A Novel Approach to Prenatal Measurement of the Fetal Frontal Lobe Using Three-Dimensional Sonography.

PubMed

Brown, Steffen A; Hall, Rebecca; Hund, Lauren; Gutierrez, Hilda L; Hurley, Timothy; Holbrook, Bradley D; Bakhireva, Ludmila N

2017-01-01

While prenatal 3D ultrasonography results in improved diagnostic accuracy, no data are available on biometric assessment of the fetal frontal lobe. This study was designed to assess feasibility of a standardized approach to biometric measurement of the fetal frontal lobe and to construct frontal lobe growth trajectories throughout gestation. A sonographic 3D volume set was obtained and measured in 101 patients between 16.1 and 33.7 gestational weeks. Measurements were obtained by two independent raters. To model the relationship between gestational age and each frontal lobe measurement, flexible linear regression models were fit using penalized regression splines. The sample contained an ethnically diverse population (7.9% Native Americans, 45.5% Hispanic/Latina). There was high inter-rater reliability (correlation coefficients: 0.95, 1.0, and 0.87 for frontal lobe length, width, and height; p-values < 0.001). Graphs of the growth trajectories and corresponding percentiles were estimated as a function of gestational age. The estimated rates of frontal lobe growth were 0.096 cm/week, 0.247 cm/week, and 0.111 cm/week for length, width, and height. To our knowledge, this is the first study to examine fetal frontal lobe growth trajectories through 3D prenatal ultrasound examination. Such normative data will allow for future prenatal evaluation of a particular disease state by 3D ultrasound imaging.

Responses of primate frontal cortex neurons during natural vocal communication.

PubMed

Miller, Cory T; Thomas, A Wren; Nummela, Samuel U; de la Mothe, Lisa A

2015-08-01

The role of primate frontal cortex in vocal communication and its significance in language evolution have a controversial history. While evidence indicates that vocalization processing occurs in ventrolateral prefrontal cortex neurons, vocal-motor activity has been conjectured to be primarily subcortical and suggestive of a distinctly different neural architecture from humans. Direct evidence of neural activity during natural vocal communication is limited, as previous studies were performed in chair-restrained animals. Here we recorded the activity of single neurons across multiple regions of prefrontal and premotor cortex while freely moving marmosets engaged in a natural vocal behavior known as antiphonal calling. Our aim was to test whether neurons in marmoset frontal cortex exhibited responses during vocal-signal processing and/or vocal-motor production in the context of active, natural communication. We observed motor-related changes in single neuron activity during vocal production, but relatively weak sensory responses for vocalization processing during this natural behavior. Vocal-motor responses occurred both prior to and during call production and were typically coupled to the timing of each vocalization pulse. Despite the relatively weak sensory responses a population classifier was able to distinguish between neural activity that occurred during presentations of vocalization stimuli that elicited an antiphonal response and those that did not. These findings are suggestive of the role that nonhuman primate frontal cortex neurons play in natural communication and provide an important foundation for more explicit tests of the functional contributions of these neocortical areas during vocal behaviors. Copyright © 2015 the American Physiological Society.

Responses of primate frontal cortex neurons during natural vocal communication

PubMed Central

Thomas, A. Wren; Nummela, Samuel U.; de la Mothe, Lisa A.

2015-01-01

The role of primate frontal cortex in vocal communication and its significance in language evolution have a controversial history. While evidence indicates that vocalization processing occurs in ventrolateral prefrontal cortex neurons, vocal-motor activity has been conjectured to be primarily subcortical and suggestive of a distinctly different neural architecture from humans. Direct evidence of neural activity during natural vocal communication is limited, as previous studies were performed in chair-restrained animals. Here we recorded the activity of single neurons across multiple regions of prefrontal and premotor cortex while freely moving marmosets engaged in a natural vocal behavior known as antiphonal calling. Our aim was to test whether neurons in marmoset frontal cortex exhibited responses during vocal-signal processing and/or vocal-motor production in the context of active, natural communication. We observed motor-related changes in single neuron activity during vocal production, but relatively weak sensory responses for vocalization processing during this natural behavior. Vocal-motor responses occurred both prior to and during call production and were typically coupled to the timing of each vocalization pulse. Despite the relatively weak sensory responses a population classifier was able to distinguish between neural activity that occurred during presentations of vocalization stimuli that elicited an antiphonal response and those that did not. These findings are suggestive of the role that nonhuman primate frontal cortex neurons play in natural communication and provide an important foundation for more explicit tests of the functional contributions of these neocortical areas during vocal behaviors. PMID:26084912

Local administration of a cannabinoid agonist alters norepinephrine efflux in the rat frontal cortex.

PubMed

Page, M E; Oropeza, V C; Van Bockstaele, E J

2008-01-24

Delta(9)-tetrahydrocannabinol, the main psychoactive ingredient in marijuana, activates specific cannabinoid (CB) receptors to exert complex actions on modulatory neurotransmitters involved in attention and cognition. Previous research has demonstrated that systemic administration of the synthetic cannabinoid agonist, WIN 55,212-2, increases norepinephrine efflux in the frontal cortex. The distribution of CB1 receptors on noradrenergic fibers in the frontal cortex suggests this may be one potential site for the regulation of norepinephrine release. In the present study, we first examined the ability of a CB1 antagonist, applied locally in the frontal cortex of adult male Sprague-Dawley rats, to block the actions of systemic WIN 55,212-2. Pretreatment with SR 141716A (300 microM) significantly attenuated the excitatory effects of WIN 55,212-2 (15 mg/kg, i.p.). Next, the impact of direct perfusion of WIN 55,212-2 into the frontal cortex on extracellular norepinephrine efflux was measured. Direct application of WIN 55,212-2 (100 microM) into the frontal cortex elicited a significant increase in extracellular norepinephrine efflux suggesting that activation of cortical cannabinoid receptors contributes to alterations in norepinephrine levels in this brain region. Finally, local administration of SR 141716A followed by local administration of WIN 55,212-2 revealed a paradoxical inhibition of norepinephrine efflux.

Learning a New Selection Rule in Visual and Frontal Cortex.

PubMed

van der Togt, Chris; Stănişor, Liviu; Pooresmaeili, Arezoo; Albantakis, Larissa; Deco, Gustavo; Roelfsema, Pieter R

2016-08-01

How do you make a decision if you do not know the rules of the game? Models of sensory decision-making suggest that choices are slow if evidence is weak, but they may only apply if the subject knows the task rules. Here, we asked how the learning of a new rule influences neuronal activity in the visual (area V1) and frontal cortex (area FEF) of monkeys. We devised a new icon-selection task. On each day, the monkeys saw 2 new icons (small pictures) and learned which one was relevant. We rewarded eye movements to a saccade target connected to the relevant icon with a curve. Neurons in visual and frontal cortex coded the monkey's choice, because the representation of the selected curve was enhanced. Learning delayed the neuronal selection signals and we uncovered the cause of this delay in V1, where learning to select the relevant icon caused an early suppression of surrounding image elements. These results demonstrate that the learning of a new rule causes a transition from fast and random decisions to a more considerate strategy that takes additional time and they reveal the contribution of visual and frontal cortex to the learning process. © The Author 2016. Published by Oxford University Press.

Downregulation of the posterior medial frontal cortex prevents social conformity.

PubMed

Klucharev, Vasily; Munneke, Moniek A M; Smidts, Ale; Fernández, Guillén

2011-08-17

We often change our behavior to conform to real or imagined group pressure. Social influence on our behavior has been extensively studied in social psychology, but its neural mechanisms have remained largely unknown. Here we demonstrate that the transient downregulation of the posterior medial frontal cortex by theta-burst transcranial magnetic stimulation reduces conformity, as indicated by reduced conformal adjustments in line with group opinion. Both the extent and probability of conformal behavioral adjustments decreased significantly relative to a sham and a control stimulation over another brain area. The posterior part of the medial frontal cortex has previously been implicated in behavioral and attitudinal adjustments. Here, we provide the first interventional evidence of its critical role in social influence on human behavior.

On the functional relevance of frontal cortex for passive and voluntarily controlled bistable vision.

PubMed

de Graaf, Tom A; de Jong, Maartje C; Goebel, Rainer; van Ee, Raymond; Sack, Alexander T

2011-10-01

In bistable vision, one constant ambiguous stimulus leads to 2 alternating conscious percepts. This perceptual switching occurs spontaneously but can also be influenced through voluntary control. Neuroimaging studies have reported that frontal regions are activated during spontaneous perceptual switches, leading some researchers to suggest that frontal regions causally induce perceptual switches. But the opposite also seems possible: frontal activations may themselves be caused by spontaneous switches. Classically implicated in attentional processes, these same regions are also candidates for the origins of voluntary control over bistable vision. Here too, it remains unknown whether frontal cortex is actually functionally relevant. It is even possible that spontaneous perceptual switches and voluntarily induced switches are mediated by the same top-down mechanisms. To directly address these issues, we here induced "virtual lesions," with transcranial magnetic stimulation, in frontal, parietal, and 2 lower level visual cortices using an established ambiguous structure-from-motion stimulus. We found that dorsolateral prefrontal cortex was causally relevant for voluntary control over perceptual switches. In contrast, we failed to find any evidence for an active role of frontal cortex in passive bistable vision. Thus, it seems the same pathway used for willed top-down modulation of bistable vision is not used during passive bistable viewing.

Modulating phonemic fluency performance in healthy subjects with transcranial magnetic stimulation over the left or right lateral frontal cortex.

PubMed

Smirni, Daniela; Turriziani, Patrizia; Mangano, Giuseppa Renata; Bracco, Martina; Oliveri, Massimiliano; Cipolotti, Lisa

2017-07-28

A growing body of evidence have suggested that non-invasive brain stimulation techniques, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), can improve the performance of aphasic patients in language tasks. For example, application of inhibitory rTMS or tDCs over the right frontal lobe of dysphasic patients resulted in improved naming abilities. Several studies have also reported that in healthy controls (HC) tDCS application over the left prefrontal cortex (PFC) improve performance in naming and semantic fluency tasks. The aim of this study was to investigate in HC, for the first time, the effects of inhibitory repetitive TMS (rTMS) over left and right lateral frontal cortex (BA 47) on two phonemic fluency tasks (FAS or FPL). 44 right-handed HCs were administered rTMS or sham over the left or right lateral frontal cortex in two separate testing sessions, with a 24h interval, followed by the two phonemic fluency tasks. To account for possible practice effects, an additional 22 HCs were tested on only the phonemic fluency task across two sessions with no stimulation. We found that rTMS-inhibition over the left lateral frontal cortex significantly worsened phonemic fluency performance when compared to sham. In contrast, rTMS-inhibition over the right lateral frontal cortex significantly improved phonemic fluency performance when compared to sham. These results were not accounted for practice effects. We speculated that rTMS over the right lateral frontal cortex may induce plastic neural changes to the left lateral frontal cortex by suppressing interhemispheric inhibitory interactions. This resulted in an increased excitability (disinhibition) of the contralateral unstimulated left lateral frontal cortex, consequently enhancing phonemic fluency performance. Conversely, application of rTMS over the left lateral frontal cortex may induce a temporary, virtual lesion, with effects similar to those reported in left frontal

The medial frontal cortex contributes to but does not organize rat exploratory behavior.

PubMed

Blankenship, Philip A; Stuebing, Sarah L; Winter, Shawn S; Cheatwood, Joseph L; Benson, James D; Whishaw, Ian Q; Wallace, Douglas G

2016-11-12

Animals use multiple strategies to maintain spatial orientation. Dead reckoning is a form of spatial navigation that depends on self-movement cue processing. During dead reckoning, the generation of self-movement cues from a starting position to an animal's current position allow for the estimation of direction and distance to the position movement originated. A network of brain structures has been implicated in dead reckoning. Recent work has provided evidence that the medial frontal cortex may contribute to dead reckoning in this network of brain structures. The current study investigated the organization of rat exploratory behavior subsequent to medial frontal cortex aspiration lesions under light and dark conditions. Disruptions in exploratory behavior associated with medial frontal lesions were consistent with impaired motor coordination, response inhibition, or egocentric reference frame. These processes are necessary for spatial orientation; however, they are not sufficient for self-movement cue processing. Therefore it is possible that the medial frontal cortex provides processing resources that support dead reckoning in other brain structures but does not of itself compute the kinematic details of dead reckoning. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Influence of motivation on control hierarchy in the human frontal cortex.

PubMed

Bahlmann, Jörg; Aarts, Esther; D'Esposito, Mark

2015-02-18

The frontal cortex mediates cognitive control and motivation to shape human behavior. It is generally observed that medial frontal areas are involved in motivational aspects of behavior, whereas lateral frontal regions are involved in cognitive control. Recent models of cognitive control suggest a rostro-caudal gradient in lateral frontal regions, such that progressively more rostral (anterior) regions process more complex aspects of cognitive control. How motivation influences such a control hierarchy is still under debate. Although some researchers argue that both systems work in parallel, others argue in favor of an interaction between motivation and cognitive control. In the latter case it is yet unclear how motivation would affect the different levels of the control hierarchy. This was investigated in the present functional MRI study applying different levels of cognitive control under different motivational states (low vs high reward anticipation). Three levels of cognitive control were tested by varying rule complexity: stimulus-response mapping (low-level), flexible task updating (mid-level), and sustained cue-task associations (high-level). We found an interaction between levels of cognitive control and motivation in medial and lateral frontal subregions. Specifically, flexible updating (mid-level of control) showed the strongest beneficial effect of reward and only this level exhibited functional coupling between dopamine-rich midbrain regions and the lateral frontal cortex. These findings suggest that motivation differentially affects the levels of a control hierarchy, influencing recruitment of frontal cortical control regions depending on specific task demands. Copyright © 2015 the authors 0270-6474/15/353207-11$15.00/0.

A frontal cortex event-related potential driven by the basal forebrain

PubMed Central

Nguyen, David P; Lin, Shih-Chieh

2014-01-01

Event-related potentials (ERPs) are widely used in both healthy and neuropsychiatric conditions as physiological indices of cognitive functions. Contrary to the common belief that cognitive ERPs are generated by local activity within the cerebral cortex, here we show that an attention-related ERP in the frontal cortex is correlated with, and likely generated by, subcortical inputs from the basal forebrain (BF). In rats performing an auditory oddball task, both the amplitude and timing of the frontal ERP were coupled with BF neuronal activity in single trials. The local field potentials (LFPs) associated with the frontal ERP, concentrated in deep cortical layers corresponding to the zone of BF input, were similarly coupled with BF activity and consistently triggered by BF electrical stimulation within 5–10 msec. These results highlight the important and previously unrecognized role of long-range subcortical inputs from the BF in the generation of cognitive ERPs. DOI: http://dx.doi.org/10.7554/eLife.02148.001 PMID:24714497

Dyslexic children lack word selectivity gradients in occipito-temporal and inferior frontal cortex.

PubMed

Olulade, O A; Flowers, D L; Napoliello, E M; Eden, G F

2015-01-01

fMRI studies using a region-of-interest approach have revealed that the ventral portion of the left occipito-temporal cortex, which is specialized for orthographic processing of visually presented words (and includes the so-called "visual word form area", VWFA), is characterized by a posterior-to-anterior gradient of increasing selectivity for words in typically reading adults, adolescents, and children (e.g. Brem et al., 2006, 2009). Similarly, the left inferior frontal cortex (IFC) has been shown to exhibit a medial-to-lateral gradient of print selectivity in typically reading adults (Vinckier et al., 2007). Functional brain imaging studies of dyslexia have reported relative underactivity in left hemisphere occipito-temporal and inferior frontal regions using whole-brain analyses during word processing tasks. Hence, the question arises whether gradient sensitivities in these regions are altered in dyslexia. Indeed, a region-of-interest analysis revealed the gradient-specific functional specialization in the occipito-temporal cortex to be disrupted in dyslexic children (van der Mark et al., 2009). Building on these studies, we here (1) investigate if a word-selective gradient exists in the inferior frontal cortex in addition to the occipito-temporal cortex in normally reading children, (2) compare typically reading with dyslexic children, and (3) examine functional connections between these regions in both groups. We replicated the previously reported anterior-to-posterior gradient of increasing selectivity for words in the left occipito-temporal cortex in typically reading children, and its absence in the dyslexic children. Our novel finding is the detection of a pattern of increasing selectivity for words along the medial-to-lateral axis of the left inferior frontal cortex in typically reading children and evidence of functional connectivity between the most lateral aspect of this area and the anterior aspects of the occipito-temporal cortex. We report absence

Vulnerability of the Medial Frontal Corticospinal Projection Accompanies Combined Lateral Frontal and Parietal Cortex Injury in Rhesus Monkey

PubMed Central

Morecraft, R.J.; Ge, J.; Stilwell-Morecraft, K.S.; McNeal, D.W.; Hynes, S.M.; Pizzimenti, M.A.; Rotella, D.L.; Darling, W.G.

2014-01-01

Concurrent damage to the lateral frontal and parietal cortex is common following middle cerebral artery infarction leading to upper extremity paresis, paresthesia and sensory loss. Motor recovery is often poor and the mechanisms that support, or impede this process are unclear. Since the medial wall of the cerebral hemisphere is commonly spared following stroke, we investigated the long-term (6 and 12 month) effects of lateral frontoparietal injury (F2P2 lesion) on the terminal distribution of the corticospinal projection (CSP) from intact, ipsilesional supplementary motor cortex (M2) at spinal levels C5 to T1. Isolated injury to the frontoparietal arm/hand region resulted in a significant loss of contralateral corticospinal boutons from M2 compared to controls. Specifically, reductions occurred in the medial and lateral parts of lamina VII and the dorsal quadrants of lamina IX. There were no statistical differences in the ipsilateral corticospinal projection. Contrary to isolated lateral frontal motor injury (F2 lesion) which results in substantial increases in contralateral M2 labeling in laminae VII and IX (McNeal et al., Journal of Comparative Neurology 518:586-621, 2010), the added effect of adjacent parietal cortex injury to the frontal motor lesion (F2P2 lesion) not only impedes a favorable compensatory neuroplastic response, but results in a substantial loss of M2 CSP terminals. This dramatic reversal of the CSP response suggests a critical trophic role for cortical somatosensory influence on spared ipsilesional frontal corticospinal projections, and that restoration of a favorable compensatory response will require therapeutic intervention. PMID:25349147

Autobiographical memory of the recent past following frontal cortex or temporal lobe excisions.

PubMed

Thaiss, Laila; Petrides, Michael

2008-08-01

Previous research has raised questions regarding the necessity of the frontal cortex in autobiographical memory and the role that it plays in actively retrieving contextual information associated with personally relevant events. Autobiographical memory was studied in patients with unilateral excisions restricted to the frontal cortex or temporal lobe involving the amygdalo-hippocampal region and in normal controls using an event-sampling method. We examined accuracy of free recall, use of strategies during retrieval and memory for specific aspects of the autobiographical events, including temporal order. Patients with temporal lobe excisions were impaired in autobiographical recall. By contrast, patients with frontal cortical excisions exhibited normal autobiographical recall but were less likely to use temporal order spontaneously to organize event retrieval. Instruction to organize retrieval by temporal order failed to improve recall in temporal lobe patients and increased the incidence of plausible intrusion errors in left temporal patients. In contrast, patients with frontal cortical excisions now surpassed control subjects in recall of autobiographical events. Furthermore, the retrieval accuracy for the temporal order of diary events was not impaired in these patients. In a subsequent cued recall test, temporal lobe patients were impaired in their memory for the details of the diary events and their context. In conclusion, a basic impairment in autobiographical memory (including memory for temporal context) results from damage to the temporal lobe and not the frontal cortex. Patients with frontal excisions fail to use organizational strategies spontaneously to aid retrieval but can use these effectively if instructed to do so.

Orbito-Frontal Cortex Is Necessary for Temporal Context Memory

ERIC Educational Resources Information Center

Duarte, Audrey; Henson, Richard N.; Knight, Robert T.; Emery, Tina; Graham, Kim S.

2010-01-01

Lesion and neuroimaging studies suggest that orbito-frontal cortex (OFC) supports temporal aspects of episodic memory. However, it is unclear whether OFC contributes to the encoding and/or retrieval of temporal context and whether it is selective for temporal relative to nontemporal (spatial) context memory. We addressed this issue with two…

The threshold for conscious report: Signal loss and response bias in visual and frontal cortex.

PubMed

van Vugt, Bram; Dagnino, Bruno; Vartak, Devavrat; Safaai, Houman; Panzeri, Stefano; Dehaene, Stanislas; Roelfsema, Pieter R

2018-05-04

Why are some visual stimuli consciously detected, whereas others remain subliminal? We investigated the fate of weak visual stimuli in the visual and frontal cortex of awake monkeys trained to report stimulus presence. Reported stimuli were associated with strong sustained activity in the frontal cortex, and frontal activity was weaker and quickly decayed for unreported stimuli. Information about weak stimuli could be lost at successive stages en route from the visual to the frontal cortex, and these propagation failures were confirmed through microstimulation of area V1. Fluctuations in response bias and sensitivity during perception of identical stimuli were traced back to prestimulus brain-state markers. A model in which stimuli become consciously reportable when they elicit a nonlinear ignition process in higher cortical areas explained our results. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

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

OBscure but not OBsolete: Perturbations of the frontal cortex in common between rodent olfactory bulbectomy model and major depression.

PubMed

Rajkumar, Ramamoorthy; Dawe, Gavin S

2018-04-07

Olfactory bulbectomy (OBX) has been used as a model of depression over several decades. This model presupposes a mechanism that is still not proven in clinical depression. A wealth of clinical literature has focused on the derangements in frontal cortex (prefrontal, orbitofrontal and anterior cingulate cortices) associated with depression. In this comprehensive review, anatomical, electrophysiological and molecular sequelae of bulbectomy in the rodent frontal cortex are explored and compared with findings on brains of humans with major depression. Certain commonalities in neurobiological features of the perturbed frontal cortex in the bulbectomised rodent and the depressed human brain are evident. Also, meta-analysis reports on clinical studies on depressed patients provide prima facie evidence that perturbations in the frontal cortex are associated with major depression. Analysing the pattern of perturbations in the chemical neuroanatomy of the frontal cortex will contribute to understanding of the neurobiology of depression. Revisiting the OBX model of depression to examine these neurobiological changes in frontal cortex with contemporary imaging, proteomics, lipidomics, metabolomics and epigenomics technologies is proposed as an approach to enhance the translational value of this animal model to facilitate identification of targets and biomarkers for clinical depression. Copyright © 2018 Elsevier B.V. All rights reserved.

Bilateral lesions of the medial frontal cortex disrupt recognition of social hierarchy during antiphonal communication in naked mole-rats (Heterocephalus glaber).

PubMed

Yosida, Shigeto; Okanoya, Kazuo

2012-02-01

Generation of the motor patterns of emotional sounds in mammals occurs in the periaqueductal gray matter of the midbrain and is not directly controlled by the cortex. The medial frontal cortex indirectly controls vocalizations, based on the recognition of social context. We examined whether the medial frontal cortex was responsible for antiphonal vocalization, or turn-taking, in naked mole-rats. In normal turn-taking, naked mole-rats vocalize more frequently to dominant individuals than to subordinate ones. Bilateral lesions of the medial frontal cortex disrupted differentiation of call rates to the stimulus animals, which had varied social relationships to the subject. However, medial frontal cortex lesions did not affect either the acoustic properties of the vocalizations or the timing of the vocal exchanges. This suggests that the medial frontal cortex may be involved in social cognition or decision making during turn-taking, while other regions of the brain regulate when animals vocalize and the vocalizations themselves.

A direct GABAergic output from the basal ganglia to frontal cortex

PubMed Central

Saunders, Arpiar; Oldenburg, Ian A.; Berezovskii, Vladimir K.; Johnson, Caroline A.; Kingery, Nathan D.; Elliott, Hunter L.; Xie, Tiao; Gerfen, Charles R.; Sabatini, Bernardo L.

2014-01-01

The basal ganglia (BG) are phylogenetically conserved subcortical nuclei necessary for coordinated motor action and reward learning1. Current models postulate that the BG modulate cerebral cortex indirectly via an inhibitory output to thalamus, bidirectionally controlled by the BG via direct (dSPNs) and indirect (iSPNs) pathway striatal projection neurons2–4. The BG thalamic output sculpts cortical activity by interacting with signals from sensory and motor systems5. Here we describe a direct projection from the globus pallidus externus (GP), a central nucleus of the BG, to frontal regions of the cerebral cortex (FC). Two cell types make up the GP-FC projection, distinguished by their electrophysiological properties, cortical projections and expression of choline acetyltransferase (ChAT), a synthetic enzyme for the neurotransmitter acetylcholine (ACh). Despite these differences, ChAT+ cells, which have been historically identified as an extension of the nucleus basalis (NB), as well as ChAT− cells, release the inhibitory neurotransmitter GABA (γ-aminobutyric acid) and are inhibited by iSPNs and dSPNs of dorsal striatum. Thus GP-FC cells comprise a direct GABAergic/cholinergic projection under the control of striatum that activates frontal cortex in vivo. Furthermore, iSPN inhibition of GP-FC cells is sensitive to dopamine 2 receptor signaling, revealing a pathway by which drugs that target dopamine receptors for the treatment of neuropsychiatric disorders can act in the BG to modulate frontal cortices. PMID:25739505

Comparing development of synaptic proteins in rat visual, somatosensory, and frontal cortex.

PubMed

Pinto, Joshua G A; Jones, David G; Murphy, Kathryn M

2013-01-01

Two theories have influenced our understanding of cortical development: the integrated network theory, where synaptic development is coordinated across areas; and the cascade theory, where the cortex develops in a wave-like manner from sensory to non-sensory areas. These different views on cortical development raise challenges for current studies aimed at comparing detailed maturation of the connectome among cortical areas. We have taken a different approach to compare synaptic development in rat visual, somatosensory, and frontal cortex by measuring expression of pre-synaptic (synapsin and synaptophysin) proteins that regulate vesicle cycling, and post-synaptic density (PSD-95 and Gephyrin) proteins that anchor excitatory or inhibitory (E-I) receptors. We also compared development of the balances between the pairs of pre- or post-synaptic proteins, and the overall pre- to post-synaptic balance, to address functional maturation and emergence of the E-I balance. We found that development of the individual proteins and the post-synaptic index overlapped among the three cortical areas, but the pre-synaptic index matured later in frontal cortex. Finally, we applied a neuroinformatics approach using principal component analysis and found that three components captured development of the synaptic proteins. The first component accounted for 64% of the variance in protein expression and reflected total protein expression, which overlapped among the three cortical areas. The second component was gephyrin and the E-I balance, it emerged as sequential waves starting in somatosensory, then frontal, and finally visual cortex. The third component was the balance between pre- and post-synaptic proteins, and this followed a different developmental trajectory in somatosensory cortex. Together, these results give the most support to an integrated network of synaptic development, but also highlight more complex patterns of development that vary in timing and end point among the

Systemic administration of WIN 55,212-2 increases norepinephrine release in the rat frontal cortex.

PubMed

Oropeza, V C; Page, M E; Van Bockstaele, E J

2005-06-07

Cannabinoid agonists modulate a variety of behavioral functions by activating cannabinoid receptors that are widely distributed throughout the central nervous system. In the present study, norepinephrine efflux was assessed in the frontal cortex of rats that received a systemic administration of the cannabinoid agonist, WIN 55,212-2. The synthetic cannabinoid agonist dose-dependently increased the release of norepinephrine in this brain region. Pretreatment with the cannabinoid receptor antagonist, SR 141716A, blocked the increase in norepinephrine release. To identify sites of cellular activation, immunocytochemical detection of c-Fos was combined with detection of the catecholamine synthesizing enzyme, tyrosine hydroxylase (TH), in the brainstem nucleus locus coeruleus (LC), a region that is the sole source of norepinephrine to the frontal cortex. Systemic administration of WIN 55,212-2 significantly increased the number of c-Fos immunoreactive cells within TH-containing neurons in the LC compared to vehicle-treated rats. Pretreatment with SR 141716A inhibited the WIN 55,212-2 induced c-Fos expression, while the antagonist alone did not affect c-Fos expression. Taken together, these data indicate that systemically administered cannabinoid agonists stimulate norepinephrine release in the frontal cortex by activating noradrenergic neurons in the coeruleo-frontal cortex pathway. These effects may partially underlie changes in attention, arousal and anxiety observed following exposure to cannabis-based drugs.

Grammatical distinctions in the left frontal cortex.

PubMed

Shapiro, K A; Pascual-Leone, A; Mottaghy, F M; Gangitano, M; Caramazza, A

2001-08-15

Selective deficits in producing verbs relative to nouns in speech are well documented in neuropsychology and have been associated with left hemisphere frontal cortical lesions resulting from stroke and other neurological disorders. The basis for these impairments is unresolved: Do they arise because of differences in the way grammatical categories of words are organized in the brain, or because of differences in the neural representation of actions and objects? We used repetitive transcranial magnetic stimulation (rTMS) to suppress the excitability of a portion of left prefrontal cortex and to assess its role in producing nouns and verbs. In one experiment subjects generated real words; in a second, they produced pseudowords as nouns or verbs. In both experiments, response latencies increased for verbs but were unaffected for nouns following rTMS. These results demonstrate that grammatical categories have a neuroanatomical basis and that the left prefrontal cortex is selectively engaged in processing verbs as grammatical objects.

Neuroanatomical correlates of personality in chimpanzees (Pan troglodytes): Associations between personality and frontal cortex.

PubMed

Latzman, Robert D; Hecht, Lisa K; Freeman, Hani D; Schapiro, Steven J; Hopkins, William D

2015-12-01

Converging empirical data suggests that a set of largely consistent personality traits exist in both human and nonhuman primates; despite these similarities, almost nothing is known concerning the neurobiological basis of these traits in nonhuman primates. The current study examined associations between chimpanzee personality traits and the grey matter volume and asymmetry of various frontal cortex regions in 107 captive chimpanzees. Chimpanzees rated as higher on Openness and Extraversion had greater bilateral grey matter volumes in the anterior cingulate cortex. Further, chimpanzee rated as higher on Dominance had larger grey volumes in the left anterior cingulate cortex and right Prefrontal Cortex (PFC). Finally, apes rated higher on Reactivity/Unpredictability had higher grey matter volumes in the right mesial PFC. All associations survived after applying False Discovery Rate (FDR) thresholds. Results are discussed in terms of current neuroscientific models of personality which suggest that the frontal cortex, and asymmetries in this region, play an important role in the neurobiological foundation of broad dispositional traits. Copyright © 2015 Elsevier Inc. All rights reserved.

Role of Frontal Cortex in Attentional Capture by Singleton Distractors

ERIC Educational Resources Information Center

de Fockert, Jan W.; Theeuwes, Jan

2012-01-01

The role of frontal cortex in selective attention to visual distractors was examined in an attentional capture task in which participants searched for a unique shape in the presence or absence of an additional colour singleton distractor. The presence of the additional singleton was associated with slower behavioural responses to the shape target,…

Functional organization of human intraparietal and frontal cortex for attending, looking, and pointing

NASA Technical Reports Server (NTRS)

Astafiev, Serguei V.; Shulman, Gordon L.; Stanley, Christine M.; Snyder, Abraham Z.; Van Essen, David C.; Corbetta, Maurizio

2003-01-01

We studied the functional organization of human posterior parietal and frontal cortex using functional magnetic resonance imaging (fMRI) to map preparatory signals for attending, looking, and pointing to a peripheral visual location. The human frontal eye field and two separate regions in the intraparietal sulcus were similarly recruited in all conditions, suggesting an attentional role that generalizes across response effectors. However, the preparation of a pointing movement selectively activated a different group of regions, suggesting a stronger role in motor planning. These regions were lateralized to the left hemisphere, activated by preparation of movements of either hand, and included the inferior and superior parietal lobule, precuneus, and posterior superior temporal sulcus, plus the dorsal premotor and anterior cingulate cortex anteriorly. Surface-based registration of macaque cortical areas onto the map of fMRI responses suggests a relatively good spatial correspondence between human and macaque parietal areas. In contrast, large interspecies differences were noted in the topography of frontal areas.

Preconditioning of Spatial and Auditory Cues: Roles of the Hippocampus, Frontal Cortex, and Cue-Directed Attention

PubMed Central

Talk, Andrew C.; Grasby, Katrina L.; Rawson, Tim; Ebejer, Jane L.

2016-01-01

Loss of function of the hippocampus or frontal cortex is associated with reduced performance on memory tasks, in which subjects are incidentally exposed to cues at specific places in the environment and are subsequently asked to recollect the location at which the cue was experienced. Here, we examined the roles of the rodent hippocampus and frontal cortex in cue-directed attention during encoding of memory for the location of a single incidentally experienced cue. During a spatial sensory preconditioning task, rats explored an elevated platform while an auditory cue was incidentally presented at one corner. The opposite corner acted as an unpaired control location. The rats demonstrated recollection of location by avoiding the paired corner after the auditory cue was in turn paired with shock. Damage to either the dorsal hippocampus or the frontal cortex impaired this memory ability. However, we also found that hippocampal lesions enhanced attention directed towards the cue during the encoding phase, while frontal cortical lesions reduced cue-directed attention. These results suggest that the deficit in spatial sensory preconditioning caused by frontal cortical damage may be mediated by inattention to the location of cues during the latent encoding phase, while deficits following hippocampal damage must be related to other mechanisms such as generation of neural plasticity. PMID:27999366

Acute mobile phones exposure affects frontal cortex hemodynamics as evidenced by functional near-infrared spectroscopy.

PubMed

Curcio, Giuseppe; Ferrara, Michele; Limongi, Tania; Tempesta, Daniela; Di Sante, Gabriele; De Gennaro, Luigi; Quaresima, Valentina; Ferrari, Marco

2009-05-01

This study aimed to evaluate by functional near-infrared spectroscopy (fNIRS), the effects induced by an acute exposure (40 mins) to a GSM (Global System for Mobile Communications) signal emitted by a mobile phone (MP) on the oxygenation of the frontal cortex. Eleven healthy volunteers underwent two sessions (Real and Sham exposure) after a crossover, randomized, double-blind paradigm. The whole procedure lasted 60 mins: 10-mins baseline (Bsl), 40-mins (Exposure), and 10-mins recovery (Post-Exp). Together with frontal hemodynamics, heart rate, objective and subjective vigilance, and self-evaluation of subjective symptoms were also assessed. The fNIRS results showed a slight influence of the GSM signal on frontal cortex, with a linear increase in [HHb] as a function of time in the Real exposure condition (F(4,40)=2.67; P=0.04). No other measure showed any GSM exposure-dependent changes. These results suggest that fNIRS is a convenient tool for safely and noninvasively investigating the cortical activation in MP exposure experimental settings. Given the short-term effects observed in this study, the results should be confirmed on a larger sample size and using a multichannel instrument that allows the investigation of a wider portion of the frontal cortex.

Prenatal stress decreases glycogen synthase kinase-3 phosphorylation in the rat frontal cortex.

PubMed

Szymańska, Magdalena; Suska, Anna; Budziszewska, Bogusława; Jaworska-Feil, Lucylla; Basta-Kaim, Agnieszka; Leśkiewicz, Monika; Kubera, Marta; Gergont, Aleksandra; Kroczka, Sławomir; Kaciński, Marek; Lasoń, Władysław

2009-01-01

It has been postulated that hyperactive glycogen synthase kinase-3 (GSK-3) is an important factor in the pathogenesis of depression, and that this enzyme also contributes to the mechanism of antidepressant drug action. In the present study, we investigated the effect of prenatal stress (an animal model of depression) and long-term treatment with antidepressant drugs on the concentration of GSK-3beta and its main regulating protein kinase B (PKB, Akt). The concentration of GSK-3beta, its inactive form (phospho-Ser9-GSK-3beta), and the amounts of active (phospho-Akt) and total Akt were determined in the hippocampus and frontal cortex in rats. In order to verify our animal model of depression, immobility time in the forced swim test (Porsolt test) was also determined.We found that prenatally stressed rats display a high level of immobility in the Porsolt test and chronic treatment with imipramine, fluoxetine, mirtazapine and tianeptine normalize this change. Western blot analysis demonstrated that GSK-3beta levels were significantly elevated in the frontal cortex, but not in the hippocampus, of prenatally stressed rats. The concentration of its non-active form (phospho-Ser9-GSK-3beta) was decreased only in the former brain structure. No changes were found in the amounts of active (phospho-Akt) and total Akt in both studied brain structures. Chronic treatment with antidepressant drugs diminished stress-induced alterations in GSK-3beta and phospho-GSK-3beta the frontal cortex, but had no effect on the concentration of these enzymes in the hippocampus. Moreover, levels of Akt and phospho-Akt in all experimental groups remained unchanged. Since our animal model of depression is connected with hyperactivity of the HPA axis, our results suggest that GSK-3beta is an important intracellular target for maladaptive glucocorticoid action on frontal cortex neurons and in antidepressant drug effects. Furthermore, the influence of stress and antidepressant drugs on GSK-3beta does

The behavior of chronic cats with lesions in the frontal association cortex.

PubMed

Warren, J M; Warren, H B; Akert, K

1972-01-01

Cats with lesions in the proreal and anterior sigmoid gyri and substantial but subtotal degeneration in the mediodorsal thalamic nucleus were studied for 6 years post-operatively. The control group consisted of normal cats matched for age and previous experience. The results reported here and in Warren's previous progress report indicate that frontal cortical lesions result in several behavioral changes in cats which are like those seen in rhesus monkeys after frontal ablations: impairments in discrimination reversal, double alternation and active avoidance learning, retardation in the rate of habituation to novel neutral stimuli, and a decrease in aggression in competitive social situations. Cats with larger frontal lesions made more errors in reversal learning than cats with smaller lesions. Frontal cats, unlike frontal rhesus monkeys, are not hyperactive post-operatively and retain some capacity for learning delayed response in the WGTA. It is impossible at present to tell whether these discrepancies reflect species differences in the organization of the frontal lobe system or whether the frontal cortex spared in this series of cats is sufficient to mediate delayed response and to prevent the occurrence of hyperactivity.

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.

Upregulation of Neurotrophic Factors Selectively in Frontal Cortex in Response to Olfactory Discrimination Learning

PubMed Central

Naimark, Ari; Barkai, Edi; Matar, Michael A.; Kaplan, Zeev; Kozlovsky, Nitzan; Cohen, Hagit

2007-01-01

We have previously shown that olfactory discrimination learning is accompanied by several forms of long-term enhancement in synaptic connections between layer II pyramidal neurons selectively in the piriform cortex. This study sought to examine whether the previously demonstrated olfactory-learning-task-induced modifications are preceded by suitable changes in the expression of mRNA for neurotrophic factors and in which brain areas this occurs. Rats were trained to discriminate positive cues in pair of odors for a water reward. The relationship between the learning task and local levels of mRNA for brain-derived neurotrophic factor, tyrosine kinase B, nerve growth factor, and neurotrophin-3 in the frontal cortex, hippocampal subregions, and other regions were assessed 24 hours post olfactory learning. The olfactory discrimination learning activated production of endogenous neurotrophic factors and induced their signal transduction in the frontal cortex, but not in other brain areas. These findings suggest that different brain areas may be preferentially involved in different learning/memory tasks. PMID:17710248

Acute seizure activity promotes lipid peroxidation, increased nitrite levels and adaptive pathways against oxidative stress in the frontal cortex and striatum

PubMed Central

Júnior, Hélio Vitoriano Nobre; de França Fonteles, Marta Maria

2009-01-01

Previous experiments have shown that the generation of free radicals in rat brain homogenates is increased following pilocarpine-induced seizures and status epilepticus (SE). This study was aimed at investigating the changes in neurochemical mechanisms such as lipid peroxidation levels, nitrite content, glutathione reduced (GSH) concentration, superoxide dismutase and catalase activities in the frontal cortex and the striatum of Wistar adult rats after seizures and SE induced by pilocarpine. The control group was treated with 0.9% saline and another group of rats received pilocarpine (400 mg/kg, i.p.). Both groups were sacrificed 24 h after the treatments. Lipid peroxidation level, nitrite content, GSH concentration and enzymatic activities were measured by using spectrophotometric methods. Our findings showed that pilocarpine administration and its resulting seizures and SE produced a significant increase of lipid peroxidation level in the striatum (47%) and frontal cortex (59%). Nitrite contents increased 49% and 73% in striatum and frontal cortex in pilocarpine group, respectively. In GSH concentrations were decreases of 54% and 58% in the striatum and frontal cortex in pilocarpine group, respectively. The catalase activity increased 39% and 49% in the striatum and frontal cortex, respectively. The superoxide dismutase activity was not altered in the striatum, but it was present at a 24% increase in frontal cortex. These results suggest that there is a direct relationship between the lipid peroxidation and nitrite contents during epileptic activity that can be responsible for the superoxide dismutase and catalase enzymatic activity changes observed during the establishment of seizures and SE induced by pilocarpine. PMID:20592767

[Visuoperceptual processing in Parkinson's disease: from the retina to the frontal cortex].

