquired and longitudinal brain surface contractions were assessed using Cortical Pattern Matching. Results Significantly greater brain contraction was found in the right prefrontal region in the ‘converters’ compared with UHR cases who did not develop psychosis (‘non-converters’). Conclusions These findings show cortical volume loss is associated with the onset of psychosis, indicating ongoing pathological processes during the transition stage to illness. The prefrontal volume loss is in line with structural and functional abnormalities in schizophrenia, suggesting a critical role for this change in the development of psychosis. PMID:19138834

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.

Dissociable effects of prefrontal and anterior temporal cortical lesions on stereotypical gender attitudes.

PubMed

Gozzi, Marta; Raymont, Vanessa; Solomon, Jeffrey; Koenigs, Michael; Grafman, Jordan

2009-08-01

Clinical observations of patients with ventral frontal and anterior temporal cortical lesions reveal marked abnormalities in social attitudes. A previous study in seven patients with ventral prefrontal lesions provided the first direct experimental evidence for abnormalities in social attitudes using a well-established measure of gender stereotypes, the Implicit Association Test (IAT). Here, we were able to test whether these first findings could be reproduced in a larger sample of 154 patients with penetrating head injuries, and to determine the differential effects of ventromedial prefrontal (vmPFC) and ventrolateral prefrontal (vlPFC) cortical lesions on IAT performance. In addition, we investigated the role of the superior anterior temporal lobe (aTL), recently shown to represent conceptual social knowledge. First, we used a linear regression model to identify the role of each of the three regions, while controlling for the extent of damage to other regions. We found that larger lesions in either the vmPFC or the superior aTL were associated with increased stereotypical attitudes, whereas larger lesions in the vlPFC were associated with decreased stereotypical attitudes. Second, in a confirmatory analysis, we grouped patients by lesion location and compared their performance on the IAT with that of healthy volunteers. Compared to controls, patients with lesions in either the vmPFC or the superior aTL showed increased stereotypical attitudes, whereas patients with lesions in the vlPFC showed decreased stereotypical attitudes. The functional contributions of these regions in social attitudes are discussed.

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

The cortical language circuit: from auditory perception to sentence comprehension.

PubMed

Friederici, Angela D

2012-05-01

Over the years, a large body of work on the brain basis of language comprehension has accumulated, paving the way for the formulation of a comprehensive model. The model proposed here describes the functional neuroanatomy of the different processing steps from auditory perception to comprehension as located in different gray matter brain regions. It also specifies the information flow between these regions, taking into account white matter fiber tract connections. Bottom-up, input-driven processes proceeding from the auditory cortex to the anterior superior temporal cortex and from there to the prefrontal cortex, as well as top-down, controlled and predictive processes from the prefrontal cortex back to the temporal cortex are proposed to constitute the cortical language circuit. Copyright © 2012 Elsevier Ltd. All rights reserved.

Increased Cortical Thickness in Professional On-Line Gamers

PubMed Central

Hyun, Gi Jung; Shin, Yong Wook; Kim, Bung-Nyun; Cheong, Jae Hoon; Jin, Seong Nam

2013-01-01

Objective The bulk of recent studies have tested whether video games change the brain in terms of activity and cortical volume. However, such studies are limited by several factors including cross-sectional comparisons, co-morbidity, and short-term follow-up periods. In the present study, we hypothesized that cognitive flexibility and the volume of brain cortex would be correlated with the career length of on-line pro-gamers. Methods High-resolution magnetic resonance scans were acquired in twenty-three pro-gamers recruited from StarCraft pro-game teams. We measured cortical thickness in each individual using FreeSurfer and the cortical thickness was correlated with the career length and the performance of the pro-gamers. Results Career length was positively correlated with cortical thickness in three brain regions: right superior frontal gyrus, right superior parietal gyrus, and right precentral gyrus. Additionally, increased cortical thickness in the prefrontal cortex was correlated with winning rates of the pro-game league. Increased cortical thickness in the prefrontal and parietal cortices was also associated with higher performance of Wisconsin Card Sorting Test. Conclusion Our results suggest that in individuals without pathologic conditions, regular, long-term playing of on-line games is associated with volume changes in the prefrontal and parietal cortices, which are associated with cognitive flexibility. PMID:24474988

Thalamo-cortical activation and connectivity during response preparation in adults with persistent and remitted ADHD.

PubMed

Clerkin, Suzanne M; Schulz, Kurt P; Berwid, Olga G; Fan, Jin; Newcorn, Jeffrey H; Tang, Cheuk Y; Halperin, Jeffrey M

2013-09-01

The neural correlates of stimulus-driven processes, such as response preparation, have been posited to be associated with the onset of attention deficit hyperactivity disorder (ADHD) while being distinct from the neural mechanisms associated with recovery. The authors tested this hypothesis in adults with remitted and persistent ADHD. Thirty-eight young adults who were diagnosed with combined-type ADHD in childhood (probands) and 32 carefully matched comparison subjects were followed longitudinally and scanned with functional MRI while performing an event-related cued reaction time task. Probands were characterized as individuals with persistent or remitted ADHD. Differences in thalamo-cortical activation and functional connectivity during response preparation between comparison subjects and probands and between individuals with persistent ADHD and those with remitted ADHD were assessed by contrasting neural activation and functional connectivity during cue or noncue events. Probands exhibited less cue-related activation than comparison subjects in the thalamus, anterior cingulate cortex, supplementary motor area, inferior parietal lobe, and dorsolateral prefrontal cortex despite similar overall patterns of activation. There were no differences in activation between individuals in the remitted ADHD group and those in the persistent ADHD group in any hypothesized regions. However, cue-related functional connectivity between the right thalamus and brainstem was greater in comparison subjects relative to probands, and cue-related connectivity was greater between the right thalamus and prefrontal regions in individuals with remitted ADHD relative to those with persistent ADHD. Decreased thalamo-cortical activation during response preparation was present in adults diagnosed with ADHD in childhood regardless of symptom remission in adulthood, and may be partly driven by less functional coordination between the brainstem and thalamus. Greater functional integration of the thalamo-cortical network might parallel symptom recovery.

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.

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.

Catechol-O-methyltransferase genotype modifies executive functioning and prefrontal functional connectivity in women with anorexia nervosa.

PubMed

Favaro, Angela; Clementi, Maurizio; Manara, Renzo; Bosello, Romina; Forzan, Monica; Bruson, Alice; Tenconi, Elena; Degortes, Daniela; Titton, Francesca; Di Salle, Francesco; Santonastaso, Paolo

2013-07-01

Anorexia nervosa is characterized by high levels of perseveration and inflexibility, which interfere with successful treatments. Dopamine (DA) signalling seems to play a key role in modulating the prefrontal cortex, since both DA deficiency and excess nega tively influence the efficiency of cognitive functions. The present study explores the effect of a functional polymorphism (Val158Met) in the catechol-O-methyltransferase (COMT) gene on the set-shifting abilities and prefrontal functional connectivity of patients with anorexia nervosa. All participants performed the Wisconsin Card Sorting Task, and a subsample underwent resting-state functional magnetic resonance imaging. We included 166 patients with DSM-IV lifetime anorexia nervosa and 140 healthy women in our study. Both underweight and weight-recovered patients with anorexia nervosa showed high levels of perseveration, but only in the underweight group did the Val158Met polymorphism affect cognitive performance, showing the U-shaped curve characteristic of increased DA signalling in the prefrontal cortex. Underweight patients with anorexia nervosa who are Met homozygotes had significantly higher levels of perseveration and increased prefrontal functional connectivity than underweight patients in the other genotype groups, indicating abnormal regional cortical processing. Although our data show that grey matter reduction in starving patients with anorexia nervosa did not explain our findings, the cross-sectional design of the present study did not allow us to distinguish between the effects of starvation and those of low estrogen levels. Starvation affects DA release in the prefrontal cortex of patients with anorexia nervosa with different effects on executive functioning and prefrontal functional connectivity according to the COMT genotype. This observation has several therapeutic implications that need to be addressed by future studies.

Catechol-O-methyltransferase genotype modifies executive functioning and prefrontal functional connectivity in women with anorexia nervosa

PubMed Central

Favaro, Angela; Clementi, Maurizio; Manara, Renzo; Bosello, Romina; Forzan, Monica; Bruson, Alice; Tenconi, Elena; Degortes, Daniela; Titton, Francesca; Di Salle, Francesco; Santonastaso, Paolo

2013-01-01

Background Anorexia nervosa is characterized by high levels of perseveration and inflexibility, which interfere with successful treatments. Dopamine (DA) signalling seems to play a key role in modulating the prefrontal cortex, since both DA deficiency and excess negatively influence the efficiency of cognitive functions. The present study explores the effect of a functional polymorphism (Val158Met) in the catechol-O-methyltransferase (COMT) gene on the set-shifting abilities and prefrontal functional connectivity of patients with anorexia nervosa. Methods All participants performed the Wisconsin Card Sorting Task, and a subsample underwent resting-state functional magnetic resonance imaging. Results We included 166 patients with DSM-IV lifetime anorexia nervosa and 140 healthy women in our study. Both underweight and weight-recovered patients with anorexia nervosa showed high levels of perseveration, but only in the underweight group did the Val158Met polymorphism affect cognitive performance, showing the U-shaped curve characteristic of increased DA signalling in the prefrontal cortex. Underweight patients with anorexia nervosa who are Met homozygotes had significantly higher levels of perseveration and increased prefrontal functional connectivity than underweight patients in the other genotype groups, indicating abnormal regional cortical processing. Limitations Although our data show that grey matter reduction in starving patients with anorexia nervosa did not explain our findings, the cross-sectional design of the present study did not allow us to distinguish between the effects of starvation and those of low estrogen levels. Conclusion Starvation affects DA release in the prefrontal cortex of patients with anorexia nervosa with different effects on executive functioning and prefrontal functional connectivity according to the COMT genotype. This observation has several therapeutic implications that need to be addressed by future studies. PMID:23046831

Pain perception and hypnosis: findings from recent functional neuroimaging studies.

PubMed

Del Casale, Antonio; Ferracuti, Stefano; Rapinesi, Chiara; Serata, Daniele; Caltagirone, Saverio Simone; Savoja, Valeria; Piacentino, Daria; Callovini, Gemma; Manfredi, Giovanni; Sani, Gabriele; Kotzalidis, Georgios D; Girardi, Paolo

2015-01-01

Hypnosis modulates pain perception and tolerance by affecting cortical and subcortical activity in brain regions involved in these processes. By reviewing functional neuroimaging studies focusing on pain perception under hypnosis, the authors aimed to identify brain activation-deactivation patterns occurring in hypnosis-modulated pain conditions. Different changes in brain functionality occurred throughout all components of the pain network and other brain areas. The anterior cingulate cortex appears to be central in modulating pain circuitry activity under hypnosis. Most studies also showed that the neural functions of the prefrontal, insular, and somatosensory cortices are consistently modified during hypnosis-modulated pain conditions. Functional neuroimaging studies support the clinical use of hypnosis in the management of pain conditions.

Different Brain Responses to Pain and Its Expectation in the Dental Chair.

PubMed

Racek, A J; Hu, X; Nascimento, T D; Bender, M C; Khatib, L; Chiego, D; Holland, G R; Bauer, P; McDonald, N; Ellwood, R P; DaSilva, A F

2015-07-01

A dental appointment commonly prompts fear of a painful experience, yet we have never fully understood how our brains react to the expectation of imminent tooth pain once in a dental chair. In our study, 21 patients with hypersensitive teeth were tested using nonpainful and painful stimuli in a clinical setting. Subjects were tested in a dental chair using functional near-infrared spectroscopy to measure cortical activity during a stepwise cold stimulation of a hypersensitive tooth, as well as nonpainful control stimulation on the same tooth. Patients' sensory-discriminative and emotional-cognitive cortical regions were studied through the transition of a neutral to a painful stimulation. In the putative somatosensory cortex contralateral to the stimulus, 2 well-defined hemodynamic peaks were detected in the homuncular orofacial region: the first peak during the nonpainful phase and a second peak after the pain threshold was reached. Moreover, in the upper-left and lower-right prefrontal cortices, there was a significant active hemodynamic response in only the first phase, before the pain. Subsequently, the same prefrontal cortical areas deactivated after a painful experience had been reached. Our study indicates for the first time that pain perception and expectation elicit different hemodynamic cortical responses in a dental clinical setting. © International & American Associations for Dental Research 2015.

Biological and cognitive correlates of cortical curvature in schizophrenia.

PubMed

Lubeiro, Alba; de Luis-García, Rodrigo; Rodríguez, Margarita; Álvarez, Aldara; de la Red, Henar; Molina, Vicente

2017-10-27

Mean cortical curvature may relate to cortico-cortical connections integrity. We explored the association between prefrontal (PFC) cortical curvature and fractional anisotropy (FA) values for tracts connecting PFC and relevant cortical regions. In schizophrenia Anatomical and diffusion magnetic resonance images were obtained from 34 patients (16 of them first-episodes) and 32 healthy controls. We calculated curvature at rostral lateral prefrontal (RLPF) and superior medial prefrontal (SMPF) areas and mean FA for the tracts respectively connecting RLPF and SMPF areas with anterior caudal cingulate (ACC), superior temporal gyrus (STG) and superior parietal SP regions. Cognitive and clinical data were collected, including baseline symptoms, Clinical Global Impression change scores from baseline to follow-up, illness duration and treatment dosage. Patients showed significantly lower FA values in the tracts linking right RLPF-ACC, right SMPF-SPG and bilaterally PFC-STG. FA values in short-range cortico-cortical connections (linking PFC and ACC) were inversely associated with PFC curvature. In patients, cognitive performance was negatively associated with PFC curvature. Larger curvature values were associated to lack of clinical improvement at follow-up. We conclude that cortical curvature is influenced by integrity in short-range cortico-cortical connections and relates to cognition and clinical outcome in schizophrenia patients. Copyright © 2017 Elsevier B.V. All rights reserved.

[Dysfunctional resting-state connectivity of default mode network in adolescent patients with first-episode drug-naive major depressive disorder].

PubMed

Li, S Y; Zhu, Y; Wang, Y L; Lü, P P; Zuo, W B; Li, F Y

2017-12-05

Objective: To study resting-state functional connectivity (FC) of default mode network (DMN) in adolescent patients with first-episode drug-naive major depressive disorder (MDD). Methods: We enrolled thirty first-episode and drug-naive adolescent MDD patients and twenty-nine adolescent healthy control (HC) participants in the First Affiliated Hospital of Zhengzhou University. There were no differences in age, sex, and education between the MDD and HC group. Resting-state functional magnetic resonance images (fMRI) was performed. We selected posterior cingulate cortex (PCC) and medial prefrontal cortex (MPFC) of DMN as regions of interests (ROI). The differences of these regions from the whole brain functional connectivity were analyzed. The relations between abnormalities in FCs of DMN and clinical variables were further investigated. Results: Compared to the HCs, the MDD patients had congruently reduced FCs between the PCC and cerebellum, temporal cortices, occipital cortices, fusiform, dorsolateral prefrontal cortex. MPFC not only had reduced FCs with fusiform, temporal cortices, anterior cingulate cortex, but also had enhanced FCs with occipital cortices, parietal cortices, and precentral gyrus. In addition, the increased FC between the right MPFC and right precentral gyrus was positive correlated with Hamilton Rating Scale for Depression (HAMD) scores ( r =0.38, P =0.04). The reduced FC between the left middle temporal gyrus and left PCC as well as the enhanced FC between the right middle cingulum and right MPFC were positive correlated with the duration of depression since onset ( r =0.39, P =0.03; r =0.38, P =0.04). Conclusions: These findings show dysfunctional DMN connectivity of adolescent MDD patients. Neurodevelopmental abnormalities in DMN may present in adolescent MDD.

Interactions between the nucleus accumbens and auditory cortices predict music reward value.

PubMed

Salimpoor, Valorie N; van den Bosch, Iris; Kovacevic, Natasa; McIntosh, Anthony Randal; Dagher, Alain; Zatorre, Robert J

2013-04-12

We used functional magnetic resonance imaging to investigate neural processes when music gains reward value the first time it is heard. The degree of activity in the mesolimbic striatal regions, especially the nucleus accumbens, during music listening was the best predictor of the amount listeners were willing to spend on previously unheard music in an auction paradigm. Importantly, the auditory cortices, amygdala, and ventromedial prefrontal regions showed increased activity during listening conditions requiring valuation, but did not predict reward value, which was instead predicted by increasing functional connectivity of these regions with the nucleus accumbens as the reward value increased. Thus, aesthetic rewards arise from the interaction between mesolimbic reward circuitry and cortical networks involved in perceptual analysis and valuation.

"I know you can hear me": neural correlates of feigned hearing loss.

PubMed

McPherson, Bradley; McMahon, Katie; Wilson, Wayne; Copland, David

2012-08-01

In the assessment of human hearing, it is often important to determine whether hearing loss is organic or nonorganic in nature. Nonorganic, or functional, hearing loss is often associated with deceptive intention on the part of the listener. Over the past decade, functional neuroimaging has been used to study the neural correlates of deception, and studies have consistently highlighted the contribution of the prefrontal cortex in such behaviors. Can patterns of brain activity be similarly used to detect when an individual is feigning a hearing loss? To answer this question, 15 adult participants were requested to respond to pure tones and simple words correctly, incorrectly, randomly, or with the intent to feign a hearing loss. As predicted, more activity was observed in the prefrontal cortices (as measured by functional magnetic resonance imaging), and delayed behavioral reaction times were noted, when the participants feigned a hearing loss or responded randomly versus when they responded correctly or incorrectly. The results suggest that cortical imaging techniques could play a role in identifying individuals who are feigning hearing loss. Copyright © 2011 Wiley Periodicals, Inc.

Dynamic functional brain networks involved in simple visual discrimination learning.

PubMed

Fidalgo, Camino; Conejo, Nélida María; González-Pardo, Héctor; Arias, Jorge Luis

2014-10-01

Visual discrimination tasks have been widely used to evaluate many types of learning and memory processes. However, little is known about the brain regions involved at different stages of visual discrimination learning. We used cytochrome c oxidase histochemistry to evaluate changes in regional brain oxidative metabolism during visual discrimination learning in a water-T maze at different time points during training. As compared with control groups, the results of the present study reveal the gradual activation of cortical (prefrontal and temporal cortices) and subcortical brain regions (including the striatum and the hippocampus) associated to the mastery of a simple visual discrimination task. On the other hand, the brain regions involved and their functional interactions changed progressively over days of training. Regions associated with novelty, emotion, visuo-spatial orientation and motor aspects of the behavioral task seem to be relevant during the earlier phase of training, whereas a brain network comprising the prefrontal cortex was found along the whole learning process. This study highlights the relevance of functional interactions among brain regions to investigate learning and memory processes. Copyright © 2014 Elsevier Inc. All rights reserved.

Functional neuroimaging studies of sexual arousal and orgasm in healthy men and women: a review and meta-analysis.

PubMed

Stoléru, Serge; Fonteille, Véronique; Cornélis, Christel; Joyal, Christian; Moulier, Virginie

2012-07-01

In the last fifteen years, functional neuroimaging techniques have been used to investigate the neuroanatomical correlates of sexual arousal in healthy human subjects. In most studies, subjects have been requested to watch visual sexual stimuli and control stimuli. Our review and meta-analysis found that in heterosexual men, sites of cortical activation consistently reported across studies are the lateral occipitotemporal, inferotemporal, parietal, orbitofrontal, medial prefrontal, insular, anterior cingulate, and frontal premotor cortices as well as, for subcortical regions, the amygdalas, claustrum, hypothalamus, caudate nucleus, thalami, cerebellum, and substantia nigra. Heterosexual and gay men show a similar pattern of activation. Visual sexual stimuli activate the amygdalas and thalami more in men than in women. Ejaculation is associated with decreased activation throughout the prefrontal cortex. We present a neurophenomenological model to understand how these multiple regional brain responses could account for the varied facets of the subjective experience of sexual arousal. Further research should shift from passive to active paradigms, focus on functional connectivity and use subliminal presentation of stimuli. Copyright © 2012 Elsevier Ltd. All rights reserved.

Functional neuroimaging of recovery from motor conversion disorder: A case report.

PubMed

Dogonowski, Anne-Marie; Andersen, Kasper W; Sellebjerg, Finn; Schreiber, Karen; Madsen, Kristoffer H; Siebner, Hartwig R

2018-03-27

A patient with motor conversion disorder presented with a functional paresis of the left hand. After exclusion of structural brain damage, she was repeatedly examined with whole-brain functional magnetic resonance imaging, while she performed visually paced finger-tapping tasks. The dorsal premotor cortex showed a bilateral deactivation in the acute-subacute phase. Recovery from unilateral hand paresis was associated with a gradual increase in task-based activation of the dorsal premotor cortex bilaterally. The right medial prefrontal cortex displayed the opposite pattern, showing initial task-based activation that gradually diminished with recovery. The inverse dynamics of premotor and medial prefrontal activity over time were found during unimanual finger-tapping with the affected and non-affected hand as well as during bimanual finger-tapping. These observations suggest that reduced premotor and increased medial prefrontal activity reflect an effector-independent cortical dysfunction in conversion paresis which gradually disappears in parallel with clinical remission of paresis. The results link the medial prefrontal and dorsal premotor areas to the generation of intentional actions. We hypothesise that an excessive 'veto' signal generated in medial prefrontal cortex along with decreased premotor activity might constitute the functional substrate of conversion disorder. This notion warrants further examination in a larger group of affected patients. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Age-related changes in the topological organization of the white matter structural connectome across the human lifespan.

PubMed

Zhao, Tengda; Cao, Miao; Niu, Haijing; Zuo, Xi-Nian; Evans, Alan; He, Yong; Dong, Qi; Shu, Ni

2015-10-01

Lifespan is a dynamic process with remarkable changes in brain structure and function. Previous neuroimaging studies have indicated age-related microstructural changes in specific white matter tracts during development and aging. However, the age-related alterations in the topological architecture of the white matter structural connectome across the human lifespan remain largely unknown. Here, a cohort of 113 healthy individuals (ages 9-85) with both diffusion and structural MRI acquisitions were examined. For each participant, the high-resolution white matter structural networks were constructed by deterministic fiber tractography among 1024 parcellation units and were quantified with graph theoretical analyses. The global network properties, including network strength, cost, topological efficiency, and robustness, followed an inverted U-shaped trajectory with a peak age around the third decade. The brain areas with the most significantly nonlinear changes were located in the prefrontal and temporal cortices. Different brain regions exhibited heterogeneous trajectories: the posterior cingulate and lateral temporal cortices displayed prolonged maturation/degeneration compared with the prefrontal cortices. Rich-club organization was evident across the lifespan, whereas hub integration decreased linearly with age, especially accompanied by the loss of frontal hubs and their connections. Additionally, age-related changes in structural connections were predominantly located within and between the prefrontal and temporal modules. Finally, based on the graph metrics of structural connectome, accurate predictions of individual age were obtained (r = 0.77). Together, the data indicated a dynamic topological organization of the brain structural connectome across human lifespan, which may provide possible structural substrates underlying functional and cognitive changes with age. © 2015 Wiley Periodicals, Inc.

Reduced Synapse and Axon Numbers in the Prefrontal Cortex of Rats Subjected to a Chronic Stress Model for Depression

PubMed Central

Csabai, Dávid; Wiborg, Ove; Czéh, Boldizsár

2018-01-01

Stressful experiences can induce structural changes in neurons of the limbic system. These cellular changes contribute to the development of stress-induced psychopathologies like depressive disorders. In the prefrontal cortex of chronically stressed animals, reduced dendritic length and spine loss have been reported. This loss of dendritic material should consequently result in synapse loss as well, because of the reduced dendritic surface. But so far, no one studied synapse numbers in the prefrontal cortex of chronically stressed animals. Here, we examined synaptic contacts in rats subjected to an animal model for depression, where animals are exposed to a chronic stress protocol. Our hypothesis was that long term stress should reduce the number of axo-spinous synapses in the medial prefrontal cortex. Adult male rats were exposed to daily stress for 9 weeks and afterward we did a post mortem quantitative electron microscopic analysis to quantify the number and morphology of synapses in the infralimbic cortex. We analyzed asymmetric (Type I) and symmetric (Type II) synapses in all cortical layers in control and stressed rats. We also quantified axon numbers and measured the volume of the infralimbic cortex. In our systematic unbiased analysis, we examined 21,000 axon terminals in total. We found the following numbers in the infralimbic cortex of control rats: 1.15 × 109 asymmetric synapses, 1.06 × 108 symmetric synapses and 1.00 × 108 myelinated axons. The density of asymmetric synapses was 5.5/μm3 and the density of symmetric synapses was 0.5/μm3. Average synapse membrane length was 207 nm and the average axon terminal membrane length was 489 nm. Stress reduced the number of synapses and myelinated axons in the deeper cortical layers, while synapse membrane lengths were increased. These stress-induced ultrastructural changes indicate that neurons of the infralimbic cortex have reduced cortical network connectivity. Such reduced network connectivity is likely to form the anatomical basis for the impaired functioning of this brain area. Indeed, impaired functioning of the prefrontal cortex, such as cognitive deficits are common in stressed individuals as well as in depressed patients. PMID:29440995

Cranial nerve clock. Part II: functional MR imaging of brain activation during a declarative memory task.

PubMed

Weiss, K L; Welsh, R C; Eldevik, P; Bieliauskas, L A; Steinberg, B A

2001-12-01

The authors performed this study to assess brain activation during encoding and successful recall with a declarative memory paradigm that has previously been demonstrated to be effective for teaching students about the cranial nerves. Twenty-four students underwent functional magnetic resonance (MR) imaging during encoding and recall of the name, number, and function of the 12 cranial nerves. The students viewed mnemonic graphic and text slides related to individual nerves, as well as their respective control slides. For the recall paradigm, students were prompted with the numbers 1-12 (test condition) intermixed with the number 14 (control condition). Subjects were tested about their knowledge of cranial nerves outside the MR unit before and after functional MR imaging. Students learned about the cranial nerves while undergoing functional MR imaging (mean post- vs preparadigm score, 8.1 +/- 3.4 [of a possible 12] vs 0.75 +/- 0.94, bilateral prefrontal cortex, left greater than right; P < 2.0 x 10(-12)) and maintained this knowledge at I week. The encoding and recall paradigms elicited distributed networks of brain activation. Encoding revealed statistically significant activation in the bilateral prefrontal cortex, left greater than right [corrected]; bilateral occipital and parietal associative cortices, parahippocampus region, fusiform gyri, and cerebellum. Successful recall activated the left much more than the right prefrontal, parietal associative, and anterior cingulate cortices; bilateral precuneus and cerebellum; and right more than the left posterior cingulate. A predictable pattern of brain activation at functional MR imaging accompanies the encoding and successful recall of the cranial nerves with this declarative memory paradigm.

Distorted images of one's own body activates the prefrontal cortex and limbic/paralimbic system in young women: a functional magnetic resonance imaging study.

PubMed

Kurosaki, Mitsuhaya; Shirao, Naoko; Yamashita, Hidehisa; Okamoto, Yasumasa; Yamawaki, Shigeto

2006-02-15

Our aim was to study the gender differences in brain activation upon viewing visual stimuli of distorted images of one's own body. We performed functional magnetic resonance imaging on 11 healthy young men and 11 healthy young women using the "body image tasks" which consisted of fat, real, and thin shapes of the subject's own body. Comparison of the brain activation upon performing the fat-image task versus real-image task showed significant activation of the bilateral prefrontal cortex and left parahippocampal area including the amygdala in the women, and significant activation of the right occipital lobe including the primary and secondary visual cortices in the men. Comparison of brain activation upon performing the thin-image task versus real-image task showed significant activation of the left prefrontal cortex, left limbic area including the cingulate gyrus and paralimbic area including the insula in women, and significant activation of the occipital lobe including the left primary and secondary visual cortices in men. These results suggest that women tend to perceive distorted images of their own bodies by complex cognitive processing of emotion, whereas men tend to perceive distorted images of their own bodies by object visual processing and spatial visual processing.

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

Enriched Encoding: Reward Motivation Organizes Cortical Networks for Hippocampal Detection of Unexpected Events

PubMed Central

Murty, Vishnu P.; Adcock, R. Alison

2014-01-01

Learning how to obtain rewards requires learning about their contexts and likely causes. How do long-term memory mechanisms balance the need to represent potential determinants of reward outcomes with the computational burden of an over-inclusive memory? One solution would be to enhance memory for salient events that occur during reward anticipation, because all such events are potential determinants of reward. We tested whether reward motivation enhances encoding of salient events like expectancy violations. During functional magnetic resonance imaging, participants performed a reaction-time task in which goal-irrelevant expectancy violations were encountered during states of high- or low-reward motivation. Motivation amplified hippocampal activation to and declarative memory for expectancy violations. Connectivity of the ventral tegmental area (VTA) with medial prefrontal, ventrolateral prefrontal, and visual cortices preceded and predicted this increase in hippocampal sensitivity. These findings elucidate a novel mechanism whereby reward motivation can enhance hippocampus-dependent memory: anticipatory VTA-cortical–hippocampal interactions. Further, the findings integrate literatures on dopaminergic neuromodulation of prefrontal function and hippocampus-dependent memory. We conclude that during reward motivation, VTA modulation induces distributed neural changes that amplify hippocampal signals and records of expectancy violations to improve predictions—a potentially unique contribution of the hippocampus to reward learning. PMID:23529005

Near-infrared spectroscopy can reveal increases in brain activity related to animal-assisted therapy.

PubMed

Morita, Yuka; Ebara, Fumio; Morita, Yoshimitsu; Horikawa, Etsuo

2017-08-01

[Purpose] Previous studies have indicated that animal-assisted therapy can promote recovery of psychological, social, and physiological function in mental disorders. This study was designed as a pilot evaluation of the use of near-infrared spectroscopy to objectively identify changes in brain activity that could mediate the effect of animal-assisted therapy. [Subjects and Methods] The participants were 20 healthy students (10 males and 10 females; age 19-21 years) of the Faculty of Agriculture, Saga University. Participants were shown a picture of a Tokara goat or shack (control) while prefrontal cortical oxygenated haemoglobin levels (representing neural activity) were measured by near-infrared spectroscopy. [Results] The prefrontal cortical near-infrared spectroscopy signal was significantly higher during viewing of the animal picture than during a rest condition or during viewing of the control picture. [Conclusion] Our results suggest that near-infrared spectroscopy can be used to objectively identify brain activity changes during human mentation regarding animals; furthermore, these preliminary results suggest the efficacy of animal-assisted therapy could be related to increased activation of the prefrontal cortex.

Prefrontal Cortical GABA Levels in Panic Disorder Determined by Proton Magnetic Resonance Spectroscopy

PubMed Central

Hasler, Gregor; van der Veen, Jan Willem; Geraci, Marilla; Shen, Jun; Pine, Daniel; Drevets, Wayne C.

2009-01-01

Background Panic disorder (PD) is hypothesized to be associated with altered function of the major inhibitory neurotransmitter, gamma-amino butyric acid (GABA). Previous proton magnetic resonance spectroscopy (MRS) studies found lower GABA concentrations in the occipital cortex of subjects with PD relative to healthy controls. The current study is the first MRS study to compare GABA concentrations between unmedicated PD subjects and controls in the prefrontal cortex (PFC). Methods Unmedicated subjects with PD (n=17) and age- and sex-matched healthy controls (n=17) were scanned on a 3 Tesla scanner using a transmit-receive head coil that provided a sufficiently homogenous radiofrequency field to obtain spectroscopic measurements in the dorsomedial/dorsal anterolateral and ventromedial areas of the PFC. Results The prefrontal cortical GABA concentrations did not differ significantly between PD subjects and controls. There also was no statistically significant difference in Glx, choline or N-acetyl-aspartate concentrations. Conclusions The previously reported finding of reduced GABA concentrations in the occipital cortex of PD subjects does not appear to extend to the PFC. PMID:18692172

Abnormal prefrontal cortex resting state functional connectivity and severity of internet gaming disorder.

PubMed

Jin, Chenwang; Zhang, Ting; Cai, Chenxi; Bi, Yanzhi; Li, Yangding; Yu, Dahua; Zhang, Ming; Yuan, Kai

2016-09-01

Internet Gaming Disorder (IGD) among adolescents has become an important public concern and gained more and more attention internationally. Recent studies focused on IGD and revealed brain abnormalities in the IGD group, especially the prefrontal cortex (PFC). However, the role of PFC-striatal circuits in pathology of IGD remains unknown. Twenty-five adolescents with IGD and 21 age- and gender-matched healthy controls were recruited in our study. Voxel-based morphometric (VBM) and functional connectivity analysis were employed to investigate the abnormal structural and resting-state properties of several frontal regions in individuals with online gaming addiction. Relative to healthy comparison subjects, IGD subjects showed significant decreased gray matter volume in PFC regions including the bilateral dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC), anterior cingulate cortex (ACC) and the right supplementary motor area (SMA) after controlling for age and gender effects. We chose these regions as the seeding areas for the resting-state analysis and found that IGD subjects showed decreased functional connectivity between several cortical regions and our seeds, including the insula, and temporal and occipital cortices. Moreover, significant decreased functional connectivity between some important subcortical regions, i.e., dorsal striatum, pallidum, and thalamus, and our seeds were found in the IGD group and some of those changes were associated with the severity of IGD. Our results revealed the involvement of several PFC regions and related PFC-striatal circuits in the process of IGD and suggested IGD may share similar neural mechanisms with substance dependence at the circuit level.

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

COMT haplotypes modulate associations of antenatal maternal anxiety and neonatal cortical morphology.

PubMed

Qiu, Anqi; Tuan, Ta Anh; Ong, Mei Lyn; Li, Yue; Chen, Helen; Rifkin-Graboi, Anne; Broekman, Birit F P; Kwek, Kenneth; Saw, Seang-Mei; Chong, Yap-Seng; Gluckman, Peter D; Fortier, Marielle V; Holbrook, Joanna Dawn; Meaney, Michael J

2015-02-01

Exposure to antenatal maternal anxiety and complex genetic variations may shape fetal brain development. In particular, the catechol-O-methyltransferase (COMT) gene, located on chromosome 22q11.2, regulates catecholamine signaling in the prefrontal cortex and is implicated in anxiety, pain, and stress responsivity. This study examined whether individual single-nucleotide polymorphisms (SNPs) of the COMT gene and their haplotypes moderate the association between antenatal maternal anxiety and in utero cortical development. A total of 146 neonates were genotyped and underwent MRI shortly after birth. Neonatal cortical morphology was characterized using cortical thickness. Antenatal maternal anxiety was assessed using the State-Trait Anxiety Inventory at week 26 of pregnancy. Individual COMT SNPs (val158met, rs737865, and rs165599) modulated the association between antenatal maternal anxiety and the prefrontal and parietal cortical thickness in neonates. Based on haplotype trend regression analysis, findings also showed that among rs737865-val158met-rs165599 haplotypes, the A-val-G (AGG) haplotype probabilities modulated positive associations of antenatal maternal anxiety with cortical thickness in the right ventrolateral prefrontal cortex and the right superior parietal cortex and precuneus. In contrast, the G-met-A (GAA) haplotype probabilities modulated negative associations of antenatal maternal anxiety with cortical thickness in bilateral precentral gyrus and the dorsolateral prefrontal cortex. These results suggest that the association between maternal anxiety and in utero neurodevelopment is modified through complex genetic variation in COMT. Such genetic moderation may explain, in part, the variation in phenotypic outcomes in offspring associated with maternal emotional well-being.

Behavioral activation system modulation on brain activation during appetitive and aversive stimulus processing.

PubMed

Barrós-Loscertales, Alfonso; Ventura-Campos, Noelia; Sanjuán-Tomás, Ana; Belloch, Vicente; Parcet, Maria-Antònia; Avila, César

2010-03-01

The reinforcement sensitivity theory (RST) proposed the behavioral activation system (BAS) as a neurobehavioral system that is dependent on dopamine-irrigated structures and that mediates the individual differences in sensitivity and reactivity to appetitive stimuli associated with BAS-related personality traits. Theoretical developments propose that high BAS sensitivity is associated with both enhanced appetitive stimuli processing and the diminished processing of aversive stimuli. The objective of this study was to analyze how individual differences in BAS functioning were associated with brain activation during erotic and aversive picture processing while subjects were involved in a simple goal-directed task. Forty-five male participants took part in this study. The task activation results confirm the activation of the reward and punishment brain-related structures while viewing erotic and aversive pictures, respectively. The SR scores show a positive correlation with activation of the left lateral prefrontal cortex, the mesial prefrontal cortex and the right occipital cortex while viewing erotic pictures, and a negative correlation with the right lateral prefrontal cortex and the left occipital cortex while viewing aversive pictures. In summary, the SR scores modulate the activity of the cortical areas in the prefrontal and the occipital cortices that are proposed to modulate the BAS and the BIS-FFFS.

Prefrontal-limbic connectivity during worry in older adults with generalized anxiety disorder.

PubMed

Mohlman, Jan; Eldreth, Dana A; Price, Rebecca B; Staples, Alison M; Hanson, Catherine

2017-04-01

Although generalized anxiety disorder (GAD) is one of the most prevalent anxiety disorders in older adults, very little is known about the neurobiology of worry, the hallmark symptom of GAD in adults over the age of 60. This study investigated the neurobiology and neural circuitry of worry in older GAD patients and controls. Twenty older GAD patients and 16 age-matched controls (mean age = 67.88) were compared on clinical measures and neural activity during worry using functional magnetic resonance imaging. As expected, worry elicited activation in frontal regions, amygdala, and insula within the GAD group, with a similar but less prominent frontal pattern was observed in controls. Effective connectivity analyses revealed a positive directional circuit in the GAD group extending from ventromedial through dorsolateral prefrontal cortices, converging on the amygdala. A less complex circuit was observed in controls with only dorsolateral prefrontal regions converging on the amygdala; however, a separate circuit passing through the orbitofrontal cortex converged on the insula. Results elucidate a different neurobiology of pathological versus normal worry in later life. A limited resource model is implicated wherein worry in GAD competes for the same neural resources (e.g. prefrontal cortical areas) that are involved in the adaptive regulation of emotion through cognitive and behavioral strategies.

Decreased functional brain activation in Friedreich ataxia using the Simon effect task.

PubMed

Georgiou-Karistianis, N; Akhlaghi, H; Corben, L A; Delatycki, M B; Storey, E; Bradshaw, J L; Egan, G F

2012-08-01

The present study applied the Simon effect task to examine the pattern of functional brain reorganization in individuals with Friedreich ataxia (FRDA), using functional magnetic resonance imaging (fMRI). Thirteen individuals with FRDA and 14 age and sex matched controls participated, and were required to respond to either congruent or incongruent arrow stimuli, presented either to the left or right of a screen, via laterally-located button press responses. Although the Simon effect (incongruent minus congruent stimuli) showed common regions of activation in both groups, including the superior and middle prefrontal cortices, insulae, superior and inferior parietal lobules (LPs, LPi), occipital cortex and cerebellum, there was reduced functional activation across a range of brain regions (cortical, subcortical and cerebellar) in individuals with FRDA. The greater Simon effect behaviourally in individuals with FRDA, compared with controls, together with concomitant reductions in functional brain activation and reduced functional connectivity between cortical and sub-cortical regions, implies a likely disruption of cortico-cerebellar loops and ineffective engagement of cognitive/attention regions required for response suppression. Copyright © 2012 Elsevier Inc. All rights reserved.

Nonmonotonic spatial structure of interneuronal correlations in prefrontal microcircuits

PubMed Central

Safavi, Shervin; Dwarakanath, Abhilash; Kapoor, Vishal; Werner, Joachim; Hatsopoulos, Nicholas G.; Logothetis, Nikos K.; Panagiotaropoulos, Theofanis I.

2018-01-01

Correlated fluctuations of single neuron discharges, on a mesoscopic scale, decrease as a function of lateral distance in early sensory cortices, reflecting a rapid spatial decay of lateral connection probability and excitation. However, spatial periodicities in horizontal connectivity and associational input as well as an enhanced probability of lateral excitatory connections in the association cortex could theoretically result in nonmonotonic correlation structures. Here, we show such a spatially nonmonotonic correlation structure, characterized by significantly positive long-range correlations, in the inferior convexity of the macaque prefrontal cortex. This functional connectivity kernel was more pronounced during wakefulness than anesthesia and could be largely attributed to the spatial pattern of correlated variability between functionally similar neurons during structured visual stimulation. These results suggest that the spatial decay of lateral functional connectivity is not a common organizational principle of neocortical microcircuits. A nonmonotonic correlation structure could reflect a critical topological feature of prefrontal microcircuits, facilitating their role in integrative processes. PMID:29588415

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.

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

NASA Astrophysics Data System (ADS)

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

2005-01-01

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

Normalization of Cortical Gray Matter Deficits in Nonpsychotic Siblings of Patients With Childhood-Onset Schizophrenia

PubMed Central

Mattai, Anand A.; Weisinger, Brian; Greenstein, Deanna; Stidd, Reva; Clasen, Liv; Miller, Rachel; Tossell, Julia W.; Rapoport, Judith L.; Gogtay, Nitin

2012-01-01

Objective Cortical gray matter (GM) abnormalities in patients with childhood-onset schizophrenia (COS) progress during adolescence ultimately localizing to prefrontal and temporal cortices by early adult age. A previous study of 52 nonpsychotic siblings of COS probands had significant prefrontal and temporal GM deficits that appeared to “normalize” by age 17 years. Here we present a replication with nonoverlapping groups of healthy full siblings and healthy controls. Method Using an automated measure and prospectively acquired anatomical brain magnetic resonance images, we mapped cortical GM thickness in nonpsychotic full siblings (n = 43, 68 scans; ages 5 through 26 years) of patients with COS, contrasting them with age-, gender-, and scan interval–matched healthy controls (n = 86, 136 scans). The false-discovery rate procedure was used to control for type I errors due to multiple comparisons. Results As in our previous study, young nonpsychotic siblings (<17 years) showed significant GM deficits in bilateral prefrontal and left temporal cortices and, in addition, smaller deficits in the parietal and right inferior temporal cortices. These deficits in nonpsychotic siblings normalized with age with minimal abnormalities remaining by age 17. Conclusions Our results support previous findings showing nonpsychotic siblings of COS probands to have early GM deficits that ameliorate with time. At early ages, prefrontal and/or temporal loss may serve as a familial/trait marker for COS. Late adolescence appears to be a critical period for greatest localization of deficits in probands or normalization in nonpsychotic siblings. PMID:21703497

Effect of age at onset on cortical thickness and cognition in posterior cortical atrophy

PubMed Central

Suárez-González, Aida; Lehmann, Manja; Shakespeare, Timothy J.; Yong, Keir X.X.; Paterson, Ross W.; Slattery, Catherine F.; Foulkes, Alexander J.M.; Rabinovici, Gil D.; Gil-Néciga, Eulogio; Roldán-Lora, Florinda; Schott, Jonathan M.; Fox, Nick C.; Crutch, Sebastian J.

2016-01-01

Age at onset (AAO) has been shown to influence the phenotype of Alzheimer’s disease (AD), but how it affects atypical presentations of AD remains unknown. Posterior cortical atrophy (PCA) is the most common form of atypical AD. In this study, we aimed to investigate the effect of AAO on cortical thickness and cognitive function in 98 PCA patients. We used Freesurfer (v5.3.0) to compare cortical thickness with AAO both as a continuous variable, and by dichotomizing the groups based on median age (58 years). In both the continuous and dichotomized analyses, we found a pattern suggestive of thinner cortex in precuneus and parietal areas in earlier-onset PCA, and lower cortical thickness in anterior cingulate and prefrontal cortex in later-onset PCA. These cortical thickness differences between PCA subgroups were consistent with earlier-onset PCA patients performing worse on cognitive tests involving parietal functions. Our results provide a suggestion that AAO may not only affect the clinico-anatomical characteristics in AD but may also affect atrophy patterns and cognition within atypical AD phenotypes. PMID:27318138

Double dissociation of working memory and attentional processes in smokers and non-smokers with and without nicotine.

PubMed

Grundey, Jessica; Amu, Rosa; Ambrus, Géza Gergely; Batsikadze, Georgi; Paulus, Walter; Nitsche, Michael A

2015-07-01

Nicotine has been shown to affect cortical excitability measured using transcranial magnetic stimulation in smoking and non-smoking subjects in different ways. In tobacco-deprived smokers, administration of nicotine restores compromised cortical facilitation while in non-smokers, it enhances cortical inhibition. As cortical excitability and activity are closely linked to cognitive processes, we aimed to explore whether nicotine-induced physiological alterations in non-smokers and smokers are associated with cognitive changes. Specifically, we assessed the impact of nicotine on working memory performance (n-back letter task) and on attentional processes (Stroop interference test) in healthy smokers and non-smokers. Both tasks have been shown to rely on prefrontal areas, and nicotinic receptors are relevantly involved in prefrontal function. Sixteen smoking and 16 non-smoking subjects participated in the 3-back letter task and 21 smoking and 21 non-smoking subjects in the Stroop test after the respective application of placebo or nicotine patches. The results show that working memory and attentional processes are compromised in nicotine-deprived smokers compared to non-smoking individuals. After administration of nicotine, working memory performance in smokers improved, while non-smoking subjects displayed decreased accuracy with increased number of errors. The effects have been shown to be more apparent for working memory performance than attentional processes. In summary, cognitive functions can be restored by nicotine in deprived smokers, whereas non-smokers do not gain additional benefit. The respective changes are in accordance with related effects of nicotine on cortical excitability in both groups.

Decreased prefrontal functional brain response during memory testing in women with Cushing's syndrome in remission.

PubMed

Ragnarsson, Oskar; Stomby, Andreas; Dahlqvist, Per; Evang, Johan A; Ryberg, Mats; Olsson, Tommy; Bollerslev, Jens; Nyberg, Lars; Johannsson, Gudmundur

2017-08-01

Neurocognitive dysfunction is an important feature of Cushing's syndrome (CS). Our hypothesis was that patients with CS in remission have decreased functional brain responses in the prefrontal cortex and hippocampus during memory testing. In this cross-sectional study we included 19 women previously treated for CS and 19 controls matched for age, gender, and education. The median remission time was 7 (IQR 6-10) years. Brain activity was studied with functional magnetic resonance imaging during episodic- and working-memory tasks. The primary regions of interest were the prefrontal cortex and the hippocampus. A voxel-wise comparison of functional brain responses in patients and controls was performed. During episodic-memory encoding, patients displayed lower functional brain responses in the left and right prefrontal gyrus (p<0.001) and in the right inferior occipital gyrus (p<0.001) compared with controls. There was a trend towards lower functional brain responses in the left posterior hippocampus in patients (p=0.05). During episodic-memory retrieval, the patients displayed lower functional brain responses in several brain areas with the most predominant difference in the right prefrontal cortex (p<0.001). During the working memory task, patients had lower response in the prefrontal cortices bilaterally (p<0.005). Patients, but not controls, had lower functional brain response during a more complex working memory task compared with a simpler one. In conclusion, women with CS in long-term remission have reduced functional brain responses during episodic and working memory testing. This observation extends previous findings showing long-term adverse effects of severe hypercortisolaemia on brain function. Copyright © 2017 Elsevier Ltd. All rights reserved.

Increased Executive Functioning, Attention, and Cortical Thickness in White-Collar Criminals

PubMed Central

Raine, Adrian; Laufer, William S.; Yang, Yaling; Narr, Katherine L.; Thompson, Paul; Toga, Arthur W.

2011-01-01

Very little is known on white collar crime and how it differs to other forms of offending. This study tests the hypothesis that white collar criminals have better executive functioning, enhanced information processing, and structural brain superiorities compared to offender controls. Using a case-control design, executive functioning, orienting, and cortical thickness was assessed in 21 white collar criminals matched with 21 controls on age, gender, ethnicity, and general level of criminal offending. White collar criminals had significantly better executive functioning, increased electrodermal orienting, increased arousal, and increased cortical gray matter thickness in the ventromedial prefrontal cortex, inferior frontal gyrus, somatosensory cortex, and the temporal-parietal junction compared to controls. Results, while initial, constitute the first findings on neurobiological characteristics of white-collar criminals It is hypothesized that white collar criminals have information-processing and brain superiorities that give them an advantage in perpetrating criminal offenses in occupational settings. PMID:22002326

Increased executive functioning, attention, and cortical thickness in white-collar criminals.

PubMed

Raine, Adrian; Laufer, William S; Yang, Yaling; Narr, Katherine L; Thompson, Paul; Toga, Arthur W

2012-12-01

Very little is known on white-collar crime and how it differs to other forms of offending. This study tests the hypothesis that white-collar criminals have better executive functioning, enhanced information processing, and structural brain superiorities compared with offender controls. Using a case-control design, executive functioning, orienting, and cortical thickness was assessed in 21 white-collar criminals matched with 21 controls on age, gender, ethnicity, and general level of criminal offending. White-collar criminals had significantly better executive functioning, increased electrodermal orienting, increased arousal, and increased cortical gray matter thickness in the ventromedial prefrontal cortex, inferior frontal gyrus, somatosensory cortex, and the temporal-parietal junction compared with controls. Results, while initial, constitute the first findings on neurobiological characteristics of white-collar criminals. It is hypothesized that white-collar criminals have information-processing and brain superiorities that give them an advantage in perpetrating criminal offenses in occupational settings. Copyright © 2011 Wiley Periodicals, Inc.

Reduced Functional Connectivity in Adults with Persistent Post-Concussion Symptoms: A Functional Near-Infrared Spectroscopy Study

PubMed Central

Hocke, Lia M.; Duszynski, Chris C.; Debert, Chantel T.; Dleikan, Diane

2018-01-01

Abstract Concussion, or mild traumatic brain injury (mTBI), accounts for ∼80% of all TBIs across North America. The majority of mTBI patients recover within days to weeks; however, 14–36% of the time, acute mTBI symptoms persist for months or even years and develop into persistent post-concussion symptoms (PPCS). There is a need to find biomarkers in patients with PPCS, to improve prognostic ability and to provide insight into the pathophysiology underlying chronic symptoms. Recent research has pointed toward impaired network integrity and cortical communication as a biomarker. In this study we investigated functional near-infrared spectroscopy (fNIRS) as a technique to assess cortical communication deficits in adults with PPCS. Specifically, we aimed to identify cortical communication patterns in prefrontal and motor areas during rest and task, in adult patients with persistent symptoms. We found that (1) the PPCS group showed reduced connectivity compared with healthy controls, (2) increased symptom severity correlated with reduced coherence, and (3) connectivity differences were best distinguishable during task and in particular during the working memory task (n-back task) in the right and left dorsolateral prefrontal cortex (DLPFC). These data show that reduced brain communication may be associated with the pathophysiology of mTBI and that fNIRS, with a relatively simple acquisition paradigm, may provide a useful biomarker of this injury. PMID:29373947

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.

Neuroanatomical Correlates of Executive Functions in Children and Adolescents: A Magnetic Resonance Imaging (MRI) Study of Cortical Thickness

ERIC Educational Resources Information Center

Tamnes, Christian K.; Ostby, Ylva; Walhovd, Kristine B.; Westlye, Lars T.; Due-Tonnessen, Paulina; Fjell, Anders M.

2010-01-01

A range of cognitive abilities improves in childhood and adolescence. It has been proposed that the protracted development of executive functions is related to the relatively late maturation of the prefrontal cortex. However, this has rarely been directly investigated. In this cross-sectional study, 98 healthy children and adolescents (8-19 years…

[Cortical functional connectivity during retention of affective pictures in working memory: EEG-source theta coherence analysis].

PubMed

Machinskaya, R I; Rozovskaya, R I; Kurgansky, A V; Pechenkova, E V

2016-01-01

A pattern of cortical functional connectivity in the source space was studied in a group of right-handed adult participants (N = 44:17 women, 27 men, aged M = 29.61 ± 6.45 years) who retained in their working memory (WM) traces of realistic pictures of positive, neutral, and negative emotional valence while in their working memory (WM) while performing same different task in which participants had to compare an etalon picture against a target picture that followed after a specified delay. A coherence (COH) between pairs of cortical sources chosen in advance according to fMRI data was estimated in the theta frequency range for the period of time preceding the etalon stimulus, distinct sets of functional links are found. The links of the first type that presumably reflect the involvement of sustained attention were between the dorsal anterior cingulate cortex, the prefrontal areas, and temporal areas of the right hemispheres. When compared to the rest period, links of this type showed strengthening not only during the retention period but also during the period preceding the etalon picture. The links of the second type presumably reflecting a progressive neocortex-to-hippocampus functional integration with increasing memory load and strengthened exclusively during retention period. Those links were between parietal, temporal and prefrontal cortices in the lateral surface of both hemispheres with the additional inclusion of the posterior cingulate cortex and the medial parietal cortex in the left hemisphere. An impact of emotional valence onto the strength and topography of the functional links of the second type was found. In the left hemisphere, an increase in the strength of cortical interaction was more pronounced for pictures of positive valence than for pictures of either neutral or negative valences. When compared to the pictures of neutral valence, the retention of pictorial information of both positive and negative valence showed some extraneous integration of the cortical areas for the theta rhythm. This finding might be related to the additional load exerted by emotionally colored pictures onto the mechanisms of short-time retention of visual information.

Morphological alterations in the prefrontal cortex and the amygdala in unsuccessful psychopaths.

PubMed

Yang, Yaling; Raine, Adrian; Colletti, Patrick; Toga, Arthur W; Narr, Katherine L

2010-08-01

Although deficits in several cortical and subcortical structures have been found in psychopaths, it remains unclear whether the neuropathology differs between subgroups of psychopaths (i.e., unsuccessful and successful). Using both traditional and novel image analyses methods, this study aims to reveal gross and subtle morphological changes in the prefrontal cortex and the amygdala in unsuccessful and successful psychopaths. Volumetric segmentation, cortical pattern matching, and surface-based mesh modeling methods were used to examine prefrontal and amygdala structures in 16 unsuccessful psychopaths, 10 successful psychopaths, and 27 controls. Significant reduced gray matter volume and cortical thickness/surface shape in the middle frontal, orbitofrontal cortex and the amygdala were found in unsuccessful psychopaths but not successful psychopaths, compared with controls. This study provides the first evidence of greater prefrontal and amygdala structural deficits in unsuccessful psychopaths, which may predispose them to poor behavioral control and impaired decision-making, thus making them more prone to convictions. Copyright 2010 APA, all rights reserved

Thinking about eating food activates visual cortex with reduced bilateral cerebellar activation in females with anorexia nervosa: an fMRI study.

PubMed

Brooks, Samantha J; O'Daly, Owen; Uher, Rudolf; Friederich, Hans-Christoph; Giampietro, Vincent; Brammer, Michael; Williams, Steven C R; Schiöth, Helgi B; Treasure, Janet; Campbell, Iain C

2012-01-01

Women with anorexia nervosa (AN) have aberrant cognitions about food and altered activity in prefrontal cortical and somatosensory regions to food images. However, differential effects on the brain when thinking about eating food between healthy women and those with AN is unknown. Functional magnetic resonance imaging (fMRI) examined neural activation when 42 women thought about eating the food shown in images: 18 with AN (11 RAN, 7 BPAN) and 24 age-matched controls (HC). Group contrasts between HC and AN revealed reduced activation in AN in the bilateral cerebellar vermis, and increased activation in the right visual cortex. Preliminary comparisons between AN subtypes and healthy controls suggest differences in cortical and limbic regions. These preliminary data suggest that thinking about eating food shown in images increases visual and prefrontal cortical neural responses in females with AN, which may underlie cognitive biases towards food stimuli and ruminations about controlling food intake. Future studies are needed to explicitly test how thinking about eating activates restraint cognitions, specifically in those with restricting vs. binge-purging AN subtypes.

Repetition-related reductions in neural activity reveal component processes of mental simulation.

PubMed

Szpunar, Karl K; St Jacques, Peggy L; Robbins, Clifford A; Wig, Gagan S; Schacter, Daniel L

2014-05-01

In everyday life, people adaptively prepare for the future by simulating dynamic events about impending interactions with people, objects and locations. Previous research has consistently demonstrated that a distributed network of frontal-parietal-temporal brain regions supports this ubiquitous mental activity. Nonetheless, little is known about the manner in which specific regions of this network contribute to component features of future simulation. In two experiments, we used a functional magnetic resonance (fMR)-repetition suppression paradigm to demonstrate that distinct frontal-parietal-temporal regions are sensitive to processing the scenarios or what participants imagined was happening in an event (e.g., medial prefrontal, posterior cingulate, temporal-parietal and middle temporal cortices are sensitive to the scenarios associated with future social events), people (medial prefrontal cortex), objects (inferior frontal and premotor cortices) and locations (posterior cingulate/retrosplenial, parahippocampal and posterior parietal cortices) that typically constitute simulations of personal future events. This pattern of results demonstrates that the neural substrates of these component features of event simulations can be reliably identified in the context of a task that requires participants to simulate complex, everyday future experiences.

Frontal-thalamic circuits associated with language

PubMed Central

Barbas, Helen; García-Cabezas, Miguel Ángel; Zikopoulos, Basilis

2012-01-01

Thalamic nuclei associated with language including the ventral lateral, ventral anterior, intralaminar and mediodorsal form a hub that uniquely receives the output of the basal ganglia and cerebellum, and is connected with frontal (premotor and prefrontal) cortices through two parallel circuits: a thalamic pathway targets the middle frontal cortical layers focally, and the other innervates widely cortical layer 1, poised to recruit other cortices and thalamic nuclei for complex cognitive operations. Return frontal pathways to the thalamus originate from cortical layers 6 and 5. Information through this integrated thalamo-cortical system is gated by the inhibitory thalamic reticular nucleus and modulated by dopamine, representing a specialization in primates. The intricate dialogue of distinct thalamic nuclei with the basal ganglia, cerebellum, and specific dorsolateral prefrontal and premotor cortices associated with language, suggests synergistic roles in the complex but seemingly effortless sequential transformation of cognitive operations for speech production in humans. PMID:23211411

Prefrontal cortical gamma-aminobutyric acid transmission and cognitive function: drawing links to schizophrenia from preclinical research.

PubMed

Tse, Maric T; Piantadosi, Patrick T; Floresco, Stan B

2015-06-01

Cognitive dysfunction in schizophrenia is one of the most pervasive and debilitating aspects of the disorder. Among the numerous neural abnormalities that may contribute to schizophrenia symptoms, perturbations in markers for the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), particularly within the frontal lobes, are some of the most reliable alterations observed at postmortem examination. However, how prefrontal GABA dysfunction contributes to cognitive impairment in schizophrenia remains unclear. We provide an overview of postmortem GABAergic perturbations in the brain affected by schizophrenia and describe circumstantial evidence linking these alterations to cognitive dysfunction. In addition, we conduct a survey of studies using neurodevelopmental, genetic, and pharmacologic rodent models that induce schizophrenia-like cognitive impairments, highlighting the convergence of these mechanistically distinct approaches to prefrontal GABAergic disruption. We review preclinical studies that have directly targeted prefrontal cortical GABAergic transmission using local application of GABAA receptor antagonists. These studies have provided an important link between GABA transmission and cognitive dysfunction in schizophrenia because they show that reducing prefrontal inhibitory transmission induces various cognitive, emotional, and dopaminergic abnormalities that resemble aspects of the disorder. These converging clinical and preclinical findings provide strong support for the idea that perturbations in GABA signaling drive certain forms of cognitive dysfunction in schizophrenia. Future studies using this approach will yield information to refine further a putative "GABA hypothesis" of schizophrenia. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Sharing self-related information is associated with intrinsic functional connectivity of cortical midline brain regions

PubMed Central

Meshi, Dar; Mamerow, Loreen; Kirilina, Evgeniya; Morawetz, Carmen; Margulies, Daniel S.; Heekeren, Hauke R.

2016-01-01

Human beings are social animals and they vary in the degree to which they share information about themselves with others. Although brain networks involved in self-related cognition have been identified, especially via the use of resting-state experiments, the neural circuitry underlying individual differences in the sharing of self-related information is currently unknown. Therefore, we investigated the intrinsic functional organization of the brain with respect to participants’ degree of self-related information sharing using resting state functional magnetic resonance imaging and self-reported social media use. We conducted seed-based correlation analyses in cortical midline regions previously shown in meta-analyses to be involved in self-referential cognition: the medial prefrontal cortex (MPFC), central precuneus (CP), and caudal anterior cingulate cortex (CACC). We examined whether and how functional connectivity between these regions and the rest of the brain was associated with participants’ degree of self-related information sharing. Analyses revealed associations between the MPFC and right dorsolateral prefrontal cortex (DLPFC), as well as the CP with the right DLPFC, the left lateral orbitofrontal cortex and left anterior temporal pole. These findings extend our present knowledge of functional brain connectivity, specifically demonstrating how the brain’s intrinsic functional organization relates to individual differences in the sharing of self-related information. PMID:26948055

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

Dopamine modulation of emotional processing in cortical and subcortical neural circuits: evidence for a final common pathway in schizophrenia?

PubMed

Laviolette, Steven R

2007-07-01

The neural regulation of emotional perception, learning, and memory is essential for normal behavioral and cognitive functioning. Many of the symptoms displayed by individuals with schizophrenia may arise from fundamental disturbances in the ability to accurately process emotionally salient sensory information. The neurotransmitter dopamine (DA) and its ability to modulate neural regions involved in emotional learning, perception, and memory formation has received considerable research attention as a potential final common pathway to account for the aberrant emotional regulation and psychosis present in the schizophrenic syndrome. Evidence from both human neuroimaging studies and animal-based research using neurodevelopmental, behavioral, and electrophysiological techniques have implicated the mesocorticolimbic DA circuit as a crucial system for the encoding and expression of emotionally salient learning and memory formation. While many theories have examined the cortical-subcortical interactions between prefrontal cortical regions and subcortical DA substrates, many questions remain as to how DA may control emotional perception and learning and how disturbances linked to DA abnormalities may underlie the disturbed emotional processing in schizophrenia. Beyond the mesolimbic DA system, increasing evidence points to the amygdala-prefrontal cortical circuit as an important processor of emotionally salient information and how neurodevelopmental perturbances within this circuitry may lead to dysregulation of DAergic modulation of emotional processing and learning along this cortical-subcortical emotional processing circuit.

Regional gray matter growth, sexual dimorphism, and cerebral asymmetry in the neonatal brain.

PubMed

Gilmore, John H; Lin, Weili; Prastawa, Marcel W; Looney, Christopher B; Vetsa, Y Sampath K; Knickmeyer, Rebecca C; Evans, Dianne D; Smith, J Keith; Hamer, Robert M; Lieberman, Jeffrey A; Gerig, Guido

2007-02-07

Although there has been recent interest in the study of childhood and adolescent brain development, very little is known about normal brain development in the first few months of life. In older children, there are regional differences in cortical gray matter development, whereas cortical gray and white matter growth after birth has not been studied to a great extent. The adult human brain is also characterized by cerebral asymmetries and sexual dimorphisms, although very little is known about how these asymmetries and dimorphisms develop. We used magnetic resonance imaging and an automatic segmentation methodology to study brain structure in 74 neonates in the first few weeks after birth. We found robust cortical gray matter growth compared with white matter growth, with occipital regions growing much faster than prefrontal regions. Sexual dimorphism is present at birth, with males having larger total brain cortical gray and white matter volumes than females. In contrast to adults and older children, the left hemisphere is larger than the right hemisphere, and the normal pattern of fronto-occipital asymmetry described in older children and adults is not present. Regional differences in cortical gray matter growth are likely related to differential maturation of sensory and motor systems compared with prefrontal executive function after birth. These findings also indicate that whereas some adult patterns of sexual dimorphism and cerebral asymmetries are present at birth, others develop after birth.

Multiple cortical thickness sub-networks and cognitive impairments in first episode, drug naïve patients with late life depression: A graph theory analysis.

PubMed

Shin, Jeong-Hyeon; Um, Yu Hyun; Lee, Chang Uk; Lim, Hyun Kook; Seong, Joon-Kyung

2018-03-15

Coordinated and pattern-wise changes in large scale gray matter structural networks reflect neural circuitry dysfunction in late life depression (LLD), which in turn is associated with emotional dysregulation and cognitive impairments. However, due to methodological limitations, there have been few attempts made to identify individual-level structural network properties or sub-networks that are involved in important brain functions in LLD. In this study, we sought to construct individual-level gray matter structural networks using average cortical thicknesses of several brain areas to investigate the characteristics of the gray matter structural networks in normal controls and LLD patients. Additionally, we investigated the structural sub-networks correlated with several clinical measurements including cognitive impairment and depression severity. We observed that small worldness, clustering coefficients, global and local efficiency, and hub structures in the brains of LLD patients were significantly different from healthy controls. We further found that a sub-network including the anterior cingulate, dorsolateral prefrontal cortex and superior prefrontal cortex is significantly associated with attention control and executive function. The severity of depression was associated with the sub-networks comprising the salience network, including the anterior cingulate and insula. We investigated cortico-cortical connectivity, but omitted the subcortical structures such as the striatum and thalamus. We report differences in patterns between several clinical measurements and sub-networks from large-scale and individual-level cortical thickness networks in LLD. Copyright © 2018 Elsevier B.V. All rights reserved.

Hippocampal-cortical interaction in decision making

PubMed Central

Yu, Jai Y.; Frank, Loren M.

2014-01-01

When making a decision it is often necessary to consider the available alternatives in order to choose the most appropriate option. This deliberative process, where the pros and cons of each option are considered, relies on memories of past actions and outcomes. The hippocampus and prefrontal cortex are required for memory encoding, memory retrieval and decision making, but it is unclear how these areas support deliberation. Here we examine the potential neural substrates of these processes in the rat. The rat is a powerful model to investigate the network mechanisms underlying deliberation in the mammalian brain given the anatomical and functional conservation of its hippocampus and prefrontal cortex to other mammalian systems. Importantly, it is amenable to large scale neural recording while performing laboratory tasks that exploit its natural decisionmaking behavior. Focusing on findings in the rat, we discuss how hippocampal-cortical interactions could provide a neural substrate for deliberative decision making. PMID:24530374

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.

Spatiotemporal characteristics of sleep spindles depend on cortical location.

PubMed

Piantoni, Giovanni; Halgren, Eric; Cash, Sydney S

2017-02-01

Since their discovery almost one century ago, sleep spindles, 0.5-2s long bursts of oscillatory activity at 9-16Hz during NREM sleep, have been thought to be global and relatively uniform throughout the cortex. Recent work, however, has brought this concept into question but it remains unclear to what degree spindles are global or local and if their properties are uniform or location-dependent. We addressed this question by recording sleep in eight patients undergoing evaluation for epilepsy with intracranial electrocorticography, which combines high spatial resolution with extensive cortical coverage. We find that spindle characteristics are not uniform but are strongly influenced by the underlying cortical regions, particularly for spindle density and fundamental frequency. We observe both highly isolated and spatially distributed spindles, but in highly skewed proportions: while most spindles are restricted to one or very few recording channels at any given time, there are spindles that occur over widespread areas, often involving lateral prefrontal cortices and superior temporal gyri. Their co-occurrence is affected by a subtle but significant propagation of spindles from the superior prefrontal regions and the temporal cortices towards the orbitofrontal cortex. This work provides a brain-wide characterization of sleep spindles as mostly local graphoelements with heterogeneous characteristics that depend on the underlying cortical area. We propose that the combination of local characteristics and global organization reflects the dual properties of the thalamo-cortical generators and provides a flexible framework to support the many functions ascribed to sleep in general and spindles specifically. Copyright © 2016 Elsevier Inc. All rights reserved.

Localized Cortical Thinning in Patients with Obstructive Sleep Apnea Syndrome

PubMed Central

Joo, Eun Yeon; Jeon, Seun; Kim, Sung Tae; Lee, Jong-Min; Hong, Seung Bong

2013-01-01

Study Objectives: To investigate differences in cortical thickness in patients with obstructive sleep apnea (OSA) syndrome and healthy controls. Design: Cortical thickness was measured using a three-dimensional surface-based method that enabled more accurate measurement in deep sulci and localized regional mapping. Setting: University hospital. Patients: Thirty-eight male patients with severe OSA (mean apnea-hypopnea index > 30/h) and 36 age-matched male healthy controls were enrolled. Interventions: Cortical thickness was obtained at 81,924 vertices across the entire brain by reconstructing inner and outer cortical surfaces using an automated anatomical pipeline. Measurements: Group difference in cortical thickness and correlation between patients' data and thickness were analyzed by a general linear model. Results: Localized cortical thinning in patients was found in the orbitorectal gyri, dorsolateral/ventromedial prefrontal regions, pericentral gyri, anterior cingulate, insula, inferior parietal lobule, uncus, and basolateral temporal regions at corrected P < 0.05. Patients with OSA showed impaired attention and learning difficulty in memory tests compared to healthy controls. Higher number of respiratory arousals was related to cortical thinning of the anterior cingulate and inferior parietal lobule. A significant correlation was observed between the longer apnea maximum duration and the cortical thinning of the dorsolateral prefrontal regions, pericentral gyri, and insula. Retention scores in visual memory tests were associated with cortical thickness of parahippocampal gyrus and uncus. Conclusions: Brain regions with cortical thinning may provide elucidations for prefrontal cognitive dysfunction, upper airway sensorimotor dysregulation, and cardiovascular disturbances in OSA patients, that experience sleep disruption including sleep fragmentation and oxygen desaturation. Citation: Joo EY; Jeon S; Kim ST; Lee JM; Hong SB. Localized cortical thinning in patients with obstructive sleep apnea syndrome. SLEEP 2013;36(8):1153-1162. PMID:23904675

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.

Prefrontal cortical thinning links to negative symptoms in schizophrenia via the ENIGMA consortium.

PubMed

Walton, E; Hibar, D P; van Erp, T G M; Potkin, S G; Roiz-Santiañez, R; Crespo-Facorro, B; Suarez-Pinilla, P; van Haren, N E M; de Zwarte, S M C; Kahn, R S; Cahn, W; Doan, N T; Jørgensen, K N; Gurholt, T P; Agartz, I; Andreassen, O A; Westlye, L T; Melle, I; Berg, A O; Morch-Johnsen, L; Færden, A; Flyckt, L; Fatouros-Bergman, H; Jönsson, E G; Hashimoto, R; Yamamori, H; Fukunaga, M; Jahanshad, N; De Rossi, P; Piras, F; Banaj, N; Spalletta, G; Gur, R E; Gur, R C; Wolf, D H; Satterthwaite, T D; Beard, L M; Sommer, I E; Koops, S; Gruber, O; Richter, A; Krämer, B; Kelly, S; Donohoe, G; McDonald, C; Cannon, D M; Corvin, A; Gill, M; Di Giorgio, A; Bertolino, A; Lawrie, S; Nickson, T; Whalley, H C; Neilson, E; Calhoun, V D; Thompson, P M; Turner, J A; Ehrlich, S

2018-01-01

Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity. This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores). Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (β std = -0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged. Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in 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

Application of State-Space Smoothing to fMRI Data for Calculation of Lagged Transinformation between Human Brain Activations

NASA Astrophysics Data System (ADS)

Watanabe, Jobu

2009-09-01

Mutual information can be given a directional sense by introducing a time lag in one of the variables. In an author's previous study, to investigate the network dynamics of human brain regions, lagged transinformation (LTI) was introduced using time delayed mutual information. The LTI makes it possible to quantify the time course of dynamic information transfer between regions in the temporal domain. The LTI was applied to functional magnetic resonance imaging (fMRI) data involved in neural processing of the transformation and comparison from three-dimensional (3D) visual information to a two-dimensional (2D) location to calculate directed information flows between the activated brain regions. In the present study, for more precise estimation of LTI, Kalman filter smoothing was applied to the same fMRI data. Because the smoothing method exploits the full length of the time series data for the estimation, its application increases the precision. Large information flows were found from the bilateral prefrontal cortices to the parietal cortices. The results suggest that information of the 3D images stored as working memory was retrieved and transferred from the prefrontal cortices to the parietal cortices for comparison with information of the 2D images.

Insights into Human Behavior from Lesions to the Prefrontal Cortex

PubMed Central

Szczepanski, Sara M.; Knight, Robert T.

2014-01-01

SUMMARY The prefrontal cortex (PFC), a cortical region that was once thought to be functionally insignificant, is now known to play an essential role in the organization and control of goal-directed thought and behavior. Neuroimaging, neurophysiological, and modeling techniques have lead to tremendous advances in our understanding of PFC functions over the last few decades. It should be noted, however, that neurological, neuropathological, and neuropsychological studies have contributed some of the most essential, historical, and often prescient, conclusions regarding the functions of this region. Importantly, examination of patients with brain damage allows one to draw conclusions about whether a brain area is necessary for a particular function. Here, we provide a broad overview of PFC functions based upon behavioral and neural changes resulting from damage to PFC in both human patients and non-human primates. PMID:25175878

Parafascicular thalamic nucleus deep brain stimulation decreases NMDA receptor GluN1 subunit gene expression in the prefrontal cortex.

PubMed

Fernández-Cabrera, Mónica R; Selvas, Abraham; Miguéns, Miguel; Higuera-Matas, Alejandro; Vale-Martínez, Anna; Ambrosio, Emilio; Martí-Nicolovius, Margarita; Guillazo-Blanch, Gemma

2017-04-21

The rodent parafascicular nucleus (PFn) or the centromedian-parafascicular complex of primates is a posterior intralaminar nucleus of the thalamus related to cortical activation and maintenance of states of consciousness underlying attention, learning and memory. Deep brain stimulation (DBS) of the PFn has been proved to restore arousal and consciousness in humans and to enhance performance in learning and memory tasks in rats. The primary expected effect of PFn DBS is to induce plastic changes in target neurons of brain areas associated with cognitive function. In this study, Wistar rats were stimulated for 20mins in the PFn following a DBS protocol that had previously facilitated memory in rats. NMDA and GABA B receptor binding, and gene expression of the GluN1subunit of the NMDA receptor (NMDAR) were assessed in regions related to cognitive functions, such as the prefrontal cortex and hippocampus. The results showed that PFn DBS induced a decrease in NMDAR GluN1 subunit gene expression in the cingulate and prelimbic cortices, but no significant statistical differences were found in the density of NMDA or GABA B receptors in any of the analyzed regions. Taken together, our findings suggest a possible role for the NMDAR GluN1 subunit in the prefrontal cortex in the procognitive actions of the PFn DBS. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Brain responses to social norms: Meta-analyses of fMRI studies.

PubMed

Zinchenko, Oksana; Arsalidou, Marie

2018-02-01

Social norms have a critical role in everyday decision-making, as frequent interaction with others regulates our behavior. Neuroimaging studies show that social-based and fairness-related decision-making activates an inconsistent set of areas, which sometimes includes the anterior insula, anterior cingulate cortex, and others lateral prefrontal cortices. Social-based decision-making is complex and variability in findings may be driven by socio-cognitive activities related to social norms. To distinguish among social-cognitive activities related to social norms, we identified 36 eligible articles in the functional magnetic resonance imaging (fMRI) literature, which we separate into two categories (a) social norm representation and (b) norm violations. The majority of original articles (>60%) used tasks associated with fairness norms and decision-making, such as ultimatum game, dictator game, or prisoner's dilemma; the rest used tasks associated to violation of moral norms, such as scenarios and sentences of moral depravity ratings. Using quantitative meta-analyses, we report common and distinct brain areas that show concordance as a function of category. Specifically, concordance in ventromedial prefrontal regions is distinct to social norm representation processing, whereas concordance in right insula, dorsolateral prefrontal, and dorsal cingulate cortices is distinct to norm violation processing. We propose a neurocognitive model of social norms for healthy adults, which could help guide future research in social norm compliance and mechanisms of its enforcement. © 2017 Wiley Periodicals, Inc.

Neural plasticity in amplitude of low frequency fluctuation, cortical hub construction, regional homogeneity resulting from working memory training.

PubMed

Takeuchi, Hikaru; Taki, Yasuyuki; Nouchi, Rui; Sekiguchi, Atsushi; Kotozaki, Yuka; Nakagawa, Seishu; Makoto Miyauchi, Carlos; Sassa, Yuko; Kawashima, Ryuta

2017-05-03

Working memory training (WMT) induces changes in cognitive function and various neurological systems. Here, we investigated changes in recently developed resting state functional magnetic resonance imaging measures of global information processing [degree of the cortical hub, which may have a central role in information integration in the brain, degree centrality (DC)], the magnitude of intrinsic brain activity [fractional amplitude of low frequency fluctuation (fALFF)], and local connectivity (regional homogeneity) in young adults, who either underwent WMT or received no intervention for 4 weeks. Compared with no intervention, WMT increased DC in the anatomical cluster, including anterior cingulate cortex (ACC), to the medial prefrontal cortex (mPFC). Furthermore, WMT increased fALFF in the anatomical cluster including the right dorsolateral prefrontal cortex (DLPFC), frontopolar area and mPFC. WMT increased regional homogeneity in the anatomical cluster that spread from the precuneus to posterior cingulate cortex and posterior parietal cortex. These results suggest WMT-induced plasticity in spontaneous brain activity and global and local information processing in areas of the major networks of the brain during rest.

Low dopamine striatal D2 receptors are associated with prefrontal metabolism in obese subjects: Possible contributing factors

PubMed Central

Volkow, Nora D.; Wang, Gene-Jack; Telang, Frank; Fowler, Joanna S.; Thanos, Panayotis K.; Logan, Jean; Alexoff, David; Ding, Yu-Shin; Wong, Christopher; Ma, Yeming; Pradhan, Kith

2009-01-01

Dopamine's role in inhibitory control is well recognized and its disruption may contribute to behavioral disorders of discontrol such as obesity. However, the mechanism by which impaired dopamine neurotransmission interferes with inhibitory control is poorly understood. We had previously documented a reduction in dopamine D2 receptors in morbidly obese subjects. To assess if the reductions in dopamine D2 receptors were associated with activity in prefrontal brain regions implicated in inhibitory control we assessed the relationship between dopamine D2 receptor availability in striatum with brain glucose metabolism (marker of brain function) in ten morbidly obese subjects (BMI>40 kg/m2) and compared it to that in twelve non-obese controls. PET was used with [11C]raclopride to assess D2 receptors and with [18F] FDG to assess regional brain glucose metabolism. In obese subjects striatal D2 receptor availability was lower than controls and was positively correlated with metabolism in dorsolateral prefrontal, medial orbitofrontal, anterior cingulate gyrus and somatosensory cortices. In controls correlations with prefrontal metabolism were not significant but comparisons with those in obese subjects were not significant, which does not permit to ascribe the associations as unique to obesity. The associations between striatal D2 receptors and prefrontal metabolism in obese subjects suggest that decreases in striatal D2 receptors could contribute to overeating via their modulation of striatal prefrontal pathways, which participate in inhibitory control and salience attribution. The association between striatal D2 receptors and metabolism in somatosensory cortices (regions that process palatability) could underlie one of the mechanisms through which dopamine regulates the reinforcing properties of food. PMID:18598772

Interaction Between Hippocampus and Cerebellum Crus I in Sequence-Based but not Place-Based Navigation

PubMed Central

Iglói, Kinga; Doeller, Christian F.; Paradis, Anne-Lise; Benchenane, Karim; Berthoz, Alain; Burgess, Neil; Rondi-Reig, Laure

2015-01-01

To examine the cerebellar contribution to human spatial navigation we used functional magnetic resonance imaging and virtual reality. Our findings show that the sensory-motor requirements of navigation induce activity in cerebellar lobules and cortical areas known to be involved in the motor loop and vestibular processing. By contrast, cognitive aspects of navigation mainly induce activity in a different cerebellar lobule (VIIA Crus I). Our results demonstrate a functional link between cerebellum and hippocampus in humans and identify specific functional circuits linking lobule VIIA Crus I of the cerebellum to medial parietal, medial prefrontal, and hippocampal cortices in nonmotor aspects of navigation. They further suggest that Crus I belongs to 2 nonmotor loops, involved in different strategies: place-based navigation is supported by coherent activity between left cerebellar lobule VIIA Crus I and medial parietal cortex along with right hippocampus activity, while sequence-based navigation is supported by coherent activity between right lobule VIIA Crus I, medial prefrontal cortex, and left hippocampus. These results highlight the prominent role of the human cerebellum in both motor and cognitive aspects of navigation, and specify the cortico-cerebellar circuits by which it acts depending on the requirements of the task. PMID:24947462

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

PubMed Central

Lambe, Evelyn K.; Aghajanian, George K.

2007-01-01

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

Cortical midline involvement in autobiographical memory

PubMed Central

Summerfield, Jennifer J.; Hassabis, Demis; Maguire, Eleanor A.

2009-01-01

Recollecting autobiographical memories of personal past experiences is an integral part of our everyday lives and relies on a distributed set of brain regions. Their occurrence externally in the real world (‘realness’) and their self-relevance (‘selfness’) are two defining features of these autobiographical events. Distinguishing between personally experienced events and those that happened to other individuals, and between events that really occurred and those that were mere figments of the imagination, is clearly advantageous, yet the respective neural correlates remain unclear. Here we experimentally manipulated and dissociated realness and selfness during fMRI using a novel paradigm where participants recalled self (autobiographical) and non-self (from a movie or television news clips) events that were either real or previously imagined. Distinct sub-regions within dorsal and ventral medial prefrontal cortex, retrosplenial cortex and along the parieto-occipital sulcus preferentially coded for events (real or imagined) involving the self. By contrast, recollection of autobiographical events that really happened in the external world activated different areas within ventromedial prefrontal cortex and posterior cingulate cortex. In addition, recall of externally experienced real events (self or non-self) was associated with increased activity in areas of dorsomedial prefrontal cortex and posterior cingulate cortex. Taken together our results permitted a functional deconstruction of anterior (medial prefrontal) and posterior (retrosplenial cortex, posterior cingulate cortex, precuneus) cortical midline regions widely associated with autobiographical memory but whose roles have hitherto been poorly understood. PMID:18973817

Effect of age at onset on cortical thickness and cognition in posterior cortical atrophy.

PubMed

Suárez-González, Aida; Lehmann, Manja; Shakespeare, Timothy J; Yong, Keir X X; Paterson, Ross W; Slattery, Catherine F; Foulkes, Alexander J M; Rabinovici, Gil D; Gil-Néciga, Eulogio; Roldán-Lora, Florinda; Schott, Jonathan M; Fox, Nick C; Crutch, Sebastian J

2016-08-01

Age at onset (AAO) has been shown to influence the phenotype of Alzheimer's disease (AD), but how it affects atypical presentations of AD remains unknown. Posterior cortical atrophy (PCA) is the most common form of atypical AD. In this study, we aimed to investigate the effect of AAO on cortical thickness and cognitive function in 98 PCA patients. We used Freesurfer (v5.3.0) to compare cortical thickness with AAO both as a continuous variable, and by dichotomizing the groups based on median age (58 years). In both the continuous and dichotomized analyses, we found a pattern suggestive of thinner cortex in precuneus and parietal areas in earlier-onset PCA, and lower cortical thickness in anterior cingulate and prefrontal cortex in later-onset PCA. These cortical thickness differences between PCA subgroups were consistent with earlier-onset PCA patients performing worse on cognitive tests involving parietal functions. Our results provide a suggestion that AAO may not only affect the clinico-anatomical characteristics in AD but may also affect atrophy patterns and cognition within atypical AD phenotypes. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Cortical Thickness Reduction in Combat Exposed U.S. Veterans with and without PTSD

PubMed Central

Wrocklage, Kristen M.; Averill, Lynnette A.; Scott, J. Cobb; Averill, Christopher L.; Schweinsburg, Brian; Trejo, Marcia; Roy, Alicia; Weisser, Valerie; Kelly, Christopher; Martini, Brenda; Harpaz-Rotem, Ilan; Southwick, Steven M.; Krystal, John H.; Abdallah, Chadi G.

2017-01-01

We investigated the extent of cortical thinning in U.S. Veterans exposed to combat who varied in the severity of their posttraumatic stress disorder (PTSD) symptoms. In addition, we explored the neural correlates of PTSD symptom dimensions and the interactive effects of combat exposure and PTSD upon cortical thickness. Sixty-nine combat exposed Veterans completed high-resolution magnetic resonance imaging (MRI) scans to estimate cortical thickness. The Clinician Administered PTSD Scale (CAPS) and Combat Exposure Scale (CES) assessments were completed to measure current PTSD and historical combat severity, respectively. PTSD symptom dimensions (numbing, avoidance, reexperiencing, anxious arousal, and dysphoric arousal) were studied. Vertex-wise whole cerebrum analyses were conducted. We found widespread negative correlations between CAPS severity and cortical thickness, particularly within the prefrontal cortex. This prefrontal correlation remained significant after controlling for depression severity, medication status, and other potential confounds. PTSD dimensions, except anxious arousal, negatively correlated with cortical thickness in various unique brain regions. CES negatively correlated with cortical thickness in the left lateral prefrontal, regardless of PTSD diagnosis. A significant interaction between CES and PTSD diagnosis was found, such that CES negatively correlated with cortical thickness in the non-PTSD, but not in the PTSD, participants. The results underscore the severity of cortical thinning in U.S. Veterans suffering from high level of PTSD symptoms, as well as in Veterans with no PTSD diagnosis but severe combat exposure. The latter finding raises considerable concerns about a concealed injury potentially related to combat exposure in the post-9/11 era. PMID:28279623

Cortical thickness reduction in combat exposed U.S. veterans with and without PTSD.

PubMed

Wrocklage, Kristen M; Averill, Lynnette A; Cobb Scott, J; Averill, Christopher L; Schweinsburg, Brian; Trejo, Marcia; Roy, Alicia; Weisser, Valerie; Kelly, Christopher; Martini, Brenda; Harpaz-Rotem, Ilan; Southwick, Steven M; Krystal, John H; Abdallah, Chadi G

2017-05-01

We investigated the extent of cortical thinning in U.S. Veterans exposed to combat who varied in the severity of their posttraumatic stress disorder (PTSD) symptoms. In addition, we explored the neural correlates of PTSD symptom dimensions and the interactive effects of combat exposure and PTSD upon cortical thickness. Sixty-nine combat exposed Veterans completed high-resolution magnetic resonance imaging (MRI) scans to estimate cortical thickness. The Clinician Administered PTSD Scale (CAPS) and Combat Exposure Scale (CES) assessments were completed to measure current PTSD and historical combat severity, respectively. PTSD symptom dimensions (numbing, avoidance, reexperiencing, anxious arousal, and dysphoric arousal) were studied. Vertex-wise whole cerebrum analyses were conducted. We found widespread negative correlations between CAPS severity and cortical thickness, particularly within the prefrontal cortex. This prefrontal correlation remained significant after controlling for depression severity, medication status, and other potential confounds. PTSD dimensions, except anxious arousal, negatively correlated with cortical thickness in various unique brain regions. CES negatively correlated with cortical thickness in the left lateral prefrontal, regardless of PTSD diagnosis. A significant interaction between CES and PTSD diagnosis was found, such that CES negatively correlated with cortical thickness in the non-PTSD, but not in the PTSD, participants. The results underscore the severity of cortical thinning in U.S. Veterans suffering from high level of PTSD symptoms, as well as in Veterans with no PTSD diagnosis but severe combat exposure. The latter finding raises considerable concerns about a concealed injury potentially related to combat exposure in the post-9/11 era. Published by Elsevier B.V.

Chronic stress effects on working memory: association with prefrontal cortical tyrosine hydroxylase.

PubMed

Lee, Young-A; Goto, Yukiori

2015-06-01

Chronic stress causes deficits in cognitive function including working memory, for which transmission of such catecholamines as dopamine and noradrenaline transmission in the prefrontal cortex (PFC) are crucial. Since catecholamine synthesis depends on the rate-limiting enzyme, tyrosine hydroxylase (TH), TH is thought to play an important role in PFC function. In this study, we found that two distinct population existed in Sprague-Dawley rats in terms of working memory capacity, one with higher working memory capacity, and the other with low capacity. This distinction of working memory capacity became apparent after rats were exposed to chronic stress. In addition, such working memory capacity and alterations of working memory function by chronic stress were associated with TH expression in the PFC. Copyright © 2015 Elsevier B.V. All rights reserved.

Ventromedial prefrontal cortex generates pre-stimulus theta coherence desynchronization: A schema instantiation hypothesis.

PubMed

Gilboa, Asaf; Moscovitch, Morris

2017-02-01

The ventral medial prefrontal cortex (vmPFC) has long been implicated in monitoring of memory veracity, and more recently also in memory schema functions. In our model of strategic retrieval the two are related. We have proposed that the vmPFC has two schema-dependent functions: (i) to establish context-relevant templates against which the output of memory systems can be compared; (ii) to mediate automatic decision monitoring processes to ensure that only those responses that meet the criterion are enacted. Electroencephalogram (EEG) data were used to provide evidence that vmPFC supports both functions, and that schema instantiation informs monitoring. Participants viewed pictures of acquaintances, along with those of famous and nonfamous people, and were asked to respond positively only to pictures of individuals they had met (personal familiarity). The Self serves as a super-ordinate cognitive schema, facilitating accurate endorsement of acquaintances and exclusion of non-personal but familiar faces. For the present report we focused on pre-cue tonic oscillatory activity. Controls demonstrated theta coherence desynchronization between medial prefrontal areas, inferotemporal and lateral temporal cortices. These oscillatory coherence patterns were significantly reduced in patients with vmPFC damage, especially in those with clinical histories of spontaneous confabulation. Importantly, these pre-stimulus cortico-cortical desynchronizations predicted post-cue automatic memory activation, as indexed by a familiarity modulation of the face-sensitive posterior cortical N170. Pre-cue desynchronization also predicted early post-cue frontal positive modulation (P230) and response accuracy. The data are consistent with a schema instantiation model that suggests the vmPFC biases posterior neocortical long-term memory representations that enhance automatic memory cue processing and informs frontally-mediated rapid memory monitoring (P230). Damage to these structures can lead to inaccurate, context-irrelevant activation of schemas. These, in turn, impair monitoring signals and can lead to confabulation when memory control processes are also deficient. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evidence for a role of corticopetal, noradrenergic systems in the development of executive function.

PubMed

Mokler, David J; Miller, Christine E; McGaughy, Jill A

2017-09-01

Adolescence is a period during which many aspects of executive function are maturing. Much of the literature has focused on discrepancies between sub-cortical and cortical development that is hypothesized to lead to over-processing of reinforcement related stimuli unchecked by fully matured response inhibition. Specifically, maturation of sub-cortical dopaminergic systems that terminate in the nucleus accumbens has been suggested to occur prior to the full maturation of corticopetal dopaminergic systems. However, converging evidence supports the hypothesis that many aspects of cognitive control are critically linked to cortical noradrenergic systems, that the effectiveness of drugs used to treat disorders of executive function, e.g. ADHD, may result primarily from increases in cortical norepinephrine (NE) and that cortical noradrenergic systems mature across adolescence. However, little attention has been given to the development of this system during adolescence or to its influence in executive function. In the present paper, we discuss the developmental trajectory of the noradrenergic system of the forebrain, highlight the interactions between noradrenergic and dopaminergic systems, and highlight the contribution of the immature corticopetal noradrenergic systems in the ontogeny of several aspects of executive function. Finally we compare data from adolescent rats to those gathered after selective depletion of NE in sub-regions of the prefrontal cortex with an emphasis on the similarities in performance of NE lesioned rats and adolescents. Copyright © 2017 Elsevier Inc. All rights reserved.

Amygdalo-cortical sprouting continues into early adulthood: implications for the development of normal and abnormal function during adolescence.

PubMed

Cunningham, Miles Gregory; Bhattacharyya, Sujoy; Benes, Francine Mary

2002-11-11

Adolescence is a critical stage for the development of emotional maturity and diverse forms of psychopathology. The posterior basolateral nucleus of the amygdala is known to mediate fear and anxiety and is important in assigning emotional valence to cognitive processes. The medial prefrontal cortex, a homologue of the human anterior cingulate cortex, mediates emotional, attentional, and motivational behaviors at the cortical level. We postulate that the development of connectivity between these two corticolimbic regions contributes to an enhanced integration of emotion and cognition during the postnatal period. In order to characterize the development of this relay, injections of the anterograde tracer biocytin were stereotaxically placed within the posterior basolateral nucleus of the amygdala of rats at successive postnatal time points (postnatal days 6-120). Labeled fibers in the medial prefrontal cortex were evaluated using a combination of brightfield, confocal, and electron microscopy. We found that the density of labeled fibers originating from the posterior basolateral nucleus shows a sharp curvilinear increase within layers II and V of the anterior cingulate cortex and the infralimbic subdivisions of medial prefrontal cortex during the late postweanling period. This increase was paralleled by a linear rise in the number of axospinous and axodendritic synapses present in the neuropil. Based on these results, we propose that late maturation of amygdalo-cortical connectivity may provide an anatomical basis for the development and integration of normal and possibly abnormal emotional behavior during adolescence and early adulthood. Copyright 2002 Wiley-Liss, Inc.

Differences between patterns of brain activity associated with semantics and those linked with phonological processing diminish with age.

PubMed

Martins, Ruben; Simard, France; Monchi, Oury

2014-01-01

It is widely believed that language function tends to show little age-related performance decline. Indeed, some older individuals seem to use compensatory mechanisms to maintain a high level of performance when submitted to lexical tasks. However, how these mechanisms affect cortical and subcortical activity during semantic and phonological processing has not been extensively explored. The purpose of this study was to look at the effect of healthy aging on cortico-subcortical routes related to semantic and phonological processing using a lexical analogue of the Wisconsin Cart-Sorting Task. Our results indicate that while young adults tend to show increased activity in the ventrolateral prefrontal cortex, the dorsolateral prefrontal cortex, the fusiform gyrus, the ventral temporal lobe and the caudate nucleus during semantic decisions and in the posterior Broca's area (area 44), the temporal lobe (area 37), the temporoparietal junction (area 40) and the motor cortical regions during phonological decisions, older individuals showed increased activity in the dorsolateral prefrontal cortex and motor cortical regions during both semantic and phonological decisions. Furthermore, when semantic and phonological decisions were contrasted with each other, younger individuals showed significant brain activity differences in several regions while older individuals did not. Therefore, in older individuals, the semantic and phonological routes seem to merge into a single pathway. These findings represent most probably neural reserve/compensation mechanisms, characterized by a decrease in specificity, on which the elderly rely to maintain an adequate level of performance.

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.

Auditory connections and functions of prefrontal cortex

PubMed Central

Plakke, Bethany; Romanski, Lizabeth M.

2014-01-01

The functional auditory system extends from the ears to the frontal lobes with successively more complex functions occurring as one ascends the hierarchy of the nervous system. Several areas of the frontal lobe receive afferents from both early and late auditory processing regions within the temporal lobe. Afferents from the early part of the cortical auditory system, the auditory belt cortex, which are presumed to carry information regarding auditory features of sounds, project to only a few prefrontal regions and are most dense in the ventrolateral prefrontal cortex (VLPFC). In contrast, projections from the parabelt and the rostral superior temporal gyrus (STG) most likely convey more complex information and target a larger, widespread region of the prefrontal cortex. Neuronal responses reflect these anatomical projections as some prefrontal neurons exhibit responses to features in acoustic stimuli, while other neurons display task-related responses. For example, recording studies in non-human primates indicate that VLPFC is responsive to complex sounds including vocalizations and that VLPFC neurons in area 12/47 respond to sounds with similar acoustic morphology. In contrast, neuronal responses during auditory working memory involve a wider region of the prefrontal cortex. In humans, the frontal lobe is involved in auditory detection, discrimination, and working memory. Past research suggests that dorsal and ventral subregions of the prefrontal cortex process different types of information with dorsal cortex processing spatial/visual information and ventral cortex processing non-spatial/auditory information. While this is apparent in the non-human primate and in some neuroimaging studies, most research in humans indicates that specific task conditions, stimuli or previous experience may bias the recruitment of specific prefrontal regions, suggesting a more flexible role for the frontal lobe during auditory cognition. PMID:25100931

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.

Functional and structural neural alterations in Internet gaming disorder: A systematic review and meta-analysis.

PubMed

Yao, Yuan-Wei; Liu, Lu; Ma, Shan-Shan; Shi, Xin-Hui; Zhou, Nan; Zhang, Jin-Tao; Potenza, Marc N

2017-12-01

This meta-analytic study aimed to identify the common and specific neural alterations in Internet gaming disorder (IGD) across different domains and modalities. Two separate meta-analyses for functional neural activation and gray-matter volume were conducted. Sub-meta-analyses for the domains of reward, cold-executive, and hot-executive functions were also performed, respectively. IGD subjects, compared with healthy controls, showed: (1) hyperactivation in the anterior and posterior cingulate cortices, caudate, posterior inferior frontal gyrus (IFG), which were mainly associated with studies measuring reward and cold-executive functions; and, (2) hypoactivation in the anterior IFG in relation to hot-executive function, the posterior insula, somatomotor and somatosensory cortices in relation to reward function. Furthermore, IGD subjects showed reduced gray-matter volume in the anterior cingulate, orbitofrontal, dorsolateral prefrontal, and premotor cortices. These findings suggest that IGD is associated with both functional and structural neural alterations in fronto-striatal and fronto-cingulate regions. Moreover, multi-domain assessments capture different aspects of neural alterations in IGD, which may be helpful for developing effective interventions targeting specific functions. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PKBγ/AKT3 loss-of-function causes learning and memory deficits and deregulation of AKT/mTORC2 signaling: Relevance for schizophrenia

PubMed Central

Floyd, Kirsten; Law, Amanda J.

2017-01-01

Psychiatric genetic studies have identified genome-wide significant loci for schizophrenia. The AKT3/1q44 locus is a principal risk region and gene-network analyses identify AKT3 polymorphisms as a constituent of several neurobiological pathways relevant to psychiatric risk; the neurobiological mechanisms remain unknown. AKT3 shows prenatal enrichment during human neocortical development and recurrent copy number variations involving the 1q43-44 locus are associated with cortical malformations and intellectual disability, implicating an essential role in early brain development. Here, we investigated the role of AKT3 as it relates to aspects of learning and memory and behavioral function, relevant to schizophrenia and cognitive disability, utilizing a novel murine model of Akt3 genetic deficiency. Akt3 heterozygous (Akt3-/+) or null mice (Akt3-/-) were assessed in a comprehensive test battery. Brain biochemical studies were conducted to assess the impact of Akt3 deficiency on cortical Akt/mTOR signaling. Akt3-/+ and Akt3-/- mice exhibited selective deficits of temporal order discrimination and spatial memory, tasks critically dependent on intact prefrontal-hippocampal circuitry, but showed normal prepulse inhibition, fear conditioned learning, memory for novel objects and social function. Akt3 loss-of-function, reduced brain size and dramatically impaired cortical Akt Ser473 activation in an allele-dose dependent manner. Such changes were observed in the absence of altered Akt1 or Akt2 protein expression. Concomitant reduction of the mTORC2 complex proteins, Rictor and Sin1 identifies a potential mechanism. Our findings provide novel insight into the neurodevelopmental role of Akt3, identify a non-redundant role for Akt3 in the development of prefrontal cortical-mediated cognitive function and show that Akt3 is potentially the dominant regulator of AKT/mTOR signaling in brain. PMID:28467426

Infralimbic prefrontal cortex interacts with nucleus accumbens shell to unmask expression of outcome-selective Pavlovian-to-instrumental transfer

PubMed Central

Keistler, Colby; Barker, Jacqueline M.

2015-01-01

Although several studies have examined the subcortical circuitry underlying Pavlovian-to-instrumental transfer (PIT), the role of medial prefrontal cortex in this behavior is largely unknown. Elucidating the cortical contributions to PIT will be key for understanding how reward-paired cues control behavior in both adaptive and maladaptive context (i.e., addiction). Here we use bilateral lesions in a rat model to show that infralimbic prefrontal cortex (ilPFC) is necessary for appropriate expression of PIT. Further, we show that ilPFC mediates this effect via functional connectivity with nucleus accumbens shell (NAcS). Together, these data provide the first demonstration that a specific cortico-striatal circuit is necessary for cue-invigorated reward seeking during specific PIT. PMID:26373829

Early Developmental Disturbances of Cortical Inhibitory Neurons: Contribution to Cognitive Deficits in Schizophrenia

PubMed Central

Volk, David W.; Lewis, David A.

2014-01-01

Cognitive dysfunction is a disabling and core feature of schizophrenia. Cognitive impairments have been linked to disturbances in inhibitory (gamma-aminobutyric acid [GABA]) neurons in the prefrontal cortex. Cognitive deficits are present well before the onset of psychotic symptoms and have been detected in early childhood with developmental delays reported during the first year of life. These data suggest that the pathogenetic process that produces dysfunction of prefrontal GABA neurons in schizophrenia may be related to altered prenatal development. Interestingly, adult postmortem schizophrenia brain tissue studies have provided evidence consistent with a disease process that affects different stages of prenatal development of specific subpopulations of prefrontal GABA neurons. Prenatal ontogeny (ie, birth, proliferation, migration, and phenotypic specification) of distinct subpopulations of cortical GABA neurons is differentially regulated by a host of transcription factors, chemokine receptors, and other molecular markers. In this review article, we propose a strategy to investigate how alterations in the expression of these developmental regulators of subpopulations of cortical GABA neurons may contribute to the pathogenesis of cortical GABA neuron dysfunction and consequently cognitive impairments in schizophrenia. PMID:25053651

Anti-correlated cortical networks of intrinsic connectivity in the rat brain.

PubMed

Schwarz, Adam J; Gass, Natalia; Sartorius, Alexander; Risterucci, Celine; Spedding, Michael; Schenker, Esther; Meyer-Lindenberg, Andreas; Weber-Fahr, Wolfgang

2013-01-01

In humans, resting-state blood oxygen level-dependent (BOLD) signals in the default mode network (DMN) are temporally anti-correlated with those from a lateral cortical network involving the frontal eye fields, secondary somatosensory and posterior insular cortices. Here, we demonstrate the existence of an analogous lateral cortical network in the rat brain, extending laterally from anterior secondary sensorimotor regions to the insular cortex and exhibiting low-frequency BOLD fluctuations that are temporally anti-correlated with a midline "DMN-like" network comprising posterior/anterior cingulate and prefrontal cortices. The primary nexus for this anti-correlation relationship was the anterior secondary motor cortex, close to regions that have been identified with frontal eye fields in the rat brain. The anti-correlation relationship was corroborated after global signal removal, underscoring this finding as a robust property of the functional connectivity signature in the rat brain. These anti-correlated networks demonstrate strong anatomical homology to networks identified in human and monkey connectivity studies, extend the known preserved functional connectivity relationships between rodent and primates, and support the use of resting-state functional magnetic resonance imaging as a translational imaging method between rat models and humans.

Anti-Correlated Cortical Networks of Intrinsic Connectivity in the Rat Brain

PubMed Central

Gass, Natalia; Sartorius, Alexander; Risterucci, Celine; Spedding, Michael; Schenker, Esther; Meyer-Lindenberg, Andreas; Weber-Fahr, Wolfgang

2013-01-01

Abstract In humans, resting-state blood oxygen level-dependent (BOLD) signals in the default mode network (DMN) are temporally anti-correlated with those from a lateral cortical network involving the frontal eye fields, secondary somatosensory and posterior insular cortices. Here, we demonstrate the existence of an analogous lateral cortical network in the rat brain, extending laterally from anterior secondary sensorimotor regions to the insular cortex and exhibiting low-frequency BOLD fluctuations that are temporally anti-correlated with a midline “DMN-like” network comprising posterior/anterior cingulate and prefrontal cortices. The primary nexus for this anti-correlation relationship was the anterior secondary motor cortex, close to regions that have been identified with frontal eye fields in the rat brain. The anti-correlation relationship was corroborated after global signal removal, underscoring this finding as a robust property of the functional connectivity signature in the rat brain. These anti-correlated networks demonstrate strong anatomical homology to networks identified in human and monkey connectivity studies, extend the known preserved functional connectivity relationships between rodent and primates, and support the use of resting-state functional magnetic resonance imaging as a translational imaging method between rat models and humans. PMID:23919836

A chronometric functional sub-network in the thalamo-cortical system regulates the flow of neural information necessary for conscious cognitive processes.

PubMed

León-Domínguez, Umberto; Vela-Bueno, Antonio; Froufé-Torres, Manuel; León-Carrión, Jose

2013-06-01

The thalamo-cortical system has been defined as a neural network associated with consciousness. While there seems to be wide agreement that the thalamo-cortical system directly intervenes in vigilance and arousal, a divergence of opinion persists regarding its intervention in the control of other cognitive processes necessary for consciousness. In the present manuscript, we provide a review of recent scientific findings on the thalamo-cortical system and its role in the control and regulation of the flow of neural information necessary for conscious cognitive processes. We suggest that the axis formed by the medial prefrontal cortex and different thalamic nuclei (reticular nucleus, intralaminar nucleus, and midline nucleus), represents a core component for consciousness. This axis regulates different cerebral structures which allow basic cognitive processes like attention, arousal and memory to emerge. In order to produce a synchronized coherent response, neural communication between cerebral structures must have exact timing (chronometry). Thus, a chronometric functional sub-network within the thalamo-cortical system keeps us in an optimal and continuous functional state, allowing high-order cognitive processes, essential to awareness and qualia, to take place. Copyright © 2013 Elsevier Ltd. All rights reserved.

The What and How of Prefrontal Cortical Organization

PubMed Central

O’Reilly, Randall C.