PubMed

Ruiz-Sánchez de León, J M; Fernández-Guinea, S

The growing interest in the cognitive impairment shown by patients with Parkinson's disease has led to a wealth of research in this line over recent years. In this paper we review the visuospatial alterations in these patients, which are usually linked to other disorders such as those affecting planning, sequencing, attention or mnemonic processes. We report the most relevant findings, which suggest that the existence of these visuospatial disorders shown by patients with Parkinson's disease are not always secondary to other frontal-type cognitive impairments, as has been claimed in recent years. Instead, they may be due to disorders in other anterior points of the perceptive process (as a result of dopaminergic deficits in basal-thalamic-cortical circuits). Thus, visuoperceptual disorders are classified according to their location in the brain: from the retina to the lateral geniculate nucleus, the visual cortex and the extrastriate cortex and, finally, the frontal and prefrontal cortex. We propose this classification of the disorders according to their location to aid in achieving an objective selection of the sample and of the neuropsychological tests used in studies. In this regard, we consider that there should be a higher degree of agreement among researchers when it comes to designing research projects that deal with visuospatial disorders in patients with Parkinson's disease.

Orbito-frontal cortex and thalamus volumes in the patients with obsessive-compulsive disorder before and after cognitive behavioral therapy.

PubMed

Atmaca, Murad; Yildirim, Hanefi; Yilmaz, Seda; Caglar, Neslihan; Mermi, Osman; Korkmaz, Sevda; Akaslan, Unsal; Gurok, M Gurkan; Kekilli, Yasemin; Turkcapar, Hakan

2018-07-01

Background The effect of a variety of treatment modalities including psychopharmacological and cognitive behavioral therapy on the brain volumes and neurochemicals have not been investigated enough in the patients with obsessive-compulsive disorder. Therefore, in the present study, we aimed to investigate the effect of cognitive behavioral therapy on the volumes of the orbito-frontal cortex and thalamus regions which seem to be abnormal in the patients with obsessive-compulsive disorder. We hypothesized that there would be change in the volumes of the orbito-frontal cortex and thalamus. Methods Twelve patients with obsessive-compulsive disorder and same number of healthy controls were included into the study. At the beginning of the study, the volumes of the orbito-frontal cortex and thalamus were compared by using magnetic resonance imaging. In addition, volumes of these regions were measured before and after the cognitive behavioral therapy treatment in the patient group. Results The patients with obsessive-compulsive disorder had greater left and right thalamus volumes and smaller left and right orbito-frontal cortex volumes compared to those of healthy control subjects at the beginning of the study. When we compared baseline volumes of the patients with posttreatment ones, we detected that thalamus volumes significantly decreased throughout the period for both sides and that the orbito-frontal cortex volumes significantly increased throughout the period for only left side. Conclusions In summary, we found that cognitive behavioral therapy might volumetrically affect the key brain regions involved in the neuroanatomy of obsessive-compulsive disorder. However, future studies with larger sample are required.

Increased Neuronal DNA/RNA Oxidation in the Frontal Cortex of Mice Subjected to Unpredictable Chronic Mild Stress.

PubMed

Maluach, Alfred M; Misquitta, Keith A; Prevot, Thomas D; Fee, Corey; Sibille, Etienne; Banasr, Mounira; Andreazza, Ana C

2017-01-01

Chronic stress is implicated in the development of various psychiatric illnesses including major depressive disorder. Previous reports suggest that patients with major depressive disorder have increased levels of oxidative stress, including higher levels of DNA/RNA oxidation found in postmortem studies, especially within brain regions responsible for the cognitive and emotional processes disrupted in the disorder. Here, we aimed to investigate whether unpredictable chronic mild stress in mice induces neuronal DNA/RNA oxidation in the prelimbic, infralimbic, and cingulate cortices of the frontal cortex and the basolateral amygdala and to explore potential associations with depressive-like behaviors. We expected that animals subjected to unpredictable chronic mild stress will present higher levels of DNA/RNA oxidation, which will be associated with anxiety-/depressive-like behaviors. C57BL/6J mice were assigned to unpredictable chronic mild stress or nonstress conditions (n = 10/group, 50% females). Following five weeks of unpredictable chronic mild stress exposure, mice were tested in a series of behavioral tests measuring anxiety- and depressive-like behaviors. Frontal cortex and amygdala sections were then immunolabeled for neuronal nuclei, a marker of post-mitotic neurons and anti-8-hydroxy-2-deoxyguanosine/8-oxo-7,8-dihydroguanosine, which reflects both DNA and RNA oxidation. Levels of neuronal DNA/RNA oxidation were increased in the frontal cortex of mice subjected to unpredictable chronic mild stress ( p = 0.0207). Levels of neuronal DNA/RNA oxidation in the frontal cortex were positively correlated with z-emotionality scores for latency to feed in the novelty-suppressed feeding test ( p = 0.0031). Statistically significant differences were not detected in basolateral amygdala levels of neuronal DNA/RNA oxidation between nonstress- and unpredictable chronic mild stress-exposed mice, nor were correlations found with behavioral performances for this region. Our

Functional specialization of the primate frontal cortex during decision making.

PubMed

Lee, Daeyeol; Rushworth, Matthew F S; Walton, Mark E; Watanabe, Masataka; Sakagami, Masamichi

2007-08-01

Economic theories of decision making are based on the principle of utility maximization, and reinforcement-learning theory provides computational algorithms that can be used to estimate the overall reward expected from alternative choices. These formal models not only account for a large range of behavioral observations in human and animal decision makers, but also provide useful tools for investigating the neural basis of decision making. Nevertheless, in reality, decision makers must combine different types of information about the costs and benefits associated with each available option, such as the quality and quantity of expected reward and required work. In this article, we put forward the hypothesis that different subdivisions of the primate frontal cortex may be specialized to focus on different aspects of dynamic decision-making processes. In this hypothesis, the lateral prefrontal cortex is primarily involved in maintaining the state representation necessary to identify optimal actions in a given environment. In contrast, the orbitofrontal cortex and the anterior cingulate cortex might be primarily involved in encoding and updating the utilities associated with different sensory stimuli and alternative actions, respectively. These cortical areas are also likely to contribute to decision making in a social context.

Switch-Independent Task Representations in Frontal and Parietal Cortex.

PubMed

Loose, Lasse S; Wisniewski, David; Rusconi, Marco; Goschke, Thomas; Haynes, John-Dylan

2017-08-16

Alternating between two tasks is effortful and impairs performance. Previous fMRI studies have found increased activity in frontoparietal cortex when task switching is required. One possibility is that the additional control demands for switch trials are met by strengthening task representations in the human brain. Alternatively, on switch trials, the residual representation of the previous task might impede the buildup of a neural task representation. This would predict weaker task representations on switch trials, thus also explaining the performance costs. To test this, male and female participants were cued to perform one of two similar tasks, with the task being repeated or switched between successive trials. Multivoxel pattern analysis was used to test which regions encode the tasks and whether this encoding differs between switch and repeat trials. As expected, we found information about task representations in frontal and parietal cortex, but there was no difference in the decoding accuracy of task-related information between switch and repeat trials. Using cross-classification, we found that the frontoparietal cortex encodes tasks using a generalizable spatial pattern in switch and repeat trials. Therefore, task representations in frontal and parietal cortex are largely switch independent. We found no evidence that neural information about task representations in these regions can explain behavioral costs usually associated with task switching. SIGNIFICANCE STATEMENT Alternating between two tasks is effortful and slows down performance. One possible explanation is that the representations in the human brain need time to build up and are thus weaker on switch trials, explaining performance costs. Alternatively, task representations might even be enhanced to overcome the previous task. Here, we used a combination of fMRI and a brain classifier to test whether the additional control demands under switching conditions lead to an increased or decreased strength

The scarcity heuristic impacts reward processing within the medial-frontal cortex.

PubMed

Williams, Chad C; Saffer, Boaz Y; McCulloch, Robert B; Krigolson, Olave E

2016-05-04

Objects that are rare are often perceived to be inherently more valuable than objects that are abundant - a bias brought about in part by the scarcity heuristic. In the present study, we sought to test whether perception of rarity impacted reward evaluation within the human medial-frontal cortex. Here, participants played a gambling game in which they flipped rare and abundant 'cards' on a computer screen to win financial rewards while electroencephalographic data were recorded. Unbeknownst to participants, reward outcome and frequency was random and equivalent for both rare and abundant cards; thus, only a perception of scarcity was true. Analysis of the electroencephalographic data indicated that the P300 component of the event-related brain potential differed in amplitude for wins and losses following the selection of rare cards, but not following the selection of abundant cards. Importantly, then, we found that the perception of card rarity impacted reward processing even though reward feedback was independent of and subsequent to card selection. Our data indicate a top-down influence of the scarcity heuristic on reward evaluation, and specifically the processing of reward magnitude, within the human medial-frontal cortex.

Distinct Sources of Deterministic and Stochastic Components of Action Timing Decisions in Rodent Frontal Cortex.

PubMed

Murakami, Masayoshi; Shteingart, Hanan; Loewenstein, Yonatan; Mainen, Zachary F

2017-05-17

The selection and timing of actions are subject to determinate influences such as sensory cues and internal state as well as to effectively stochastic variability. Although stochastic choice mechanisms are assumed by many theoretical models, their origin and mechanisms remain poorly understood. Here we investigated this issue by studying how neural circuits in the frontal cortex determine action timing in rats performing a waiting task. Electrophysiological recordings from two regions necessary for this behavior, medial prefrontal cortex (mPFC) and secondary motor cortex (M2), revealed an unexpected functional dissociation. Both areas encoded deterministic biases in action timing, but only M2 neurons reflected stochastic trial-by-trial fluctuations. This differential coding was reflected in distinct timescales of neural dynamics in the two frontal cortical areas. These results suggest a two-stage model in which stochastic components of action timing decisions are injected by circuits downstream of those carrying deterministic bias signals. Copyright © 2017 Elsevier Inc. All rights reserved.

Development and Function of the Human Fetal Adrenal Cortex: A Key Component in the Feto-Placental Unit

PubMed Central

Ishimoto, Hitoshi

2011-01-01

Continuous efforts have been devoted to unraveling the biophysiology and development of the human fetal adrenal cortex, which is structurally and functionally unique from other species. It plays a pivotal role, mainly through steroidogenesis, in the regulation of intrauterine homeostasis and in fetal development and maturation. The steroidogenic activity is characterized by early transient cortisol biosynthesis, followed by its suppressed synthesis until late gestation, and extensive production of dehydroepiandrosterone and its sulfate, precursors of placental estrogen, during most of gestation. The gland rapidly grows through processes including cell proliferation and angiogenesis at the gland periphery, cellular migration, hypertrophy, and apoptosis. Recent studies employing modern technologies such as gene expression profiling and laser capture microdissection have revealed that development and/or function of the fetal adrenal cortex may be regulated by a panoply of molecules, including transcription factors, extracellular matrix components, locally produced growth factors, and placenta-derived CRH, in addition to the primary regulator, fetal pituitary ACTH. The role of the fetal adrenal cortex in human pregnancy and parturition appears highly complex, probably due to redundant and compensatory mechanisms regulating these events. Mounting evidence indicates that actions of hormones operating in the human feto-placental unit are likely mediated by mechanisms including target tissue responsiveness, local metabolism, and bioavailability, rather than changes only in circulating levels. Comprehensive study of such molecular mechanisms and the newly identified factors implicated in adrenal development should help crystallize our understanding of the development and physiology of the human fetal adrenal cortex. PMID:21051591

The effects of anterior arcuate and dorsomedial frontal cortex lesions on visually guided eye movements: 2. Paired and multiple targets.

PubMed

Schiller, P H; Chou, I

2000-01-01

This study examined the effects of anterior arcuate and dorsomedial frontal cortex lesions on the execution of saccadic eye movements made to paired and multiple targets in rhesus monkeys. Identical paired targets were presented with various temporal asynchronies to determine the temporal offset required to yield equal probability choices to either target. In the intact animal equal probability choices were typically obtained when the targets appeared simultaneously. After unilateral anterior arcuate lesions a major shift arose in the temporal offset required to obtain equal probability choices for paired targets that necessitated presenting the target in the hemifield contralateral to the lesion more than 100 ms prior to the target in the ipsilateral hemifield. This deficit was still pronounced 1 year after the lesion. Dorsomedial frontal cortex lesions produced much smaller but significant shifts in target selection that recovered more rapidly. Paired lesions produced deficits similar to those observed with anterior arcuate lesions alone. Major deficits were also observed on a multiple target temporal discrimination task after anterior arcuate but not after dorsomedial frontal cortex lesions. These results suggest that the frontal eye fields that reside in anterior bank of the arcuate sulcus play an important role in temporal processing and in target selection. Dorsomedial frontal cortex, that contains the medial eye fields, plays a much less important role in the execution of these tasks.

Frontal Cortex Activation Causes Rapid Plasticity of Auditory Cortical Processing

PubMed Central

Winkowski, Daniel E.; Bandyopadhyay, Sharba; Shamma, Shihab A.

2013-01-01

Neurons in the primary auditory cortex (A1) can show rapid changes in receptive fields when animals are engaged in sound detection and discrimination tasks. The source of a signal to A1 that triggers these changes is suspected to be in frontal cortical areas. How or whether activity in frontal areas can influence activity and sensory processing in A1 and the detailed changes occurring in A1 on the level of single neurons and in neuronal populations remain uncertain. Using electrophysiological techniques in mice, we found that pairing orbitofrontal cortex (OFC) stimulation with sound stimuli caused rapid changes in the sound-driven activity within A1 that are largely mediated by noncholinergic mechanisms. By integrating in vivo two-photon Ca2+ imaging of A1 with OFC stimulation, we found that pairing OFC activity with sounds caused dynamic and selective changes in sensory responses of neural populations in A1. Further, analysis of changes in signal and noise correlation after OFC pairing revealed improvement in neural population-based discrimination performance within A1. This improvement was frequency specific and dependent on correlation changes. These OFC-induced influences on auditory responses resemble behavior-induced influences on auditory responses and demonstrate that OFC activity could underlie the coordination of rapid, dynamic changes in A1 to dynamic sensory environments. PMID:24227723

Pathological laughing and crying in amyotrophic lateral sclerosis is related to frontal cortex function.

PubMed

Hübers, Annemarie; Kassubek, Jan; Grön, Georg; Gorges, Martin; Aho-Oezhan, Helena; Keller, Jürgen; Horn, Hannah; Neugebauer, Hermann; Uttner, Ingo; Lulé, Dorothée; Ludolph, Albert C

2016-09-01

The syndrome of pathological laughing and crying (PLC) is characterized by episodes of involuntary outbursts of emotional expression. Although this phenomenon has been referred to for over a century, a clear-cut clinical definition is still lacking, and underlying pathophysiological mechanisms are not well understood. In particular, it remains ill-defined which kind of stimuli-contextually appropriate or inappropriate-elicit episodes of PLC, and if the phenomenon is a result of a lack of inhibition from the frontal cortex ("top-down-theory") or due to an altered processing of sensory inputs at the brainstem level ("bottom-up-theory"). To address these questions, we studied ten amyotrophic lateral sclerosis (ALS) patients with PLC and ten controls matched for age, sex and education. Subjects were simultaneously exposed to either emotionally congruent or incongruent visual and auditory stimuli and were asked to rate pictures according to their emotional quality. Changes in physiological parameters (heart rate, galvanic skin response, activity of facial muscles) were recorded, and a standardized self-assessment lability score (CNS-LS) was determined. Patients were influenced in their rating behaviour in a negative direction by mood-incongruent music. Compared to controls, they were influenced by negative stimuli, i.e. they rated neutral pictures more negatively when listening to sad music. Patients rated significantly higher on the CNS-LS. In patients, changes of electromyographic activity of mimic muscles during different emotion-eliciting conditions were explained by frontal cortex dysfunction. We conclude that PLC is associated with altered emotional suggestibility and that it is preferentially elicited by mood-incongruent stimuli. In addition, physiological reactions as well as behavioural changes suggest that this phenomenon is primarily an expression of reduced inhibitory activity of the frontal cortex, since frontal dysfunction could explain changes in

Fetal Alcohol Spectrum Disorder-associated depression: evidence for reductions in the levels of brain-derived neurotrophic factor in a mouse model

PubMed Central

Caldwell, Kevin K.; Sheema, S.; Paz, Rodrigo D; Samudio-Ruiz, Sabrina L.; Laughlin, Mary H.; Spence, Nathan E.; Roehlk, Michael J; Alcon, Sara N.; Allan, Andrea M.

2009-01-01

Prenatal ethanol exposure is associated with an increased incidence of depressive disorders in patient populations. However, the mechanisms that link prenatal ethanol exposure and depression are unknown. Several recent studies have implicated reduced brain-derived neurotrophic factor (BDNF) levels in the hippocampal formation and frontal cortex as important contributors to the etiology of depression. In the present studies, we sought to determine whether prenatal ethanol exposure is associated with behaviors that model depression, as well as with reduced BDNF levels in the hippocampal formation and/or medial frontal cortex, in a mouse model of fetal alcohol spectrum disorder (FASD). Compared to control adult mice, prenatal ethanol-exposed adult mice displayed increased learned helplessness behavior and increased immobility in the Porsolt forced swim test. Prenatal ethanol exposure was associated with decreased BDNF protein levels in the medial frontal cortex, but not the hippocampal formation, while total BDNF mRNA and BDNF transcripts containing exon III, IV or VI were reduced in both the medial frontal cortex and the hippocampal formation of prenatal ethanol-exposed mice. These results identify reduced BDNF levels in the medial frontal cortex and hippocampal formation as potential mediators of depressive disorders associated with FASD. PMID:18558427

Adrenergic receptors in frontal cortex in human brain.

PubMed

Cash, R; Raisman, R; Ruberg, M; Agid, Y

1985-02-05

The binding of three adrenergic ligands ([3H]prazosin, [3H]clonidine, [3H]dihydroalprenolol) was studied in the frontal cortex of human brain. alpha 1-Receptors, labeled by [3H]prazosin, predominated. [3H]Clonidine bound to two classes of sites, one of high affinity and one of low affinity. Guanosine triphosphate appeared to lower the affinity of [3H]clonidine for its receptor. [3H]Dihydroalprenolol bound to three classes of sites: the beta 1-receptor, the beta 2-receptor and a receptor with low affinity which represented about 40% of the total binding, but which was probably a non-specific site; the beta 1/beta 2 ratio was 1/2.

Selective effects of buspirone and molindone on dopamine metabolism and function in the striatum and frontal cortex of the rat.

PubMed

McMillen, B A; McDonald, C C

1983-03-01

The hypothesis that the nerve endings of the dopamine projection of the frontal cortex lack autoreceptors for regulation of tyrosine hydroxylase was tested by using the preferential inhibitors of dopamine autoreceptors, molindole and buspirone. In contrast to haloperidol, which elevates dopamine metabolism in the striatum and frontal cortex, both molindone and buspirone elicited little change in dopamine metabolism in the frontal cortex at doses up to 3.0 mg/kg, which cause the same maximal response in the corpus striatum as does haloperidol. Thus, the lack of autoreceptors in the frontal cortex is of pharmacological importance. That preferential inhibition of striatal dopamine autoreceptors may reverse catalepsy by enhancing synthesis and release of dopamine was tested by first inducing catalepsy with different drugs and then administering molindone or buspirone. Only buspirone (1.0 mg/kg) reversed catalepsy. This effect does not require presynaptic dopamine as catalepsy was reversed by buspirone in the dopamine-depleted rat (with 2.0 mg/kg R04-1284) as well as after postsynaptic dopamine receptor blockade by haloperidol of cis-flupenthixol. Thus, the mechanism for the reversal of catalepsy appears to be located efferent from the dopamine neuron. Buspirone, a non-benzodiazepine anti-anxiety drug, may prove useful for treatment of extrapyramidal motor disorders of either iatrogenic or idiosyncratic origin.

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

PubMed

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

2017-12-01

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

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.

Stimulus Expectancy Modulates Inferior Frontal Gyrus and Premotor Cortex Activity in Auditory Perception

ERIC Educational Resources Information Center

Osnes, Berge; Hugdahl, Kenneth; Hjelmervik, Helene; Specht, Karsten

2012-01-01

In studies on auditory speech perception, participants are often asked to perform active tasks, e.g. decide whether the perceived sound is a speech sound or not. However, information about the stimulus, inherent in such tasks, may induce expectations that cause altered activations not only in the auditory cortex, but also in frontal areas such as…

Attentional Control of Task and Response in Lateral and Medial Frontal Cortex: Brain Activity and Reaction Time Distributions

ERIC Educational Resources Information Center

Aarts, Esther; Roelofs, Ardi; van Turennout, Miranda

2009-01-01

It is unclear whether task conflict is reflected in the anterior cingulate cortex (ACC) or in more dorsal regions of the medial frontal cortex (MFC). When participants switch between tasks involving incongruent, congruent, and neutral stimuli, it is possible to examine both response conflict (incongruent vs. congruent) and task conflict (congruent…

Passive heat exposure induced by hot water leg immersion increased oxyhemoglobin in pre-frontal cortex to preserve oxygenation and did not contribute to impaired cognitive functioning

NASA Astrophysics Data System (ADS)

Wijayanto, Titis; Toramoto, Sayo; Tochihara, Yutaka

2013-07-01

This study investigated the effects of passive heat exposure on pre-frontal cortex oxygenation and cognitive functioning, specifically to examine whether the change in pre-frontal cortex oxygenation coincided with cognitive functioning during heat exposure. Eleven male students who participated in this study immersed their lower legs to the knees in three different water temperatures, 38 °C, 40 °C, and 42 °C water in an air temperature of 28 º C and 50 % relative humidity for 60 min. After 45 min of leg immersion they performed cognitive functioning tasks assessing their short-term memory while immersing their lower legs. There were higher rectal temperature ( P < 0.05) and higher increase of oxyhemoglobin in both left ( P < 0.05) and right ( P < 0.05) pre-frontal cortex at the final stage of 45-min leg immersion in the 42 °C condition with unaltered tissue oxygenation index among the three conditions ( P > 0.05). No statistical difference in cognitive functioning among the three conditions was observed with a higher increase of oxyhemoglobin during the cognitive functioning in the 42 °C condition for the left ( P = 0.05) and right ( P < 0.05) pre-frontal cortex. The findings of this study suggest, first, passive heat exposure increases oxygen delivery in the pre-frontal cortex to maintain pre-frontal cortex oxygenation; second, there is no evidence of passive heat exposure in cognitive functioning in this study; and third, the greater increases of oxyhemoglobin in the pre-frontal cortex during cognitive functioning at the hottest condition suggests a recruitment of available neural resources or greater effort to maintain the same performance at the same level as when they felt thermally comfortable.

Laminar recordings in frontal cortex suggest distinct layers for maintenance and control of working memory

PubMed Central

Bastos, André M.; Loonis, Roman; Kornblith, Simon; Lundqvist, Mikael; Miller, Earl K.

2018-01-01

All of the cerebral cortex has some degree of laminar organization. These different layers are composed of neurons with distinct connectivity patterns, embryonic origins, and molecular profiles. There are little data on the laminar specificity of cognitive functions in the frontal cortex, however. We recorded neuronal spiking/local field potentials (LFPs) using laminar probes in the frontal cortex (PMd, 8A, 8B, SMA/ACC, DLPFC, and VLPFC) of monkeys performing working memory (WM) tasks. LFP power in the gamma band (50–250 Hz) was strongest in superficial layers, and LFP power in the alpha/beta band (4–22 Hz) was strongest in deep layers. Memory delay activity, including spiking and stimulus-specific gamma bursting, was predominately in superficial layers. LFPs from superficial and deep layers were synchronized in the alpha/beta bands. This was primarily unidirectional, with alpha/beta bands in deep layers driving superficial layer activity. The phase of deep layer alpha/beta modulated superficial gamma bursting associated with WM encoding. Thus, alpha/beta rhythms in deep layers may regulate the superficial layer gamma bands and hence maintenance of the contents of WM. PMID:29339471

Laminar recordings in frontal cortex suggest distinct layers for maintenance and control of working memory.

PubMed

Bastos, André M; Loonis, Roman; Kornblith, Simon; Lundqvist, Mikael; Miller, Earl K

2018-01-30

All of the cerebral cortex has some degree of laminar organization. These different layers are composed of neurons with distinct connectivity patterns, embryonic origins, and molecular profiles. There are little data on the laminar specificity of cognitive functions in the frontal cortex, however. We recorded neuronal spiking/local field potentials (LFPs) using laminar probes in the frontal cortex (PMd, 8A, 8B, SMA/ACC, DLPFC, and VLPFC) of monkeys performing working memory (WM) tasks. LFP power in the gamma band (50-250 Hz) was strongest in superficial layers, and LFP power in the alpha/beta band (4-22 Hz) was strongest in deep layers. Memory delay activity, including spiking and stimulus-specific gamma bursting, was predominately in superficial layers. LFPs from superficial and deep layers were synchronized in the alpha/beta bands. This was primarily unidirectional, with alpha/beta bands in deep layers driving superficial layer activity. The phase of deep layer alpha/beta modulated superficial gamma bursting associated with WM encoding. Thus, alpha/beta rhythms in deep layers may regulate the superficial layer gamma bands and hence maintenance of the contents of WM. Copyright © 2018 the Author(s). Published by PNAS.

Chronic restraint stress promotes learning and memory impairment due to enhanced neuronal endoplasmic reticulum stress in the frontal cortex and hippocampus in male mice.

PubMed

Huang, Rong-Rong; Hu, Wen; Yin, Yan-Yan; Wang, Yu-Chan; Li, Wei-Ping; Li, Wei-Zu

2015-02-01

Chronic stress has been implicated in many types of neurodegenerative diseases, such as Alzheimer's disease (AD). In our previous study, we demonstrated that chronic restraint stress (CRS) induced reactive oxygen species (ROS) overproduction and oxidative damage in the frontal cortex and hippocampus in mice. In the present study, we investigated the effects of CRS (over a period of 8 weeks) on learning and memory impairment and endoplasmic reticulum (ER) stress in the frontal cortex and hippocampus in male mice. The Morris water maze was used to investigate the effects of CRS on learning and memory impairment. Immunohistochemistry and immunoblot analysis were also used to determine the expression levels of protein kinase C α (PKCα), 78 kDa glucose-regulated protein (GRP78), C/EBP-homologous protein (CHOP) and mesencephalic astrocyte-derived neurotrophic factor (MANF). The results revealed that CRS significantly accelerated learning and memory impairment, and induced neuronal damage in the frontal cortex and hippocampus CA1 region. Moreover, CRS significantly increased the expression of PKCα, CHOP and MANF, and decreased that of GRP78 in the frontal cortex and hippocampus. Our data suggest that exposure to CRS (for 8 weeks) significantly accelerates learning and memory impairment, and the mechanisms involved may be related to ER stress in the frontal cortex and hippocampus.

Direct cortical stimulation of inferior frontal cortex disrupts both speech and music production in highly trained musicians.

PubMed

Leonard, Matthew K; Desai, Maansi; Hungate, Dylan; Cai, Ruofan; Singhal, Nilika S; Knowlton, Robert C; Chang, Edward F

2018-05-22

Music and speech are human-specific behaviours that share numerous properties, including the fine motor skills required to produce them. Given these similarities, previous work has suggested that music and speech may at least partially share neural substrates. To date, much of this work has focused on perception, and has not investigated the neural basis of production, particularly in trained musicians. Here, we report two rare cases of musicians undergoing neurosurgical procedures, where it was possible to directly stimulate the left hemisphere cortex during speech and piano/guitar music production tasks. We found that stimulation to left inferior frontal cortex, including pars opercularis and ventral pre-central gyrus, caused slowing and arrest for both speech and music, and note sequence errors for music. Stimulation to posterior superior temporal cortex only caused production errors during speech. These results demonstrate partially dissociable networks underlying speech and music production, with a shared substrate in frontal regions.

Reciprocal activation/inactivation of ERK in the amygdala and frontal cortex is correlated with the degree of novelty of an open-field environment.

PubMed

Sanguedo, Frederico Velasco; Dias, Caio Vitor Bueno; Dias, Flavia Regina Cruz; Samuels, Richard Ian; Carey, Robert J; Carrera, Marinete Pinheiro

2016-03-01

Phosphorylated extracellular signal-regulated kinase (ERK) has been used to identify brain areas activated by exogenous stimuli including psychostimulant drugs. Assess the role of the amygdala in emotional responses. Experimental manipulations were performed in which environmental familiarity was the variable. To provide the maximal degree of familiarity, ERK was measured after removal from the home cage and re-placement back into the same cage. To maximize exposure to an unfamiliar environment, ERK was measured following placement into a novel open field. To assess whether familiarity was the critical variable in the ERK response to the novel open field, ERK was also measured after either four or eight placements into the same environment. ERK quantification was carried out in the amygdala, frontal cortex, and the nucleus accumbens. After home cage re-placement, ERK activation was found in the frontal cortex and nucleus accumbens but was absent in the amygdala. Following placement in a novel environment, ERK activation was more prominent in the amygdala than the frontal cortex or nucleus accumbens. In contrast, with habituation to the novel environment, ERK phosphors declined markedly in the amygdala but increased in the frontal cortex and nucleus accumbens to the level observed following home cage re-placement. The differential responsiveness of the amygdala versus the frontal cortex and the nucleus accumbens to a novel versus a habituated environment is consistent with a reciprocal interaction between these neural systems and points to their important role in the mediation of behavioral activation to novelty and behavioral inactivation with habituation.

Decreased GRK3 but not GRK2 expression in frontal cortex from bipolar disorder patients

PubMed Central

Rao, Jagadeesh S; Rapoport, Stanley I; Kim, Hyung-Wook

2009-01-01

Overactivation of G-protein mediated functions and altered G-protein regulation have been reported in bipolar disorder (BD) brain. Further, drugs effective in treating BD are reported to upregulate expression of G-protein receptor kinase (GRK) 3 in rat frontal cortex. We therefore hypothesized that some G-protein subunits and GRK levels would be reduced in the brains of BD patients. We determined protein and mRNA levels of G-protein β and γ subunits, GRK2, and GRK3 in postmortem frontal cortex from 10 BD patients and 10 age-matched controls by using immunoblots and real-time RT-PCR. There were the statistically significant decreases in protein and mRNA levels of G-protein subunits β and γ and of GRK3 in the BD brains but not a significant difference in the GRK2 level. Decreased expression of G-protein subunits and of GRK3 may alter neurotransmission, leading to disturbed cognition and behavior in BD. PMID:19400979

Cognition and medial frontal cortex in health and disease

PubMed Central

Nachev, Parashkev

2009-01-01

Purpose of review Recent work on the role of medial frontal cortex in cognition and its involvement in neurological disorders is critically reviewed. Recent findings The highly influential notion of conflict monitoring by the anterior cingulate has been called into question by monkey single-cell neurophysiology and lesion studies in monkeys and humans. An alternative role for this region in adapting behaviour in response to changing demands over time is gaining support. By contrast, the more dorsally placed pre-supplementary motor area and supplementary eye field have been implicated in direct executive control in situations of response conflict. Although more rostral medial areas have been linked to complex cognitive operations involving references to the self, conceptual obstacles make the evidence difficult to interpret. The role of orbitofrontal cortex in guiding action based on value has been reinforced. Summary This area continues to generate both interest and controversy. A few striking discrepancies between data from functional imaging and interventional techniques illustrate the hazards of drawing strong conclusions from merely correlative evidence. More broadly, a case can be made for tempering the empirical enthusiasm here with a little more theoretical restraint. PMID:17102698

Cognitive Functioning after Medial Frontal Lobe Damage Including the Anterior Cingulate Cortex: A Preliminary Investigation

ERIC Educational Resources Information Center

Baird, Amee; Dewar, Bonnie-Kate; Critchley, Hugo; Gilbert, Sam J.; Dolan, Raymond J.; Cipolotti, Lisa

2006-01-01

Two patients with medial frontal lobe damage involving the anterior cingulate cortex (ACC) performed a range of cognitive tasks, including tests of executive function and anterior attention. Both patients lesions extended beyond the ACC, therefore caution needs to be exerted in ascribing observed deficits to the ACC alone. Patient performance was…

Is evaluation of humorous stimuli associated with frontal cortex morphology? A pilot study using facial micro-movement analysis and MRI.

PubMed

Juckel, Georg; Mergl, Roland; Brüne, Martin; Villeneuve, Isabelle; Frodl, Thomas; Schmitt, Gisela; Zetzsche, Thomas; Born, Christine; Hahn, Klaus; Reiser, Maximilian; Möller, Hans-Jürgen; Bär, Karl-Jürgen; Hegerl, Ulrich; Meisenzahl, Eva Maria

2011-05-01

Humour involves the ability to detect incongruous ideas violating social rules and norms. Accordingly, humour requires a complex array of cognitive skills for which intact frontal lobe functioning is critical. Here, we sought to examine the association of facial expression during an emotion inducing experiment with frontal cortex morphology in healthy subjects. Thirty-one healthy male subjects (mean age: 30.8±8.9 years; all right-handers) watching a humorous movie ("Mr. Bean") were investigated. Markers fixed at certain points of the face emitting high-frequency ultrasonic signals allowed direct measurement of facial movements with high spatial-temporal resolution. Magnetic resonance images of the frontal cortex were obtained with a 1.5-T Magnetom using a coronar T2- and protondensity-weighted Dual-Echo-Sequence and a 3D-magnetization-prepared rapid gradient echo (MPRAGE) sequence. Volumetric analysis was performed using BRAINS. Frontal cortex volume was partly associated with slower speed of "laughing" movements of the eyes ("genuine" or Duchenne smile). Specifically, grey matter volume was associated with longer emotional reaction time ipsilaterally, even when controlled for age and daily alcohol intake. These results lend support to the hypothesis that superior cognitive evaluation of humorous stimuli - mediated by larger prefrontal grey and white matter volume - leads to a measurable reduction of speed of emotional expressivity in normal adults. Copyright © 2010 Elsevier Srl. All rights reserved.

What makes the dorsomedial frontal cortex active during reading the mental states of others?

PubMed Central

Isoda, Masaki; Noritake, Atsushi

2013-01-01

The dorsomedial frontal part of the cerebral cortex is consistently activated when people read the mental states of others, such as their beliefs, desires, and intentions, the ability known as having a theory of mind (ToM) or mentalizing. This ubiquitous finding has led many researchers to conclude that the dorsomedial frontal cortex (DMFC) constitutes a core component in mentalizing networks. Despite this, it remains unclear why the DMFC becomes active during ToM tasks. We argue that key psychological and behavioral aspects in mentalizing are closely associated with DMFC functions. These include executive inhibition, distinction between self and others, prediction under uncertainty, and perception of intentions, all of which are important for predicting others' intention and behavior. We review the literature supporting this claim, ranging in fields from developmental psychology to human neuroimaging and macaque electrophysiology. Because perceiving intentions in others' actions initiates mentalizing and forms the basis of virtually all types of social interaction, the fundamental issue in social neuroscience is to determine the aspects of physical entities that make an observer perceive that they are intentional beings and to clarify the neurobiological underpinnings of the perception of intentionality in others' actions. PMID:24367287

Antiamnesic effect of acyl-prolyl-containing dipeptide (GVS-111) in compression-induced damage to frontal cortex.

PubMed

Romanova, G A; Mirzoev, T K; Barskov, I V; Victorov, I V; Gudasheva, T A; Ostrovskaya, R U

2000-09-01

Antiamnestic effect of acyl-prolyl-containing dipeptide GVS-111 was demonstrated in rats with bilateral compression-induced damage to the frontal cortex. Both intraperitoneal and oral administration of the dipeptide improved retrieval of passive avoidance responses in rats with compression-induced cerebral ischemia compared to untreated controls.

Induction of hyperphagia and carbohydrate intake by mu-opioid receptor stimulation in circumscribed regions of frontal cortex

PubMed Central

Mena, Jesus D.; Sadeghian, Ken; Baldo, Brian A.

2011-01-01

Frontal cortical regions are activated by food-associated stimuli, and this activation appears to be dysregulated in individuals with eating disorders. Nevertheless, frontal control of basic unconditioned feeding responses remains poorly understood. Here we show that hyperphagia can be driven by μ-opioid receptor stimulation in restricted regions of ventral medial prefrontal cortex (vmPFC) and orbitofrontal cortex. In both ad libitum-fed and food-restricted male Sprague-Dawley rats, bilateral infusions of the μ-opioid agonist, DAMGO, markedly increased intake of standard rat chow. When given a choice between palatable fat- versus carbohydrate enriched test diets, intra-vmPFC DAMGO infusions selectively increased carbohydrate intake, even in rats with a baseline fat preference. Rats also exhibited motor hyperactivity characterized by rapid switching between brief bouts of investigatory and ingestive behaviors. Intra-vmPFC DAMGO affected neither water intake nor non-specific oral behavior. Similar DAMGO infusions into neighboring areas of lateral orbital or anterior motor cortex had minimal effects on feeding. Neither stimulation of vmPFC-localized delta-opioid, kappa-opioid, dopaminergic, serotonergic, or noradrenergic receptors, nor antagonism of D1, 5HT1A, or alpha- or beta-adrenoceptors, reproduced the profile of DAMGO effects. Muscimol-mediated inactivation of the vmPFC, and intra-vmPFC stimulation of κ-opioid receptors or blockade of 5HT2A receptors, suppressed motor activity and increased feeding bout duration-a profile opposite to that seen with DAMGO. Hence, μ-opioid-induced hyperphagia and carbohydrate intake can be elicited with remarkable pharmacological and behavioral specificity from discrete subterritories of the frontal cortex. These findings may have implications for understanding affect-driven feeding and loss of restraint in eating disorders. PMID:21368037

Induction of hyperphagia and carbohydrate intake by μ-opioid receptor stimulation in circumscribed regions of frontal cortex.

PubMed

Mena, Jesus D; Sadeghian, Ken; Baldo, Brian A

2011-03-02

Frontal cortical regions are activated by food-associated stimuli, and this activation appears to be dysregulated in individuals with eating disorders. Nevertheless, frontal control of basic unconditioned feeding responses remains poorly understood. Here we show that hyperphagia can be driven by μ-opioid receptor stimulation in restricted regions of ventral medial prefrontal cortex (vmPFC) and orbitofrontal cortex. In both ad libitum-fed and food-restricted male Sprague Dawley rats, bilateral infusions of the μ-opioid agonist [d-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO) markedly increased intake of standard rat chow. When given a choice between palatable fat-enriched versus carbohydrate-enriched test diets, intra-vmPFC DAMGO infusions selectively increased carbohydrate intake, even in rats with a baseline fat preference. Rats also exhibited motor hyperactivity characterized by rapid switching between brief bouts of investigatory and ingestive behaviors. Intra-vmPFC DAMGO affected neither water intake nor nonspecific oral behavior. Similar DAMGO infusions into neighboring areas of lateral orbital or anterior motor cortex had minimal effects on feeding. Neither stimulation of vmPFC-localized δ-opioid, κ-opioid, dopaminergic, serotonergic, or noradrenergic receptors, nor antagonism of D1, 5HT1A, or α- or β-adrenoceptors, reproduced the profile of DAMGO effects. Muscimol-mediated inactivation of the vmPFC, and intra-vmPFC stimulation of κ-opioid receptors or blockade of 5-HT2A (5-hydroxytryptamine receptor 2A) receptors, suppressed motor activity and increased feeding bout duration-a profile opposite to that seen with DAMGO. Hence, μ-opioid-induced hyperphagia and carbohydrate intake can be elicited with remarkable pharmacological and behavioral specificity from discrete subterritories of the frontal cortex. These findings may have implications for understanding affect-driven feeding and loss of restraint in eating disorders.

Repeated isoflurane exposure and neuroapoptosis in the midgestation fetal sheep brain.

PubMed

Olutoye, Olutoyin A; Sheikh, Fariha; Zamora, Irving J; Yu, Ling; Akinkuotu, Adesola C; Adesina, Adekunle M; Olutoye, Oluyinka O

2016-04-01

Advances in surgery and technology have resulted in increased in-utero procedures. However, the effect of anesthesia on the fetal brain is not fully known. The inhalational anesthetic agent, isoflurane, other gamma amino butyric acid agonists (benzodiazepines, barbiturates, propofol, other inhalation anesthetics), and N-methyl D aspartate antagonists, eg, ketamine, have been shown to induce neuroapoptosis. The ovine model has been used extensively to study maternal-fetal physiologic interactions and to investigate different surgical interventions on the fetus. The purpose of this study was to determine effects of different doses and duration of isoflurane on neuroapoptosis in midgestation fetal sheep. We hypothesized that repeated anesthetic exposure and high concentrations of isoflurane would result in increased neuroapoptosis. Time-dated, pregnant sheep at 70 days gestation (term 145 days) received either isoflurane 2% × 1 hour, 4% × 3 hours, or 2% × 1 hour every other day for 3 exposures (repeated exposure group). Euthanasia occurred following anesthetic exposure and fetal brains were processed. Neuroapoptosis was detected by immunohistochemistry using anticaspase-3 antibodies. Fetuses unexposed to anesthesia served as controls. Another midgestation group with repeated 2% isoflurane exposure was examined at day 130 (long-term group) and neuronal cell density compared to age-matched controls. Representative sections of the brain were analyzed using Aperio Digital imaging (Leica Microsystems Inc, Buffalo Grove, IL). Data, reported by number of neurons per cubic millimeter of brain tissue are presented as means and SEM. Data were analyzed using the Mann-Whitney U and Kruskal-Wallis tests as appropriate. A total of 34 fetuses were studied. There was no significant difference in neuroapoptosis observed in fetuses exposed to 2% isoflurane for 1 hour or 4% isoflurane for 3 hours. Increased neuroapoptosis was observed in the frontal cortex following repeated 2

Calbindin D-28k and parvalbumin immunoreactivity in the frontal cortex in patients with frontal lobe dementia of non-Alzheimer type associated with amyotrophic lateral sclerosis.