2010-01-01

How is the prefrontal cortex (PFC) organized such that it is capable of making people more flexible and in control of their behavior? Is there any systematic organization across the many diverse areas that comprise the PFC, or is it uniquely adaptive such that no fixed representation structure can develop? Going against the current tide, this paper argues that there is indeed a systematic organization across PFC areas, with an important functional distinction between ventral and dorsal regions characterized as processing What vs. How information, respectively. This distinction has implications for the rostro-caudal and medial-lateral axes of organization as well. The resulting large-scale functional map of PFC may prove useful in integrating diverse data, and generating novel predictions. PMID:20573407

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

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

PubMed

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

2007-01-01

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

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

PubMed Central

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

2009-01-01

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

Brain substrates of unhealthy versus healthy food choices: influence of homeostatic status and body mass index.

PubMed

Harding, I H; Andrews, Z B; Mata, F; Orlandea, S; Martínez-Zalacaín, I; Soriano-Mas, C; Stice, E; Verdejo-Garcia, A

2018-03-01

Unhealthy dietary choices are a major contributor to harmful weight gain and obesity. This study interrogated the brain substrates of unhealthy versus healthy food choices in vivo, and evaluated the influence of hunger state and body mass index (BMI) on brain activation and connectivity. Thirty adults (BMI: 18-38 kg m -2 ) performed a food-choice task involving preference-based selection between beverage pairs consisting of high-calorie (unhealthy) or low-calorie (healthy) options, concurrent with functional magnetic resonance imaging (fMRI). Selected food stimuli were delivered to participants using an MRI-compatible gustometer. fMRI scans were performed both after 10-h fasting and when sated. Brain activation and hypothalamic functional connectivity were assessed when selecting between unhealthy-healthy beverage pairings, relative to unhealthy-unhealthy and healthy-healthy options. Results were considered significant at cluster-based family-wise error corrected P<0.05. Selecting between unhealthy and healthy foods elicited significant activation in the hypothalamus, the medial and dorsolateral prefrontal cortices, the anterior insula and the posterior cingulate. Hunger was associated with higher activation within the ventromedial and dorsolateral prefrontal cortices, as well as lower connectivity between the hypothalamus and both the ventromedial prefrontal cortex and dorsal striatum. Critically, people with higher BMI showed lower activation of the hypothalamus-regardless of hunger state-and higher activation of the ventromedial prefrontal cortex when hungry. People who are overweight and obese have weaker activation of brain regions involved in energy regulation and greater activation of reward valuation regions while making choices between unhealthy and healthy foods. These results provide evidence for a shift towards hedonic-based, and away from energy-based, food selection in obesity.

Thinking about Eating Food Activates Visual Cortex with Reduced Bilateral Cerebellar Activation in Females with Anorexia Nervosa: An fMRI Study

PubMed Central

Brooks, Samantha J.; O'Daly, Owen; Uher, Rudolf; Friederich, Hans-Christoph; Giampietro, Vincent; Brammer, Michael; Williams, Steven C. R.; Schiöth, Helgi B.; Treasure, Janet; Campbell, Iain C.

2012-01-01

Background Women with anorexia nervosa (AN) have aberrant cognitions about food and altered activity in prefrontal cortical and somatosensory regions to food images. However, differential effects on the brain when thinking about eating food between healthy women and those with AN is unknown. Methods Functional magnetic resonance imaging (fMRI) examined neural activation when 42 women thought about eating the food shown in images: 18 with AN (11 RAN, 7 BPAN) and 24 age-matched controls (HC). Results Group contrasts between HC and AN revealed reduced activation in AN in the bilateral cerebellar vermis, and increased activation in the right visual cortex. Preliminary comparisons between AN subtypes and healthy controls suggest differences in cortical and limbic regions. Conclusions These preliminary data suggest that thinking about eating food shown in images increases visual and prefrontal cortical neural responses in females with AN, which may underlie cognitive biases towards food stimuli and ruminations about controlling food intake. Future studies are needed to explicitly test how thinking about eating activates restraint cognitions, specifically in those with restricting vs. binge-purging AN subtypes. PMID:22479499

Convergent dysregulation of frontal cortical cognitive and reward systems in eating disorders.

PubMed

Stefano, George B; Ptáček, Radek; Kuželová, Hana; Mantione, Kirk J; Raboch, Jiří; Papezova, Hana; Kream, Richard M

2013-05-10

A substantive literature has drawn a compelling case for the functional involvement of mesolimbic/prefrontal cortical neural reward systems in normative control of eating and in the etiology and persistence of severe eating disorders that affect diverse human populations. Presently, we provide a short review that develops an equally compelling case for the importance of dysregulated frontal cortical cognitive neural networks acting in concert with regional reward systems in the regulation of complex eating behaviors and in the presentation of complex pathophysiological symptoms associated with major eating disorders. Our goal is to highlight working models of major eating disorders that incorporate complementary approaches to elucidate functionally interactive neural circuits defined by their regulatory neurochemical phenotypes. Importantly, we also review evidence-based linkages between widely studied psychiatric and neurodegenerative syndromes (e.g., autism spectrum disorders and Parkinson's disease) and co-morbid eating disorders to elucidate basic mechanisms involving dopaminergic transmission and its regulation by endogenously expressed morphine in these same cortical regions.

Neural Correlates of Feigned Memory Impairment are Distinguishable from Answering Randomly and Answering Incorrectly: An fMRI and Behavioral Study

ERIC Educational Resources Information Center

Liang, Chun-Yu; Xu, Zhi-Yuan; Mei, Wei; Wang, Li-Li; Xue, Li; Lu, De Jian; Zhao, Hu

2012-01-01

Previous functional magnetic resonance imaging (fMRI) studies have identified activation in the prefrontal-parietal-sub-cortical circuit during feigned memory impairment when comparing with truthful telling. Here, we used fMRI to determine whether neural activity can differentiate between answering correctly, answering randomly, answering…

Neurobiological Circuits Regulating Attention, Cognitive Control, Motivation, and Emotion: Disruptions in Neurodevelopmental Psychiatric Disorders

ERIC Educational Resources Information Center

Arnsten, Amy F. T.; Rubia, Katya

2012-01-01

Objective: This article aims to review basic and clinical studies outlining the roles of prefrontal cortical (PFC) networks in the behavior and cognitive functions that are compromised in childhood neurodevelopmental disorders and how these map into the neuroimaging evidence of circuit abnormalities in these disorders. Method: Studies of animals,…

Bilateral Epidural Prefrontal Cortical Stimulation for Treatment-Resistant Depression

PubMed Central

Nahas, Ziad; Anderson, Berry S.; Borckardt, Jeff; Arana, Ashley B.; George, Mark S.; Reeves, Scott T.; Takacs, Istvan

2010-01-01

Background Treatment-resistant depression presents a serious challenge to both patients and clinicians. The anterior and midlateral prefrontal cortices play complementary roles in integrating emotional and cognitive experiences and in modulating subcortical regions. Both regions offer a distinct opportunity for targeted antidepressant treatments. We chose to pilot the safety and therapeutic benefits of chronic and intermittent epidural prefrontal cortical stimulation (EpCS) in patients with treatment-resistant depression. Methods We enrolled five adults with an average of 5.8 failed antidepressant treatments in their current depressive episode. All subjects underwent comprehensive clinical assessments, detailed neuropsychological testing, and presurgical magnetic resonance imaging. Four cortical stimulation paddle leads were stereotactically placed bilaterally over the anterior frontal poles and midlateral prefrontal cortex. We also acquired a postsurgical computed tomography scan and repeatedly assessed clinical outcomes over time of EpCS as an adjunctive treatment to constant medications. Results All patients tolerated the therapy. At 7-month follow-up, the average improvement from preimplant baseline on the Hamilton Rating Scale for Depression and the Inventory of Depressive Symptoms—Self-Report were 54.9% (± 37.7) and 60.1% (± 34.1), respectively. Three implanted subjects reached remission. One patient's left hemisphere leads were explanted 12 weeks postsurgery because of a scalp infection. Conclusions Bilateral EpCS over anterior and midlateral frontal cortex is a promising new technology for treatment-resistant depression. Future double-blind studies are warranted. PMID:19819427

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

From sensorimotor learning to memory cells in prefrontal and temporal association cortex: a neurocomputational study of disembodiment.

PubMed

Pulvermüller, Friedemann; Garagnani, Max

2014-08-01

Memory cells, the ultimate neurobiological substrates of working memory, remain active for several seconds and are most commonly found in prefrontal cortex and higher multisensory areas. However, if correlated activity in "embodied" sensorimotor systems underlies the formation of memory traces, why should memory cells emerge in areas distant from their antecedent activations in sensorimotor areas, thus leading to "disembodiment" (movement away from sensorimotor systems) of memory mechanisms? We modelled the formation of memory circuits in six-area neurocomputational architectures, implementing motor and sensory primary, secondary and higher association areas in frontotemporal cortices along with known between-area neuroanatomical connections. Sensorimotor learning driven by Hebbian neuroplasticity led to formation of cell assemblies distributed across the different areas of the network. These action-perception circuits (APCs) ignited fully when stimulated, thus providing a neural basis for long-term memory (LTM) of sensorimotor information linked by learning. Subsequent to ignition, activity vanished rapidly from APC neurons in sensorimotor areas but persisted in those in multimodal prefrontal and temporal areas. Such persistent activity provides a mechanism for working memory for actions, perceptions and symbols, including short-term phonological and semantic storage. Cell assembly ignition and "disembodied" working memory retreat of activity to multimodal areas are documented in the neurocomputational models' activity dynamics, at the level of single cells, circuits, and cortical areas. Memory disembodiment is explained neuromechanistically by APC formation and structural neuroanatomical features of the model networks, especially the central role of multimodal prefrontal and temporal cortices in bridging between sensory and motor areas. These simulations answer the "where" question of cortical working memory in terms of distributed APCs and their inner structure, which is, in part, determined by neuroanatomical structure. As the neurocomputational model provides a mechanistic explanation of how memory-related "disembodied" neuronal activity emerges in "embodied" APCs, it may be key to solving aspects of the embodiment debate and eventually to a better understanding of cognitive brain functions. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Reconfiguration of Intrinsic Functional Coupling Patterns Following Circumscribed Network Lesions.

PubMed

Eldaief, Mark C; McMains, Stephanie; Hutchison, R Matthew; Halko, Mark A; Pascual-Leone, Alvaro

2017-05-01

Communication between cortical regions is necessary for optimal cognitive processing. Functional relationships between cortical regions can be inferred through measurements of temporal synchrony in spontaneous activity patterns. These relationships can be further elaborated by surveying effects of cortical lesions upon inter-regional connectivity. Lesions to cortical hubs and heteromodal association regions are expected to induce distributed connectivity changes and higher-order cognitive deficits, yet their functional consequences remain relatively unexplored. Here, we used resting-state fMRI to investigate intrinsic functional connectivity (FC) and graph theoretical metrics in 12 patients with circumscribed lesions of the medial prefrontal cortex (mPFC) portion of the Default Network (DN), and compared these metrics with those observed in healthy matched comparison participants and a sample of 1139 healthy individuals. Despite significant mPFC destruction, patients did not demonstrate weakened intrinsic FC among undamaged DN nodes. Instead, network-specific changes were manifested as weaker negative correlations between the DN and attentional and somatomotor networks. These findings conflict with the DN being a homogenous system functionally anchored at mPFC. Rather, they implicate a role for mPFC in mediating cross-network functional interactions. More broadly, our data suggest that lesions to association cortical hubs might induce clinical deficits by disrupting communication between interacting large-scale systems. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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

Parallel trends in cortical gray and white matter architecture and connections in primates allow fine study of pathways in humans and reveal network disruptions in autism

PubMed Central

García-Cabezas, Miguel Ángel; Barbas, Helen

2018-01-01

Noninvasive imaging and tractography methods have yielded information on broad communication networks but lack resolution to delineate intralaminar cortical and subcortical pathways in humans. An important unanswered question is whether we can use the wealth of precise information on pathways from monkeys to understand connections in humans. We addressed this question within a theoretical framework of systematic cortical variation and used identical high-resolution methods to compare the architecture of cortical gray matter and the white matter beneath, which gives rise to short- and long-distance pathways in humans and rhesus monkeys. We used the prefrontal cortex as a model system because of its key role in attention, emotions, and executive function, which are processes often affected in brain diseases. We found striking parallels and consistent trends in the gray and white matter architecture in humans and monkeys and between the architecture and actual connections mapped with neural tracers in rhesus monkeys and, by extension, in humans. Using the novel architectonic portrait as a base, we found significant changes in pathways between nearby prefrontal and distant areas in autism. Our findings reveal that a theoretical framework allows study of normal neural communication in humans at high resolution and specific disruptions in diverse psychiatric and neurodegenerative diseases. PMID:29401206

Adolescent brain development in normality and psychopathology

PubMed Central

LUCIANA, MONICA

2014-01-01

Since this journal’s inception, the field of adolescent brain development has flourished, as researchers have investigated the underpinnings of adolescent risk-taking behaviors. Explanations based on translational models initially attributed such behaviors to executive control deficiencies and poor frontal lobe function. This conclusion was bolstered by evidence that the prefrontal cortex and its interconnections are among the last brain regions to structurally and functionally mature. As substantial heterogeneity of prefrontal function was revealed, applications of neuroeconomic theory to adolescent development led to dual systems models of behavior. Current epidemiological trends, behavioral observations, and functional magnetic resonance imaging based brain activity patterns suggest a quadratic increase in limbically mediated incentive motivation from childhood to adolescence and a decline thereafter. This elevation occurs in the context of immature prefrontal function, so motivational strivings may be difficult to regulate. Theoretical models explain this patterning through brain-based accounts of subcortical–cortical integration, puberty-based models of adolescent sensation seeking, and neurochemical dynamics. Empirically sound tests of these mechanisms, as well as investigations of biology–context interactions, represent the field’s most challenging future goals, so that applications to psychopathology can be refined and so that developmental cascades that incorporate neurobiological variables can be modeled. PMID:24342843

Adolescent brain development in normality and psychopathology.

PubMed

Luciana, Monica

2013-11-01

Since this journal's inception, the field of adolescent brain development has flourished, as researchers have investigated the underpinnings of adolescent risk-taking behaviors. Explanations based on translational models initially attributed such behaviors to executive control deficiencies and poor frontal lobe function. This conclusion was bolstered by evidence that the prefrontal cortex and its interconnections are among the last brain regions to structurally and functionally mature. As substantial heterogeneity of prefrontal function was revealed, applications of neuroeconomic theory to adolescent development led to dual systems models of behavior. Current epidemiological trends, behavioral observations, and functional magnetic resonance imaging based brain activity patterns suggest a quadratic increase in limbically mediated incentive motivation from childhood to adolescence and a decline thereafter. This elevation occurs in the context of immature prefrontal function, so motivational strivings may be difficult to regulate. Theoretical models explain this patterning through brain-based accounts of subcortical-cortical integration, puberty-based models of adolescent sensation seeking, and neurochemical dynamics. Empirically sound tests of these mechanisms, as well as investigations of biology-context interactions, represent the field's most challenging future goals, so that applications to psychopathology can be refined and so that developmental cascades that incorporate neurobiological variables can be modeled.

Separate neural mechanisms underlie choices and strategic preferences in risky decision making.

PubMed

Venkatraman, Vinod; Payne, John W; Bettman, James R; Luce, Mary Frances; Huettel, Scott A

2009-05-28

Adaptive decision making in real-world contexts often relies on strategic simplifications of decision problems. Yet, the neural mechanisms that shape these strategies and their implementation remain largely unknown. Using an economic decision-making task, we dissociate brain regions that predict specific choices from those predicting an individual's preferred strategy. Choices that maximized gains or minimized losses were predicted by functional magnetic resonance imaging activation in ventromedial prefrontal cortex or anterior insula, respectively. However, choices that followed a simplifying strategy (i.e., attending to overall probability of winning) were associated with activation in parietal and lateral prefrontal cortices. Dorsomedial prefrontal cortex, through differential functional connectivity with parietal and insular cortex, predicted individual variability in strategic preferences. Finally, we demonstrate that robust decision strategies follow from neural sensitivity to rewards. We conclude that decision making reflects more than compensatory interaction of choice-related regions; in addition, specific brain systems potentiate choices depending on strategies, traits, and context.

Similar patterns of neural activity predict memory function during encoding and retrieval.

PubMed

Kragel, James E; Ezzyat, Youssef; Sperling, Michael R; Gorniak, Richard; Worrell, Gregory A; Berry, Brent M; Inman, Cory; Lin, Jui-Jui; Davis, Kathryn A; Das, Sandhitsu R; Stein, Joel M; Jobst, Barbara C; Zaghloul, Kareem A; Sheth, Sameer A; Rizzuto, Daniel S; Kahana, Michael J

2017-07-15

Neural networks that span the medial temporal lobe (MTL), prefrontal cortex, and posterior cortical regions are essential to episodic memory function in humans. Encoding and retrieval are supported by the engagement of both distinct neural pathways across the cortex and common structures within the medial temporal lobes. However, the degree to which memory performance can be determined by neural processing that is common to encoding and retrieval remains to be determined. To identify neural signatures of successful memory function, we administered a delayed free-recall task to 187 neurosurgical patients implanted with subdural or intraparenchymal depth electrodes. We developed multivariate classifiers to identify patterns of spectral power across the brain that independently predicted successful episodic encoding and retrieval. During encoding and retrieval, patterns of increased high frequency activity in prefrontal, MTL, and inferior parietal cortices, accompanied by widespread decreases in low frequency power across the brain predicted successful memory function. Using a cross-decoding approach, we demonstrate the ability to predict memory function across distinct phases of the free-recall task. Furthermore, we demonstrate that classifiers that combine information from both encoding and retrieval states can outperform task-independent models. These findings suggest that the engagement of a core memory network during either encoding or retrieval shapes the ability to remember the past, despite distinct neural interactions that facilitate encoding and retrieval. Copyright © 2017 Elsevier Inc. All rights reserved.

Neural Circuitry of Impaired Emotion Regulation in Substance Use Disorders.

PubMed

Wilcox, Claire E; Pommy, Jessica M; Adinoff, Bryon

2016-04-01

Impaired emotion regulation contributes to the development and severity of substance use disorders (substance disorders). This review summarizes the literature on alterations in emotion regulation neural circuitry in substance disorders, particularly in relation to disorders of negative affect (without substance disorder), and it presents promising areas of future research. Emotion regulation paradigms during functional magnetic resonance imaging are conceptualized into four dimensions: affect intensity and reactivity, affective modulation, cognitive modulation, and behavioral control. The neural circuitry associated with impaired emotion regulation is compared in individuals with and without substance disorders, with a focus on amygdala, insula, and prefrontal cortex activation and their functional and structural connectivity. Hypoactivation of the rostral anterior cingulate cortex/ventromedial prefrontal cortex (rACC/vmPFC) is the most consistent finding across studies, dimensions, and clinical populations (individuals with and without substance disorders). The same pattern is evident for regions in the cognitive control network (anterior cingulate and dorsal and ventrolateral prefrontal cortices) during cognitive modulation and behavioral control. These congruent findings are possibly related to attenuated functional and/or structural connectivity between the amygdala and insula and between the rACC/vmPFC and cognitive control network. Although increased amygdala and insula activation is associated with impaired emotion regulation in individuals without substance disorders, it is not consistently observed in substance disorders. Emotion regulation disturbances in substance disorders may therefore stem from impairments in prefrontal functioning, rather than excessive reactivity to emotional stimuli. Treatments for emotion regulation in individuals without substance disorders that normalize prefrontal functioning may offer greater efficacy for substance disorders than treatments that dampen reactivity.

Neural Circuitry of Impaired Emotion Regulation in Substance Use Disorders

PubMed Central

Wilcox, Claire E.; Pommy, Jessica M.; Adinoff, Bryon

2016-01-01

Impaired emotion regulation contributes to the development and severity of substance use disorders (substance disorders). This review summarizes the literature on alterations in emotion regulation neural circuitry in substance disorders, particularly in relation to disorders of negative affect (without substance disorder), and it presents promising areas of future research. Emotion regulation paradigms during functional magnetic resonance imaging are conceptualized into four dimensions: affect intensity and reactivity, affective modulation, cognitive modulation, and behavioral control. The neural circuitry associated with impaired emotion regulation is compared in individuals with and without substance disorders, with a focus on amygdala, insula, and prefrontal cortex activation and their functional and structural connectivity. Hypoactivation of the rostral anterior cingulate cortex/ventromedial prefrontal cortex (rACC/vmPFC) is the most consistent finding across studies, dimensions, and clinical populations (individuals with and without substance disorders). The same pattern is evident for regions in the cognitive control network (anterior cingulate and dorsal and ventrolateral prefrontal cortices) during cognitive modulation and behavioral control. These congruent findings are possibly related to attenuated functional and/or structural connectivity between the amygdala and insula and between the rACC/vmPFC and cognitive control network. Although increased amygdala and insula activation is associated with impaired emotion regulation in individuals without substance disorders, it is not consistently observed in substance disorders. Emotion regulation disturbances in substance disorders may therefore stem from impairments in prefrontal functioning, rather than excessive reactivity to emotional stimuli. Treatments for emotion regulation in individuals without substance disorders that normalize prefrontal functioning may offer greater efficacy for substance disorders than treatments that dampen reactivity. PMID:26771738

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.

The neural basis of metacognitive ability

PubMed Central

Fleming, Stephen M.; Dolan, Raymond J.

2012-01-01

Ability in various cognitive domains is often assessed by measuring task performance, such as the accuracy of a perceptual categorization. A similar analysis can be applied to metacognitive reports about a task to quantify the degree to which an individual is aware of his or her success or failure. Here, we review the psychological and neural underpinnings of metacognitive accuracy, drawing on research in memory and decision-making. These data show that metacognitive accuracy is dissociable from task performance and varies across individuals. Convergent evidence indicates that the function of the rostral and dorsal aspect of the lateral prefrontal cortex (PFC) is important for the accuracy of retrospective judgements of performance. In contrast, prospective judgements of performance may depend upon medial PFC. We close with a discussion of how metacognitive processes relate to concepts of cognitive control, and propose a neural synthesis in which dorsolateral and anterior prefrontal cortical subregions interact with interoceptive cortices (cingulate and insula) to promote accurate judgements of performance. PMID:22492751

Meditation experience is associated with differences in default mode network activity and connectivity

PubMed Central

Brewer, Judson A.; Worhunsky, Patrick D.; Gray, Jeremy R.; Tang, Yi-Yuan; Weber, Jochen; Kober, Hedy

2011-01-01

Many philosophical and contemplative traditions teach that “living in the moment” increases happiness. However, the default mode of humans appears to be that of mind-wandering, which correlates with unhappiness, and with activation in a network of brain areas associated with self-referential processing. We investigated brain activity in experienced meditators and matched meditation-naive controls as they performed several different meditations (Concentration, Loving-Kindness, Choiceless Awareness). We found that the main nodes of the default-mode network (medial prefrontal and posterior cingulate cortices) were relatively deactivated in experienced meditators across all meditation types. Furthermore, functional connectivity analysis revealed stronger coupling in experienced meditators between the posterior cingulate, dorsal anterior cingulate, and dorsolateral prefrontal cortices (regions previously implicated in self-monitoring and cognitive control), both at baseline and during meditation. Our findings demonstrate differences in the default-mode network that are consistent with decreased mind-wandering. As such, these provide a unique understanding of possible neural mechanisms of meditation. PMID:22114193

Probing the frontostriatal loops involved in executive and limbic processing via interleaved TMS and functional MRI at two prefrontal locations: a pilot study.

PubMed

Hanlon, Colleen A; Canterberry, Melanie; Taylor, Joseph J; DeVries, William; Li, Xingbao; Brown, Truman R; George, Mark S

2013-01-01

The prefrontal cortex (PFC) is an anatomically and functionally heterogeneous area which influences cognitive and limbic processing through connectivity to subcortical targets. As proposed by Alexander et al. (1986) the lateral and medial aspects of the PFC project to distinct areas of the striatum in parallel but functionally distinct circuits. The purpose of this preliminary study was to determine if we could differentially and consistently activate these lateral and medial cortical-subcortical circuits involved in executive and limbic processing though interleaved transcranial magnetic stimulation (TMS) in the MR environment. Seventeen healthy individuals received interleaved TMS-BOLD imaging with the coil positioned over the dorsolateral (EEG: F3) and ventromedial PFC (EEG: FP1). BOLD signal change was calculated in the areas directly stimulated by the coil and in subcortical regions with afferent and efferent connectivity to the TMS target areas. Additionally, five individuals were tested on two occasions to determine test-retest reliability. Region of interest analysis revealed that TMS at both prefrontal sites led to significant BOLD signal increases in the cortex under the coil, in the striatum, and the thalamus, but not in the visual cortex (negative control region). There was a significantly larger BOLD signal change in the caudate following medial PFC TMS, relative to lateral TMS. The hippocampus in contrast was significantly more activated by lateral TMS. Post-hoc voxel-based analysis revealed that within the caudate the location of peak activity was in the ventral caudate following medial TMS and the dorsal caudate following lateral TMS. Test-retest reliability data revealed consistent BOLD responses to TMS within each individual but a large variation between individuals. These data demonstrate that, through an optimized TMS/BOLD sequence over two unique prefrontal targets, it is possible to selectively interrogate the patency of these established cortical-subcortical networks in healthy individuals, and potentially patient populations.

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

Periadolescent exposure to the NMDA antagonist MK-801 impairs the functional maturation of local GABAergic circuits in the adult prefrontal cortex

PubMed Central

Thomases, Daniel R.; Cass, Daryn K.; Tseng, Kuei Y.

2012-01-01

A developmental disruption of prefrontal cortical (PFC) inhibitory circuits is thought to contribute to the adolescent onset of cognitive deficits observed in schizophrenia. However, the developmental mechanisms underlying such a disruption remain elusive. The goal of this study is to examine how repeated exposure to the NMDA receptor antagonist dizocilpine maleate (MK-801) during periadolescence (from postnatal days -PD- 35-40) impacts the normative development of local prefrontal network response in rats. In vivo electrophysiological analyses revealed that MK-801 administration during periadolescence elicits an enduring disinhibited prefrontal local field potential response to ventral hippocampal stimulation at 20Hz (beta) and 40Hz (gamma) in adulthood (PD65-85). Such a disinhibition was not observed when MK-801 was given during adulthood, indicating that the periadolescent transition is indeed a sensitive period for the functional maturation of prefrontal inhibitory control. Accordingly, the pattern of prefrontal local field potential disinhibition induced by periadolescent MK-801 treatment resembles that observed in the normal PD30-40 PFC. Further pharmacological manipulations revealed that these developmentally immature prefrontal responses can be mimicked by single microinfusion of the GABA-A receptor antagonist picrotoxin into the normal adult PFC. Importantly, acute administration of the GABA-A positive allosteric modulator Indiplon into the PFC reversed the prefrontal disinhibitory state induced by periadolescent MK-801 to normal levels. Together, these results indicate a critical role of NMDA receptors in regulating the periadolescent maturation of GABAergic networks in the PFC, and that pharmacologically-induced augmentation of local GABA-A receptor-mediated transmission is sufficient to overcome the disinhibitory prefrontal state associated with the periadolescent MK-801 exposure. PMID:23283319

Contrasting Patterns of Cortical Input to Architectural Subdivisions of the Area 8 Complex: A Retrograde Tracing Study in Marmoset Monkeys

PubMed Central

Reser, David H.; Burman, Kathleen J.; Yu, Hsin-Hao; Chaplin, Tristan A.; Richardson, Karyn E.; Worthy, Katrina H.; Rosa, Marcello G.P.

2013-01-01

Contemporary studies recognize 3 distinct cytoarchitectural and functional areas within the Brodmann area 8 complex, in the caudal prefrontal cortex: 8b, 8aD, and 8aV. Here, we report on the quantitative characteristics of the cortical projections to these areas, using injections of fluorescent tracers in marmoset monkeys. Area 8b was distinct from both 8aD and 8aV due to its connections with medial prefrontal, anterior cingulate, superior temporal polysensory, and ventral midline/retrosplenial areas. In contrast, areas 8aD and 8aV received the bulk of the projections from posterior parietal cortex and dorsal midline areas. In the frontal lobe, area 8aV received projections primarily from ventrolateral areas, while both 8aD and 8b received dense inputs from areas on the dorsolateral surface. Whereas area 8aD received the most significant auditory projections, these were relatively sparse, in comparison with those previously reported in macaques. Finally, area 8aV was distinct from both 8aD and 8b by virtue of its widespread input from the extrastriate visual areas. These results are compatible with a homologous organization of the prefrontal cortex in New and Old World monkeys, and suggest significant parallels between the present pathways, revealed by tract-tracing, and networks revealed by functional connectivity analysis in Old World monkeys and humans. PMID:22735155

Altered brain processing of decision-making in healthy first-degree biological relatives of suicide completers.

PubMed

Ding, Y; Pereira, F; Hoehne, A; Beaulieu, M-M; Lepage, M; Turecki, G; Jollant, F

2017-08-01

Suicidal behavior is heritable, with the transmission of risk being related to the transmission of vulnerability traits. Previous studies suggest that risky decision-making may be an endophenotype of suicide. Here, we aimed at investigating brain processing of decision-making in relatives of suicide completers in order to shed light on heritable mechanisms of suicidal vulnerability. Seventeen healthy first-degree biological relatives of suicide completers with no personal history of suicidal behavior, 16 relatives of depressed patients without any personal or family history of suicidal behavior, and 19 healthy controls were recruited. Functional 3 T magnetic resonance imaging scans were acquired while participants underwent the Iowa Gambling Task, an economic decision-making test. Whole-brain analyses contrasting activations during risky vs safe choices were conducted with AFNI and FSL. Individuals with a family history of suicide in comparison to control groups showed altered contrasts in left medial orbitofrontal cortex, and right dorsomedial prefrontal cortex. This pattern was different from the neural basis of familial depression. Moreover, controls in comparison to relatives showed increased contrast in several regions including the post-central gyrus, posterior cingulate and parietal cortices, and cerebellum (culmen) in familial suicide; and inferior parietal, temporal, occipital, anteromedial and dorsolateral prefrontal cortices, and cerebellum (vermis) in familial depression. These findings most likely represent a complex combination of vulnerability and protective mechanisms in relatives. They also support a significant role for deficient risk processing, and ventral and dorsal prefrontal cortex functioning in the suicidal diathesis.

Development of thalamocortical connections between the mediodorsal thalamus and the prefrontal cortex and its implication in cognition

PubMed Central

Ferguson, Brielle R.; Gao, Wen-Jun

2015-01-01

The mediodorsal thalamus (MD) represents a fundamental subcortical relay to the prefrontal cortex (PFC), and is thought to be highly implicated in modulation of cognitive performance. Additionally, it undergoes highly conserved developmental stages, which, when dysregulated, can have detrimental consequences. Embryonically, the MD experiences a tremendous surge in neurogenesis and differentiation, and disruption of this process may underlie the pathology in certain neurodevelopmental disorders. However, during the postnatal period, a vast amount of cell loss in the MD occurs. These together may represent an extended critical period for postnatal development, in which disturbances in the normal growth or reduction of the MD afferents to the PFC, can result in PFC-dependent cognitive, affective, or psychotic abnormalities. In this review, we explore the current knowledge supporting this hypothesis of a protracted critical period, and propose how developmental changes in the MD contribute to successful prefrontal cortical development and function. Specifically, we elaborate on the unique properties of MD-PFC connections compared with other thalamocortical afferents in sensory cortices, examine how MD-PFC innervation modulates synaptic transmission in the local prefrontal circuitry, and speculate on what occurs during postnatal development, particularly within the early neonatal stage, as well as juvenile and adolescent periods. Finally, we discuss the questions that remain and propose future experiments in order to provide perspective and novel insights into the cause of neuropsychiatric disorders associated with MD-PFC development. PMID:25620923

[Schizophrenia and cortical GABA neurotransmission].

PubMed

Hashimoto, Takanori; Matsubara, Takuro; Lewis, David A

2010-01-01

Individuals with schizophrenia show disturbances in a number of brain functions that regulate cognitive, affective, motor, and sensory processing. The cognitive deficits associated with dysfunction of the dorsolateral prefrontal cortex result, at least in part, from abnormalities in GABA neurotransmission, as reflected in a specific pattern of altered expression of GABA-related molecules. First, mRNA levels for the 67-kilodalton isoform of glutamic acid decarboxylase (GAD67), an enzyme principally responsible for GABA synthesis, and the GABA membrane transporter GAT1, which regulates the reuptake of synaptically released GABA, are decreased in a subset of GABA neurons. Second, affected GABA neurons include those that express the calcium-binding protein parvalbumin (PV), because PV mRNA levels are decreased in the prefrontal cortex of subjects with schizophrenia and GAD67 mRNA is undetectable in almost half of PV-containing neurons. These changes are accompanied by decreased GAT1 expression in the presynaptic terminals of PV-containing neurons and by increased postsynaptic GABA-A receptor alpha2 subunit expression at the axon initial segments of pyramidal neurons. These findings indicate decreased GABA synthesis/release by PV-containing GABA neurons and compensatory changes at synapses formed by these neurons. Third, another subset of GABA neurons that express the neuropeptide somatostatin (SST) also appear to be affected because their specific markers, SST and neuropeptide Y mRNAs, are decreased in a manner highly correlated with the decreases in GAD67 mRNA. Finally, mRNA levels for GABA-A receptor subunits for synaptic (alpha1 and gamma2) and extra-synaptic (delta) receptors are decreased, indicating alterations in both synaptic and extra-synaptic GABA neurotransmission. Together, this pattern of changes indicates that the altered GABA neurotransmission is specific to PV-containing and SST-containing GABA neuron subsets and involves both synaptic and extra-synaptic GABA-A receptors. Our recent analyses demonstrated that this pattern exists across diverse cortical areas including the prefrontal, anterior cingulate, primary motor, and primary visual cortices. GABA neurotransmission by PV-containing and SST-containing neurons is important for the generation of cortical oscillatory activities in the gamma (30-100 Hz) and theta (4-7 Hz) bands, respectively. These oscillatory activities have been proposed to play critical roles in regulating the efficiency of information transfer between neurons and neuronal networks in the cortex. Altered cortical GABA neurotransmission appears to contribute to disturbances in diverse functions through affecting the generation of cortical oscillations in schizophrenia.

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

PubMed Central

Hofstetter, Christoph; Vuilleumier, Patrik

2014-01-01

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

Ventromedial prefrontal cortex supports affective future simulation by integrating distributed knowledge

PubMed Central

Benoit, Roland G.; Szpunar, Karl K.; Schacter, Daniel L.

2014-01-01

Although the future often seems intangible, we can make it more concrete by imagining prospective events. Here, using functional MRI, we demonstrate a mechanism by which the ventromedial prefrontal cortex supports such episodic simulations, and thereby contributes to affective foresight: This region supports processes that (i) integrate knowledge related to the elements that constitute an episode and (ii) represent the episode’s emergent affective quality. The ventromedial prefrontal cortex achieves such integration via interactions with distributed cortical regions that process the individual elements. Its activation then signals the affective quality of the ensuing episode, which goes beyond the combined affective quality of its constituting elements. The integrative process further augments long-term retention of the episode, making it available at later time points. This mechanism thus renders the future tangible, providing a basis for farsighted behavior. PMID:25368170

Ventromedial prefrontal cortex supports affective future simulation by integrating distributed knowledge.

PubMed

Benoit, Roland G; Szpunar, Karl K; Schacter, Daniel L

2014-11-18

Although the future often seems intangible, we can make it more concrete by imagining prospective events. Here, using functional MRI, we demonstrate a mechanism by which the ventromedial prefrontal cortex supports such episodic simulations, and thereby contributes to affective foresight: This region supports processes that (i) integrate knowledge related to the elements that constitute an episode and (ii) represent the episode's emergent affective quality. The ventromedial prefrontal cortex achieves such integration via interactions with distributed cortical regions that process the individual elements. Its activation then signals the affective quality of the ensuing episode, which goes beyond the combined affective quality of its constituting elements. The integrative process further augments long-term retention of the episode, making it available at later time points. This mechanism thus renders the future tangible, providing a basis for farsighted behavior.

Lateral prefrontal activity as a compensatory strategy for deficits of cortical processing in Attention Deficit Hyperactivity Disorder.

PubMed

Zamorano, Francisco; Billeke, Pablo; Kausel, Leonie; Larrain, Josefina; Stecher, Ximena; Hurtado, Jose M; López, Vladimir; Carrasco, Ximena; Aboitiz, Francisco

2017-08-03

Attention Deficit Hyperactivity Disorder (ADHD) is the most common neuropsychiatric disorder in childhood and is characterized by a delay of cortical maturation in frontal regions. In order to investigate interference control, which is a key function of frontal areas, a functional MRI study was conducted on 17 ADHD boys and 17 typically developing (TD) boys, while solving the multi source interference task (MSIT). This task consists of two conditions, a "congruent condition" and an "incongruent condition". The latter requires to inhibit information that interferes with task-relevant stimuli. Behavioral results showed that ADHD subjects committed more errors than TD children. In addition, TD children presented a larger MSIT effect -a greater difference in reaction times between the incongruent and the congruent conditions- than ADHD children. Associated to the MSIT effect, neuroimaging results showed a significant enhancement in the activation of the right lateral prefrontal cortex (rlPFC) in ADHD than in TD subjects. Finally, ADHD subjects presented greater functional connectivity between rlPFC and bilateral orbitofrontal cortex than the TD group. This difference in connectivity correlated with worse performance in both groups. Our results could reflect a compensatory strategy of ADHD children resulting from their effort to maintain an adequate performance during MSIT.

Thalamo-Cortical Disruption Contributes to Short-Term Memory Deficits in Patients with Medial Temporal Lobe Damage.

PubMed

Voets, Natalie L; Menke, Ricarda A L; Jbabdi, Saad; Husain, Masud; Stacey, Richard; Carpenter, Katherine; Adcock, Jane E

2015-11-01

Short-term (STM) and long-term memory (LTM) have largely been considered as separate brain systems reflecting fronto-parietal and medial temporal lobe (MTL) functions, respectively. This functional dichotomy has been called into question by evidence of deficits on aspects of working memory in patients with MTL damage, suggesting a potentially direct hippocampal contribution to STM. As the hippocampus has direct anatomical connections with the thalamus, we tested the hypothesis that damage to thalamic nuclei regulating cortico-cortical interactions may contribute to STM deficits in patients with hippocampal dysfunction. We used diffusion-weighted magnetic resonance imaging-based tractography to identify anatomical subdivisions in patients with MTL epilepsy. From these, we measured resting-state functional connectivity with detailed cortical divisions of the frontal, temporal, and parietal lobes. Whereas thalamo-temporal functional connectivity reflected LTM performance, thalamo-prefrontal functional connectivity specifically predicted STM performance. Notably, patients with hippocampal volume loss showed thalamic volume loss, most prominent in the pulvinar region, not detected in patients with normal hippocampal volumes. Aberrant thalamo-cortical connectivity in the epileptic hemisphere was mirrored in a loss of behavioral association with STM performance specifically in patients with hippocampal atrophy. These findings identify thalamo-cortical disruption as a potential mechanism contributing to STM deficits in the context of MTL damage. © The Author 2015. Published by Oxford University Press.

Selective deficit in personal moral judgment following damage to ventromedial prefrontal cortex.

PubMed

Ciaramelli, Elisa; Muccioli, Michela; Làdavas, Elisabetta; di Pellegrino, Giuseppe

2007-06-01

Recent fMRI evidence has detected increased medial prefrontal activation during contemplation of personal moral dilemmas compared to impersonal ones, which suggests that this cortical region plays a role in personal moral judgment. However, functional imaging results cannot definitively establish that a brain area is necessary for a particular cognitive process. This requires evidence from lesion techniques, such as studies of human patients with focal brain damage. Here, we tested 7 patients with lesions in the ventromedial prefrontal cortex and 12 healthy individuals in personal moral dilemmas, impersonal moral dilemmas and non-moral dilemmas. Compared to normal controls, patients were more willing to judge personal moral violations as acceptable behaviors in personal moral dilemmas, and they did so more quickly. In contrast, their performance in impersonal and non-moral dilemmas was comparable to that of controls. These results indicate that the ventromedial prefrontal cortex is necessary to oppose personal moral violations, possibly by mediating anticipatory, self-focused, emotional reactions that may exert strong influence on moral choice and behavior.

View-Independent Working Memory Representations of Artificial Shapes in Prefrontal and Posterior Regions of the Human Brain.

PubMed

Christophel, Thomas B; Allefeld, Carsten; Endisch, Christian; Haynes, John-Dylan

2018-06-01

Traditional views of visual working memory postulate that memorized contents are stored in dorsolateral prefrontal cortex using an adaptive and flexible code. In contrast, recent studies proposed that contents are maintained by posterior brain areas using codes akin to perceptual representations. An important question is whether this reflects a difference in the level of abstraction between posterior and prefrontal representations. Here, we investigated whether neural representations of visual working memory contents are view-independent, as indicated by rotation-invariance. Using functional magnetic resonance imaging and multivariate pattern analyses, we show that when subjects memorize complex shapes, both posterior and frontal brain regions maintain the memorized contents using a rotation-invariant code. Importantly, we found the representations in frontal cortex to be localized to the frontal eye fields rather than dorsolateral prefrontal cortices. Thus, our results give evidence for the view-independent storage of complex shapes in distributed representations across posterior and frontal brain regions.

Selective deficit in personal moral judgment following damage to ventromedial prefrontal cortex

PubMed Central

Ciaramelli, Elisa; Muccioli, Michela; Làdavas, Elisabetta

2007-01-01

Recent fMRI evidence has detected increased medial prefrontal activation during contemplation of personal moral dilemmas compared to impersonal ones, which suggests that this cortical region plays a role in personal moral judgment. However, functional imaging results cannot definitively establish that a brain area is necessary for a particular cognitive process. This requires evidence from lesion techniques, such as studies of human patients with focal brain damage. Here, we tested 7 patients with lesions in the ventromedial prefrontal cortex and 12 healthy individuals in personal moral dilemmas, impersonal moral dilemmas and non-moral dilemmas. Compared to normal controls, patients were more willing to judge personal moral violations as acceptable behaviors in personal moral dilemmas, and they did so more quickly. In contrast, their performance in impersonal and non-moral dilemmas was comparable to that of controls. These results indicate that the ventromedial prefrontal cortex is necessary to oppose personal moral violations, possibly by mediating anticipatory, self-focused, emotional reactions that may exert strong influence on moral choice and behavior. PMID:18985127

The neural correlates of regulating positive and negative emotions in medication-free major depression

PubMed Central

Greening, Steven G.; Osuch, Elizabeth A.; Williamson, Peter C.

2014-01-01

Depressive cognitive schemas play an important role in the emergence and persistence of major depressive disorder (MDD). The current study adapted emotion regulation techniques to reflect elements of cognitive behavioural therapy (CBT) and related psychotherapies to delineate neurocognitive abnormalities associated with modulating the negative cognitive style in MDD. Nineteen non-medicated patients with MDD and 19 matched controls reduced negative or enhanced positive feelings elicited by emotional scenes while undergoing functional magnetic resonance imaging. Although both groups showed significant emotion regulation success as measured by subjective ratings of affect, the controls were significantly better at modulating both negative and positive emotion. Both groups recruited regions of dorsolateral prefrontal cortex and ventrolateral prefrontal cortex (VLPFC) when regulating negative emotions. Only in controls was this accompanied by reduced activity in sensory cortices and amygdala. Similarly, both groups showed enhanced activity in VLPFC and ventral striatum when enhancing positive affect; however, only in controls was ventral striatum activity correlated with regulation efficacy. The results suggest that depression is associated with both a reduced capacity to achieve relief from negative affect despite recruitment of ventral and dorsal prefrontal cortical regions implicated in emotion regulation, coupled with a disconnect between activity in reward-related regions and subjective positive affect. PMID:23482626

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

PubMed Central

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

2013-01-01

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

Structural changes in socio-affective networks: Multi-modal MRI findings in long-term meditation practitioners.

PubMed

Engen, Haakon G; Bernhardt, Boris C; Skottnik, Leon; Ricard, Matthieu; Singer, Tania

2017-08-31

Our goal was to assess the effects of long-term mental training in socio-affective skills on structural brain networks. We studied a group of long-term meditation practitioners (LTMs) who have focused on cultivating socio-affective skills using loving-kindness and compassion meditation for an average of 40k h, comparing these to meditation-naïve controls. To maximize homogeneity of prior practice, LTMs were included only if they had undergone extensive full-time meditation retreats in the same center. MRI-based cortical thickness analysis revealed increased thickness in the LTM cohort relative to meditation-native controls in fronto-insular cortices. To identify functional networks relevant for the generation of socio-affective states, structural imaging analysis were complemented by fMRI analysis in LTMs, showing amplitude increases during a loving-kindness meditation session relative to non-meditative rest in multiple prefrontal and insular regions bilaterally. Importantly, functional findings partially overlapped with regions of cortical thickness increases in the left ventrolateral prefrontal cortex and anterior insula, suggesting that these regions may play a central role in the generation of emotional states relevant for the meditative practice. Our multi-modal MRI approach revealed structural changes in LTMs who have cultivated loving-kindness and compassion for a significant period of their life in functional networks activated by these practices. These preliminary cross-sectional findings motivate future longitudinal work studying brain plasticity following the regular practice of skills aiming at enhancing human altruism and prosocial motivation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Top-Down Control of Visual Attention by the Prefrontal Cortex. Functional Specialization and Long-Range Interactions

PubMed Central

Paneri, Sofia; Gregoriou, Georgia G.

2017-01-01

The ability to select information that is relevant to current behavioral goals is the hallmark of voluntary attention and an essential part of our cognition. Attention tasks are a prime example to study at the neuronal level, how task related information can be selectively processed in the brain while irrelevant information is filtered out. Whereas, numerous studies have focused on elucidating the mechanisms of visual attention at the single neuron and population level in the visual cortices, considerably less work has been devoted to deciphering the distinct contribution of higher-order brain areas, which are known to be critical for the employment of attention. Among these areas, the prefrontal cortex (PFC) has long been considered a source of top-down signals that bias selection in early visual areas in favor of the attended features. Here, we review recent experimental data that support the role of PFC in attention. We examine the existing evidence for functional specialization within PFC and we discuss how long-range interactions between PFC subregions and posterior visual areas may be implemented in the brain and contribute to the attentional modulation of different measures of neural activity in visual cortices. PMID:29033784

Top-Down Control of Visual Attention by the Prefrontal Cortex. Functional Specialization and Long-Range Interactions.

PubMed

Paneri, Sofia; Gregoriou, Georgia G

2017-01-01

The ability to select information that is relevant to current behavioral goals is the hallmark of voluntary attention and an essential part of our cognition. Attention tasks are a prime example to study at the neuronal level, how task related information can be selectively processed in the brain while irrelevant information is filtered out. Whereas, numerous studies have focused on elucidating the mechanisms of visual attention at the single neuron and population level in the visual cortices, considerably less work has been devoted to deciphering the distinct contribution of higher-order brain areas, which are known to be critical for the employment of attention. Among these areas, the prefrontal cortex (PFC) has long been considered a source of top-down signals that bias selection in early visual areas in favor of the attended features. Here, we review recent experimental data that support the role of PFC in attention. We examine the existing evidence for functional specialization within PFC and we discuss how long-range interactions between PFC subregions and posterior visual areas may be implemented in the brain and contribute to the attentional modulation of different measures of neural activity in visual cortices.

A decade of imaging surgeons' brain function (part II): A systematic review of applications for technical and nontechnical skills assessment.

PubMed

Modi, Hemel Narendra; Singh, Harsimrat; Yang, Guang-Zhong; Darzi, Ara; Leff, Daniel Richard

2017-11-01

Functional neuroimaging technologies enable assessment of operator brain function and can deepen our understanding of skills learning, ergonomic optima, and cognitive processes in surgeons. Although there has been a critical mass of data detailing surgeons' brain function, this literature has not been reviewed systematically. A systematic search of original neuroimaging studies assessing surgeons' brain function and published up until November 2016 was conducted using Medline, Embase, and PsycINFO databases. Twenty-seven studies fulfilled the inclusion criteria, including 3 feasibility studies, 14 studies exploring the neural correlates of technical skill acquisition, and the remainder investigating brain function in the context of intraoperative decision-making (n = 1), neurofeedback training (n = 1), robot-assisted technology (n = 5), and surgical teaching (n = 3). Early stages of learning open surgical tasks (knot-tying) are characterized by prefrontal cortical activation, which subsequently attenuates with deliberate practice. However, with complex laparoscopic skills (intracorporeal suturing), prefrontal cortical engagement requires substantial training, and attenuation occurs over a longer time course, after years of refinement. Neurofeedback and interventions that improve neural efficiency may enhance technical performance and skills learning. Imaging surgeons' brain function has identified neural signatures of expertise that might help inform objective assessment and selection processes. Interventions that improve neural efficiency may target skill-specific brain regions and augment surgical performance. Copyright © 2017 Elsevier Inc. All rights reserved.

Prefrontal cortex afferents to the anterior temporal lobe in the Macaca fascicularis monkey.

PubMed

Mohedano-Moriano, Alicia; Muñoz-López, Mónica; Sanz-Arigita, Ernesto; Pró-Sistiaga, Palma; Martínez-Marcos, Alino; Legidos-Garcia, María Ester; Insausti, Ana María; Cebada-Sánchez, Sandra; Arroyo-Jiménez, María Del Mar; Marcos, Pilar; Artacho-Pérula, Emilio; Insausti, Ricardo

2015-12-01

The anatomical organization of the lateral prefrontal cortex (LPFC) afferents to the anterior part of the temporal lobe (ATL) remains to be clarified. The LPFC has two subdivisions, dorsal (dLPFC) and ventral (vLPFC), which have been linked to cognitive processes. The ATL includes several different cortical areas, namely, the temporal polar cortex and rostral parts of the perirhinal, inferotemporal, and anterior tip of the superior temporal gyrus cortices. Multiple sensory modalities converge in the ATL. All of them (except the rostral inferotemporal and superior temporal gyrus cortices) are components of the medial temporal lobe, which is critical for long-term memory processing. We studied the LPFC connections with the ATL by placing retrograde tracer injections into the ATL: the temporal polar (n = 3), perirhinal (areas 35 and 36, n = 6), and inferotemporal cortices (area TE, n = 5), plus one additional deposit in the posterior parahippocampal cortex (area TF, n = 1). Anterograde tracer deposits into the dLPFC (A9 and A46, n = 2), the vLPFC (A46v, n = 2), and the orbitofrontal cortex (OF; n = 2) were placed for confirmation of those projections. The results showed that the vLPFC displays a moderate projection to rostral area TE and the dorsomedial portion of the temporal polar cortex; in contrast, the dLPFC connections with the ATL were weak. By comparison, the OFC and medial frontal cortices (MFC) showed dense connectivity with the ATL, namely, A13 with the temporopolar and perirhinal cortices. All areas of the MFC projected to the temporopolar cortex, albeit with a lower intensity. The functional significance of such paucity of LPFC afferents is unknown. © 2015 Wiley Periodicals, Inc.

Impaired functional connectivity within and between frontostriatal circuits and its association with compulsive drug use and trait impulsivity in cocaine addiction.

PubMed

Hu, Yuzheng; Salmeron, Betty Jo; Gu, Hong; Stein, Elliot A; Yang, Yihong

2015-06-01

Converging evidence has long identified both impulsivity and compulsivity as key psychological constructs in drug addiction. Although dysregulated striatal-cortical network interactions have been identified in cocaine addiction, the association between these brain networks and addiction is poorly understood. To test the hypothesis that cocaine addiction is associated with disturbances in striatal-cortical communication as captured by resting-state functional connectivity (rsFC), measured from coherent spontaneous fluctuations in the blood oxygenation level-dependent functional magnetic resonance imaging signal, and to explore the relationships between striatal rsFC, trait impulsivity, and uncontrolled drug use in cocaine addiction. A case-control, cross-sectional study was conducted at the National Institute on Drug Abuse Intramural Research Program outpatient magnetic resonance imaging facility. Data used in the present study were collected between December 8, 2005, and September 30, 2011. Participants included 56 non-treatment-seeking cocaine users (CUs) (52 with cocaine dependence and 3 with cocaine abuse) and 56 healthy individuals serving as controls (HCs) matched on age, sex, years of education, race, estimated intelligence, and smoking status. Voxelwise statistical parametric analysis testing the rsFC strength differences between CUs and HCs in brain regions functionally connected to 6 striatal subregions defined a priori. Increased rsFC strength was observed predominantly in striatal-frontal circuits; decreased rsFC was found between the striatum and cingulate, striatal, temporal, hippocampal/amygdalar, and insular regions in the CU group compared with the HCs. Increased striatal-dorsal lateral prefrontal cortex connectivity strength was positively correlated with the amount of recent cocaine use (uncorrected P < .046) and elevated trait impulsivity in the CUs (uncorrected P < .012), and an index reflecting the balance between striatal-dorsal anterior cingulate cortex and striatal-anterior prefrontal/orbitofrontal cortex circuits was significantly associated with loss of control over cocaine use (corrected P < .012). Cocaine addiction is associated with disturbed rsFC in several specific striatal-cortical circuits. Specifically, compulsive cocaine use, a defining characteristic of dependence, was associated with a balance of increased striatal-anterior prefrontal/orbitofrontal and decreased striatal-dorsal anterior cingulate connectivity; trait impulsivity, both a risk factor for and a consequence of cocaine use, was associated with increased dorsal striatal-dorsal lateral prefrontal cortex connectivity uniquely in CUs. These findings provide new insights toward the neurobiological mechanisms of addiction and suggest potential novel therapeutic targets for treatment.

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

PubMed Central

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

2015-01-01

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

Chemical neuromodulation of frontal-executive functions in humans and other animals.

PubMed

Robbins, T W

2000-07-01

Neuromodulation of frontal-executive function is reviewed in the context of experiments on rats, monkeys and human subjects. The different functions of the chemically identified systems of the reticular core are analysed from the perspective of their possible different interactions with the prefrontal cortex. The role of dopamine in spatial working memory is reviewed, taking account of its deleterious as well as facilitatory effects. Baseline-dependent effects of dopaminergic manipulation are described in rats on an attentional task, including evidence of enhanced function following infusions of D1 receptor agonists into the prefrontal cortex. The precise nature of the cognitive task under study is shown to be a powerful determinant of the effects of mesofrontal dopamine depletion in monkeys. Parallels are identified in human subjects receiving drugs such as the indirect catecholamine agonists L-dopa, methylphenidate and the dopamine D2 receptor blocker sulpiride. The effects of these drugs on different types of cognitive function sensitive to frontal lobe dysfunction are contrasted with those of a manipulation of 5-HT function, dietary tryptophan depletion. Hypotheses are advanced that accord the ascending systems a greater deal of specificity in modulating prefrontal cortical function than has hitherto been entertained, and clinical and theoretical implications of this hypothesis are discussed.

Functional neuroimaging insights into the physiology of human sleep.

PubMed

Dang-Vu, Thien Thanh; Schabus, Manuel; Desseilles, Martin; Sterpenich, Virginie; Bonjean, Maxime; Maquet, Pierre

2010-12-01

Functional brain imaging has been used in humans to noninvasively investigate the neural mechanisms underlying the generation of sleep stages. On the one hand, REM sleep has been associated with the activation of the pons, thalamus, limbic areas, and temporo-occipital cortices, and the deactivation of prefrontal areas, in line with theories of REM sleep generation and dreaming properties. On the other hand, during non-REM (NREM) sleep, decreases in brain activity have been consistently found in the brainstem, thalamus, and in several cortical areas including the medial prefrontal cortex (MPFC), in agreement with a homeostatic need for brain energy recovery. Benefiting from a better temporal resolution, more recent studies have characterized the brain activations related to phasic events within specific sleep stages. In particular, they have demonstrated that NREM sleep oscillations (spindles and slow waves) are indeed associated with increases in brain activity in specific subcortical and cortical areas involved in the generation or modulation of these waves. These data highlight that, even during NREM sleep, brain activity is increased, yet regionally specific and transient. Besides refining the understanding of sleep mechanisms, functional brain imaging has also advanced the description of the functional properties of sleep. For instance, it has been shown that the sleeping brain is still able to process external information and even detect the pertinence of its content. The relationship between sleep and memory has also been refined using neuroimaging, demonstrating post-learning reactivation during sleep, as well as the reorganization of memory representation on the systems level, sometimes with long-lasting effects on subsequent memory performance. Further imaging studies should focus on clarifying the role of specific sleep patterns for the processing of external stimuli, as well as the consolidation of freshly encoded information during sleep.

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.

Prefrontal cortex-projecting glutamatergic thalamic paraventricular nucleus-excited by hypocretin: a feedforward circuit that may enhance cognitive arousal.

PubMed

Huang, Hao; Ghosh, Prabhat; van den Pol, Anthony N

2006-03-01

The paraventricular thalamic nucleus (PVT) receives one of the most dense innervations by hypothalamic hypocretin/orexin (Hcrt) neurons, which play important roles in sleep-wakefulness, attention, and autonomic function. The PVT projects to several loci, including the medial prefrontal cortex (mPFC), a cortical region involved in associative function and attention. To study the effect of Hcrt on excitatory PVT neurons that project to the mPFC, we used a new line of transgenic mice expressing green fluorescent protein (GFP) under the control of the vesicular glutamate-transporter-2 promoter. These neurons were retrogradely labeled with cholera toxin subunit B that had been microinjected into the mPFC. Membrane characteristics and responses to hypocretin-1 and -2 (Hcrt-1 and -2) were studied using whole cell recording (n > 300). PVT neurons showed distinct membrane properties including inward rectification, H-type potassium currents, low threshold spikes, and spike frequency adaptation. Cortically projecting neurons were depolarized and excited by Hcrt-2. Hcrt-2 actions were stronger than those of Hcrt-1, and the action persisted in TTX and in low calcium/high magnesium artificial cerebrospinal fluid, consistent with direct actions mediated by Hcrt receptor-2. Two mechanisms of Hcrt excitation were found: an increase in input resistance caused by closure of potassium channels and activation of nonselective cation channels. The robust excitation evoked by Hcrt-2 on cortically projecting glutamate PVT neurons could generate substantial excitation in multiple layers of the mPFC, adding to the more selective direct excitatory actions of Hcrt in the mPFC and potentially increasing cortical arousal and attention to limbic or visceral states.

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.

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.

Brain differences between persistent and remitted attention deficit hyperactivity disorder.

PubMed

Mattfeld, Aaron T; Gabrieli, John D E; Biederman, Joseph; Spencer, Thomas; Brown, Ariel; Kotte, Amelia; Kagan, Elana; Whitfield-Gabrieli, Susan

2014-09-01

Previous resting state studies examining the brain basis of attention deficit hyperactivity disorder have not distinguished between patients who persist versus those who remit from the diagnosis as adults. To characterize the neurobiological differences and similarities of persistence and remittance, we performed resting state functional magnetic resonance imaging in individuals who had been longitudinally and uniformly characterized as having or not having attention deficit hyperactivity disorder in childhood and again in adulthood (16 years after baseline assessment). Intrinsic functional brain organization was measured in patients who had a persistent diagnosis in childhood and adulthood (n = 13), in patients who met diagnosis in childhood but not in adulthood (n = 22), and in control participants who never had attention deficit hyperactivity disorder (n = 17). A positive functional correlation between posterior cingulate and medial prefrontal cortices, major components of the default-mode network, was reduced only in patients whose diagnosis persisted into adulthood. A negative functional correlation between medial and dorsolateral prefrontal cortices was reduced in both persistent and remitted patients. The neurobiological dissociation between the persistence and remittance of attention deficit hyperactivity disorder may provide a framework for the relation between the clinical diagnosis, which indicates the need for treatment, and additional deficits that are common, such as executive dysfunctions. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

What is the function of hippocampal theta rhythm?--Linking behavioral data to phasic properties of field potential and unit recording data.

PubMed

Hasselmo, Michael E

2005-01-01

The extensive physiological data on hippocampal theta rhythm provide an opportunity to evaluate hypotheses about the role of theta rhythm for hippocampal network function. Computational models based on these hypotheses help to link behavioral data with physiological measurements of different variables during theta rhythm. This paper reviews work on network models in which theta rhythm contributes to the following functions: (1) separating the dynamics of encoding and retrieval, (2) enhancing the context-dependent retrieval of sequences, (3) buffering of novel information in entorhinal cortex (EC) for episodic encoding, and (4) timing interactions between prefrontal cortex and hippocampus for memory-guided action selection. Modeling shows how these functional mechanisms are related to physiological data from the hippocampal formation, including (1) the phase relationships of synaptic currents during theta rhythm measured by current source density analysis of electroencephalographic data from region CA1 and dentate gyrus, (2) the timing of action potentials, including the theta phase precession of single place cells during running on a linear track, the context-dependent changes in theta phase precession across trials on each day, and the context-dependent firing properties of hippocampal neurons in spatial alternation (e.g., "splitter cells"), (3) the cholinergic regulation of sustained activity in entorhinal cortical neurons, and (4) the phasic timing of prefrontal cortical neurons relative to hippocampal theta rhythm. Copyright 2005 Wiley-Liss, Inc.

Auditory Cortical Plasticity Drives Training-Induced Cognitive Changes in Schizophrenia

PubMed Central

Dale, Corby L.; Brown, Ethan G.; Fisher, Melissa; Herman, Alexander B.; Dowling, Anne F.; Hinkley, Leighton B.; Subramaniam, Karuna; Nagarajan, Srikantan S.; Vinogradov, Sophia

2016-01-01

Schizophrenia is characterized by dysfunction in basic auditory processing, as well as higher-order operations of verbal learning and executive functions. We investigated whether targeted cognitive training of auditory processing improves neural responses to speech stimuli, and how these changes relate to higher-order cognitive functions. Patients with schizophrenia performed an auditory syllable identification task during magnetoencephalography before and after 50 hours of either targeted cognitive training or a computer games control. Healthy comparison subjects were assessed at baseline and after a 10 week no-contact interval. Prior to training, patients (N = 34) showed reduced M100 response in primary auditory cortex relative to healthy participants (N = 13). At reassessment, only the targeted cognitive training patient group (N = 18) exhibited increased M100 responses. Additionally, this group showed increased induced high gamma band activity within left dorsolateral prefrontal cortex immediately after stimulus presentation, and later in bilateral temporal cortices. Training-related changes in neural activity correlated with changes in executive function scores but not verbal learning and memory. These data suggest that computerized cognitive training that targets auditory and verbal learning operations enhances both sensory responses in auditory cortex as well as engagement of prefrontal regions, as indexed during an auditory processing task with low demands on working memory. This neural circuit enhancement is in turn associated with better executive function but not verbal memory. PMID:26152668

Structural brain and neuropsychometric changes associated with pediatric bipolar disorder with psychosis.

PubMed

James, Anthony; Hough, Morgan; James, Susan; Burge, Linda; Winmill, Louise; Nijhawan, Sunita; Matthews, Paul M; Zarei, Mojtaba

2011-02-01

To identify neuropsychological and structural brain changes using a combination of high-resolution structural and diffusion tensor imaging in pediatric bipolar disorder (PBD) with psychosis (presence of delusions and or hallucinations). We recruited 15 patients and 20 euthymic age- and gender-matched healthy controls. All subjects underwent high-resolution structural and diffusion tensor imaging. Voxel-based morphometry (VBM), tract-based spatial statistics (TBSS), and probabilistic tractography were used to analyse magnetic resonance imaging data. The PBD subjects had normal overall intelligence with specific impairments in working memory, executive function, language function, and verbal memory. Reduced gray matter (GM) density was found in the left orbitofrontal cortex, left pars triangularis, right premotor cortex, occipital cortex, right occipital fusiform gyrus, and right crus of the cerebellum. TBSS analysis showed reduced fractional anisotropy (FA) in the anterior corpus callosum. Probabilistic tractography from this cluster showed that this region of the corpus callosum is connected with the prefrontal cortices, including those regions whose density is decreased in PBD. In addition, FA change was correlated with verbal memory and working memory, while more widespread reductions in GM density correlated with working memory, executive function, language function, and verbal memory. The findings suggest widespread cortical changes as well as specific involvement of interhemispheric prefrontal tracts in PBD, which may reflect delayed myelination in these tracts. © 2011 John Wiley and Sons A/S.

Altered Cortical Swallowing Processing in Patients with Functional Dysphagia: A Preliminary Study

PubMed Central

Wollbrink, Andreas; Warnecke, Tobias; Winkels, Martin; Pantev, Christo; Dziewas, Rainer

2014-01-01

Objective Current neuroimaging research on functional disturbances provides growing evidence for objective neuronal correlates of allegedly psychogenic symptoms, thereby shifting the disease concept from a psychological towards a neurobiological model. Functional dysphagia is such a rare condition, whose pathogenetic mechanism is largely unknown. In the absence of any organic reason for a patient's persistent swallowing complaints, sensorimotor processing abnormalities involving central neural pathways constitute a potential etiology. Methods In this pilot study we measured cortical swallow-related activation in 5 patients diagnosed with functional dysphagia and a matched group of healthy subjects applying magnetoencephalography. Source localization of cortical activation was done with synthetic aperture magnetometry. To test for significant differences in cortical swallowing processing between groups, a non-parametric permutation test was afterwards performed on individual source localization maps. Results Swallowing task performance was comparable between groups. In relation to control subjects, in whom activation was symmetrically distributed in rostro-medial parts of the sensorimotor cortices of both hemispheres, patients showed prominent activation of the right insula, dorsolateral prefrontal cortex and lateral premotor, motor as well as inferolateral parietal cortex. Furthermore, activation was markedly reduced in the left medial primary sensory cortex as well as right medial sensorimotor cortex and adjacent supplementary motor area (p<0.01). Conclusions Functional dysphagia - a condition with assumed normal brain function - seems to be associated with distinctive changes of the swallow-related cortical activation pattern. Alterations may reflect exaggerated activation of a widely distributed vigilance, self-monitoring and salience rating network that interferes with down-stream deglutition sensorimotor control. PMID:24586948

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.

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.

Trail making test performance in youth varies as a function of anatomical coupling between the prefrontal cortex and distributed cortical regions

PubMed Central

Lee, Nancy Raitano; Wallace, Gregory L.; Raznahan, Armin; Clasen, Liv S.; Giedd, Jay N.

2014-01-01

While researchers have gained a richer understanding of the neural correlates of executive function in adulthood, much less is known about how these abilities are represented in the developing brain and what structural brain networks underlie them. Thus, the current study examined how individual differences in executive function, as measured by the Trail Making Test (TMT), relate to structural covariance in the pediatric brain. The sample included 146 unrelated, typically developing youth (80 females), ages 9–14 years, who completed a structural MRI scan of the brain and the Halstead-Reitan TMT (intermediate form). TMT scores used to index executive function included those that evaluated set-shifting ability: Trails B time (number-letter sequencing) and the difference in time between Trails B and A (number sequencing only). Anatomical coupling was measured by examining correlations between mean cortical thickness (MCT) across the entire cortical ribbon and individual vertex thickness measured at ~81,000 vertices. To examine how TMT scores related to anatomical coupling strength, linear regression was utilized and the interaction between age-normed TMT scores and both age and sex-normed MCT was used to predict vertex thickness. Results revealed that stronger Trails B scores were associated with greater anatomical coupling between a large swath of prefrontal cortex and the rest of cortex. For the difference between Trails B and A, a network of regions in the frontal, temporal, and parietal lobes was found to be more tightly coupled with the rest of cortex in stronger performers. This study is the first to highlight the importance of structural covariance in in the prediction of individual differences in executive function skills in youth. Thus, it adds to the growing literature on the neural correlates of childhood executive functions and identifies neuroanatomic coupling as a biological substrate that may contribute to executive function and dysfunction in childhood. PMID:25071613

A magnetoencephalography study of visual processing of pain anticipation.

PubMed

Machado, Andre G; Gopalakrishnan, Raghavan; Plow, Ela B; Burgess, Richard C; Mosher, John C

2014-07-15

Anticipating pain is important for avoiding injury; however, in chronic pain patients, anticipatory behavior can become maladaptive, leading to sensitization and limiting function. Knowledge of networks involved in pain anticipation and conditioning over time could help devise novel, better-targeted therapies. With the use of magnetoencephalography, we evaluated in 10 healthy subjects the neural processing of pain anticipation. Anticipatory cortical activity elicited by consecutive visual cues that signified imminent painful stimulus was compared with cues signifying nonpainful and no stimulus. We found that the neural processing of visually evoked pain anticipation involves the primary visual cortex along with cingulate and frontal regions. Visual cortex could quickly and independently encode and discriminate between visual cues associated with pain anticipation and no pain during preconscious phases following object presentation. When evaluating the effect of task repetition on participating cortical areas, we found that activity of prefrontal and cingulate regions was mostly prominent early on when subjects were still naive to a cue's contextual meaning. Visual cortical activity was significant throughout later phases. Although visual cortex may precisely and time efficiently decode cues anticipating pain or no pain, prefrontal areas establish the context associated with each cue. These findings have important implications toward processes involved in pain anticipation and maladaptive pain conditioning. Copyright © 2014 the American Physiological Society.

Altered dynamics between neural systems sub-serving decisions for unhealthy food

PubMed Central

He, Qinghua; Xiao, Lin; Xue, Gui; Wong, Savio; Ames, Susan L.; Xie, Bin; Bechara, Antoine

2014-01-01

Using BOLD functional magnetic resonance imaging (fMRI) techniques, we examined the relationships between activities in the neural systems elicited by the decision stage of the Iowa Gambling Task (IGT), and food choices of either vegetables or snacks high in fat and sugar. Twenty-three healthy normal weight adolescents and young adults, ranging in age from 14 to 21, were studied. Neural systems implicated in decision-making and inhibitory control were engaged by having participants perform the IGT during fMRI scanning. The Youth/Adolescent Questionnaire, a food frequency questionnaire, was used to obtain daily food choices. Higher consumption of vegetables correlated with higher activity in prefrontal cortical regions, namely the left superior frontal gyrus (SFG), and lower activity in sub-cortical regions, namely the right insular cortex. In contrast, higher consumption of fatty and sugary snacks correlated with lower activity in the prefrontal regions, combined with higher activity in the sub-cortical, insular cortex. These results provide preliminary support for our hypotheses that unhealthy food choices in real life are reflected by neuronal changes in key neural systems involved in habits, decision-making and self-control processes. These findings have implications for the creation of decision-making based intervention strategies that promote healthier eating. PMID:25414630

Anosmia leads to a loss of gray matter in cortical brain areas.

PubMed

Bitter, Thomas; Gudziol, Hilmar; Burmeister, Hartmut Peter; Mentzel, Hans-Joachim; Guntinas-Lichius, Orlando; Gaser, Christian

2010-06-01

Chronic olfactory disorders, including the complete loss of the sense of smell (anosmia), are common. Using voxel-based morphometry (VBM) in magnetic resonance imaging (MRI), structural changes in the cerebral gray matter (GM) of a group of patients with anosmia compared with a normosmic, healthy control group were evaluated. Patients with anosmia presented a significant decrease of GM volume mainly in the nucleus accumbens with adjacent subcallosal gyrus, in the medial prefrontal cortex (MPC) including the middle and anterior cingulate cortices, and in the dorsolateral prefrontal cortex (dlPFC). These areas are part of the limbic loop of the basal ganglia and except the dlPFC secondary olfactory areas. They also play an important role in many neurological diseases. Furthermore, volume decreases in smaller areas like the piriform cortex, insular cortex, orbitofrontal cortex, hippocampus, parahippocampal gyrus, supramarginal gyrus, and cerebellum could be seen. Longer disease duration was associated with a stronger atrophy in the described areas. No local increases in the GM volume could be observed. A comparison with results of an additionally executed functional MRI study on olfaction in healthy subjects was performed to evaluate the significance of the observed atrophy areas in cerebral olfactory processing. To our knowledge, this is the first study on persisting structural changes in cortical GM volume after complete olfactory loss.

Cortical gyrification in autistic and Asperger disorders: a preliminary magnetic resonance imaging study.

PubMed

Jou, Roger J; Minshew, Nancy J; Keshavan, Matcheri S; Hardan, Antonio Y

2010-12-01

The validity of Asperger disorder as a distinct syndrome from autism is unclear partly because of the paucity of differentiating neurobiological evidence. Frontal lobe cortical folding between these disorders was compared using the gyrification index. Twenty-three boys underwent structural magnetic resonance imaging: 6 with high-functioning autism, 9 with Asperger disorder, and 8 controls. Using the first coronal slice anterior to the corpus callosum, total and outer cortical contours were traced to calculate the gyrification index. This index was also calculated for superior and inferior regions to examine dorsolateral prefrontal and orbitofrontal cortices, respectively. Analysis of variance revealed differences in the left inferior gyrification index, which was higher in the autism group compared with Asperger and control groups. There were no differences in age, intelligence quotient, and brain volume. These preliminary findings suggest that cortical folding may be abnormally high in the frontal lobe in autism but not Asperger disorder, suggesting distinct frontal lobe neuropathology.

Functional differentiation between convergence and non-convergence zones of the striatum in children.

PubMed

Darki, Fahimeh; Klingberg, Torkel

2018-06-01

Most cortical areas send projections to the striatum. In some parts of the striatum, the connections converge from several cortical areas. It is unknown whether the convergence and non-convergence zones of the striatum differ functionally. Here, we used diffusion-weighted magnetic resonance imaging and probabilistic fiber tracking to parcellate the striatum based on its connections to dorsolateral prefrontal, parietal and orbitofrontal cortices in two different datasets (children aged 6-7 years and adults). In both samples, quantitative susceptibility mapping (QSM) values were significantly correlated with working memory (WM) in convergence zones, but not in non-convergence zones. In children, this was also true for mean diffusivity, MD. The association of MD to WM specifically in the convergent zone was replicated in the Pediatric Imaging, Neurocognition, and Genetics (PING) dataset for 135 children aged 6-9 years. QSM data was not available in the PING dataset, and the association to QSM still needs to be replicated. These results suggest that connectivity-based segments of the striatum exhibit functionally different characteristics. The association between convergence zones and WM performance might relate to a role in integrating and coordinating activity in different cortical areas. Copyright © 2018 Elsevier Inc. All rights reserved.

Transcranial Direct Current Stimulation Targeting Primary Motor Versus Dorsolateral Prefrontal Cortices: Proof-of-Concept Study Investigating Functional Connectivity of Thalamocortical Networks Specific to Sensory-Affective Information Processing.

PubMed

Sankarasubramanian, Vishwanath; Cunningham, David A; Potter-Baker, Kelsey A; Beall, Erik B; Roelle, Sarah M; Varnerin, Nicole M; Machado, Andre G; Jones, Stephen E; Lowe, Mark J; Plow, Ela B

2017-04-01

The pain matrix is comprised of an extensive network of brain structures involved in sensory and/or affective information processing. The thalamus is a key structure constituting the pain matrix. The thalamus serves as a relay center receiving information from multiple ascending pathways and relating information to and from multiple cortical areas. However, it is unknown how thalamocortical networks specific to sensory-affective information processing are functionally integrated. Here, in a proof-of-concept study in healthy humans, we aimed to understand this connectivity using transcranial direct current stimulation (tDCS) targeting primary motor (M1) or dorsolateral prefrontal cortices (DLPFC). We compared changes in functional connectivity (FC) with DLPFC tDCS to changes in FC with M1 tDCS. FC changes were also compared to further investigate its relation with individual's baseline experience of pain. We hypothesized that resting-state FC would change based on tDCS location and would represent known thalamocortical networks. Ten right-handed individuals received a single application of anodal tDCS (1 mA, 20 min) to right M1 and DLPFC in a single-blind, sham-controlled crossover study. FC changes were studied between ventroposterolateral (VPL), the sensory nucleus of thalamus, and cortical areas involved in sensory information processing and between medial dorsal (MD), the affective nucleus, and cortical areas involved in affective information processing. Individual's perception of pain at baseline was assessed using cutaneous heat pain stimuli. We found that anodal M1 tDCS and anodal DLPFC tDCS both increased FC between VPL and sensorimotor cortices, although FC effects were greater with M1 tDCS. Similarly, anodal M1 tDCS and anodal DLPFC tDCS both increased FC between MD and motor cortices, but only DLPFC tDCS modulated FC between MD and affective cortices, like DLPFC. Our findings suggest that M1 stimulation primarily modulates FC of sensory networks, whereas DLPFC stimulation modulates FC of both sensory and affective networks. Our findings when replicated in a larger group of individuals could provide useful evidence that may inform future studies on pain to differentiate between effects of M1 and DLPFC stimulation. Notably, our finding that individuals with high baseline pain thresholds experience greater FC changes with DLPFC tDCS implies the role of DLPFC in pain modulation, particularly pain tolerance.

Transcranial Direct Current Stimulation Targeting Primary Motor Versus Dorsolateral Prefrontal Cortices: Proof-of-Concept Study Investigating Functional Connectivity of Thalamocortical Networks Specific to Sensory-Affective Information Processing

PubMed Central

Sankarasubramanian, Vishwanath; Cunningham, David A.; Potter-Baker, Kelsey A.; Beall, Erik B.; Roelle, Sarah M.; Varnerin, Nicole M.; Machado, Andre G.; Jones, Stephen E.; Lowe, Mark J.

2017-01-01

Abstract The pain matrix is comprised of an extensive network of brain structures involved in sensory and/or affective information processing. The thalamus is a key structure constituting the pain matrix. The thalamus serves as a relay center receiving information from multiple ascending pathways and relating information to and from multiple cortical areas. However, it is unknown how thalamocortical networks specific to sensory-affective information processing are functionally integrated. Here, in a proof-of-concept study in healthy humans, we aimed to understand this connectivity using transcranial direct current stimulation (tDCS) targeting primary motor (M1) or dorsolateral prefrontal cortices (DLPFC). We compared changes in functional connectivity (FC) with DLPFC tDCS to changes in FC with M1 tDCS. FC changes were also compared to further investigate its relation with individual's baseline experience of pain. We hypothesized that resting-state FC would change based on tDCS location and would represent known thalamocortical networks. Ten right-handed individuals received a single application of anodal tDCS (1 mA, 20 min) to right M1 and DLPFC in a single-blind, sham-controlled crossover study. FC changes were studied between ventroposterolateral (VPL), the sensory nucleus of thalamus, and cortical areas involved in sensory information processing and between medial dorsal (MD), the affective nucleus, and cortical areas involved in affective information processing. Individual's perception of pain at baseline was assessed using cutaneous heat pain stimuli. We found that anodal M1 tDCS and anodal DLPFC tDCS both increased FC between VPL and sensorimotor cortices, although FC effects were greater with M1 tDCS. Similarly, anodal M1 tDCS and anodal DLPFC tDCS both increased FC between MD and motor cortices, but only DLPFC tDCS modulated FC between MD and affective cortices, like DLPFC. Our findings suggest that M1 stimulation primarily modulates FC of sensory networks, whereas DLPFC stimulation modulates FC of both sensory and affective networks. Our findings when replicated in a larger group of individuals could provide useful evidence that may inform future studies on pain to differentiate between effects of M1 and DLPFC stimulation. Notably, our finding that individuals with high baseline pain thresholds experience greater FC changes with DLPFC tDCS implies the role of DLPFC in pain modulation, particularly pain tolerance. PMID:28142257

Effect of Armodafinil on Cortical Activity and Working Memory in Patients with Residual Excessive Sleepiness Associated with CPAP-Treated OSA: A Multicenter fMRI Study

PubMed Central

Greve, Douglas N.; Duntley, Stephen P.; Larson-Prior, Linda; Krystal, Andrew D.; Diaz, Michele T.; Drummond, Sean P. A.; Thein, Stephen G.; Kushida, Clete A.; Yang, Ronghua; Thomas, Robert J.

2014-01-01

Study Objective: To assess the effect of armodafinil on task-related prefrontal cortex activation using functional magnetic resonance imaging (fMRI) in patients with obstructive sleep apnea (OSA) and excessive sleepiness despite continuous positive airway pressure (CPAP) therapy. Methods: This 2-week, multicenter, prospective, randomized, double-blind, placebo-controlled, parallel-group study was conducted at five neuroimaging sites and four collaborating clinical study centers in the United States. Patients were 40 right-handed or ambidextrous men and women aged between 18 and 60 years, with OSA and persistent sleepiness, as determined by multiple sleep latency and Epworth Sleepiness Scale scores, despite effective, stable use of CPAP. Treatment was randomized (1:1) to once-daily armodafinil 200 mg or placebo. The primary efficacy outcome was a change from baseline at week 2 in the volume of activation meeting the predefined threshold in the dorsolateral prefrontal cortex during a 2-back working memory task. The key secondary measure was the change in task response latency. Results: No significant differences were observed between treatment groups in the primary or key secondary outcomes. Armodafinil was generally well tolerated. The most common adverse events (occurring in more than one patient [5%]) were headache (19%), nasopharyngitis (14%), and diarrhea (10%). Conclusions: Armodafinil did not improve fMRI-measured functional brain activation in CPAP-treated patients with OSA and excessive sleepiness. Study Registration: Double-Blind, Placebo-Controlled, Functional Neuroimaging Study of Armodafinil (200 mg/Day) on Prefrontal Cortical Activation in Patients With Residual Excessive Sleepiness Associated With Obstructive Sleep Apnea/Hypopnea. ClinicalTrials.gov Identifier: NCT00711516. http://www.clinicaltrials.gov/ct2/show/study/NCT00711516 Citation: Greve DN; Duntley SP; Larson-Prior L; Krystal AD; Diaz MT; Drummond SP; Thein SG; Kushida CA; Yang R; Thomas RJ. Effect of armodafinil on cortical activity and working memory in patients with residual excessive sleepiness associated with CPAP-treated OSA: a multicenter fMRI study. J Clin Sleep Med 2014;10(2):143-153. PMID:24532997

Loss of MeCP2 From Forebrain Excitatory Neurons Leads to Cortical Hyperexcitation and Seizures

PubMed Central

Zhang, Wen; Peterson, Matthew; Beyer, Barbara; Frankel, Wayne N.

2014-01-01

Mutations of MECP2 cause Rett syndrome (RTT), a neurodevelopmental disorder leading to loss of motor and cognitive functions, impaired social interactions, and seizure at young ages. Defects of neuronal circuit development and function are thought to be responsible for the symptoms of RTT. The majority of RTT patients show recurrent seizures, indicating that neuronal hyperexcitation is a common feature of RTT. However, mechanisms underlying hyperexcitation in RTT are poorly understood. Here we show that deletion of Mecp2 from cortical excitatory neurons but not forebrain inhibitory neurons in the mouse leads to spontaneous seizures. Selective deletion of Mecp2 from excitatory but not inhibitory neurons in the forebrain reduces GABAergic transmission in layer 5 pyramidal neurons in the prefrontal and somatosensory cortices. Loss of MeCP2 from cortical excitatory neurons reduces the number of GABAergic synapses in the cortex, and enhances the excitability of layer 5 pyramidal neurons. Using single-cell deletion of Mecp2 in layer 2/3 pyramidal neurons, we show that GABAergic transmission is reduced in neurons without MeCP2, but is normal in neighboring neurons with MeCP2. Together, these results suggest that MeCP2 in cortical excitatory neurons plays a critical role in the regulation of GABAergic transmission and cortical excitability. PMID:24523563

Major Thought Restructuring: The Roles of Different Prefrontal Cortical Regions.

PubMed

Seyed-Allaei, Shima; Avanaki, Zahra Nasiri; Bahrami, Bahador; Shallice, Tim

2017-07-01

An important question for understanding the neural basis of problem solving is whether the regions of human prefrontal cortices play qualitatively different roles in the major cognitive restructuring required to solve difficult problems. However, investigating this question using neuroimaging faces a major dilemma: either the problems do not require major cognitive restructuring, or if they do, the restructuring typically happens once, rendering repeated measurements of the critical mental process impossible. To circumvent these problems, young adult participants were challenged with a one-dimensional Subtraction (or Nim) problem [Bouton, C. L. Nim, a game with a complete mathematical theory. The Annals of Mathematics, 3, 35-39, 1901] that can be tackled using two possible strategies. One, often used initially, is effortful, slow, and error-prone, whereas the abstract solution, once achieved, is easier, quicker, and more accurate. Behaviorally, success was strongly correlated with sex. Using voxel-based morphometry analysis controlling for sex, we found that participants who found the more abstract strategy (i.e., Solvers) had more gray matter volume in the anterior medial, ventrolateral prefrontal, and parietal cortices compared with those who never switched from the initial effortful strategy (i.e., Explorers). Removing the sex covariate showed higher gray matter volume in Solvers (vs. Explorers) in the right ventrolateral prefrontal and left parietal cortex.

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.

Rescue of Impaired mGluR5-Driven Endocannabinoid Signaling Restores Prefrontal Cortical Output to Inhibit Pain in Arthritic Rats.

PubMed

Kiritoshi, Takaki; Ji, Guangchen; Neugebauer, Volker

2016-01-20

The medial prefrontal cortex (mPFC) serves executive functions that are impaired in neuropsychiatric disorders and pain. Underlying mechanisms remain to be determined. Here we advance the novel concept that metabotropic glutamate receptor 5 (mGluR5) fails to engage endocannabinoid (2-AG) signaling to overcome abnormal synaptic inhibition in pain, but restoring endocannabinoid signaling allows mGluR5 to increase mPFC output hence inhibit pain behaviors and mitigate cognitive deficits. Whole-cell patch-clamp recordings were made from layer V pyramidal cells in the infralimbic mPFC in rat brain slices. Electrical and optogenetic stimulations were used to analyze amygdala-driven mPFC activity. A selective mGluR5 activator (VU0360172) increased pyramidal output through an endocannabinoid-dependent mechanism because intracellular inhibition of the major 2-AG synthesizing enzyme diacylglycerol lipase or blockade of CB1 receptors abolished the facilitatory effect of VU0360172. In an arthritis pain model mGluR5 activation failed to overcome abnormal synaptic inhibition and increase pyramidal output. mGluR5 function was rescued by restoring 2-AG-CB1 signaling with a CB1 agonist (ACEA) or inhibitors of postsynaptic 2-AG hydrolyzing enzyme ABHD6 (intracellular WWL70) and monoacylglycerol lipase MGL (JZL184) or by blocking GABAergic inhibition with intracellular picrotoxin. CB1-mediated depolarization-induced suppression of synaptic inhibition (DSI) was also impaired in the pain model but could be restored by coapplication of VU0360172 and ACEA. Stereotaxic coadministration of VU0360172 and ACEA into the infralimbic, but not anterior cingulate, cortex mitigated decision-making deficits and pain behaviors of arthritic animals. The results suggest that rescue of impaired endocannabinoid-dependent mGluR5 function in the mPFC can restore mPFC output and cognitive functions and inhibit pain. Significance statement: Dysfunctions in prefrontal cortical interactions with subcortical brain regions, such as the amygdala, are emerging as important players in neuropsychiatric disorders and pain. This study identifies a novel mechanism and rescue strategy for impaired medial prefrontal cortical function in an animal model of arthritis pain. Specifically, an integrative approach of optogenetics, pharmacology, electrophysiology, and behavior is used to advance the novel concept that a breakdown of metabotropic glutamate receptor subtype mGluR5 and endocannabinoid signaling in infralimbic pyramidal cells fails to control abnormal amygdala-driven synaptic inhibition in the arthritis pain model. Restoring endocannabinoid signaling allows mGluR5 activation to increase infralimbic output hence inhibit pain behaviors and mitigate pain-related cognitive deficits. Copyright © 2016 the authors 0270-6474/16/360837-14$15.00/0.

Individual variation in the propensity for prospective thought is associated with functional integration between visual and retrosplenial cortex.

PubMed

Villena-Gonzalez, Mario; Wang, Hao-Ting; Sormaz, Mladen; Mollo, Giovanna; Margulies, Daniel S; Jefferies, Elizabeth A; Smallwood, Jonathan

2018-02-01

It is well recognized that the default mode network (DMN) is involved in states of imagination, although the cognitive processes that this association reflects are not well understood. The DMN includes many regions that function as cortical "hubs", including the posterior cingulate/retrosplenial cortex, anterior temporal lobe and the hippocampus. This suggests that the role of the DMN in cognition may reflect a process of cortical integration. In the current study we tested whether functional connectivity from uni-modal regions of cortex into the DMN is linked to features of imaginative thought. We found that strong intrinsic communication between visual and retrosplenial cortex was correlated with the degree of social thoughts about the future. Using an independent dataset, we show that the same region of retrosplenial cortex is functionally coupled to regions of primary visual cortex as well as core regions that make up the DMN. Finally, we compared the functional connectivity of the retrosplenial cortex, with a region of medial prefrontal cortex implicated in the integration of information from regions of the temporal lobe associated with future thought in a prior study. This analysis shows that the retrosplenial cortex is preferentially coupled to medial occipital, temporal lobe regions and the angular gyrus, areas linked to episodic memory, scene construction and navigation. In contrast, the medial prefrontal cortex shows preferential connectivity with motor cortex and lateral temporal and prefrontal regions implicated in language, motor processes and working memory. Together these findings suggest that integrating neural information from visual cortex into retrosplenial cortex may be important for imagining the future and may do so by creating a mental scene in which prospective simulations play out. We speculate that the role of the DMN in imagination may emerge from its capacity to bind together distributed representations from across the cortex in a coherent manner. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed Central

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

2015-01-01

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

Neural correlates of social exclusion across ages: A coordinate-based meta-analysis of functional MRI studies.

PubMed

Vijayakumar, Nandita; Cheng, Theresa W; Pfeifer, Jennifer H

2017-06-01

Given the recent surge in functional neuroimaging studies on social exclusion, the current study employed activation likelihood estimation (ALE) based meta-analyses to identify brain regions that have consistently been implicated across different experimental paradigms used to investigate exclusion. We also examined the neural correlates underlying Cyberball, the most commonly used paradigm to study exclusion, as well as differences in exclusion-related activation between developing (7-18 years of age, from pre-adolescence up to late adolescence) and emerging adult (broadly defined as undergraduates, including late adolescence and young adulthood) samples. Results revealed involvement of the bilateral medial prefrontal and posterior cingulate cortices, right precuneus and left ventrolateral prefrontal cortex across the different paradigms used to examine social exclusion; similar activation patterns were identified when restricting the analysis to Cyberball studies. Investigations into age-related effects revealed that ventrolateral prefrontal activations identified in the full sample were driven by (i.e. present in) developmental samples, while medial prefrontal activations were driven by emerging adult samples. In addition, the right ventral striatum was implicated in exclusion, but only in developmental samples. Subtraction analysis revealed significantly greater activation likelihood in striatal and ventrolateral prefrontal clusters in the developmental samples as compared to emerging adults, though the opposite contrast failed to identify any significant regions. Findings integrate the knowledge accrued from functional neuroimaging studies on social exclusion to date, highlighting involvement of lateral prefrontal regions implicated in regulation and midline structures involved in social cognitive and self-evaluative processes across experimental paradigms and ages, as well as limbic structures in developing samples specifically. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of transcranial direct current stimulation on craving, heart-rate variability and prefrontal hemodynamics during smoking cue exposure.

PubMed

Kroczek, A M; Häußinger, F B; Rohe, T; Schneider, S; Plewnia, C; Batra, A; Fallgatter, A J; Ehlis, A-C

2016-11-01

Drug-related cue exposure elicits craving and risk for relapse during recovery. Transcranial direct current stimulation is a promising research tool and possible treatment for relapse prevention. Enhanced functional neuroconnectivity is discussed as a treatment target. The goal of this research was to examine whether transcranial direct current stimulation affected cortical hemodynamic indicators of functional connectivity, craving, and heart rate variability during smoking-related cue exposure in non-treatment-seeking smokers. In vivo smoking cue exposure supported by a 2mA transcranial direct current stimulation (anode: dorsolateral prefrontal cortex, cathode: orbitofrontal cortex; placebo-controlled, randomized, double-blind) in 29 (age: M=25, SD=5) German university students (smoking at least once a week). Cue reactivity was assessed on an autonomous (heart rate variability) and a subjective level (craving ratings). Functional near-infrared spectroscopy measured changes in the concentration of deoxygenated hemoglobin, and seed-based correlation analysis was used to quantify prefrontal connectivity of brain regions involved in cue reactivity. Cue exposure elicited increased subjective craving and heart rate variability changes in smokers. Connectivity between the orbitofrontal and dorsolateral prefrontal cortex was increased in subjects receiving verum compared to placebo stimulation (d=0.66). Hemodynamics in the left dorsolateral prefrontal cortex, however, increased in the group receiving sham stimulation (η 2 =0.140). Transcranial direct current stimulation did not significantly alter craving or heart rate variability during cue exposure. Prefrontal connectivity - between regions involved in the processing of reinforcement value and cognitive control - was increased by anodal transcranial direct current stimulation during smoking cue exposure. Possible clinical implications should be considered in future studies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Treatment with a Clinically-Relevant Dose of Methylphenidate Alters NMDA Receptor Composition and Synaptic Plasticity in the Juvenile Rat Prefrontal Cortex

PubMed Central

Urban, Kimberly R.; Li, Yan-Chun; Gao, Wen-Jun

2013-01-01

Methylphenidate (Ritalin, MPH) is the most commonly prescribed psychoactive drug for children. Used to treat attention-deficit/hyperactivity disorder (ADHD) and for cognitive enhancement in healthy individuals, its cellular mechanisms of action and potential long-term effects are poorly understood. We recently reported that a clinically relevant (1 mg/kg i.p., single injection) dose of MPH significantly decreased neuronal excitability in the juvenile rat prefrontal cortical neurons. Here we further explore the actions of acute treatment with MPH on the level of NMDA receptor subunits and NMDA receptor-mediated short- and long-term synaptic plasticity in the juvenile rat prefrontal cortical neurons. We found that a single dose of MPH treatment (1 mg/kg, intraperitoneal) significantly decreased the surface and total protein levels of NMDA receptor subunits NR1 and NR2B, but not NR2A, in the juvenile prefrontal cortex. In addition, the amplitude, decay time and charge transfer of NMDA receptor-mediated EPSCs were significantly decreased whereas the amplitude and short-term depression of AMPA receptor-mediated EPSCs were significantly increased in the prefrontal neurons. Furthermore, MPH treatment also significantly increased the probability and magnitude of LTP induction, but had only a small effect on LTD induction in juvenile rat prefrontal cortical neurons. Our data thus present a novel mechanism of action of MPH, i.e., changes in glutamatergic receptor-mediated synaptic plasticity following early-life treatment. Furthermore, since a single dosage resulted in significant changes in NMDA receptors, off-label usage by healthy individuals, especially children and adolescents, may result in altered potential for plastic learning. PMID:23333502

Subthalamic stimulation modulates cortical motor network activity and synchronization in Parkinson's disease.

PubMed

Weiss, Daniel; Klotz, Rosa; Govindan, Rathinaswamy B; Scholten, Marlieke; Naros, Georgios; Ramos-Murguialday, Ander; Bunjes, Friedemann; Meisner, Christoph; Plewnia, Christian; Krüger, Rejko; Gharabaghi, Alireza

2015-03-01

Dynamic modulations of large-scale network activity and synchronization are inherent to a broad spectrum of cognitive processes and are disturbed in neuropsychiatric conditions including Parkinson's disease. Here, we set out to address the motor network activity and synchronization in Parkinson's disease and its modulation with subthalamic stimulation. To this end, 20 patients with idiopathic Parkinson's disease with subthalamic nucleus stimulation were analysed on externally cued right hand finger movements with 1.5-s interstimulus interval. Simultaneous recordings were obtained from electromyography on antagonistic muscles (right flexor digitorum and extensor digitorum) together with 64-channel electroencephalography. Time-frequency event-related spectral perturbations were assessed to determine cortical and muscular activity. Next, cross-spectra in the time-frequency domain were analysed to explore the cortico-cortical synchronization. The time-frequency modulations enabled us to select a time-frequency range relevant for motor processing. On these time-frequency windows, we developed an extension of the phase synchronization index to quantify the global cortico-cortical synchronization and to obtain topographic differentiations of distinct electrode sites with respect to their contributions to the global phase synchronization index. The spectral measures were used to predict clinical and reaction time outcome using regression analysis. We found that movement-related desynchronization of cortical activity in the upper alpha and beta range was significantly facilitated with 'stimulation on' compared to 'stimulation off' on electrodes over the bilateral parietal, sensorimotor, premotor, supplementary-motor, and prefrontal areas, including the bilateral inferior prefrontal areas. These spectral modulations enabled us to predict both clinical and reaction time improvement from subthalamic stimulation. With 'stimulation on', interhemispheric cortico-cortical coherence in the beta band was significantly attenuated over the bilateral sensorimotor areas. Similarly, the global cortico-cortical phase synchronization was attenuated, and the topographic differentiation revealed stronger desynchronization over the (ipsilateral) right-hemispheric prefrontal, premotor and sensorimotor areas compared to 'stimulation off'. We further demonstrated that the cortico-cortical phase synchronization was largely dominated by genuine neuronal coupling. The clinical improvement with 'stimulation on' compared to 'stimulation off' could be predicted from this cortical decoupling with multiple regressions, and the reduction of synchronization over the right prefrontal area showed a linear univariate correlation with clinical improvement. Our study demonstrates wide-spread activity and synchronization modulations of the cortical motor network, and highlights subthalamic stimulation as a network-modulating therapy. Accordingly, subthalamic stimulation may release bilateral cortical computational resources by facilitating movement-related desynchronization. Moreover, the subthalamic nucleus is critical to balance inhibitory and facilitatory cortical players within the motor program. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Subthalamic stimulation modulates cortical motor network activity and synchronization in Parkinson’s disease

PubMed Central

Klotz, Rosa; Govindan, Rathinaswamy B.; Scholten, Marlieke; Naros, Georgios; Ramos-Murguialday, Ander; Bunjes, Friedemann; Meisner, Christoph; Plewnia, Christian; Krüger, Rejko

2015-01-01

Dynamic modulations of large-scale network activity and synchronization are inherent to a broad spectrum of cognitive processes and are disturbed in neuropsychiatric conditions including Parkinson’s disease. Here, we set out to address the motor network activity and synchronization in Parkinson’s disease and its modulation with subthalamic stimulation. To this end, 20 patients with idiopathic Parkinson’s disease with subthalamic nucleus stimulation were analysed on externally cued right hand finger movements with 1.5-s interstimulus interval. Simultaneous recordings were obtained from electromyography on antagonistic muscles (right flexor digitorum and extensor digitorum) together with 64-channel electroencephalography. Time-frequency event-related spectral perturbations were assessed to determine cortical and muscular activity. Next, cross-spectra in the time-frequency domain were analysed to explore the cortico-cortical synchronization. The time-frequency modulations enabled us to select a time-frequency range relevant for motor processing. On these time-frequency windows, we developed an extension of the phase synchronization index to quantify the global cortico-cortical synchronization and to obtain topographic differentiations of distinct electrode sites with respect to their contributions to the global phase synchronization index. The spectral measures were used to predict clinical and reaction time outcome using regression analysis. We found that movement-related desynchronization of cortical activity in the upper alpha and beta range was significantly facilitated with ‘stimulation on’ compared to ‘stimulation off’ on electrodes over the bilateral parietal, sensorimotor, premotor, supplementary-motor, and prefrontal areas, including the bilateral inferior prefrontal areas. These spectral modulations enabled us to predict both clinical and reaction time improvement from subthalamic stimulation. With ‘stimulation on’, interhemispheric cortico-cortical coherence in the beta band was significantly attenuated over the bilateral sensorimotor areas. Similarly, the global cortico-cortical phase synchronization was attenuated, and the topographic differentiation revealed stronger desynchronization over the (ipsilateral) right-hemispheric prefrontal, premotor and sensorimotor areas compared to ‘stimulation off’. We further demonstrated that the cortico-cortical phase synchronization was largely dominated by genuine neuronal coupling. The clinical improvement with ‘stimulation on’ compared to ‘stimulation off’ could be predicted from this cortical decoupling with multiple regressions, and the reduction of synchronization over the right prefrontal area showed a linear univariate correlation with clinical improvement. Our study demonstrates wide-spread activity and synchronization modulations of the cortical motor network, and highlights subthalamic stimulation as a network-modulating therapy. Accordingly, subthalamic stimulation may release bilateral cortical computational resources by facilitating movement-related desynchronization. Moreover, the subthalamic nucleus is critical to balance inhibitory and facilitatory cortical players within the motor program. PMID:25558877

Genetic variation in MAOA modulates prefrontal cortical regulation of approach-avoidance reactions.

PubMed

Ernst, Lena H; Lutz, Elisabeth; Ehlis, Ann-Christine; Fallgatter, Andreas J; Reif, Andreas; Plichta, Michael M

2013-01-01

Regulation of automatic approach and avoidance behavior requires affective and cognitive control, which are both influenced by a genetic variation in the gene encoding Monoamine Oxidase A (termed MAOA-uVNTR). The current study investigated MAOA genotype as a moderator of prefrontal cortical activation measured with functional near-infrared spectroscopy (fNIRS) in 37 healthy young adults during performance of the approach-avoidance task with positive and negative pictures. Carriers of the low- compared to the high-expressing genetic variant (MAOA-L vs. MAOA-H) showed increasing regulatory activity in the right dorsolateral prefrontal cortex (DLPFC) during incompatible conditions (approach negative, avoid positive). This might have been a compensatory mechanism for stronger emotional reactions as shown in previous studies and might have prevented any influence of incompatibility on behavior. In contrast, fewer errors but also lower activity in the right DLPFC during processing of negative compared to positive stimuli indicated MAOA-H carriers to have used other regulatory areas. This resulted in slower reaction times in incompatible conditions, but--in line with the known better cognitive regulation efficiency--allowed them to perform incompatible reactions without activating the DLPFC as the highest control instance. Carriers of one low- and one high-expressing allele lay as an intermediate group between the reactions of the low- and high-expressing groups. The relatively small sample size and restriction to fNIRS for assessment of cortical activity limit our findings. Nevertheless, these first results suggest monoam-inergic mechanisms to contribute to interindividual differences in the two basic behavioral principles of approach and avoidance and their neuronal correlates. Copyright © 2013 S. Karger AG, Basel.

Reduction of N-acetylaspartate in the medial prefrontal cortex correlated with symptom severity in obsessive-compulsive disorder: meta-analyses of 1H-MRS studies

PubMed Central

Aoki, Yuta; Aoki, Ai; Suwa, Hiroshi

2012-01-01

Structural and functional neuroimaging findings suggest that disturbance of the cortico–striato–thalamo–cortical (CSTC) circuits may underlie obsessive-compulsive disorder (OCD). However, some studies with 1H-magnetic resonance spectroscopy (1H-MRS) reported altered level of N-acetylaspartate (NAA), they yielded inconsistency in direction and location of abnormality within CSTC circuits. We conducted a comprehensive literature search and a meta-analysis of 1H-MRS studies in OCD. Seventeen met the inclusion criteria for a meta-analysis. Data were separated by frontal cortex region: medial prefrontal cortex (mPFC), dorsolateral prefrontal cortex, orbitofrontal cortex, basal ganglia and thalamus. The mean and s.d. of the NAA measure were calculated for each region. A random effects model integrating 16 separate datasets with 225 OCD patients and 233 healthy comparison subjects demonstrated that OCD patients exhibit decreased NAA levels in the frontal cortex (P=0.025), but no significant changes in the basal ganglia (P=0.770) or thalamus (P=0.466). Sensitivity analysis in an anatomically specified subgroup consisting of datasets examining the mPFC demonstrated marginally significant reduction of NAA (P=0.061). Meta-regression revealed that NAA reduction in the mPFC was positively correlated with symptom severity measured by Yale–Brown Obsessive Compulsive Scale (P=0.011). The specific reduction of NAA in the mPFC and significant relationship between neurochemical alteration in the mPFC and symptom severity indicate that the mPFC is one of the brain regions that directly related to abnormal behavior in the pathophysiology of OCD. The current meta-analysis indicates that cortices and sub-cortices contribute in different ways to the etiology of OCD. PMID:22892718

Impact of different intensities of intermittent theta burst stimulation on the cortical properties during TMS-EEG and working memory performance.

PubMed

Chung, Sung Wook; Rogasch, Nigel C; Hoy, Kate E; Sullivan, Caley M; Cash, Robin F H; Fitzgerald, Paul B

2018-02-01

Intermittent theta burst stimulation (iTBS) is a noninvasive brain stimulation technique capable of increasing cortical excitability beyond the stimulation period. Due to the rapid induction of modulatory effects, prefrontal application of iTBS is gaining popularity as a therapeutic tool for psychiatric disorders such as depression. In an attempt to increase efficacy, higher than conventional intensities are currently being applied. The assumption that this increases neuromodulatory may be mechanistically false for iTBS. This study examined the influence of intensity on the neurophysiological and behavioural effects of iTBS in the prefrontal cortex. Sixteen healthy participants received iTBS over prefrontal cortex at either 50, 75 or 100% resting motor threshold in separate sessions. Single-pulse TMS and concurrent electroencephalography (EEG) was used to assess changes in cortical reactivity measured as TMS-evoked potentials and oscillations. The n-back task was used to assess changes in working memory performance. The data can be summarised as an inverse U-shape relationship between intensity and iTBS plastic effects, where 75% iTBS yielded the largest neurophysiological changes. Improvement in reaction time in the 3-back task was supported by the change in alpha power, however, comparison between conditions revealed no significant differences. The assumption that higher intensity results in greater neuromodulatory effects may be false, at least in healthy individuals, and should be carefully considered for clinical populations. Neurophysiological changes associated with working memory following iTBS suggest functional relevance. However, the effects of different intensities on behavioural performance remain elusive in the present healthy sample. © 2017 Wiley Periodicals, Inc.