PubMed Central

Ferrer, I; Tuñón, T; Serrano, M T; Casas, R; Alcántara, S; Zújar, M J; Rivera, R M

1993-01-01

The morphology and distribution of local-circuit neurons (interneurons) were examined, by calbindin D-28k and parvalbumin immunocytochemistry, in the frontal cortex (area 8) in two patients with frontal lobe dementia of non-Alzheimer type associated with classical amyotrophic lateral sclerosis (ALS), and in seven normal cases. The density of calbindin D-28k immunoreactive cells was dramatically reduced in ALS patients, but the density of parvalbumin-immunoreactive neurons was preserved. Decreased density of calbindin D-28k-immunoreactive neurons, which are mainly located in the upper cortical layers, may interfere with the normal processing of cortico-cortical connections, whereas integrity of parvalbumin-immunoreactive cells may be associated with the preservation of the major inhibitory intracortical circuits in patients with frontal lobe dementia. Images PMID:8459241

Amyotrophic lateral sclerosis, gene deregulation in the anterior horn of the spinal cord and frontal cortex area 8: implications in frontotemporal lobar degeneration

PubMed Central

Andrés-Benito, Pol; Moreno, Jesús; Aso, Ester; Povedano, Mónica; Ferrer, Isidro

2017-01-01

Transcriptome arrays identifies 747 genes differentially expressed in the anterior horn of the spinal cord and 2,300 genes differentially expressed in frontal cortex area 8 in a single group of typical sALS cases without frontotemporal dementia compared with age-matched controls. Main up-regulated clusters in the anterior horn are related to inflammation and apoptosis; down-regulated clusters are linked to axoneme structures and protein synthesis. In contrast, up-regulated gene clusters in frontal cortex area 8 involve neurotransmission, synaptic proteins and vesicle trafficking, whereas main down-regulated genes cluster into oligodendrocyte function and myelin-related proteins. RT-qPCR validates the expression of 58 of 66 assessed genes from different clusters. The present results: a. reveal regional differences in de-regulated gene expression between the anterior horn of the spinal cord and frontal cortex area 8 in the same individuals suffering from sALS; b. validate and extend our knowledge about the complexity of the inflammatory response in the anterior horn of the spinal cord; and c. identify for the first time extensive gene up-regulation of neurotransmission and synaptic-related genes, together with significant down-regulation of oligodendrocyte- and myelin-related genes, as important contributors to the pathogenesis of frontal cortex alterations in the sALS/frontotemporal lobar degeneration spectrum complex at stages with no apparent cognitive impairment. PMID:28283675

Treatment of obstructive sleep apnoea-hypopnea syndrome by mandible advanced device reduced neuron apoptosis in frontal cortex of rabbits.

PubMed

Lu, Hai-Yan; Wang, Wen; Zhou, Zheng; Liu, Chun-Yan; Liu, Ye; Xiao, Wei; Dong, Fu-Sheng; Wang, Jie

2018-05-25

To investigate effects of mandible advanced device (MAD) therapy for obstructive sleep apnoea-hypopnea syndrome (OSAHS) on the neuron apoptosis and acetylcholine esterase activity in frontal cortex. Thirty male New Zealand white rabbits were randomly divided into three groups (n = 10 in each group): group OSAHS, group MAD, and control group. Hydrophilic polyacrylamide gel was injected into soft palate of the animals to induce OSAHS in group OSAHS and group MAD. The group MAD animals wore MAD to relief the obstructiveness. The control group was not given any treatment. Computed tomography (CT) examination of the upper airway and polysomnography (PSG) recordings were performed in supine position. All rabbits were induced to sleep in a supine position for 4 to 6 hours every day and were observed for consecutive 8 weeks. The frontal cortices of three groups were dissected and the neuron apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and flow cytometry. Acetylcholine esterase (AchE) activity in the frontal cortex was measured by spectrophotometry. The group OSAHS exhibited high neuron apoptosis rate and low AchE activity than those of group MAD and control group. The blood oxygen saturation was negatively correlated with neuronal apoptosis rate and positively correlated with AchE activity. Applying MAD in OSAHS animals significantly improve the neuronal damage and function deficits by apnoea-hypoxia caused by narrowed upper airway. This study provided evidence that MAD therapy for OSAHS can significantly decrease neuronal apoptosis and increase AchE activity in the frontal cortex.

An Herbal Nasal Drop Enhanced Frontal and Anterior Cingulate Cortex Activity

PubMed Central

Chan, Agnes S.; Cheung, Mei-chun; Sze, Sophia L.; Leung, Winnie W.; Shi, Dejian

2011-01-01

The present study examined the neuro-electrophysiological activity of the brain associated with the application of a herbal remedy developed by a Shaolin monk based upon the Chan healing principle of clearing the orifices (i.e., the nasal cavities). A repeated-measures design was used. Fourteen normal adults were administered herbal remedy and saline solution intranasally on separate sessions. Two intervals of eyes-closed resting EEG data were obtained individually before and after each administration. Results showed that only the herbal remedy but not the saline solution induced elevation in cordance, an index correlated with cerebral perfusion, in the anterior brain region. In addition, the activity of the anterior cingulate cortex (ACC), as examined by the LORETA analysis, was also increased after the application of the herbal remedy but not saline solution. The present study provided some preliminary evidence suggesting that the herbal nasal drop enhanced the activity of the frontal lobe and ACC. Implications for the potential clinical application of the herbal remedy to treat patients with frontal lobe disorders were discussed. PMID:19996154

Amygdala Contributions to Stimulus–Reward Encoding in the Macaque Medial and Orbital Frontal Cortex during Learning

PubMed Central

Averbeck, Bruno B.

2017-01-01

Orbitofrontal cortex (OFC), medial frontal cortex (MFC), and amygdala mediate stimulus–reward learning, but the mechanisms through which they interact are unclear. Here, we investigated how neurons in macaque OFC and MFC signaled rewards and the stimuli that predicted them during learning with and without amygdala input. Macaques performed a task that required them to evaluate two stimuli and then choose one to receive the reward associated with that option. Four main findings emerged. First, amygdala lesions slowed the acquisition and use of stimulus–reward associations. Further analyses indicated that this impairment was due, at least in part, to ineffective use of negative feedback to guide subsequent decisions. Second, the activity of neurons in OFC and MFC rapidly evolved to encode the amount of reward associated with each stimulus. Third, amygdalectomy reduced encoding of stimulus–reward associations during the evaluation of different stimuli. Reward encoding of anticipated and received reward after choices were made was not altered. Fourth, amygdala lesions led to an increase in the proportion of neurons in MFC, but not OFC, that encoded the instrumental response that monkeys made on each trial. These correlated changes in behavior and neural activity after amygdala lesions strongly suggest that the amygdala contributes to the ability to learn stimulus–reward associations rapidly by shaping encoding within OFC and MFC. SIGNIFICANCE STATEMENT Altered functional interactions among orbital frontal cortex (OFC), medial frontal cortex (MFC), and amygdala are thought to underlie several psychiatric conditions, many related to reward learning. Here, we investigated the causal contribution of the amygdala to the development of neuronal activity in macaque OFC and MFC related to rewards and the stimuli that predict them during learning. Without amygdala inputs, neurons in both OFC and MFC showed decreased encoding of stimulus–reward associations. MFC also

Prenatal exposure to moderate levels of ethanol alters social behavior in adult rats: relationship to structural plasticity and immediate early gene expression in frontal cortex.

PubMed

Hamilton, Derek A; Akers, Katherine G; Rice, James P; Johnson, Travis E; Candelaria-Cook, Felicha T; Maes, Levi I; Rosenberg, Martina; Valenzuela, C Fernando; Savage, Daniel D

2010-03-05

The goals of the present study were to characterize the effects of prenatal exposure to moderate levels of ethanol on adult social behavior, and to evaluate fetal-ethanol-related effects on dendritic morphology, structural plasticity and activity-related immediate early gene (IEG) expression in the agranular insular (AID) and prelimbic (Cg3) regions of frontal cortex. Baseline fetal-ethanol-related alterations in social behavior were limited to reductions in social investigation in males. Repeated experience with novel cage-mates resulted in comparable increases in wrestling and social investigation among saccharin- and ethanol-exposed females, whereas social behavioral effects among males were more evident in ethanol-exposed animals. Male ethanol-exposed rats also displayed profound increases in wrestling when social interaction was motivated by 24h of isolation. Baseline decreases in dendritic length and spine density in AID were observed in ethanol-exposed rats that were always housed with the same cage-mate. Modest experience-related decreases in dendritic length and spine density in AID were observed in saccharin-exposed rats housed with various cage-mates. In contrast, fetal-ethanol-exposed rats displayed experience-related increases in dendritic length in AID, and no experience-related changes in spine density. The only effect observed in Cg3 was a baseline increase in basilar dendritic length among male ethanol-exposed rats. Robust increases in activity-related IEG expression in AID (c-fos and Arc) and Cg3 (c-fos) were observed following social interaction in saccharin-exposed rats, however, activity-related increases in IEG expression were not observed in fetal-ethanol-exposed rats in either region. The results indicate that deficits in social behavior are among the long-lasting behavioral consequences of moderate ethanol exposure during brain development, and implicate AID, and to a lesser degree Cg3, in fetal-ethanol-related social behavior abnormalities

Abnormal structural connectivity between the basal ganglia, thalamus, and frontal cortex in patients with disorders of consciousness.

PubMed

Weng, Ling; Xie, Qiuyou; Zhao, Ling; Zhang, Ruibin; Ma, Qing; Wang, Junjing; Jiang, Wenjie; He, Yanbin; Chen, Yan; Li, Changhong; Ni, Xiaoxiao; Xu, Qin; Yu, Ronghao; Huang, Ruiwang

2017-05-01

Consciousness loss in patients with severe brain injuries is associated with reduced functional connectivity of the default mode network (DMN), fronto-parietal network, and thalamo-cortical network. However, it is still unclear if the brain white matter connectivity between the above mentioned networks is changed in patients with disorders of consciousness (DOC). In this study, we collected diffusion tensor imaging (DTI) data from 13 patients and 17 healthy controls, constructed whole-brain white matter (WM) structural networks with probabilistic tractography. Afterward, we estimated and compared topological properties, and revealed an altered structural organization in the patients. We found a disturbance in the normal balance between segregation and integration in brain structural networks and detected significantly decreased nodal centralities primarily in the basal ganglia and thalamus in the patients. A network-based statistical analysis detected a subnetwork with uniformly significantly decreased structural connections between the basal ganglia, thalamus, and frontal cortex in the patients. Further analysis indicated that along the WM fiber tracts linking the basal ganglia, thalamus, and frontal cortex, the fractional anisotropy was decreased and the radial diffusivity was increased in the patients compared to the controls. Finally, using the receiver operating characteristic method, we found that the structural connections within the NBS-derived component that showed differences between the groups demonstrated high sensitivity and specificity (>90%). Our results suggested that major consciousness deficits in DOC patients may be related to the altered WM connections between the basal ganglia, thalamus, and frontal cortex. Copyright © 2017 Elsevier Ltd. All rights reserved.

Intra- and Interindividual Differences in Lateralized Cognitive Performance and Asymmetrical EEG Activity in the Frontal Cortex

ERIC Educational Resources Information Center

Papousek, Ilona; Murhammer, Daniela; Schulter, Gunter

2011-01-01

The study shows that changes in relative verbal vs. figural working memory and fluency performance from one session to a second session two to 3 weeks apart covary with spontaneously occurring changes of cortical asymmetry in the lateral frontal and central cortex, measured by electroencephalography (EEG) in resting conditions before the execution…

[Effects of the removal of the orbito-frontal cortex on the development of reflex analgesia].

PubMed

Reshetniak, V K; Kukushkin, M L

1989-07-01

The authors studied the effect of electric acupuncture stimulation (EAP) on the changes in pain thresholds prior to and after removal of the orbito-frontal cortex (OFC) of the brain in behavioral experiments on adult cats. Removal of OFC increased the thresholds of pain response at the 4th and the 5th levels of the conventional scale, reflecting emotionally-affective manifestations of pain, and intensified the effect of antinociceptive EAP. The results obtained are analysed in relation to the inhibitory tonic effect of OFC on antinociceptive structures of the brain. Different effects of OFC and somatosensory cortex on the antinociceptive structures of the brain are discussed.

Facilitation of learning and modulation of frontal cortex acetylcholine by ventral pallidal injection of heparin glucosaminoglycan.

PubMed

De Souza Silva, M A; Jezek, K; Weth, K; Müller, H W; Huston, J P; Brandao, M L; Hasenöhrl, R U

2002-01-01

We examined the effects of heparin on learning and frontal cortex acetylcholine parameters following injection of the glucosaminoglycan into the ventral pallidum. In Experiment 1, possible mnemoactive effects of intrapallidal heparin injection were assessed. Rats with chronically implanted cannulae were administered heparin (0.1, 1.0, 10 ng) or vehicle (0.5 microl) and were tested on a one-trial step-through avoidance task. Two retention tests were carried out in each animal, one at 1.5 h after training to measure short-term memory and another at 24 h to measure long-term memory. Post-trial intrapallidal injection of 1.0 ng heparin improved both short- and long-term retention of the task, whereas the lower and the higher dose of the glucosaminoglycan had no effect. When the effective dose of heparin was injected 5 h, rather than immediately after training, it no longer facilitated long-term retention of the conditioned avoidance response. In Experiment 2, the effects of ventral pallidal heparin injection on frontal cortex acetylcholine and choline concentrations were investigated with in vivo microdialysis in anaesthetized rats. Heparin, administered in the dose of 1.0 ng, which was effective in facilitating avoidance performance, produced a delayed increase in cortical acetylcholine levels ipsi- and contralaterally to the side of intrabasalis injection, resembling the known neurochemical effects obtained for another glycosaminoglycan, chondroitin sulfate, which recently was shown to facilitate inhibitory avoidance learning and to increase frontal cortex acetylcholine. The present findings indicate that heparin, like other extracellular matrix proteoglycans, can exert beneficial effects on memory and strengthen the presumptive relationship between such promnestic effects of proteoglycans and basal forebrain cholinergic mechanisms. The data are discussed with respect to the presumed roles of matrix molecules in extrasynaptic volume transmission and in the 'cross

Reduced frontal cortex thickness and cortical volume associated with pathological narcissism.

PubMed

Mao, Yu; Sang, Na; Wang, Yongchao; Hou, Xin; Huang, Hui; Wei, Dongtao; Zhang, Jinfu; Qiu, Jiang

2016-07-22

Pathological narcissism is often characterized by arrogant behavior, a lack of empathy, and willingness to exploit other individuals. Generally, individuals with high levels of narcissism are more likely to suffer mental disorders. However, the brain structural basis of individual pathological narcissism trait among healthy people has not yet been investigated with surface-based morphometry. Thus, in this study, we investigated the relationship between cortical thickness (CT), cortical volume (CV), and individual pathological narcissism in a large healthy sample of 176 college students. Multiple regression was used to analyze the correlation between regional CT, CV, and the total Pathological Narcissism Inventory (PNI) score, adjusting for age, sex, and total intracranial volume. The results showed that the PNI score was significantly negatively associated with CT and CV in the right dorsolateral prefrontal cortex (DLPFC, key region of the central executive network, CEN), which might be associated with impaired emotion regulation processes. Furthermore, the PNI score showed significant negative associations with CV in the right postcentral gyrus, left medial prefrontal cortex (MPFC), and the CT in the right inferior frontal cortex (IFG, overlap with social brain network), which may be related to impairments in social cognition. Together, these findings suggest a unique structural basis for individual differences in pathological narcissism, distributed across different gray matter regions of the social brain network and CEN. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Midline Frontal Cortex Low-Frequency Activity Drives Subthalamic Nucleus Oscillations during Conflict

PubMed Central

Zavala, Baltazar A.; Tan, Huiling; Little, Simon; Ashkan, Keyoumars; Hariz, Marwan; Foltynie, Thomas; Zrinzo, Ludvic; Zaghloul, Kareem A.

2014-01-01

Making the right decision from conflicting information takes time. Recent computational, electrophysiological, and clinical studies have implicated two brain areas as being crucial in assuring sufficient time is taken for decision-making under conditions of conflict: the medial prefrontal cortex and the subthalamic nucleus (STN). Both structures exhibit an elevation of activity at low frequencies (<10 Hz) during conflict that correlates with the amount of time taken to respond. This suggests that the two sites could become functionally coupled during conflict. To establish the nature of this interaction we recorded from deep-brain stimulation electrodes implanted bilaterally in the STN of 13 Parkinson's disease patients while they performed a sensory integration task involving randomly moving dots. By gradually increasing the number of dots moving coherently in one direction, we were able to determine changes in the STN associated with response execution. Furthermore, by occasionally having 10% of the dots move in the opposite direction as the majority, we were able to identify an independent increase in STN theta-delta activity triggered by conflict. Crucially, simultaneous midline frontal electroencephalographic recordings revealed an increase in the theta-delta band coherence between the two structures that was specific to high-conflict trials. Activity over the midline frontal cortex was Granger causal to that in STN. These results establish the cortico-subcortical circuit enabling successful choices to be made under conditions of conflict and provide support for the hypothesis that the brain uses frequency-specific channels of communication to convey behaviorally relevant information. PMID:24849364

Midline frontal cortex low-frequency activity drives subthalamic nucleus oscillations during conflict.

PubMed

Zavala, Baltazar A; Tan, Huiling; Little, Simon; Ashkan, Keyoumars; Hariz, Marwan; Foltynie, Thomas; Zrinzo, Ludvic; Zaghloul, Kareem A; Brown, Peter

2014-05-21

Making the right decision from conflicting information takes time. Recent computational, electrophysiological, and clinical studies have implicated two brain areas as being crucial in assuring sufficient time is taken for decision-making under conditions of conflict: the medial prefrontal cortex and the subthalamic nucleus (STN). Both structures exhibit an elevation of activity at low frequencies (<10 Hz) during conflict that correlates with the amount of time taken to respond. This suggests that the two sites could become functionally coupled during conflict. To establish the nature of this interaction we recorded from deep-brain stimulation electrodes implanted bilaterally in the STN of 13 Parkinson's disease patients while they performed a sensory integration task involving randomly moving dots. By gradually increasing the number of dots moving coherently in one direction, we were able to determine changes in the STN associated with response execution. Furthermore, by occasionally having 10% of the dots move in the opposite direction as the majority, we were able to identify an independent increase in STN theta-delta activity triggered by conflict. Crucially, simultaneous midline frontal electroencephalographic recordings revealed an increase in the theta-delta band coherence between the two structures that was specific to high-conflict trials. Activity over the midline frontal cortex was Granger causal to that in STN. These results establish the cortico-subcortical circuit enabling successful choices to be made under conditions of conflict and provide support for the hypothesis that the brain uses frequency-specific channels of communication to convey behaviorally relevant information. Copyright © 2014 Zavala et al.

Propofol attenuates low-frequency fluctuations of resting-state fMRI BOLD signal in the anterior frontal cortex upon loss of consciousness

PubMed Central

Liu, Xiaolin; Lauer, Kathryn K.; Ward, B. Douglas; Roberts, Christopher; Liu, Suyan; Gollapudy, Suneeta; Rohloff, Robert; Gross, William; Chen, Guangyu; Xu, Zhan; Binder, Jeffrey R.; Li, Shi-Jiang; Hudetz, Anthony G.

2017-01-01

Recent studies indicate that spontaneous low-frequency fluctuations (LFFs) of resting-state functional magnetic resonance imaging (rs-fMRI) blood oxygen level-dependent (BOLD) signals are driven by the slow (<0.1 Hz) modulation of ongoing neuronal activity synchronized locally and across remote brain regions. How regional LFFs of the BOLD fMRI signal are altered during anesthetic-induced alteration of consciousness is not well understood. Using rs-fMRI in 15 healthy participants, we show that during administration of propofol to achieve loss of behavioral responsiveness indexing unconsciousness, the fractional amplitude of LFF (fALFF index) was reduced in comparison to wakeful baseline in the anterior frontal regions, temporal pole, hippocampus, parahippocampal gyrus, and amygdala. Such changes were absent in large areas of the motor, parietal, and sensory cortices. During light sedation characterized by the preservation of overt responsiveness and therefore consciousness, fALFF was reduced in the subcortical areas, temporal pole, medial orbital frontal cortex, cingulate cortex, and cerebellum. Between light sedation and deep sedation, fALFF was reduced primarily in the medial and dorsolateral frontal areas. The preferential reduction of LFFs in the anterior frontal regions is consistent with frontal to sensory-motor cortical disconnection and may contribute to the suppression of consciousness during general anesthesia. PMID:27993673

Greater Activity in the Frontal Cortex on Left Curves: A Vector-Based fNIRS Study of Left and Right Curve Driving.

PubMed

Oka, Noriyuki; Yoshino, Kayoko; Yamamoto, Kouji; Takahashi, Hideki; Li, Shuguang; Sugimachi, Toshiyuki; Nakano, Kimihiko; Suda, Yoshihiro; Kato, Toshinori

2015-01-01

In the brain, the mechanisms of attention to the left and the right are known to be different. It is possible that brain activity when driving also differs with different horizontal road alignments (left or right curves), but little is known about this. We found driver brain activity to be different when driving on left and right curves, in an experiment using a large-scale driving simulator and functional near-infrared spectroscopy (fNIRS). The participants were fifteen healthy adults. We created a course simulating an expressway, comprising straight line driving and gentle left and right curves, and monitored the participants under driving conditions, in which they drove at a constant speed of 100 km/h, and under non-driving conditions, in which they simply watched the screen (visual task). Changes in hemoglobin concentrations were monitored at 48 channels including the prefrontal cortex, the premotor cortex, the primary motor cortex and the parietal cortex. From orthogonal vectors of changes in deoxyhemoglobin and changes in oxyhemoglobin, we calculated changes in cerebral oxygen exchange, reflecting neural activity, and statistically compared the resulting values from the right and left curve sections. Under driving conditions, there were no sites where cerebral oxygen exchange increased significantly more during right curves than during left curves (p > 0.05), but cerebral oxygen exchange increased significantly more during left curves (p < 0.05) in the right premotor cortex, the right frontal eye field and the bilateral prefrontal cortex. Under non-driving conditions, increases were significantly greater during left curves (p < 0.05) only in the right frontal eye field. Left curve driving was thus found to require more brain activity at multiple sites, suggesting that left curve driving may require more visual attention than right curve driving. The right frontal eye field was activated under both driving and non-driving conditions.

Enoxacin Elevates MicroRNA Levels in Rat Frontal Cortex and Prevents Learned Helplessness

PubMed Central

Smalheiser, Neil R.; Zhang, Hui; Dwivedi, Yogesh

2014-01-01

Major depressive disorder (MDD) is a major public health concern. Despite tremendous advancement, the pathogenic mechanisms associated with MDD are still unclear. Moreover, a significant number of MDD subjects do not respond to the currently available medication. MicroRNAs (miRNAs) are a class of small non-coding RNAs that control gene expression by modulating translation, mRNA degradation or stability of mRNA targets. The role of miRNAs in disease pathophysiology is emerging rapidly. Recently, we reported that miRNA expression is down-regulated in frontal cortex of depressed suicide subjects, and that rats exposed to repeated inescapable shock show differential miRNA changes depending on whether they exhibited normal adaptive responses or learned helpless (LH) behavior. Enoxacin, a fluoroquinolone used clinically as an anti-bacterial compound, enhances the production of miRNAs in vitro and in peripheral tissues in vivo, but has not yet been tested as an experimental tool to study the relation of miRNA expression to neural functions or behavior. Treatment of rats with 10 or 25 mg/kg enoxacin for 1 week increased the expression of miRNAs in frontal cortex and decreased the proportion of rats exhibiting LH behavior following inescapable shock. Further studies are warranted to learn whether enoxacin may ameliorate depressive behavior in other rodent paradigms and in human clinical situations, and if so whether its mechanism is due to upregulation of miRNAs. PMID:24575053

Amygdala Contributions to Stimulus-Reward Encoding in the Macaque Medial and Orbital Frontal Cortex during Learning.

PubMed

Rudebeck, Peter H; Ripple, Joshua A; Mitz, Andrew R; Averbeck, Bruno B; Murray, Elisabeth A

2017-02-22

Orbitofrontal cortex (OFC), medial frontal cortex (MFC), and amygdala mediate stimulus-reward learning, but the mechanisms through which they interact are unclear. Here, we investigated how neurons in macaque OFC and MFC signaled rewards and the stimuli that predicted them during learning with and without amygdala input. Macaques performed a task that required them to evaluate two stimuli and then choose one to receive the reward associated with that option. Four main findings emerged. First, amygdala lesions slowed the acquisition and use of stimulus-reward associations. Further analyses indicated that this impairment was due, at least in part, to ineffective use of negative feedback to guide subsequent decisions. Second, the activity of neurons in OFC and MFC rapidly evolved to encode the amount of reward associated with each stimulus. Third, amygdalectomy reduced encoding of stimulus-reward associations during the evaluation of different stimuli. Reward encoding of anticipated and received reward after choices were made was not altered. Fourth, amygdala lesions led to an increase in the proportion of neurons in MFC, but not OFC, that encoded the instrumental response that monkeys made on each trial. These correlated changes in behavior and neural activity after amygdala lesions strongly suggest that the amygdala contributes to the ability to learn stimulus-reward associations rapidly by shaping encoding within OFC and MFC. SIGNIFICANCE STATEMENT Altered functional interactions among orbital frontal cortex (OFC), medial frontal cortex (MFC), and amygdala are thought to underlie several psychiatric conditions, many related to reward learning. Here, we investigated the causal contribution of the amygdala to the development of neuronal activity in macaque OFC and MFC related to rewards and the stimuli that predict them during learning. Without amygdala inputs, neurons in both OFC and MFC showed decreased encoding of stimulus-reward associations. MFC also showed

Using fNIRS to Examine Occipital and Temporal Responses to Stimulus Repetition in Young Infants: Evidence of Selective Frontal Cortex Involvement

PubMed Central

Emberson, Lauren L.; Cannon, Grace; Palmeri, Holly; Richards, John E.; Aslin, Richard N.

2016-01-01

How does the developing brain respond to recent experience? Repetition suppression (RS) is a robust and well-characterized response of to recent experience found, predominantly, in the perceptual cortices of the adult brain. We use functional near-infrared spectroscopy (fNIRS) to investigate how perceptual (temporal and occipital) and frontal cortices in the infant brain respond to auditory and visual stimulus repetitions (spoken words and faces). In Experiment 1, we find strong evidence of repetition suppression in the frontal cortex but only for auditory stimuli. In perceptual cortices, we find only suggestive evidence of auditory RS in the temporal cortex and no evidence of visual RS in any ROI. In Experiments 2 and 3, we replicate and extend these findings. Overall, we provide the first evidence that infant and adult brains respond differently to stimulus repetition. We suggest that the frontal lobe may support the development of RS in perceptual cortices. PMID:28012401

Near-infrared measurements of hemodynamic and oxygenation changes on the frontal cortex during breath holding, hyperventilation, and natural sleep

NASA Astrophysics Data System (ADS)

Noponen, Tommi E.; Kotilahti, Kalle; Toppila, Jussi; Nissila, Ilkka T.; Salmi, Tapani; Kajava, Timo T.; Katila, Toivo E.

2003-07-01

We have developed a frequency-domain near-infrared device suitable for physiological studies in human. In this work, a four-channel configuration of the instrument is applied to monitor hemodynamic and oxygenation changes in the frontal cortex of volunteers during different ventilation tasks. We use four different source-receiver separations (2, 3, 4, and 5 cm) and three wavelengths (760, 808, and 830 nm) to test the sensitivity of these parameters to cardiovascular and metabolic changes. Low-frequency oscillations (~ 0.02 Hz) and variations in heart rate during different ventilation tasks are investigated as well. We also study physiological changes during natural sleep using the frequency-domain instrument simultaneously with a polysomnography system containing a pulse oximeter. Our results indicate that hemodynamic and oxygenation changes in the frontal cortex during natural sleep can be detected using near-infrared measurements.

Less efficient and costly processes of frontal cortex in childhood chronic fatigue syndrome.

PubMed

Mizuno, Kei; Tanaka, Masaaki; Tanabe, Hiroki C; Joudoi, Takako; Kawatani, Junko; Shigihara, Yoshihito; Tomoda, Akemi; Miike, Teruhisa; Imai-Matsumura, Kyoko; Sadato, Norihiro; Watanabe, Yasuyoshi

2015-01-01

The ability to divide one's attention deteriorates in patients with childhood chronic fatigue syndrome (CCFS). We conducted a study using a dual verbal task to assess allocation of attentional resources to two simultaneous activities (picking out vowels and reading for story comprehension) and functional magnetic resonance imaging. Patients exhibited a much larger area of activation, recruiting additional frontal areas. The right middle frontal gyrus (MFG), which is included in the dorsolateral prefrontal cortex, of CCFS patients was specifically activated in both the single and dual tasks; this activation level was positively correlated with motivation scores for the tasks and accuracy of story comprehension. In addition, in patients, the dorsal anterior cingulate gyrus (dACC) and left MFG were activated only in the dual task, and activation levels of the dACC and left MFG were positively associated with the motivation and fatigue scores, respectively. Patients with CCFS exhibited a wider area of activated frontal regions related to attentional resources in order to increase their poorer task performance with massive mental effort. This is likely to be less efficient and costly in terms of energy requirements. It seems to be related to the pathophysiology of patients with CCFS and to cause a vicious cycle of further increases in fatigue.

Less efficient and costly processes of frontal cortex in childhood chronic fatigue syndrome

PubMed Central

Mizuno, Kei; Tanaka, Masaaki; Tanabe, Hiroki C.; Joudoi, Takako; Kawatani, Junko; Shigihara, Yoshihito; Tomoda, Akemi; Miike, Teruhisa; Imai-Matsumura, Kyoko; Sadato, Norihiro; Watanabe, Yasuyoshi

2015-01-01

The ability to divide one's attention deteriorates in patients with childhood chronic fatigue syndrome (CCFS). We conducted a study using a dual verbal task to assess allocation of attentional resources to two simultaneous activities (picking out vowels and reading for story comprehension) and functional magnetic resonance imaging. Patients exhibited a much larger area of activation, recruiting additional frontal areas. The right middle frontal gyrus (MFG), which is included in the dorsolateral prefrontal cortex, of CCFS patients was specifically activated in both the single and dual tasks; this activation level was positively correlated with motivation scores for the tasks and accuracy of story comprehension. In addition, in patients, the dorsal anterior cingulate gyrus (dACC) and left MFG were activated only in the dual task, and activation levels of the dACC and left MFG were positively associated with the motivation and fatigue scores, respectively. Patients with CCFS exhibited a wider area of activated frontal regions related to attentional resources in order to increase their poorer task performance with massive mental effort. This is likely to be less efficient and costly in terms of energy requirements. It seems to be related to the pathophysiology of patients with CCFS and to cause a vicious cycle of further increases in fatigue. PMID:26594619

Microglia recapitulate a hematopoietic master regulator network in the aging human frontal cortex

PubMed Central

Wehrspaun, Claudia C.; Haerty, Wilfried; Ponting, Chris P.

2015-01-01

Microglia form the immune system of the brain. Previous studies in cell cultures and animal models suggest altered activation states and cellular senescence in the aged brain. Instead, we analyzed 3 transcriptome data sets from the postmortem frontal cortex of 381 control individuals to show that microglia gene markers assemble into a transcriptional module in a gene coexpression network. These markers predominantly represented M1 and M1/M2b activation phenotypes. Expression of genes in this module generally declines over the adult life span. This decrease was more pronounced in microglia surface receptors for microglia and/or neuron crosstalk than in markers for activation state phenotypes. In addition to these receptors for exogenous signals, microglia are controlled by brain-expressed regulatory factors. We identified a subnetwork of transcription factors, including RUNX1, IRF8, PU.1, and TAL1, which are master regulators (MRs) for the age-dependent microglia module. The causal contributions of these MRs on the microglia module were verified using publicly available ChIP-Seq data. Interactions of these key MRs were preserved in a protein-protein interaction network. Importantly, these MRs appear to be essential for regulating microglia homeostasis in the adult human frontal cortex in addition to their crucial roles in hematopoiesis and myeloid cell-fate decisions during embryogenesis. PMID:26002684

Parallel pathways from whisker and visual sensory cortices to distinct frontal regions of mouse neocortex

PubMed Central

Sreenivasan, Varun; Kyriakatos, Alexandros; Mateo, Celine; Jaeger, Dieter; Petersen, Carl C.H.

2016-01-01

Abstract. The spatial organization of mouse frontal cortex is poorly understood. Here, we used voltage-sensitive dye to image electrical activity in the dorsal cortex of awake head-restrained mice. Whisker-deflection evoked the earliest sensory response in a localized region of primary somatosensory cortex and visual stimulation evoked the earliest responses in a localized region of primary visual cortex. Over the next milliseconds, the initial sensory response spread within the respective primary sensory cortex and into the surrounding higher order sensory cortices. In addition, secondary hotspots in the frontal cortex were evoked by whisker and visual stimulation, with the frontal hotspot for whisker deflection being more anterior and lateral compared to the frontal hotspot evoked by visual stimulation. Investigating axonal projections, we found that the somatosensory whisker cortex and the visual cortex directly innervated frontal cortex, with visual cortex axons innervating a region medial and posterior to the innervation from somatosensory cortex, consistent with the location of sensory responses in frontal cortex. In turn, the axonal outputs of these two frontal cortical areas innervate distinct regions of striatum, superior colliculus, and brainstem. Sensory input, therefore, appears to map onto modality-specific regions of frontal cortex, perhaps participating in distinct sensorimotor transformations, and directing distinct motor outputs. PMID:27921067

Long-term continuous corticosterone treatment decreases VEGF receptor-2 expression in frontal cortex.

PubMed

Howell, Kristy R; Kutiyanawalla, Ammar; Pillai, Anilkumar

2011-01-01

Stress and increased glucocorticoid levels are associated with many neuropsychiatric disorders including schizophrenia and depression. Recently, the role of vascular endothelial factor receptor-2 (VEGFR2/Flk1) signaling has been implicated in stress-mediated neuroplasticity. However, the mechanism of regulation of VEGF/Flk1 signaling under long-term continuous glucocorticoid exposure has not been elucidated. We examined the possible effects of long-term continuous glucocorticoid exposure on VEGF/Flk1 signaling in cultured cortical neurons in vitro, mouse frontal cortex in vivo, and in post mortem human prefrontal cortex of both control and schizophrenia subjects. We found that long-term continuous exposure to corticosterone (CORT, a natural glucocorticoid) reduced Flk1 protein levels both in vitro and in vivo. CORT treatment resulted in alterations in signaling molecules downstream to Flk1 such as PTEN, Akt and mTOR. We demonstrated that CORT-induced changes in Flk1 levels are mediated through glucocorticoid receptor (GR) and calcium. A significant reduction in Flk1-GR interaction was observed following CORT exposure. Interestingly, VEGF levels were increased in cortex, but decreased in serum following CORT treatment. Moreover, significant reductions in Flk1 and GR protein levels were found in postmortem prefrontal cortex samples from schizophrenia subjects. The alterations in VEGF/Flk1 signaling following long-term continuous CORT exposure represents a molecular mechanism of the neurobiological effects of chronic stress.

Propofol attenuates low-frequency fluctuations of resting-state fMRI BOLD signal in the anterior frontal cortex upon loss of consciousness.

PubMed

Liu, Xiaolin; Lauer, Kathryn K; Douglas Ward, B; Roberts, Christopher; Liu, Suyan; Gollapudy, Suneeta; Rohloff, Robert; Gross, William; Chen, Guangyu; Xu, Zhan; Binder, Jeffrey R; Li, Shi-Jiang; Hudetz, Anthony G

2017-02-15

Recent studies indicate that spontaneous low-frequency fluctuations (LFFs) of resting-state functional magnetic resonance imaging (rs-fMRI) blood oxygen level-dependent (BOLD) signals are driven by the slow (<0.1Hz) modulation of ongoing neuronal activity synchronized locally and across remote brain regions. How regional LFFs of the BOLD fMRI signal are altered during anesthetic-induced alteration of consciousness is not well understood. Using rs-fMRI in 15 healthy participants, we show that during administration of propofol to achieve loss of behavioral responsiveness indexing unconsciousness, the fractional amplitude of LFF (fALFF index) was reduced in comparison to wakeful baseline in the anterior frontal regions, temporal pole, hippocampus, parahippocampal gyrus, and amygdala. Such changes were absent in large areas of the motor, parietal, and sensory cortices. During light sedation characterized by the preservation of overt responsiveness and therefore consciousness, fALFF was reduced in the subcortical areas, temporal pole, medial orbital frontal cortex, cingulate cortex, and cerebellum. Between light sedation and deep sedation, fALFF was reduced primarily in the medial and dorsolateral frontal areas. The preferential reduction of LFFs in the anterior frontal regions is consistent with frontal to sensory-motor cortical disconnection and may contribute to the suppression of consciousness during general anesthesia. Copyright © 2016 Elsevier Inc. All rights reserved.

Subliminal semantic priming changes the dynamic causal influence between the left frontal and temporal cortex.

PubMed

Matsumoto, Atsushi; Kakigi, Ryusuke

2014-01-01

Recent neuroimaging experiments have revealed that subliminal priming of a target stimulus leads to the reduction of neural activity in specific regions concerned with processing the target. Such findings lead to questions about the degree to which the subliminal priming effect is based only on decreased activity in specific local brain regions, as opposed to the influence of neural mechanisms that regulate communication between brain regions. To address this question, this study recorded EEG during performance of a subliminal semantic priming task. We adopted an information-based approach that used independent component analysis and multivariate autoregressive modeling. Results indicated that subliminal semantic priming caused significant modulation of alpha band activity in the left inferior frontal cortex and modulation of gamma band activity in the left inferior temporal regions. The multivariate autoregressive approach confirmed significant increases in information flow from the inferior frontal cortex to inferior temporal regions in the early time window that was induced by subliminal priming. In the later time window, significant enhancement of bidirectional causal flow between these two regions underlying subliminal priming was observed. Results suggest that unconscious processing of words influences not only local activity of individual brain regions but also the dynamics of neural communication between those regions.

Common medial frontal mechanisms of adaptive control in humans and rodents

PubMed Central

Frank, Michael J.; Laubach, Mark

2013-01-01

In this report, we describe how common brain networks within the medial frontal cortex facilitate adaptive behavioral control in rodents and humans. We demonstrate that low frequency oscillations below 12 Hz are dramatically modulated after errors in humans over mid-frontal cortex and in rats within prelimbic and anterior cingulate regions of medial frontal cortex. These oscillations were phase-locked between medial frontal cortex and motor areas in both rats and humans. In rats, single neurons that encoded prior behavioral outcomes were phase-coherent with low-frequency field oscillations particularly after errors. Inactivating medial frontal regions in rats led to impaired behavioral adjustments after errors, eliminated the differential expression of low frequency oscillations after errors, and increased low-frequency spike-field coupling within motor cortex. Our results describe a novel mechanism for behavioral adaptation via low-frequency oscillations and elucidate how medial frontal networks synchronize brain activity to guide performance. PMID:24141310

Automated MRI parcellation of the frontal lobe.