Self-Disturbances as a Possible Premorbid Indicator of Schizophrenia Risk: A Neurodevelopmental Perspective

PubMed Central

Brent, Benjamin K.; Seidman, Larry J.; Thermenos, Heidi W.; Holt, Daphne J.; Keshavan, Matcheri S.

2013-01-01

Self-disturbances (SDs) are increasingly identified in schizophrenia and are theorized to confer vulnerability to psychosis. Neuroimaging research has shed some light on the neural correlates of SDs in schizophrenia. But, the onset and trajectory of the neural alterations underlying SDs in schizophrenia remain incompletely understood. We hypothesize that the aberrant structure and function of brain areas (e.g., prefrontal, lateral temporal, and parietal cortical structures) comprising the “neural circuitry of self” may represent an early, premorbid (i.e., pre-prodromal) indicator of schizophrenia risk. Consistent with neurodevelopmental models, we argue that “early” (i.e., perinatal) dysmaturational processes (e.g., abnormal cortical neural cell migration and mini-columnar formation) affecting key prefrontal (e.g., medial prefrontal cortex), lateral temporal cortical (e.g., superior temporal sulcus), parietal (e.g., inferior parietal lobule) structures involved in self-processing may lead to subtle disruptions of “self” during childhood in persons at risk for schizophrenia. During adolescence, progressive neurodevelopmental alterations (e.g., aberrant synaptic pruning) affecting the neural circuitry of self may contribute to worsening of SDs. This could result in the emergence of prodromal symptoms and, eventually, full-blown psychosis. To highlight why adolescence may be a period of heightened risk for SDs, we first summarize the literature regarding the neural correlates of self in typically developing children. Next, we present evidence from neuroimaging studies in genetic high-risk youth suggesting that fronto-temporal-parietal structures mediating self-reflection may be abnormal in the premorbid period. Our goal is that the ideas presented here might provide future directions for research into the neurobiology of SDs during the pre-psychosis development of youth at risk for schizophrenia. PMID:23932148

Visual Receptive Field Heterogeneity and Functional Connectivity of Adjacent Neurons in Primate Frontoparietal Association Cortices.

PubMed

Viswanathan, Pooja; Nieder, Andreas

2017-09-13

The basic organization principles of the primary visual cortex (V1) are commonly assumed to also hold in the association cortex such that neurons within a cortical column share functional connectivity patterns and represent the same region of the visual field. We mapped the visual receptive fields (RFs) of neurons recorded at the same electrode in the ventral intraparietal area (VIP) and the lateral prefrontal cortex (PFC) of rhesus monkeys. We report that the spatial characteristics of visual RFs between adjacent neurons differed considerably, with increasing heterogeneity from VIP to PFC. In addition to RF incongruences, we found differential functional connectivity between putative inhibitory interneurons and pyramidal cells in PFC and VIP. These findings suggest that local RF topography vanishes with hierarchical distance from visual cortical input and argue for increasingly modified functional microcircuits in noncanonical association cortices that contrast V1. SIGNIFICANCE STATEMENT Our visual field is thought to be represented faithfully by the early visual brain areas; all the information from a certain region of the visual field is conveyed to neurons situated close together within a functionally defined cortical column. We examined this principle in the association areas, PFC, and ventral intraparietal area of rhesus monkeys and found that adjacent neurons represent markedly different areas of the visual field. This is the first demonstration of such noncanonical organization of these brain areas. Copyright © 2017 the authors 0270-6474/17/378919-10$15.00/0.

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

Brain imaging studies of the cocaine addict: Implications for reinforcement and addiction

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

Volkow, N.D.; Fowler, J.S.

1995-07-01

These studies document dopaminergic abnormalities in cocaine abusers. They also suggest a regulatory role of Dopamine (DA) in frontal metabolism. The correlation of striatal D{sub 2} receptor availability with metabolism was strongest for orbital frontal cortex (OFC) cingulate and prefrontal cortices. In cocaine abusers tested during early withdrawal (<1 week) the OFC was found to be hypermetabolic and metabolism in OFC and prefrontal cortices were found to be significantly associated with cocaine craving . Thus, we postulate that repeated and intermittent DA stimulation, as seen during a cocaine binge, activates the prefrontal and OFC cortices increasing the drive to compulsivelymore » self-administer cocaine. During cocaine discontinuation and protracted withdrawal and with decreased DA stimulation, these frontal cortical regions become hyponietabolic. Dopaminergic stimulation by a DA-enhancing drug and/or environmental conditioning will reactivate these frontal regions resetting the compulsion to self-administer cocaine and the inability to terminate this behavior. The pharmacokionetic studies with [11C]cocaine are consistent with behavioral and pharmacological studies in animals as well as in vitro studies which have revealed that while the mechanisms for cocaine`s reinforcing properties are complex, they partly involve the brain`s dopamine system and also highlight the importance of cocaine`s pharmacokinetic on its unique reinforcing properties.« less

Intentionality as a link between the neuropsychology and the symptoms of schizophrenia.

PubMed

Kaiser, Stefan; Weisbrod, Matthias

2007-01-01

Cognitive deficits are an important feature of schizophrenia, particularly in the areas of working memory and executive function. However, their relationship to other clinical dimensions of the illness has remained elusive. We suggest that a phenomenological exploration of disordered intentionality in schizophrenia symptoms might provide us with a framework for understanding the role of cognitive deficits. We propose an understanding of intentionality as having a layered structure, which facilitates a mapping onto neuropsychological concepts. A disturbance of basic intentional processes can explain some of the 'positive' symptoms of schizophrenia. We focus on the temporal aspect of intentionality, which will be related to recent conceptions of prefrontal cortical function as the temporal organization of thought and behavior. A compensation of these basic disturbances leads to a 'minimization of change', which can explain some of the 'negative' symptoms. The compensatory strategies are thought to rely on the higher-order executive functions of the prefrontal cortex. These are also disturbed in schizophrenia, which often renders the process of compensation ineffective, leading to a fragmentation of thought and behavior. Thus the concept of intentionality might help us relate different aspects of prefrontal dysfunction to specific schizophrenic symptom clusters. (c) 2007 S. Karger AG, Basel.

The role of the thalamic nuclei in recognition memory accompanied by recall during encoding and retrieval: an fMRI study.

PubMed

Pergola, Giulio; Ranft, Alexander; Mathias, Klaus; Suchan, Boris

2013-07-01

The present functional imaging study aimed at investigating the contribution of the mediodorsal nucleus and the anterior nuclei of the thalamus with their related cortical networks to recognition memory and recall. Eighteen subjects performed associative picture encoding followed by a single item recognition test during the functional magnetic resonance imaging session. After scanning, subjects performed a cued recall test using the formerly recognized pictures as cues. This post-scanning test served to classify recognition trials according to subsequent recall performance. In general, single item recognition accompanied by successful recall of the associations elicited stronger activation in the mediodorsal nucleus of the thalamus and in the prefrontal cortices both during encoding and retrieval compared to recognition without recall. In contrast, the anterior nuclei of the thalamus were selectively active during the retrieval phase of recognition followed by recall. A correlational analysis showed that activation of the anterior thalamus during retrieval as assessed by measuring the percent signal changes predicted lower rates of recognition without recall. These findings show that the thalamus is critical for recognition accompanied by recall, and provide the first evidence of a functional segregation of the thalamic nuclei with respect to the memory retrieval phase. In particular, the mediodorsal thalamic-prefrontal cortical network is activated during successful encoding and retrieval of associations, which suggests a role of this system in recall and recollection. The activity of the anterior thalamic-temporal network selectively during retrieval predicts better memory performances across subjects and this confirms the paramount role of this network in recall and recollection. Copyright © 2013 Elsevier Inc. All rights reserved.

Task-relevant output signals are sent from monkey dorsolateral prefrontal cortex to the superior colliculus during a visuospatial working memory task.

PubMed

Johnston, Kevin; Everling, Stefan

2009-05-01

Visuospatial working memory is one of the most extensively investigated functions of the dorsolateral prefrontal cortex (DLPFC). Theories of prefrontal cortical function have suggested that this area exerts cognitive control by modulating the activity of structures to which it is connected. Here, we used the oculomotor system as a model in which to characterize the output signals sent from the DLPFC to a target structure during a classical spatial working memory task. We recorded the activity of identified DLPFC-superior colliculus (SC) projection neurons while monkeys performed a memory-guided saccade task in which they were required to generate saccades toward remembered stimulus locations. DLPFC neurons sent signals related to all aspects of the task to the SC, some of which were spatially tuned. These data provide the first direct evidence that the DLPFC sends task-relevant information to the SC during a spatial working memory task, and further support a role for the DLPFC in the direct modulation of other brain areas.

Multiple anatomical systems embedded within the primate medial temporal lobe: implications for hippocampal function.

PubMed

Aggleton, John P

2012-08-01

A review of medial temporal lobe connections reveals three distinct groupings of hippocampal efferents. These efferent systems and their putative memory functions are: (1) The 'extended-hippocampal system' for episodic memory, which involves the anterior thalamic nuclei, mammillary bodies and retrosplenial cortex, originates in the subicular cortices, and has a largely laminar organisation; (2) The 'rostral hippocampal system' for affective and social learning, which involves prefrontal cortex, amygdala and nucleus accumbens, has a columnar organisation, and originates from rostral CA1 and subiculum; (3) The 'reciprocal hippocampal-parahippocampal system' for sensory processing and integration, which originates from the length of CA1 and the subiculum, and is characterised by columnar, connections with reciprocal topographies. A fourth system, the 'parahippocampal-prefrontal system' that supports familiarity signalling and retrieval processing, has more widespread prefrontal connections than those of the hippocampus, along with different thalamic inputs. Despite many interactions between these four systems, they may retain different roles in memory which when combined explain the importance of the medial temporal lobe for the formation of declarative memories. Copyright © 2011 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.

Diffusion imaging and transcranial magnetic stimulation assessment of transcallosal pathways in chronic stroke.

PubMed

Mang, Cameron S; Borich, Michael R; Brodie, Sonia M; Brown, Katlyn E; Snow, Nicholas J; Wadden, Katie P; Boyd, Lara A

2015-10-01

To examine the relationship of transcallosal pathway microstructure and transcallosal inhibition (TCI) with motor function and impairment in chronic stroke. Diffusion-weighted magnetic resonance imaging and transcranial magnetic stimulation (TMS) data were collected from 24 participants with chronic stroke and 11 healthy older individuals. Post-stroke motor function (Wolf Motor Function Test) and level of motor impairment (Fugl-Meyer score) were evaluated. Fractional anisotropy (FA) of transcallosal tracts between prefrontal cortices and the mean amplitude decrease in muscle activity during the ipsilateral silent period evoked by TMS over the non-lesioned hemisphere (termed NL-iSPmean) were significantly associated with level of motor impairment and motor function after stroke (p<0.05). A regression model including age, post-stroke duration, lesion volume, lesioned corticospinal tract FA, transcallosal prefrontal tract FA and NL-iSPmean accounted for 84% of variance in motor impairment (p<0.01). Both transcallosal prefrontal tract FA (ΔR(2)=0.12, p=0.04) and NL-iSPmean (ΔR(2)=0.09, p=0.04) accounted for unique variance in motor impairment level. Prefrontal transcallosal tract microstructure and TCI are each uniquely associated with motor impairment in chronic stroke. Utilizing a multi-modal approach to assess transcallosal pathways may improve our capacity to identify important neural substrates of motor impairment in the chronic phase of stroke. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Cortical underconnectivity coupled with preserved visuospatial cognition in autism: Evidence from an fMRI study of an embedded figures task.

PubMed

Damarla, Saudamini Roy; Keller, Timothy A; Kana, Rajesh K; Cherkassky, Vladimir L; Williams, Diane L; Minshew, Nancy J; Just, Marcel Adam

2010-10-01

Individuals with high-functioning autism sometimes exhibit intact or superior performance on visuospatial tasks, in contrast to impaired functioning in other domains such as language comprehension, executive tasks, and social functions. The goal of the current study was to investigate the neural bases of preserved visuospatial processing in high-functioning autism from the perspective of the cortical underconnectivity theory. We used a combination of behavioral, functional magnetic resonance imaging, functional connectivity, and corpus callosum morphometric methodological tools. Thirteen participants with high-functioning autism and 13 controls (age-, IQ-, and gender-matched) were scanned while performing an Embedded Figures Task. Despite the ability of the autism group to attain behavioral performance comparable to the control group, the brain imaging results revealed several group differences consistent with the cortical underconnectivity account of autism. First, relative to controls, the autism group showed less activation in the left dorsolateral prefrontal and inferior parietal areas and more activation in visuospatial (bilateral superior parietal extending to inferior parietal and right occipital) areas. Second, the autism group demonstrated lower functional connectivity between higher-order working memory/executive areas and visuospatial regions (between frontal and parietal-occipital). Third, the size of the corpus callosum (an index of anatomical connectivity) was positively correlated with frontal-posterior (parietal and occipital) functional connectivity in the autism group. Thus, even in the visuospatial domain, where preserved performance among people with autism is observed, the neuroimaging signatures of cortical underconnectivity persist.

Cortical underconnectivity coupled with preserved visuospatial cognition in autism: Evidence from an fMRI study of an embedded figures task

PubMed Central

Damarla, Saudamini Roy; Keller, Timothy A.; Kana, Rajesh K.; Cherkassky, Vladimir L.; Williams, Diane L.; Minshew, Nancy J.; Just, Marcel Adam

2010-01-01

Individuals with high-functioning autism sometimes exhibit intact or superior performance on visuospatial tasks, in contrast to impaired functioning in other domains such as language comprehension, executive tasks, and social functions. The goal of the current study was to investigate the neural bases of preserved visuospatial processing in high-functioning autism from the perspective of the cortical underconnectivity theory. We used a combination of behavioral, functional magnetic resonance imaging (fMRI), functional connectivity, and corpus callosum morphometric methodological tools. Thirteen participants with high-functioning autism and thirteen controls (age-, IQ-, and gender-matched) were scanned while performing an Embedded Figures Task (EFT). Despite the ability of the autism group to attain behavioral performance comparable to the control group, the brain imaging results revealed several group differences consistent with the cortical underconnectivity account of autism. First, relative to controls, the autism group showed less activation in left dorsolateral prefrontal and inferior parietal areas and more activation in visuospatial (bilateral superior parietal extending to inferior parietal and right occipital) areas. Second, the autism group demonstrated lower functional connectivity between higher-order working memory/executive areas and visuospatial regions (between frontal and parietal-occipital). Third, the size of the corpus callosum (an index of anatomical connectivity) was positively correlated with frontal-posterior (parietal and occipital) functional connectivity in the autism group. Thus, even in the visuospatial domain, where preserved performance among people with autism is observed, the neuroimaging signatures of cortical underconnectivity persist. PMID:20740492

Psychogenic seizures and frontal disconnection: EEG synchronisation study.

PubMed

Knyazeva, Maria G; Jalili, Mahdi; Frackowiak, Richard S; Rossetti, Andrea O

2011-05-01

Psychogenic non-epileptic seizures (PNES) are paroxysmal events that, in contrast to epileptic seizures, are related to psychological causes without the presence of epileptiform EEG changes. Recent models suggest a multifactorial basis for PNES. A potentially paramount, but currently poorly understood factor is the interplay between psychiatric features and a specific vulnerability of the brain leading to a clinical picture that resembles epilepsy. Hypothesising that functional cerebral network abnormalities may predispose to the clinical phenotype, the authors undertook a characterisation of the functional connectivity in PNES patients. The authors analysed the whole-head surface topography of multivariate phase synchronisation (MPS) in interictal high-density EEG of 13 PNES patients as compared with 13 age- and sex-matched controls. MPS mapping reduces the wealth of dynamic data obtained from high-density EEG to easily readable synchronisation maps, which provide an unbiased overview of any changes in functional connectivity associated with distributed cortical abnormalities. The authors computed MPS maps for both Laplacian and common-average-reference EEGs. In a between-group comparison, only patchy, non-uniform changes in MPS survived conservative statistical testing. However, against the background of these unimpressive group results, the authors found widespread inverse correlations between individual PNES frequency and MPS within the prefrontal and parietal cortices. PNES appears to be associated with decreased prefrontal and parietal synchronisation, possibly reflecting dysfunction of networks within these regions.

Neural circuits in Auditory and Audiovisual Memory

PubMed Central

Plakke, B.; Romanski, L.M.

2016-01-01

Working memory is the ability to employ recently seen or heard stimuli and apply them to changing cognitive context. Although much is known about language processing and visual working memory, the neurobiological basis of auditory working memory is less clear. Historically, part of the problem has been the difficulty in obtaining a robust animal model to study auditory short-term memory. In recent years there has been neurophysiological and lesion studies indicating a cortical network involving both temporal and frontal cortices. Studies specifically targeting the role of the prefrontal cortex (PFC) in auditory working memory have suggested that dorsal and ventral prefrontal regions perform different roles during the processing of auditory mnemonic information, with the dorsolateral PFC performing similar functions for both auditory and visual working memory. In contrast, the ventrolateral PFC (VLPFC), which contains cells that respond robustly to auditory stimuli and that process both face and vocal stimuli may be an essential locus for both auditory and audiovisual working memory. These findings suggest a critical role for the VLPFC in the processing, integrating, and retaining of communication information. PMID:26656069

Neural mechanisms of interference control in working memory capacity.

PubMed

Bomyea, Jessica; Taylor, Charles T; Spadoni, Andrea D; Simmons, Alan N

2018-02-01

The extent to which one can use cognitive resources to keep information in working memory is known to rely on (1) active maintenance of target representations and (2) downregulation of interference from irrelevant representations. Neurobiologically, the global capacity of working memory is thought to depend on the prefrontal and parietal cortices; however, the neural mechanisms involved in controlling interference specifically in working memory capacity tasks remain understudied. In this study, 22 healthy participants completed a modified complex working memory capacity task (Reading Span) with trials of varying levels of interference control demands while undergoing functional MRI. Neural activity associated with interference control demands was examined separately during encoding and recall phases of the task. Results suggested a widespread network of regions in the prefrontal, parietal, and occipital cortices, and the cingulate and cerebellum associated with encoding, and parietal and occipital regions associated with recall. Results align with prior findings emphasizing the importance of frontoparietal circuits for working memory performance, including the role of the inferior frontal gyrus, cingulate, occipital cortex, and cerebellum in regulation of interference demands. © 2017 Wiley Periodicals, Inc.

Comparable cortical activation with inferior performance in women during a novel cognitive inhibition task.

PubMed

Halari, R; Kumari, V

2005-03-07

Men are hypothesised to perform better than women at tasks requiring cognitive inhibition. The present study applied whole-brain functional magnetic resonance imaging to investigate the neural correlates of cognitive inhibition using a novel task, requiring detection of numbers decreasing in numerical order, in relation to sex. The study involved 19 young healthy subjects (9 men, 10 women). Behavioural sex differences favouring men were found on the inhibition, but not on the automatization (i.e. detection of numbers increasing in numerical order), condition of the task. Significant areas of activation associated with cognitive inhibition included the right inferior prefrontal and bilateral dorsolateral prefrontal cortices, left inferior and superior parietal lobes, and bilateral temporal regions across men and women. No brain region was significantly differently activated in men and women. Our findings demonstrate that (a) cognitive inhibition is dependent on intact processes within frontal and parietal regions, and (b) women show inferior cognitive inhibition despite of comparable activation to men in relevant regions. Equated behavioural performance may elicit sex differences in brain activation.

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

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.

Change in emotional self-concept following socio-cognitive training relates to structural plasticity of the prefrontal cortex.

PubMed

Lumma, Anna-Lena; Valk, Sofie L; Böckler, Anne; Vrtička, Pascal; Singer, Tania

2018-04-01

Self-referential processing is a key component of the emotional self-concept. Previous studies have shown that emotional self-referential processing is related to structure and function of cortical midline areas such as medial prefrontal cortex (mPFC), and that it can be altered on a behavioral level by specific mental training practices. However, it remains unknown how behavioral training-related change in emotional self-concept content relates to structural plasticity. To address this issue, we examined the relationship between training-induced change in participant's emotional self-concept measured through emotional word use in the Twenty Statement Test and change in cortical thickness in the context of a large-scale longitudinal mental training study called the ReSource Project . Based on prior behavioral findings showing increased emotional word use particularly after socio-cognitive training targeting perspective-taking capacities, this study extended these results by revealing that individual differences in the degree to which participants changed their emotional self-concept after training was positively related to cortical thickness change in right mPFC extending to dorsolateral PFC (dlPFC). Furthermore, increased self-related negative emotional word use after training was positively associated with cortical thickness change in left pars orbitalis and bilateral dlPFC. Our findings reveal training-related structural brain change in regions known to be involved in self-referential processing and cognitive control, and could indicate a relationship between restructuring of the emotional self-concept content as well as reappraisal of negative aspects and cortical thickness change. As such, our findings can guide the development of psychological interventions targeted to alter specific facets of the self-concept.

Altered Gradients of Glutamate and Gamma-Aminobutyric Acid Transcripts in the Cortical Visuospatial Working Memory Network in Schizophrenia.

PubMed

Hoftman, Gil D; Dienel, Samuel J; Bazmi, Holly H; Zhang, Yun; Chen, Kehui; Lewis, David A

2018-04-15

Visuospatial working memory (vsWM), which is impaired in schizophrenia, requires information transfer across multiple nodes in the cerebral cortex, including visual, posterior parietal, and dorsolateral prefrontal regions. Information is conveyed across these regions via the excitatory projections of glutamatergic pyramidal neurons located in layer 3, whose activity is modulated by local inhibitory gamma-aminobutyric acidergic (GABAergic) neurons. Key properties of these neurons differ across these cortical regions. Consequently, in schizophrenia, alterations in the expression of gene products regulating these properties could disrupt vsWM function in different ways, depending on the region(s) affected. Here, we quantified the expression of markers of glutamate and GABA neurotransmission selectively in layer 3 of four cortical regions in the vsWM network from 20 matched pairs of schizophrenia and unaffected comparison subjects. In comparison subjects, levels of glutamate transcripts tended to increase, whereas GABA transcript levels tended to decrease, from caudal to rostral, across cortical regions of the vsWM network. Composite measures across all transcripts revealed a significant effect of region, with the glutamate measure lowest in the primary visual cortex and highest in the dorsolateral prefrontal cortex, whereas the GABA measure showed the opposite pattern. In schizophrenia subjects, the expression levels of many of these transcripts were altered. However, this disease effect differed across regions, such that the caudal-to-rostral increase in the glutamate measure was blunted and the caudal-to-rostral decline in the GABA measure was enhanced in the illness. Differential alterations in layer 3 glutamate and GABA neurotransmission across cortical regions may contribute to vsWM deficits in schizophrenia. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Resting state functional connectivity of the anterior striatum and prefrontal cortex predicts reading performance in school-age children.

PubMed

Alcauter, Sarael; García-Mondragón, Liliana; Gracia-Tabuenca, Zeus; Moreno, Martha B; Ortiz, Juan J; Barrios, Fernando A

2017-11-01

The current study investigated the neural basis of reading performance in 60 school-age Spanish-speaking children, aged 6 to 9years. By using a data-driven approach and an automated matching procedure, we identified a left-lateralized resting state network that included typical language regions (Wernicke's and Broca's regions), prefrontal cortex, pre- and post-central gyri, superior and middle temporal gyri, cerebellum, and subcortical regions, and explored its relevance for reading performance (accuracy, comprehension and speed). Functional connectivity of the left frontal and temporal cortices and subcortical regions predicted reading speed. These results extend previous findings on the relationship between functional connectivity and reading competence in children, providing new evidence about such relationships in previously unexplored regions in the resting brain, including the left caudate, putamen and thalamus. This work highlights the relevance of a broad network, functionally synchronized in the resting state, for the acquisition and perfecting of reading abilities in young children. Copyright © 2017 Elsevier Inc. All rights reserved.

Methylphenidate and the Juvenile Brain: Enhancement of Attention at the Expense of Cortical Plasticity?

PubMed Central

Urban, Kimberly R.; Gao, Wen-Jun

2013-01-01

Methylphenidate (Ritalin) is the most commonly prescribed psychoactive drug for juveniles and adolescents. Used to treat attention-deficit/hyperactivity disorder (ADHD) and for cognitive enhancement in healthy individuals, it has been regarded as a relatively safe medication for the past several decades. However, a thorough review of the literature reveals that the age-dependent activities of the drug, as well as potential developmental effects, are largely ignored. In addition, the diagnosis of ADHD is subjective, leaving open the possibility of misdiagnosis and excessive prescription of the drug. Recent studies have suggested that early life exposure of healthy rodent models to methylphenidate resulted in altered sleep/wake cycle, heightened stress reactivity, and, in fact, a dosage previously thought of as therapeutic depressed neuronal function in juvenile rats. Furthermore, juvenile rats exposed to low-dose methylphenidate displayed alterations in neural markers of plasticity, indicating that the drug might alter the basic properties of prefrontal cortical circuits. In this review of the current literature, we propose that juvenile exposure to methylphenidate may cause abnormal prefrontal function and impaired plasticity in the healthy brain, strengthening the case for developing a more thorough understanding of methylphenidate’s actions on the developing, juvenile brain, as well as better diagnostic measures for ADHD. PMID:24095262

Functional inactivation of hypocretin 1 receptors in the medial prefrontal cortex affects the pyramidal neuron activity and gamma oscillations: An in vivo multiple-channel single-unit recording study.

PubMed

He, C; Chen, Q-H; Ye, J-N; Li, C; Yang, L; Zhang, J; Xia, J-X; Hu, Z-A

2015-06-25

The hypocretin signaling is thought to play a critical role in maintaining wakefulness via stimulating the subcortical arousal pathways. Although the cortical areas, including the medial prefrontal cortex (mPFC), receive dense hypocretinergic fibers and express its receptors, it remains unclear whether the hypocretins can directly regulate the neural activity of the mPFC in vivo. In the present study, using multiple-channel single-unit recording study, we found that infusion of the SB-334867, a blocker for the Hcrtr1, beside the recording sites within the mPFC substantially exerted an inhibitory effect on the putative pyramidal neuron (PPN) activity in naturally behaving rats. In addition, functional blockade of the Hcrtr1 also selectively reduced the power of the gamma oscillations. The PPN activity and the power of the neural oscillations were not affected after microinjection of the TCS-OX2-29, a blocker for the Hcrtr2, within the mPFC. Together, these data indicate that endogenous hypocretins acting on the Hcrtr1 are required for the normal neural activity in the mPFC in vivo, and thus might directly contribute cortical arousal and mPFC-dependent cognitive processes. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Is There a Canonical Cortical Circuit for the Cholinergic System? Anatomical Differences Across Common Model Systems.

PubMed

Coppola, Jennifer J; Disney, Anita A

2018-01-01

Acetylcholine (ACh) is believed to act as a neuromodulator in cortical circuits that support cognition, specifically in processes including learning, memory consolidation, vigilance, arousal and attention. The cholinergic modulation of cortical processes is studied in many model systems including rodents, cats and primates. Further, these studies are performed in cortical areas ranging from the primary visual cortex to the prefrontal cortex and using diverse methodologies. The results of these studies have been combined into singular models of function-a practice based on an implicit assumption that the various model systems are equivalent and interchangeable. However, comparative anatomy both within and across species reveals important differences in the structure of the cholinergic system. Here, we will review anatomical data including innervation patterns, receptor expression, synthesis and release compared across species and cortical area with a focus on rodents and primates. We argue that these data suggest no canonical cortical model system exists for the cholinergic system. Further, we will argue that as a result, care must be taken both in combining data from studies across cortical areas and species, and in choosing the best model systems to improve our understanding and support of human health.

Functional Neuroimaging Insights into the Physiology of Human Sleep

PubMed Central

Dang-Vu, Thien Thanh; Schabus, Manuel; Desseilles, Martin; Sterpenich, Virginie; Bonjean, Maxime; Maquet, Pierre

2010-01-01

Functional brain imaging has been used in humans to noninvasively investigate the neural mechanisms underlying the generation of sleep stages. On the one hand, REM sleep has been associated with the activation of the pons, thalamus, limbic areas, and temporo-occipital cortices, and the deactivation of prefrontal areas, in line with theories of REM sleep generation and dreaming properties. On the other hand, during non-REM (NREM) sleep, decreases in brain activity have been consistently found in the brainstem, thalamus, and in several cortical areas including the medial prefrontal cortex (MPFC), in agreement with a homeostatic need for brain energy recovery. Benefiting from a better temporal resolution, more recent studies have characterized the brain activations related to phasic events within specific sleep stages. In particular, they have demonstrated that NREM sleep oscillations (spindles and slow waves) are indeed associated with increases in brain activity in specific subcortical and cortical areas involved in the generation or modulation of these waves. These data highlight that, even during NREM sleep, brain activity is increased, yet regionally specific and transient. Besides refining the understanding of sleep mechanisms, functional brain imaging has also advanced the description of the functional properties of sleep. For instance, it has been shown that the sleeping brain is still able to process external information and even detect the pertinence of its content. The relationship between sleep and memory has also been refined using neuroimaging, demonstrating post-learning reactivation during sleep, as well as the reorganization of memory representation on the systems level, sometimes with long-lasting effects on subsequent memory performance. Further imaging studies should focus on clarifying the role of specific sleep patterns for the processing of external stimuli, as well as the consolidation of freshly encoded information during sleep. Citation: Dang-Vu TT; Schabus M; Desseilles M; Sterpenich V; Bonjean M; Maquet P. Functional neuroimaging insights into the physiology of human sleep. SLEEP 2010;33(12):1589-1603. PMID:21120121

The Development of Human Amygdala Functional Connectivity at Rest from 4 to 23 Years: a cross-sectional study

PubMed Central

Gabard-Durnam, Laurel J.; Flannery, Jessica; Goff, Bonnie; Gee, Dylan G.; Humphreys, Kathryn L.; Telzer, Eva; Hare, Todd; Tottenham, Nim

2014-01-01

Functional connections (FC) between the amygdala and cortical and subcortical regions underlie a range of affective and cognitive processes. Despite the central role amygdala networks have in these functions, the normative developmental emergence of FC between the amygdala and the rest of the brain is still largely undefined. This study employed amygdala subregion maps and resting-state functional magnetic resonance imaging to characterize the typical development of human amygdala FC from age 4 to 23 years old (n = 58). Amygdala FC with subcortical and limbic regions was largely stable across this developmental period. However, three cortical regions exhibited age-dependent changes in FC: amygdala FC with the medial prefrontal cortex (mPFC) increased with age, while amygdala FC with a region including the insula and superior temporal sulcus decreased with age, and amygdala FC with a region encompassing the parahippocampal gyrus and posterior cingulate also decreased with age. The transition from childhood to adolescence (around age 10 years) marked an important change-point in the nature of amygdala-cortical FC. We distinguished unique developmental patterns of coupling for three amygdala subregions and found particularly robust convergence of FC for all subregions with the mPFC. These findings suggest that there are extensive changes in amygdala-cortical functional connectivity that emerge between childhood and adolescence. PMID:24662579

A model for integrating elementary neural functions into delayed-response behavior.

PubMed

Gisiger, Thomas; Kerszberg, Michel

2006-04-01

It is well established that various cortical regions can implement a wide array of neural processes, yet the mechanisms which integrate these processes into behavior-producing, brain-scale activity remain elusive. We propose that an important role in this respect might be played by executive structures controlling the traffic of information between the cortical regions involved. To illustrate this hypothesis, we present a neural network model comprising a set of interconnected structures harboring stimulus-related activity (visual representation, working memory, and planning), and a group of executive units with task-related activity patterns that manage the information flowing between them. The resulting dynamics allows the network to perform the dual task of either retaining an image during a delay (delayed-matching to sample task), or recalling from this image another one that has been associated with it during training (delayed-pair association task). The model reproduces behavioral and electrophysiological data gathered on the inferior temporal and prefrontal cortices of primates performing these same tasks. It also makes predictions on how neural activity coding for the recall of the image associated with the sample emerges and becomes prospective during the training phase. The network dynamics proves to be very stable against perturbations, and it exhibits signs of scale-invariant organization and cooperativity. The present network represents a possible neural implementation for active, top-down, prospective memory retrieval in primates. The model suggests that brain activity leading to performance of cognitive tasks might be organized in modular fashion, simple neural functions becoming integrated into more complex behavior by executive structures harbored in prefrontal cortex and/or basal ganglia.

Age-Dependent Effects of Catechol-O-Methyltransferase (COMT) Gene Val158Met Polymorphism on Language Function in Developing Children.

PubMed

Sugiura, Lisa; Toyota, Tomoko; Matsuba-Kurita, Hiroko; Iwayama, Yoshimi; Mazuka, Reiko; Yoshikawa, Takeo; Hagiwara, Hiroko

2017-01-01

The genetic basis controlling language development remains elusive. Previous studies of the catechol-O-methyltransferase (COMT) Val158Met genotype and cognition have focused on prefrontally guided executive functions involving dopamine. However, COMT may further influence posterior cortical regions implicated in language perception. We investigated whether COMT influences language ability and cortical language processing involving the posterior language regions in 246 children aged 6-10 years. We assessed language ability using a language test and cortical responses recorded during language processing using a word repetition task and functional near-infrared spectroscopy. The COMT genotype had significant effects on language performance and processing. Importantly, Met carriers outperformed Val homozygotes in language ability during the early elementary school years (6-8 years), whereas Val homozygotes exhibited significant language development during the later elementary school years. Both genotype groups exhibited equal language performance at approximately 10 years of age. Val homozygotes exhibited significantly less cortical activation compared with Met carriers during word processing, particularly at older ages. These findings regarding dopamine transmission efficacy may be explained by a hypothetical inverted U-shaped curve. Our findings indicate that the effects of the COMT genotype on language ability and cortical language processing may change in a narrow age window of 6-10 years. © The Author 2016. Published by Oxford University Press.

Prenatal Ontogeny as a Susceptibility Period for Cortical GABA Neuron Disturbances in Schizophrenia

PubMed Central

Volk, David W.; Lewis, David A.

2013-01-01

Cognitive deficits in schizophrenia have been linked to disturbances in GABA neurons in the prefrontal cortex. Furthermore, cognitive deficits in schizophrenia appear well before the onset of psychosis and have been reported to be present during early childhood and even during the first year of life. Taken together, these data raise the following question: Does the disease process that produces abnormalities in prefrontal GABA neurons in schizophrenia begin prenatally and disrupt the ontogeny of cortical GABA neurons? Here, we address this question through a consideration of evidence that genetic and/or environmental insults that occur during gestation initiate a pathogenetic process that alters cortical GABA neuron ontogeny and produces the pattern of GABA neuron abnormalities, and consequently cognitive difficulties, seen in schizophrenia. First, we review available evidence from postmortem human brain tissue studies characterizing alterations in certain subpopulations of prefrontal GABA neuron that provide clues to a prenatal origin in schizophrenia. Second, we review recent discoveries of transcription factors, cytokine receptors, and other developmental regulators that govern the birth, migration, specification, maturation, and survival of different subpopulations of prefrontal GABA neurons. Third, we discuss recent studies demonstrating altered expression of these ontogenetic factors in the prefrontal cortex in schizophrenia. Fourth, we discuss the potential role of disturbances in the maternal-fetal environment such as maternal immune activation in the development of GABA neuron dysfunction. Finally, we propose critical questions that need to be answered in future research to further investigate the role of altered GABA neuron ontogeny in the pathogenesis of schizophrenia. PMID:23769891

Altered prefrontal cortical function during processing of fear-relevant stimuli in pregnancy.

PubMed

Roos, Annerine; Robertson, Frances; Lochner, Christine; Vythilingum, Bavanisha; Stein, Dan J

2011-09-12

In non-pregnant individuals, the prefrontal cortex (PFC) is involved in the regulation of emotion, and appears to play a role in anxiety. Near-infrared spectroscopy (NIRS) detects cortical neural activation without harmful radiation making it safe for use in pregnancy. The aims of this study were to assess neural circuitry involved in processing fear-relevant stimuli during pregnancy using NIRS, and to determine associations between activation of this circuitry, distress and anxiety symptoms, attention to threat, cortisol, estrogen, progesterone and testosterone levels. There was significant activation of the PFC in response to fearful faces compared to rest in both pregnant and control groups. Within pregnancy, the activation was most pronounced at trimester 2, compared to the other trimesters. In pregnant women only (all trimesters), PFC activation was significantly associated with increased distress and anxiety, but with decreased selective attention to masked fear. PFC activation was also significantly associated with increased levels of cortisol and testosterone in pregnancy. PFC function appears to be altered during processing of fear-relevant stimuli in pregnancy. Changes in hormone levels may lead to changes in PFC function, and in turn to changes in cognitive-affective processing and anxiety. Further work is needed, however, to explore precisely how PFC function is altered in pregnancy; it is possible that certain changes reflect altered processing of threat stimuli, while others reflect attempts to compensate for distressing and anxious symptoms that emerge during pregnancy. Copyright © 2011 Elsevier B.V. All rights reserved.

Investigating the Neural Correlates of Emotion–Cognition Interaction Using an Affective Stroop Task

PubMed Central

Raschle, Nora M.; Fehlbaum, Lynn V.; Menks, Willeke M.; Euler, Felix; Sterzer, Philipp; Stadler, Christina

2017-01-01

The human brain has the capacity to integrate various sources of information and continuously adapts our behavior according to situational needs in order to allow a healthy functioning. Emotion–cognition interactions are a key example for such integrative processing. However, the neuronal correlates investigating the effects of emotion on cognition remain to be explored and replication studies are needed. Previous neuroimaging studies have indicated an involvement of emotion and cognition related brain structures including parietal and prefrontal cortices and limbic brain regions. Here, we employed whole brain event-related functional magnetic resonance imaging (fMRI) during an affective number Stroop task and aimed at replicating previous findings using an adaptation of an existing task design in 30 healthy young adults. The Stroop task is an indicator of cognitive control and enables the quantification of interference in relation to variations in cognitive load. By the use of emotional primes (negative/neutral) prior to Stroop task performance, an emotional variation is added as well. Behavioral in-scanner data showed that negative primes delayed and disrupted cognitive processing. Trials with high cognitive demand furthermore negatively influenced cognitive control mechanisms. Neuronally, the emotional primes consistently activated emotion-related brain regions (e.g., amygdala, insula, and prefrontal brain regions) while Stroop task performance lead to activations in cognition networks of the brain (prefrontal cortices, superior temporal lobe, and insula). When assessing the effect of emotion on cognition, increased cognitive demand led to decreases in neural activation in response to emotional stimuli (negative > neutral) within prefrontal cortex, amygdala, and insular cortex. Overall, these results suggest that emotional primes significantly impact cognitive performance and increasing cognitive demand leads to reduced neuronal activation in emotion related brain regions, and therefore support previous findings investigating emotion–cognition interaction in healthy adults. Moreover, emotion and cognition seem to be tightly related to each other, as indicated by shared neural networks involved in both of these processes. Emotion processing, cognitive control, and their interaction are crucial for healthy functioning and a lack thereof is related to psychiatric disorders such as, disruptive behavior disorders. Future studies may investigate the neural characteristics of children and adolescents with disruptive behavior disorders. PMID:28919871

Changes in morning salivary melatonin correlate with prefrontal responses during working memory performance.

PubMed

Killgore, William D S; Kent, Haley C; Knight, Sara A; Alkozei, Anna

2018-04-11

Humans demonstrate a circadian rhythm of melatonin production that closely tracks the daily light/dark cycle, with profound increases in circulating levels during the night-time and nearly nonexistent levels during daylight hours. Although melatonin is known to play a role in preparing the brain and body for sleep, its effects on cognition and brain function are not well understood. We hypothesized that declines in morning melatonin would be associated with increased functional activation within cortical regions involved in alertness, attention, and executive function. We measured the change in salivary melatonin from mid-morning to late-morning in 26 healthy young adults who were also exposed to a 30-min period of blue or amber light followed by functional MRI during a working memory task (N-back). Brain activation was regressed on the change in melatonin scores from the mid-morning to late-morning saliva samples and the role of light exposure was also assessed. Although overall melatonin levels did not change significantly over the morning at the group level, individual declines in salivary melatonin were associated with significant increases in activation within the left dorsomedial and right inferior lateral prefrontal cortex during the 2-back condition (P<0.05, cluster corrected). Medial prefrontal activation also correlated modestly with better vigilance performance during the 0-back (P<0.05), but not the 1-back or 2-back conditions. The light condition did not affect the outcomes. These findings suggest declining melatonin levels in the morning are associated with increased prefrontal cortex functioning and may play a role in the increased frontal activation that occurs following awakening.

Functional brain organization of working memory in adolescents varies in relation to family income and academic achievement.

PubMed

Finn, Amy S; Minas, Jennifer E; Leonard, Julia A; Mackey, Allyson P; Salvatore, John; Goetz, Calvin; West, Martin R; Gabrieli, Christopher F O; Gabrieli, John D E

2017-09-01

Working memory (WM) capacity reflects executive functions associated with performance on a wide range of cognitive tasks and education outcomes, including mathematics achievement, and is associated with dorsolateral prefrontal and parietal cortices. Here we asked if family income is associated with variation in the functional brain organization of WM capacity among adolescents, and whether that variation is associated with performance on a statewide test of academic achievement in mathematics. Participants were classified into higher-income and lower-income groups based on family income, and performed a WM task with a parametric manipulation of WM load (N-back task) during functional magnetic resonance imaging (fMRI). Behaviorally, the higher-income group had greater WM capacity and higher mathematics achievement scores. Neurally, the higher-income group showed greater activation as a function of WM load in bilateral prefrontal, parietal, and other regions, although the lower-income group exhibited greater activation at the lowest load. Both groups exhibited positive correlations between parietal activations and mathematics achievement scores, but only the higher-income group exhibited a positive correlation between prefrontal activations and mathematics scores. Most of these findings were maintained when higher- and lower-income groups were matched on WM task performance or nonverbal IQ. Findings indicate that the functional neural architecture of WM varies with family income and is associated with education measures of mathematics achievement. © 2016 John Wiley & Sons Ltd.

Theta Synchronizes the Activity of Medial Prefrontal Neurons during Learning

ERIC Educational Resources Information Center

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

2008-01-01

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

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.

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.

Injury to the Premature Cerebellum: Outcome is Related to Remote Cortical Development

PubMed Central

Limperopoulos, Catherine; Chilingaryan, Gevorg; Sullivan, Nancy; Guizard, Nicolas; Robertson, Richard L.; du Plessis, Adré J.

2014-01-01

Cerebellar injury is an important complication of preterm birth with far-reaching neuropsychiatric sequelae. We have previously shown a significant association between isolated injury to the premature cerebellum and subsequent impairment of regional volumetric growth in the contralateral cerebrum. In the current study, we examine the relationship between these remote regional impairments of cerebral volumetric growth and domain-specific functional deficits in these children. In 40 ex-preterm infants with isolated cerebellar injury, we performed neurodevelopmental evaluations and quantitative magnetic resonance imaging (MRI) studies at a mean age of 34 months. We measured cortical gray matter volumes in 8 parcellated regions of each cerebral hemisphere, as well as right and left cerebellar volumes. We show highly significant associations between early signs of autism and dorsolateral prefrontal cortex volume (P < 0.001); gross motor scores and sensorimotor cortical volumes (P < 0.001); and cognitive and expressive language scores and premotor and mid-temporal cortical volumes (P < 0.001). By multivariate analyses, each unit increase in the corresponding regional cerebral volume was associated with lower odds of abnormal outcome score, adjusted for age at MRI and contralateral cerebellar volume. This is the first report linking secondary impairment of remote cerebral cortical growth and functional disabilities in survivors of prematurity-related cerebellar brain injury. PMID:23146968

The prefrontal cortex: a target for antipsychotic drugs.

PubMed

Artigas, F

2010-01-01

At therapeutic doses, classical antipsychotic drugs occupy a large proportion of subcortical dopamine D2 receptors, whereas atypical antipsychotics preferentially occupy cortical 5-HT(2) receptors. However, the exact cellular and network basis of their therapeutic action is not fully understood. To review the mechanism of action of antipsychotic drugs with a particular emphasis on their action in the prefrontal cortex (PFC). The PFC controls a large number of higher brain functions altered in schizophrenia. Histological studies indicate the presence of a large proportion of PFC neurons expressing monoaminergic receptors sensitive to the action of atypical- and to a lesser extentclassical antipsychotic drugs. Functional studies also indicate that both drug families act at PFC level. Atypical antipsychotic drugs likely exert their therapeutic activity by a preferential action on PFC neurons, thus modulating the PFC output to basal ganglia circuits. Classical antipsychotics also interact with these PFC targets in addition to blocking massively striatal D2 receptors.

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

Large-scale Cortical Network Properties Predict Future Sound-to-Word Learning Success

PubMed Central

Sheppard, John Patrick; Wang, Ji-Ping; Wong, Patrick C. M.

2013-01-01

The human brain possesses a remarkable capacity to interpret and recall novel sounds as spoken language. These linguistic abilities arise from complex processing spanning a widely distributed cortical network and are characterized by marked individual variation. Recently, graph theoretical analysis has facilitated the exploration of how such aspects of large-scale brain functional organization may underlie cognitive performance. Brain functional networks are known to possess small-world topologies characterized by efficient global and local information transfer, but whether these properties relate to language learning abilities remains unknown. Here we applied graph theory to construct large-scale cortical functional networks from cerebral hemodynamic (fMRI) responses acquired during an auditory pitch discrimination task and found that such network properties were associated with participants’ future success in learning words of an artificial spoken language. Successful learners possessed networks with reduced local efficiency but increased global efficiency relative to less successful learners and had a more cost-efficient network organization. Regionally, successful and less successful learners exhibited differences in these network properties spanning bilateral prefrontal, parietal, and right temporal cortex, overlapping a core network of auditory language areas. These results suggest that efficient cortical network organization is associated with sound-to-word learning abilities among healthy, younger adults. PMID:22360625

Distinct pathways of neural coupling for different basic emotions.

PubMed

Tettamanti, Marco; Rognoni, Elena; Cafiero, Riccardo; Costa, Tommaso; Galati, Dario; Perani, Daniela

2012-01-16

Emotions are complex events recruiting distributed cortical and subcortical cerebral structures, where the functional integration dynamics within the involved neural circuits in relation to the nature of the different emotions are still unknown. Using fMRI, we measured the neural responses elicited by films representing basic emotions (fear, disgust, sadness, happiness). The amygdala and the associative cortex were conjointly activated by all basic emotions. Furthermore, distinct arrays of cortical and subcortical brain regions were additionally activated by each emotion, with the exception of sadness. Such findings informed the definition of three effective connectivity models, testing for the functional integration of visual cortex and amygdala, as regions processing all emotions, with domain-specific regions, namely: i) for fear, the frontoparietal system involved in preparing adaptive motor responses; ii) for disgust, the somatosensory system, reflecting protective responses against contaminating stimuli; iii) for happiness: medial prefrontal and temporoparietal cortices involved in understanding joyful interactions. Consistently with these domain-specific models, the results of the effective connectivity analysis indicate that the amygdala is involved in distinct functional integration effects with cortical networks processing sensorimotor, somatosensory, or cognitive aspects of basic emotions. The resulting effective connectivity networks may serve to regulate motor and cognitive behavior based on the quality of the induced emotional experience. Copyright © 2011. Published by Elsevier Inc.

Cigarette smoking and schizophrenia independently and reversibly altered intrinsic brain activity.

PubMed

Liu, Huan; Luo, Qi; Du, Wanyi; Li, Xingbao; Zhang, Zhiwei; Yu, Renqiang; Chen, Xiaolu; Meng, Huaqing; Du, Lian

2018-01-03

Schizophrenia patients are at high risk for cigarette smoking, but the neurobiological mechanisms of this comorbid association are relatively unknown. Long-term nicotine intake may impact brain that are independently and additively associated with schizophrenia. We investigated whether altered intrinsic brain activity (iBA) related to schizophrenia pathology is also associated with nicotine addiction. Forty-two schizophrenia patients (21 smokers and 21 nonsmokers) and 21 sex- and age-matched healthy nonsmokers underwent task-free functional MRI. Whole brain iBA was measured by the amplitude of spontaneous low frequency fluctuation. Furthermore, correlation analyses between iBA, symptom severity and nicotine addiction severity were performed. We found that prefrontal cortex, right caudate, and right postcentral gyrus were related to both disease and nicotine addiction effects. More importantly, schizophrenia smokers, compared to schizophrenia nonsmokers showed reversed iBA in the above brain regions. In addition, schizophrenia smokers, relative to nonsmokers, altered iBA in the left striatal and motor cortices. The iBA of the right caudate was negatively correlated with symptom severity. The iBA of the right postcentral gyrus negatively correlated with nicotine addiction severity. The striatal and motor cortices could potentially increase the vulnerability of smoking in schizophrenia. More importantly, smoking reversed iBA in the right striatal and prefrontal cortices, consistent with the self-medication theory in schizophrenia. Smoking altered left striatal and motor cortices activity, suggesting that the nicotine addiction effect was independent of disease. These results provide a local property of intrinsic brain activity mechanism that contributes to cigarette smoking and schizophrenia.

Developmental effects of aggressive behavior in male adolescents assessed with structural and functional brain imaging

PubMed Central

Strenziok, Maren; Krueger, Frank; Heinecke, Armin; Lenroot, Rhoshel K.; Knutson, Kristine M.; van der Meer, Elke

2011-01-01

Aggressive behavior is common during adolescence. Although aggression-related functional changes in the ventromedial prefrontal cortex (vmPFC) and frontopolar cortex (FPC) have been reported in adults, the neural correlates of aggressive behavior in adolescents, particularly in the context of structural neurodevelopment, are obscure. We used functional and structural magnetic resonance imaging (MRI) to measure the blood oxygenation level-depended signal and cortical thickness. In a block-designed experiment, 14–17-year old adolescents imagined aggressive and non-aggressive interactions with a peer. We show reduced vmPFC activation associated with imagined aggressive behavior as well as enhanced aggression-related activation and cortical thinning in the FPC with increasing age. Changes in FPC activation were also associated with judgments of the severity of aggressive acts. Reduced vmPFC activation was associated with greater aggression indicating its normal function is to exert inhibitory control over aggressive impulses. Concurrent FPC activation likely reflects foresight of harmful consequences that result from aggressive acts. The correlation of age-dependent activation changes and cortical thinning demonstrates ongoing maturation of the FPC during adolescence towards a refinement of social and cognitive information processing that can potentially facilitate mature social behavior in aggressive contexts. PMID:19770220

Routes of Motivation: Stable Psychological Dispositions Are Associated with Dynamic Changes in Cortico-Cortical Functional Connectivity

PubMed Central

Viola, Vanda; Tosoni, Annalisa; Kruglanski, Arie W.; Galati, Gaspare; Mannetti, Lucia

2014-01-01

The present study provides a neurobiological framework to the theory of epistemic motivation that has been extensively studied for the last three decades in the domain of social cognition. Epistemic motivations affect the way people generate and validate hypotheses, and ultimately form and modify knowledge. Strong dispositional measures such as need for cognitive closure (NCC), the desire for a quick firm answer (any answer) to a question, show gross and stable inter-individual differences. The cognitive mechanisms and neural underpinnings of such differences, however, remain largely unexplored. Here we show that high (compared to low) levels of NCC, measured with need for cognitive closure scale, are associated with reduced online adjustment in cognitive control, as indexed by behavioral conflict adaptation. This behavioral effect is mediated by dynamic changes in cortico-cortical functional connectivity between prefrontal regions involved in conflict monitoring and implementation of cognitive control. In particular, these regions show increased functional connectivity after exposure to conflict in low but not high NCC individuals. These results demonstrate that the level of flexibility of functional cortico-cortical connections can mediate stable psychological dispositions. PMID:24892718

The effect of single and repeated prefrontal intermittent theta burst stimulation on cortical reactivity and working memory.

PubMed

Chung, Sung Wook; Rogasch, Nigel C; Hoy, Kate E; Fitzgerald, Paul B

With an increasing interest in the use of theta burst stimulation (TBS) as a cognitive enhancer and a potential therapeutic tool for psychiatric disorders, there is a need to identify optimal parameters of TBS in the prefrontal cortex. This study examined the effect of two blocks of prefrontal intermittent TBS (iTBS) on cortical reactivity and working memory performance, compared to one block of iTBS and sham stimulation. We hypothesized that greater cortical effects would be obtained with two blocks of iTBS. Eighteen healthy participants attended three experimental sessions and received either sham, one block or two blocks of iTBS with a 15-min interval. Concurrent transcranial magnetic stimulation with electroencephalography (TMS-EEG) was used to assess the change in cortical reactivity via TMS-evoked potentials. Working memory performance was assessed using the N-back task. Cluster-based permutation statistics and two-way ANOVAs were used for neurophysiological and behavioural data, respectively. Both single and two blocks of iTBS resulted in a significant increase in the amplitude of TMS-evoked N100 and P200. No significant differences were observed between active conditions in either neurophysiological changes or working memory performance, and both failed to improve working memory performance relative to sham. Two blocks of iTBS did not result in stronger measured effects as compared to one block of iTBS. Future studies are needed to identify the optimal stimulation pattern in order to achieve a desired effect. It is also important to establish the best approach in quantifying neuromodulatory effects targeting the prefrontal cortex. Copyright © 2018 Elsevier Inc. All rights reserved.