PubMed

Ranta, Marin E; Chen, Min; Crocetti, Deana; Prince, Jerry L; Subramaniam, Krish; Fischl, Bruce; Kaufmann, Walter E; Mostofsky, Stewart H

2014-05-01

Examination of associations between specific disorders and physical properties of functionally relevant frontal lobe sub-regions is a fundamental goal in neuropsychiatry. Here, we present and evaluate automated methods of frontal lobe parcellation with the programs FreeSurfer(FS) and TOADS-CRUISE(T-C), based on the manual method described in Ranta et al. [2009]: Psychiatry Res 172:147-154 in which sulcal-gyral landmarks were used to manually delimit functionally relevant regions within the frontal lobe: i.e., primary motor cortex, anterior cingulate, deep white matter, premotor cortex regions (supplementary motor complex, frontal eye field, and lateral premotor cortex) and prefrontal cortex (PFC) regions (medial PFC, dorsolateral PFC, inferior PFC, lateral orbitofrontal cortex [OFC] and medial OFC). Dice's coefficient, a measure of overlap, and percent volume difference were used to measure the reliability between manual and automated delineations for each frontal lobe region. For FS, mean Dice's coefficient for all regions was 0.75 and percent volume difference was 21.2%. For T-C the mean Dice's coefficient was 0.77 and the mean percent volume difference for all regions was 20.2%. These results, along with a high degree of agreement between the two automated methods (mean Dice's coefficient = 0.81, percent volume difference = 12.4%) and a proof-of-principle group difference analysis that highlights the consistency and sensitivity of the automated methods, indicate that the automated methods are valid techniques for parcellation of the frontal lobe into functionally relevant sub-regions. Thus, the methodology has the potential to increase efficiency, statistical power and reproducibility for population analyses of neuropsychiatric disorders with hypothesized frontal lobe contributions. Copyright © 2013 Wiley Periodicals, Inc.

Automated MRI parcellation of the frontal lobe

PubMed Central

Ranta, Marin E.; Chen, Min; Crocetti, Deana; Prince, Jerry L.; Subramaniam, Krish; Fischl, Bruce; Kaufmann, Walter E.; Mostofsky, Stewart H.

2014-01-01

Examination of associations between specific disorders and physical properties of functionally relevant frontal lobe sub-regions is a fundamental goal in neuropsychiatry. Here we present and evaluate automated methods of frontal lobe parcellation with the programs FreeSurfer(FS) and TOADS-CRUISE(T-C), based on the manual method described in Ranta et al. (2009) in which sulcal-gyral landmarks were used to manually delimit functionally relevant regions within the frontal lobe: i.e., primary motor cortex, anterior cingulate, deep white matter, premotor cortex regions (supplementary motor complex, frontal eye field and lateral premotor cortex) and prefrontal cortex (PFC) regions (medial PFC, dorsolateral PFC, inferior PFC, lateral orbitofrontal cortex (OFC) and medial OFC). Dice's coefficient, a measure of overlap, and percent volume difference were used to measure the reliability between manual and automated delineations for each frontal lobe region. For FS, mean Dice's coefficient for all regions was 0.75 and percent volume difference was 21.2%. For T-C the mean Dice's coefficient was 0.77 and the mean percent volume difference for all regions was 20.2%. These results, along with a high degree of agreement between the two automated methods (mean Dice's coefficient = 0.81, percent volume difference = 12.4%) and a proof-of-principle group difference analysis that highlights the consistency and sensitivity of the automated methods, indicate that the automated methods are valid techniques for parcellation of the frontal lobe into functionally relevant sub-regions. Thus, the methodology has the potential to increase efficiency, statistical power and reproducibility for population analyses of neuropsychiatric disorders with hypothesized frontal lobe contributions. PMID:23897577

Greater Activity in the Frontal Cortex on Left Curves: A Vector-Based fNIRS Study of Left and Right Curve Driving

PubMed Central

Oka, Noriyuki; Yoshino, Kayoko; Yamamoto, Kouji; Takahashi, Hideki; Li, Shuguang; Sugimachi, Toshiyuki; Nakano, Kimihiko; Suda, Yoshihiro; Kato, Toshinori

2015-01-01

Objectives In the brain, the mechanisms of attention to the left and the right are known to be different. It is possible that brain activity when driving also differs with different horizontal road alignments (left or right curves), but little is known about this. We found driver brain activity to be different when driving on left and right curves, in an experiment using a large-scale driving simulator and functional near-infrared spectroscopy (fNIRS). Research Design and Methods The participants were fifteen healthy adults. We created a course simulating an expressway, comprising straight line driving and gentle left and right curves, and monitored the participants under driving conditions, in which they drove at a constant speed of 100 km/h, and under non-driving conditions, in which they simply watched the screen (visual task). Changes in hemoglobin concentrations were monitored at 48 channels including the prefrontal cortex, the premotor cortex, the primary motor cortex and the parietal cortex. From orthogonal vectors of changes in deoxyhemoglobin and changes in oxyhemoglobin, we calculated changes in cerebral oxygen exchange, reflecting neural activity, and statistically compared the resulting values from the right and left curve sections. Results Under driving conditions, there were no sites where cerebral oxygen exchange increased significantly more during right curves than during left curves (p > 0.05), but cerebral oxygen exchange increased significantly more during left curves (p < 0.05) in the right premotor cortex, the right frontal eye field and the bilateral prefrontal cortex. Under non-driving conditions, increases were significantly greater during left curves (p < 0.05) only in the right frontal eye field. Conclusions Left curve driving was thus found to require more brain activity at multiple sites, suggesting that left curve driving may require more visual attention than right curve driving. The right frontal eye field was activated under both

Issues in localization of brain function: The case of lateralized frontal cortex in cognition, emotion, and psychopathology.

PubMed

Miller, Gregory A; Crocker, Laura D; Spielberg, Jeffrey M; Infantolino, Zachary P; Heller, Wendy

2013-01-01

The appeal of simple, sweeping portraits of large-scale brain mechanisms relevant to psychological phenomena competes with a rich, complex research base. As a prominent example, two views of frontal brain organization have emphasized dichotomous lateralization as a function of either emotional valence (positive/negative) or approach/avoidance motivation. Compelling findings support each. The literature has struggled to choose between them for three decades, without success. Both views are proving untenable as comprehensive models. Evidence of other frontal lateralizations, involving distinctions among dimensions of depression and anxiety, make a dichotomous view even more problematic. Recent evidence indicates that positive valence and approach motivation are associated with different areas in the left-hemisphere. Findings that appear contradictory at the level of frontal lobes as the units of analysis can be accommodated because hemodynamic and electromagnetic neuroimaging studies suggest considerable functional differentiation, in specialization and activation, of subregions of frontal cortex, including their connectivity to each other and to other regions. Such findings contribute to a more nuanced understanding of functional localization that accommodates aspects of multiple theoretical perspectives.

Issues in localization of brain function: The case of lateralized frontal cortex in cognition, emotion, and psychopathology

PubMed Central

Miller, Gregory A.; Crocker, Laura D.; Spielberg, Jeffrey M.; Infantolino, Zachary P.; Heller, Wendy

2013-01-01

The appeal of simple, sweeping portraits of large-scale brain mechanisms relevant to psychological phenomena competes with a rich, complex research base. As a prominent example, two views of frontal brain organization have emphasized dichotomous lateralization as a function of either emotional valence (positive/negative) or approach/avoidance motivation. Compelling findings support each. The literature has struggled to choose between them for three decades, without success. Both views are proving untenable as comprehensive models. Evidence of other frontal lateralizations, involving distinctions among dimensions of depression and anxiety, make a dichotomous view even more problematic. Recent evidence indicates that positive valence and approach motivation are associated with different areas in the left-hemisphere. Findings that appear contradictory at the level of frontal lobes as the units of analysis can be accommodated because hemodynamic and electromagnetic neuroimaging studies suggest considerable functional differentiation, in specialization and activation, of subregions of frontal cortex, including their connectivity to each other and to other regions. Such findings contribute to a more nuanced understanding of functional localization that accommodates aspects of multiple theoretical perspectives. PMID:23386814

Reduced N-acetylaspartate levels in the frontal cortex of 3,4-methylenedioxymethamphetamine (Ecstasy) users: preliminary results.

PubMed

Reneman, Liesbeth; Majoie, Charles B L M; Flick, Herman; den Heeten, Gerard J

2002-02-01

The perceived safety of the recreational drug methylenedioxymethamphetamine (MDMA), or Ecstasy, conflicts with animal evidence indicating that MDMA damages cortical serotonin (5-HT) neurons at doses similar to those used by humans. Few data are available about the effects of MDMA on the human brain. This study was designed to evaluate MDMA-related alterations in metabolite ratios with single-voxel proton ((1)H) MR spectroscopy. Fifteen male MDMA users (mean lifetime exposure, 723 tablets; mean time since last tablet, 12.0 weeks) and 12 age-matched control subjects underwent single-voxel (1)H MR spectroscopy. N-Acetylaspartate (NAA)/creatine (Cr), NAA/Choline (Cho), and myoinositol (MI)/Cr ratios were measured in midfrontal gray matter, midoccipital gray matter, and right parietal white matter. Data were analyzed with linear model-based multivariate analysis of variance. NAA/Cr (P =.04) and NAA/Cho (P =.03) ratios, markers associated with neuronal loss or dysfunction, were reduced in the frontal cortex of MDMA users. Neither NAA/Cr (P =.72) nor NAA/Cho (P =.12) ratios were different between both groups in occipital gray matter and parietal white matter (P =.18). Extent of previous MDMA use and frontal cortical NAA/Cr (rho = -.50, P =.012) or NAA/Cho (rho = -.550, P <.01) ratios were significantly associated. Reduced NAA/Cr and NAA/Cho ratios at (1)H MR spectroscopy provide evidence for neuronal abnormality in the frontal cortex of MDMA users; these are correlated with the degree of MDMA exposure. These data suggest that MDMA may be a neurotoxin in humans, as it is in animals.

Acute ethanol and taurine intake affect absolute alpha power in frontal cortex before and after exercise.

PubMed

Paulucio, Dailson; da Costa, Bruno M; Santos, Caleb G; Velasques, Bruna; Ribeiro, Pedro; Gongora, Mariana; Cagy, Mauricio; Alvarenga, Renato L; Pompeu, Fernando A M S

2017-09-14

Taurine and alcohol has been popularly ingested through energy drinks. Reports from both compounds shows they are active on nervous system but little is known about the acute effect of these substances on the frontal cortex in an exercise approach. The aim of this study was to determine the effects of 0,6mldL -1 of ethanol (ET), 6g of taurine (TA), and taurine with ethanol (TA+ET) intake on absolute alpha power (AAP) in the frontal region, before and after exercise. Nine participants were recruited, five women (22±3years) and four men (26±5years), for a counterbalanced experimental design. For each treatment, the tests were performed considering three moments: "baseline", "peak" and "post-exercise". In the placebo treatment (PL), the frontal areas showed AAP decrease at the post-exercise. However, in the TA, AAP decreased at peak and increased at post-exercise. In the ET treatment, AAP increased at the peak moment for the left frontal electrodes. In the TA+ET treatment, an AAP increase was observed at peak, and it continued after exercise ended. These substances were able to produce electrocortical activity changes in the frontal regions after a short duration and low intensity exercise. Left and right regions showed different AAP dynamics during peak and post-exercise moments when treatments were compared. Copyright © 2017 Elsevier B.V. All rights reserved.

Reversed Procrastination by Focal Disruption of Medial Frontal Cortex.

PubMed

Jha, Ashwani; Diehl, Beate; Scott, Catherine; McEvoy, Andrew W; Nachev, Parashkev

2016-11-07

An enduring puzzle in the neuroscience of voluntary action is the origin of the remarkably wide dispersion of the reaction time distribution, an interval far greater than is explained by synaptic or signal transductive noise [1, 2]. That we are able to change our planned actions-a key criterion of volition [3]-so close to the time of their onset implies decision-making must reach deep into the execution of action itself [4-6]. It has been influentially suggested the reaction time distribution therefore reflects deliberate neural procrastination [7], giving alternative response tendencies sufficient time for fair competition in pursuing a decision threshold that determines which one is behaviorally manifest: a race model, where action selection and execution are closely interrelated [8-11]. Although the medial frontal cortex exhibits a sensitivity to reaction time on functional imaging that is consistent with such a mechanism [12-14], direct evidence from disruptive studies has hitherto been lacking. If movement-generating and movement-delaying neural substrates are closely co-localized here, a large-scale lesion will inevitably mask any acceleration, for the movement itself could be disrupted. Circumventing this problem, here we observed focal intracranial electrical disruption of the medial frontal wall in the context of the pre-surgical evaluation of two patients with epilepsy temporarily reversing such hypothesized procrastination. Effector-specific behavioral acceleration, time-locked to the period of electrical disruption, occurred exclusively at a specific locus at the ventral border of the pre-supplementary motor area. A cardinal prediction of race models of voluntary action is thereby substantiated in the human brain. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Cognitive flexibility impairment and reduced frontal cortex BDNF expression in the ouabain model of mania

PubMed Central

Amodeo, Dionisio A.; Grospe, Gena; Zang, Hui; Dwivedi, Yogesh; Ragozzino, Michael E.

2016-01-01

Central infusion of the Na+/K+-ATPase inhibitor, ouabain in rats serves as an animal model of mania because it leads to hyperactivity, as well as reproduces ion dysregulation and reduced BDNF levels similar to that observed in bipolar disorder. Bipolar disorder is also associated with cognitive inflexibility and working memory deficits. It is unknown whether ouabain treatment in rats leads to similar cognitive flexibility and working memory deficits. The present study examined the effects of an intracerebral ventricular infusion of ouabain in rats on spontaneous alternation, probabilistic reversal learning and BDNF expression levels in the frontal cortex. Ouabain treatment significantly increased locomotor activity, but did not affect alternation performance in a Y-maze. Ouabain treatment selectively impaired reversal learning in a spatial discrimination task using an 80/20 probabilistic reinforcement procedure. The reversal learning deficit in ouabain-treated rats resulted from an impaired ability to maintain a new choice pattern (increased regressive errors). Ouabain treatment also decreased sensitivity to negative feedback during the initial phase of reversal learning. Expression of BDNF mRNA and protein levels was downregulated in the frontal cortex which also negatively correlated with regressive errors. These findings suggest that the ouabain model of mania may be useful in understanding the neuropathophysiology that contributes to cognitive flexibility deficits and test potential treatments to alleviate cognitive deficits in bipolar disorder. PMID:27267245

Chronometric Electrical Stimulation of Right Inferior Frontal Cortex Increases Motor Braking

PubMed Central

Conner, Christopher R.; Aron, Adam R.; Tandon, Nitin

2013-01-01

The right inferior frontal cortex (rIFC) is important for stopping responses. Recent research shows that it is also activated when response emission is slowed down when stopping is anticipated. This suggests that rIFC also functions as a goal-driven brake. Here, we investigated the causal role of rIFC in goal-driven braking by using computer-controlled, event-related (chronometric), direct electrical stimulation (DES). We compared the effects of rIFC stimulation on trials in which responses were made in the presence versus absence of a stopping-goal (“Maybe Stop” [MS] vs “No Stop” [NS]). We show that DES of rIFC slowed down responses (compared with control-site stimulation) and that rIFC stimulation induced more slowing when motor braking was required (MS) compared with when it was not (NS). Our results strongly support a causal role of a rIFC-based network in inhibitory motor control. Importantly, the results extend this causal role beyond externally driven stopping to goal-driven inhibitory control, which is a richer model of human self-control. These results also provide the first demonstration of double-blind chronometric DES of human prefrontal cortex, and suggest that—in the case of rIFC—this could lead to augmentation of motor braking. PMID:24336725

Changes in acetylcholinesterase, Na+,K+-ATPase, and Mg2+-ATPase activities in the frontal cortex and the hippocampus of hyper- and hypothyroid adult rats.

PubMed

Carageorgiou, Haris; Pantos, Constantinos; Zarros, Apostolos; Stolakis, Vasileios; Mourouzis, Iordanis; Cokkinos, Dennis; Tsakiris, Stylianos

2007-08-01

The thyroid hormones (THs) are crucial determinants of normal development and metabolism, especially in the central nervous system. The metabolic rate is known to increase in hyperthyroidism and decrease in hypothyroidism. The aim of this work was to investigate how changes in metabolism induced by THs could affect the activities of acetylcholinesterase (AChE), (Na+,K+)- and Mg2+-adenosinetriphosphatase (ATPase) in the frontal cortex and the hippocampus of adult rats. Hyperthyroidism was induced by subcutaneous administration of thyroxine (25 microg/100 g body weight) once daily for 14 days, and hypothyroidism was induced by oral administration of propylthiouracil (0.05%) for 21 days. All enzyme activities were evaluated spectrophotometrically in the homogenated brain regions of 10 three-animal pools. A region-specific behavior was observed concerning the examined enzyme activities in hyper- and hypothyroidism. In hyperthyroidism, AChE activity was significantly increased only in the hippocampus (+22%), whereas Na+,K+-ATPase activity was significantly decreased in the hyperthyroid rat hippocampus (-47%) and remained unchanged in the frontal cortex. In hypothyroidism, AChE activity was significantly decreased in the frontal cortex (-23%) and increased in the hippocampus (+21%). Na+,K+-ATPase activity was significantly decreased in both the frontal cortex (-35%) and the hippocampus (-43%) of hypothyroid rats. Mg2+-ATPase remained unchanged in the regions of both hyper- and hypothyroid rat brains. Our data revealed that THs affect the examined adult rat brain parameters in a region- and state-specific way. The TH-reduced Na+,K+-ATPase activity may increase the synaptic acetylcholine release and, thus, modulate AChE activity. Moreover, the above TH-induced changes may affect the monoamine neurotransmitter systems in the examined brain regions.

Effects of Crocin on Learning and Memory in Rats Under Chronic Restraint Stress with Special Focus on the Hippocampal and Frontal Cortex Corticosterone Levels.

PubMed

Dastgerdi, Azadehalsadat Hosseini; Radahmadi, Maryam; Pourshanazari, Ali Asghar; Dastgerdi, Hajaralsadat Hosseini

2017-01-01

Chronic stress adversely influences brain functions while crocin, as an effective component of saffron, exhibits positive effects on memory processes. This study investigated the effects of different doses of crocin on the improvement of learning and memory as well as corticosterone (CORT) levels in the hippocampus and frontal cortex of rats subjected to chronic stress. Forty male rats were randomly allocated to five different groups ( n = 8): Control, sham; stress (6 h/day for 21 days) groups, and two groups receiving daily intraperitoneal injections of one of two doses (30 and 60 mg/kg) of crocin accompanied by 21 days of restraint stress. Latency was evaluated as a brain function using the passive avoidance test before and one-day after a foot shock. CORT levels were measured in the homogenized hippocampus and frontal cortex. Results revealed that chronic stress had a significantly ( P < 0.01) negative effect on memory. Crocin (30 and 60 mg/kg), however, gave increase to significantly ( P < 0.01 and P < 0.05; respectively) improved memory functions in the stressed rats. Furthermore, the CORT levels in the hippocampus and frontal cortex declined significantly ( P < 0.05) in the stress group compared to the control. Only a crocin dose of 30 mg/kg was observed modulate significantly ( P < 0.05) the CORT levels in the hippocampus and frontal cortex in the stressed group. It was found that the lower crocin dose (30 mg/kg) had more beneficial effects than its higher (60 mg/kg) dose on learning and memory under chronic stress conditions. Moreover, it was speculated that different doses of crocin act on different neurotransmitters and biochemical factors in the brain.

The perinatal effects of maternal caffeine intake on fetal and neonatal brain levels of testosterone, estradiol, and dihydrotestosterone in rats.

PubMed

Karaismailoglu, S; Tuncer, M; Bayrak, S; Erdogan, G; Ergun, E L; Erdem, A

2017-08-01

Testosterone, estradiol, and dihydrotestosterone are the main sex steroid hormones responsible for the organization and sexual differentiation of brain structures during early development. The hypothalamo-pituitary-adrenocortical axis, adrenal cells, and gonads play a key role in the production of sex steroids and express adenosine receptors. Caffeine is a non-selective adenosine antagonist; therefore, it can modulate metabolic pathways in these tissues. Besides, the proportion of pregnant women that consume caffeine is ∼60%. That is why the relationship between maternal caffeine consumption and fetal development is important. Therefore, we aimed to investigate this modulatory effect of maternal caffeine consumption on sex steroids in the fetal and neonatal brain tissues. Pregnant rats were treated with a low (0.3 g/L) or high (0.8 g/L) dose of caffeine in their drinking water during pregnancy and lactation. The testosterone, estradiol, and dihydrotestosterone levels in the frontal cortex and hypothalamus were measured using radioimmunoassay at embryonic day 19 (E19), birth (PN0), and postnatal day 4 (PN4). The administration of low-dose caffeine increased the body weight in PN4 male and female rats and anogenital index in PN4 males. The administration of high-dose caffeine decreased the adrenal weight in E19 male rats and increased testosterone levels in the frontal cortex of E19 female rats and the hypothalamus of PN0 male rats. Maternal caffeine intake during pregnancy affects sex steroid levels in the frontal cortex and hypothalamus of the offspring. This concentration changes of the sex steroids in the brain may influence behavioral and neuroendocrine functions at some point in adult life.

Modeling conflict and error in the medial frontal cortex.

PubMed

Mayer, Andrew R; Teshiba, Terri M; Franco, Alexandre R; Ling, Josef; Shane, Matthew S; Stephen, Julia M; Jung, Rex E

2012-12-01

Despite intensive study, the role of the dorsal medial frontal cortex (dMFC) in error monitoring and conflict processing remains actively debated. The current experiment manipulated conflict type (stimulus conflict only or stimulus and response selection conflict) and utilized a novel modeling approach to isolate error and conflict variance during a multimodal numeric Stroop task. Specifically, hemodynamic response functions resulting from two statistical models that either included or isolated variance arising from relatively few error trials were directly contrasted. Twenty-four participants completed the task while undergoing event-related functional magnetic resonance imaging on a 1.5-Tesla scanner. Response times monotonically increased based on the presence of pure stimulus or stimulus and response selection conflict. Functional results indicated that dMFC activity was present during trials requiring response selection and inhibition of competing motor responses, but absent during trials involving pure stimulus conflict. A comparison of the different statistical models suggested that relatively few error trials contributed to a disproportionate amount of variance (i.e., activity) throughout the dMFC, but particularly within the rostral anterior cingulate gyrus (rACC). Finally, functional connectivity analyses indicated that an empirically derived seed in the dorsal ACC/pre-SMA exhibited strong connectivity (i.e., positive correlation) with prefrontal and inferior parietal cortex but was anti-correlated with the default-mode network. An empirically derived seed from the rACC exhibited the opposite pattern, suggesting that sub-regions of the dMFC exhibit different connectivity patterns with other large scale networks implicated in internal mentations such as daydreaming (default-mode) versus the execution of top-down attentional control (fronto-parietal). Copyright © 2011 Wiley Periodicals, Inc.

Human Medial Frontal Cortex Mediates Unconscious Inhibition of Voluntary Action

PubMed Central

Sumner, Petroc; Nachev, Parashkev; Morris, Peter; Peters, Andrew M.; Jackson, Stephen R.; Kennard, Christopher; Husain, Masud

2007-01-01

Summary Within the medial frontal cortex, the supplementary eye field (SEF), supplementary motor area (SMA), and pre-SMA have been implicated in the control of voluntary action, especially during motor sequences or tasks involving rapid choices between competing response plans. However, the precise roles of these areas remain controversial. Here, we study two extremely rare patients with microlesions of the SEF and SMA to demonstrate that these areas are critically involved in unconscious and involuntary motor control. We employed masked-prime stimuli that evoked automatic inhibition in healthy people and control patients with lateral premotor or pre-SMA damage. In contrast, our SEF/SMA patients showed a complete reversal of the normal inhibitory effect—ocular or manual—corresponding to the functional subregion lesioned. These findings imply that the SEF and SMA mediate automatic effector-specific suppression of motor plans. This automatic mechanism may contribute to the participation of these areas in the voluntary control of action. PMID:17553420

Effects of Crocin on Learning and Memory in Rats Under Chronic Restraint Stress with Special Focus on the Hippocampal and Frontal Cortex Corticosterone Levels

PubMed Central

Dastgerdi, Azadehalsadat Hosseini; Radahmadi, Maryam; Pourshanazari, Ali Asghar; Dastgerdi, Hajaralsadat Hosseini

2017-01-01

Background: Chronic stress adversely influences brain functions while crocin, as an effective component of saffron, exhibits positive effects on memory processes. This study investigated the effects of different doses of crocin on the improvement of learning and memory as well as corticosterone (CORT) levels in the hippocampus and frontal cortex of rats subjected to chronic stress. Materials and Methods: Forty male rats were randomly allocated to five different groups (n = 8): Control, sham; stress (6 h/day for 21 days) groups, and two groups receiving daily intraperitoneal injections of one of two doses (30 and 60 mg/kg) of crocin accompanied by 21 days of restraint stress. Latency was evaluated as a brain function using the passive avoidance test before and one-day after a foot shock. CORT levels were measured in the homogenized hippocampus and frontal cortex. Results: Results revealed that chronic stress had a significantly (P < 0.01) negative effect on memory. Crocin (30 and 60 mg/kg), however, gave increase to significantly (P < 0.01 and P < 0.05; respectively) improved memory functions in the stressed rats. Furthermore, the CORT levels in the hippocampus and frontal cortex declined significantly (P < 0.05) in the stress group compared to the control. Only a crocin dose of 30 mg/kg was observed modulate significantly (P < 0.05) the CORT levels in the hippocampus and frontal cortex in the stressed group. Conclusions: It was found that the lower crocin dose (30 mg/kg) had more beneficial effects than its higher (60 mg/kg) dose on learning and memory under chronic stress conditions. Moreover, it was speculated that different doses of crocin act on different neurotransmitters and biochemical factors in the brain. PMID:29387668

Antioxidant activity of Bacopa monniera in rat frontal cortex, striatum and hippocampus.

PubMed

Bhattacharya, S K; Bhattacharya, A; Kumar, A; Ghosal, S

2000-05-01

The effect of a standardized extract of Bacopa monniera Linn. was assessed on rat brain frontal cortical, striatal and hippocampal superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) activities, following administration for 7, 14 or 21 days. The effects induced by this extract (bacoside A content 82% +/- 0.5%), administered in doses of 5 and 10 mg/kg, orally, were compared with the effects induced by (-) deprenyl (2 mg/kg, p. o.) administered for the same time periods. Bacopa monniera (BM) induced a dose-related increase in SOD, CAT and GPX activities, in all the brain regions investigated, after 14 and 21 days of drug administration. On the contrary, deprenyl induced an increase in SOD, CAT and GPX activities in the frontal cortex and striatum, but not in the hippocampus, after treatment for 14 or 21 days. The results suggest that BM, like deprenyl, exhibits a significant antioxidant effect after subchronic administration which, unlike the latter, extends to the hippocampus as well. The results suggest that the increase in oxidative free radical scavenging activity by BM may explain, at least in part, the cognition- facilitating action of BM, recorded in Ayurvedic texts, and demonstrated experimentally and clinically. Copyright 2000 John Wiley & Sons, Ltd.

Monoamine oxidase-A and B activities in the cerebellum and frontal cortex of children and young adults with autism.

PubMed

Gu, Feng; Chauhan, Ved; Chauhan, Abha

2017-10-01

Monoamine oxidases (MAOs) catalyze the metabolism of monoamine neurotransmitters, such as serotonin, dopamine, and norepinephrine, and are key regulators for brain function. In this study, we analyzed the activities of MAO-A and MAO-B in the cerebellum and frontal cortex from subjects with autism and age-matched control subjects. In the cerebellum, MAO-A activity in subjects with autism (aged 4-38 years) was significantly lower by 20.6% than in controls. When the subjects were divided into children (aged 4-12 years) and young adults (aged 13-38 years) subgroups, a significant decrease by 27.8% in the MAO-A activity was observed only in children with autism compared with controls. When the 95% confidence interval of the control group was taken as a reference range, reduced activity of MAO-A was observed in 70% of children with autism. In the frontal cortex, MAO-A activity in children with autism was also lower by 30% than in the control group, and impaired activity of MAO-A was observed in 55.6% of children with autism, although the difference between the autism and control groups was not significant when all subjects were considered. On the contrary, there was no significant difference in MAO-B activity in both the cerebellum and frontal cortex between children with autism and the control group as well as in adults. These results suggest impaired MAO-A activity in the brain of subjects with autism, especially in children with autism. Decreased activity of MAOs may lead to increased levels of monoaminergic neurotransmitters, such as serotonin, which have been suggested to have a critical role in autism. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Multiple parietal-frontal pathways mediate grasping in macaque monkeys

PubMed Central

Gharbawie, Omar A.; Stepniewska, Iwona; Qi, Huixin; Kaas, Jon H.

2011-01-01

The nodes of a parietal-frontal pathway that mediates grasping in primates are in anterior intraparietal area (AIP) and ventral premotor cortex (PMv). Nevertheless, multiple somatosensory and motor representations of the hand, respectively in parietal and frontal cortex, suggest that additional pathways remain unrealized. We explored this possibility in macaque monkeys by injecting retrograde tracers into grasp zones identified in M1, PMv, and area 2 with long train electrical stimulation. The M1 grasp zone was densely connected with other frontal cortex motor regions. The remainder of the connections originated from somatosensory areas 3a and S2/PV, and from the medial bank and fundus of the intraparietal sulcus (IPS). The PMv grasp zone was also densely connected with frontal cortex motor regions, albeit to a lesser extent than the M1 grasp zone. The remainder of the connections originated from areas S2/PV and aspects of the inferior parietal lobe such as PF, PFG, AIP, and the tip of the IPS. The area 2 grasp zone was densely connected with the hand representations of somatosensory areas 3b, 1, and S2/PV. The remainder of the connections was with areas 3a and 5 and the medial bank and fundus of the IPS. Connections with frontal cortex were relatively weak and concentrated in caudal M1. Thus, the three grasp zones may be nodes of parallel parietal-frontal pathways. Differential points of origin and termination of each pathway suggest varying functional specializations. Direct and indirect connections between those parietal-frontal pathways likely coordinate their respective functions into an accurate grasp. PMID:21832196

Frontal cortex absolute beta power measurement in Panic Disorder with Agoraphobia patients.

PubMed

de Carvalho, Marcele Regine; Velasques, Bruna Brandão; Freire, Rafael C; Cagy, Maurício; Marques, Juliana Bittencourt; Teixeira, Silmar; Thomaz, Rafael; Rangé, Bernard P; Piedade, Roberto; Akiskal, Hagop Souren; Nardi, Antonio Egidio; Ribeiro, Pedro

2015-09-15

Panic disorder patients are hypervigilant to danger cues and highly sensitive to unpredictable aversive events, what leads to anticipatory anxiety, that is one key component of the disorder maintenance. Prefrontal cortex seems to be involved in these processes and beta band activity may be related to the involvement of top-down processing, whose function is supposed to be disrupted in pathological anxiety. The objective of this study was to measure frontal absolute beta-power (ABP) with qEEG in panic disorder and agoraphobia (PDA) patients compared to healthy controls. qEEG data were acquired while participants (24 PDA patients and 21 controls) watched a computer simulation (CS), consisting of moments classified as "high anxiety" (HAM) and "low anxiety" (LAM). qEEG data were also acquired during two rest conditions, before and after the computer simulation display. The statistical analysis was performed by means of a repeated measure analysis of variance (two-way ANOVA) and ABP was the dependent variable of interest. The main hypothesis was that a higher ABP in PDA patients would be found related to controls. Moreover, in HAM the ABP would be different than in LAM. the main finding was an interaction between the moment and group for the electrodes F7, F8, Fp1 and Fp2. We observed a higher ABP in PDA patients when compared to controls while watching the CS. The higher beta-power in the frontal cortex for the PDA group may reflect a state of high excitability, together with anticipatory anxiety and maintenance of hypervigilant cognitive state. our results suggest a possible deficiency in top-down processing reflected by a higher ABP in the PDA group while watching the CS and they highlight the recruitment of prefrontal regions during the exposure to anxiogenic stimuli. the small sample, the wide age range of participants and the use of psychotropic medications by most of the PDA patients. Copyright © 2015 Elsevier B.V. All rights reserved.

Direct evidence for attention-dependent influences of the frontal eye-fields on feature-responsive visual cortex.

PubMed

Heinen, Klaartje; Feredoes, Eva; Weiskopf, Nikolaus; Ruff, Christian C; Driver, Jon

2014-11-01

Voluntary selective attention can prioritize different features in a visual scene. The frontal eye-fields (FEF) are one potential source of such feature-specific top-down signals, but causal evidence for influences on visual cortex (as was shown for "spatial" attention) has remained elusive. Here, we show that transcranial magnetic stimulation (TMS) applied to right FEF increased the blood oxygen level-dependent (BOLD) signals in visual areas processing "target feature" but not in "distracter feature"-processing regions. TMS-induced BOLD signals increase in motion-responsive visual cortex (MT+) when motion was attended in a display with moving dots superimposed on face stimuli, but in face-responsive fusiform area (FFA) when faces were attended to. These TMS effects on BOLD signal in both regions were negatively related to performance (on the motion task), supporting the behavioral relevance of this pathway. Our findings provide new causal evidence for the human FEF in the control of nonspatial "feature"-based attention, mediated by dynamic influences on feature-specific visual cortex that vary with the currently attended property. © The Author 2013. Published by Oxford University Press.

Taurine restores the exploratory behavior following alcohol withdrawal and decreases BDNF mRNA expression in the frontal cortex of chronic alcohol-treated rats.

PubMed

Hansen, Alana Witt; Almeida, Felipe Borges; Bandiera, Solange; Pulcinelli, Rianne Remus; Fragoso, Ana Luiza Rodrigues; Schneider, Ricardo; Barros, Helena Maria Tannhauser; Gomez, Rosane

2017-10-01

Alcohol use disorder is an alarming health problem, and the withdrawal symptoms increase the risk of relapse. We have hypothesized that taurine, a multitarget substance acting as a gamma-aminobutyric acid A receptor (GABA A R) positive modulator and a partial inhibitor of N-methyl-d-aspartate (NMDA) glutamate receptors, may reduce the withdrawal symptoms or modify behaviors when combined with alcohol. Therefore, we investigated the effects of taurine on behavior in the open field test (OFT), the GABA A R α 2 subunit and BDNF mRNA expression in the frontal cortex of rats after chronic alcohol treatment or upon withdrawal. Rats received alcohol 2g/kg (alcohol and withdrawal groups) or water (control group) twice daily by oral gavage for 28days. On day 29, the withdrawal rats received water instead of alcohol, and all groups were reallocated to receive 100mg/kg taurine or vehicle intraperitoneally, once a day for 5days. On day 33, the rats were exposed to OFT; 18h later, they were euthanized, and the frontal cortex was dissected for GABA A R α 2 subunit detection and BDNF mRNA expression determination by real-time quantitative PCR. Taurine administration restored rearing behavior to the control levels in the withdrawal rats. Taurine also showed anxiolytic-like effects in control rats and did not change the behaviors in the chronic alcohol group. Chronic alcohol treatment or withdrawal did not change the GABA A R α 2 subunit or BDNF mRNA expression in the frontal cortex, but taurine decreased the α 2 subunit level in control rats and to the BDNF levels in the alcohol rat group. We conclude that taurine restored exploratory behavior after alcohol withdrawal but that this effect was not related to the GABA A R α 2 subunit or BDNF mRNA expression in the frontal cortex of the rats. Copyright © 2017 Elsevier Inc. All rights reserved.

Downregulation of GABA[Subscript A] Receptor Protein Subunits a6, ß2, d, e, ?2, ?, and ?2 in Superior Frontal Cortex of Subjects with Autism

ERIC Educational Resources Information Center

Fatemi, S. Hossein; Reutiman, Teri J.; Folsom, Timothy D.; Rustan, Oyvind G.; Rooney, Robert J.; Thuras, Paul D.

2014-01-01

We measured protein and mRNA levels for nine gamma-aminobutyric acid A (GABA[subscript A]) receptor subunits in three brain regions (cerebellum, superior frontal cortex, and parietal cortex) in subjects with autism versus matched controls. We observed changes in mRNA for a number of GABA[subscript A] and GABA[subscript B] subunits and overall…

Left dorsolateral prefrontal cortex atrophy is associated with frontal lobe function in Alzheimer's disease and contributes to caregiver burden.

PubMed

Matsuoka, Kiwamu; Yasuno, Fumihiko; Hashimoto, Akiko; Miyasaka, Toshiteru; Takahashi, Masato; Kiuchi, Kuniaki; Iida, Junzo; Kichikawa, Kimihiko; Kishimoto, Toshifumi

2018-05-01

Caregivers of patients with dementia experience physical and mental deterioration. We have previously reported a correlation between caregiver burden and the Frontal Assessment Battery (FAB) total scores of patients with Alzheimer's disease (AD), especially regarding the dependency factor from the Zarit Burden Interview. The present study aimed to identify an objective biomarker for predicting caregiver burden. The participants were 26 pairs of caregivers and patients with AD and mild-to-moderate dementia. Correlations between regional gray matter volumes in the patients with AD and the FAB total scores were explored by using whole-brain voxel-based morphometric analysis. Path analysis was used to estimate the relationships between regional gray matter volumes, FAB total scores, and caregiver burden based on the Zarit Burden Interview. The voxel-based morphometric revealed a significant positive correlation between the FAB total scores and the volume of the left dorsolateral prefrontal cortex. This positive correlation persisted after controlling for the effect of general cognitive dysfunction, which was assessed by using the Mini-Mental State Examination. Path analysis revealed that decreases in FAB scores, caused by reduced frontal lobe volumes, negatively affected caregiver burden. The present study revealed that frontal lobe function, based on FAB scores, was affected by the volume of the left dorsolateral prefrontal cortex. Decreased scores were associated with greater caregiver burden, especially for the dependency factor. These findings may facilitate the development of an objective biomarker for predicting caregiver burden. Copyright © 2017 John Wiley & Sons, Ltd.

Topographic analysis of individual activation patterns in medial frontal cortex in schizophrenia

PubMed Central

Stern, Emily R.; Welsh, Robert C.; Fitzgerald, Kate D.; Taylor, Stephan F.

2009-01-01

Individual variability in the location of neural activations poses a unique problem for neuroimaging studies employing group averaging techniques to investigate the neural bases of cognitive and emotional functions. This may be especially challenging for studies examining patient groups, which often have limited sample sizes and increased intersubject variability. In particular, medial frontal cortex (MFC) dysfunction is thought to underlie performance monitoring dysfunction among patients with previous studies using group averaging to have yielded conflicting results. schizophrenia, yet compare schizophrenic patients to controls To examine individual activations in MFC associated with two aspects of performance monitoring, interference and error processing, functional magnetic resonance imaging (fMRI) data were acquired while 17 patients with schizophrenia and 21 healthy controls performed an event-related version of the multi-source interference task. Comparisons of averaged data revealed few differences between the groups. By contrast, topographic analysis of individual activations for errors showed that control subjects exhibited activations spanning across both posterior and anterior regions of MFC while patients primarily activated posterior MFC, possibly reflecting an impaired emotional response to errors in schizophrenia. This discrepancy between topographic and group-averaged results may be due to the significant dispersion among individual activations, particularly among healthy controls, highlighting the importance of considering intersubject variability when interpreting the medial frontal response to error commission. PMID:18819107

Echo-planar magnetic resonance imaging studies of frontal cortex activation during word generation in humans.

PubMed Central

McCarthy, G; Blamire, A M; Rothman, D L; Gruetter, R; Shulman, R G

1993-01-01

Nine subjects were studied by high-speed magnetic resonance imaging while performing language-based tasks. Subjects were asked either to repeat or to generate verbs associated with nouns read by an experimenter while magnetic resonance images were obtained of the left inferior frontal lobe. The echo-planar imaging sequence was used with a gradient echo time of 70 ms to give an apparent transverse relaxation time weighting (T2* that is sensitive to local hemoglobin levels. Images were acquired every 3 s (repetition time) in series of 32. In plane resolution was 6 x 4.5 mm and slice thickness was 10 mm. An increase in signal accompanied performance of the tasks, with significantly more activation for verb generation than for repeating. The activation effect occurred within 3 s after task onset and could be observed in single images from individual subjects. The primary focus of activation appeared in gray matter along a sulcus anterior to the lateral sulcus that included the anterior insula, Brodmann's area 47, and extending to area 10. Little or no activation of this region was found for a passive listening, covert generation, or mouth-movement control tasks. Significant activation was also found for a homologous region in the right frontal cortex but not for control regions in calcarine cortex. These results are consistent with prior studies that have used positron emission tomography imaging with 15O-labeled water as a blood flow tracer. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:8506340

Dysregulated glutamate and dopamine transporters in postmortem frontal cortex from bipolar and schizophrenic patients

PubMed Central

Rao, Jagadeesh Sridhara; Kellom, Matthew; Reese, Edmund Arthur; Rapoport, Stanley Isaac; Kim, Hyung-Wook

2012-01-01

Background Dysregulated glutamate, serotonin and dopamine neurotransmission has been reported in bipolar disorder (BD) and schizophrenia (SZ), but the underlying mechanisms of dysregulation are not clear. We hypothesized that they involve alterations in excitatory amino acid transporters (EAATs), the serotonin reuptake transporter (SERT), and the dopamine reuptake transporter (DAT). Methods To test this hypothesis, we determined protein and mRNA levels of EAAT subtypes 1–4, of the SERT and of the DAT in postmortem frontal cortex from BD (n=10) and SZ (n=10) patients and from healthy control (n=10) subjects. Results Compared to control levels, protein and mRNA levels of EAAT1 were increased significantly in cortex from both BD and SZ patients. EAAT2 protein and mRNA levels were decreased significantly in BD but not in SZ cortices. EAAT3 and EAAT 4 protein and mRNA levels were significantly higher in SZ but not in BD compared with control. DAT protein and mRNA levels were decreased significantly in both BD and SZ cortex. There was no significant change in SERT expression in either BD or SZ. Conclusions The altered EAATs and DAT expression could result in altered glutamatergic and hyperdopaminergic function in BD and SZ. Differently altered EAATs involved in glutamatergic transmission could be therapeutic targets for treating BD and SZ. PMID:21925739

Orbital frontal cortex updates state-induced value change for decision-making.

PubMed

Baltz, Emily T; Yalcinbas, Ege A; Renteria, Rafael; Gremel, Christina M

2018-06-13

Recent hypotheses have posited that orbital frontal cortex (OFC) is important for using inferred consequences to guide behavior. Less clear is OFC's contribution to goal-directed or model-based behavior, where the decision to act is controlled by previous experience with the consequence or outcome. Investigating OFC's role in learning about changed outcomes separate from decision-making is not trivial and often the two are confounded. Here we adapted an incentive learning task to mice, where we investigated processes controlling experience-based outcome updating independent from inferred action control. We found chemogenetic OFC attenuation did not alter the ability to perceive motivational state-induced changes in outcome value but did prevent the experience-based updating of this change. Optogenetic inhibition of OFC excitatory neuron activity selectively when experiencing an outcome change disrupted the ability to update, leaving mice unable to infer the appropriate behavior. Our findings support a role for OFC in learning that controls decision-making. © 2018, Baltz et al.

Acoustic and higher-level representations of naturalistic auditory scenes in human auditory and frontal cortex.

PubMed

Hausfeld, Lars; Riecke, Lars; Formisano, Elia

2018-06-01

Often, in everyday life, we encounter auditory scenes comprising multiple simultaneous sounds and succeed to selectively attend to only one sound, typically the most relevant for ongoing behavior. Studies using basic sounds and two-talker stimuli have shown that auditory selective attention aids this by enhancing the neural representations of the attended sound in auditory cortex. It remains unknown, however, whether and how this selective attention mechanism operates on representations of auditory scenes containing natural sounds of different categories. In this high-field fMRI study we presented participants with simultaneous voices and musical instruments while manipulating their focus of attention. We found an attentional enhancement of neural sound representations in temporal cortex - as defined by spatial activation patterns - at locations that depended on the attended category (i.e., voices or instruments). In contrast, we found that in frontal cortex the site of enhancement was independent of the attended category and the same regions could flexibly represent any attended sound regardless of its category. These results are relevant to elucidate the interacting mechanisms of bottom-up and top-down processing when listening to real-life scenes comprised of multiple sound categories. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Plasticity and Functions of the Orbital Frontal Cortex

ERIC Educational Resources Information Center

Kolb, Bryan; Pellis, Sergio; Robinson, Terry E.

2004-01-01

We compare the effects of psychoactive drugs such as morphine and amphetamine on the synaptic organization of neurons in the orbital frontal (OFC) and medial frontal (mPFC) regions in the rat. Both regions are altered chronically by exposure to intermittent doses of either drug but the effects are area-dependent. For example, whereas morphine…

Prenatal exposure to the cannabinoid receptor agonist WIN 55,212-2 increases glutamate uptake through overexpression of GLT1 and EAAC1 glutamate transporter subtypes in rat frontal cerebral cortex.

PubMed

Castaldo, Pasqualina; Magi, Simona; Gaetani, Silvana; Cassano, Tommaso; Ferraro, Luca; Antonelli, Tiziana; Amoroso, Salvatore; Cuomo, Vincenzo

2007-09-01

Prenatal exposure to the CB1 receptor agonist (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)-pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone) mesylate (WIN) at a daily dose of 0.5 mg/kg, and Delta9-tetrahydrocannabinol (Delta9-THC) at a daily dose of 5 mg/kg, reduced dialysate glutamate levels in frontal cerebral cortex of adolescent offspring (40-day-old) with respect to those born from vehicle-treated mothers. WIN treatment induced a statistically significant enhancement of Vmaxl-[3H]glutamate uptake, whereas it did not modify glutamate Km, in frontal cerebral cortex synaptosomes of adolescent rats. Western blotting analysis, performed either in membrane proteins derived from homogenates and in proteins extracted from synaptosomes of frontal cerebral cortex, revealed that prenatal WIN exposure enhanced the expression of glutamate transporter 1 (GLT1) and excitatory amino acid carrier 1 (EAAC1). Moreover, immunocytochemical analyses of frontal cortex area revealed a more intense GLT1 and EAAC1 immunoreactivity (ir) distribution in the WIN-treated group. Collectively these results show that prenatal exposure to the cannabinoid CB1 receptor agonist WIN increases expression and functional activity of GLT1 and EAAC1 glutamate transporters (GluTs) associated to a decrease of cortical glutamate outflow, in adolescent rats. These findings may contribute to explain the mechanism underlying the cognitive impairment observed in the offspring of mothers who used marijuana during pregnancy.

Long-range functional interactions of anterior insula and medial frontal cortex are differently modulated by visuospatial and inductive reasoning tasks.

PubMed

Ebisch, Sjoerd J H; Mantini, Dante; Romanelli, Roberta; Tommasi, Marco; Perrucci, Mauro G; Romani, Gian Luca; Colom, Roberto; Saggino, Aristide

2013-09-01

The brain is organized into functionally specific networks as characterized by intrinsic functional relationships within discrete sets of brain regions. However, it is poorly understood whether such functional networks are dynamically organized according to specific task-states. The anterior insular cortex (aIC)-dorsal anterior cingulate cortex (dACC)/medial frontal cortex (mFC) network has been proposed to play a central role in human cognitive abilities. The present functional magnetic resonance imaging (fMRI) study aimed at testing whether functional interactions of the aIC-dACC/mFC network in terms of temporally correlated patterns of neural activity across brain regions are dynamically modulated by transitory, ongoing task demands. For this purpose, functional interactions of the aIC-dACC/mFC network are compared during two distinguishable fluid reasoning tasks, Visualization and Induction. The results show an increased functional coupling of bilateral aIC with visual cortices in the occipital lobe during the Visualization task, whereas coupling of mFC with right anterior frontal cortex was enhanced during the Induction task. These task-specific modulations of functional interactions likely reflect ability related neural processing. Furthermore, functional connectivity strength between right aIC and right dACC/mFC reliably predicts general task performance. The findings suggest that the analysis of long-range functional interactions may provide complementary information about brain-behavior relationships. On the basis of our results, it is proposed that the aIC-dACC/mFC network contributes to the integration of task-common and task-specific information based on its within-network as well as its between-network dynamic functional interactions. Copyright © 2013 Elsevier Inc. All rights reserved.

Dorso-Lateral Frontal Cortex of the Ferret Encodes Perceptual Difficulty during Visual Discrimination

PubMed Central

Zhou, Zhe Charles; Yu, Chunxiu; Sellers, Kristin K.; Fröhlich, Flavio

2016-01-01

Visual discrimination requires sensory processing followed by a perceptual decision. Despite a growing understanding of visual areas in this behavior, it is unclear what role top-down signals from prefrontal cortex play, in particular as a function of perceptual difficulty. To address this gap, we investigated how neurons in dorso-lateral frontal cortex (dl-FC) of freely-moving ferrets encode task variables in a two-alternative forced choice visual discrimination task with high- and low-contrast visual input. About two-thirds of all recorded neurons in dl-FC were modulated by at least one of the two task variables, task difficulty and target location. More neurons in dl-FC preferred the hard trials; no such preference bias was found for target location. In individual neurons, this preference for specific task types was limited to brief epochs. Finally, optogenetic stimulation confirmed the functional role of the activity in dl-FC before target touch; suppression of activity in pyramidal neurons with the ArchT silencing opsin resulted in a decrease in reaction time to touch the target but not to retrieve reward. In conclusion, dl-FC activity is differentially recruited for high perceptual difficulty in the freely-moving ferret and the resulting signal may provide top-down behavioral inhibition. PMID:27025995

Dorso-Lateral Frontal Cortex of the Ferret Encodes Perceptual Difficulty during Visual Discrimination.

PubMed

Zhou, Zhe Charles; Yu, Chunxiu; Sellers, Kristin K; Fröhlich, Flavio

2016-03-30

Visual discrimination requires sensory processing followed by a perceptual decision. Despite a growing understanding of visual areas in this behavior, it is unclear what role top-down signals from prefrontal cortex play, in particular as a function of perceptual difficulty. To address this gap, we investigated how neurons in dorso-lateral frontal cortex (dl-FC) of freely-moving ferrets encode task variables in a two-alternative forced choice visual discrimination task with high- and low-contrast visual input. About two-thirds of all recorded neurons in dl-FC were modulated by at least one of the two task variables, task difficulty and target location. More neurons in dl-FC preferred the hard trials; no such preference bias was found for target location. In individual neurons, this preference for specific task types was limited to brief epochs. Finally, optogenetic stimulation confirmed the functional role of the activity in dl-FC before target touch; suppression of activity in pyramidal neurons with the ArchT silencing opsin resulted in a decrease in reaction time to touch the target but not to retrieve reward. In conclusion, dl-FC activity is differentially recruited for high perceptual difficulty in the freely-moving ferret and the resulting signal may provide top-down behavioral inhibition.

Expression and function of dopamine receptors in the developing medial frontal cortex and striatum of the rat

PubMed Central

Sillivan, Stephanie E.; Konradi, Christine

2011-01-01

The timeline of dopamine (DA) system maturation and the signaling properties of dopamine receptors (DRs) during rat brain development are not fully characterized. We used in situ hybridization and quantitative PCR to map DR mRNA transcripts in the medial frontal cortex (mFC) and striatum (STR) of the rat from embryonic day (E) 15 to E21. The developmental trajectory of DR mRNAs revealed distinct patterns of DA receptors 1 and 2 (DRD1, DRD2) in these brain regions. Whereas the mFC had a steeper increase in DRD1 mRNA, the STR had a steeper increase in DRD2 mRNA. Both DR mRNAs were expressed at a higher level in the STR compared to the mFC. To identify the functional properties of DRs during embryonic development, the phosphorylation states of cyclic AMP response element binding protein (CREB), extracellular signal-regulated kinase 1/2 (ERK1/2), and glycogen synthase kinase 3 beta (GSK3β) were examined after DR stimulation in primary neuronal cultures obtained from E15 and E18 embryos and cultured for 3 days to ensure a stable baseline level. DR-mediated signaling cascades were functional in E15 cultures in both brain regions. Because DA fibers do not reach the mFC by E15, and DA was not present in cultures, these data indicate that DRs can become functional in the absence of DA innervation. Since activation of DR signal transduction pathways can affect network organization of the developing brain, maternal exposure to drugs that affect DR activity may be liable to interfere with fetal brain development. PMID:22015925

Longitudinal Effects of Ketamine on Dendritic Architecture In Vivo in the Mouse Medial Frontal Cortex123

PubMed Central

Phoumthipphavong, Victoria; Barthas, Florent; Hassett, Samantha

2016-01-01

Abstract A single subanesthetic dose of ketamine, an NMDA receptor antagonist, leads to fast-acting antidepressant effects. In rodent models, systemic ketamine is associated with higher dendritic spine density in the prefrontal cortex, reflecting structural remodeling that may underlie the behavioral changes. However, turnover of dendritic spines is a dynamic process in vivo, and the longitudinal effects of ketamine on structural plasticity remain unclear. The purpose of the current study is to use subcellular resolution optical imaging to determine the time course of dendritic alterations in vivo following systemic ketamine administration in mice. We used two-photon microscopy to visualize repeatedly the same set of dendritic branches in the mouse medial frontal cortex (MFC) before and after a single injection of ketamine or saline. Compared to controls, ketamine-injected mice had higher dendritic spine density in MFC for up to 2 weeks. This prolonged increase in spine density was driven by an elevated spine formation rate, and not by changes in the spine elimination rate. A fraction of the new spines following ketamine injection was persistent, which is indicative of functional synapses. In a few cases, we also observed retraction of distal apical tuft branches on the day immediately after ketamine administration. These results indicate that following systemic ketamine administration, certain dendritic inputs in MFC are removed immediately, while others are added gradually. These dynamic structural modifications are consistent with a model of ketamine action in which the net effect is a rebalancing of synaptic inputs received by frontal cortical neurons. PMID:27066532

Folding, But Not Surface Area Expansion, Is Associated with Cellular Morphological Maturation in the Fetal Cerebral Cortex

PubMed Central

Studholme, Colin; Frias, Antonio E.

2017-01-01

Altered macroscopic anatomical characteristics of the cerebral cortex have been identified in individuals affected by various neurodevelopmental disorders. However, the cellular developmental mechanisms that give rise to these abnormalities are not understood. Previously, advances in image reconstruction of diffusion magnetic resonance imaging (MRI) have made possible high-resolution in utero measurements of water diffusion anisotropy in the fetal brain. Here, diffusion anisotropy within the developing fetal cerebral cortex is longitudinally characterized in the rhesus macaque, focusing on gestation day (G85) through G135 of the 165 d term. Additionally, for subsets of animals characterized at G90 and G135, immunohistochemical staining was performed, and 3D structure tensor analyses were used to identify the cellular processes that most closely parallel changes in water diffusion anisotropy with cerebral cortical maturation. Strong correlations were found between maturation of dendritic arbors on the cellular level and the loss of diffusion anisotropy with cortical development. In turn, diffusion anisotropy changes were strongly associated both regionally and temporally with cortical folding. Notably, the regional and temporal dependence of diffusion anisotropy and folding were distinct from the patterns observed for cerebral cortical surface area expansion. These findings strengthen the link proposed in previous studies between cellular-level changes in dendrite morphology and noninvasive diffusion MRI measurements of the developing cerebral cortex and support the possibility that, in gyroencephalic species, structural differentiation within the cortex is coupled to the formation of gyri and sulci. SIGNIFICANCE STATEMENT Abnormal brain morphology has been found in populations with neurodevelopmental disorders. However, the mechanisms linking cellular level and macroscopic maturation are poorly understood, even in normal brains. This study contributes new

The vestibular-related frontal cortex and its role in smooth-pursuit eye movements and vestibular-pursuit interactions

PubMed Central

Fukushima, Junko; Akao, Teppei; Kurkin, Sergei; Kaneko, Chris R.S.; Fukushima, Kikuro

2006-01-01

In order to see clearly when a target is moving slowly, primates with high acuity foveae use smooth-pursuit and vergence eye movements. The former rotates both eyes in the same direction to track target motion in frontal planes, while the latter rotates left and right eyes in opposite directions to track target motion in depth. Together, these two systems pursue targets precisely and maintain their images on the foveae of both eyes. During head movements, both systems must interact with the vestibular system to minimize slip of the retinal images. The primate frontal cortex contains two pursuit-related areas; the caudal part of the frontal eye fields (FEF) and supplementary eye fields (SEF). Evoked potential studies have demonstrated vestibular projections to both areas and pursuit neurons in both areas respond to vestibular stimulation. The majority of FEF pursuit neurons code parameters of pursuit such as pursuit and vergence eye velocity, gaze velocity, and retinal image motion for target velocity in frontal and depth planes. Moreover, vestibular inputs contribute to the predictive pursuit responses of FEF neurons. In contrast, the majority of SEF pursuit neurons do not code pursuit metrics and many SEF neurons are reported to be active in more complex tasks. These results suggest that FEF- and SEF-pursuit neurons are involved in different aspects of vestibular-pursuit interactions and that eye velocity coding of SEF pursuit neurons is specialized for the task condition. PMID:16917164

The differing roles of the frontal cortex in fluency tests

PubMed Central

Shallice, Tim; Bozzali, Marco; Cipolotti, Lisa

2012-01-01

Fluency tasks have been widely used to tap the voluntary generation of responses. The anatomical correlates of fluency tasks and their sensitivity and specificity have been hotly debated. However, investigation of the cognitive processes involved in voluntary generation of responses and whether generation is supported by a common, general process (e.g. fluid intelligence) or specific cognitive processes underpinned by particular frontal regions has rarely been addressed. This study investigates a range of verbal and non-verbal fluency tasks in patients with unselected focal frontal (n = 47) and posterior (n = 20) lesions. Patients and controls (n = 35) matched for education, age and sex were administered fluency tasks including word (phonemic/semantic), design, gesture and ideational fluency as well as background cognitive tests. Lesions were analysed by standard anterior/posterior and left/right frontal subdivisions as well as a finer-grained frontal localization method. Thus, patients with right and left lateral lesions were compared to patients with superior medial lesions. The results show that all eight fluency tasks are sensitive to frontal lobe damage although only the phonemic word and design fluency tasks were specific to the frontal region. Superior medial patients were the only group to be impaired on all eight fluency tasks, relative to controls, consistent with an energization deficit. The most marked fluency deficits for lateral patients were along material specific lines (i.e. left—phonemic and right—design). Phonemic word fluency that requires greater selection was most severely impaired following left inferior frontal damage. Overall, our results support the notion that frontal functions comprise a set of specialized cognitive processes, supported by distinct frontal regions. PMID:22669082

High-alpha band synchronization across frontal, parietal and visual cortex mediates behavioral and neuronal effects of visuospatial attention.

PubMed

Lobier, Muriel; Palva, J Matias; Palva, Satu

2018-01-15

Visuospatial attention prioritizes processing of attended visual stimuli. It is characterized by lateralized alpha-band (8-14 Hz) amplitude suppression in visual cortex and increased neuronal activity in a network of frontal and parietal areas. It has remained unknown what mechanisms coordinate neuronal processing among frontoparietal network and visual cortices and implement the attention-related modulations of alpha-band amplitudes and behavior. We investigated whether large-scale network synchronization could be such a mechanism. We recorded human cortical activity with magnetoencephalography (MEG) during a visuospatial attention task. We then identified the frequencies and anatomical networks of inter-areal phase synchronization from source localized MEG data. We found that visuospatial attention is associated with robust and sustained long-range synchronization of cortical oscillations exclusively in the high-alpha (10-14 Hz) frequency band. This synchronization connected frontal, parietal and visual regions and was observed concurrently with amplitude suppression of low-alpha (6-9 Hz) band oscillations in visual cortex. Furthermore, stronger high-alpha phase synchronization was associated with decreased reaction times to attended stimuli and larger suppression of alpha-band amplitudes. These results thus show that high-alpha band phase synchronization is functionally significant and could coordinate the neuronal communication underlying the implementation of visuospatial attention. Copyright © 2017 Elsevier Inc. All rights reserved.

Effective Connectivity Hierarchically Links Temporoparietal and Frontal Areas of the Auditory Dorsal Stream with the Motor Cortex Lip Area during Speech Perception

ERIC Educational Resources Information Center

Murakami, Takenobu; Restle, Julia; Ziemann, Ulf

2012-01-01

A left-hemispheric cortico-cortical network involving areas of the temporoparietal junction (Tpj) and the posterior inferior frontal gyrus (pIFG) is thought to support sensorimotor integration of speech perception into articulatory motor activation, but how this network links with the lip area of the primary motor cortex (M1) during speech…

5-HT has contrasting effects in the frontal cortex, but not the hypothalamus, on changes in noradrenaline efflux induced by the monoamine releasing-agent, d-amphetamine, and the reuptake inhibitor, BTS 54 354.

PubMed

Géranton, Sandrine M; Heal, David J; Stanford, S Clare

2004-03-01

There is extensive evidence for functional interactions between central noradrenergic and serotonergic neurones. Here, dual-probe microdialysis was used in freely-moving rats to compare the effects of 5-HT on noradrenergic transmission in the rat frontal cortex and hypothalamus. We studied the effects of the 5-HT synthesis inhibitor, para-chlorophenylalanine (pCPA; which depleted 5-HT stores in both the frontal cortex and the hypothalamus), on spontaneous efflux of noradrenaline and on the noradrenergic responses to d-amphetamine, and the monoamine reuptake inhibitor, BTS 54 354. pCPA pretreatment alone did not affect spontaneous noradrenaline efflux in either brain region, whether or not alpha2-autoreceptors were inactivated by administration of the alpha2-antagonist, atipamezole (1 mg/kg i.p). However, in the frontal cortex, pCPA pretreatment augmented the amplitude of, and prolonged, the noradrenergic response to local infusion of d-amphetamine (10 microM). In contrast, pCPA abolished the increase in cortical noradrenaline efflux induced by local infusion of BTS 54 354 (50 microM). In the hypothalamus, pCPA did not affect the amplitude of the response to either of these agents but did prolong the effects of d-amphetamine on noradrenaline efflux. These findings suggest that serotonergic transmission has complex effects on the noradrenergic response to drugs that increase noradrenergic transmission in the frontal cortex, but has less influence in the hypothalamus.

Early growth hormone (GH) treatment promotes relevant motor functional improvement after severe frontal cortex lesion in adult rats.

PubMed

Heredia, Margarita; Fuente, A; Criado, J; Yajeya, J; Devesa, J; Riolobos, A S

2013-06-15

A number of studies, in animals and humans, describe the positive effects of the growth hormone (GH) treatment combined with rehabilitation on brain reparation after brain injury. We examined the effect of GH treatment and rehabilitation in adult rats with severe frontal motor cortex ablation. Thirty-five male rats were trained in the paw-reaching-for-food task and the preferred forelimb was recorded. Under anesthesia, the motor cortex contralateral to the preferred forelimb was aspirated or sham-operated. Animals were then treated with GH (0.15 mg/kg/day, s.c) or vehicle during 5 days, commencing immediately or 6 days post-lesion. Rehabilitation was applied at short- and long-term after GH treatment. Behavioral data were analized by ANOVA following Bonferroni post hoc test. After sacrifice, immunohistochemical detection of glial fibrillary acid protein (GFAP) and nestin were undertaken in the brain of all groups. Animal group treated with GH immediately after the lesion, but not any other group, showed a significant improvement of the motor impairment induced by the motor lesion, and their performances in the motor test were no different from sham-operated controls. GFAP immunolabeling and nestin immunoreactivity were observed in the perilesional area in all injured animals; nestin immunoreactivity was higher in GH-treated injured rats (mainly in animals GH-treated 6 days post-lesion). GFAP immunoreactivity was similar among injured rats. Interestingly, nestin re-expression was detected in the contralateral undamaged motor cortex only in GH-treated injured rats, being higher in animals GH-treated immediately after the lesion than in animals GH-treated 6 days post-lesion. Early GH treatment induces significant recovery of the motor impairment produced by frontal cortical ablation. GH effects include increased neurogenesis for reparation (perilesional area) and for increased brain plasticity (contralateral motor area). Copyright © 2013 Elsevier B.V. All rights

Left frontal hub connectivity delays cognitive impairment in autosomal-dominant and sporadic Alzheimer's disease.

PubMed

Franzmeier, Nicolai; Düzel, Emrah; Jessen, Frank; Buerger, Katharina; Levin, Johannes; Duering, Marco; Dichgans, Martin; Haass, Christian; Suárez-Calvet, Marc; Fagan, Anne M; Paumier, Katrina; Benzinger, Tammie; Masters, Colin L; Morris, John C; Perneczky, Robert; Janowitz, Daniel; Catak, Cihan; Wolfsgruber, Steffen; Wagner, Michael; Teipel, Stefan; Kilimann, Ingo; Ramirez, Alfredo; Rossor, Martin; Jucker, Mathias; Chhatwal, Jasmeer; Spottke, Annika; Boecker, Henning; Brosseron, Frederic; Falkai, Peter; Fliessbach, Klaus; Heneka, Michael T; Laske, Christoph; Nestor, Peter; Peters, Oliver; Fuentes, Manuel; Menne, Felix; Priller, Josef; Spruth, Eike J; Franke, Christiana; Schneider, Anja; Kofler, Barbara; Westerteicher, Christine; Speck, Oliver; Wiltfang, Jens; Bartels, Claudia; Araque Caballero, Miguel Ángel; Metzger, Coraline; Bittner, Daniel; Weiner, Michael; Lee, Jae-Hong; Salloway, Stephen; Danek, Adrian; Goate, Alison; Schofield, Peter R; Bateman, Randall J; Ewers, Michael

2018-04-01

Patients with Alzheimer's disease vary in their ability to sustain cognitive abilities in the presence of brain pathology. A major open question is which brain mechanisms may support higher reserve capacity, i.e. relatively high cognitive performance at a given level of Alzheimer's pathology. Higher functional MRI-assessed functional connectivity of a hub in the left frontal cortex is a core candidate brain mechanism underlying reserve as it is associated with education (i.e. a protective factor often associated with higher reserve) and attenuated cognitive impairment in prodromal Alzheimer's disease. However, no study has yet assessed whether such hub connectivity of the left frontal cortex supports reserve throughout the evolution of pathological brain changes in Alzheimer's disease, including the presymptomatic stage when cognitive decline is subtle. To address this research gap, we obtained cross-sectional resting state functional MRI in 74 participants with autosomal dominant Alzheimer's disease, 55 controls from the Dominantly Inherited Alzheimer's Network and 75 amyloid-positive elderly participants, as well as 41 amyloid-negative cognitively normal elderly subjects from the German Center of Neurodegenerative Diseases multicentre study on biomarkers in sporadic Alzheimer's disease. For each participant, global left frontal cortex connectivity was computed as the average resting state functional connectivity between the left frontal cortex (seed) and each voxel in the grey matter. As a marker of disease stage, we applied estimated years from symptom onset in autosomal dominantly inherited Alzheimer's disease and cerebrospinal fluid tau levels in sporadic Alzheimer's disease cases. In both autosomal dominant and sporadic Alzheimer's disease patients, higher levels of left frontal cortex connectivity were correlated with greater education. For autosomal dominant Alzheimer's disease, a significant left frontal cortex connectivity × estimated years of onset

Gene expression analysis indicates CB1 receptor upregulation in the hippocampus and neurotoxic effects in the frontal cortex 3 weeks after single-dose MDMA administration in Dark Agouti rats

PubMed Central

2013-01-01

Background 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") is a widely used recreational drug known to impair cognitive functions on the long-run. Both hippocampal and frontal cortical regions have well established roles in behavior, memory formation and other cognitive tasks and damage of these regions is associated with altered behavior and cognitive functions, impairments frequently described in heavy MDMA users. The aim of this study was to examine the hippocampus, frontal cortex and dorsal raphe of Dark Agouti rats with gene expression arrays (Illumina RatRef bead arrays) looking for possible mechanisms and new candidates contributing to the effects of a single dose of MDMA (15 mg/kg) 3 weeks earlier. Results The number of differentially expressed genes in the hippocampus, frontal cortex and the dorsal raphe were 481, 155, and 15, respectively. Gene set enrichment analysis of the microarray data revealed reduced expression of 'memory’ and 'cognition’, 'dendrite development’ and 'regulation of synaptic plasticity’ gene sets in the hippocampus, parallel to the upregulation of the CB1 cannabinoid- and Epha4, Epha5, Epha6 ephrin receptors. Downregulated gene sets in the frontal cortex were related to protein synthesis, chromatin organization, transmembrane transport processes, while 'dendrite development’, 'regulation of synaptic plasticity’ and 'positive regulation of synapse assembly’ gene sets were upregulated. Changes in the dorsal raphe region were mild and in most cases not significant. Conclusion The present data raise the possibility of new synapse formation/synaptic reorganization in the frontal cortex three weeks after a single neurotoxic dose of MDMA. In contrast, a prolonged depression of new neurite formation in the hippocampus is suggested by the data, which underlines the particular vulnerability of this brain region after the drug treatment. Finally, our results also suggest the substantial contribution of CB1 receptor and

Storage and executive processes in the frontal lobes.

PubMed

Smith, E E; Jonides, J

1999-03-12

The human frontal cortex helps mediate working memory, a system that is used for temporary storage and manipulation of information and that is involved in many higher cognitive functions. Working memory includes two components: short-term storage (on the order of seconds) and executive processes that operate on the contents of storage. Recently, these two components have been investigated in functional neuroimaging studies. Studies of storage indicate that different frontal regions are activated for different kinds of information: storage for verbal materials activates Broca's area and left-hemisphere supplementary and premotor areas; storage of spatial information activates the right-hemisphere premotor cortex; and storage of object information activates other areas of the prefrontal cortex. Two of the fundamental executive processes are selective attention and task management. Both processes activate the anterior cingulate and dorsolateral prefrontal cortex.

Brain activity in the right-frontal pole and lateral occipital cortex predicts successful post-operatory outcome after surgery for anterior glenoumeral instability.

PubMed

Zanchi, Davide; Cunningham, Gregory; Lädermann, Alexandre; Ozturk, Mehmet; Hoffmeyer, Pierre; Haller, Sven

2017-03-29

Shoulder apprehension is more complex than a pure mechanical problem of the shoulder, creating a scar at the brain level that prevents the performance of specific movements. Surgery corrects for shoulder instability at the physical level, but a re-dislocation within the first year is rather common. Predicting which patient will be likely to have re-dislocation is therefore crucial. We hypothesized that the assessment of neural activity at baseline and follow-up is the key factor to predict the post-operatory outcome. 13 patients with shoulder apprehension (30.03 ± 7.64 years) underwent clinical and fMRI examination before and one year after surgery for shoulder dislocation contrasting apprehension cue videos and control videos. Data analyses included task-related general linear model (GLM) and correlations imaging results with clinical scores. Clinical examination showed decreased pain and increased shoulder functions for post-op vs. pre-op. Coherently, GLM results show decreased activation of the left pre-motor cortex for post-surgery vs. pre-surgery. Right-frontal pole and right-occipital cortex activity predicts good recovery of shoulder function measured by STT. Our findings demonstrate that beside physical changes, changes at the brain level also occur one year after surgery. In particular, decreased activity in pre-motor and orbito-frontal cortex is key factor for a successful post-operatory outcome.

Dissociable effects of cingulate and medial frontal cortex lesions on stimulus-reward learning using a novel Pavlovian autoshaping procedure for the rat: implications for the neurobiology of emotion.

PubMed

Bussey, T J; Everitt, B J; Robbins, T W

1997-10-01

The effects of quinolinic acid-induced lesions of the anterior cingulate, posterior cingulate, and medial frontal cortices on stimulus-reward learning were investigated with a novel Pavlovian autoshaping procedure in an apparatus allowing the automated presentation of computer-graphic stimuli to rats (T. J. Bussey, J. L. Muir, & T. W. Robbins, 1994). White vertical rectangles were presented on the left or the right of a computer screen. One of these conditioned stimuli (the CS+) was always followed by the presentation of a sucrose pellet; the other, the CS-, was never followed by reward. With training, rats came to approach the CS+ more often than the CS-. Anterior cingulate cortex-lesioned rats failed to demonstrate normal discriminated approach, making significantly more approaches to the CS- than did sham-operated controls. Medial frontal cortex-lesioned rats acquired the task normally but had longer overall approach latencies. Posterior cingulate cortex lesions did not affect acquisition.

Social isolation stress and chronic glutathione deficiency have a common effect on the glutamine-to-glutamate ratio and myo-inositol concentration in the mouse frontal cortex.

PubMed

Corcoba, Alberto; Gruetter, Rolf; Do, Kim Q; Duarte, João M N

2017-09-01

Environmental stress can interact with genetic predisposition to increase the risk of developing psychopathology. In this work, we tested the hypothesis that social isolation stress interacts with impaired glutathione synthesis and have cumulative effects on the neurochemical profile of the frontal cortex. A mouse model with chronic glutathione deficit induced by knockout (-/-) of the glutamate-cysteine ligase modulatory subunit (Gclm) was exposed to social isolation stress from weaning to post-natal day 65. Using magnetic resonance methods at high-field (14.1 T), we analysed the neurochemical profile in the frontal cortex, brain size and ventricular volume of adult animals. Glutathione deficit was accompanied by elevated concentrations of N-acetylaspartate, alanine, and glutamine, as well as the ratio of glutamine-to-glutamate (Gln/Glu), and by a reduction in levels of myo-inositol and choline-containing compounds in the frontal cortex of -/- animals with respect to wild-type littermates. Although there was no significant interaction between social isolation stress and glutathione deficiency, mice reared in isolation displayed lower myo-inositol concentration (-8.4%, p < 0.05) and larger Gln/Glu (+7.6%, p < 0.05), relative to those in group housing. Furthermore, glutathione deficiency caused a reduction in whole brain volume and enlargement of ventricles, but social isolation had no effect on these parameters. We conclude that social isolation caused neurochemical alterations that may add to those associated to impaired glutathione synthesis. © 2017 International Society for Neurochemistry.

Increased neuroinflammatory and arachidonic acid cascade markers, and reduced synaptic proteins, in the postmortem frontal cortex from schizophrenia patients

PubMed Central

Rao, Jagadeesh Sridhara; Kim, Hyung-Wook; Harry, Gaylia Jean; Rapoport, Stanley Isaac; Reese, Edmund Arthur

2013-01-01

Schizophrenia (SZ) is a progressive, neuropsychiatric disorder associated with cognitive impairment. A number of brain alterations have been linked to cognitive impairment, including neuroinflammation, excitotoxicity, increased arachidonic acid (AA) signaling and reduced synaptic protein. On this basis, we tested the hypothesis that SZ pathology is associated with these pathological brain changes. To do this, we examined postmortem frontal cortex from 10 SZ patients and 10 controls and measured protein and mRNA levels of cytokines, and astroglial, microglial, neuroinflammatory excitotoxic, AA cascade, apoptotic and synaptic markers. Mean protein and mRNA levels of interleukin-1β, tumor necrosis factor-α, glial acidic fibrillary protein (GFAP), a microglial marker CD11b, and nuclear factor kappa B subunits were significantly increased in SZ compared with control brain. Protein and mRNA levels of cytosolic and secretory phospholipase A2 and cyclooxygenase were significantly elevated in postmortem brains from SZ patients. N-methyl-D-aspartate receptor subunits 1 and 2B, inducible nitric oxide synthase and c-FOS were not significantly different. In addition, reduced protein and mRNA levels of brain-derived neurotrophic factor, synaptophysin and drebrin were found in SZ compared with control frontal cortex. Increased neuroinflammation and AA cascade enzyme markers with synaptic protein loss could promote disease progression and cognitive defects in SZ patients. Drugs that downregulate these changes might be considered for new therapies in SZ. PMID:23566496

Severe Alterations in Lipid Composition of Frontal Cortex Lipid Rafts from Parkinson’s Disease and Incidental Parkinson’s Disease

PubMed Central

Fabelo, Noemí; Martín, Virginia; Santpere, Gabriel; Marín, Raquel; Torrent, Laia; Ferrer, Isidre; Díaz, Mario

2011-01-01

Lipid rafts are cholesterol- and sphingomyelin-enriched microdomains that provide a highly saturated and viscous physicochemical microenvironment to promote protein–lipid and protein–protein interactions. We purified lipid rafts from human frontal cortex from normal, early motor stages of Parkinson’s disease (PD) and incidental Parkinson’s disease (iPD) subjects and analyzed their lipid composition. We observed that lipid rafts from PD and iPD cortices exhibit dramatic reductions in their contents of n-3 and n-6 long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (22:6-n3) and arachidonic acid (20:4n-6). Also, saturated fatty acids (16:0 and 18:0) were significantly higher than in control brains. Paralleling these findings, unsaturation and peroxidability indices were considerably reduced in PD and iPD lipid rafts. Lipid classes were also affected in PD and iPD lipid rafts. Thus, phosphatidylserine and phosphatidylinositol were increased in PD and iPD, whereas cerebrosides and sulfatides and plasmalogen levels were considerably diminished. Our data pinpoint a dramatic increase in lipid raft order due to the aberrant biochemical structure in PD and iPD and indicate that these abnormalities of lipid rafts in the frontal cortex occur at early stages of PD pathology. The findings correlate with abnormal lipid raft signaling and cognitive decline observed during the development of these neurodegenerative disorders. PMID:21717034

Drug Addiction and Its Underlying Neurobiological Basis: Neuroimaging Evidence for the Involvement of the Frontal Cortex

PubMed Central

Goldstein, Rita Z.; Volkow, Nora D.

2005-01-01

Objective Studies of the neurobiological processes underlying drug addiction primarily have focused on limbic subcortical structures. Here the authors evaluated the role of frontal cortical structures in drug addiction. Method An integrated model of drug addiction that encompasses intoxication, bingeing, withdrawal, and craving is proposed. This model and findings from neuroimaging studies on the behavioral, cognitive, and emotional processes that are at the core of drug addiction were used to analyze the involvement of frontal structures in drug addiction. Results The orbitofrontal cortex and the anterior cingulate gyrus, which are regions neuroanatomically connected with limbic structures, are the frontal cortical areas most frequently implicated in drug addiction. They are activated in addicted subjects during intoxication, craving, and bingeing, and they are deactivated during withdrawal. These regions are also involved in higher-order cognitive and motivational functions, such as the ability to track, update, and modulate the salience of a reinforcer as a function of context and expectation and the ability to control and inhibit prepotent responses. Conclusions These results imply that addiction connotes cortically regulated cognitive and emotional processes, which result in the overvaluing of drug reinforcers, the undervaluing of alternative reinforcers, and deficits in inhibitory control for drug responses. These changes in addiction, which the authors call I-RISA (impaired response inhibition and salience attribution), expand the traditional concepts of drug dependence that emphasize limbic-regulated responses to pleasure and reward. PMID:12359667

Left frontal hub connectivity delays cognitive impairment in autosomal-dominant and sporadic Alzheimer’s disease

PubMed Central

Franzmeier, Nicolai; Düzel, Emrah; Jessen, Frank; Buerger, Katharina; Levin, Johannes; Duering, Marco; Dichgans, Martin; Haass, Christian; Suárez-Calvet, Marc; Fagan, Anne M; Paumier, Katrina; Benzinger, Tammie; Masters, Colin L; Morris, John C; Perneczky, Robert; Janowitz, Daniel; Catak, Cihan; Wolfsgruber, Steffen; Wagner, Michael; Teipel, Stefan; Kilimann, Ingo; Ramirez, Alfredo; Rossor, Martin; Jucker, Mathias; Chhatwal, Jasmeer; Spottke, Annika; Boecker, Henning; Brosseron, Frederic; Falkai, Peter; Fliessbach, Klaus; Heneka, Michael T; Laske, Christoph; Nestor, Peter; Peters, Oliver; Fuentes, Manuel; Menne, Felix; Priller, Josef; Spruth, Eike J; Franke, Christiana; Schneider, Anja; Kofler, Barbara; Westerteicher, Christine; Speck, Oliver; Wiltfang, Jens; Bartels, Claudia; Araque Caballero, Miguel Ángel; Metzger, Coraline; Bittner, Daniel; Weiner, Michael; Lee, Jae-Hong; Salloway, Stephen; Danek, Adrian; Goate, Alison; Schofield, Peter R; Bateman, Randall J; Ewers, Michael

2018-01-01

Abstract Patients with Alzheimer’s disease vary in their ability to sustain cognitive abilities in the presence of brain pathology. A major open question is which brain mechanisms may support higher reserve capacity, i.e. relatively high cognitive performance at a given level of Alzheimer’s pathology. Higher functional MRI-assessed functional connectivity of a hub in the left frontal cortex is a core candidate brain mechanism underlying reserve as it is associated with education (i.e. a protective factor often associated with higher reserve) and attenuated cognitive impairment in prodromal Alzheimer’s disease. However, no study has yet assessed whether such hub connectivity of the left frontal cortex supports reserve throughout the evolution of pathological brain changes in Alzheimer’s disease, including the presymptomatic stage when cognitive decline is subtle. To address this research gap, we obtained cross-sectional resting state functional MRI in 74 participants with autosomal dominant Alzheimer’s disease, 55 controls from the Dominantly Inherited Alzheimer’s Network and 75 amyloid-positive elderly participants, as well as 41 amyloid-negative cognitively normal elderly subjects from the German Center of Neurodegenerative Diseases multicentre study on biomarkers in sporadic Alzheimer’s disease. For each participant, global left frontal cortex connectivity was computed as the average resting state functional connectivity between the left frontal cortex (seed) and each voxel in the grey matter. As a marker of disease stage, we applied estimated years from symptom onset in autosomal dominantly inherited Alzheimer’s disease and cerebrospinal fluid tau levels in sporadic Alzheimer’s disease cases. In both autosomal dominant and sporadic Alzheimer’s disease patients, higher levels of left frontal cortex connectivity were correlated with greater education. For autosomal dominant Alzheimer’s disease, a significant left frontal cortex connectivity �

The contribution of distinct subregions of the ventromedial frontal cortex to emotion, social behavior, and decision making.