Contribution of NMDA receptor hypofunction in prefrontal and cortical excitatory neurons to schizophrenia-like phenotypes.

PubMed

Rompala, Gregory R; Zsiros, Veronika; Zhang, Shuqin; Kolata, Stefan M; Nakazawa, Kazu

2013-01-01

Pharmacological and genetic studies support a role for NMDA receptor (NMDAR) hypofunction in the etiology of schizophrenia. We have previously demonstrated that NMDAR obligatory subunit 1 (GluN1) deletion in corticolimbic interneurons during early postnatal development is sufficient to confer schizophrenia-like phenotypes in mice. However, the consequence of NMDAR hypofunction in cortical excitatory neurons is not well delineated. Here, we characterize a conditional knockout mouse strain (CtxGluN1 KO mice), in which postnatal GluN1 deletion is largely confined to the excitatory neurons in layer II/III of the medial prefrontal cortex and sensory cortices, as evidenced by the lack of GluN1 mRNA expression in in situ hybridization immunocytochemistry as well as the lack of NMDA currents with in vitro recordings. Mutants were impaired in prepulse inhibition of the auditory startle reflex as well as object-based short-term memory. However, they did not exhibit impairments in additional hallmarks of schizophrenia-like phenotypes (e.g. spatial working memory, social behavior, saccharine preference, novelty and amphetamine-induced hyperlocomotion, and anxiety-related behavior). Furthermore, upon administration of the NMDA receptor antagonist, MK-801, there were no differences in locomotor activity versus controls. The mutant mice also showed negligible levels of reactive oxygen species production following chronic social isolation, and recording of miniature-EPSC/IPSCs from layer II/III excitatory neurons in medial prefrontal cortex suggested no alteration in GABAergic activity. All together, the mutant mice displayed cognitive deficits in the absence of additional behavioral or cellular phenotypes reflecting schizophrenia pathophysiology. Thus, NMDAR hypofunction in prefrontal and cortical excitatory neurons may recapitulate only a cognitive aspect of human schizophrenia symptoms.

Enhanced pain expectation in migraine: EEG-based evidence for impaired prefrontal function.

PubMed

Lev, Rina; Granovsky, Yelena; Yarnitsky, David

2013-01-01

Dysexcitability characterizes the interictal migraineous brain. The main central expressions of this dysexcitability are decreased habituation and enhanced anticipation and attention to pain and other external sensory stimuli. This study evaluates the effects of anticipation on pain modulation and their neural correlates in migraine. In 39 migraineurs (20 migraine with aura [MWA] and 19 migraine without aura [MOA]) and 22 healthy controls, cortical responses to 2 successive trains of noxious contact-heat stimuli, presented in either predicted or unpredicted manner, were analyzed using standardized low-resolution electromagnetic tomography key. A lack of habituation to repeated predicted pain was associated with significantly increased pain-evoked potential amplitudes in MWAs (increase of 3.9 μV) and unchanged ones in MOAs (1.1 μV) but not in controls (decrease of 5 μV). Repeated unpredicted pain resulted in enhanced pain-evoked potential amplitudes in both MWA and MOA groups (increase of 5.5 μV and 4.4 μV, respectively) compared with controls (decrease of 0.2 μV). Source localization revealed reduced activations in the anterior-medial prefrontal cortices and subsequent increased somatosensory activity in migraineurs (P < .05). The prefrontal-somatosensory dysfunction positively correlated with lifetime headache duration (P < .05) and concern of upcoming migraine attacks (P < .05) in MWAs, and with frequency of migraine attacks in MOAs (P < .05). Our findings of impaired modulation of anticipated pain in migraine suggest a heightened state of anticipatory readiness combined with ineffective recruitment of prefrontal inhibitory pathways during experience of pain; the latter might account for the former, at least partially. In line, less efficient inhibitory capability is a plausible mechanistic explanation for patients' high concern about their upcoming migraine attacks. © 2012 American Headache Society.

Time Processing in Children with Tourette's Syndrome

ERIC Educational Resources Information Center

Vicario, Carmelo Mario; Martino, Davide; Spata, Felice; Defazio, Giovanni; Giacche, Roberta; Martino, Vito; Rappo, Gaetano; Pepi, Anna Maria; Silvestri, Paola Rosaria; Cardona, Francesco

2010-01-01

Background: Tourette syndrome (TS) is characterized by dysfunctional connectivity between prefrontal cortex and sub-cortical structures, and altered meso-cortical and/or meso-striatal dopamine release. Since time processing is also regulated by fronto-striatal circuits and modulated by dopaminergic transmission, we hypothesized that time…

Multispectral brain morphometry in Tourette syndrome persisting into adulthood

PubMed Central

Martino, Davide; Cavanna, Andrea E.; Hutton, Chloe; Orth, Michael; Robertson, Mary M.; Critchley, Hugo D.; Frackowiak, Richard S.

2010-01-01

Tourette syndrome is a childhood-onset neuropsychiatric disorder with a high prevalence of attention deficit hyperactivity and obsessive-compulsive disorder co-morbidities. Structural changes have been found in frontal cortex and striatum in children and adolescents. A limited number of morphometric studies in Tourette syndrome persisting into adulthood suggest ongoing structural alterations affecting frontostriatal circuits. Using cortical thickness estimation and voxel-based analysis of T1- and diffusion-weighted structural magnetic resonance images, we examined 40 adults with Tourette syndrome in comparison with 40 age- and gender-matched healthy controls. Patients with Tourette syndrome showed relative grey matter volume reduction in orbitofrontal, anterior cingulate and ventrolateral prefrontal cortices bilaterally. Cortical thinning extended into the limbic mesial temporal lobe. The grey matter changes were modulated additionally by the presence of co-morbidities and symptom severity. Prefrontal cortical thickness reduction correlated negatively with tic severity, while volume increase in primary somatosensory cortex depended on the intensity of premonitory sensations. Orbitofrontal cortex volume changes were further associated with abnormal water diffusivity within grey matter. White matter analysis revealed changes in fibre coherence in patients with Tourette syndrome within anterior parts of the corpus callosum. The severity of motor tics and premonitory urges had an impact on the integrity of tracts corresponding to cortico-cortical and cortico-subcortical connections. Our results provide empirical support for a patho-aetiological model of Tourette syndrome based on developmental abnormalities, with perturbation of compensatory systems marking persistence of symptoms into adulthood. We interpret the symptom severity related grey matter volume increase in distinct functional brain areas as evidence of ongoing structural plasticity. The convergence of evidence from volume and water diffusivity imaging strengthens the validity of our findings and attests to the value of a novel multimodal combination of volume and cortical thickness estimations that provides unique and complementary information by exploiting their differential sensitivity to structural change. PMID:21071387

Thalamo-Cortical Connectivity: What Can Diffusion Tractography Tell Us About Reading Difficulties in Children?

PubMed Central

Fan, Qiuyun; Davis, Nicole; Anderson, Adam W.

2014-01-01

Abstract Reading is an essential skill in modern society, but many people have deficits in the decoding and word recognition aspects of reading, a difficulty often referred to as dyslexia. The primary focus of neuroimaging studies to date in dyslexia has been on cortical regions; however, subcortical regions may also be important for explaining this disability. Here, we used diffusion tensor imaging to examine the association between thalamo-cortical connectivity and children's reading ability in 20 children with typically developed reading ability (age range 8–17/10–17 years old from two imaging centers) and 19 children with developmental dyslexia (DYS) (age range 9–17/9–16 years old). To measure thalamo-cortical connections, the structural images were segmented into cortical and subcortical anatomical regions that were used as target and seed regions in the probabilistic tractography analysis. Abnormal thalamic connectivity was found in the dyslexic group in the sensorimotor and lateral prefrontal cortices. These results suggest that the thalamus may play a key role in reading behavior by mediating the functions of task-specific cortical regions; such findings lay the foundation for future studies to investigate further neurobiological anomalies in the development of thalamo-cortical connectivity in DYS. PMID:24963547

Dynamic Reconfiguration of the Supplementary Motor Area Network during Imagined Music Performance

PubMed Central

Tanaka, Shoji; Kirino, Eiji

2017-01-01

The supplementary motor area (SMA) has been shown to be the center for motor planning and is active during music listening and performance. However, limited data exist on the role of the SMA in music. Music performance requires complex information processing in auditory, visual, spatial, emotional, and motor domains, and this information is integrated for the performance. We hypothesized that the SMA is engaged in multimodal integration of information, distributed across several regions of the brain to prepare for ongoing music performance. To test this hypothesis, functional networks involving the SMA were extracted from functional magnetic resonance imaging (fMRI) data that were acquired from musicians during imagined music performance and during the resting state. Compared with the resting condition, imagined music performance increased connectivity of the SMA with widespread regions in the brain including the sensorimotor cortices, parietal cortex, posterior temporal cortex, occipital cortex, and inferior and dorsolateral prefrontal cortex. Increased connectivity of the SMA with the dorsolateral prefrontal cortex suggests that the SMA is under cognitive control, while increased connectivity with the inferior prefrontal cortex suggests the involvement of syntax processing. Increased connectivity with the parietal cortex, posterior temporal cortex, and occipital cortex is likely for the integration of spatial, emotional, and visual information. Finally, increased connectivity with the sensorimotor cortices was potentially involved with the translation of thought planning into motor programs. Therefore, the reconfiguration of the SMA network observed in this study is considered to reflect the multimodal integration required for imagined and actual music performance. We propose that the SMA network construct “the internal representation of music performance” by integrating multimodal information required for the performance. PMID:29311870

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

Neural substrate of the late positive potential in emotional processing

PubMed Central

Liu, Yuelu; Huang, Haiqing; McGinnis, Menton; Keil, Andreas; Ding, Mingzhou

2012-01-01

The late positive potential (LPP) is a reliable electrophysiological index of emotional perception in humans. Despite years of research the brain structures that contribute to the generation and modulation of LPP are not well understood. Recording EEG and fMRI simultaneously, and applying a recently proposed single-trial ERP analysis method, we addressed the problem by correlating the single-trial LPP amplitude evoked by affective pictures with the blood-oxygen-level-dependent (BOLD) activity. Three results were found. First, relative to neutral pictures, pleasant and unpleasant pictures elicited enhanced LPP, as well as heightened BOLD activity in both visual cortices and emotion-processing structures such as amygdala and prefrontal cortex, consistent with previous findings. Second, the LPP amplitude across three picture categories was significantly correlated with BOLD activity in visual cortices, temporal cortices, amygdala, orbitofrontal cortex, and insula. Third, within each picture category, LPP-BOLD coupling revealed category-specific differences. For pleasant pictures, the LPP amplitude was coupled with BOLD in occipitotemporal junction, medial prefrontal cortex, amygdala, and precuneus, whereas for unpleasant pictures, significant LPP-BOLD correlation was observed in ventrolateral prefrontal cortex, insula, and posterior cingulate cortex. These results suggest that LPP is generated and modulated by an extensive brain network comprised of both cortical and subcortical structures associated with visual and emotional processing and the degree of contribution by each of these structures to the LPP modulation is valence-specific. PMID:23077042

A Developmental Shift from Positive to Negative Connectivity in Human Amygdala-Prefrontal Circuitry

PubMed Central

Gee, Dylan G.; Humphreys, Kathryn L.; Flannery, Jessica; Goff, Bonnie; Telzer, Eva H.; Shapiro, Mor; Hare, Todd A.; Bookheimer, Susan Y.; Tottenham, Nim

2013-01-01

Recent human imaging and animal studies highlight the importance of frontoamygdala circuitry in the regulation of emotional behavior and its disruption in anxiety-related disorders. While tracing studies have suggested changes in amygdala-cortical connectivity through the adolescent period in rodents, less is known about the reciprocal connections within this circuitry across human development, when these circuits are being fine-tuned and substantial changes in emotional control are observed. The present study examined developmental changes in amygdala-prefrontal circuitry across the ages of 4 to 22 years using task-based functional magnetic resonance imaging (fMRI). Results suggest positive amygdala-prefrontal connectivity in early childhood that switches to negative functional connectivity during the transition to adolescence. Amygdala-mPFC functional connectivity was significantly positive (greater than zero) among participants younger than ten, whereas functional connectivity was significantly negative (less than zero) among participants ten years and older, over and above the effect of amygdala reactivity. The developmental switch in functional connectivity was paralleled by a steady decline in amygdala reactivity. Moreover, the valence switch might explain age-related improvement in task performance and a developmentally normative decline in anxiety. Initial positive connectivity followed by a valence shift to negative connectivity provides a neurobiological basis for regulatory development and may present novel insight into a more general process of developing regulatory connections. PMID:23467374

Abnormal resting-state connectivity of motor and cognitive networks in early manifest Huntington's disease.

PubMed

Wolf, R C; Sambataro, F; Vasic, N; Depping, M S; Thomann, P A; Landwehrmeyer, G B; Süssmuth, S D; Orth, M

2014-11-01

Functional magnetic resonance imaging (fMRI) of multiple neural networks during the brain's 'resting state' could facilitate biomarker development in patients with Huntington's disease (HD) and may provide new insights into the relationship between neural dysfunction and clinical symptoms. To date, however, very few studies have examined the functional integrity of multiple resting state networks (RSNs) in manifest HD, and even less is known about whether concomitant brain atrophy affects neural activity in patients. Using MRI, we investigated brain structure and RSN function in patients with early HD (n = 20) and healthy controls (n = 20). For resting-state fMRI data a group-independent component analysis identified spatiotemporally distinct patterns of motor and prefrontal RSNs of interest. We used voxel-based morphometry to assess regional brain atrophy, and 'biological parametric mapping' analyses to investigate the impact of atrophy on neural activity. Compared with controls, patients showed connectivity changes within distinct neural systems including lateral prefrontal, supplementary motor, thalamic, cingulate, temporal and parietal regions. In patients, supplementary motor area and cingulate cortex connectivity indices were associated with measures of motor function, whereas lateral prefrontal connectivity was associated with cognition. This study provides evidence for aberrant connectivity of RSNs associated with motor function and cognition in early manifest HD when controlling for brain atrophy. This suggests clinically relevant changes of RSN activity in the presence of HD-associated cortical and subcortical structural abnormalities.

Evidence for involvement of nitric oxide and GABAB receptors in MK-801- stimulated release of glutamate in rat prefrontal cortex

PubMed Central

Roenker, Nicole L.; Gudelsky, Gary A.; Ahlbrand, Rebecca; Horn, Paul S.; Richtand, Neil M.

2012-01-01

Systemic administration of NMDA receptor antagonists elevates extracellular glutamate within prefrontal cortex. The cognitive and behavioral effects of NMDA receptor blockade have direct relevance to symptoms of schizophrenia, and recent studies demonstrate an important role for nitric oxide and GABAB receptors in mediating the effects of NMDA receptor blockade on these behaviors. We sought to extend those observations by directly measuring the effects of nitric oxide and GABAB receptor mechanisms on MK-801-induced glutamate release in the prefrontal cortex. Systemic MK-801 injection (0.3 mg/kg) to male Sprague-Dawley rats significantly increased extracellular glutamate levels in prefrontal cortex, as determined by microdialysis. This effect was blocked by pretreatment with the nitric oxide synthase inhibitor L-NAME (60 mg/kg). Reverse dialysis of the nitric oxide donor SNAP (0.5 – 5 mM) directly into prefrontal cortex mimicked the effect of systemic MK-801, dose-dependently elevating cortical extracellular glutamate. The effect of MK-801 was also blocked by systemic treatment with the GABAB receptor agonist baclofen (5 mg/kg). In combination, these data suggest increased nitric oxide formation is necessary for NMDA antagonist-induced elevations of extracellular glutamate in the prefrontal cortex. Additionally, the data suggest GABAB receptor activation can modulate the NMDA antagonist-induced increase in cortical glutamate release. PMID:22579658

A hierarchy of time-scales and the brain.

PubMed

Kiebel, Stefan J; Daunizeau, Jean; Friston, Karl J

2008-11-01

In this paper, we suggest that cortical anatomy recapitulates the temporal hierarchy that is inherent in the dynamics of environmental states. Many aspects of brain function can be understood in terms of a hierarchy of temporal scales at which representations of the environment evolve. The lowest level of this hierarchy corresponds to fast fluctuations associated with sensory processing, whereas the highest levels encode slow contextual changes in the environment, under which faster representations unfold. First, we describe a mathematical model that exploits the temporal structure of fast sensory input to track the slower trajectories of their underlying causes. This model of sensory encoding or perceptual inference establishes a proof of concept that slowly changing neuronal states can encode the paths or trajectories of faster sensory states. We then review empirical evidence that suggests that a temporal hierarchy is recapitulated in the macroscopic organization of the cortex. This anatomic-temporal hierarchy provides a comprehensive framework for understanding cortical function: the specific time-scale that engages a cortical area can be inferred by its location along a rostro-caudal gradient, which reflects the anatomical distance from primary sensory areas. This is most evident in the prefrontal cortex, where complex functions can be explained as operations on representations of the environment that change slowly. The framework provides predictions about, and principled constraints on, cortical structure-function relationships, which can be tested by manipulating the time-scales of sensory input.

Rostral and caudal prefrontal contribution to creativity: a meta-analysis of functional imaging data

PubMed Central

Gonen-Yaacovi, Gil; de Souza, Leonardo Cruz; Levy, Richard; Urbanski, Marika; Josse, Goulven; Volle, Emmanuelle

2013-01-01

Creativity is of central importance for human civilization, yet its neurocognitive bases are poorly understood. The aim of the present study was to integrate existing functional imaging data by using the meta-analysis approach. We reviewed 34 functional imaging studies that reported activation foci during tasks assumed to engage creative thinking in healthy adults. A coordinate-based meta-analysis using Activation Likelihood Estimation (ALE) first showed a set of predominantly left-hemispheric regions shared by the various creativity tasks examined. These regions included the caudal lateral prefrontal cortex (PFC), the medial and lateral rostral PFC, and the inferior parietal and posterior temporal cortices. Further analyses showed that tasks involving the combination of remote information (combination tasks) activated more anterior areas of the lateral PFC than tasks involving the free generation of unusual responses (unusual generation tasks), although both types of tasks shared caudal prefrontal areas. In addition, verbal and non-verbal tasks involved the same regions in the left caudal prefrontal, temporal, and parietal areas, but also distinct domain-oriented areas. Taken together, these findings suggest that several frontal and parieto-temporal regions may support cognitive processes shared by diverse creativity tasks, and that some regions may be specialized for distinct types of processes. In particular, the lateral PFC appeared to be organized along a rostro-caudal axis, with rostral regions involved in combining ideas creatively and more posterior regions involved in freely generating novel ideas. PMID:23966927

Frontal Lobe Contusion in Mice Chronically Impairs Prefrontal-Dependent Behavior

PubMed Central

Rosi, Susanna

2016-01-01

Traumatic brain injury (TBI) is a major cause of chronic disability in the world. Moderate to severe TBI often results in damage to the frontal lobe region and leads to cognitive, emotional, and social behavioral sequelae that negatively affect quality of life. More specifically, TBI patients often develop persistent deficits in social behavior, anxiety, and executive functions such as attention, mental flexibility, and task switching. These deficits are intrinsically associated with prefrontal cortex (PFC) functionality. Currently, there is a lack of analogous, behaviorally characterized TBI models for investigating frontal lobe injuries despite the prevalence of focal contusions to the frontal lobe in TBI patients. We used the controlled cortical impact (CCI) model in mice to generate a frontal lobe contusion and studied behavioral changes associated with PFC function. We found that unilateral frontal lobe contusion in mice produced long-term impairments to social recognition and reversal learning while having only a minor effect on anxiety and completely sparing rule shifting and hippocampal-dependent behavior. PMID:26964036

Dissociation and Convergence of the Dorsal and Ventral Visual Streams in the Human Prefrontal Cortex

PubMed Central

Takahashi, Emi; Ohki, Kenichi; Kim, Dae-Shik

2012-01-01

Visual information is largely processed through two pathways in the primate brain: an object pathway from the primary visual cortex to the temporal cortex (ventral stream) and a spatial pathway to the parietal cortex (dorsal stream). Whether and to what extent dissociation exists in the human prefrontal cortex (PFC) has long been debated. We examined anatomical connections from functionally defined areas in the temporal and parietal cortices to the PFC, using noninvasive functional and diffusion-weighted magnetic resonance imaging. The right inferior frontal gyrus (IFG) received converging input from both streams, while the right superior frontal gyrus received input only from the dorsal stream. Interstream functional connectivity to the IFG was dynamically recruited only when both object and spatial information were processed. These results suggest that the human PFC receives dissociated and converging visual pathways, and that the right IFG region serves as an integrator of the two types of information. PMID:23063444

Decrease of Prefrontal-Posterior EEG Coherence: Loose Control during Social-Emotional Stimulation

ERIC Educational Resources Information Center

Reiser, Eva M.; Schulter, Gunter; Weiss, Elisabeth M.; Fink, Andreas; Rominger, Christian; Papousek, Ilona

2012-01-01

In two experiments we aimed to investigate if individual differences in state-dependent decreases or increases of EEG coherence between prefrontal and posterior cortical regions may be indicative of a mechanism modulating the impact social-emotional information has on an individual. Two independent samples were exposed to an emotional stimulation…

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.

Shared and distinct contributions of rostrolateral prefrontal cortex to analogical reasoning and episodic memory retrieval.

PubMed

Westphal, Andrew J; Reggente, Nicco; Ito, Kaori L; Rissman, Jesse

2016-03-01

Rostrolateral prefrontal cortex (RLPFC) is widely appreciated to support higher cognitive functions, including analogical reasoning and episodic memory retrieval. However, these tasks have typically been studied in isolation, and thus it is unclear whether they involve common or distinct RLPFC mechanisms. Here, we introduce a novel functional magnetic resonance imaging (fMRI) task paradigm to compare brain activity during reasoning and memory tasks while holding bottom-up perceptual stimulation and response demands constant. Univariate analyses on fMRI data from twenty participants identified a large swath of left lateral prefrontal cortex, including RLPFC, that showed common engagement on reasoning trials with valid analogies and memory trials with accurately retrieved source details. Despite broadly overlapping recruitment, multi-voxel activity patterns within left RLPFC reliably differentiated these two trial types, highlighting the presence of at least partially distinct information processing modes. Functional connectivity analyses demonstrated that while left RLPFC showed consistent coupling with the fronto-parietal control network across tasks, its coupling with other cortical areas varied in a task-dependent manner. During the memory task, this region strengthened its connectivity with the default mode and memory retrieval networks, whereas during the reasoning task it coupled more strongly with a nearby left prefrontal region (BA 45) associated with semantic processing, as well as with a superior parietal region associated with visuospatial processing. Taken together, these data suggest a domain-general role for left RLPFC in monitoring and/or integrating task-relevant knowledge representations and showcase how its function cannot solely be attributed to episodic memory or analogical reasoning computations. © 2015 Wiley Periodicals, Inc.

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.

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

Brain structure–function associations in multi-generational families genetically enriched for bipolar disorder

PubMed Central

Schür, Remmelt; Sjouwerman, Rachel; Service, Susan K.; Araya, Carmen; Araya, Xinia; Bejarano, Julio; Knowles, Emma; Gomez-Makhinson, Juliana; Lopez, Maria C.; Aldana, Ileana; Teshiba, Terri M.; Abaryan, Zvart; Al-Sharif, Noor B.; Navarro, Linda; Tishler, Todd A.; Altshuler, Lori; Bartzokis, George; Escobar, Javier I.; Glahn, David C.; Thompson, Paul M.; Lopez-Jaramillo, Carlos; Macaya, Gabriel; Molina, Julio; Reus, Victor I.; Sabatti, Chiara; Cantor, Rita M.; Freimer, Nelson B.; Bearden, Carrie E.

2015-01-01

Recent theories regarding the pathophysiology of bipolar disorder suggest contributions of both neurodevelopmental and neurodegenerative processes. While structural neuroimaging studies indicate disease-associated neuroanatomical alterations, the behavioural correlates of these alterations have not been well characterized. Here, we investigated multi-generational families genetically enriched for bipolar disorder to: (i) characterize neurobehavioural correlates of neuroanatomical measures implicated in the pathophysiology of bipolar disorder; (ii) identify brain–behaviour associations that differ between diagnostic groups; (iii) identify neurocognitive traits that show evidence of accelerated ageing specifically in subjects with bipolar disorder; and (iv) identify brain–behaviour correlations that differ across the age span. Structural neuroimages and multi-dimensional assessments of temperament and neurocognition were acquired from 527 (153 bipolar disorder and 374 non-bipolar disorder) adults aged 18–87 years in 26 families with heavy genetic loading for bipolar disorder. We used linear regression models to identify significant brain–behaviour associations and test whether brain–behaviour relationships differed: (i) between diagnostic groups; and (ii) as a function of age. We found that total cortical and ventricular volume had the greatest number of significant behavioural associations, and included correlations with measures from multiple cognitive domains, particularly declarative and working memory and executive function. Cortical thickness measures, in contrast, showed more specific associations with declarative memory, letter fluency and processing speed tasks. While the majority of brain–behaviour relationships were similar across diagnostic groups, increased cortical thickness in ventrolateral prefrontal and parietal cortical regions was associated with better declarative memory only in bipolar disorder subjects, and not in non-bipolar disorder family members. Additionally, while age had a relatively strong impact on all neurocognitive traits, the effects of age on cognition did not differ between diagnostic groups. Most brain–behaviour associations were also similar across the age range, with the exception of cortical and ventricular volume and lingual gyrus thickness, which showed weak correlations with verbal fluency and inhibitory control at younger ages that increased in magnitude in older subjects, regardless of diagnosis. Findings indicate that neuroanatomical traits potentially impacted by bipolar disorder are significantly associated with multiple neurobehavioural domains. Structure–function relationships are generally preserved across diagnostic groups, with the notable exception of ventrolateral prefrontal and parietal association cortex, volumetric increases in which may be associated with cognitive resilience specifically in individuals with bipolar disorder. Although age impacted all neurobehavioural traits, we did not find any evidence of accelerated cognitive decline specific to bipolar disorder subjects. Regardless of diagnosis, greater global brain volume may represent a protective factor for the effects of ageing on executive functioning. PMID:25943422

Changes in the neural bases of emotion regulation associated with clinical improvement in children with behavior problems.

PubMed

Lewis, Marc D; Granic, Isabela; Lamm, Connie; Zelazo, Philip David; Stieben, Jim; Todd, Rebecca M; Moadab, Ida; Pepler, Debra

2008-01-01

Children's behavior problems may stem from ineffective cortical mechanisms for regulating negative emotions, and the success of interventions may depend on their impact on such mechanisms. We examined neurophysiological markers associated with emotion regulation in children comorbid for externalizing and internalizing problems before and after treatment. We hypothesized that treatment success would correspond with reduced ventral prefrontal activation, and increased dorsomedial prefrontal activation, at the time point of an event-related potential (ERP) associated with inhibitory control. Twenty-seven 8- to 12-year-old children (with usable data) were tested before and after a 14-week community-based treatment program and assessed as to improvement status. Fifteen 8- to 12-year-olds from the normal population (with usable data) were tested over the same interval. All children completed an emotion-induction go/no-go task while fitted with a 128-channel electrode net at each test session. ERP amplitudes, and estimates of cortical activation in prefrontal regions of interest, were measured at the peak of the "inhibitory" N2 and compared between improvers, nonimprovers, and nonclinical children. ERP amplitudes showed no group differences. However, improvers showed an overall reduction in ventral prefrontal activation from pretreatment to posttreatment, bringing them in line with nonclinical children, whereas ventral activation remained high for nonimprovers. Both improvers and nonimprovers showed high dorsal activation relative to nonclinical children. Supplementary analyses indicated that only ventral prefrontal regions, and only within the N2 time window, showed decreased activity from pre- to posttreatment, suggesting changes in regulatory processes rather than in overall emotional arousal. These cortically mediated changes may permit a reduction in the overengaged, rigid style of emotion regulation characteristic of children with behavior problems.

Mapping the Primate Visual System with [2-14C]Deoxyglucose

NASA Astrophysics Data System (ADS)

Macko, Kathleen A.; Jarvis, Charlene D.; Kennedy, Charles; Miyaoka, Mikoto; Shinohara, Mami; Sokoloff, Louis; Mishkin, Mortimer

1982-10-01

The [2-14C]deoxyglucose method was used to identify the cerebral areas related to vision in the rhesus monkey (Macaca mulatta). This was achieved by comparing glucose utilization in a visually stimulated with that in a visually deafferented hemisphere. The cortical areas related to vision included the entire expanse of striate, prestriate, and inferior temporal cortex as far forward as the temporal pole, the posterior part of the inferior parietal lobule, and the prearcuate and inferior prefrontal cortex. Subcortically, in addition to the dorsal lateral geniculate nucleus and superficial layers of the superior colliculus, the structures related to vision included large parts of the pulvinar, caudate, putamen, claustrum, and amygdala. These results, which are consonant with a model of visual function that postulates an occipito-temporo-prefrontal pathway for object vision and an occipito-parieto-prefrontal pathway for spatial vision, reveal the full extent of those pathways and identify their points of contact with limbic, striatal, and diencephalic structures.

Separate neural mechanisms underlie choices and strategic preferences in risky decision making

PubMed Central

Venkatraman, Vinod; Payne, John W.; Bettman, James R.; Luce, Mary Frances; Huettel, Scott A.

2011-01-01

Adaptive decision making in real-world contexts often relies on strategic simplifications of decision problems. Yet, the neural mechanisms that shape these strategies and their implementation remain largely unknown. Using a novel economic decision-making task, we dissociate brain regions that predict specific choices from those predicting an individual’s preferred strategy. Choices that maximized gains or minimized losses were predicted by fMRI activation in ventromedial prefrontal cortex or anterior insula, respectively. However, choices that followed a simplifying strategy (i.e., attending to overall probability of winning) were associated with activation in parietal and lateral prefrontal cortices. Dorsomedial prefrontal cortex, through differential functional connectivity with parietal and insular cortex, predicted individual variability in strategic preferences. Finally, we demonstrate that robust decision strategies follow from neural sensitivity to rewards. We conclude that decision making reflects more than compensatory interaction of choice-related regions; in addition, specific brain systems potentiate choices depending upon strategies, traits, and context. PMID:19477159

Mind over motor mapping: Driver response to changing vehicle dynamics.

PubMed

Bruno, Jennifer L; Baker, Joseph M; Gundran, Andrew; Harbott, Lene K; Stuart, Zachary; Piccirilli, Aaron M; Hosseini, S M Hadi; Gerdes, J Christian; Reiss, Allan L

2018-06-08

Improvements in vehicle safety require understanding of the neural systems that support the complex, dynamic task of real-world driving. We used functional near infrared spectroscopy (fNIRS) and pupilometry to quantify cortical and physiological responses during a realistic, simulated driving task in which vehicle dynamics were manipulated. Our results elucidate compensatory changes in driver behavior in response to changes in vehicle handling. We also describe associated neural and physiological responses under different levels of mental workload. The increased cortical activation we observed during the late phase of the experiment may indicate motor learning in prefrontal-parietal networks. Finally, relationships among cortical activation, steering control, and individual personality traits suggest that individual brain states and traits may be useful in predicting a driver's response to changes in vehicle dynamics. Results such as these will be useful for informing the design of automated safety systems that facilitate safe and supportive driver-car communication. © 2018 Wiley Periodicals, Inc.

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

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.

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

NMDA receptor antagonist-enhanced high frequency oscillations: are they generated broadly or regionally specific?

PubMed

Olszewski, Maciej; Dolowa, Wioleta; Matulewicz, Pawel; Kasicki, Stefan; Hunt, Mark J

2013-12-01

Systemic administration of NMDA receptor antagonists, used to model schizophrenia, increase the power of high-frequency oscillations (130-180Hz, HFO) in a variety of neuroanatomical and functionally distinct brain regions. However, it is unclear whether HFO are independently and locally generated or instead spread from a distant source. To address this issue, we used local infusion of tetrodotoxin (TTX) to distinct brain areas to determine how accurately HFO recorded after injection of NMDAR antagonists reflect the activity actually generated at the electrode tip. Changes in power were evaluated in local field potentials (LFPs) recorded from the nucleus accumbens (NAc), prefrontal cortex and caudate and in electrocorticograms (ECoGs) from visual and frontal areas. HFO recorded in frontal and visual cortices (ECoGs) or in the prefrontal cortex, caudate (LFPs) co-varied in power and frequency with observed changes in the NAc. TTX infusion to the NAc immediately and profoundly reduced the power of accumbal HFO which correlated with changes in HFO recorded in distant cortical sites. In contrast, TTX infusion to the prefrontal cortex did not change HFO power recorded locally, although gamma power was reduced. A very similar result was found after TTX infusion to the caudate. These findings raise the possibility that the NAc is an important neural generator. Our data also support existing studies challenging the idea that high frequencies recorded in LFPs are necessarily generated at the recording site. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

Tactile spatial working memory activates the dorsal extrastriate cortical pathway in congenitally blind individuals.

PubMed

Bonino, D; Ricciardi, E; Sani, L; Gentili, C; Vanello, N; Guazzelli, M; Vecchi, T; Pietrini, P

2008-09-01

In sighted individuals, both the visual and tactile version of the same spatial working memory task elicited neural responses in the dorsal "where" cortical pathway (Ricciardi et al., 2006). Whether the neural response during the tactile working memory task is due to visually-based spatial imagery or rather reflects a more abstract, supramodal organization of the dorsal cortical pathway remains to be determined. To understand the role of visual experience on the functional organization of the dorsal cortical stream, using functional magnetic resonance imaging (fMRI) here we examined brain response in four individuals with congenital or early blindness and no visual recollection, while they performed the same tactile spatial working memory task, a one-back recognition of 2D and 3D matrices. The blind subjects showed a significant activation in bilateral posterior parietal cortex, dorsolateral and inferior prefrontal areas, precuneus, lateral occipital cortex, and cerebellum. Thus, dorsal occipito-parietal areas are involved in mental imagery dealing with spatial components in subjects without prior visual experience and in response to a non-visual task. These data indicate that recruitment of the dorsal cortical pathway in response to the tactile spatial working memory task is not mediated by visually-based imagery and that visual experience is not a prerequisite for the development of a more abstract functional organization of the dorsal stream. These findings, along with previous data indicating a similar supramodal functional organization within the ventral cortical pathway and the motion processing brain regions, may contribute to explain how individuals who are born deprived of sight are able to interact effectively with the surrounding world.

Absence of visual experience modifies the neural basis of numerical thinking.

PubMed

Kanjlia, Shipra; Lane, Connor; Feigenson, Lisa; Bedny, Marina

2016-10-04

In humans, the ability to reason about mathematical quantities depends on a frontoparietal network that includes the intraparietal sulcus (IPS). How do nature and nurture give rise to the neurobiology of numerical cognition? We asked how visual experience shapes the neural basis of numerical thinking by studying numerical cognition in congenitally blind individuals. Blind (n = 17) and blindfolded sighted (n = 19) participants solved math equations that varied in difficulty (e.g., 27 - 12 = x vs. 7 - 2 = x), and performed a control sentence comprehension task while undergoing fMRI. Whole-cortex analyses revealed that in both blind and sighted participants, the IPS and dorsolateral prefrontal cortices were more active during the math task than the language task, and activity in the IPS increased parametrically with equation difficulty. Thus, the classic frontoparietal number network is preserved in the total absence of visual experience. However, surprisingly, blind but not sighted individuals additionally recruited a subset of early visual areas during symbolic math calculation. The functional profile of these "visual" regions was identical to that of the IPS in blind but not sighted individuals. Furthermore, in blindness, number-responsive visual cortices exhibited increased functional connectivity with prefrontal and IPS regions that process numbers. We conclude that the frontoparietal number network develops independently of visual experience. In blindness, this number network colonizes parts of deafferented visual cortex. These results suggest that human cortex is highly functionally flexible early in life, and point to frontoparietal input as a mechanism of cross-modal plasticity in blindness.

Rhinal and Dorsolateral Prefrontal Cortex Lesions Produce Selective Impairments in Object and Spatial Learning and Memory in Canines

PubMed Central

Christie, Lori-Ann; Saunders, Richard C.; Kowalska, Danuta, M.; MacKay, William A.; Head, Elizabeth; Cotman, Carl W.; Milgram, Norton W.

2014-01-01

To examine the effects of rhinal and dorsolateral prefrontal cortex lesions on object and spatial recognition memory in canines, we used a protocol in which both an object (delayed non-matching to sample, or DNMS) and a spatial (delayed non-matching to position or DNMP) recognition task were administered daily. The tasks used similar procedures such that only the type of stimulus information to be remembered differed. Rhinal cortex (RC) lesions produced a selective deficit on the DNMS task, both in retention of the task rules at short delays and in object recognition memory. By contrast, performance on the DNMP task remained intact at both short and long delay intervals in RC animals. Subjects who received dorsolateral prefrontal cortex (dlPFC) lesions were impaired on a spatial task at a short, 5-sec delay, suggesting disrupted retention of the general task rules, however, this impairment was transient; long-term spatial memory performance was unaffected in dlPFC subjects. The present results provide support for the involvement of the RC in object, but not visuospatial, processing and recognition memory, whereas the dlPFC appears to mediate retention of a non-matching rule. These findings support theories of functional specialization within the medial temporal lobe and frontal cortex and suggest that rhinal and dorsolateral prefrontal cortices in canines are functionally similar to analogous regions in other mammals. PMID:18792072

MRI correlates of interaction between gender and expressive suppression among the Chinese population.

PubMed

Wang, Kangcheng; Huang, Hui; Chen, Li; Hou, Xin; Zhang, Yong; Yang, Junyi; Hao, Xin; Qiu, Jiang

2017-04-07

Expressive suppression is a kind of emotion regulation strategies by suppressing behaviors related to emotional responding. Despite the amount of behavioral research on expressive suppression, the structural and functional mechanisms underlying the interaction between gender and expressive suppression in Chinese healthy subjects have remained unknown. In the current study, we assessed the levels of expressive suppression and acquired the structural and functional imaging data from 273 Chinese individuals. A nearly automatic cortical processing technique was used to calculate cortical thickness for each subject. The results from cortical thickness analyses revealed a significant interaction between gender and expressive suppression in the superior frontal gyrus. Then, we conducted the whole-brain functional connectivity analysis with the seed of the superior frontal gyrus to explore the functionally related regions of brain. Subsequent analysis of the interaction between gender and expressive suppression indicated a significant functional connectivity between the superior frontal gyrus and default mode network (DMN) core regions, including the medial prefrontal cortex, precuneus and parahippocampal gyrus. Our results provided the robust empirical evidence illustrating the role of the superior frontal gyrus and DMN in gender difference of expressive suppression among the Chinese population. These findings might have implications for understanding gender difference in emotion processing and regulation. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Prefrontal Cortex Activation Upon a Demanding Virtual Hand-Controlled Task: A New Frontier for Neuroergonomics

PubMed Central

Carrieri, Marika; Petracca, Andrea; Lancia, Stefania; Basso Moro, Sara; Brigadoi, Sabrina; Spezialetti, Matteo; Ferrari, Marco; Placidi, Giuseppe; Quaresima, Valentina

2016-01-01

Functional near-infrared spectroscopy (fNIRS) is a non-invasive vascular-based functional neuroimaging technology that can assess, simultaneously from multiple cortical areas, concentration changes in oxygenated-deoxygenated hemoglobin at the level of the cortical microcirculation blood vessels. fNIRS, with its high degree of ecological validity and its very limited requirement of physical constraints to subjects, could represent a valid tool for monitoring cortical responses in the research field of neuroergonomics. In virtual reality (VR) real situations can be replicated with greater control than those obtainable in the real world. Therefore, VR is the ideal setting where studies about neuroergonomics applications can be performed. The aim of the present study was to investigate, by a 20-channel fNIRS system, the dorsolateral/ventrolateral prefrontal cortex (DLPFC/VLPFC) in subjects while performing a demanding VR hand-controlled task (HCT). Considering the complexity of the HCT, its execution should require the attentional resources allocation and the integration of different executive functions. The HCT simulates the interaction with a real, remotely-driven, system operating in a critical environment. The hand movements were captured by a high spatial and temporal resolution 3-dimensional (3D) hand-sensing device, the LEAP motion controller, a gesture-based control interface that could be used in VR for tele-operated applications. Fifteen University students were asked to guide, with their right hand/forearm, a virtual ball (VB) over a virtual route (VROU) reproducing a 42 m narrow road including some critical points. The subjects tried to travel as long as possible without making VB fall. The distance traveled by the guided VB was 70.2 ± 37.2 m. The less skilled subjects failed several times in guiding the VB over the VROU. Nevertheless, a bilateral VLPFC activation, in response to the HCT execution, was observed in all the subjects. No correlation was found between the distance traveled by the guided VB and the corresponding cortical activation. These results confirm the suitability of fNIRS technology to objectively evaluate cortical hemodynamic changes occurring in VR environments. Future studies could give a contribution to a better understanding of the cognitive mechanisms underlying human performance either in expert or non-expert operators during the simulation of different demanding/fatiguing activities. PMID:26909033

Prefrontal Cortex Activation Upon a Demanding Virtual Hand-Controlled Task: A New Frontier for Neuroergonomics.

PubMed

Carrieri, Marika; Petracca, Andrea; Lancia, Stefania; Basso Moro, Sara; Brigadoi, Sabrina; Spezialetti, Matteo; Ferrari, Marco; Placidi, Giuseppe; Quaresima, Valentina

2016-01-01

Functional near-infrared spectroscopy (fNIRS) is a non-invasive vascular-based functional neuroimaging technology that can assess, simultaneously from multiple cortical areas, concentration changes in oxygenated-deoxygenated hemoglobin at the level of the cortical microcirculation blood vessels. fNIRS, with its high degree of ecological validity and its very limited requirement of physical constraints to subjects, could represent a valid tool for monitoring cortical responses in the research field of neuroergonomics. In virtual reality (VR) real situations can be replicated with greater control than those obtainable in the real world. Therefore, VR is the ideal setting where studies about neuroergonomics applications can be performed. The aim of the present study was to investigate, by a 20-channel fNIRS system, the dorsolateral/ventrolateral prefrontal cortex (DLPFC/VLPFC) in subjects while performing a demanding VR hand-controlled task (HCT). Considering the complexity of the HCT, its execution should require the attentional resources allocation and the integration of different executive functions. The HCT simulates the interaction with a real, remotely-driven, system operating in a critical environment. The hand movements were captured by a high spatial and temporal resolution 3-dimensional (3D) hand-sensing device, the LEAP motion controller, a gesture-based control interface that could be used in VR for tele-operated applications. Fifteen University students were asked to guide, with their right hand/forearm, a virtual ball (VB) over a virtual route (VROU) reproducing a 42 m narrow road including some critical points. The subjects tried to travel as long as possible without making VB fall. The distance traveled by the guided VB was 70.2 ± 37.2 m. The less skilled subjects failed several times in guiding the VB over the VROU. Nevertheless, a bilateral VLPFC activation, in response to the HCT execution, was observed in all the subjects. No correlation was found between the distance traveled by the guided VB and the corresponding cortical activation. These results confirm the suitability of fNIRS technology to objectively evaluate cortical hemodynamic changes occurring in VR environments. Future studies could give a contribution to a better understanding of the cognitive mechanisms underlying human performance either in expert or non-expert operators during the simulation of different demanding/fatiguing activities.

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.

Neural signatures of economic parameters during decision-making: a functional MRI (FMRI), electroencephalography (EEG) and autonomic monitoring study.

PubMed

Minati, Ludovico; Grisoli, Marina; Franceschetti, Silvana; Epifani, Francesca; Granvillano, Alice; Medford, Nick; Harrison, Neil A; Piacentini, Sylvie; Critchley, Hugo D

2012-01-01

Adaptive behaviour requires an ability to obtain rewards by choosing between different risky options. Financial gambles can be used to study effective decision-making experimentally, and to distinguish processes involved in choice option evaluation from outcome feedback and other contextual factors. Here, we used a paradigm where participants evaluated 'mixed' gambles, each presenting a potential gain and a potential loss and an associated variable outcome probability. We recorded neural responses using autonomic monitoring, electroencephalography (EEG) and functional neuroimaging (fMRI), and used a univariate, parametric design to test for correlations with the eleven economic parameters that varied across gambles, including expected value (EV) and amount magnitude. Consistent with behavioural economic theory, participants were risk-averse. Gamble evaluation generated detectable autonomic responses, but only weak correlations with outcome uncertainty were found, suggesting that peripheral autonomic feedback does not play a major role in this task. Long-latency stimulus-evoked EEG potentials were sensitive to expected gain and expected value, while alpha-band power reflected expected loss and amount magnitude, suggesting parallel representations of distinct economic qualities in cortical activation and central arousal. Neural correlates of expected value representation were localized using fMRI to ventromedial prefrontal cortex, while the processing of other economic parameters was associated with distinct patterns across lateral prefrontal, cingulate, insula and occipital cortices including default-mode network and early visual areas. These multimodal data provide complementary evidence for distributed substrates of choice evaluation across multiple, predominantly cortical, brain systems wherein distinct regions are preferentially attuned to specific economic features. Our findings extend biologically-plausible models of risky decision-making while providing potential biomarkers of economic representations that can be applied to the study of deficits in motivational behaviour in neurological and psychiatric patients.

Increased corticolimbic connectivity in cocaine dependence versus pathological gambling is associated with drug severity and emotion-related impulsivity.

PubMed

Contreras-Rodríguez, Oren; Albein-Urios, Natalia; Vilar-López, Raquel; Perales, Jose C; Martínez-Gonzalez, Jose M; Fernández-Serrano, Maria J; Lozano-Rojas, Oscar; Clark, Luke; Verdejo-García, Antonio

2016-05-01

Neural biomarkers for the active detrimental effects of cocaine dependence (CD) are lacking. Direct comparisons of brain connectivity in cocaine-targeted networks between CD and behavioural addictions (i.e. pathological gambling, PG) may be informative. This study therefore contrasted the resting-state functional connectivity networks of 20 individuals with CD, 19 individuals with PG and 21 healthy individuals (controls). Study groups were assessed to rule out psychiatric co-morbidities (except alcohol abuse and nicotine dependence) and current substance use or gambling (except PG). We first examined global connectivity differences in the corticolimbic reward network and then utilized seed-based analyses to characterize the connectivity of regions displaying between-group differences. We examined the relationships between seed-based connectivity and trait impulsivity and cocaine severity. CD compared with PG displayed increased global functional connectivity in a large-scale ventral corticostriatal network involving the orbitofrontal cortex, caudate, thalamus and amygdala. Seed-based analyses showed that CD compared with PG exhibited enhanced connectivity between the orbitofrontal and subgenual cingulate cortices and between caudate and lateral prefrontal cortex, which are involved in representing the value of decision-making feedback. CD and PG compared with controls showed overlapping connectivity changes between the orbitofrontal and dorsomedial prefrontal cortices and between amygdala and insula, which are involved in stimulus-outcome learning. Orbitofrontal-subgenual cingulate cortical connectivity correlated with impulsivity and caudate/amygdala connectivity correlated with cocaine severity. We conclude that CD is linked to enhanced connectivity in a large-scale ventral corticostriatal-amygdala network that is relevant to decision making and likely to reflect an active cocaine detrimental effect. © 2015 Society for the Study of Addiction.

Infralimbic Prefrontal Cortex Interacts with Nucleus Accumbens Shell to Unmask Expression of Outcome-Selective Pavlovianto- Instrumental Transfer

ERIC Educational Resources Information Center

Keistler, Colby; Barker, Jacqueline M.; Taylor, Jane R.

2015-01-01

Although several studies have examined the subcortical circuitry underlying Pavlovian-to-instrumental transfer (PIT), the role of medial prefrontal cortex in this behavior is largely unknown. Elucidating the cortical contributions to PIT will be key for understanding how reward-paired cues control behavior in both adaptive and maladaptive context…

Neural circuits in auditory and audiovisual memory.

PubMed

Plakke, B; Romanski, L M

2016-06-01

Working memory is the ability to employ recently seen or heard stimuli and apply them to changing cognitive context. Although much is known about language processing and visual working memory, the neurobiological basis of auditory working memory is less clear. Historically, part of the problem has been the difficulty in obtaining a robust animal model to study auditory short-term memory. In recent years there has been neurophysiological and lesion studies indicating a cortical network involving both temporal and frontal cortices. Studies specifically targeting the role of the prefrontal cortex (PFC) in auditory working memory have suggested that dorsal and ventral prefrontal regions perform different roles during the processing of auditory mnemonic information, with the dorsolateral PFC performing similar functions for both auditory and visual working memory. In contrast, the ventrolateral PFC (VLPFC), which contains cells that respond robustly to auditory stimuli and that process both face and vocal stimuli may be an essential locus for both auditory and audiovisual working memory. These findings suggest a critical role for the VLPFC in the processing, integrating, and retaining of communication information. This article is part of a Special Issue entitled SI: Auditory working memory. Copyright © 2015 Elsevier B.V. All rights reserved.

In favor of general probability distributions: lateral prefrontal and insular cortices respond to stimulus inherent, but irrelevant differences.

PubMed

Mestres-Missé, Anna; Trampel, Robert; Turner, Robert; Kotz, Sonja A

2016-04-01

A key aspect of optimal behavior is the ability to predict what will come next. To achieve this, we must have a fairly good idea of the probability of occurrence of possible outcomes. This is based both on prior knowledge about a particular or similar situation and on immediately relevant new information. One question that arises is: when considering converging prior probability and external evidence, is the most probable outcome selected or does the brain represent degrees of uncertainty, even highly improbable ones? Using functional magnetic resonance imaging, the current study explored these possibilities by contrasting words that differ in their probability of occurrence, namely, unbalanced ambiguous words and unambiguous words. Unbalanced ambiguous words have a strong frequency-based bias towards one meaning, while unambiguous words have only one meaning. The current results reveal larger activation in lateral prefrontal and insular cortices in response to dominant ambiguous compared to unambiguous words even when prior and contextual information biases one interpretation only. These results suggest a probability distribution, whereby all outcomes and their associated probabilities of occurrence--even if very low--are represented and maintained.

Reducing proactive aggression through non-invasive brain stimulation

PubMed Central

Schuhmann, Teresa; Lobbestael, Jill; Arntz, Arnoud; Brugman, Suzanne; Sack, Alexander T.

2015-01-01

Aggressive behavior poses a threat to human collaboration and social safety. It is of utmost importance to identify the functional mechanisms underlying aggression and to develop potential interventions capable of reducing dysfunctional aggressive behavior already at a brain level. We here experimentally shifted fronto-cortical asymmetry to manipulate the underlying motivational emotional states in both male and female participants while assessing the behavioral effects on proactive and reactive aggression. Thirty-two healthy volunteers received either anodal transcranial direct current stimulation to increase neural activity within right dorsolateral prefrontal cortex, or sham stimulation. Aggressive behavior was measured with the Taylor Aggression Paradigm. We revealed a general gender effect, showing that men displayed more behavioral aggression than women. After the induction of right fronto-hemispheric dominance, proactive aggression was reduced in men. This study demonstrates that non-invasive brain stimulation can reduce aggression in men. This is a relevant and promising step to better understand how cortical brain states connect to impulsive actions and to examine the causal role of the prefrontal cortex in aggression. Ultimately, such findings could help to examine whether the brain can be a direct target for potential supportive interventions in clinical settings dealing with overly aggressive patients and/or violent offenders. PMID:25680991

Time-dependent in-vivo effects of interleukin-2 on neurotransmitters in various cortices: relationships with depressive-related and anxiety-like behaviour.

PubMed

Karrenbauer, B D; Müller, C P; Ho, Y J; Spanagel, R; Huston, J P; Schwarting, R K W; Pawlak, C R

2011-08-15

We investigated the impact of systemically injected IL-2 (2.5 μg/kg, i.p.) on serotonergic and dopaminergic neurotransmission in various cortical areas by in-vivo microdialysis. IL-2 lastingly reduced extracellular 5-HT levels in the medial prefrontal (-75%), occipital (-70%), and temporal cortices (-45%), whereas dopamine was only moderately reduced in the medial prefrontal cortex. Based on the serotonergic time profile, we conducted further experiments to test for acute and delayed (2 h post injection) depressive-related effects of systemic IL-2 (0-5.0 μg/kg) in a forced swim test and delayed effects on anxiety-like behaviour in the elevated plus-maze. IL-2 had dose-dependent effects on depressive-related behaviour after delayed but not acute testing, but no effects on anxiety-like behaviour. Copyright © 2011 Elsevier B.V. All rights reserved.

Anticipation of a mentally effortful task recruits Dorsolateral Prefrontal Cortex: An fNIRS validation study.