PubMed

Rudebeck, P H; Bannerman, D M; Rushworth, M F S

2008-12-01

Damage to the ventromedial frontal cortex (VMFC) in humans is associated with deficits in decision making. Decision making, however, often happens while people are interacting with others, where it is important to take the social consequences of a course of action into account. It is well known that VMFC lesions also lead to marked alterations in patients' emotions and ability to interact socially; however, it has not been clear which parts of the VMFC are critical for these changes. Recently, there has been considerable interest in the role of the VMFC in choice behavior during interpersonal exchanges. Here, we highlight recent research that suggests that two areas within or adjacent to the VMFC, the orbitofrontal cortex (OFC) and the anterior cingulate cortex (ACC), may play distinct but complementary roles in mediating normal patterns of emotion and social behavior. Converging lines of evidence from human, macaque, and rat studies now suggest that the OFC may be more specialized for simple emotional responses, such as fear and aggression, through its role in representing primary reinforcement or punishment. By contrast, the ACC may play a distinct role in more complex aspects of emotion, such as social interaction, by virtue of its connections with the discrete parts of the temporal lobe and subcortical structures that control autonomic responses.

Interactions between neurons in the frontal cortex and hippocampus in cats trained to select reinforcements of different value in conditions of cholinergic deficiency.

PubMed

Dolbakyan, E E; Merzhanova, G Kh

2007-09-01

An operant food-related conditioned reflex was developed in six cats by the "active choice" protocol: short-latency pedal presses were followed by presentation of low-quality reinforcement (bread-meat mix), while long-latency pedal presses were followed by presentation of high-quality reinforcement (meat). Animals differed in terms of their food-procuring strategies, displaying "self-control," "ambivalence," or "impulsivity." Multineuron activity was recorded from the frontal cortex and hippocampus (field CA3). Cross-correlation analysis of interneuronal interactions within (local networks) and between (distributed networks) study structures showed that the numbers of interneuronal interactions in both local and distributed networks were maximal in animals with "self-control." On the background of systemic administration of the muscarinic cholinoreceptor blockers scopolamine and trihexyphenidyl, the numbers of interneuronal interactions decreased, while "common source" influences increased. This correlated with impairment of the reproduction of the selected strategy, primarily affecting the animals' self-controlled behavior. These results show that the "self-control" strategy is determined by the organization of local and distributed networks in the frontal cortex and hippocampus.

Development of a neurofeedback protocol targeting the frontal pole using near-infrared spectroscopy.

PubMed

Kinoshita, Akihide; Takizawa, Ryu; Yahata, Noriaki; Homae, Fumitaka; Hashimoto, Ryuichiro; Sakakibara, Eisuke; Kawasaki, Shingo; Nishimura, Yukika; Koike, Shinsuke; Kasai, Kiyoto

2016-11-01

Neurofeedback has been studied with the aim of controlling cerebral activity. Near-infrared spectroscopy is a non-invasive neuroimaging technique used for measuring hemoglobin concentration changes in cortical surface areas with high temporal resolution. Thus, near-infrared spectroscopy may be useful for neurofeedback, which requires real-time feedback of repeated brain activation measurements. However, no study has specifically targeted neurofeedback, using near-infrared spectroscopy, in the frontal pole cortex. We developed an original near-infrared spectroscopy neurofeedback system targeting the frontal pole cortex. Over a single day of testing, each healthy participant (n = 24) received either correct or incorrect (Sham) feedback from near-infrared spectroscopy signals, based on a crossover design. Under correct feedback conditions, significant activation was observed in the frontal pole cortex (P = 0.000073). Additionally, self-evaluation of control and metacognitive beliefs were associated with near-infrared spectroscopy signals (P = 0.006). The neurofeedback system developed in this study might be useful for developing control of frontal pole cortex activation. © 2016 The Authors. Psychiatry and Clinical Neurosciences © 2016 Japanese Society of Psychiatry and Neurology.

Neurons in the Frontal Lobe Encode the Value of Multiple Decision Variables

PubMed Central

Kennerley, Steven W.; Dahmubed, Aspandiar F.; Lara, Antonio H.; Wallis, Jonathan D.

2009-01-01

A central question in behavioral science is how we select among choice alternatives to obtain consistently the most beneficial outcomes. Three variables are particularly important when making a decision: the potential payoff, the probability of success, and the cost in terms of time and effort. A key brain region in decision making is the frontal cortex as damage here impairs the ability to make optimal choices across a range of decision types. We simultaneously recorded the activity of multiple single neurons in the frontal cortex while subjects made choices involving the three aforementioned decision variables. This enabled us to contrast the relative contribution of the anterior cingulate cortex (ACC), the orbito-frontal cortex, and the lateral prefrontal cortex to the decision-making process. Neurons in all three areas encoded value relating to choices involving probability, payoff, or cost manipulations. However, the most significant signals were in the ACC, where neurons encoded multiplexed representations of the three different decision variables. This supports the notion that the ACC is an important component of the neural circuitry underlying optimal decision making. PMID:18752411

Frontal Eye Fields Control Attentional Modulation of Alpha and Gamma Oscillations in Contralateral Occipitoparietal Cortex

PubMed Central

O'Shea, Jacinta; Jensen, Ole; Bergmann, Til O.

2015-01-01

Covertly directing visuospatial attention produces a frequency-specific modulation of neuronal oscillations in occipital and parietal cortices: anticipatory alpha (8–12 Hz) power decreases contralateral and increases ipsilateral to attention, whereas stimulus-induced gamma (>40 Hz) power is boosted contralaterally and attenuated ipsilaterally. These modulations must be under top-down control; however, the control mechanisms are not yet fully understood. Here we investigated the causal contribution of the human frontal eye field (FEF) by combining repetitive transcranial magnetic stimulation (TMS) with subsequent magnetoencephalography. Following inhibitory theta burst stimulation to the left FEF, right FEF, or vertex, participants performed a visual discrimination task requiring covert attention to either visual hemifield. Both left and right FEF TMS caused marked attenuation of alpha modulation in the occipitoparietal cortex. Notably, alpha modulation was consistently reduced in the hemisphere contralateral to stimulation, leaving the ipsilateral hemisphere relatively unaffected. Additionally, right FEF TMS enhanced gamma modulation in left visual cortex. Behaviorally, TMS caused a relative slowing of response times to targets contralateral to stimulation during the early task period. Our results suggest that left and right FEF are causally involved in the attentional top-down control of anticipatory alpha power in the contralateral visual system, whereas a right-hemispheric dominance seems to exist for control of stimulus-induced gamma power. These findings contrast the assumption of primarily intrahemispheric connectivity between FEF and parietal cortex, emphasizing the relevance of interhemispheric interactions. The contralaterality of effects may result from a transient functional reorganization of the dorsal attention network after inhibition of either FEF. PMID:25632139

Chronic Ritalin Administration during Adulthood Increases Serotonin Pool in Rat Medial Frontal Cortex

PubMed Central

Daniali, Samira; Nahavandi, Arezo; Madjd, Zahra; Shahbazi, Ali; Niknazar, Somayeh; Shahbazzadeh, Delavar

2013-01-01

Background: Ritalin has high tendency to be abused. It has been the main indication to control attention deficit hyperactivity disorder. The college students may seek for it to improve their memory, decrease the need for sleep (especially during exams), which at least partially, can be related to serotonergic system. Therefore, it seems worthy to evaluate the effect of Ritalin intake on mature brain. There are many studies on Ritalin effect on developing brain, but only few studies on adults are available. This study was undertaken to find Ritalin effect on serotonin transporter (SERT) density in medial frontal cortex (MFC) of mature rat. Methods: Thirty male Wistar rats were used in the study. Rats were assigned into five groups (n = 6 per group): one control, two Ritalin and two vehicle groups. Twelve rats received Ritalin (20 mg/kg/twice a day) orally for eleven continuous days. After one week of withdrawal and another two weeks of rest, in order to evaluate short-term effects of Ritalin, six rats were sacrificed. Another six rats were studied to detect the long-term effects of Ritalin; therefore, they were sacrificed 12 weeks after the previous group. The immunohistochemistry was performed to evaluate the results. Results: Immunohistochemistry studies showed a higher density of SERT in both 2 and 12 weeks after withdrawal from Ritalin intake in MFC of rat and there was no significant difference between these two groups. Conclusions: Our findings demonstrated both short- and long-term effects of Ritalin on frontal serotonergic system after withdrawal period. PMID:23748891

A hierarchy of timescales explains distinct effects of local inhibition of primary visual cortex and frontal eye fields

PubMed Central

Cocchi, Luca; Sale, Martin V; L Gollo, Leonardo; Bell, Peter T; Nguyen, Vinh T; Zalesky, Andrew; Breakspear, Michael; Mattingley, Jason B

2016-01-01

Within the primate visual system, areas at lower levels of the cortical hierarchy process basic visual features, whereas those at higher levels, such as the frontal eye fields (FEF), are thought to modulate sensory processes via feedback connections. Despite these functional exchanges during perception, there is little shared activity between early and late visual regions at rest. How interactions emerge between regions encompassing distinct levels of the visual hierarchy remains unknown. Here we combined neuroimaging, non-invasive cortical stimulation and computational modelling to characterize changes in functional interactions across widespread neural networks before and after local inhibition of primary visual cortex or FEF. We found that stimulation of early visual cortex selectively increased feedforward interactions with FEF and extrastriate visual areas, whereas identical stimulation of the FEF decreased feedback interactions with early visual areas. Computational modelling suggests that these opposing effects reflect a fast-slow timescale hierarchy from sensory to association areas. DOI: http://dx.doi.org/10.7554/eLife.15252.001 PMID:27596931

A hierarchy of timescales explains distinct effects of local inhibition of primary visual cortex and frontal eye fields.

PubMed

Cocchi, Luca; Sale, Martin V; L Gollo, Leonardo; Bell, Peter T; Nguyen, Vinh T; Zalesky, Andrew; Breakspear, Michael; Mattingley, Jason B

2016-09-06

Within the primate visual system, areas at lower levels of the cortical hierarchy process basic visual features, whereas those at higher levels, such as the frontal eye fields (FEF), are thought to modulate sensory processes via feedback connections. Despite these functional exchanges during perception, there is little shared activity between early and late visual regions at rest. How interactions emerge between regions encompassing distinct levels of the visual hierarchy remains unknown. Here we combined neuroimaging, non-invasive cortical stimulation and computational modelling to characterize changes in functional interactions across widespread neural networks before and after local inhibition of primary visual cortex or FEF. We found that stimulation of early visual cortex selectively increased feedforward interactions with FEF and extrastriate visual areas, whereas identical stimulation of the FEF decreased feedback interactions with early visual areas. Computational modelling suggests that these opposing effects reflect a fast-slow timescale hierarchy from sensory to association areas.

Loss of Sleep Affects the Ultrastructure of Pyramidal Neurons in the Adolescent Mouse Frontal Cortex

PubMed Central

de Vivo, Luisa; Nelson, Aaron B.; Bellesi, Michele; Noguti, Juliana; Tononi, Giulio; Cirelli, Chiara

2016-01-01

Study Objective: The adolescent brain may be uniquely affected by acute sleep deprivation (ASD) and chronic sleep restriction (CSR), but direct evidence is lacking. We used electron microscopy to examine how ASD and CSR affect pyramidal neurons in the frontal cortex of adolescent mice, focusing on mitochondria, endosomes, and lysosomes that together perform most basic cellular functions, from nutrient intake to prevention of cellular stress. Methods: Adolescent (1-mo-old) mice slept (S) or were sleep deprived (ASD, with novel objects and running wheels) during the first 6–8 h of the light period, chronically sleep restricted (CSR) for > 4 days (using novel objects, running wheels, social interaction, forced locomotion, caffeinated water), or allowed to recover sleep (RS) for ∼32 h after CSR. Ultrastructural analysis of 350 pyramidal neurons was performed (S = 82; ASD = 86; CSR = 103; RS = 79; 4 to 5 mice/group). Results: Several ultrastructural parameters differed in S versus ASD, S versus CSR, CSR versus RS, and S versus RS, although the different methods used to enforce wake may have contributed to some of the differences between short and long sleep loss. Differences included larger cytoplasmic area occupied by mitochondria in CSR versus S, and higher number of secondary lysosomes in CSR versus S and RS. We also found that sleep loss may unmask interindividual differences not obvious during baseline sleep. Moreover, using a combination of 11 ultrastructural parameters, we could predict in up to 80% of cases whether sleep or wake occurred at the single cell level. Conclusions: Ultrastructural analysis may be a powerful tool to identify which cellular organelles, and thus which cellular functions, are most affected by sleep and sleep loss. Citation: de Vivo L, Nelson AB, Bellesi M, Noguti J, Tononi G, Cirelli C. Loss of sleep affects the ultrastructure of pyramidal neurons in the adolescent mouse frontal cortex. SLEEP 2016;39(4):861–874. PMID:26715225

Modulation of sibutramine-induced increases in extracellular noradrenaline concentration in rat frontal cortex and hypothalamus by α2-adrenoceptors

PubMed Central

Wortley, K E; Heal, D J; Stanford, S C

1999-01-01

The effects of sibutramine (0.25–10 mg kg−1 i.p.) on extracellular noradrenaline concentration in the frontal cortex and hypothalamus of freely-moving rats were investigated using microdialysis. The role of presynaptic α2-adrenoceptors in modulating the effects of sibutramine in these brain areas was also determined.Sibutramine induced an increase in extracellular noradrenaline concentration, the magnitude of which paralleled dose, in both brain areas. In the cortex, this increase was gradual and sustained, whereas in the hypothalamus it was more rapid and of shorter duration.In both the cortex and hypothalamus, pretreatment of rats with the α2-adrenoceptor antagonist RX821002 (3 mg kg−1 i.p.) potentiated increases in the accumulation of extracellular noradrenaline induced by sibutramine (10 mg kg−1 i.p.), by 7 and 10 fold respectively. RX821002 also reduced the latency of sibutramine to reach its maximum effect in the cortex, but not in the hypothalamus.Infusion of RX821002 (1 μM) via the probe increased the accumulation of extracellular noradrenaline induced by sibutramine (10 mg kg−1 i.p.) in both brain areas. In the hypothalamus, the effects of RX821002 on the accumulation of noradrenaline induced by sibutramine were 2 fold greater than those in the cortex.These findings support evidence that sibutramine inhibits the reuptake of noradrenaline in vivo, but that the accumulation of extracellular noradrenaline is limited by noradrenergic activation of presynaptic α2-adrenoceptors. Furthermore, the data suggest that terminal α2-adrenoceptors in the hypothalamus exert a greater inhibitory effect over the control of extracellular noradrenaline accumulation than do those in the cortex. PMID:10516646

Short-Term Memory for Space and Time Flexibly Recruit Complementary Sensory-Biased Frontal Lobe Attention Networks.

PubMed

Michalka, Samantha W; Kong, Lingqiang; Rosen, Maya L; Shinn-Cunningham, Barbara G; Somers, David C

2015-08-19

The frontal lobes control wide-ranging cognitive functions; however, functional subdivisions of human frontal cortex are only coarsely mapped. Here, functional magnetic resonance imaging reveals two distinct visual-biased attention regions in lateral frontal cortex, superior precentral sulcus (sPCS) and inferior precentral sulcus (iPCS), anatomically interdigitated with two auditory-biased attention regions, transverse gyrus intersecting precentral sulcus (tgPCS) and caudal inferior frontal sulcus (cIFS). Intrinsic functional connectivity analysis demonstrates that sPCS and iPCS fall within a broad visual-attention network, while tgPCS and cIFS fall within a broad auditory-attention network. Interestingly, we observe that spatial and temporal short-term memory (STM), respectively, recruit visual and auditory attention networks in the frontal lobe, independent of sensory modality. These findings not only demonstrate that both sensory modality and information domain influence frontal lobe functional organization, they also demonstrate that spatial processing co-localizes with visual processing and that temporal processing co-localizes with auditory processing in lateral frontal cortex. Copyright © 2015 Elsevier Inc. All rights reserved.

5-HT2A Receptor Binding in the Frontal Cortex of Parkinson's Disease Patients and Alpha-Synuclein Overexpressing Mice: A Postmortem Study

PubMed Central

Rasmussen, Nadja Bredo; Olesen, Mikkel Vestergaard; Plenge, Per; Klein, Anders Bue; Westin, Jenny E.; Fog, Karina

2016-01-01

The 5-HT2A receptor is highly involved in aspects of cognition and executive function and seen to be affected in neurodegenerative diseases like Alzheimer's disease and related to the disease pathology. Even though Parkinson's disease (PD) is primarily a motor disorder, reports of impaired executive function are also steadily being associated with this disease. Not much is known about the pathophysiology behind this. The aim of this study was thereby twofold: (1) to investigate 5-HT2A receptor binding levels in Parkinson's brains and (2) to investigate whether PD associated pathology, alpha-synuclein (AS) overexpression, could be associated with 5-HT2A alterations. Binding density for the 5-HT2A-specific radioligand [3H]-MDL 100.907 was measured in membrane suspensions of frontal cortex tissue from PD patients. Protein levels of AS were further measured using western blotting. Results showed higher AS levels accompanied by increased 5-HT2A receptor binding in PD brains. In a separate study, we looked for changes in 5-HT2A receptors in the prefrontal cortex in 52-week-old transgenic mice overexpressing human AS. We performed region-specific 5-HT2A receptor binding measurements followed by gene expression analysis. The transgenic mice showed lower 5-HT2A binding in the frontal association cortex that was not accompanied by changes in gene expression levels. This study is one of the first to look at differences in serotonin receptor levels in PD and in relation to AS overexpression. PMID:27579212

Dissociable contributions of the orbitofrontal and infralimbic cortex to pavlovian autoshaping and discrimination reversal learning: further evidence for the functional heterogeneity of the rodent frontal cortex.

PubMed

Chudasama, Y; Robbins, Trevor W

2003-09-24

To examine possible heterogeneity of function within the ventral regions of the rodent frontal cortex, the present study compared the effects of excitotoxic lesions of the orbitofrontal cortex (OFC) and the infralimbic cortex (ILC) on pavlovian autoshaping and discrimination reversal learning. During the pavlovian autoshaping task, in which rats learn to approach a stimulus predictive of reward [conditional stimulus (CS+)], only the OFC group failed to acquire discriminated approach but was unimpaired when preoperatively trained. In the visual discrimination learning and reversal task, rats were initially required to discriminate a stimulus positively associated with reward. There was no effect of either OFC or ILC lesions on discrimination learning. When the stimulus-reward contingencies were reversed, both groups of animals committed more errors, but only the OFC-lesioned animals were unable to suppress the previously rewarded stimulus-reward association, committing more "stimulus perseverative" errors. In contrast, the ILC group showed a pattern of errors that was more attributable to "learning" than perseveration. These findings suggest two types of dissociation between the effects of OFC and ILC lesions: (1) OFC lesions impaired the learning processes implicated in pavlovian autoshaping but not instrumental simultaneous discrimination learning, whereas ILC lesions were unimpaired at autoshaping and their reversal learning deficit did not reflect perseveration, and (2) OFC lesions induced perseverative responding in reversal learning but did not disinhibit responses to pavlovian CS-. In contrast, the ILC lesion had no effect on response inhibitory control in either of these settings. The findings are discussed in the context of dissociable executive functions in ventral sectors of the rat prefrontal cortex.

Role of medio-dorsal frontal and posterior parietal neurons during auditory detection performance in rats.

PubMed

Bohon, Kaitlin S; Wiest, Michael C

2014-01-01

To further characterize the role of frontal and parietal cortices in rat cognition, we recorded action potentials simultaneously from multiple sites in the medio-dorsal frontal cortex and posterior parietal cortex of rats while they performed a two-choice auditory detection task. We quantified neural correlates of task performance, including response movements, perception of a target tone, and the differentiation between stimuli with distinct features (different pitches or durations). A minority of units--15% in frontal cortex, 23% in parietal cortex--significantly distinguished hit trials (successful detections, response movement to the right) from correct rejection trials (correct leftward response to the absence of the target tone). Estimating the contribution of movement-related activity to these responses suggested that more than half of these units were likely signaling correct perception of the auditory target, rather than merely movement direction. In addition, we found a smaller and mostly not overlapping population of units that differentiated stimuli based on task-irrelevant details. The detection-related spiking responses we observed suggest that correlates of perception in the rat are sparsely represented among neurons in the rat's frontal-parietal network, without being concentrated preferentially in frontal or parietal areas.

Effects of early weaning and social isolation on the expression of glucocorticoid and mineralocorticoid receptor and 11beta-hydroxysteroid dehydrogenase 1 and 2 mRNAs in the frontal cortex and hippocampus of piglets.

PubMed

Poletto, R; Steibel, J P; Siegford, J M; Zanella, A J

2006-01-05

Pigs weaned at young ages show more abnormal and aggressive behaviors and cognitive deficits compared to later weaned pigs. We investigated the effects of age, weaning and/or social isolation on the expression of genes regulating glucocorticoid response [glucocorticoid receptor (GR), mineralocorticoid receptor (MR), 11beta-hydroxysteroid dehydrogenases 1 and 2 (11beta-HSD1 and 11beta-HSD2)] in the frontal cortex and hippocampus. Early- (EW; n = 6) and conventionally-weaned (CW; n = 6) piglets were weaned at 10 and 21 days after birth, respectively. Non-weaned (NW) piglets of both ages (NW; n = 6/group) remained with their dams. Immediately before euthanasia, half of CW, EW and NW animals were socially isolated for 15 min at 12 (EW, NW) and 23 (CW, NW) days of age. Differences in amounts of 11beta-HSD1, 11beta-HSD2, GR and MR mRNA were determined by quantitative real-time RT-PCR and data subjected to multivariate linear mixed model analysis. When compared with NW piglets at 12 days of age, the hippocampi of EW piglets showed decreased gene expression (P < 0.01). Social isolation decreased gene expression (P < 0.05) in the frontal cortex of all piglets. Twelve-day-old piglets showed higher MR mRNA in the frontal cortex (P < 0.01) and lower 11beta-HSD2 and GR mRNA (P < 0.05) in the hippocampus compared to 23-day-old animals. Results indicate that EW affected the hippocampus of piglets at 12 days of age, while social isolation affected frontal cortex regardless of age. These results may be correlated with behavioral and cognitive changes reported in EW piglets.

The role of the frontal cortex in memory: an investigation of the Von Restorff effect

PubMed Central

Elhalal, Anat; Davelaar, Eddy J.; Usher, Marius

2014-01-01

Evidence from neuropsychology and neuroimaging indicate that the pre-frontal cortex (PFC) plays an important role in human memory. Although frontal patients are able to form new memories, these memories appear qualitatively different from those of controls by lacking distinctiveness. Neuroimaging studies of memory indicate activation in the PFC under deep encoding conditions, and under conditions of semantic elaboration. Based on these results, we hypothesize that the PFC enhances memory by extracting differences and commonalities in the studied material. To test this hypothesis, we carried out an experimental investigation to test the relationship between the PFC-dependent factors and semantic factors associated with common and specific features of words. These experiments were performed using Free-Recall of word lists with healthy adults, exploiting the correlation between PFC function and fluid intelligence. As predicted, a correlation was found between fluid intelligence and the Von-Restorff effect (better memory for semantic isolates, e.g., isolate “cat” within category members of “fruit”). Moreover, memory for the semantic isolate was found to depend on the isolate's serial position. The isolate item tends to be recalled first, in comparison to non-isolates, suggesting that the process interacts with short term memory. These results are captured within a computational model of free recall, which includes a PFC mechanism that is sensitive to both commonality and distinctiveness, sustaining a trade-off between the two. PMID:25018721

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

Frontal eye fields control attentional modulation of alpha and gamma oscillations in contralateral occipitoparietal cortex.

PubMed

Marshall, Tom R; O'Shea, Jacinta; Jensen, Ole; Bergmann, Til O

2015-01-28

Covertly directing visuospatial attention produces a frequency-specific modulation of neuronal oscillations in occipital and parietal cortices: anticipatory alpha (8-12 Hz) power decreases contralateral and increases ipsilateral to attention, whereas stimulus-induced gamma (>40 Hz) power is boosted contralaterally and attenuated ipsilaterally. These modulations must be under top-down control; however, the control mechanisms are not yet fully understood. Here we investigated the causal contribution of the human frontal eye field (FEF) by combining repetitive transcranial magnetic stimulation (TMS) with subsequent magnetoencephalography. Following inhibitory theta burst stimulation to the left FEF, right FEF, or vertex, participants performed a visual discrimination task requiring covert attention to either visual hemifield. Both left and right FEF TMS caused marked attenuation of alpha modulation in the occipitoparietal cortex. Notably, alpha modulation was consistently reduced in the hemisphere contralateral to stimulation, leaving the ipsilateral hemisphere relatively unaffected. Additionally, right FEF TMS enhanced gamma modulation in left visual cortex. Behaviorally, TMS caused a relative slowing of response times to targets contralateral to stimulation during the early task period. Our results suggest that left and right FEF are causally involved in the attentional top-down control of anticipatory alpha power in the contralateral visual system, whereas a right-hemispheric dominance seems to exist for control of stimulus-induced gamma power. These findings contrast the assumption of primarily intrahemispheric connectivity between FEF and parietal cortex, emphasizing the relevance of interhemispheric interactions. The contralaterality of effects may result from a transient functional reorganization of the dorsal attention network after inhibition of either FEF. Copyright © 2015 the authors 0270-6474/15/351638-10$15.00/0.

A high-fat diet decreases GABA concentration in the frontal cortex and hippocampus of rats.

PubMed

Sandoval-Salazar, Cuauhtemoc; Ramírez-Emiliano, Joel; Trejo-Bahena, Aurora; Oviedo-Solís, Cecilia I; Solís-Ortiz, Martha Silvia

2016-02-29

It has been proposed that the γ-aminobutyric acid (GABA) plays a key role in the regulation of food intake and body weight by controlling the excitability, plasticity and the synchronization of neuronal activity in the frontal cortex (FC). It has been also proposed that the high-fat diet (HFD) could disturb the metabolism of glutamate and consequently the GABA levels, but the mechanism is not yet clearly understood. Therefore, the aim of this study was to investigate the effect of a HFD on the GABA levels in the FC and hippocampus of rats. The HFD significantly increased weight gain and blood glucose levels, whereas decreased the GABA levels in the FC and hippocampus compared with standard diet-fed rats. HFD decreases GABA levels in the FC and hippocampus of rat, which likely disrupts the GABAergic inhibitory processes, underlying feeding behavior.

Evaluating choices by single neurons in the frontal lobe: outcome value encoded across multiple decision variables

PubMed Central

Kennerley, Steven W.; Wallis, Jonathan D.

2009-01-01

Damage to the frontal lobe can cause severe decision-making impairments. A mechanism that may underlie this is that neurons in the frontal cortex encode many variables that contribute to the valuation of a choice, such as its costs, benefits and probability of success. However, optimal decision-making requires that one considers these variables, not only when faced with the choice, but also when evaluating the outcome of the choice, in order to adapt future behaviour appropriately. To examine the role of the frontal cortex in encoding the value of different choice outcomes, we simultaneously recorded the activity of multiple single neurons in the anterior cingulate cortex (ACC), orbitofrontal cortex (OFC) and lateral prefrontal cortex (LPFC) while subjects evaluated the outcome of choices involving manipulations of probability, payoff and cost. Frontal neurons encoded many of the parameters that enabled the calculation of the value of these variables, including the onset and offset of reward and the amount of work performed, and often encoded the value of outcomes across multiple decision variables. In addition, many neurons encoded both the predicted outcome during the choice phase of the task as well as the experienced outcome in the outcome phase of the task. These patterns of selectivity were more prevalent in ACC relative to OFC and LPFC. These results support a role for the frontal cortex, principally ACC, in selecting between choice alternatives and evaluating the outcome of that selection thereby ensuring that choices are optimal and adaptive. PMID:19453638

Fetal functional imaging portrays heterogeneous development of emerging human brain networks

PubMed Central

Jakab, András; Schwartz, Ernst; Kasprian, Gregor; Gruber, Gerlinde M.; Prayer, Daniela; Schöpf, Veronika; Langs, Georg

2014-01-01

The functional connectivity architecture of the adult human brain enables complex cognitive processes, and exhibits a remarkably complex structure shared across individuals. We are only beginning to understand its heterogeneous structure, ranging from a strongly hierarchical organization in sensorimotor areas to widely distributed networks in areas such as the parieto-frontal cortex. Our study relied on the functional magnetic resonance imaging (fMRI) data of 32 fetuses with no detectable morphological abnormalities. After adapting functional magnetic resonance acquisition, motion correction, and nuisance signal reduction procedures of resting-state functional data analysis to fetuses, we extracted neural activity information for major cortical and subcortical structures. Resting fMRI networks were observed for increasing regional functional connectivity from 21st to 38th gestational weeks (GWs) with a network-based statistical inference approach. The overall connectivity network, short range, and interhemispheric connections showed sigmoid expansion curve peaking at the 26–29 GW. In contrast, long-range connections exhibited linear increase with no periods of peaking development. Region-specific increase of functional signal synchrony followed a sequence of occipital (peak: 24.8 GW), temporal (peak: 26 GW), frontal (peak: 26.4 GW), and parietal expansion (peak: 27.5 GW). We successfully adapted functional neuroimaging and image post-processing approaches to correlate macroscopical scale activations in the fetal brain with gestational age. This in vivo study reflects the fact that the mid-fetal period hosts events that cause the architecture of the brain circuitry to mature, which presumably manifests in increasing strength of intra- and interhemispheric functional macro connectivity. PMID:25374531

Fetal functional imaging portrays heterogeneous development of emerging human brain networks.

PubMed

Jakab, András; Schwartz, Ernst; Kasprian, Gregor; Gruber, Gerlinde M; Prayer, Daniela; Schöpf, Veronika; Langs, Georg

2014-01-01

The functional connectivity architecture of the adult human brain enables complex cognitive processes, and exhibits a remarkably complex structure shared across individuals. We are only beginning to understand its heterogeneous structure, ranging from a strongly hierarchical organization in sensorimotor areas to widely distributed networks in areas such as the parieto-frontal cortex. Our study relied on the functional magnetic resonance imaging (fMRI) data of 32 fetuses with no detectable morphological abnormalities. After adapting functional magnetic resonance acquisition, motion correction, and nuisance signal reduction procedures of resting-state functional data analysis to fetuses, we extracted neural activity information for major cortical and subcortical structures. Resting fMRI networks were observed for increasing regional functional connectivity from 21st to 38th gestational weeks (GWs) with a network-based statistical inference approach. The overall connectivity network, short range, and interhemispheric connections showed sigmoid expansion curve peaking at the 26-29 GW. In contrast, long-range connections exhibited linear increase with no periods of peaking development. Region-specific increase of functional signal synchrony followed a sequence of occipital (peak: 24.8 GW), temporal (peak: 26 GW), frontal (peak: 26.4 GW), and parietal expansion (peak: 27.5 GW). We successfully adapted functional neuroimaging and image post-processing approaches to correlate macroscopical scale activations in the fetal brain with gestational age. This in vivo study reflects the fact that the mid-fetal period hosts events that cause the architecture of the brain circuitry to mature, which presumably manifests in increasing strength of intra- and interhemispheric functional macro connectivity.

Caveolin1 Identifies a Specific Subpopulation of Cerebral Cortex Callosal Projection Neurons (CPN) Including Dual Projecting Cortical Callosal/Frontal Projection Neurons (CPN/FPN)

PubMed Central

2018-01-01

Abstract The neocortex is composed of many distinct subtypes of neurons that must form precise subtype-specific connections to enable the cortex to perform complex functions. Callosal projection neurons (CPN) are the broad population of commissural neurons that connect the cerebral hemispheres via the corpus callosum (CC). Currently, how the remarkable diversity of CPN subtypes and connectivity is specified, and how they differentiate to form highly precise and specific circuits, are largely unknown. We identify in mouse that the lipid-bound scaffolding domain protein Caveolin 1 (CAV1) is specifically expressed by a unique subpopulation of Layer V CPN that maintain dual ipsilateral frontal projections to premotor cortex. CAV1 is expressed by over 80% of these dual projecting callosal/frontal projection neurons (CPN/FPN), with expression peaking early postnatally as axonal and dendritic targets are being reached and refined. CAV1 is localized to the soma and dendrites of CPN/FPN, a unique population of neurons that shares information both between hemispheres and with premotor cortex, suggesting function during postmitotic development and refinement of these neurons, rather than in their specification. Consistent with this, we find that Cav1 function is not necessary for the early specification of CPN/FPN, or for projecting to their dual axonal targets. CPN subtype-specific expression of Cav1 identifies and characterizes a first molecular component that distinguishes this functionally unique projection neuron population, a population that expands in primates, and is prototypical of additional dual and higher-order projection neuron subtypes. PMID:29379878

Parkinson's disease: in vivo metabolic changes in the frontal and parietal cortices in 6-OHDA treated rats during different periods.

PubMed

Hou, Zhongyu; Zhang, Zhonghe; Meng, Haiwei; Lin, Xiangtao; Sun, Bo; Lei, Hao; Fang, Ke; Fang, Fang; Liu, Maili; Liu, Shuwei

2014-02-01

This study aims to investigate metabolic changes in frontal and parietal cortices in the 6-OHDA induced Parkinson's rats. Ratios of N-acetyl-aspartic acid/creatine (NAA/Cr), choline/creatine (Cho/Cr), and glumatic acid and glutamine glutaminic acid/creatine (Glx/Cr) of regions of interests (ROIs) in the frontal and parietal cortices, and the substantia nigra were analyzed. NAA/Cr, Cho/Cr and Glx/Cr in the frontal and parietal cortices in the lesion side did not show any significant differences two weeks after operation compared with the contralateral side (p > 0.05). NAA/Cr in the frontal cortex in the lesion side was significantly lower in the five weeks after operation; Cho/Cr remained normal; Glx/Cr increased (p < 0.05), and all ratios of parietal cortex were normal. In the eight weeks after operation, NAA/Cr in the frontal cortex in the lesion side was lower than that of the five weeks (p < 0.01), Cho/Cr still remained normal while Glx/Cr was higher than before (p < 0.01). Regarding the parietal cortex, NAA/Cr increased significantly, while Cho/Cr and Glx/Cr remained normal. In the 12 weeks after operation, NAA/Cr, Cho/Cr and Glx/Cr in frontal cortex were consistent with that of the eight weeks, while they remained at the normal level in parietal cortex. The NAA/Cr in the substantia nigra decreased and Cho/Cr increased significantly during 2-8 weeks, and remained at the same level during 8-12 weeks. There are metabolic disturbances in PD rats. The transient hyperfunction in the parietal cortex can be considered as a compensation for the dysfunction of the frontal cortex and substantia nigra.

Transcriptional response of rat frontal cortex following acute In Vivo exposure to the pyrethroid insecticides permethrin and deltamethrin

PubMed Central

Harrill, Joshua A; Li, Zhen; Wright, Fred A; Radio, Nicholas M; Mundy, William R; Tornero-Velez, Rogelio; Crofton, Kevin M

2008-01-01

Background Pyrethroids are neurotoxic pesticides that interact with membrane bound ion channels in neurons and disrupt nerve function. The purpose of this study was to characterize and explore changes in gene expression that occur in the rat frontal cortex, an area of CNS affected by pyrethroids, following an acute low-dose exposure. Results Rats were acutely exposed to either deltamethrin (0.3 – 3 mg/kg) or permethrin (1 – 100 mg/kg) followed by collection of cortical tissue at 6 hours. The doses used range from those that cause minimal signs of intoxication at the behavioral level to doses well below apparent no effect levels in the whole animal. A statistical framework based on parallel linear (SAM) and isotonic regression (PIR) methods identified 95 and 53 probe sets as dose-responsive. The PIR analysis was most sensitive for detecting transcripts with changes in expression at the NOAEL dose. A sub-set of genes (Camk1g, Ddc, Gpd3, c-fos and Egr1) was then confirmed by qRT-PCR and examined in a time course study. Changes in mRNA levels were typically less than 3-fold in magnitude across all components of the study. The responses observed are consistent with pyrethroids producing increased neuronal excitation in the cortex following a low-dose in vivo exposure. In addition, Significance Analysis of Function and Expression (SAFE) identified significantly enriched gene categories common for both pyrethroids, including some relating to branching morphogenesis. Exposure of primary cortical cell cultures to both compounds resulted in an increase (~25%) in the number of neurite branch points, supporting the results of the SAFE analysis. Conclusion In the present study, pyrethroids induced changes in gene expression in the frontal cortex near the threshold for decreases in ambulatory motor activity in vivo. The penalized regression methods performed similarly in detecting dose-dependent changes in gene transcription. Finally, SAFE analysis of gene expression data

Modulation of oxidative stress, inflammation, autophagy and expression of Nrf2 in hippocampus and frontal cortex of rats fed with açaí-enriched diets.

PubMed

Poulose, Shibu M; Bielinski, Donna F; Carey, Amanda; Schauss, Alexander G; Shukitt-Hale, Barbara

2017-06-01

Açaí (Euterpe spp.), an exotic palm fruit, has recently emerged as a promising source of natural antioxidants with wide pharmacological and nutritional value. In this study, two different species of açaí pulp extracts, naturally grown in two distinct regions of the Amazon, namely, Euterpe oleracea Mart. (habitat: Brazilian floodplains of the Amazon) and Euterpe precatoria Mart. (habitat: Bolivian Amazon), were studied for their effects on brain health and cognition. Neurochemical analyses were performed in critical brain regions associated with memory and cognition of 19-month-old açaí-fed rats, in whom the cognitive benefits of açaí had been established. Results indicated significant reductions (P< 0.05) in prooxidant NADPH-oxidoreductase-2 (NOX2) and proinflammatory transcription factor NF-κB in açaí-fed rats. Measurement of Nrf2 expression, a transcription factor for antioxidant enzymes, and a possible link between oxidative stress, neuroinflammation and autophagy mechanisms, indicated significant overexpression (P<0.005) in the hippocampus and frontal cortex of the açaí-fed rats. Furthermore, significant activation of endogenous antioxidant enzymes GST and SOD were also observed in the açaí-fed animals when compared to control. Analysis of autophagy markers such as p62, phospho-mTOR, beclin1 and MAP1B-LC3 revealed differential expression in frontal cortex and hippocampus, mostly indicating an upregulation in the açaí-fed rats. In general, results were more profound for EP than EO in hippocampus as well as frontal cortex. Therefore, an açaí-enriched diet could possibly modulate Nrf2, which is known to modulate the intracellular redox status, thereby regulating the ubiquitin-proteosomal pathway, ultimately affecting cognitive function in the aging brain.

Motor Deficits Are Produced By Removing Some Cortical Transplants Grafted Into Injured Sensorimotor Cortex of Neonatal Rats

PubMed Central

Sandor, Rick; Gonzalez, Manuel F.; Moseley, Michael; Sharp, Frank R.

1991-01-01

Fetal frontal cortex was transplanted into cavities formed in the right, motor cortex of neonatal rats. As adults, the animals were trained to press two levers in rapid succession with their left forelimb to receive food rewards. Once they had reached an optimal level of performance, the effect of removing their transplants was assessed. Surgical removal of transplants significantly impaired the performance of 2 of 4 subjects. Placing a crossstrain skin graft to induce the immunological rejection of the transplants produced a behavioral deficit in 1 of 2 subjects with complete transplant removal. Skin grafts produced no behavioral effects in four subjects that had surviving transplants. Since the motor deficit produced by transplant removal resembled those observed following the removal of normal motor cortex, we propose that these three transplants functioned within the host brain. Histology Showed that the procedures used to remove cortical grafts did not injure any host brains. Therefore, host brain damage is unlikely to account for the behavioral deterioration that followed transplant removals. PMID:1782254

Developmental Alterations of Frontal-Striatal-Thalamic Connectivity in Obsessive-Compulsive Disorder

ERIC Educational Resources Information Center

Fitzgerald, Kate Dimond; Welsh, Robert C.; Stern, Emily R.; Angstadt, Mike; Hanna, Gregory L.; Abelson, James L.; Taylor, Stephan F.

2011-01-01

Objective: Pediatric obsessive-compulsive disorder is characterized by abnormalities of frontal-striatal-thalamic circuitry that appear near illness onset and persist over its course. Distinct frontal-striatal-thalamic loops through cortical centers for cognitive control (anterior cingulate cortex) and emotion processing (ventral medial frontal…

A Novel Role for the Rat Retrosplenial Cortex in Cognitive Control

ERIC Educational Resources Information Center

Nelson, Andrew J. D.; Hindley, Emma L.; Haddon, Josephine E.; Vann, Seralynne D.; Aggleton, John P.

2014-01-01

By virtue of its frontal and hippocampal connections, the retrosplenial cortex is uniquely placed to support cognition. Here, we tested whether the retrosplenial cortex is required for frontal tasks analogous to the Stroop Test, i.e., for the ability to select between conflicting responses and inhibit responding to task-irrelevant cues. Rats first…

Exploratory Metabolomic Analyses Reveal Compounds Correlated with Lutein Concentration in Frontal Cortex, Hippocampus, and Occipital Cortex of Human Infant Brain

PubMed Central

Lieblein-Boff, Jacqueline C.; Johnson, Elizabeth J.; Kennedy, Adam D.; Lai, Chron-Si; Kuchan, Matthew J.