PubMed

Vassena, Eliana; Gerrits, Robin; Demanet, Jelle; Verguts, Tom; Siugzdaite, Roma

2018-04-26

Preparing for a mentally demanding task calls upon cognitive and motivational resources. The underlying neural implementation of these mechanisms is receiving growing attention because of its implications for professional, social, and medical contexts. While several fMRI studies converge in assigning a crucial role to a cortico-subcortical network including Anterior Cigulate Cortex (ACC) and striatum, the involvement of Dorsolateral Prefrontal Cortex (DLPFC) during mental effort anticipation has yet to be replicated. This study was designed to target DLPFC contribution to anticipation of a difficult task using functional Near Infrared Spectroscopy (fNIRS), as a more cost-effective tool measuring cortical hemodynamics. We adapted a validated mental effort task, where participants performed easy and difficult mental calculation, and measured DLPFC activity during the anticipation phase. As hypothesized, DLPFC activity increased during anticipation of a hard task as compared to an easy task. Besides replicating previous fMRI work, these results establish fNIRS as an effective tool to investigate cortical contributions to anticipation of effortful behavior. This is especially useful if one requires testing large samples (e.g., to target individual differences), populations with contraindication for functional MRI (e.g., infants or patients with metal implants), or subjects in more naturalistic environments (e.g., work or sport). Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

[Psychotherapy of Depression as Neurobiological Process - Evidence from Neuroimaging].

PubMed

Rubart, Antonie; Hohagen, Fritz; Zurowski, Bartosz

2018-06-01

Research on neurobiological effects of psychotherapy in depression facilitates the improvement of treatment strategies. The cortico-limbic dysregulation model serves as a framework for numerous studies on neurobiological changes in depression. In this model, depression is described as hypoactivation of dorsal cortical brain regions in conjunction with hyperactivation of ventral paralimbic regions. This assumption has been supported by various studies of structural and functional brain abnormalities in depression. However, also regions not included in the original cortico-limbic dysregulation model, such as the dorsomedial prefrontal cortex, seem to play an important role in depression. Functional connectivity studies of depression have revealed an enhanced connectivity within the so-called default mode network which is involved in self-referential thinking. Studies also point to a normalization of limbic and cortical brain activity, especially in the anterior cingulate cortex, during psychotherapy. Some neurobiological markers like the activity of the anterior cingulate cortex, striatum and insula as well as hippocampal volume have been proposed to predict treatment response on a group-level. The activity of the anterior insula appears to be a candidate bio-marker for differential indication for psychotherapy or pharmacotherapy. The cortico-limbic dysregulation model and following research have inspired new forms of treatment for depression like deep brain stimulation of the subgenual anterior cingulate cortex, repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex, neurofeedback and attention training. © Georg Thieme Verlag KG Stuttgart · New York.

Semantic encoding and retrieval in the left inferior prefrontal cortex: a functional MRI study of task difficulty and process specificity.

PubMed

Demb, J B; Desmond, J E; Wagner, A D; Vaidya, C J; Glover, G H; Gabrieli, J D

1995-09-01

Prefrontal cortical function was examined during semantic encoding and repetition priming using functional magnetic resonance imaging (fMRI), a noninvasive technique for localizing regional changes in blood oxygenation, a correlate of neural activity. Words studied in a semantic (deep) encoding condition were better remembered than words studied in both easier and more difficult nonsemantic (shallow) encoding conditions, with difficulty indexed by response time. The left inferior prefrontal cortex (LIPC) (Brodmann's areas 45, 46, 47) showed increased activation during semantic encoding relative to nonsemantic encoding regardless of the relative difficulty of the nonsemantic encoding task. Therefore, LIPC activation appears to be related to semantic encoding and not task difficulty. Semantic encoding decisions are performed faster the second time words are presented. This represents semantic repetition priming, a facilitation in semantic processing for previously encoded words that is not dependent on intentional recollection. The same LIPC area activated during semantic encoding showed decreased activation during repeated semantic encoding relative to initial semantic encoding of the same words. This decrease in activation during repeated encoding was process specific; it occurred when words were semantically reprocessed but not when words were nonsemantically reprocessed. The results were apparent in both individual and averaged functional maps. These findings suggest that the LIPC is part of a semantic executive system that contributes to the on-line retrieval of semantic information.

The neuroscience of musical improvisation.

PubMed

Beaty, Roger E

2015-04-01

Researchers have recently begun to examine the neural basis of musical improvisation, one of the most complex forms of creative behavior. The emerging field of improvisation neuroscience has implications not only for the study of artistic expertise, but also for understanding the neural underpinnings of domain-general processes such as motor control and language production. This review synthesizes functional magnetic resonance imagining (fMRI) studies of musical improvisation, including vocal and instrumental improvisation, with samples of jazz pianists, classical musicians, freestyle rap artists, and non-musicians. A network of prefrontal brain regions commonly linked to improvisatory behavior is highlighted, including the pre-supplementary motor area, medial prefrontal cortex, inferior frontal gyrus, dorsolateral prefrontal cortex, and dorsal premotor cortex. Activation of premotor and lateral prefrontal regions suggests that a seemingly unconstrained behavior may actually benefit from motor planning and cognitive control. Yet activation of cortical midline regions points to a role of spontaneous cognition characteristic of the default network. Together, such results may reflect cooperation between large-scale brain networks associated with cognitive control and spontaneous thought. The improvisation literature is integrated with Pressing's theoretical model, and discussed within the broader context of research on the brain basis of creative cognition. Copyright © 2015 Elsevier Ltd. All rights reserved.

Neural and cognitive plasticity: from maps to minds.

PubMed

Mercado, Eduardo

2008-01-01

Some species and individuals are able to learn cognitive skills more flexibly than others. Learning experiences and cortical function are known to contribute to such differences, but the specific factors that determine an organism's intellectual capacities remain unclear. Here, an integrative framework is presented suggesting that variability in cognitive plasticity reflects neural constraints on the precision and extent of an organism's stimulus representations. Specifically, it is hypothesized that cognitive plasticity depends on the number and diversity of cortical modules that an organism has available as well as the brain's capacity to flexibly reconfigure and customize networks of these modules. The author relates this framework to past proposals on the neural mechanisms of intelligence, including (a) the relationship between brain size and intellectual capacity; (b) the role of prefrontal cortex in cognitive control and the maintenance of stimulus representations; and (c) the impact of neural plasticity and efficiency on the acquisition and performance of cognitive skills. The proposed framework provides a unified account of variability in cognitive plasticity as a function of species, age, and individual, and it makes specific predictions about how manipulations of cortical structure and function will impact intellectual capacity. Copyright (c) 2008 APA.

Cortico-hippocampal systems involved in memory and cognition: the PMAT framework.

PubMed

Ritchey, Maureen; Libby, Laura A; Ranganath, Charan

2015-01-01

In this chapter, we review evidence that the cortical pathways to the hippocampus appear to extend from two large-scale cortical systems: a posterior medial (PM) system that includes the parahippocampal cortex and retrosplenial cortex, and an anterior temporal (AT) system that includes the perirhinal cortex. This "PMAT" framework accounts for differences in the anatomical and functional connectivity of the medial temporal lobes, which may underpin differences in cognitive function between the systems. The PM and AT systems make distinct contributions to memory and to other cognitive domains, and convergent findings suggest that they are involved in processing information about contexts and items, respectively. In order to support the full complement of memory-guided behavior, the two systems must interact, and the hippocampal and ventromedial prefrontal cortex may serve as sites of integration between the two systems. We conclude that when considering the "connected hippocampus," inquiry should extend beyond the medial temporal lobes to include the large-scale cortical systems of which they are a part. © 2015 Elsevier B.V. All rights reserved.

Is autism a disease of the cerebellum? An integration of clinical and pre-clinical research

PubMed Central

Rogers, Tiffany D.; McKimm, Eric; Dickson, Price E.; Goldowitz, Dan; Blaha, Charles D.; Mittleman, Guy

2013-01-01

Autism spectrum disorders are a group of neurodevelopmental disorders characterized by deficits in social skills and communication, stereotyped and repetitive behavior, and a range of deficits in cognitive function. While the etiology of autism is unknown, current research indicates that abnormalities of the cerebellum, now believed to be involved in cognitive function and the prefrontal cortex (PFC), are associated with autism. The current paper proposes that impaired cerebello-cortical circuitry could, at least in part, underlie autistic symptoms. The use of animal models that allow for manipulation of genetic and environmental influences are an effective means of elucidating both distal and proximal etiological factors in autism and their potential impact on cerebello-cortical circuitry. Some existing rodent models of autism, as well as some models not previously applied to the study of the disorder, display cerebellar and behavioral abnormalities that parallel those commonly seen in autistic patients. The novel findings produced from research utilizing rodent models could provide a better understanding of the neurochemical and behavioral impact of changes in cerebello-cortical circuitry in autism. PMID:23717269

Grey matter volume and cortical structure in Prader-Willi syndrome compared to typically developing young adults.

PubMed

Manning, Katherine E; Tait, Roger; Suckling, John; Holland, Anthony J

2018-01-01

Prader-Willi syndrome (PWS) is a neurodevelopmental disorder of genomic imprinting, presenting with a characteristic overeating disorder, mild to moderate intellectual disability, and a variable range of social and behavioral difficulties. Consequently, widespread alterations in neural structure and developmental and maturational trajectory would be expected. To date, there have been few quantitative and systematic studies of brain morphology in PWS, although alterations of volume and of cortical organisation have been reported. This study aimed to investigate, in detail, the structure of grey matter and cortex in the brain in a sample of young adults with PWS in a well-matched case-controlled analysis. 20 young adults with PWS, aged 19-27 years, underwent multiparameter mapping magnetic resonance imaging sequences, from which measures of grey matter volume, cortical thickness and magnetisation transfer saturation, as a proxy measure of myelination, were examined. These variables were investigated in comparison to a control group of 40 typically developing young adults, matched for age and sex. A voxel-based morphometry analysis identified large and widespread bilateral clusters of both increased and decreased grey matter volume in the brain in PWS. In particular, widespread areas of increased volume encompassed parts of the prefrontal cortex, especially medially, the majority of the cingulate cortices, from anterior to posterior aspects, insula cortices, and areas of the parietal and temporal cortices. Increased volume was also reported in the caudate, putamen and thalamus. The most ventromedial prefrontal areas, in contrast, showed reduced volume, as did the parts of the medial temporal lobe, bilateral temporal poles, and a small cluster in the right lateral prefrontal cortex. Analysis of cortical structure revealed that areas of increased volume in the PWS group were largely driven by greater cortical thickness. Conversely, analysis of myelin content using magnetisation transfer saturation indicated that myelination of the cortex was broadly similar in the PWS and control groups, with the exception of highly localised areas, including the insula. The bilateral nature of these abnormalities suggests a systemic biological cause, with possible developmental and maturational mechanisms discussed, and may offer insight into the contribution of imprinted genes to neural development.

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

PubMed

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

2017-01-15

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

Stepwise Connectivity of the Modal Cortex Reveals the Multimodal Organization of the Human Brain

PubMed Central

Sepulcre, Jorge; Sabuncu, Mert R.; Yeo, Thomas B.; Liu, Hesheng; Johnson, Keith A.

2012-01-01

How human beings integrate information from external sources and internal cognition to produce a coherent experience is still not well understood. During the past decades, anatomical, neurophysiological and neuroimaging research in multimodal integration have stood out in the effort to understand the perceptual binding properties of the brain. Areas in the human lateral occipito-temporal, prefrontal and posterior parietal cortices have been associated with sensory multimodal processing. Even though this, rather patchy, organization of brain regions gives us a glimpse of the perceptual convergence, the articulation of the flow of information from modality-related to the more parallel cognitive processing systems remains elusive. Using a method called Stepwise Functional Connectivity analysis, the present study analyzes the functional connectome and transitions from primary sensory cortices to higher-order brain systems. We identify the large-scale multimodal integration network and essential connectivity axes for perceptual integration in the human brain. PMID:22855814

Methamphetamine users show greater than normal age-related cortical gray matter loss.

PubMed

Nakama, Helenna; Chang, Linda; Fein, George; Shimotsu, Ryan; Jiang, Caroline S; Ernst, Thomas

2011-08-01

Methamphetamine (Meth) abuse continues to be a major illicit drug of abuse. Neuroimaging findings suggest that Meth is neurotoxic and may alter various brain structures, but the effect of Meth on the aging brain has not been studied. The aim was to determine regional volumes of cortical gray matter in the brains of adult Meth users versus healthy control subjects, and their interaction with age and Meth-usage variables. Cross-sectional study Magnetic resonance imaging (MRI) Research Center located in a university-affiliated hospital. Thirty-four Meth-dependent subjects (21 men and 13 women; ages 33.1 ± 8.9 years), diagnosed according to DSM-IV criteria, and 31 healthy non-Meth user comparison subjects (23 men and 8 women ages 35.7 ± 8.4 years). Regional gray matter volumes were segmented automatically in all subjects and evaluated in relation to age, using high-resolution MRIs at 3.0 Tesla. After adjustment for the effects of cranium size, the Meth users showed enhanced cortical gray matter volume loss with age in the frontal (analysis of covariance interaction P = 0.02), occipital (interaction P = 0.01), temporal (interaction P < 0.001) and the insular lobes (interaction P = 0.01) compared to controls, independently of Meth-usage patterns. Additionally, Meth users showed smaller gray matter volumes than control subjects in several subregions (dorsolateral prefrontal: P = 0.02; orbitofrontal: P = 0.03; prefrontal: P = 0.047; superior temporal: P = 0.04). Methamphetamine users appear to show increased cortical gray matter loss with age which raises the possibility of accelerated decline in mental functioning. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

Coordinated prefrontal-hippocampal activity and navigation strategy-related prefrontal firing during spatial memory formation.

PubMed

Negrón-Oyarzo, Ignacio; Espinosa, Nelson; Aguilar, Marcelo; Fuenzalida, Marco; Aboitiz, Francisco; Fuentealba, Pablo

2018-06-18

Learning the location of relevant places in the environment is crucial for survival. Such capacity is supported by a distributed network comprising the prefrontal cortex and hippocampus, yet it is not fully understood how these structures cooperate during spatial reference memory formation. Hence, we examined neural activity in the prefrontal-hippocampal circuit in mice during acquisition of spatial reference memory. We found that interregional oscillatory coupling increased with learning, specifically in the slow-gamma frequency (20 to 40 Hz) band during spatial navigation. In addition, mice used both spatial and nonspatial strategies to navigate and solve the task, yet prefrontal neuronal spiking and oscillatory phase coupling were selectively enhanced in the spatial navigation strategy. Lastly, a representation of the behavioral goal emerged in prefrontal spiking patterns exclusively in the spatial navigation strategy. These results suggest that reference memory formation is supported by enhanced cortical connectivity and evolving prefrontal spiking representations of behavioral goals.

Childhood abuse and reduced cortical thickness in brain regions involved in emotional processing.

PubMed

Gold, Andrea L; Sheridan, Margaret A; Peverill, Matthew; Busso, Daniel S; Lambert, Hilary K; Alves, Sonia; Pine, Daniel S; McLaughlin, Katie A

2016-10-01

Alterations in gray matter development represent a potential pathway through which childhood abuse is associated with psychopathology. Several prior studies find reduced volume and thickness of prefrontal (PFC) and temporal cortex regions in abused compared with nonabused adolescents, although most prior research is based on adults and volume-based measures. This study tests the hypothesis that child abuse, independent of parental education, predicts reduced cortical thickness in prefrontal and temporal cortices as well as reduced gray mater volume (GMV) in subcortical regions during adolescence. Structural MRI scans were obtained from 21 adolescents exposed to physical and/or sexual abuse and 37 nonabused adolescents (ages 13-20). Abuse was operationalized using dichotomous and continuous measures. We examined associations between abuse and brain structure in several a priori-defined regions, controlling for parental education, age, sex, race, and total brain volume for subcortical GMV. Significance was evaluated at p < .05 with a false discovery rate correction. Child abuse exposure and severity were associated with reduced thickness in ventromedial prefrontal cortex (PFC), right lateral orbitofrontal cortex, right inferior frontal gyrus, bilateral parahippocampal gyrus (PHG), left temporal pole, and bilateral inferior, right middle, and right superior temporal gyri. Neither abuse measure predicted cortical surface area or subcortical GMV. Bilateral PHG thickness was inversely related to externalizing symptoms. Child abuse, an experience characterized by a high degree of threat, is associated with reduced cortical thickness in ventromedial and ventrolateral PFC and medial and lateral temporal cortex in adolescence. Reduced PHG thickness may be a mediator linking abuse with externalizing psychopathology, although prospective research is needed to evaluate this possibility. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Best facilitated cortical activation during different stepping, treadmill, and robot-assisted walking training paradigms and speeds: A functional near-infrared spectroscopy neuroimaging study.

PubMed

Kim, Ha Yeon; Yang, Sung Phil; Park, Gyu Lee; Kim, Eun Joo; You, Joshua Sung Hyun

2016-01-01

Robot-assisted and treadmill-gait training are promising neurorehabilitation techniques, with advantages over conventional gait training, but the neural substrates underpinning locomotor control remain unknown particularly during different gait training modes and speeds. The present optical imaging study compared cortical activities during conventional stepping walking (SW), treadmill walking (TW), and robot-assisted walking (RW) at different speeds. Fourteen healthy subjects (6 women, mean age 30.06, years ± 4.53) completed three walking training modes (SW, TW, and RW) at various speeds (self-selected, 1.5, 2.0, 2.5, and 3.0  km/h). A functional near-infrared spectroscopy (fNIRS) system determined cerebral hemodynamic changes associated with cortical locomotor network areas in the primary sensorimotor cortex (SMC), premotor cortex (PMC), supplementary motor area (SMA), prefrontal cortex (PFC), and sensory association cortex (SAC). There was increased cortical activation in the SMC, PMC, and SMA during different walking training modes. More global locomotor network activation was observed during RW than TW or SW. As walking speed increased, multiple locomotor network activations were observed, and increased activation power spectrum. This is the first empirical evidence highlighting the neural substrates mediating dynamic locomotion for different gait training modes and speeds. Fast, robot-assisted gait training best facilitated cortical activation associated with locomotor control.

Alterations of decision making and underlying neural correlates after resection of a mediofrontal cortical dysplasia: A single case study.

PubMed

Labudda, Kirsten; Brand, Matthias; Mertens, Markus; Ebner, Alois; Markowitsch, Hans J; Woermann, Friedrich G

2010-02-01

We investigated the impact of a congenital prefrontal lesion and its resection on decision making under risk and under ambiguity in a patient with right mediofrontal cortical dysplasia. Both kinds of decision making are normally associated with the medial prefrontal cortex. We additionally studied pre- and postsurgical fMRI activations when processing information relevant for risky decision making. Results indicate selective impairments of ambiguous decision making pre- and postsurgically. Decision making under risk was intact. In contrast to healthy subjects the patient exhibited no activation within the dysplastic anterior cingulate cortex but left-sided orbitofrontal activation on the fMRI task suggesting early reorganization processes.

Changes of cortical excitability as markers of antidepressant response in bipolar depression: preliminary data obtained by combining transcranial magnetic stimulation (TMS) and electroencephalography (EEG).

PubMed

Canali, Paola; Sferrazza Papa, Giovanna; Casali, Adenauer G; Schiena, Giandomenico; Fecchio, Matteo; Pigorini, Andrea; Smeraldi, Enrico; Colombo, Cristina; Benedetti, Francesco

2014-12-01

It is still unclear which biological changes are needed to recover from a major depressive episode. Current perspectives focus on cortical synaptic neuroplasticity. Measures of cortical responses evoked by transcranial magnetic stimulation (TMS) change with sleep homeostasic pressure in humans and approximate measures of synaptic strength in animal models. Using repeated total sleep deprivation as a model of antidepressant treatment, we aimed to correlate recovery from depression with these measures of cortical excitability. We recorded electroencephalographic responses to TMS in the prefrontal cortex of 21 depressed inpatients with bipolar disorder treated with repeated sleep deprivation combined with light therapy. We performed seven TMS/electroencephalography sessions during one week and calculated three measures of cortical excitability. Cortical excitability progressively increased during the antidepressant treatment and as a function of time awake. Higher values differentiated responders from non-responders at baseline and during and after treatment on all measures. Changes in measures of cortical excitability parallel and predict antidepressant response to combined sleep deprivation and light therapy. Data suggest that promoting cortical plasticity in bipolar depression could be a major effect of successful antidepressant treatments, and that patients not responding could suffer a persistent impairment in their neuroplasticity mechanisms. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Region-Specific Dissociation between Cortical Noradrenaline Levels and the Sleep/Wake Cycle

PubMed Central

Bellesi, Michele; Tononi, Giulio; Cirelli, Chiara; Serra, Pier Andrea

2016-01-01

Study Objectives: The activity of the noradrenergic system of the locus coeruleus (LC) is high in wake and low in sleep. LC promotes arousal and EEG activation, as well as attention, working memory, and cognitive flexibility. These functions rely on prefrontal cortex and are impaired by sleep deprivation, but the extent to which LC activity changes during wake remains unclear. Moreover, it is unknown whether noradrenergic neurons can sustain elevated firing during extended wake. Recent studies show that relative to LC neurons targeting primary motor cortex (M1), those projecting to medial prefrontal cortex (mPFC) have higher spontaneous firing rates and are more excitable. These results suggest that noradrenaline (NA) levels should be higher in mPFC than M1, and that during prolonged wake LC cells targeting mPFC may fatigue more, but direct evidence is lacking. Methods: We performed in vivo microdialysis experiments in adult (9–10 weeks old) C57BL/6 mice implanted for chronic electroencephalographic recordings. Cortical NA levels were measured during spontaneous sleep and wake (n = 8 mice), and in the course of sleep deprivation (n = 6). Results: We found that absolute NA levels are higher in mPFC than in M1. Moreover, in both areas they decline during sleep and increase during wake, but these changes are faster in M1 than mPFC. Finally, by the end of sleep deprivation NA levels decline only in mPFC. Conclusions: Locus coeruleus (LC) neurons targeting prefrontal cortex may fatigue more markedly, or earlier, than other LC cells, suggesting one of the mechanisms underlying the cognitive impairment and the increased sleep presure associated with sleep deprivation. Commentary: A commentary on this article appears in this issue on page 11. Citation: Bellesi M, Tononi G, Cirelli C, Serra PA. Region-specific dissociation between cortical noradrenaline levels and the sleep/wake cycle. SLEEP 2016;39(1):143–154. PMID:26237776

N-methyl-D-aspartate receptor antagonist effects on prefrontal cortical connectivity better model early than chronic schizophrenia.

PubMed

Anticevic, Alan; Corlett, Philip R; Cole, Michael W; Savic, Aleksandar; Gancsos, Mark; Tang, Yanqing; Repovs, Grega; Murray, John D; Driesen, Naomi R; Morgan, Peter T; Xu, Ke; Wang, Fei; Krystal, John H

2015-03-15

Prefrontal cortex (PFC) function contributes to schizophrenia onset and progression. However, little is known about neural mechanisms behind PFC functional alterations along illness stages. Recent pharmacologic studies indicate that glutamate dysfunction may produce increased functional connectivity. However, pharmacologic models of schizophrenia overlook effects of illness progression on PFC function. This study compared N-methyl-D-aspartate glutamate receptor (NMDAR) antagonist effects in healthy volunteers with stages of schizophrenia with respect to PFC functional connectivity. First, we tested ketamine effects on PFC functional connectivity in healthy volunteers in a data-driven way (n = 19). Next, we compared healthy subjects (n = 96) with three clinical groups: individuals at high risk for schizophrenia (n = 21), people early in their course of schizophrenia (EC-SCZ) (n = 28), and patients with chronic illness (n = 20). Across independent analyses, we used data-driven global brain connectivity techniques restricted to PFC to identify functional dysconnectivity. Results revealed robust PFC hyperconnectivity in healthy volunteers administered ketamine (Cohen's d = 1.46), resembling individuals at high risk for schizophrenia and EC-SCZ. Hyperconnectivity was not found in patients with chronic illness relative to EC-SCZ patients. Results provide the first evidence that ketamine effects on PFC functional connectivity resemble early course but not chronic schizophrenia. Results suggest an illness phase-specific relevance of NMDAR antagonist administration for prefrontal dysconnectivity associated with schizophrenia. This finding has implications for the neurobiology of illness progression and for the widespread use of NMDAR antagonists in the development of therapeutics for schizophrenia. Copyright © 2015. Published by Elsevier Inc.

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

PubMed

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

2017-01-01

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

Neural correlates of reduced depressive symptoms following cognitive training for chronic traumatic brain injury.

PubMed

Han, Kihwan; Martinez, David; Chapman, Sandra B; Krawczyk, Daniel C

2018-03-23

Depression is the most frequent comorbid psychiatric condition among individuals with traumatic brain injury (TBI). Yet, little is known about changes in the brain associated with reduced depressive symptoms following rehabilitation for TBI. We identified whether cognitive training alleviates comorbid depressive symptoms in chronic TBI (>6 months post-injury) as a secondary effect. Further, we elucidated neural correlates of alleviated depressive symptoms following cognitive training. A total of seventy-nine individuals with chronic TBI (53 depressed and 26 non-depressed individuals, measured using the Beck Depressive Inventory [BDI]), underwent either strategy- or information-based cognitive training in a small group for 8 weeks. We measured psychological functioning scores, cortical thickness, and resting-state functional connectivity (rsFC) for these individuals before training, immediately post-training, and 3 months post-training. After confirming that changes in BDI scores were independent of training group affiliation, we identified that the depressive-symptoms group showed reductions in BDI scores over time relative to the non-depressed TBI controls (p < .01). Within the depressive-symptoms group, reduced BDI scores was associated with improvements in scores for post-traumatic stress disorder, TBI symptom awareness, and functional status (p < .00625), increases in cortical thickness in four regions within the right prefrontal cortex (p vertex  < .01, p cluster <.05), and decreases in rsFC with each of these four prefrontal regions (p vertex  < .01, p cluster  < .0125). Overall, these findings suggest that cognitive training can reduce depressive symptoms in TBI even when the training does not directly target psychiatric symptoms. Importantly, cortical thickness and brain connectivity may offer promising neuroimaging markers of training-induced improvement in mental health status in TBI. © 2018 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Virtual reality training improves balance function.

PubMed

Mao, Yurong; Chen, Peiming; Li, Le; Huang, Dongfeng

2014-09-01

Virtual reality is a new technology that simulates a three-dimensional virtual world on a computer and enables the generation of visual, audio, and haptic feedback for the full immersion of users. Users can interact with and observe objects in three-dimensional visual space without limitation. At present, virtual reality training has been widely used in rehabilitation therapy for balance dysfunction. This paper summarizes related articles and other articles suggesting that virtual reality training can improve balance dysfunction in patients after neurological diseases. When patients perform virtual reality training, the prefrontal, parietal cortical areas and other motor cortical networks are activated. These activations may be involved in the reconstruction of neurons in the cerebral cortex. Growing evidence from clinical studies reveals that virtual reality training improves the neurological function of patients with spinal cord injury, cerebral palsy and other neurological impairments. These findings suggest that virtual reality training can activate the cerebral cortex and improve the spatial orientation capacity of patients, thus facilitating the cortex to control balance and increase motion function.

Virtual reality training improves balance function

PubMed Central

Mao, Yurong; Chen, Peiming; Li, Le; Huang, Dongfeng

2014-01-01

Virtual reality is a new technology that simulates a three-dimensional virtual world on a computer and enables the generation of visual, audio, and haptic feedback for the full immersion of users. Users can interact with and observe objects in three-dimensional visual space without limitation. At present, virtual reality training has been widely used in rehabilitation therapy for balance dysfunction. This paper summarizes related articles and other articles suggesting that virtual reality training can improve balance dysfunction in patients after neurological diseases. When patients perform virtual reality training, the prefrontal, parietal cortical areas and other motor cortical networks are activated. These activations may be involved in the reconstruction of neurons in the cerebral cortex. Growing evidence from clinical studies reveals that virtual reality training improves the neurological function of patients with spinal cord injury, cerebral palsy and other neurological impairments. These findings suggest that virtual reality training can activate the cerebral cortex and improve the spatial orientation capacity of patients, thus facilitating the cortex to control balance and increase motion function. PMID:25368651

[The neural mechanisms of cigarette craving and self-control].

PubMed

Hayashi, Takuya

2014-01-01

A craving for cigarettes or drugs has been believed to be a fundamental psychopathological factor that drives drug-seeking behavior and relapse. Behavioral economics has revealed context-dependent changes in drug craving. Neuroimaging studies have also found craving-related signals that were altered depending on the context of the experiments. A rational decision-making theory modeled such context-dependency and uncovered a pivotal role of the prefrontal cortical circuit in both self-control and craving. Future studies should address how dopaminergic function and stress circuits can modify the function of decision-making circuits, and produce either craving or self-control.

Developmental disruption of medial prefrontal cortical GABAergic function by non-contingent cocaine exposure during early adolescence

PubMed Central

Cass, Daryn K.; Thomases, Daniel R.; Caballero, Adriana; Tseng, Kuei Y.

2013-01-01

Background Drug experimentation during adolescence is associated with increased risk of drug addiction relative to any other age group. To further our understanding on the neurobiology underlying such liability, we investigate how early adolescent cocaine experience impacts the overall medial prefrontal cortex (mPFC) network function in adulthood. Methods A non-contingent administration paradigm was used to assess the impact of early adolescent cocaine treatment (rats; postnatal days -PD- 35-40) on the overall inhibitory regulation of mPFC activity in adulthood (PD65-75) by means of histochemical and in vivo electrophysiological measures combined with pharmacological manipulations. Results Cocaine exposure during early adolescence yields a distinctive hyper-metabolic PFC state that was not observed in adult (PD75-80)-treated rats. Local field potential recordings expand upon these findings by showing that early adolescent cocaine exposure is associated with an attenuation of mPFC GABAergic inhibition evoked by ventral hippocampal stimulation at beta and gamma frequencies that endures throughout adulthood. Such cocaine-induced mPFC disinhibition was not observed in adult-exposed animals. Furthermore, the normal developmental upregulation of parvalbumin immunoreactivity observed in the mPFC from PD35 to PD65 is lacking following early adolescent cocaine treatment. Conclusion Our data indicate that repeated cocaine exposure during early adolescence can elicit a state of mPFC disinhibition resulting from a functional impairment of the local prefrontal GABAergic network that endures through adulthood. A lack of acquisition of prefrontal GABAergic function during adolescence could trigger long-term deficits in the mPFC that may increase the susceptibility for the onset of substance abuse and related psychiatric disorders. PMID:23558299

Decreased Regional Cortical Thickness and Thinning Rate Are Associated with Inattention Symptoms in Healthy Children

PubMed Central

Ducharme, Simon; Hudziak, James J.; Botteron, Kelly N.; Albaugh, Matthew D.; Nguyen, Tuong-Vi; Karama, Sherif; Evans, Alan C.

2011-01-01

Objective Children with attention-deficit/hyperactivity disorder (ADHD) have delayed cortical maturation, evidenced by regionally specific slower cortical thinning. However, the relationship between cortical maturation and attention capacities in typically developing children is unknown. This study examines cortical thickness correlates of inattention symptoms in a large sample of healthy children. Method Data from 357 healthy subjects (6.0–18.4 years of age) were obtained from the NIH MRI Study of Normal Brain Development. In cross-sectional analysis (first visit, n = 257), Child Behavior Checklist Attention Problems (AP) scores were linearly regressed against cortical thickness, controlling for age, gender, total brain volume, and site. For longitudinal data (up to three visits, n = 357/672 scans), similar analyses were performed using mixed-effects linear regressions. Interactions of AP with age and gender were tested. Results A cross-sectional “AP by age” interaction was found in bilateral orbito-frontal cortex, right inferior frontal cortex, bilateral ventromedial prefrontal cortex, bilateral dorsolateral prefrontal cortex, and several additional attention network regions. The interaction was due to negative associations between AP and thickness in younger subjects (6–10 years of age) that gradually disappeared over time secondary to slower cortical thinning. Similar trends were present in longitudinal analyses. Conclusions Higher AP scores were associated with thinner cortex at baseline and slower cortical thinning with aging in multiple areas involved in attention processes. Similar patterns have been identified in ADHD, suggesting a dimensional component to the link between attention and cortical maturation. The identified association between cortical maturation and attention in healthy development will help to inform studies of neuroimaging biomarkers of ADHD. PMID:22176936

Cardiovascular fitness, cortical plasticity, and aging.

PubMed

Colcombe, Stanley J; Kramer, Arthur F; Erickson, Kirk I; Scalf, Paige; McAuley, Edward; Cohen, Neal J; Webb, Andrew; Jerome, Gerry J; Marquez, David X; Elavsky, Steriani

2004-03-02

Cardiovascular fitness is thought to offset declines in cognitive performance, but little is known about the cortical mechanisms that underlie these changes in humans. Research using animal models shows that aerobic training increases cortical capillary supplies, the number of synaptic connections, and the development of new neurons. The end result is a brain that is more efficient, plastic, and adaptive, which translates into better performance in aging animals. Here, in two separate experiments, we demonstrate for the first time to our knowledge, in humans that increases in cardiovascular fitness results in increased functioning of key aspects of the attentional network of the brain during a cognitively challenging task. Specifically, highly fit (Study 1) or aerobically trained (Study 2) persons show greater task-related activity in regions of the prefrontal and parietal cortices that are involved in spatial selection and inhibitory functioning, when compared with low-fit (Study 1) or nonaerobic control (Study 2) participants. Additionally, in both studies there exist groupwise differences in activation of the anterior cingulate cortex, which is thought to monitor for conflict in the attentional system, and signal the need for adaptation in the attentional network. These data suggest that increased cardiovascular fitness can affect improvements in the plasticity of the aging human brain, and may serve to reduce both biological and cognitive senescence in humans.

[Neural mechanism underlying autistic savant and acquired savant syndrome].

PubMed

Takahata, Keisuke; Kato, Motoichiro

2008-07-01

It is well known that the cases with savant syndrome, demonstrate outstanding mental capability despite coexisting severe mental disabilities. In many cases, savant skills are characterized by its domain-specificity, enhanced memory capability, and excessive focus on low-level perceptual processing. In addition, impaired integrative cognitive processing such as social cognition or executive function, restricted interest, and compulsive repetition of the same act are observed in savant individuals. All these are significantly relevant to the behavioral characteristics observed in individuals with autistic spectrum disorders (ASD). A neurocognitive model of savant syndrome should explain these cognitive features and the juxtaposition of outstanding talents with cognitive disabilities. In recent neuropsychological studies, Miller (1998) reported clinical cases of "acquired savant," i.e., patients who improved or newly acquired an artistic savant-like skill in the early stage of frontotemporal dementia (FTD). Although the relationship between an autistic savant and acquired savant remains to be elucidated, the advent of neuroimaging study of ASD and the clarification of FTD patients with savant-like skills may clarify the shared neural mechanisms of both types of talent. In this review, we classified current cognitive models of savant syndrome into the following 3 categories. (1) A hypermnesic model that suggests that savant skills develop from existing or dormant cognitive functions such as memory. However, recent findings obtained through neuropsychological examinations imply that savant individuals solve problems using a strategy that is fairly different from a non-autistic one. (2) A paradoxical functional facilitation model (Kapur, 1996) that offers possible explanations about how pathological states in the brain lead to development of prodigious skills. This model emphasizes the role of reciprocal inhibitory interaction among adjacent or distant cortical regions, especially that of the prefrontal cortex and the posterior regions of the brain. (3) Autistic models, including those based on weak central coherence theory (Frith, 1989), that focus on how savant skills emerge from an autistic brain. Based on recent neuroimaging studies of ASD, Just et al. (2004) suggested the underconnectivity theory, which emphasizes the disruption of long-range connectivity and the relative intact or even more enhanced local connectivity in the autistic brain. All the models listed above have certain advantages and shortcomings. At the end of this review, we propose another integrative model of savant syndrome. In this model, we predict an altered balance of local/global connectivity patterns that contribute to an altered functional segregation/integration ratio. In particular, we emphasize the crucial role played by the disruption of global connectivity in a parallel distributed cortical network, which might result in impairment in integrated cognitive processing, such as impairment in executive function and social cognition. On the other hand, the reduced inter-regional collaboration could lead to a disinhibitory enhancement of neural activity and connectivity in local cortical regions. In addition, enhanced connectivity in the local brain regions is partly due to the abnormal organization of the cortical network as a result of developmental and pathological states. This enhanced local connectivity results in the specialization and facilitation of low-level cognitive processing. The disruption of connectivity between the prefrontal cortex and other regions is considered to be a particularly important factor because the prefrontal region shows the most influential inhibitory control on other cortical areas. We propose that these neural mechanisms as the underlying causes for the emergence of savant ability in ASD and FTD patients.

The role of prefrontal and parietal cortices in esthetic appreciation of representational and abstract art: a TMS study.

PubMed

Cattaneo, Zaira; Lega, Carlotta; Gardelli, Chiara; Merabet, Lotfi B; Cela-Conde, Camilo J; Nadal, Marcos

2014-10-01

To explain the biological foundations of art appreciation is to explain one of our species' distinctive traits. Previous neuroimaging and electrophysiological studies have pointed to the prefrontal and the parietal cortex as two critical regions mediating esthetic appreciation of visual art. In this study, we applied transcranial magnetic stimulation (TMS) over the left prefrontal cortex and the right posterior parietal cortex while participants were evaluating whether they liked, and by how much, a particular painting. By depolarizing cell membranes in the targeted regions, TMS transiently interferes with the activity of specific cortical areas, which allows clarifying their role in a given task. Our results show that both regions play a fundamental role in mediating esthetic appreciation. Critically though, the effects of TMS varied depending on the type of art considered (i.e. representational vs. abstract) and on participants' a-priori inclination toward one or the other. Copyright © 2014 Elsevier Inc. All rights reserved.

Pictionary-based fMRI paradigm to study the neural correlates of spontaneous improvisation and figural creativity.

PubMed

Saggar, Manish; Quintin, Eve-Marie; Kienitz, Eliza; Bott, Nicholas T; Sun, Zhaochun; Hong, Wei-Chen; Chien, Yin-hsuan; Liu, Ning; Dougherty, Robert F; Royalty, Adam; Hawthorne, Grace; Reiss, Allan L

2015-05-28

A novel game-like and creativity-conducive fMRI paradigm is developed to assess the neural correlates of spontaneous improvisation and figural creativity in healthy adults. Participants were engaged in the word-guessing game of Pictionary(TM), using an MR-safe drawing tablet and no explicit instructions to be "creative". Using the primary contrast of drawing a given word versus drawing a control word (zigzag), we observed increased engagement of cerebellum, thalamus, left parietal cortex, right superior frontal, left prefrontal and paracingulate/cingulate regions, such that activation in the cingulate and left prefrontal cortices negatively influenced task performance. Further, using parametric fMRI analysis, increasing subjective difficulty ratings for drawing the word engaged higher activations in the left pre-frontal cortices, whereas higher expert-rated creative content in the drawings was associated with increased engagement of bilateral cerebellum. Altogether, our data suggest that cerebral-cerebellar interaction underlying implicit processing of mental representations has a facilitative effect on spontaneous improvisation and figural creativity.

Evidence for a modulatory effect of sulbutiamine on glutamatergic and dopaminergic cortical transmissions in the rat brain.

PubMed

Trovero, F; Gobbi, M; Weil-Fuggaza, J; Besson, M J; Brochet, D; Pirot, S

2000-09-29

Chronic treatment of rats by sulbutiamine induced no change in density of N-methyl-D-aspartate (NMDA) and (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors in the cingular cortex, but a significant decrease of the kainate binding sites, as measured by quantitative autoradiography. In the same treated animals, an increase of D1 dopaminergic (DA) binding sites was measured both in the prefrontal and the cingular cortex, while no modification of the D2 binding sites was detected. Furthermore, an acute sulbutiamine administration induced a decrease of kainate binding sites but no change of the density of D1 and D2 DA receptors. Acute sulbutiamine injection led to a decrease of the DA levels in the prefrontal cortex and 3,4-dihydroxyphenylacetic acid levels in both the cingular and the prefrontal cortex. These observations are discussed in terms of a modulatory effect of sulbutiamine on both dopaminergic and glutamatergic cortical transmissions.

Pictionary-based fMRI paradigm to study the neural correlates of spontaneous improvisation and figural creativity

PubMed Central

Saggar, Manish; Quintin, Eve-Marie; Kienitz, Eliza; Bott, Nicholas T.; Sun, Zhaochun; Hong, Wei-Chen; Chien, Yin-hsuan; Liu, Ning; Dougherty, Robert F.; Royalty, Adam; Hawthorne, Grace; Reiss, Allan L.

2015-01-01

A novel game-like and creativity-conducive fMRI paradigm is developed to assess the neural correlates of spontaneous improvisation and figural creativity in healthy adults. Participants were engaged in the word-guessing game of PictionaryTM, using an MR-safe drawing tablet and no explicit instructions to be “creative”. Using the primary contrast of drawing a given word versus drawing a control word (zigzag), we observed increased engagement of cerebellum, thalamus, left parietal cortex, right superior frontal, left prefrontal and paracingulate/cingulate regions, such that activation in the cingulate and left prefrontal cortices negatively influenced task performance. Further, using parametric fMRI analysis, increasing subjective difficulty ratings for drawing the word engaged higher activations in the left pre-frontal cortices, whereas higher expert-rated creative content in the drawings was associated with increased engagement of bilateral cerebellum. Altogether, our data suggest that cerebral-cerebellar interaction underlying implicit processing of mental representations has a facilitative effect on spontaneous improvisation and figural creativity. PMID:26018874

Cortical Amyloid Beta in Cognitively Normal Elderly Adults is Associated with Decreased Network Efficiency within the Cerebro-Cerebellar System

PubMed Central

Steininger, Stefanie C.; Liu, Xinyang; Gietl, Anton; Wyss, Michael; Schreiner, Simon; Gruber, Esmeralda; Treyer, Valerie; Kälin, Andrea; Leh, Sandra; Buck, Alfred; Nitsch, Roger M.; Prüssmann, Klaas P.; Hock, Christoph; Unschuld, Paul G.

2014-01-01

Background: Deposition of cortical amyloid beta (Aβ) is a correlate of aging and a risk factor for Alzheimer disease (AD). While several higher order cognitive processes involve functional interactions between cortex and cerebellum, this study aims to investigate effects of cortical Aβ deposition on coupling within the cerebro-cerebellar system. Methods: We included 15 healthy elderly subjects with normal cognitive performance as assessed by neuropsychological testing. Cortical Aβ was quantified using (11)carbon-labeled Pittsburgh compound B positron-emission-tomography late frame signals. Volumes of brain structures were assessed by applying an automated parcelation algorithm to three dimensional magnetization-prepared rapid gradient-echo T1-weighted images. Basal functional network activity within the cerebro-cerebellar system was assessed using blood-oxygen-level dependent resting state functional magnetic resonance imaging at the high field strength of 7 T for measuring coupling between cerebellar seeds and cerebral gray matter. A bivariate regression approach was applied for identification of brain regions with significant effects of individual cortical Aβ load on coupling. Results: Consistent with earlier reports, a significant degree of positive and negative coupling could be observed between cerebellar seeds and cerebral voxels. Significant positive effects of cortical Aβ load on cerebro-cerebellar coupling resulted for cerebral brain regions located in inferior temporal lobe, prefrontal cortex, hippocampus, parahippocampal gyrus, and thalamus. Conclusion: Our findings indicate that brain amyloidosis in cognitively normal elderly subjects is associated with decreased network efficiency within the cerebro-cerebellar system. While the identified cerebral regions are consistent with established patterns of increased sensitivity for Aβ-associated neurodegeneration, additional studies are needed to elucidate the relationship between dysfunction of the cerebro-cerebellar system and risk for AD. PMID:24672483

Cortical Amyloid Beta in Cognitively Normal Elderly Adults is Associated with Decreased Network Efficiency within the Cerebro-Cerebellar System.

PubMed

Steininger, Stefanie C; Liu, Xinyang; Gietl, Anton; Wyss, Michael; Schreiner, Simon; Gruber, Esmeralda; Treyer, Valerie; Kälin, Andrea; Leh, Sandra; Buck, Alfred; Nitsch, Roger M; Prüssmann, Klaas P; Hock, Christoph; Unschuld, Paul G

2014-01-01

Deposition of cortical amyloid beta (Aβ) is a correlate of aging and a risk factor for Alzheimer disease (AD). While several higher order cognitive processes involve functional interactions between cortex and cerebellum, this study aims to investigate effects of cortical Aβ deposition on coupling within the cerebro-cerebellar system. We included 15 healthy elderly subjects with normal cognitive performance as assessed by neuropsychological testing. Cortical Aβ was quantified using (11)carbon-labeled Pittsburgh compound B positron-emission-tomography late frame signals. Volumes of brain structures were assessed by applying an automated parcelation algorithm to three dimensional magnetization-prepared rapid gradient-echo T1-weighted images. Basal functional network activity within the cerebro-cerebellar system was assessed using blood-oxygen-level dependent resting state functional magnetic resonance imaging at the high field strength of 7 T for measuring coupling between cerebellar seeds and cerebral gray matter. A bivariate regression approach was applied for identification of brain regions with significant effects of individual cortical Aβ load on coupling. Consistent with earlier reports, a significant degree of positive and negative coupling could be observed between cerebellar seeds and cerebral voxels. Significant positive effects of cortical Aβ load on cerebro-cerebellar coupling resulted for cerebral brain regions located in inferior temporal lobe, prefrontal cortex, hippocampus, parahippocampal gyrus, and thalamus. Our findings indicate that brain amyloidosis in cognitively normal elderly subjects is associated with decreased network efficiency within the cerebro-cerebellar system. While the identified cerebral regions are consistent with established patterns of increased sensitivity for Aβ-associated neurodegeneration, additional studies are needed to elucidate the relationship between dysfunction of the cerebro-cerebellar system and risk for AD.

Negative symptoms in schizophrenia are associated with aberrant striato-cortical connectivity in a rewarded perceptual decision-making task.

PubMed

Reckless, Greg E; Andreassen, Ole A; Server, Andres; Østefjells, Tiril; Jensen, Jimmy

2015-01-01

Negative symptoms in schizophrenia have been associated with structural and functional changes in the prefrontal cortex. They often persist after treatment with antipsychotic medication which targets, in particular, the ventral striatum (VS). As schizophrenia has been suggested to arise from dysfunctional connectivity between neural networks, it is possible that residual aberrant striato-cortical connectivity in medicated patients plays a role in enduring negative symptomology. The present study examined the relationship between striato-cortical connectivity and negative symptoms in medicated schizophrenia patients. We manipulated motivation in a perceptual decision-making task during functional magnetic resonance imaging. Comparing healthy controls (n = 21) and medicated patients with schizophrenia (n = 18) we investigated how motivation-mediated changes in VS activation affected functional connectivity with the frontal cortex, and how changes in connectivity strength from the neutral to motivated condition related to negative symptom severity. A pattern of aberrant striato-cortical connectivity was observed in the presence of intact VS, but altered left inferior frontal gyrus (IFG) motivation-mediated activation in patients. The more severe the patient's negative symptoms, the less the connectivity strength between the right VS and left IFG changed from the neutral to the motivated condition. Despite aberrant striato-cortical connectivity and altered recruitment of the left IFG among patients, both patients and healthy controls adopted a more liberal response strategy in the motivated compared to the neutral condition. The present findings suggest that there is a link between dysfunctional striato-cortical connectivity and negative symptom severity, and offer a possible explanation as to why negative symptoms persist after treatment with antipsychotics.

The neuropsychopharmacology of fronto-executive function: monoaminergic modulation.

PubMed

Robbins, T W; Arnsten, A F T

2009-01-01

We review the modulatory effects of the catecholamine neurotransmitters noradrenaline and dopamine on prefrontal cortical function. The effects of pharmacologic manipulations of these systems, sometimes in comparison with the indoleamine serotonin (5-HT), on performance on a variety of tasks that tap working memory, attentional-set formation and shifting, reversal learning, and response inhibition are compared in rodents, nonhuman primates, and humans using, in a behavioral context, several techniques ranging from microiontophoresis and single-cell electrophysiological recording to pharmacologic functional magnetic resonance imaging. Dissociable effects of drugs and neurotoxins affecting these monoamine systems suggest new ways of conceptualizing state-dependent fronto-executive functions, with implications for understanding the molecular genetic basis of mental illness and its treatment.

Resting state glucose utilization and the CERAD cognitive battery in patients with Alzheimer's disease.

PubMed

Teipel, S J; Willoch, F; Ishii, K; Bürger, K; Drzezga, A; Engel, R; Bartenstein, P; Möller, H-J; Schwaiger, M; Hampel, H

2006-05-01

The present study examined the cortical functional representation of neuropsychological domains in Alzheimer's disease (AD) using positron emission tomography (PET) and the neuropsychological assessment battery of the Consortium to Establish a Registry of Alzheimer's Disease (CERAD). Thirty patients with clinical probable AD and 10 elderly healthy controls underwent (18)FDG brain PET imaging during a resting state. Correlations between metabolic values and cognitive measures were determined using a region of interest analysis with NEUROSTAT (University of Michigan, USA) and a voxel-based analysis with SPM96 (Wellcome Department, London, UK). Specific correlations were seen between measures of episodic memory, verbal fluency and naming and left hemispheric temporal and prefrontal metabolism. Drawing was correlated with metabolism in left prefrontal and left inferior parietal regions. The presented data support the use of metabolic-cognitive correlations to demonstrate the neuronal substrates of cognitive impairment in AD. Subtests of the CERAD battery give a good representation of left, but not of right hemisphere function in AD.

Neural correlates of direct and reflected self-appraisals in adolescents and adults: when social perspective-taking informs self-perception.

PubMed

Pfeifer, Jennifer H; Masten, Carrie L; Borofsky, Larissa A; Dapretto, Mirella; Fuligni, Andrew J; Lieberman, Matthew D

2009-01-01

Classic theories of self-development suggest people define themselves in part through internalized perceptions of other people's beliefs about them, known as reflected self-appraisals. This study uses functional magnetic resonance imaging to compare the neural correlates of direct and reflected self-appraisals in adolescence (N = 12, ages 11-14 years) and adulthood (N = 12, ages 23-30 years). During direct self-reflection, adolescents demonstrated greater activity than adults in networks relevant to self-perception (medial prefrontal and parietal cortices) and social-cognition (dorsomedial prefrontal cortex, temporal-parietal junction, and posterior superior temporal sulcus), suggesting adolescent self-construals may rely more heavily on others' perspectives about the self. Activity in the medial fronto-parietal network was also enhanced when adolescents took the perspective of someone more relevant to a given domain.

Electrophysiological evidence for differential processing of numerical quantity and order in humans.

PubMed

Turconi, Eva; Jemel, Boutheina; Rossion, Bruno; Seron, Xavier

2004-09-01

It is yet unclear whether the processing of number magnitude and order rely on common or different functional processes and neural substrates. On the one hand, recent neuroimaging studies show that quantity and order coding activate the same areas in the parietal and prefrontal cortices. On the other hand, evidence from developmental and neuropsychological studies suggest dissociated mechanisms for processing quantity and order information. To clarify this issue, the present study investigated the spatio-temporal course of quantity and order coding operations using event-related potentials (ERPs). Twenty-four subjects performed a quantity task (classifying numbers as smaller or larger than 15) and an order task on the same material (classifying numbers as coming before or after 15), as well as a control order task on letters (classifying letters as coming before or after M). Behavioral results showed a classical distance effect (decreasing reaction times [RTs] with increasing distance from the standard) for all tasks. In agreement with previous electrophysiological evidence, this effect was significant on a P2 parietal component for numerical material. However, the difference between processing numbers close or far from the target appeared earlier and was larger on the left hemisphere for quantity processing, while it was delayed and bilateral for order processing. There was also a significant distance effect in all tasks on parietal sites for the following P3 component elicited by numbers, but this effect was larger on prefrontal areas for the order judgment. In conclusion, both quantity and order show similar behavioral effects, but they are associated with different spatio-temporal courses in parietal and prefrontal cortices.

Neural predictors and mechanisms of cognitive behavioral therapy on threat processing in social anxiety disorder.