2015-01-01

Lutein is a dietary carotenoid well known for its role as an antioxidant in the macula, and recent reports implicate a role for lutein in cognitive function. Lutein is the dominant carotenoid in both pediatric and geriatric brain tissue. In addition, cognitive function in older adults correlated with macular and postmortem brain lutein concentrations. Furthermore, lutein was found to preferentially accumulate in the infant brain in comparison to other carotenoids that are predominant in diet. While lutein is consistently related to cognitive function, the mechanisms by which lutein may influence cognition are not clear. In an effort to identify potential mechanisms through which lutein might influence neurodevelopment, an exploratory study relating metabolite signatures and lutein was completed. Post-mortem metabolomic analyses were performed on human infant brain tissues in three regions important for learning and memory: the frontal cortex, hippocampus, and occipital cortex. Metabolomic profiles were compared to lutein concentration, and correlations were identified and reported here. A total of 1276 correlations were carried out across all brain regions. Of 427 metabolites analyzed, 257 were metabolites of known identity. Unidentified metabolite correlations (510) were excluded. In addition, moderate correlations with xenobiotic relationships (2) or those driven by single outliers (3) were excluded from further study. Lutein concentrations correlated with lipid pathway metabolites, energy pathway metabolites, brain osmolytes, amino acid neurotransmitters, and the antioxidant homocarnosine. These correlations were often brain region—specific. Revealing relationships between lutein and metabolic pathways may help identify potential candidates on which to complete further analyses and may shed light on important roles of lutein in the human brain during development. PMID:26317757

Auditory and visual connectivity gradients in frontoparietal cortex

PubMed Central

Hellyer, Peter J.; Wise, Richard J. S.; Leech, Robert

2016-01-01

Abstract A frontoparietal network of brain regions is often implicated in both auditory and visual information processing. Although it is possible that the same set of multimodal regions subserves both modalities, there is increasing evidence that there is a differentiation of sensory function within frontoparietal cortex. Magnetic resonance imaging (MRI) in humans was used to investigate whether different frontoparietal regions showed intrinsic biases in connectivity with visual or auditory modalities. Structural connectivity was assessed with diffusion tractography and functional connectivity was tested using functional MRI. A dorsal–ventral gradient of function was observed, where connectivity with visual cortex dominates dorsal frontal and parietal connections, while connectivity with auditory cortex dominates ventral frontal and parietal regions. A gradient was also observed along the posterior–anterior axis, although in opposite directions in prefrontal and parietal cortices. The results suggest that the location of neural activity within frontoparietal cortex may be influenced by these intrinsic biases toward visual and auditory processing. Thus, the location of activity in frontoparietal cortex may be influenced as much by stimulus modality as the cognitive demands of a task. It was concluded that stimulus modality was spatially encoded throughout frontal and parietal cortices, and was speculated that such an arrangement allows for top–down modulation of modality‐specific information to occur within higher‐order cortex. This could provide a potentially faster and more efficient pathway by which top–down selection between sensory modalities could occur, by constraining modulations to within frontal and parietal regions, rather than long‐range connections to sensory cortices. Hum Brain Mapp 38:255–270, 2017. © 2016 Wiley Periodicals, Inc. PMID:27571304

Projections of Somatosensory Cortex and Frontal Eye Fields onto Incertotectal Neurons in the Cat

PubMed Central

Perkins, Eddie; Warren, Susan; Lin, Rick C.-S.; May, Paul J.

2014-01-01

The goal of this study was to determine whether the input-output characteristics of the zona incerta (ZI) are appropriate for it to serve as a conduit for cortical control over saccade-related activity in the superior colliculus. The study utilized the neuronal tracers wheat germ agglutinin-horseradish peroxidase (WGA-HRP) and biotinylated dextran amine (BDA) in the cat. Injections of WGA-HRP into primary somatosensory cortex (SI) revealed sparse, widespread nontopographic projections throughout ZI. In addition, region-specific areas of more intense termination were present in ventral ZI, although strict topography was not observed. In comparison, the frontal eye fields (FEF) also projected sparsely throughout ZI, but terminated more heavily, medially, along the border between the two sublaminae. Furthermore, retrogradely labeled incertocortical neurons were observed in both experiments. The relationship of these two cortical projections to incertotectal cells was also directly examined by retrogradely labeling incertotectal cells with WGA-HRP in animals that had also received cortical BDA injections. Labeled axonal arbors from both SI and FEF had thin, sparsely branched axons with numerous en passant boutons. They formed numerous close associations with the somata and dendrites of WGA-HRP-labeled incertotectal cells. In summary, these results indicate that both sensory and motor cortical inputs to ZI display similar morphologies and distributions. In addition, both display close associations with incertotectal cells, suggesting direct synaptic contact. From these data, we conclude that inputs from somatosensory and FEF cortex both play a role in controlling gaze-related activity in the superior colliculus by way of the inhibitory incertotectal projection. PMID:17083121

Fetal brain hypometabolism during prolonged hypoxaemia in the llama

PubMed Central

Ebensperger, Germán; Ebensperger, Renato; Herrera, Emilio A; Riquelme, Raquel A; Sanhueza, Emilia M; Lesage, Florian; Marengo, Juan J; Tejo, Rodrigo I; Llanos, Aníbal J; Reyes, Roberto V

2005-01-01

In this study we looked for additional evidence to support the hypothesis that fetal llama reacts to hypoxaemia with adaptive brain hypometabolism. We determined fetal llama brain temperature, Na+ and K+ channel density and Na+–K+-ATPase activity. Additionally, we looked to see whether there were signs of cell death in the brain cortex of llama fetuses submitted to prolonged hypoxaemia. Ten fetal llamas were instrumented under general anaesthesia to measure pH, arterial blood gases, mean arterial pressure, heart rate, and brain and core temperatures. Measurements were made 1 h before and every hour during 24 h of hypoxaemia (n = 5), which was imposed by reducing maternal inspired oxygen fraction to reach a fetal arterial partial pressure of oxygen (Pa,O2) of about 12 mmHg. A normoxaemic group was the control (n = 5). After 24 h of hypoxaemia, we determined brain cortex Na+–K+-ATPase activity, ouabain binding, and the expression of NaV1.1, NaV1.2, NaV1.3, NaV1.6, TREK1, TRAAK and KATP channels. The lack of brain cortex damage was assessed as poly ADP-ribose polymerase (PARP) proteolysis. We found a mean decrease of 0.56°C in brain cortex temperature during prolonged hypoxaemia, which was accompanied by a 51% decrease in brain cortex Na+–K+-ATPase activity, and by a 44% decrease in protein content of NaV1.1, a voltage-gated Na+ channel. These changes occurred in absence of changes in PARP protein degradation, suggesting that the cell death of the brain was not enhanced in the fetal llama during hypoxaemia. Taken together, these results provide further evidence to support the hypothesis that the fetal llama responds to prolonged hypoxaemia with adaptive brain hypometabolism, partly mediated by decreases in Na+–K+-ATPase activity and expression of NaV channels. PMID:16037083

Bi-frontal direct current stimulation affects delay discounting choices.

PubMed

Hecht, David; Walsh, Vincent; Lavidor, Michal

2013-01-01

In delay discounting tasks, participants decide between receiving a certain amount of money now or a larger sum sometime in the future. This study investigated the effects of transcranial direct current stimulation on delay discounting. Participants made delay discounting choices while receiving a bi-frontal stimulation of right-hemisphere anodal/left-hemisphere cathodal, left-hemisphere anodal/right-hemisphere cathodal, and sham stimulation, in three separate sessions. When the difference between the alternatives was 10% or more, participants generally preferred to wait for the larger sum. Nevertheless, there were more choices of smaller "immediate" gains, instead of the larger delayed options, when the left dorsolateral prefrontal cortex (DLPFC) was facilitated and the right DLPFC inhibited, compared to the sham stimulation. These observations indicate the significant role of the prefrontal cortex in delay discounting choices, and demonstrate that increased left frontal activation combined with decreased right frontal activation can alter decision-making by intensifying a tendency to choose immediate gains.

Segregated Excitatory–Inhibitory Recurrent Subnetworks in Layer 5 of the Rat Frontal Cortex

PubMed Central

Morishima, Mieko; Kobayashi, Kenta; Kato, Shigeki; Kobayashi, Kazuto; Kawaguchi, Yasuo

2017-01-01

Abstract A prominent feature of neocortical pyramidal cells (PCs) is their numerous projections to diverse brain areas. In layer 5 (L5) of the rat frontal cortex, there are 2 major subtypes of PCs that differ in their long-range axonal projections, corticopontine (CPn) cells and crossed corticostriatal (CCS) cells. The outputs of these L5 PCs can be regulated by feedback inhibition from neighboring cortical GABAergic cells. Two major subtypes of GABAergic cells are parvalbumin (PV)-positive and somatostatin (SOM)-positive cells. PV cells have a fast-spiking (FS) firing pattern, while SOM cells have a low threshold spike (LTS) and regular spiking. In this study, we found that the 2 PC subtypes in L5 selectively make recurrent connections with LTS cells. The connection patterns correlated with the morphological and physiological diversity of LTS cells. LTS cells with high input resistance (Ri) exhibited more compact dendrites and more rebound spikes than LTS cells with low Ri, which had vertically elongated dendrites. LTS subgroups differently inhibited the PC subtypes, although FS cells made nonselective connections with both projection subtypes. These results demonstrate a novel recurrent network of inhibitory and projection-specific excitatory neurons within the neocortex. PMID:29045559

Frontal and Parietal Cortical Interactions with Distributed Visual Representations during Selective Attention and Action Selection

PubMed Central

Stokes, Mark; Nobre, Anna C.; Rushworth, Matthew F. S.

2013-01-01

Using multivoxel pattern analysis (MVPA), we studied how distributed visual representations in human occipitotemporal cortex are modulated by attention and link their modulation to concurrent activity in frontal and parietal cortex. We detected similar occipitotemporal patterns during a simple visuoperceptual task and an attention-to-working-memory task in which one or two stimuli were cued before being presented among other pictures. Pattern strength varied from highest to lowest when the stimulus was the exclusive focus of attention, a conjoint focus, and when it was potentially distracting. Although qualitatively similar effects were seen inside regions relatively specialized for the stimulus category and outside, the former were quantitatively stronger. By regressing occipitotemporal pattern strength against activity elsewhere in the brain, we identified frontal and parietal areas exerting top-down control over, or reading information out from, distributed patterns in occipitotemporal cortex. Their interactions with patterns inside regions relatively specialized for that stimulus category were higher than those with patterns outside those regions and varied in strength as a function of the attentional condition. One area, the frontal operculum, was distinguished by selectively interacting with occipitotemporal patterns only when they were the focus of attention. There was no evidence that any frontal or parietal area actively inhibited occipitotemporal representations even when they should be ignored and were suppressed. Using MVPA to decode information within these frontal and parietal areas showed that they contained information about attentional context and/or readout information from occipitotemporal cortex to guide behavior but that frontal regions lacked information about category identity. PMID:24133250

Frontal and parietal cortical interactions with distributed visual representations during selective attention and action selection.

PubMed

Nelissen, Natalie; Stokes, Mark; Nobre, Anna C; Rushworth, Matthew F S

2013-10-16

Using multivoxel pattern analysis (MVPA), we studied how distributed visual representations in human occipitotemporal cortex are modulated by attention and link their modulation to concurrent activity in frontal and parietal cortex. We detected similar occipitotemporal patterns during a simple visuoperceptual task and an attention-to-working-memory task in which one or two stimuli were cued before being presented among other pictures. Pattern strength varied from highest to lowest when the stimulus was the exclusive focus of attention, a conjoint focus, and when it was potentially distracting. Although qualitatively similar effects were seen inside regions relatively specialized for the stimulus category and outside, the former were quantitatively stronger. By regressing occipitotemporal pattern strength against activity elsewhere in the brain, we identified frontal and parietal areas exerting top-down control over, or reading information out from, distributed patterns in occipitotemporal cortex. Their interactions with patterns inside regions relatively specialized for that stimulus category were higher than those with patterns outside those regions and varied in strength as a function of the attentional condition. One area, the frontal operculum, was distinguished by selectively interacting with occipitotemporal patterns only when they were the focus of attention. There was no evidence that any frontal or parietal area actively inhibited occipitotemporal representations even when they should be ignored and were suppressed. Using MVPA to decode information within these frontal and parietal areas showed that they contained information about attentional context and/or readout information from occipitotemporal cortex to guide behavior but that frontal regions lacked information about category identity.

Selective visual attention to emotional words: Early parallel frontal and visual activations followed by interactive effects in visual cortex.

PubMed

Schindler, Sebastian; Kissler, Johanna

2016-10-01

Human brains spontaneously differentiate between various emotional and neutral stimuli, including written words whose emotional quality is symbolic. In the electroencephalogram (EEG), emotional-neutral processing differences are typically reflected in the early posterior negativity (EPN, 200-300 ms) and the late positive potential (LPP, 400-700 ms). These components are also enlarged by task-driven visual attention, supporting the assumption that emotional content naturally drives attention. Still, the spatio-temporal dynamics of interactions between emotional stimulus content and task-driven attention remain to be specified. Here, we examine this issue in visual word processing. Participants attended to negative, neutral, or positive nouns while high-density EEG was recorded. Emotional content and top-down attention both amplified the EPN component in parallel. On the LPP, by contrast, emotion and attention interacted: Explicit attention to emotional words led to a substantially larger amplitude increase than did explicit attention to neutral words. Source analysis revealed early parallel effects of emotion and attention in bilateral visual cortex and a later interaction of both in right visual cortex. Distinct effects of attention were found in inferior, middle and superior frontal, paracentral, and parietal areas, as well as in the anterior cingulate cortex (ACC). Results specify separate and shared mechanisms of emotion and attention at distinct processing stages. Hum Brain Mapp 37:3575-3587, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

MRI volumetry of prefrontal cortex

NASA Astrophysics Data System (ADS)

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

1995-05-01

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

Transient hyper-17-OHPnemia unrelated to cross-reactions with residual fetal adrenal cortex products.

PubMed

Mizuno, Haruo; Ohro, Yoichiro; Sugiyama, Yukari; Ito, Tetsuya; Hasegawa, Tomonobu; Homma, Keiko; Ueshiba, Hajime; Ono, Makoto; Togari, Hajime

2004-01-01

To clarify the pathogenesis of transient hyper-17alpha-hydroxyprogesteronemia, we initiated a laboratory investigation in a pre-term infant with persistently high serum 17alpha-hydroxyprogesterone (17-OHP) until 2 months of age. Serum 17-OHP level was measured by high-performance liquid chromatography and radioimmunoassay, and gene analysis of CYP21A2 (21-hydroxylase) was performed. Serum 17-OHP level on the 29th day of life was 25.4 ng/ml, and the urinary steroid profile showed low pregnanetriolone. Gene analysis of 21-hydroxylase disclosed no mutation, and 17-OHP normalized by 3 months of age without specific treatment. Transient elevations in 17-OHP, which do not appear related to cross-reactions with products of a residual fetal adrenal cortex, may occur in the first few months of life. Copyright 2004 S. Karger AG, Basel

Transcranial direct current stimulation over left inferior frontal cortex improves speech fluency in adults who stutter.

PubMed

Chesters, Jennifer; Möttönen, Riikka; Watkins, Kate E

2018-04-01

See Crinion (doi:10.1093/brain/awy075) for a scientific commentary on this article.Stuttering is a neurodevelopmental condition affecting 5% of children, and persisting in 1% of adults. Promoting lasting fluency improvement in adults who stutter is a particular challenge. Novel interventions to improve outcomes are of value, therefore. Previous work in patients with acquired motor and language disorders reported enhanced benefits of behavioural therapies when paired with transcranial direct current stimulation. Here, we report the results of the first trial investigating whether transcranial direct current stimulation can improve speech fluency in adults who stutter. We predicted that applying anodal stimulation to the left inferior frontal cortex during speech production with temporary fluency inducers would result in longer-lasting fluency improvements. Thirty male adults who stutter completed a randomized, double-blind, controlled trial of anodal transcranial direct current stimulation over left inferior frontal cortex. Fifteen participants received 20 min of 1-mA stimulation on five consecutive days while speech fluency was temporarily induced using choral and metronome-timed speech. The other 15 participants received the same speech fluency intervention with sham stimulation. Speech fluency during reading and conversation was assessed at baseline, before and after the stimulation on each day of the 5-day intervention, and at 1 and 6 weeks after the end of the intervention. Anodal stimulation combined with speech fluency training significantly reduced the percentage of disfluent speech measured 1 week after the intervention compared with fluency intervention alone. At 6 weeks after the intervention, this improvement was maintained during reading but not during conversation. Outcome scores at both post-intervention time points on a clinical assessment tool (the Stuttering Severity Instrument, version 4) also showed significant improvement in the group receiving

Impaired decision-making and selective cortical frontal thinning in Cushing's syndrome.

PubMed

Crespo, Iris; Esther, Granell-Moreno; Santos, Alicia; Valassi, Elena; Yolanda, Vives-Gilabert; De Juan-Delago, Manel; Webb, Susan M; Gómez-Ansón, Beatriz; Resmini, Eugenia

2014-12-01

Cushing's syndrome (CS) is caused by a glucocorticoid excess. This hypercortisolism can damage the prefrontal cortex, known to be important in decision-making. Our aim was to evaluate decision-making in CS and to explore cortical thickness. Thirty-five patients with CS (27 cured, eight medically treated) and thirty-five matched controls were evaluated using Iowa gambling task (IGT) and 3 Tesla magnetic resonance imaging (MRI) to assess cortical thickness. The IGT evaluates decision-making, including strategy and learning during the test. Cortical thickness was determined on MRI using freesurfer software tools, including a whole-brain analysis. There were no differences between medically treated and cured CS patients. They presented an altered decision-making strategy compared to controls, choosing a lower number of the safer cards (P < 0·05). They showed more difficulties than controls to learn the correct profiles of wins and losses for each card group (P < 0·05). In whole-brain analysis, patients with CS showed decreased cortical thickness in the left superior frontal cortex, left precentral cortex, left insular cortex, left and right rostral anterior cingulate cortex, and right caudal middle frontal cortex compared to controls (P < 0·001). Patients with CS failed to learn advantageous strategies and their behaviour was driven by short-term reward and long-term punishment, indicating learning problems because they did not use previous experience as a feedback factor to regulate their choices. These alterations in decision-making and the decreased cortical thickness in frontal areas suggest that chronic hypercortisolism promotes brain changes which are not completely reversible after endocrine remission. © 2014 John Wiley & Sons Ltd.

Dual streams of auditory afferents target multiple domains in the primate prefrontal cortex

PubMed Central

Romanski, L. M.; Tian, B.; Fritz, J.; Mishkin, M.; Goldman-Rakic, P. S.; Rauschecker, J. P.

2009-01-01

‘What’ and ‘where’ visual streams define ventrolateral object and dorsolateral spatial processing domains in the prefrontal cortex of nonhuman primates. We looked for similar streams for auditory–prefrontal connections in rhesus macaques by combining microelectrode recording with anatomical tract-tracing. Injection of multiple tracers into physiologically mapped regions AL, ML and CL of the auditory belt cortex revealed that anterior belt cortex was reciprocally connected with the frontal pole (area 10), rostral principal sulcus (area 46) and ventral prefrontal regions (areas 12 and 45), whereas the caudal belt was mainly connected with the caudal principal sulcus (area 46) and frontal eye fields (area 8a). Thus separate auditory streams originate in caudal and rostral auditory cortex and target spatial and non-spatial domains of the frontal lobe, respectively. PMID:10570492

Modulation of frontal effective connectivity during speech.

PubMed

Holland, Rachel; Leff, Alex P; Penny, William D; Rothwell, John C; Crinion, Jenny

2016-10-15

Noninvasive neurostimulation methods such as transcranial direct current stimulation (tDCS) can elicit long-lasting, polarity-dependent changes in neocortical excitability. In a previous concurrent tDCS-fMRI study of overt picture naming, we reported significant behavioural and regionally specific neural facilitation effects in left inferior frontal cortex (IFC) with anodal tDCS applied to left frontal cortex (Holland et al., 2011). Although distributed connectivity effects of anodal tDCS have been modelled at rest, the mechanism by which 'on-line' tDCS may modulate neuronal connectivity during a task-state remains unclear. Here, we used Dynamic Causal Modelling (DCM) to determine: (i) how neural connectivity within the frontal speech network is modulated during anodal tDCS; and, (ii) how individual variability in behavioural response to anodal tDCS relates to changes in effective connectivity strength. Results showed that compared to sham, anodal tDCS elicited stronger feedback from inferior frontal sulcus (IFS) to ventral premotor (VPM) accompanied by weaker self-connections within VPM, consistent with processes of neuronal adaptation. During anodal tDCS individual variability in the feedforward connection strength from IFS to VPM positively correlated with the degree of facilitation in naming behaviour. These results provide an essential step towards understanding the mechanism of 'online' tDCS paired with a cognitive task. They also identify left IFS as a 'top-down' hub and driver for speech change. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Rule-Guided Executive Control of Response Inhibition: Functional Topography of the Inferior Frontal Cortex

PubMed Central

Cai, Weidong; Leung, Hoi-Chung

2011-01-01

Background The human inferior frontal cortex (IFC) is a large heterogeneous structure with distinct cytoarchitectonic subdivisions and fiber connections. It has been found involved in a wide range of executive control processes from target detection, rule retrieval to response control. Since these processes are often being studied separately, the functional organization of executive control processes within the IFC remains unclear. Methodology/Principal Findings We conducted an fMRI study to examine the activities of the subdivisions of IFC during the presentation of a task cue (rule retrieval) and during the performance of a stop-signal task (requiring response generation and inhibition) in comparison to a not-stop task (requiring response generation but not inhibition). We utilized a mixed event-related and block design to separate brain activity in correspondence to transient control processes from rule-related and sustained control processes. We found differentiation in control processes within the IFC. Our findings reveal that the bilateral ventral-posterior IFC/anterior insula are more active on both successful and unsuccessful stop trials relative to not-stop trials, suggesting their potential role in the early stage of stopping such as triggering the stop process. Direct countermanding seems to be outside of the IFC. In contrast, the dorsal-posterior IFC/inferior frontal junction (IFJ) showed transient activity in correspondence to the infrequent presentation of the stop signal in both tasks and the left anterior IFC showed differential activity in response to the task cues. The IFC subdivisions also exhibited similar but distinct patterns of functional connectivity during response control. Conclusions/Significance Our findings suggest that executive control processes are distributed across the IFC and that the different subdivisions of IFC may support different control operations through parallel cortico-cortical and cortico-striatal circuits. PMID

Jealousy increased by induced relative left frontal cortical activity.

PubMed

Kelley, Nicholas J; Eastwick, Paul W; Harmon-Jones, Eddie; Schmeichel, Brandon J

2015-10-01

Asymmetric frontal cortical activity may be one key to the process linking social exclusion to jealous feelings. The current research examined the causal role of asymmetric frontal brain activity in modulating jealousy in response to social exclusion. Transcranial direct-current stimulation (tDCS) over the frontal cortex to manipulate asymmetric frontal cortical activity was combined with a modified version of the Cyberball paradigm designed to induce jealousy. After receiving 15 min of tDCS, participants were excluded by a desired partner and reported how jealous they felt. Among individuals who were excluded, tDCS to increase relative left frontal cortical activity caused greater levels of self-reported jealousy compared to tDCS to increase relative right frontal cortical activity or sham stimulation. Limitations concerning the specificity of this effect and implications for the role of the asymmetric prefrontal cortical activity in motivated behaviors are discussed. (c) 2015 APA, all rights reserved).

Spatial organization of neurons in the frontal pole sets humans apart from great apes.

PubMed

Semendeferi, Katerina; Teffer, Kate; Buxhoeveden, Dan P; Park, Min S; Bludau, Sebastian; Amunts, Katrin; Travis, Katie; Buckwalter, Joseph

2011-07-01

Few morphological differences have been identified so far that distinguish the human brain from the brains of our closest relatives, the apes. Comparative analyses of the spatial organization of cortical neurons, including minicolumns, can aid our understanding of the functionally relevant aspects of microcircuitry. We measured horizontal spacing distance and gray-level ratio in layer III of 4 regions of human and ape cortex in all 6 living hominoid species: frontal pole (Brodmann area [BA] 10), and primary motor (BA 4), primary somatosensory (BA 3), and primary visual cortex (BA 17). Our results identified significant differences between humans and apes in the frontal pole (BA 10). Within the human brain, there were also significant differences between the frontal pole and 2 of the 3 regions studied (BA 3 and BA 17). Differences between BA 10 and BA 4 were present but did not reach significance. These findings in combination with earlier findings on BA 44 and BA 45 suggest that human brain evolution was likely characterized by an increase in the number and width of minicolumns and the space available for interconnectivity between neurons in the frontal lobe, especially the prefrontal cortex.

Frontal auditory evoked potentials and augmenting-reducing.

PubMed

Bruneau, N; Roux, S; Garreau, B; Lelord, G

1985-09-01

Auditory evoked potentials (AEPs) to tones (750 Hz--200 msec) ranging from 50 to 80 dB SPL were studied at Cz and Fz leads in 29 normal adults (15 males) ranging in age from 20 to 22. Peak-to-trough amplitudes were measured for the P1-N1 and the N1-P2 wave forms as well as baseline (500 msec prestimulus)-to-peak amplitudes for each component, i.e., P1, N1 and P2. Amplitudes were examined as a function of intensity and electrode location. Cz-Fz amplitude differences increased with increasing stimulus intensity, the differentiating peak being the N1 component. An overall reducing phenomenon was found at Fz in the 70-80 dB range whereas an augmenting effect was observed at Cz for these intensities. The augmenting/reducing groups defined by analysis of individual amplitude-intensity patterns were different whether we considered Fz or Cz results: Fz reducers were more numerous than Cz reducers. These results on prominent reducing at the frontal level were examined in relation to the data concerning the modulatory function of the frontal cortex on auditory EPs. Implications were drawn for the role of the frontal cortex in cortical augmenting-reducing.

Environmental Enrichment Alters Neurotrophin Levels After Fetal Alcohol Exposure in Rats

PubMed Central

Parks, Elizabeth A.; McMechan, Andrew P.; Hannigan, John H.; Berman, Robert F.

2014-01-01

Background Prenatal alcohol exposure causes abnormal brain development, leading to behavioral deficits, some of which can be ameliorated by environmental enrichment. As both environmental enrichment and prenatal alcohol exposure can individually alter neurotrophin expression, we studied the interaction of prenatal alcohol and postweaning environmental enrichment on brain neurotrophin levels in rats. Methods Pregnant rats received alcohol by gavage, 0, 4, or 6 g / kg / d (Zero, Low, or High groups), or no treatment (Naïve group), on gestational days 8 to 20. After weaning on postnatal day 21, offspring were housed for 6 weeks in Isolated, Social, or Enriched conditions. Levels of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) were then measured in frontal cortex, occipital cortex, hippocampus, and cerebellar vermis. Results Prenatal alcohol exposure increased NGF levels in frontal cortex (High-dose group) and cerebellar vermis (High- and Low-dose groups); increased BDNF in frontal cortex, occipital cortex and hippocampus (Low-dose groups), and increased NT-3 in hippocampus and cerebellar vermis (High-dose). Environmental enrichment resulted in lower NGF, BDNF, and NT-3 levels in occipital cortex and lower NGF in frontal cortex. The only significant interaction between prenatal alcohol treatment and environment was in cerebellar vermis where NT-3 levels were higher for enriched animals after prenatal alcohol exposure, but not for animals housed under Isolated or Social conditions. Conclusions Both prenatal alcohol exposure and postweaning housing conditions alter brain neurotrophin levels, but the effects appear to be largely independent. Although environmental enrichment can improve functional outcomes, these results do not provide strong support for the hypothesis that rearing in a complex environment ameliorates prenatal alcohol effects on brain neurotrophin levels in rats. PMID:18652597

Manipulation of the extrastriate frontal loop can resolve visual disability in blindsight patients.

PubMed

Badgaiyan, Rajendra D

2012-12-01

Patients with blindsight are not consciously aware of visual stimuli in the affected field of vision but retain nonconscious perception. This disability can be resolved if nonconsciously perceived information can be brought to their conscious awareness. It can be accomplished by manipulating neural network of visual awareness. To understand this network, we studied the pattern of cortical activity elicited during processing of visual stimuli with or without conscious awareness. The analysis indicated that a re-entrant signaling loop between the area V3A (located in the extrastriate cortex) and the frontal cortex is critical for processing conscious awareness. The loop is activated by visual signals relayed in the primary visual cortex, which is damaged in blindsight patients. Because of the damage, V3A-frontal loop is not activated and the signals are not processed for conscious awareness. These patients however continue to receive visual signals through the lateral geniculate nucleus. Since these signals do not activate the V3A-frontal loop, the stimuli are not consciously perceived. If visual input from the lateral geniculate nucleus is appropriately manipulated and made to activate the V3A-frontal loop, blindsight patients can regain conscious vision. Published by Elsevier Ltd.

Mismatch negativity results from bilateral asymmetric dipole sources in the frontal and temporal lobes.

PubMed

Jemel, Boutheina; Achenbach, Christiane; Müller, Bernhard W; Röpcke, Bernd; Oades, Robert D

2002-01-01

The event-related potential (ERP) reflecting auditory change detection (mismatch negativity, MMN) registers automatic selective processing of a deviant sound with respect to a working memory template resulting from a series of standard sounds. Controversy remains whether MMN can be generated in the frontal as well as the temporal cortex. Our aim was to see if frontal as well as temporal lobe dipoles could explain MMN recorded after pitch-deviants (Pd-MMN) and duration deviants (Dd-MMN). EEG recordings were taken from 32 sites in 14 healthy subjects during a passive 3-tone oddball presented during a simple visual discrimination and an active auditory discrimination condition. Both conditions were repeated after one month. The Pd-MMN was larger, peaked earlier and correlated better between sessions than the Dd-MMN. Two dipoles in the auditory cortex and two in the frontal lobe (left cingulate and right inferior frontal cortex) were found to be similarly placed for Pd- and Dd-MMN, and were well replicated on retest. This study confirms interactions between activity generated in the frontal and auditory temporal cortices in automatic attention-like processes that resemble initial brain imaging reports of unconscious visual change detection. The lack of interference between sessions shows that the situation is likely to be sensitive to treatment or illness effects on fronto-temporal interactions involving repeated measures.

Hemispheric differences in the voluntary control of spatial attention: direct evidence for a right-hemispheric dominance within frontal cortex.

PubMed

Duecker, Felix; Formisano, Elia; Sack, Alexander T

2013-08-01

Lesion studies in neglect patients have inspired two competing models of spatial attention control, namely, Heilman's "hemispatial" theory and Kinsbourne's "opponent processor" model. Both assume a functional asymmetry between the two hemispheres but propose very different mechanisms. Neuroimaging studies have identified a bilateral dorsal frontoparietal network underlying voluntary shifts of spatial attention. However, lateralization of attentional processes within this network has not been consistently reported. In the current study, we aimed to provide direct evidence concerning the functional asymmetry of the right and left FEF during voluntary shifts of spatial attention. To this end, we applied fMRI-guided neuronavigation to disrupt individual FEF activation foci with a longer-lasting inhibitory patterned TMS protocol followed by a spatial cueing task. Our results indicate that right FEF stimulation impaired the ability of shifting spatial attention toward both hemifields, whereas the effects of left FEF stimulation were limited to the contralateral hemifield. These results provide strong direct evidence for right-hemispheric dominance in spatial attention within frontal cortex supporting Heilman's "hemispatial" theory. This complements previous TMS studies that generally conform to Kinsbourne's "opponent processor" model after disruption of parietal cortex, and we therefore propose that both theories are not mutually exclusive.

Distinct frontal lobe morphology in girls and boys with ADHD.

PubMed

Dirlikov, Benjamin; Shiels Rosch, Keri; Crocetti, Deana; Denckla, Martha B; Mahone, E Mark; Mostofsky, Stewart H

2015-01-01

This study investigated whether frontal lobe cortical morphology differs for boys and girls with ADHD (ages 8-12 years) in comparison to typically developing (TD) peers. Participants included 226 children between the ages of 8-12 including 93 children with ADHD (29 girls) and 133 TD children (42 girls) for which 3T MPRAGE MRI scans were obtained. A fully automated frontal lobe atlas was used to generate functionally distinct frontal subdivisions, with surface area (SA) and cortical thickness (CT) assessed in each region. Analyses focused on overall diagnostic differences as well as examinations of the effect of diagnosis within boys and girls. Girls, but not boys, with ADHD showed overall reductions in total prefrontal cortex (PFC) SA. Localization revealed that girls showed widely distributed reductions in the bilateral dorsolateral PFC, left inferior lateral PFC, right medial PFC, right orbitofrontal cortex, and left anterior cingulate; and boys showed reduced SA only in the right anterior cingulate and left medial PFC. In contrast, boys, but not girls, with ADHD showed overall reductions in total premotor cortex (PMC) SA. Further localization revealed that in boys, premotor reductions were observed in bilateral lateral PMC regions; and in girls reductions were observed in bilateral supplementary motor complex. In line with diagnostic group differences, PMC and PFC SAs were inversely correlated with symptom severity in both girls and boys with ADHD. These results elucidate sex-based differences in cortical morphology of functional subdivisions of the frontal lobe and provide additional evidence of associations among SA and symptom severity in children with ADHD.

Left frontal cortex connectivity underlies cognitive reserve in prodromal Alzheimer disease

PubMed Central

Franzmeier, Nicolai; Duering, Marco; Weiner, Michael; Dichgans, Martin

2017-01-01

Objective: To test whether higher global functional connectivity of the left frontal cortex (LFC) in Alzheimer disease (AD) is associated with more years of education (a proxy of cognitive reserve [CR]) and mitigates the association between AD-related fluorodeoxyglucose (FDG)-PET hypometabolism and episodic memory. Methods: Forty-four amyloid-PET–positive patients with amnestic mild cognitive impairment (MCI-Aβ+) and 24 amyloid-PET–negative healthy controls (HC) were included. Voxel-based linear regression analyses were used to test the association between years of education and FDG-PET in MCI-Aβ+, controlled for episodic memory performance. Global LFC (gLFC) connectivity was computed through seed-based resting-state fMRI correlations between the LFC (seed) and each voxel in the gray matter. In linear regression analyses, education as a predictor of gLFC connectivity and the interaction of gLFC connectivity × FDG-PET hypometabolism on episodic memory were tested. Results: FDG-PET metabolism in the precuneus was reduced in MCI-Aβ+ compared to HC (p = 0.028), with stronger reductions observed in MCI-Aβ+ with more years of education (p = 0.006). In MCI-Aβ+, higher gLFC connectivity was associated with more years of education (p = 0.021). At higher levels of gLFC connectivity, the association between precuneus FDG-PET hypometabolism and lower memory performance was attenuated (p = 0.027). Conclusions: Higher gLFC connectivity is a functional substrate of CR that helps to maintain episodic memory relatively well in the face of emerging FDG-PET hypometabolism in early-stage AD. PMID:28188306

Left frontal cortex connectivity underlies cognitive reserve in prodromal Alzheimer disease.

PubMed

Franzmeier, Nicolai; Duering, Marco; Weiner, Michael; Dichgans, Martin; Ewers, Michael

2017-03-14

To test whether higher global functional connectivity of the left frontal cortex (LFC) in Alzheimer disease (AD) is associated with more years of education (a proxy of cognitive reserve [CR]) and mitigates the association between AD-related fluorodeoxyglucose (FDG)-PET hypometabolism and episodic memory. Forty-four amyloid-PET-positive patients with amnestic mild cognitive impairment (MCI-Aβ+) and 24 amyloid-PET-negative healthy controls (HC) were included. Voxel-based linear regression analyses were used to test the association between years of education and FDG-PET in MCI-Aβ+, controlled for episodic memory performance. Global LFC (gLFC) connectivity was computed through seed-based resting-state fMRI correlations between the LFC (seed) and each voxel in the gray matter. In linear regression analyses, education as a predictor of gLFC connectivity and the interaction of gLFC connectivity × FDG-PET hypometabolism on episodic memory were tested. FDG-PET metabolism in the precuneus was reduced in MCI-Aβ+ compared to HC ( p = 0.028), with stronger reductions observed in MCI-Aβ+ with more years of education ( p = 0.006). In MCI-Aβ+, higher gLFC connectivity was associated with more years of education ( p = 0.021). At higher levels of gLFC connectivity, the association between precuneus FDG-PET hypometabolism and lower memory performance was attenuated ( p = 0.027). Higher gLFC connectivity is a functional substrate of CR that helps to maintain episodic memory relatively well in the face of emerging FDG-PET hypometabolism in early-stage AD. © 2017 American Academy of Neurology.

Lower Activation in Frontal Cortex and Posterior Cingulate Cortex Observed during Sex Determination Test in Early-Stage Dementia of the Alzheimer Type.

PubMed

Rajmohan, Ravi; Anderson, Ronald C; Fang, Dan; Meyer, Austin G; Laengvejkal, Pavis; Julayanont, Parunyou; Hannabas, Greg; Linton, Kitten; Culberson, John; Khan, Hafiz; De Toledo, John; Reddy, P Hemachandra; O'Boyle, Michael W

2017-01-01

Face-labeling refers to the ability to classify faces into social categories. This plays a critical role in human interaction as it serves to define concepts of socially acceptable interpersonal behavior. The purpose of the current study was to characterize, what, if any, impairments in face-labeling are detectable in participants with early-stage clinically diagnosed dementia of the Alzheimer type (CDDAT) through the use of the sex determination test (SDT). In the current study, four (1 female, 3 males) CDDAT and nine (4 females, 5 males) age-matched neurotypicals (NT) completed the SDT using chimeric faces while undergoing BOLD fMRI. It was expected that CDDAT participants would have poor verbal fluency, which would correspond to poor performance on the SDT. This could be explained by decreased activation and connectivity patterns within the fusiform face area (FFA) and anterior cingulate cortex (ACC). DTI was also performed to test the association of pathological deterioration of connectivity in the uncinate fasciculus (UF) and verbally-mediated performance. CDDAT showed lower verbal fluency test (VFT) performance, but VFT was not significantly correlated to SDT and no significant difference was seen between CDDAT and NT for SDT performance as half of the CDDAT performed substantially worse than NT while the other half performed similarly. BOLD fMRI of SDT displayed differences in the left superior frontal gyrus and posterior cingulate cortex (PCC), but not the FFA or ACC. Furthermore, although DTI showed deterioration of the right inferior and superior longitudinal fasciculi, as well as the PCC, it did not demonstrate significant deterioration of UF tracts. Taken together, early-stage CDDAT may represent a common emerging point for the loss of face labeling ability.

Medial cortex activity, self-reflection and depression.

PubMed

Johnson, Marcia K; Nolen-Hoeksema, Susan; Mitchell, Karen J; Levin, Yael

2009-12-01

Using functional magnetic resonance imaging, we investigated neural activity associated with self-reflection in depressed [current major depressive episode (MDE)] and healthy control participants, focusing on medial cortex areas previously shown to be associated with self-reflection. Both the MDE and healthy control groups showed greater activity in anterior medial cortex (medial frontal gyrus, anterior cingulate gyrus) when cued to think about hopes and aspirations compared with duties and obligations, and greater activity in posterior medial cortex (precuneus, posterior cingulate) when cued to think about duties and obligations (Experiment 1). However, the MDE group showed less activity than controls in the same area of medial frontal cortex when self-referential cues were more ambiguous with respect to valence (Experiment 2), and less deactivation in a non-self-referential condition in both experiments. Furthermore, individual differences in rumination were positively correlated with activity in both anterior and posterior medial cortex during non-self-referential conditions. These results provide converging evidence for a dissociation of anterior and posterior medial cortex depending on the focus of self-relevant thought. They also provide neural evidence consistent with behavioral findings that depression is associated with disruption of positively valenced thoughts in response to ambiguous cues, and difficulty disengaging from self-reflection when it is appropriate to do so.