PubMed

Klumpp, Heide; Fitzgerald, Daniel A; Phan, K Luan

2013-08-01

Cognitive behavioral therapy (CBT) is "gold standard" psychotherapy for social anxiety disorder (SAD). Cognitive models posit that preferential processing of threat mediates excessive forms of anxiety, which is supported by exaggerated amygdala, insula, and cortical reactivity to threatening socio-emotional signals in SAD. However, little is known about neural predictors of CBT success or the mechanisms by which CBT exerts its therapeutic effects. Functional magnetic resonance imaging (fMRI) was conducted during responses to social signals of threat (fearful/angry faces) against positive signals (happy faces) in 14 patients with SAD before and after 12 weeks of CBT. For comparison, 14 healthy control (HC) participants also underwent two fMRI scans, 12 weeks apart. Whole-brain voxel-wise analyses showed therapeutic success was predicted by enhanced pre-treatment activation to threatening faces in higher-order visual (superior and middle temporal gyrus), cognitive, and emotion processing areas (dorsal anterior cingulate cortex, dorsomedial prefrontal cortex). Moreover, a group by time interaction was revealed in prefrontal regions (dorsomedial, medial gyrus) and insula. The interaction was driven by relatively greater activity during threat processing in SAD, which significantly reduced after CBT but did not significantly predict response to CBT. Therefore, pre-treatment cortical hyperactivity to social threat signals may serve as a prognostic indicator of CBT success in SAD. Collectively, CBT-related brain changes involved a reduction in activity in insula, prefrontal, and extrastriate regions. Results are consistent with cognitive models, which associate decreases in threat processing bias with recovery. Copyright © 2013 Elsevier Inc. All rights reserved.

Mirror trends of plasticity and stability indicators in primate prefrontal cortex.

PubMed

García-Cabezas, Miguel Á; Joyce, Mary Kate P; John, Yohan J; Zikopoulos, Basilis; Barbas, Helen

2017-10-01

Research on plasticity markers in the cerebral cortex has largely focused on their timing of expression and role in shaping circuits during critical and normal periods. By contrast, little attention has been focused on the spatial dimension of plasticity-stability across cortical areas. The rationale for this analysis is based on the systematic variation in cortical structure that parallels functional specialization and raises the possibility of varying levels of plasticity. Here, we investigated in adult rhesus monkeys the expression of markers related to synaptic plasticity or stability in prefrontal limbic and eulaminate areas that vary in laminar structure. Our findings revealed that limbic areas are impoverished in three markers of stability: intracortical myelin, the lectin Wisteria floribunda agglutinin, which labels perineuronal nets, and parvalbumin, which is expressed in a class of strong inhibitory neurons. By contrast, prefrontal limbic areas were enriched in the enzyme calcium/calmodulin-dependent protein kinase II (CaMKII), known to enhance plasticity. Eulaminate areas have more elaborate laminar architecture than limbic areas and showed the opposite trend: they were enriched in markers of stability and had lower expression of the plasticity-related marker CaMKII. The expression of glial fibrillary acidic protein (GFAP), a marker of activated astrocytes, was also higher in limbic areas, suggesting that cellular stress correlates with the rate of circuit reshaping. Elevated markers of plasticity may endow limbic areas with flexibility necessary for learning and memory within an affective context, but may also render them vulnerable to abnormal structural changes, as seen in neurologic and psychiatric diseases. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Age-related changes in prefrontal norepinephrine transporter density: The basis for improved cognitive flexibility after low doses of atomoxetine in adolescent rats

PubMed Central

Bradshaw, Sarah E.; Agster, Kara L.; Waterhouse, Barry D.; McGaughy, Jill A.

2016-01-01

Adolescence is a period of major behavioral and brain reorganization. As diagnoses and treatment of disorders like attention deficit hyperactivity disorder (ADHD) often occur during adolescence, it is important to understand how the prefrontal cortices change and how these changes may influence the response to drugs during development. The current study uses an adolescent rat model to study the effect of standard ADHD treatments, atomoxetine and methylphenidate on attentional set shifting and reversal learning. While both of these drugs act as norepinephrine reuptake inhibitors, higher doses of atomoxetine and all doses of methylphenidate also block dopamine transporters (DAT). Low doses of atomoxetine, were effective at remediating cognitive rigidity found in adolescents. In contrast, methylphenidate improved performance in rats unable to form an attentional set due to distractibility but was without effect in normal subjects. We also assessed the effects of GBR 12909, a selective DAT inhibitor, but found no effect of any dose on behavior. A second study in adolescent rats investigated changes in norepinephrine transporter (NET) and dopamine beta hydroxylase (DBH) density in five functionally distinct subregions of the prefrontal cortex: infralimbic, prelimbic, anterior cingulate, medial and lateral orbitofrontal cortices. These regions are implicated in impulsivity and distractibility. We found that NET, but not DBH, changed across adolescence in a regionally selective manner. The prelimbic cortex, which is critical to cognitive rigidity, and the lateral orbitofrontal cortex, critical to reversal learning and some forms of response inhibition, showed higher levels of NET at early than mid- to late adolescence. PMID:26774596

Individual Differences in Reasoning and Visuospatial Attention are Associated with Prefrontal and Parietal White Matter Tracts in Healthy Older Adults

PubMed Central

Monge, Zachary A.; Greenwood, Pamela M.; Parasuraman, Raja; Strenziok, Maren

2016-01-01

Objective Although reasoning and attention are two cognitive processes necessary for ensuring the efficiency of many everyday activities in older adults, the role of white matter integrity in these processes has been little studied. This is an important question due to the role of white matter integrity as a neural substrate of cognitive aging. Here, we sought to examine the white matter tracts subserving reasoning and visuospatial attention in healthy older adults. Method Sixty-one adults aged 60 and older completed a battery of cognitive tests to assess reasoning and visuospatial attention. In addition, diffusion tensor images were collected to assess Fractional Anisotropy (FA) – a measure of white matter integrity. A principle component analysis of the test scores yielded two components: reasoning and visuospatial attention. Whole-brain correlations between FA and the cognitive components were submitted to probabilistic tractography analyses for visualization of cortical targets of tracts. Results For reasoning, bilateral thalamo-anterior prefrontal, anterior corpus callosum, and corpus callosum body tracts interconnecting the superior frontal cortices and right cingulum bundle were found. For visuospatial attention, a right inferior fronto-parietal tract, and bilateral parietal and temporal connections were found. Conclusions We conclude that in older adults, prefrontal cortex white matter tracts and interhemispheric communication are important in higher order cognitive functioning. On the other hand, right-sided fronto-parietal tracts appear to be critical for supporting control of cognitive processes, such as redirecting attention. Researchers may use our results to develop neuroscience-based interventions for older adults targeting brain mechanisms involved in cognitive plasticity. PMID:26986750

Increase in Prefrontal Cortical Volume following Cognitive Behavioural Therapy in Patients with Chronic Fatigue Syndrome

ERIC Educational Resources Information Center

de Lange, Floris P.; Koers, Anda; Kalkman, Joke S.; Bleijenberg, Gijs; Hagoort, Peter; van der Meer, Jos W. M.; Toni, Ivan

2008-01-01

Chronic fatigue syndrome (CFS) is a disabling disorder, characterized by persistent or relapsing fatigue. Recent studies have detected a decrease in cortical grey matter volume in patients with CFS, but it is unclear whether this cerebral atrophy constitutes a cause or a consequence of the disease. Cognitive behavioural therapy (CBT) is an…

The Teaching and the Learning Brain: A Cortical Hemodynamic Marker of Teacher-Student Interactions in the Socratic Dialog

ERIC Educational Resources Information Center

Holper, Lisa; Goldin, Andrea P.; Shalom, Diego E.; Battro, Antonio M.; Wolf, Martin; Sigman, Mariano

2013-01-01

The study aimed to step into two-person (teacher-student) educational neuroscience. We describe a physiological marker of cortical hemodynamic correlates involved in teacher-student interactions during performance of a classical teaching model, the Socratic dialog. We recorded prefrontal brain activity during dialog execution simultaneously in…

Auditory Resting-State Network Connectivity in Tinnitus: A Functional MRI Study

PubMed Central

Maudoux, Audrey; Lefebvre, Philippe; Cabay, Jean-Evrard; Demertzi, Athena; Vanhaudenhuyse, Audrey; Laureys, Steven; Soddu, Andrea

2012-01-01

The underlying functional neuroanatomy of tinnitus remains poorly understood. Few studies have focused on functional cerebral connectivity changes in tinnitus patients. The aim of this study was to test if functional MRI “resting-state” connectivity patterns in auditory network differ between tinnitus patients and normal controls. Thirteen chronic tinnitus subjects and fifteen age-matched healthy controls were studied on a 3 tesla MRI. Connectivity was investigated using independent component analysis and an automated component selection approach taking into account the spatial and temporal properties of each component. Connectivity in extra-auditory regions such as brainstem, basal ganglia/NAc, cerebellum, parahippocampal, right prefrontal, parietal, and sensorimotor areas was found to be increased in tinnitus subjects. The right primary auditory cortex, left prefrontal, left fusiform gyrus, and bilateral occipital regions showed a decreased connectivity in tinnitus. These results show that there is a modification of cortical and subcortical functional connectivity in tinnitus encompassing attentional, mnemonic, and emotional networks. Our data corroborate the hypothesized implication of non-auditory regions in tinnitus physiopathology and suggest that various regions of the brain seem involved in the persistent awareness of the phenomenon as well as in the development of the associated distress leading to disabling chronic tinnitus. PMID:22574141

Absence of visual experience modifies the neural basis of numerical thinking

PubMed Central

Kanjlia, Shipra; Lane, Connor; Feigenson, Lisa; Bedny, Marina

2016-01-01

In humans, the ability to reason about mathematical quantities depends on a frontoparietal network that includes the intraparietal sulcus (IPS). How do nature and nurture give rise to the neurobiology of numerical cognition? We asked how visual experience shapes the neural basis of numerical thinking by studying numerical cognition in congenitally blind individuals. Blind (n = 17) and blindfolded sighted (n = 19) participants solved math equations that varied in difficulty (e.g., 27 − 12 = x vs. 7 − 2 = x), and performed a control sentence comprehension task while undergoing fMRI. Whole-cortex analyses revealed that in both blind and sighted participants, the IPS and dorsolateral prefrontal cortices were more active during the math task than the language task, and activity in the IPS increased parametrically with equation difficulty. Thus, the classic frontoparietal number network is preserved in the total absence of visual experience. However, surprisingly, blind but not sighted individuals additionally recruited a subset of early visual areas during symbolic math calculation. The functional profile of these “visual” regions was identical to that of the IPS in blind but not sighted individuals. Furthermore, in blindness, number-responsive visual cortices exhibited increased functional connectivity with prefrontal and IPS regions that process numbers. We conclude that the frontoparietal number network develops independently of visual experience. In blindness, this number network colonizes parts of deafferented visual cortex. These results suggest that human cortex is highly functionally flexible early in life, and point to frontoparietal input as a mechanism of cross-modal plasticity in blindness. PMID:27638209

Influence of the cortical midline structures on moral emotion and motivation in moral decision-making.

PubMed

Han, Hyemin; Chen, Jingyuan; Jeong, Changwoo; Glover, Gary H

2016-04-01

The present study aims to examine the relationship between the cortical midline structures (CMS), which have been regarded to be associated with selfhood, and moral decision making processes at the neural level. Traditional moral psychological studies have suggested the role of moral self as the moderator of moral cognition, so activity of moral self would present at the neural level. The present study examined the interaction between the CMS and other moral-related regions by conducting psycho-physiological interaction analysis of functional images acquired while 16 subjects were solving moral dilemmas. Furthermore, we performed Granger causality analysis to demonstrate the direction of influences between activities in the regions in moral decision-making. We first demonstrate there are significant positive interactions between two central CMS seed regions-i.e., the medial prefrontal cortex (MPFC) and posterior cingulate cortex (PCC)-and brain regions associated with moral functioning including the cerebellum, brainstem, midbrain, dorsolateral prefrontal cortex, orbitofrontal cortex and anterior insula (AI); on the other hand, the posterior insula (PI) showed significant negative interaction with the seed regions. Second, several significant Granger causality was found from CMS to insula regions particularly under the moral-personal condition. Furthermore, significant dominant influence from the AI to PI was reported. Moral psychological implications of these findings are discussed. The present study demonstrated the significant interaction and influence between the CMS and morality-related regions while subject were solving moral dilemmas. Given that, activity in the CMS is significantly involved in human moral functioning. Copyright © 2016 Elsevier B.V. All rights reserved.

Catecholamine and second messenger influences on prefrontal cortical networks of "representational knowledge": a rational bridge between genetics and the symptoms of mental illness.

PubMed

Arnsten, Amy F T

2007-09-01

Both dopamine (DA) and norepinephrine (NE) have powerful, inverted U influences on prefrontal cortical (PFC) cognitive function. Optimal NE levels engage alpha2A-adrenoceptors and increase "signals" via inhibition of cAMP-HCN (cAMP-hyperpolarization-activated cyclic nucleotide-gated cation channel) signaling near preferred inputs, whereas optimal levels of DA D1 receptor stimulation decrease "noise" by increasing cAMP signaling near nonpreferred inputs. Excessive levels of catecholamine release during stress impair working memory 1) by very high levels of cAMP-HCN signaling diminishing preferred as well as nonpreferred inputs and 2) by high levels of NE engaging alpha1 stimulation of phosphotidyl inositol (PI) signaling that suppresses cell firing. Common mental illnesses are associated with extracellular changes in these pathways: Attention Deficit Hyperactivity Disorder is linked to genetic changes that reduce catecholamine transmission to suboptimal levels and is treated with agents that increase catecholamine transmission, whereas Post-Traumatic Stress Disorder (PTSD) is associated with amplified noradrenergic transmission that impairs PFC but strengthens amygdala function. PTSD is now treated with agents that block alpha1 or beta adrenoceptors. In contrast, the more severe mental illnesses, schizophrenia and bipolar disorder, are associated with genetic changes in molecules regulating intracellular signaling pathways activated by stress. Specifically, DISC1 inhibits cAMP signaling whereas regulator of G-protein signaling 4 inhibits PI signaling. Loss of function in these genes may render patients vulnerable to profound stress-induced PFC dysfunction including symptoms of thought disorder.

Functional connectivity analysis of brain hemodynamics during rubber hand illusion.

PubMed

Arizono, Naoki; Kondo, Toshiyuki

2015-08-01

Embodied cognition has been eagerly studied in the recent neuroscience research field. In particular, hand ownership has been investigated through the rubber hand illusion (RHI). Most of the research measured the brain activities during the RHI by using EEG, fMRI, etc., however, near-infrared spectroscopy (NIRS) has not yet been utilized. Here we attempt to measure the brain activities during the RHI task with NIRS, and analyze the functional connectivity so as to understand the relationship between NIRS features and the state of embodied cognition. For the purpose, we developed a visuo-tactile stimulator in the study. As a result, we found that the subjects felt illusory experience showed significant peaks of oxy-Hb in both prefrontal and premotor cortices during RHI. Furthermore, we confirmed a reliable causality connection from right prefrontal to right premotor cortex. This result suggests that the RHI is associated with the neural circuits underlying motor control. Therefore, we considered that the RHI with the functional connectivity analysis will become an appropriate model investigating a biomarker for neurorehabilitation, and the diagnosis of the mental disorders.

Neurobiological and clinical effects of fNIRS-controlled rTMS in patients with panic disorder/agoraphobia during cognitive-behavioural therapy.

PubMed

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

2017-01-01

A relevant proportion of patients with panic disorder (PD) does not improve even though they receive state of the art treatment for anxiety disorders such as cognitive-behavioural therapy (CBT). At the same time, it is known, that from a neurobiological point of view, PD patients are often characterised by prefrontal hypoactivation. Intermittent Theta Burst Stimulation (iTBS) is a non-invasive type of neurostimulation which can modulate cortical activity and thus has the potential to normalise prefrontal hypoactivity found in PD. We therefore aimed at investigating the effects of iTBS as an innovative add-on to CBT in the treatment for PD. In this double-blind, bicentric study, 44 PD patients, randomised to sham or verum stimulation, received 15 sessions of iTBS over the left prefrontal cortex (PFC) in addition to 9 weeks of group CBT. Cortical activity during a cognitive as well as an emotional (Emotional Stroop) paradigm was assessed both at baseline and post-iTBS treatment using functional near-infrared spectroscopy (fNIRS) and compared to healthy controls. In this manuscript we only report the results of the emotional paradigm; for the results of the cognitive paradigm please refer to Deppermann et al. (2014). During the Emotional Stroop test, PD patients showed significantly reduced activation to panic-related compared to neutral stimuli for the left PFC at baseline. Bilateral prefrontal activation for panic-related stimuli significantly increased after verum iTBS only. Clinical ratings significantly improved during CBT and remained stable at follow-up. However, no clinical differences between the verum- and sham-stimulated group were identified, except for a more stable reduction of agoraphobic avoidance during follow-up in the verum iTBS group. Limitations include insufficient blinding, the missing control for possible state-dependent iTBS effects, and the timing of iTBS application during CBT. Prefrontal hypoactivity in PD patients was normalised by add-on iTBS. Clinical improvement of anxiety symptoms was not affected by iTBS.

Brain abnormalities in murderers indicated by positron emission tomography.

PubMed

Raine, A; Buchsbaum, M; LaCasse, L

1997-09-15

Murderers pleading not guilty by reason of insanity (NGRI) are thought to have brain dysfunction, but there have been no previous studies reporting direct measures of both cortical and subcortical brain functioning in this specific group. Positron emission tomography brain imaging using a continuous performance challenge task was conducted on 41 murderers pleading not guilty by reason of insanity and 41 age- and sex-matched controls. Murderers were characterized by reduced glucose metabolism in the prefrontal cortex, superior parietal gyrus, left angular gyrus, and the corpus callosum, while abnormal asymmetries of activity (left hemisphere lower than right) were also found in the amygdala, thalamus, and medial temporal lobe. These preliminary findings provide initial indications of a network of abnormal cortical and subcortical brain processes that may predispose to violence in murderers pleading NGRI.

Lower "N"-Acetyl-Aspartate Levels in Prefrontal Cortices in Pediatric Bipolar Disorder: A (Superscript 1]H Magnetic Resonance Spectroscopy Study

ERIC Educational Resources Information Center

Caetano, Sheila C.; Olvera, Rene L.; Hatch, John P.; Sanches, Marsal; Chen, Hua Hsuan; Nicoletti, Mark; Stanley, Jeffrey A.; Fonseca, Manoela; Hunter, Kristina; Lafer, Beny; Pliszka, Steven R.; Soares, Jair C.

2011-01-01

Objective: The few studies applying single-voxel [superscript 1]H spectroscopy in children and adolescents with bipolar disorder (BD) have reported low "N"-acetyl-aspartate (NAA) levels in the dorsolateral prefrontal cortex (DLPFC), and high myo-inositol/phosphocreatine plus creatine (PCr+Cr) ratios in the anterior cingulate. The aim of this study…

TAAR1 Modulates Cortical Glutamate NMDA Receptor Function

PubMed Central

Espinoza, Stefano; Lignani, Gabriele; Caffino, Lucia; Maggi, Silvia; Sukhanov, Ilya; Leo, Damiana; Mus, Liudmila; Emanuele, Marco; Ronzitti, Giuseppe; Harmeier, Anja; Medrihan, Lucian; Sotnikova, Tatyana D; Chieregatti, Evelina; Hoener, Marius C; Benfenati, Fabio; Tucci, Valter; Fumagalli, Fabio; Gainetdinov, Raul R

2015-01-01

Trace Amine-Associated Receptor 1 (TAAR1) is a G protein-coupled receptor expressed in the mammalian brain and known to influence subcortical monoaminergic transmission. Monoamines, such as dopamine, also play an important role within the prefrontal cortex (PFC) circuitry, which is critically involved in high-o5rder cognitive processes. TAAR1-selective ligands have shown potential antipsychotic, antidepressant, and pro-cognitive effects in experimental animal models; however, it remains unclear whether TAAR1 can affect PFC-related processes and functions. In this study, we document a distinct pattern of expression of TAAR1 in the PFC, as well as altered subunit composition and deficient functionality of the glutamate N-methyl-D-aspartate (NMDA) receptors in the pyramidal neurons of layer V of PFC in mice lacking TAAR1. The dysregulated cortical glutamate transmission in TAAR1-KO mice was associated with aberrant behaviors in several tests, indicating a perseverative and impulsive phenotype of mutants. Conversely, pharmacological activation of TAAR1 with selective agonists reduced premature impulsive responses observed in the fixed-interval conditioning schedule in normal mice. Our study indicates that TAAR1 plays an important role in the modulation of NMDA receptor-mediated glutamate transmission in the PFC and related functions. Furthermore, these data suggest that the development of TAAR1-based drugs could provide a novel therapeutic approach for the treatment of disorders related to aberrant cortical functions. PMID:25749299

Mapping longitudinal development of local cortical gyrification in infants from birth to 2 years of age.

PubMed

Li, Gang; Wang, Li; Shi, Feng; Lyall, Amanda E; Lin, Weili; Gilmore, John H; Shen, Dinggang

2014-03-19

Human cortical folding is believed to correlate with cognitive functions. This likely correlation may have something to do with why abnormalities of cortical folding have been found in many neurodevelopmental disorders. However, little is known about how cortical gyrification, the cortical folding process, develops in the first 2 years of life, a period of dynamic and regionally heterogeneous cortex growth. In this article, we show how we developed a novel infant-specific method for mapping longitudinal development of local cortical gyrification in infants. By using this method, via 219 longitudinal 3T magnetic resonance imaging scans from 73 healthy infants, we systemically and quantitatively characterized for the first time the longitudinal cortical global gyrification index (GI) and local GI (LGI) development in the first 2 years of life. We found that the cortical GI had age-related and marked development, with 16.1% increase in the first year and 6.6% increase in the second year. We also found marked and regionally heterogeneous cortical LGI development in the first 2 years of life, with the high-growth regions located in the association cortex, whereas the low-growth regions located in sensorimotor, auditory, and visual cortices. Meanwhile, we also showed that LGI growth in most cortical regions was positively correlated with the brain volume growth, which is particularly significant in the prefrontal cortex in the first year. In addition, we observed gender differences in both cortical GIs and LGIs in the first 2 years, with the males having larger GIs than females at 2 years of age. This study provides valuable information on normal cortical folding development in infancy and early childhood.

Catechol-o-methyl transferase (COMT) val158met polymorphism and adolescent cortical development in patients with childhood-onset schizophrenia, their non-psychotic siblings, and healthy controls

PubMed Central

Raznahan, Armin; Greenstein, Deanna; Lee, Yohan; Long, Robert; Clasen, Liv; Gochman, Pete; Addington, Anjene; Giedd, Jay N.; Rapoport, Judith L.; Gogtay, Nitin

2012-01-01

Non-psychotic individuals at increased risk for schizophrenia show alterations in fronto-striatal dopamine signaling and cortical gray matter maturation reminiscent of those seen in schizophrenia. It remains unclear however if variations in dopamine signaling influence rates of structural cortical maturation in typically developing individuals, and whether such influences are disrupted in patients with schizophrenia and their non-psychotic siblings. We sought to address these issues by relating a functional Val→Met polymorphism within the gene encoding catechol-o-methyltransferase (COMT)—a key enzymatic regulator of cortical dopamine levels—to longitudinal structural neuroimaging measures of cortical gray matter thickness. We included a total of 792 magnetic resonance imaging brain scans, acquired between ages 9 and 22 years from patients with childhood-onset schizophrenia (COS), their non-psychotic full siblings, and matched healthy controls. Whereas greater Val allele dose (which confers enhanced dopamine catabolism and is proposed to aggravate cortical deficits in schizophrenia) accelerated adolescent cortical thinning in both schizophrenia probands and their siblings, it attenuated cortical thinning in healthy controls. This similarity between COS patients and their siblings was accompanied by differences between the two groups in the timing and spatial distribution of disrupted COMT influences on cortical maturation. Consequently, whereas greater Val “dose” conferred persistent dorsolateral prefrontal cortical deficits amongst affected probands by adulthood, cortical thickness differences associated with varying Val dose in non-psychotic siblings resolved over the age-range studied. These findings suggest that cortical abnormalities in pedigrees affected by schizophrenia may be contributed to by a disruption of dopaminergic infleunces on cortical maturation. PMID:21620981

Brain structure-function associations in multi-generational families genetically enriched for bipolar disorder.

PubMed

Fears, Scott C; Schür, Remmelt; Sjouwerman, Rachel; Service, Susan K; Araya, Carmen; Araya, Xinia; Bejarano, Julio; Knowles, Emma; Gomez-Makhinson, Juliana; Lopez, Maria C; Aldana, Ileana; Teshiba, Terri M; Abaryan, Zvart; Al-Sharif, Noor B; Navarro, Linda; Tishler, Todd A; Altshuler, Lori; Bartzokis, George; Escobar, Javier I; Glahn, David C; Thompson, Paul M; Lopez-Jaramillo, Carlos; Macaya, Gabriel; Molina, Julio; Reus, Victor I; Sabatti, Chiara; Cantor, Rita M; Freimer, Nelson B; Bearden, Carrie E

2015-07-01

Recent theories regarding the pathophysiology of bipolar disorder suggest contributions of both neurodevelopmental and neurodegenerative processes. While structural neuroimaging studies indicate disease-associated neuroanatomical alterations, the behavioural correlates of these alterations have not been well characterized. Here, we investigated multi-generational families genetically enriched for bipolar disorder to: (i) characterize neurobehavioural correlates of neuroanatomical measures implicated in the pathophysiology of bipolar disorder; (ii) identify brain-behaviour associations that differ between diagnostic groups; (iii) identify neurocognitive traits that show evidence of accelerated ageing specifically in subjects with bipolar disorder; and (iv) identify brain-behaviour correlations that differ across the age span. Structural neuroimages and multi-dimensional assessments of temperament and neurocognition were acquired from 527 (153 bipolar disorder and 374 non-bipolar disorder) adults aged 18-87 years in 26 families with heavy genetic loading for bipolar disorder. We used linear regression models to identify significant brain-behaviour associations and test whether brain-behaviour relationships differed: (i) between diagnostic groups; and (ii) as a function of age. We found that total cortical and ventricular volume had the greatest number of significant behavioural associations, and included correlations with measures from multiple cognitive domains, particularly declarative and working memory and executive function. Cortical thickness measures, in contrast, showed more specific associations with declarative memory, letter fluency and processing speed tasks. While the majority of brain-behaviour relationships were similar across diagnostic groups, increased cortical thickness in ventrolateral prefrontal and parietal cortical regions was associated with better declarative memory only in bipolar disorder subjects, and not in non-bipolar disorder family members. Additionally, while age had a relatively strong impact on all neurocognitive traits, the effects of age on cognition did not differ between diagnostic groups. Most brain-behaviour associations were also similar across the age range, with the exception of cortical and ventricular volume and lingual gyrus thickness, which showed weak correlations with verbal fluency and inhibitory control at younger ages that increased in magnitude in older subjects, regardless of diagnosis. Findings indicate that neuroanatomical traits potentially impacted by bipolar disorder are significantly associated with multiple neurobehavioural domains. Structure-function relationships are generally preserved across diagnostic groups, with the notable exception of ventrolateral prefrontal and parietal association cortex, volumetric increases in which may be associated with cognitive resilience specifically in individuals with bipolar disorder. Although age impacted all neurobehavioural traits, we did not find any evidence of accelerated cognitive decline specific to bipolar disorder subjects. Regardless of diagnosis, greater global brain volume may represent a protective factor for the effects of ageing on executive functioning. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Illness Progression, Recent Stress and Morphometry of Hippocampal Subfields and Medial Prefrontal Cortex in Major Depression

PubMed Central

Treadway, Michael T.; Waskom, Michael L.; Dillon, Daniel G.; Holmes, Avram J.; Park, Min Tae M.; Chakravarty, M. Mallar; Dutra, Sunny J.; Polli, Frida E.; Iosifescu, Dan V.; Fava, Maurizio; Gabrieli, John D.E.; Pizzagalli, Diego A.

2014-01-01

Background Longitudinal studies of illness progression in Major Depressive Disorder (MDD) indicate that the onset of subsequent depressive episodes becomes increasingly decoupled from external stressors. A possible mechanism underlying this phenomenon is that multiple episodes induce long-lasting neurobiological changes that confer increased risk for recurrence. Prior morphometric studies have frequently reported volumetric reductions in MDD—especially in medial prefrontal cortex (mPFC) and the hippocampus— but few studies have investigated whether these changes are exacerbated by prior episodes. Methods We used structural magnetic resonance imaging (sMRI) to examine relationships between number of prior episodes, current stress, and brain volume and cortical thickness in a sample of 103 medication-free depressed patients and never-depressed controls. Volumetric analyses of the hippocampus were performed using a recently-validated subfield segmentation approach, while cortical thickness estimates were obtained using Vertex-Based Cortical Thickness (VBCT). Participants were grouped on the basis of the number of prior depressive episodes as well as current depressive state. Results Number of prior episodes was associated with both lower reported stress levels as well as reduced volume in the dentate gyrus. Cortical thinning of the left medial prefrontal cortex (mPFC) was associated with a greater number of prior depressive episodes, but not current depressive state. Conclusions Collectively, these findings are consistent with preclinical models suggesting that the dentate gyrus and mPFC are especially vulnerable to stress exposure, and provide evidence for morphometric changes that are consistent with stress-sensitization models of recurrence in MDD. PMID:25109665

Cocaine cue-induced dopamine release in the human prefrontal cortex.

PubMed

Milella, Michele S; Fotros, Aryandokht; Gravel, Paul; Casey, Kevin F; Larcher, Kevin; Verhaeghe, Jeroen A J; Cox, Sylvia M L; Reader, Andrew J; Dagher, Alain; Benkelfat, Chawki; Leyton, Marco

2016-08-01

Accumulating evidence indicates that drug-related cues can induce dopamine (DA) release in the striatum of substance abusers. Whether these same cues provoke DA release in the human prefrontal cortex remains unknown. We used high-resolution positron emission tomography with [18F]fallypride to measure cortical and striatal DA D2/3 receptor availability in the presence versus absence of drug-related cues in volunteers with current cocaine dependence. Twelve individuals participated in our study. Among participants reporting a craving response (9 of 12), exposure to the cocaine cues significantly decreased [18F]fallypride binding potential (BPND) values in the medial orbitofrontal cortex and striatum. In all 12 participants, individual differences in the magnitude of craving correlated with BPND changes in the medial orbitofrontal cortex, dorsolateral prefrontal cortex, anterior cingulate, and striatum. Consistent with the presence of autoreceptors on mesostriatal but not mesocortical DA cell bodies, midbrain BPND values were significantly correlated with changes in BPND within the striatum but not the cortex. The lower the midbrain D2 receptor levels, the greater the striatal change in BPND and self-reported craving. Limitations of this study include its modest sample size, with only 2 female participants. Newer tracers might have greater sensitivity to cortical DA release. In people with cocaine use disorders, the presentation of drug-related cues induces DA release within cortical and striatal regions. Both effects are associated with craving, but only the latter is regulated by midbrain autoreceptors. Together, the results suggest that cortical and subcortical DA responses might both influence drug-focused incentive motivational states, but with separate regulatory mechanisms.

Prefrontal cortex modulates posterior alpha oscillations during top-down guided visual perception

PubMed Central

Helfrich, Randolph F.; Huang, Melody; Wilson, Guy; Knight, Robert T.

2017-01-01

Conscious visual perception is proposed to arise from the selective synchronization of functionally specialized but widely distributed cortical areas. It has been suggested that different frequency bands index distinct canonical computations. Here, we probed visual perception on a fine-grained temporal scale to study the oscillatory dynamics supporting prefrontal-dependent sensory processing. We tested whether a predictive context that was embedded in a rapid visual stream modulated the perception of a subsequent near-threshold target. The rapid stream was presented either rhythmically at 10 Hz, to entrain parietooccipital alpha oscillations, or arrhythmically. We identified a 2- to 4-Hz delta signature that modulated posterior alpha activity and behavior during predictive trials. Importantly, delta-mediated top-down control diminished the behavioral effects of bottom-up alpha entrainment. Simultaneous source-reconstructed EEG and cross-frequency directionality analyses revealed that this delta activity originated from prefrontal areas and modulated posterior alpha power. Taken together, this study presents converging behavioral and electrophysiological evidence for frontal delta-mediated top-down control of posterior alpha activity, selectively facilitating visual perception. PMID:28808023

[Brain Organization of the Preparation for Visual Recognition in Preadolescent Children].

PubMed

Farber, D A; Kurganskii, A V; Petrenko, N E

2015-01-01

The brain organization of the process of preparation for the perception of incomplete images fragmented to different extents. The functional connections of ventrolateral and dorsoventral cortical zones with other zones in 10-11-year-old and 11-12-year-old children were studied at three successive stages of the preparation for the perception of incomplete images. These data were compared with those obtained for adults. In order to reveal the effect of preparatory processes on the image recognition, we also analyzed the regional event-related potentials. In adults, the functional interaction between dorsolateral and ventrolateral prefrontal cortex and other cortical zones of the right hemisphere was found to be enhanced at the stage of waiting for not-yet-recognizable image, while in the left hemisphere the links became stronger shortly before the successful recognition of a stimulus. In children the stage-related changes in functional interactions are similar in both hemispheres, with peak of interaction activity.at the stage preceding the successful recognition. It was found that in 11-12-year-old children the ventrolateral cortex is involved in both preparatory stage and recognition processes to a smaller extent as compared with adults and 10-11-year-old children. At the same time, the group of 11-12-year-old children had more mature pattern of the dorsolateral cortex involvement, which provided more effective recognition of incomplete images in this group as compared with 10-11-year-old children. It is suggested that the features of the brain organization of visual recognition and preceding preparatory processes in 11-12-year-old children are caused by multidirectional effects of sex hormones on the functioning of different zones of the prefrontal cortex at early stages of sexual maturation.

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

Theory of mind and frontal lobe pathology in schizophrenia: a voxel-based morphometry study.

PubMed

Hirao, Kazuyuki; Miyata, Jun; Fujiwara, Hironobu; Yamada, Makiko; Namiki, Chihiro; Shimizu, Mitsuaki; Sawamoto, Nobukatsu; Fukuyama, Hidenao; Hayashi, Takuji; Murai, Toshiya

2008-10-01

Impaired ability to infer the mental states of others (theory of mind; ToM) is considered to be a key contributor to the poor social functioning of patients with schizophrenia. Although neuroimaging and lesion studies have provided empirical evidence for the neural basis of ToM ability, including the involvement of several prefrontal and temporal structures, the association between pathology of these structures and ToM impairment in schizophrenia patients is less well understood. To address this issue, we investigated structural brain abnormalities and ToM impairment in patients with schizophrenia, and examined the relationship between them. Twenty schizophrenia patients and 20 age-, sex- and education-matched healthy participants underwent magnetic resonance imaging (MRI) and were examined for ToM ability based on the revised version of the "Reading the Mind in the Eyes" (or Eyes) test [Baron-Cohen, S., Wheelwright, S., Hill, J., Raste, Y., Plumb, I., 2001. The 'Reading the Mind in the Eyes' test revised version: A study with normal adults, and adults with Asperger syndrome or high-functioning autism. J. Child Psychol. Psychiatry 42, 241-251]. Voxel-based morphometry (VBM) was performed to investigate regional brain alterations. Relative to normal controls, schizophrenia patients exhibited gray matter reductions in the dorsomedial prefrontal cortex (DMPFC), left ventrolateral prefrontal cortex (VLPFC), ventromedial prefrontal cortex (VMPFC), anterior cingulate cortex (ACC), right superior temporal gyrus (STG) and right insula. The patients performed poorly on the Eyes test. Importantly, poor performance on the Eyes test was found to be associated with gray matter reduction in the left VLPFC in the patient group. These results suggest that prefrontal cortical reduction, especially in the left VLPFC, is a key pathology underlying the difficulties faced by schizophrenia patients in inferring the mental states of others.

Where Is the Semantic System? A Critical Review and Meta-Analysis of 120 Functional Neuroimaging Studies

PubMed Central

Desai, Rutvik H.; Graves, William W.; Conant, Lisa L.

2009-01-01

Semantic memory refers to knowledge about people, objects, actions, relations, self, and culture acquired through experience. The neural systems that store and retrieve this information have been studied for many years, but a consensus regarding their identity has not been reached. Using strict inclusion criteria, we analyzed 120 functional neuroimaging studies focusing on semantic processing. Reliable areas of activation in these studies were identified using the activation likelihood estimate (ALE) technique. These activations formed a distinct, left-lateralized network comprised of 7 regions: posterior inferior parietal lobe, middle temporal gyrus, fusiform and parahippocampal gyri, dorsomedial prefrontal cortex, inferior frontal gyrus, ventromedial prefrontal cortex, and posterior cingulate gyrus. Secondary analyses showed specific subregions of this network associated with knowledge of actions, manipulable artifacts, abstract concepts, and concrete concepts. The cortical regions involved in semantic processing can be grouped into 3 broad categories: posterior multimodal and heteromodal association cortex, heteromodal prefrontal cortex, and medial limbic regions. The expansion of these regions in the human relative to the nonhuman primate brain may explain uniquely human capacities to use language productively, plan, solve problems, and create cultural and technological artifacts, all of which depend on the fluid and efficient retrieval and manipulation of semantic knowledge. PMID:19329570

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.

Influence of inter-stimulus interval of spinal cord stimulation in patients with disorders of consciousness: A preliminary functional near-infrared spectroscopy study.

PubMed

Zhang, Yujin; Yang, Yi; Si, Juanning; Xia, Xiaoyu; He, Jianghong; Jiang, Tianzi

2018-01-01

Spinal cord stimulation (SCS) is a promising treatment for disorders of consciousness (DOC), but the underlying mechanism and most effective procedures remain uncertain. To optimize the protocol, previous studies evaluated the frequency-specific effects of SCS on neurophysiological activities. However, whether and how the inter-stimulus interval (ISI) parameter affects the SCS neuromodulation in DOC remains unknown. We enrolled nine DOC patients who had implanted SCS devices and conducted three different durations of ISIs. Using functional near-infrared spectroscopy (fNIRS), we monitored the blood volume fluctuations in the prefrontal and occipital cortices during the SCS. The results showed that short stimuli (30 s) induced significant cerebral blood volume changes, especially in the prefrontal cortex, an important area in the consciousness system. By comparing the mean value of the responses from the first and the last block in each session, a shorter ISI was found to improve the blood volume in the prefrontal cortex. This phenomenon was more significant for the subgroup of patients with a favorable prognosis. These preliminary results imply that the ISI may be an important factor for SCS. The research paradigm proposed here also provides insights for further quantitative evaluations of the therapeutic effects of neuromodulation.

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

Obesity-related differences in neural correlates of force control.

PubMed

Mehta, Ranjana K; Shortz, Ashley E

2014-01-01

Greater body segment mass due to obesity has shown to impair gross and fine motor functions and reduce balance control. While recent studies suggest that obesity may be linked with altered brain functions involved in fine motor tasks, this association is not well investigated. The purpose of this study was to examine the neural correlates of motor performance in non-obese and obese adults during force control of two upper extremity muscles. Nine non-obese and eight obese young adults performed intermittent handgrip and elbow flexion exertions at 30% of their respective muscle strengths for 4 min. Functional near infrared spectroscopy was employed to measure neural activity in the prefrontal cortex bilaterally, joint steadiness was computed using force fluctuations, and ratings of perceived exertions (RPEs) were obtained to assess perceived effort. Obesity was associated with higher force fluctuations and lower prefrontal cortex activation during handgrip exertions, while RPE scores remained similar across both groups. No obesity-related differences in neural activity, force fluctuation, or RPE scores were observed during elbow flexion exertions. The study is one of the first to examine obesity-related differences on prefrontal cortex activation during force control of the upper extremity musculature. The study findings indicate that the neural correlates of motor activity in the obese may be muscle-specific. Future work is warranted to extend the investigation to monitoring multiple motor-function related cortical regions and examining obesity differences with different task parameters (e.g., longer duration, increased precision demands, larger muscles, etc.).

Thalamocortical dysconnectivity in schizophrenia

PubMed Central

Woodward, Neil D.; Karbasforoushan, Haleh; Heckers, Stephan

2013-01-01

Objective The thalamus and cerebral cortex are connected via topographically organized, reciprocal connections. Previous studies revealed thalamic abnormalities in schizophrenia; however, it is not known if thalamocortical networks are differentially affected in the disorder. To explore this possibility, we examined functional connectivity in intrinsic low frequency blood-oxygen-level-dependent (BOLD) signal fluctuations between major divisions of the cortex and thalamus using resting-state functional magnetic resonance imaging. Method 77 healthy subjects and 62 patients with schizophrenia underwent resting-state fMRI. To identify functional subdivisions of the thalamus, we parceled the cortex into six regions-of-interest; prefrontal, motor, somatosensory, temporal, posterior parietal, and occipital cortex. Mean BOLD time-series was extracted from each of the regions-of-interest and entered into a seed-based functional connectivity analysis. Results Consistent with prior reports, activity in distinct cortical areas correlated with specific, largely non-overlapping regions of the thalamus in both healthy subjects and schizophrenia patients. Direct comparison between groups revealed reduced prefrontal-thalamic connectivity and increased motor/somatosensory-thalamic connectivity in schizophrenia. The changes in connectivity were unrelated to local grey matter content within the thalamus and antipsychotic medication dosage. No differences were observed in temporal, posterior parietal, and occipital cortex connectivity with the thalamus. Conclusions This study establishes differential abnormalities of thalamocortical networks in schizophrenia. The etiology of schizophrenia may disrupt the development of prefrontal-thalamic connectivity and refinement of somatomotor connectivity with the thalamus that occurs during brain maturation. PMID:23032387

The experience of art: insights from neuroimaging.

PubMed

Nadal, Marcos

2013-01-01

The experience of art is a complex one. It emerges from the interaction of multiple cognitive and affective processes. Neuropsychological and neuroimaging studies are revealing the broadly distributed network of brain regions upon which it relies. This network can be divided into three functional components: (i) prefrontal, parietal, and temporal cortical regions support evaluative judgment, attentional processing, and memory retrieval; (ii) the reward circuit, including cortical, subcortical regions, and some of its regulators, is involved in the generation of pleasurable feelings and emotions, and the valuation and anticipation of reward; and (iii) attentional modulation of activity in low-, mid-, and high-level cortical sensory regions enhances the perceptual processing of certain features, relations, locations, or objects. Understanding how these regions act in concert to produce unique and moving art experiences and determining the impact of personal and cultural meaning and context on this network the biological foundation of the experience of art--remain future challenges. © 2013 Elsevier B.V. All rights reserved.

Neuropsychology of selective attention and magnetic cortical stimulation.

PubMed

Sabatino, M; Di Nuovo, S; Sardo, P; Abbate, C S; La Grutta, V

1996-01-01

Informed volunteers were asked to perform different neuropsychological tests involving selective attention under control conditions and during transcranial magnetic cortical stimulation. The tests chosen involved the recognition of a specific letter among different letters (verbal test) and the search for three different spatial orientations of an appendage to a square (visuo-spatial test). For each test the total time taken and the error rate were calculated. Results showed that cortical stimulation did not cause a worsening in performance. Moreover, magnetic stimulation of the temporal lobe neither modified completion time in both verbal and visuo-spatial tests nor changed error rate. In contrast, magnetic stimulation of the pre-frontal area induced a significant reduction in the performance time of both the verbal and visuo-spatial tests always without an increase in the number of errors. The experimental findings underline the importance of the pre-frontal area in performing tasks requiring a high level of controlled attention and suggest the need to adopt an interdisciplinary approach towards the study of neurone/mind interface mechanisms.

Spike-timing-dependent plasticity in the human dorso-lateral prefrontal cortex.

PubMed

Casula, Elias Paolo; Pellicciari, Maria Concetta; Picazio, Silvia; Caltagirone, Carlo; Koch, Giacomo

2016-12-01

Changes in the synaptic strength of neural connections are induced by repeated coupling of activity of interconnected neurons with precise timing, a phenomenon known as spike-timing-dependent plasticity (STDP). It is debated if this mechanism exists in large-scale cortical networks in humans. We combined transcranial magnetic stimulation (TMS) with concurrent electroencephalography (EEG) to directly investigate the effects of two paired associative stimulation (PAS) protocols (fronto-parietal and parieto-frontal) of pre and post-synaptic inputs within the human fronto-parietal network. We found evidence that the dorsolateral prefrontal cortex (DLPFC) has the potential to form robust STDP. Long-term potentiation/depression of TMS-evoked cortical activity is prompted after that DLPFC stimulation is followed/preceded by posterior parietal stimulation. Such bidirectional changes are paralleled by sustained increase/decrease of high-frequency oscillatory activity, likely reflecting STDP responsivity. The current findings could be important to drive plasticity of damaged cortical circuits in patients with cognitive or psychiatric disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

Dopamine and serotonin interactions in the prefrontal cortex: insights on antipsychotic drugs and their mechanism of action.

PubMed

Di Pietro, N C; Seamans, J K

2007-12-01

Diminished activity within the prefrontal cortex (PFC) has been associated with many of the cognitive deficits that are observed in schizophrenia. It has been hypothesized that antipsychotic drugs (APDs) used to treat schizophrenia restore normal activity by antagonizing the dopamine (DA) D2 receptor, which is also known to modulate key ionic currents in the PFC. However, the hypothesis that an under-active cortical DA system is responsible for schizophrenic symptoms has been challenged by evidence that newer atypical APDs are weak antagonists at the D2 receptor but potent antagonists at the serotonin (5-HT) 2A receptor . This review examines how DA and 5-HT modulate cortical activity and how they may interact in ways that are relevant to schizophrenia. It is concluded that although D2 receptor antagonism remains a critical factor in restoring impaired cortical activity, effects on 5-HT receptors may act in a synergistic manner on NMDA and GABA currents to potentiate antipsychotic actions in the PFC.

Cortical Thinning and Altered Cortico-Cortical Structural Covariance of the Default Mode Network in Patients with Persistent Insomnia Symptoms.

PubMed

Suh, Sooyeon; Kim, Hosung; Dang-Vu, Thien Thanh; Joo, Eunyeon; Shin, Chol

2016-01-01

Recent studies have suggested that structural abnormalities in insomnia may be linked with alterations in the default-mode network (DMN). This study compared cortical thickness and structural connectivity linked to the DMN in patients with persistent insomnia (PI) and good sleepers (GS). The current study used a clinical subsample from the longitudinal community-based Korean Genome and Epidemiology Study (KoGES). Cortical thickness and structural connectivity linked to the DMN in patients with persistent insomnia symptoms (PIS; n = 57) were compared to good sleepers (GS; n = 40). All participants underwent MRI acquisition. Based on literature review, we selected cortical regions corresponding to the DMN. A seed-based structural covariance analysis measured cortical thickness correlation between each seed region of the DMN and other cortical areas. Association of cortical thickness and covariance with sleep quality and neuropsychological assessments were further assessed. Compared to GS, cortical thinning was found in PIS in the anterior cingulate cortex, precentral cortex, and lateral prefrontal cortex. Decreased structural connectivity between anterior and posterior regions of the DMN was observed in the PIS group. Decreased structural covariance within the DMN was associated with higher PSQI scores. Cortical thinning in the lateral frontal lobe was related to poor performance in executive function in PIS. Disrupted structural covariance network in PIS might reflect malfunctioning of antero-posterior disconnection of the DMN during the wake to sleep transition that is commonly found during normal sleep. The observed structural network alteration may further implicate commonly observed sustained sleep difficulties and cognitive impairment in insomnia. © 2016 Associated Professional Sleep Societies, LLC.

Regional entropy of functional imaging signals varies differently in sensory and cognitive systems during propofol-modulated loss and return of behavioral responsiveness.

PubMed

Liu, Xiaolin; Lauer, Kathryn K; Ward, B Douglas; Roberts, Christopher J; Liu, Suyan; Gollapudy, Suneeta; Rohloff, Robert; Gross, William; Xu, Zhan; Chen, Shanshan; Wang, Lubin; Yang, Zheng; Li, Shi-Jiang; Binder, Jeffrey R; Hudetz, Anthony G

2018-05-08

The level and richness of consciousness depend on information integration in the brain. Altered interregional functional interactions may indicate disrupted information integration during anesthetic-induced unconsciousness. How anesthetics modulate the amount of information in various brain regions has received less attention. Here, we propose a novel approach to quantify regional information content in the brain by the entropy of the principal components of regional blood oxygen-dependent imaging signals during graded propofol sedation. Fifteen healthy individuals underwent resting-state scans in wakeful baseline, light sedation (conscious), deep sedation (unconscious), and recovery (conscious). Light sedation characterized by lethargic behavioral responses was associated with global reduction of entropy in the brain. Deep sedation with completely suppressed overt responsiveness was associated with further reductions of entropy in sensory (primary and higher sensory plus orbital prefrontal cortices) but not high-order cognitive (dorsal and medial prefrontal, cingulate, parietotemporal cortices and hippocampal areas) systems. Upon recovery of responsiveness, entropy was restored in the sensory but not in high-order cognitive systems. These findings provide novel evidence for a reduction of information content of the brain as a potential systems-level mechanism of reduced consciousness during propofol anesthesia. The differential changes of entropy in the sensory and high-order cognitive systems associated with losing and regaining overt responsiveness are consistent with the notion of "disconnected consciousness", in which a complete sensory-motor disconnection from the environment occurs with preserved internal mentation.

Dorsomedial prefontal cortex supports spontaneous thinking per se.

PubMed

Raij, T T; Riekki, T J J

2017-06-01

Spontaneous thinking, an action to produce, consider, integrate, and reason through mental representations, is central to our daily experience and has been suggested to serve crucial adaptive purposes. Such thinking occurs among other experiences during mind wandering that is associated with activation of the default mode network among other brain circuitries. Whether and how such brain activation is linked to the experience of spontaneous thinking per se remains poorly known. We studied 51 healthy subjects using a comprehensive experience-sampling paradigm during 3T functional magnetic resonance imaging. In comparison with fixation, the experiences of spontaneous thinking and spontaneous perception were related to activation of wide-spread brain circuitries, including the cortical midline structures, the anterior cingulate cortex and the visual cortex. In direct comparison of the spontaneous thinking versus spontaneous perception, activation was observed in the anterior dorsomedial prefrontal cortex. Modality congruence of spontaneous-experience-related brain activation was suggested by several findings, including association of the lingual gyrus with visual in comparison with non-verbal-non-visual thinking. In the context of current literature, these findings suggest that the cortical midline structures are involved in the integrative core substrate of spontaneous thinking that is coupled with other brain systems depending on the characteristics of thinking. Furthermore, involvement of the anterior dorsomedial prefrontal cortex suggests the control of high-order abstract functions to characterize spontaneous thinking per se. Hum Brain Mapp 38:3277-3288, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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.

Neural networks involved in artistic creativity.

PubMed

Kowatari, Yasuyuki; Lee, Seung Hee; Yamamura, Hiromi; Nagamori, Yusuke; Levy, Pierre; Yamane, Shigeru; Yamamoto, Miyuki

2009-05-01

Creativity has been proposed to be either the result of solely right hemisphere processes or of interhemispheric interactions. Little information is available, however, concerning the neuronal foundations of creativity. In this study, we introduced a new artistic task, designing a new tool (a pen), which let us quantitatively evaluate creativity by three indices of originality. These scores were analyzed in combination with brain activities measured by functional magnetic resonance imaging (fMRI). The results were compared between subjects who had been formally trained in design (experts) and novice subjects. In the experts, creativity was quantitatively correlated with the degree of dominance of the right prefrontal cortex over that of the left, but not with that of the right or left prefrontal cortex alone. In contrast, in novice subjects, only a negative correlation with creativity was observed in the bilateral inferior parietal cortex. We introduced structure equation modeling to analyze the interactions among these four brain areas and originality indices. The results predicted that training exerts a direct effect on the left parietal cortex. Additionally, as a result of the indirect effects, the activity of the right prefrontal cortex was facilitated, and the left prefrontal and right parietal cortices were suppressed. Our results supported the hypothesis that training increases creativity via reorganized intercortical interactions. (c) 2008 Wiley-Liss, Inc.

Dissociable neural systems resolve conflict from emotional versus nonemotional distracters.

PubMed

Egner, Tobias; Etkin, Amit; Gale, Seth; Hirsch, Joy

2008-06-01

The human brain protects the processing of task-relevant stimuli from interference ("conflict") by task-irrelevant stimuli via attentional biasing mechanisms. The lateral prefrontal cortex has been implicated in resolving conflict between competing stimuli by selectively enhancing task-relevant stimulus representations in sensory cortices. Conversely, recent data suggest that conflict from emotional distracters may be resolved by an alternative route, wherein the rostral anterior cingulate cortex inhibits amygdalar responsiveness to task-irrelevant emotional stimuli. Here we tested the proposal of 2 dissociable, distracter-specific conflict resolution mechanisms, by acquiring functional magnetic resonance imaging data during resolution of conflict from either nonemotional or emotional distracters. The results revealed 2 distinct circuits: a lateral prefrontal "cognitive control" system that resolved nonemotional conflict and was associated with enhanced processing of task-relevant stimuli in sensory cortices, and a rostral anterior cingulate "emotional control" system that resolved emotional conflict and was associated with decreased amygdalar responses to emotional distracters. By contrast, activations related to both emotional and nonemotional conflict monitoring were observed in a common region of the dorsal anterior cingulate. These data suggest that the neuroanatomical networks recruited to overcome conflict vary systematically with the nature of the conflict, but that they may share a common conflict-detection mechanism.