Medial cortex activity, self-reflection and depression

PubMed Central

Nolen-Hoeksema, Susan; Mitchell, Karen J.; Levin, Yael

2009-01-01

Using functional magnetic resonance imaging, we investigated neural activity associated with self-reflection in depressed [current major depressive episode (MDE)] and healthy control participants, focusing on medial cortex areas previously shown to be associated with self-reflection. Both the MDE and healthy control groups showed greater activity in anterior medial cortex (medial frontal gyrus, anterior cingulate gyrus) when cued to think about hopes and aspirations compared with duties and obligations, and greater activity in posterior medial cortex (precuneus, posterior cingulate) when cued to think about duties and obligations (Experiment 1). However, the MDE group showed less activity than controls in the same area of medial frontal cortex when self-referential cues were more ambiguous with respect to valence (Experiment 2), and less deactivation in a non-self-referential condition in both experiments. Furthermore, individual differences in rumination were positively correlated with activity in both anterior and posterior medial cortex during non-self-referential conditions. These results provide converging evidence for a dissociation of anterior and posterior medial cortex depending on the focus of self-relevant thought. They also provide neural evidence consistent with behavioral findings that depression is associated with disruption of positively valenced thoughts in response to ambiguous cues, and difficulty disengaging from self-reflection when it is appropriate to do so. PMID:19620180

Distinct roles of three frontal cortical areas in reward-guided behavior

PubMed Central

Noonan, M.P.; Mars, R.B.; Rushworth, M.F.S

2011-01-01

Functional magnetic resonance imaging (fMRI) was used to measure activity in three frontal cortical areas, lateral orbitofrontal cortex (lOFC), medial orbitofrontal cortex/ventromedial frontal cortex (mOFC/vmPFC), and anterior cingulate cortex (ACC) when expectations about type of reward, and not just reward presence or absence, could be learned. Two groups of human subjects learned twelve stimulus-response pairings. In one group (Consistent), correct performances of a given pairing were always reinforced with a specific reward outcome whereas in the other group (Inconsistent), correct performances were reinforced with randomly selected rewards. MOFC/vmPFC and lOFC were not distinguished by simple differences in relative preference for positive and negative outcomes. Instead lOFC activity reflected updating of reward-related associations specific to reward type; lOFC was active whenever informative outcomes allowed updating of reward-related associations regardless of whether the outcomes were positive or negative and the effects were greater when consistent stimulus-outcome and response-outcome mappings were present. A psycho-physiological interaction (PPI) analysis demonstrated changed coupling between lOFC and brain areas for visual object representation, such as perirhinal cortex, and reward-guided learning, such as amygdala, ventral striatum, and habenula /mediodorsal thalamus. By contrast mOFC/vmPFC activity reflected expected values of outcomes and occurrence of positive outcomes, irrespective of consistency of outcome mappings. The third frontal cortical region, ACC, reflected the use of reward type information to guide response selection. ACC activity reflected the probability of selecting the correct response, was greater when consistent outcome mappings were present, and was related to individual differences in propensity to select the correct response. PMID:21976525

Moderate effects of noninvasive brain stimulation of the frontal cortex for improving negative symptoms in schizophrenia: Meta-analysis of controlled trials.

PubMed

Aleman, André; Enriquez-Geppert, Stefanie; Knegtering, Henderikus; Dlabac-de Lange, Jozarni J

2018-06-01

Negative symptoms in schizophrenia concern a clinically relevant reduction of goal-directed behavior that strongly and negatively impacts daily functioning. Existing treatments are of marginal effect and novel approaches are needed. Noninvasive neurostimulation by means of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are novel approaches that may hold promise. To provide a quantitative integration of the published evidence regarding effects of rTMS and tDCS over the frontal cortex on negative symptoms, including an analysis of effects of sham stimulation. Meta-analysis was applied, using a random effects model, to calculate mean weighted effect sizes (Cohen's d). Heterogeneity was assessed by using Cochrans Q and I 2 tests. For rTMS treatment, the mean weighted effect size compared to sham stimulation was 0.64 (0.32-0.96; k = 22, total N = 827). Studies with younger participants showed stronger effects as compared to studies with older participants. For tDCS studies a mean weighted effect size of 0.50 (-0.07 to 1.07; k = 5, total N = 134) was found. For all frontal noninvasive neurostimulation studies together (i.e., TMS and tDCS studies combined) active stimulation was superior to sham, the mean weighted effect size was 0.61 (24 studies, 27 comparisons, 95% confidence interval 0.33-0.89; total N = 961). Sham rTMS (baseline - posttreatment comparison) showed a significant improvement of negative symptoms, d = 0.31 (0.09-0.52; k = 16, total N = 333). Whereas previous meta-analyses were underpowered, our meta-analysis had a power of 0.87 to detect a small effect. The available evidence indicates that noninvasive prefrontal neurostimulation can improve negative symptoms. This finding suggests a causal role for the lateral frontal cortex in self-initiated goal-directed behavior. The evidence is stronger for rTMS than for tDCS, although this may be due to the small number of

Investigation of human frontal cortex under noxious thermal stimulation of temporo-mandibular joint using functional near infrared spectroscopy

NASA Astrophysics Data System (ADS)

Yennu, Amarnath; Rawat, Rohit; Manry, Michael T.; Gatchel, Robert; Liu, Hanli

2013-03-01

According to American Academy of Orofacial Pain, 75% of the U.S. population experiences painful symptoms of temporo-mandibular joint and muscle disorder (TMJMD) during their lifetime. Thus, objective assessment of pain is crucial for efficient pain management. We used near infrared spectroscopy (NIRS) as a tool to explore hemodynamic responses in the frontal cortex to noxious thermal stimulation of temporomadibular joint (TMJ). NIRS experiments were performed on 9 healthy volunteers under both low pain stimulation (LPS) and high pain stimulation (HPS), using a temperature-controlled thermal stimulator. To induce thermal pain, a 16X16 mm2 thermode was strapped onto the right TMJ of each subject. Initially, subjects were asked to rate perceived pain on a scale of 0 to 10 for the temperatures from 41°C to 47°C. For the NIRS measurement, two magnitudes of temperatures, one rated as 3 and another rated as 7, were chosen as LPS and HPS, respectively. By analyzing the temporal profiles of changes in oxy-hemoglobin concentration (HbO) using cluster-based statistical tests, we were able to identify several regions of interest (ROI), (e.g., secondary somatosensory cortex and prefrontal cortex), where significant differences (p<0.05) between HbO responses to LPS and HPS are shown. In order to classify these two levels of pain, a neural-network-based classification algorithm was used. With leave-one-out cross validation from 9 subjects, the two levels of pain were identified with 100% mean sensitivity, 98% mean specificity and 99% mean accuracy to high pain. From the receiver operating characteristics curve, 0.99 mean area under curve was observed.

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

Norepinephrine in the Medial Pre-frontal Cortex Supports Accumbens Shell Responses to a Novel Palatable Food in Food-Restricted Mice Only

PubMed Central

Latagliata, Emanuele Claudio; Puglisi-Allegra, Stefano; Ventura, Rossella; Cabib, Simona

2018-01-01

Previous findings from this laboratory demonstrate: (1) that different classes of addictive drugs require intact norepinephrine (NE) transmission in the medial pre Frontal Cortex (mpFC) to promote conditioned place preference and to increase dopamine (DA) tone in the nucleus accumbens shell (NAc Shell); (2) that only food-restricted mice require intact NE transmission in the mpFC to develop conditioned preference for a context associated with milk chocolate; and (3) that food-restricted mice show a significantly larger increase of mpFC NE outflow then free fed mice when experiencing the palatable food for the first time. In the present study we tested the hypothesis that only the high levels of frontal cortical NE elicited by the natural reward in food restricted mice stimulate mesoaccumbens DA transmission. To this aim we investigated the ability of a first experience with milk chocolate to increase DA outflow in the accumbens Shell and c-fos expression in striatal and limbic areas of food–restricted and ad-libitum fed mice. Moreover, we tested the effects of a selective depletion of frontal cortical NE on both responses in either feeding group. Only in food-restricted mice milk chocolate induced an increase of DA outflow beyond baseline in the accumbens Shell and a c-fos expression larger than that promoted by a novel inedible object in the nucleus accumbens. Moreover, depletion of frontal cortical NE selectively prevented both the increase of DA outflow and the large expression of c-fos promoted by milk chocolate in the NAc Shell of food-restricted mice. These findings support the conclusion that in food-restricted mice a novel palatable food activates the motivational circuit engaged by addictive drugs and support the development of noradrenergic pharmacology of motivational disturbances. PMID:29434542

Lower Activation in Frontal Cortex and Posterior Cingulate Cortex Observed during Sex Determination Test in Early-Stage Dementia of the Alzheimer Type

PubMed Central

Rajmohan, Ravi; Anderson, Ronald C.; Fang, Dan; Meyer, Austin G.; Laengvejkal, Pavis; Julayanont, Parunyou; Hannabas, Greg; Linton, Kitten; Culberson, John; Khan, Hafiz; De Toledo, John; Reddy, P. Hemachandra; O’Boyle, Michael W.

2017-01-01

Face-labeling refers to the ability to classify faces into social categories. This plays a critical role in human interaction as it serves to define concepts of socially acceptable interpersonal behavior. The purpose of the current study was to characterize, what, if any, impairments in face-labeling are detectable in participants with early-stage clinically diagnosed dementia of the Alzheimer type (CDDAT) through the use of the sex determination test (SDT). In the current study, four (1 female, 3 males) CDDAT and nine (4 females, 5 males) age-matched neurotypicals (NT) completed the SDT using chimeric faces while undergoing BOLD fMRI. It was expected that CDDAT participants would have poor verbal fluency, which would correspond to poor performance on the SDT. This could be explained by decreased activation and connectivity patterns within the fusiform face area (FFA) and anterior cingulate cortex (ACC). DTI was also performed to test the association of pathological deterioration of connectivity in the uncinate fasciculus (UF) and verbally-mediated performance. CDDAT showed lower verbal fluency test (VFT) performance, but VFT was not significantly correlated to SDT and no significant difference was seen between CDDAT and NT for SDT performance as half of the CDDAT performed substantially worse than NT while the other half performed similarly. BOLD fMRI of SDT displayed differences in the left superior frontal gyrus and posterior cingulate cortex (PCC), but not the FFA or ACC. Furthermore, although DTI showed deterioration of the right inferior and superior longitudinal fasciculi, as well as the PCC, it did not demonstrate significant deterioration of UF tracts. Taken together, early-stage CDDAT may represent a common emerging point for the loss of face labeling ability. PMID:28588478

Reduced Mitochondrial Activity is Early and Steady in the Entorhinal Cortex but it is Mainly Unmodified in the Frontal Cortex in Alzheimer's Disease.

PubMed

Armand-Ugon, Mercedes; Ansoleaga, Belen; Berjaoui, Sara; Ferrer, Isidro

2017-01-01

It is well established that mitochondrial damage plays a role in the pathophysiology of Alzheimer's disease (AD). However, studies carried out in humans barely contemplate regional differences with disease progression. To study the expression of selected nuclear genes encoding subunits of the mitochondrial complexes and the activity of mitochondrial complexes in AD, in two regions: the entorhinal cortex (EC) and frontal cortex area 8 (FC). Frozen samples from 148 cases processed for gene expression by qRT-PCR and determination of individual activities of mitochondrial complexes I, II, IV and V using commercial kits and home-made assays. Decreased expression of NDUFA2, NDUFB3, UQCR11, COX7C, ATPD, ATP5L and ATP50, covering subunits of complex I, II, IV and V, occurs in total homogenates of the EC in AD stages V-VI when compared with stages I-II. However reduced activity of complexes I, II and V of isolated mitochondria occurs as early as stages I-II when compared with middle-aged individuals in the EC. In contrast, no alterations in the expression of the same genes and no alterations in the activity of mitochondrial complexes are found in the FC in the same series. Different mechanisms of impaired energy metabolism may occur in AD, one of them, represented by the EC, is the result of primary and early alteration of mitochondria; the other one is probably the result, at least in part, of decreased functional input and is represented by hypometabolism in the FC in AD patients aged 86 or younger. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Region-, age-, and sex-specific effects of fetal diazepam exposure on the postnatal development of neurosteroids

PubMed Central

Kellogg, Carol K.; Kenjarski, Thomas P.; Pleger, Gloria L.; Frye, Cheryl A.

2013-01-01

Fetal exposure to diazepam (DZ), a positive modulator of GABAA receptors and an agonist at mitochondrial benzodiazine receptors, induces long-term neural and behavioral effects. This study evaluated whether the early manipulation influenced the normal development of brain levels of neurosteroids or altered steroid action at GABAA receptors. Pregnant dams were injected over gestation days 14 through 20 with DZ (2.5 mg/kg) or the vehicle. Male and female offspring were analyzed at five postnatal ages. The levels of progesterone (P), dihydroprogesterone (DHP), 3α-hydroxy-5α-pregnan-20-one (3α,5α-THP), testosterone (T), dihydrotestosterone, and 5α-androstan-3α,17β diol were measured in the cerebral cortex and diencephalon. The results indicated that development of brain steroid levels and the impact of fetal DZ exposure were region- and sex-specific. Age-related changes in brain steroids did not mirror associated changes in circulating P and T. Age regulated the levels of all 3 progestins in the cerebral cortex, and fetal DZ exposure interacted with the development of P and DHP. The development of 3α,5α-THP in the cortex was markedly influenced by sex, with levels in males decreasing over postnatal development whereas they increased over postpubertal development in females. An adolescent surge in T levels was observed in male cortex and fetal DZ exposure prevented that surge. Steroid levels in the diencephalon were altered by age mainly in females, and DZ exposure had little effect in this region. The data support region-specific regulation of brain steroid synthesis. Only in the cerebral cortex are relevant mechanisms readily modifiable by fetal DZ exposure. However, neither sex nor fetal DZ exposure altered the response of GABAA receptors in adult cortex to neurosteroid. PMID:16376310

Neurotoxic lesions of ventrolateral prefrontal cortex impair object-in-place scene memory

PubMed Central

Wilson, Charles R E; Gaffan, David; Mitchell, Anna S; Baxter, Mark G

2007-01-01

Disconnection of the frontal lobe from the inferotemporal cortex produces deficits in a number of cognitive tasks that require the application of memory-dependent rules to visual stimuli. The specific regions of frontal cortex that interact with the temporal lobe in performance of these tasks remain undefined. One capacity that is impaired by frontal–temporal disconnection is rapid learning of new object-in-place scene problems, in which visual discriminations between two small typographic characters are learned in the context of different visually complex scenes. In the present study, we examined whether neurotoxic lesions of ventrolateral prefrontal cortex in one hemisphere, combined with ablation of inferior temporal cortex in the contralateral hemisphere, would impair learning of new object-in-place scene problems. Male macaque monkeys learned 10 or 20 new object-in-place problems in each daily test session. Unilateral neurotoxic lesions of ventrolateral prefrontal cortex produced by multiple injections of a mixture of ibotenate and N-methyl-d-aspartate did not affect performance. However, when disconnection from inferotemporal cortex was completed by ablating this region contralateral to the neurotoxic prefrontal lesion, new learning was substantially impaired. Sham disconnection (injecting saline instead of neurotoxin contralateral to the inferotemporal lesion) did not affect performance. These findings support two conclusions: first, that the ventrolateral prefrontal cortex is a critical area within the frontal lobe for scene memory; and second, the effects of ablations of prefrontal cortex can be confidently attributed to the loss of cell bodies within the prefrontal cortex rather than to interruption of fibres of passage through the lesioned area. PMID:17445247

Transient shifts in frontal and parietal circuits scale with enhanced visual feedback and changes in force variability and error

PubMed Central

Poon, Cynthia; Coombes, Stephen A.; Corcos, Daniel M.; Christou, Evangelos A.

2013-01-01

When subjects perform a learned motor task with increased visual gain, error and variability are reduced. Neuroimaging studies have identified a corresponding increase in activity in parietal cortex, premotor cortex, primary motor cortex, and extrastriate visual cortex. Much less is understood about the neural processes that underlie the immediate transition from low to high visual gain within a trial. This study used 128-channel electroencephalography to measure cortical activity during a visually guided precision grip task, in which the gain of the visual display was changed during the task. Force variability during the transition from low to high visual gain was characterized by an inverted U-shape, whereas force error decreased from low to high gain. Source analysis identified cortical activity in the same structures previously identified using functional magnetic resonance imaging. Source analysis also identified a time-varying shift in the strongest source activity. Superior regions of the motor and parietal cortex had stronger source activity from 300 to 600 ms after the transition, whereas inferior regions of the extrastriate visual cortex had stronger source activity from 500 to 700 ms after the transition. Force variability and electrical activity were linearly related, with a positive relation in the parietal cortex and a negative relation in the frontal cortex. Force error was nonlinearly related to electrical activity in the parietal cortex and frontal cortex by a quadratic function. This is the first evidence that force variability and force error are systematically related to a time-varying shift in cortical activity in frontal and parietal cortex in response to enhanced visual gain. PMID:23365186

Performance monitoring in the medial frontal cortex and related neural networks: From monitoring self actions to understanding others' actions.

PubMed

Ninomiya, Taihei; Noritake, Atsushi; Ullsperger, Markus; Isoda, Masaki

2018-04-27

Action is a key channel for interacting with the outer world. As such, the ability to monitor actions and their consequences - regardless as to whether they are self-generated or other-generated - is of crucial importance for adaptive behavior. The medial frontal cortex (MFC) has long been studied as a critical node for performance monitoring in nonsocial contexts. Accumulating evidence suggests that the MFC is involved in a wide range of functions necessary for one's own performance monitoring, including error detection, and monitoring and resolving response conflicts. Recent studies, however, have also pointed to the importance of the MFC in performance monitoring under social conditions, ranging from monitoring and understanding others' actions to reading others' mental states, such as their beliefs and intentions (i.e., mentalizing). Here we review the functional roles of the MFC and related neural networks in performance monitoring in both nonsocial and social contexts, with an emphasis on the emerging field of a social systems neuroscience approach using macaque monkeys as a model system. Future work should determine the way in which the MFC exerts its monitoring function via interactions with other brain regions, such as the superior temporal sulcus in the mentalizing system and the ventral premotor cortex in the mirror system. Copyright © 2018. Published by Elsevier B.V.

The dorsal medial frontal cortex is sensitive to time on task, not response conflict or error likelihood.

PubMed

Grinband, Jack; Savitskaya, Judith; Wager, Tor D; Teichert, Tobias; Ferrera, Vincent P; Hirsch, Joy

2011-07-15

The dorsal medial frontal cortex (dMFC) is highly active during choice behavior. Though many models have been proposed to explain dMFC function, the conflict monitoring model is the most influential. It posits that dMFC is primarily involved in detecting interference between competing responses thus signaling the need for control. It accurately predicts increased neural activity and response time (RT) for incompatible (high-interference) vs. compatible (low-interference) decisions. However, it has been shown that neural activity can increase with time on task, even when no decisions are made. Thus, the greater dMFC activity on incompatible trials may stem from longer RTs rather than response conflict. This study shows that (1) the conflict monitoring model fails to predict the relationship between error likelihood and RT, and (2) the dMFC activity is not sensitive to congruency, error likelihood, or response conflict, but is monotonically related to time on task. Copyright © 2010 Elsevier Inc. All rights reserved.

Bilingualism Alters Children's Frontal Lobe Functioning for Attentional Control

PubMed Central

Arredondo, Maria M.; Hu, Xiao-Su; Satterfield, Teresa; Kovelman, Ioulia

2017-01-01

Bilingualism is a typical linguistic experience, yet relatively little is known about its impact on children's cognitive and brain development. Theories of bilingualism suggest early dual-language acquisition can improve children's cognitive abilities, specifically those relying on frontal lobe functioning. While behavioral findings present much conflicting evidence, little is known about its effects on children's frontal lobe development. Using functional Near-Infrared Spectroscopy (fNIRS), the findings suggest that Spanish-English bilingual children (n=13, ages 7-13) had greater activation in left prefrontal cortex during a non-verbal attentional control task relative to age-matched English monolinguals. In contrast, monolinguals (n=14) showed greater right prefrontal activation than bilinguals. The present findings suggest early bilingualism yields significant changes to the functional organization of children's prefrontal cortex for attentional control and carry implications for understanding how early life experiences impact cognition and brain development. PMID:26743118

Working memory load impairs the evaluation of behavioral errors in the medial frontal cortex.

PubMed

Maier, Martin E; Steinhauser, Marco

2017-10-01

Early error monitoring in the medial frontal cortex enables error detection and the evaluation of error significance, which helps prioritize adaptive control. This ability has been assumed to be independent from central capacity, a limited pool of resources assumed to be involved in cognitive control. The present study investigated whether error evaluation depends on central capacity by measuring the error-related negativity (Ne/ERN) in a flanker paradigm while working memory load was varied on two levels. We used a four-choice flanker paradigm in which participants had to classify targets while ignoring flankers. Errors could be due to responding either to the flankers (flanker errors) or to none of the stimulus elements (nonflanker errors). With low load, the Ne/ERN was larger for flanker errors than for nonflanker errors-an effect that has previously been interpreted as reflecting differential significance of these error types. With high load, no such effect of error type on the Ne/ERN was observable. Our findings suggest that working memory load does not impair the generation of an Ne/ERN per se but rather impairs the evaluation of error significance. They demonstrate that error monitoring is composed of capacity-dependent and capacity-independent mechanisms. © 2017 Society for Psychophysiological Research.

Early Alzheimer's disease-type pathology in the frontal cortex of wild mountain gorillas (Gorilla beringei beringei).

PubMed

Perez, Sylvia E; Sherwood, Chet C; Cranfield, Michael R; Erwin, Joseph M; Mudakikwa, Antoine; Hof, Patrick R; Mufson, Elliott J

2016-03-01

Amyloid beta (Aβ) and tau pathology have been described in the brains of captive aged great apes, but the natural progression of these age-related pathologies from wild great apes, including the gorilla, is unknown. In our previous study of Western lowland gorillas (Gorilla gorilla gorilla) who were housed in American Zoos and Aquariums-accredited facilities, we found an age-related increase in Aβ-positive plaques and vasculature, tau-positive astrocytes, oligodendrocyte coiled bodies, and neuritic clusters in the neocortex as well as hippocampus in older animals. Here, we demonstrate that aged wild mountain gorillas (Gorilla beringei beringei), who spent their entire lives in their natural habitat, also display an age-related increase in amyloid precursor protein (APP) and/or Aβ-immunoreactive blood vessels and plaques, but very limited tau pathology, in the frontal cortex. These results indicate that Aβ and tau lesions are age-related events that occur in the brain of gorillas living in captivity and in the wild. Copyright © 2016 Elsevier Inc. All rights reserved.

Glutamine synthetase activity and glutamate uptake in hippocampus and frontal cortex in portal hypertensive rats

PubMed Central

Acosta, Gabriela Beatriz; Fernández, María Alejandra; Roselló, Diego Martín; Tomaro, María Luján; Balestrasse, Karina; Lemberg, Abraham

2009-01-01

AIM: To study glutamine synthetase (GS) activity and glutamate uptake in the hippocampus and frontal cortex (FC) from rats with prehepatic portal vein hypertension. METHODS: Male Wistar rats were divided into sham-operated group and a portal hypertension (PH) group with a regulated stricture of the portal vein. Animals were sacrificed by decapitation 14 d after portal vein stricture. GS activity was determined in the hippocampus and FC. Specific uptake of radiolabeled L-glutamate was studied using synaptosome-enriched fractions that were freshly prepared from both brain areas. RESULTS: We observed that the activity of GS increased in the hippocampus of PH rats, as compared to control animals, and decreased in the FC. A significant decrease in glutamate uptake was found in both brain areas, and was more marked in the hippocampus. The decrease in glutamate uptake might have been caused by a deficient transport function, significantly and persistent increase in this excitatory neurotransmitter activity. CONCLUSION: The presence of moderate ammonia blood levels may add to the toxicity of excitotoxic glutamate in the brain, which causes alterations in brain function. Portal vein stricture that causes portal hypertension modifies the normal function in some brain regions. PMID:19533812

Differences in the neural correlates of frontal lobe tests.

PubMed

Matsuoka, Teruyuki; Kato, Yuka; Imai, Ayu; Fujimoto, Hiroshi; Shibata, Keisuke; Nakamura, Kaeko; Yamada, Kei; Narumoto, Jin

2018-01-01

The Executive Interview (EXIT25), the executive clock-drawing task (CLOX1), and the Frontal Assessment Battery (FAB) are used to assess executive function at the bedside. These tests assess distinct psychometric properties. The aim of this study was to examine differences in the neural correlates of the EXIT25, CLOX1, and FAB based on magnetic resonance imaging. Fifty-eight subjects (30 with Alzheimer's disease, 10 with mild cognitive impairment, and 18 healthy controls) participated in this study. Multiple regression analyses were performed to examine the brain regions correlated with the EXIT25, CLOX1, and FAB scores. Age, gender, and years of education were included as covariates. Statistical thresholds were set to uncorrected P-values of 0.001 at the voxel level and 0.05 at the cluster level. The EXIT25 score correlated inversely with the regional grey matter volume in the left lateral frontal lobe (Brodmann areas 6, 9, 44, and 45). The CLOX1 score correlated positively with the regional grey matter volume in the right orbitofrontal cortex (Brodmann area 11) and the left supramarginal gyrus (Brodmann area 40). The FAB score correlated positively with the regional grey matter volume in the right precentral gyrus (Brodmann area 6). The left lateral frontal lobe (Brodmann area 9) and the right lateral frontal lobe (Brodmann area 46) were identified as common brain regions that showed association with EXIT25, CLOX1, and FAB based only a voxel-level threshold. The results of this study suggest that the EXIT25, CLOX1, and FAB may be associated with the distinct neural correlates of the frontal cortex. © 2018 Japanese Psychogeriatric Society.

α2-Adrenoceptor Functionality in Postmortem Frontal Cortex of Depressed Suicide Victims

PubMed Central

Valdizán, Elsa M.; Díez-Alarcia, Rebeca; González-Maeso, Javier; Pilar-Cuéllar, Fuencisla; García-Sevilla, Jesús A.; Meana, J. Javier; Pazos, Angel

2013-01-01

Background Alterations in brain density and signaling associated with monoamine receptors are believed to play a role in depressive disorders. This study evaluates the functional status of α2A-adrenoceptors in postmortem frontal cortex of depressed subjects. Methods G-protein activation and inhibition of adenylyl cyclase (AC) activity induced by the α2-adrenoceptor agonist UK14304 were measured in triplicate in samples from 15 suicide victims with an antemortem diagnosis of major depression and 15 matched control subjects. Results Basal [35S] guanosine γ thio-phosphate (GTPγS) binding and cyclic adenosine monophosphate accumulation did not differ between groups. In depressed victims, an increase in [35S] GTPγS binding potency (EC50 = .58 μmol/L vs. EC50 = 3.31 μmol/L; p < .01; depressed vs. control) and a significant reduction in the maximal inhibition of AC activity (Imax = 27 ± 4% vs. Imax = 47 ± 5%; p < .01) were observed after incubation with the α2-adrenoceptor agonist UK14304. No differences were found between antidepressant-free and antidepressant-treated subjects. A significant relationship between EC50 values for [35S] GTPγS and Imax values for AC assay was found (n = 30; r = −.43; p < .05). Conclusions The dual regulation of α2A-adrenoceptor signaling pathways raises the possibility that factors affecting the G-protein cycle and/or selective access of Gαi/o–protein to AC might be relevant to receptor abnormalities in depression, providing further support for the involvement of α2A-adrenoceptors in the pathogenesis of depression. PMID:20864091

Sex-related differences in auditory processing in adolescents with fetal alcohol spectrum disorder: A magnetoencephalographic study.

PubMed

Tesche, Claudia D; Kodituwakku, Piyadasa W; Garcia, Christopher M; Houck, Jon M

2015-01-01

Children exposed to substantial amounts of alcohol in utero display a broad range of morphological and behavioral outcomes, which are collectively referred to as fetal alcohol spectrum disorders (FASDs). Common to all children on the spectrum are cognitive and behavioral problems that reflect central nervous system dysfunction. Little is known, however, about the potential effects of variables such as sex on alcohol-induced brain damage. The goal of the current research was to utilize magnetoencephalography (MEG) to examine the effect of sex on brain dynamics in adolescents and young adults with FASD during the performance of an auditory oddball task. The stimuli were short trains of 1 kHz "standard" tone bursts (80%) randomly interleaved with 1.5 kHz "target" tone bursts (10%) and "novel" digital sounds (10%). Participants made motor responses to the target tones. Results are reported for 44 individuals (18 males and 26 females) ages 12 through 22 years. Nine males and 13 females had a diagnosis of FASD and the remainder were typically-developing age- and sex-matched controls. The main finding was widespread sex-specific differential activation of the frontal, medial and temporal cortex in adolescents with FASD compared to typically developing controls. Significant differences in evoked-response and time-frequency measures of brain dynamics were observed for all stimulus types in the auditory cortex, inferior frontal sulcus and hippocampus. These results underscore the importance of considering the influence of sex when analyzing neurophysiological data in children with FASD.

Working memory load modulation of parieto-frontal connections: evidence from dynamic causal modeling

PubMed Central

Ma, Liangsuo; Steinberg, Joel L.; Hasan, Khader M.; Narayana, Ponnada A.; Kramer, Larry A.; Moeller, F. Gerard

2011-01-01

Previous neuroimaging studies have shown that working memory load has marked effects on regional neural activation. However, the mechanism through which working memory load modulates brain connectivity is still unclear. In this study, this issue was addressed using dynamic causal modeling (DCM) based on functional magnetic resonance imaging (fMRI) data. Eighteen normal healthy subjects were scanned while they performed a working memory task with variable memory load, as parameterized by two levels of memory delay and three levels of digit load (number of digits presented in each visual stimulus). Eight regions of interest, i.e., bilateral middle frontal gyrus (MFG), anterior cingulate cortex (ACC), inferior frontal cortex (IFC), and posterior parietal cortex (PPC), were chosen for DCM analyses. Analysis of the behavioral data during the fMRI scan revealed that accuracy decreased as digit load increased. Bayesian inference on model structure indicated that a bilinear DCM in which memory delay was the driving input to bilateral PPC and in which digit load modulated several parieto-frontal connections was the optimal model. Analysis of model parameters showed that higher digit load enhanced connection from L PPC to L IFC, and lower digit load inhibited connection from R PPC to L ACC. These findings suggest that working memory load modulates brain connectivity in a parieto-frontal network, and may reflect altered neuronal processes, e.g., information processing or error monitoring, with the change in working memory load. PMID:21692148

The role of left inferior frontal cortex during audiovisual speech perception in infants.

PubMed

Altvater-Mackensen, Nicole; Grossmann, Tobias

2016-06-01

In the first year of life, infants' speech perception attunes to their native language. While the behavioral changes associated with native language attunement are fairly well mapped, the underlying mechanisms and neural processes are still only poorly understood. Using fNIRS and eye tracking, the current study investigated 6-month-old infants' processing of audiovisual speech that contained matching or mismatching auditory and visual speech cues. Our results revealed that infants' speech-sensitive brain responses in inferior frontal brain regions were lateralized to the left hemisphere. Critically, our results further revealed that speech-sensitive left inferior frontal regions showed enhanced responses to matching when compared to mismatching audiovisual speech, and that infants with a preference to look at the speaker's mouth showed an enhanced left inferior frontal response to speech compared to infants with a preference to look at the speaker's eyes. These results suggest that left inferior frontal regions play a crucial role in associating information from different modalities during native language attunement, fostering the formation of multimodal phonological categories. Copyright © 2016 Elsevier Inc. All rights reserved.

Neurophysiologic markers of primary motor cortex for laryngeal muscles and premotor cortex in caudal opercular part of inferior frontal gyrus investigated in motor speech disorder: a navigated transcranial magnetic stimulation (TMS) study.

PubMed

Rogić Vidaković, Maja; Jerković, Ana; Jurić, Tomislav; Vujović, Igor; Šoda, Joško; Erceg, Nikola; Bubić, Andreja; Zmajević Schönwald, Marina; Lioumis, Pantelis; Gabelica, Dragan; Đogaš, Zoran

2016-11-01

Transcranial magnetic stimulation studies have so far reported the results of mapping the primary motor cortex (M1) for hand and tongue muscles in stuttering disorder. This study was designed to evaluate the feasibility of repetitive navigated transcranial magnetic stimulation (rTMS) for locating the M1 for laryngeal muscle and premotor cortical area in the caudal opercular part of inferior frontal gyrus, corresponding to Broca's area in stuttering subjects by applying new methodology for mapping these motor speech areas. Sixteen stuttering and eleven control subjects underwent rTMS motor speech mapping using modified patterned rTMS. The subjects performed visual object naming task during rTMS applied to the (a) left M1 for laryngeal muscles for recording corticobulbar motor-evoked potentials (CoMEP) from cricothyroid muscle and (b) left premotor cortical area in the caudal opercular part of inferior frontal gyrus while recording long latency responses (LLR) from cricothyroid muscle. The latency of CoMEP in control subjects was 11.75 ± 2.07 ms and CoMEP amplitude was 294.47 ± 208.87 µV, and in stuttering subjects CoMEP latency was 12.13 ± 0.75 ms and 504.64 ± 487.93 µV CoMEP amplitude. The latency of LLR in control subjects was 52.8 ± 8.6 ms and 54.95 ± 4.86 in stuttering subjects. No significant differences were found in CoMEP latency, CoMEP amplitude, and LLR latency between stuttering and control-fluent speakers. These results indicate there are probably no differences in stuttering compared to controls in functional anatomy of the pathway used for transmission of information from premotor cortex to the M1 cortices for laryngeal muscle representation and from there via corticobulbar tract to laryngeal muscles.

Rivastigmine is Associated with Restoration of Left Frontal Brain Activity in Parkinson’s Disease

PubMed Central

Possin, Katherine L.; Kang, Gail A.; Guo, Christine; Fine, Eric M.; Trujillo, Andrew J.; Racine, Caroline A.; Wilheim, Reva; Johnson, Erica T.; Witt, Jennifer L.; Seeley, William W.; Miller, Bruce L.; Kramer, Joel H.

2013-01-01

Objective To investigate how acetylcholinesterase inhibitor (ChEI) treatment impacts brain function in Parkinson’s disease (PD). Methods Twelve patients with PD and either dementia or mild cognitive impairment underwent task-free functional magnetic resonance imaging before and after three months of ChEI treatment and were compared to 15 age and sex matched neurologically healthy controls. Regional spontaneous brain activity was measured using the fractional amplitude of low frequency fluctuations. Results At baseline, patients showed reduced spontaneous brain activity in regions important for motor control (e.g., caudate, supplementary motor area, precentral gyrus, thalamus), attention and executive functions (e.g., lateral prefrontal cortex), and episodic memory (e.g., precuneus, angular gyrus, hippocampus). After treatment, the patients showed a similar but less extensive pattern of reduced spontaneous brain activity relative to controls. Spontaneous brain activity deficits in the left premotor cortex, inferior frontal gyrus, and supplementary motor area were restored such that the activity was increased post-treatment compared to baseline and was no longer different from controls. Treatment-related increases in left premotor and inferior frontal cortex spontaneous brain activity correlated with parallel reaction time improvement on a test of controlled attention. Conclusions PD patients with cognitive impairment show numerous regions of decreased spontaneous brain function compared to controls, and rivastigmine is associated with performance-related normalization in left frontal cortex function. PMID:23847120

Dynamic Variation in Pleasure in Children Predicts Nonlinear Change in Lateral Frontal Brain Electrical Activity

ERIC Educational Resources Information Center

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

2009-01-01

Individual variation in the experience and expression of pleasure may relate to differential patterns of lateral frontal activity. Brain electrical measures have been used to study the asymmetric involvement of lateral frontal cortex in positive emotion, but the excellent time resolution of these measures has not been used to capture…

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

Dysregulation of major functional genes in frontal cortex by maternal exposure to carbon black nanoparticle is not ameliorated by ascorbic acid pretreatment.

PubMed

Onoda, Atsuto; Takeda, Ken; Umezawa, Masakazu

2018-09-01

Recent cohort studies have revealed that perinatal exposure to particulate air pollution, including carbon-based nanoparticles, increases the risk of brain disorders. Although developmental neurotoxicity is currently a major issue in the toxicology of nanoparticles, critical information for understanding the mechanisms underlying the developmental neurotoxicity of airway exposure to carbon black nanoparticle (CB-NP) is still lacking. In order to investigate these mechanisms, we comprehensively analyzed fluctuations in the gene expression profile of the frontal cortex of offspring mice exposed maternally to CB-NP, using microarray analysis combined with Gene Ontology information. We also analyzed differences in the enriched function of genes dysregulated by maternal CB-NP exposure with and without ascorbic acid pretreatment to refine specific alterations in gene expression induced by CB-NP. Total of 652 and 775 genes were dysregulated by CB-NP in the frontal cortex of 6- and 12-week-old offspring mice, respectively. Among the genes dysregulated by CB-NP, those related to extracellular matrix structural constituent, cellular response to interferon-beta, muscle organ development, and cysteine-type endopeptidase inhibitor activity were ameliorated by ascorbic acid pretreatment. A large proportion of the dysregulated genes, categorized in hemostasis, growth factor, chemotaxis, cell proliferation, blood vessel, and dopaminergic neurotransmission, were, however, not ameliorated by ascorbic acid pretreatment. The lack of effects of ascorbic acid on the dysregulation of genes following maternal CB-NP exposure suggests that the contribution of oxidative stress to the effects of CB-NP on these biological functions, i.e., cell migration and proliferation, blood vessel maintenance, and dopaminergic neuron system, may be limited. At least, ascorbic acid pretreatment is hardly likely to be able to protect the brain of offspring from developmental neurotoxicity of CB-NP. The

Lateral Prefrontal Cortex Subregions Make Dissociable Contributions during Fluid Reasoning

PubMed Central

Thompson, Russell; Duncan, John; Owen, Adrian M.

2011-01-01

Reasoning is a key component of adaptable “executive” behavior and is known to depend on a network of frontal and parietal brain regions. However, the mechanisms by which this network supports reasoning and adaptable behavior remain poorly defined. Here, we examine the relationship between reasoning, executive control, and frontoparietal function in a series of nonverbal reasoning experiments. Our results demonstrate that, in accordance with previous studies, a network of frontal and parietal brain regions is recruited during reasoning. Our results also reveal that this network can be fractionated according to how different subregions respond when distinct reasoning demands are manipulated. While increased rule complexity modulates activity within a right lateralized network including the middle frontal gyrus and the superior parietal cortex, analogical reasoning demand—or the requirement to remap rules on to novel features—recruits the left inferior rostrolateral prefrontal cortex and the lateral occipital complex. In contrast, the posterior extent of the inferior frontal gyrus, associated with simpler executive demands, is not differentially sensitive to rule complexity or analogical demand. These findings accord well with the hypothesis that different reasoning demands are supported by different frontal and parietal subregions. PMID:20483908

Neuropsychology of prefrontal cortex

PubMed Central

Siddiqui, Shazia Veqar; Chatterjee, Ushri; Kumar, Devvarta; Siddiqui, Aleem; Goyal, Nishant

2008-01-01

The history of clinical frontal lobe study is long and rich which provides valuable insights into neuropsychologic determinants of functions of prefrontal cortex (PFC). PFC is often classified as multimodal association cortex as extremely processed information from various sensory modalities is integrated here in a precise fashion to form the physiologic constructs of memory, perception, and diverse cognitive processes. Human neuropsychologic studies also support the notion of different functional operations within the PFC. The specification of the component ‘executive’ processes and their localization to particular regions of PFC have been implicated in a wide variety of psychiatric disorders. PMID:19742233

Frontal Cortex Transcriptome Analysis of Mice Exposed to Electronic Cigarettes During Early Life Stages

PubMed Central

Lauterstein, Dana E.; Tijerina, Pamella B.; Corbett, Kevin; Akgol Oksuz, Betul; Shen, Steven S.; Gordon, Terry; Klein, Catherine B.; Zelikoff, Judith T.

2016-01-01

Electronic cigarettes (e-cigarettes), battery-powered devices containing nicotine, glycerin, propylene glycol, flavorings, and other substances, are increasing in popularity. They pose a potential threat to the developing brain, as nicotine is a known neurotoxicant. We hypothesized that exposure to e-cigarettes during early life stages induce changes in central nervous system (CNS) transcriptome associated with adverse neurobiological outcomes and long-term disease states. To test the hypothesis, pregnant C57BL/6 mice were exposed daily (via whole body inhalation) throughout gestation (3 h/day; 5 days/week) to aerosols produced from e-cigarettes either with nicotine (13–16 mg/mL) or without nicotine; following birth, pups and dams were exposed together to e-cigarette aerosols throughout lactation beginning at postnatal day (PND) 4–6 and using the same exposure conditions employed during gestational exposure. Following exposure, frontal cortex recovered from ~one-month-old male and female offspring were excised and analyzed for gene expression by RNA Sequencing (RNA-Seq). Comparisons between the treatment groups revealed that e-cigarette constituents other than nicotine might be partly responsible for the observed biological effects. Transcriptome alterations in both offspring sexes and treatment groups were all significantly associated with downstream adverse neurobiological outcomes. Results from this study demonstrate that e-cigarette exposure during early life alters CNS development potentially leading to chronic neuropathology. PMID:27077873

Frontal Cortex Transcriptome Analysis of Mice Exposed to Electronic Cigarettes During Early Life Stages.

PubMed

Lauterstein, Dana E; Tijerina, Pamella B; Corbett, Kevin; Akgol Oksuz, Betul; Shen, Steven S; Gordon, Terry; Klein, Catherine B; Zelikoff, Judith T

2016-04-12

Electronic cigarettes (e-cigarettes), battery-powered devices containing nicotine, glycerin, propylene glycol, flavorings, and other substances, are increasing in popularity. They pose a potential threat to the developing brain, as nicotine is a known neurotoxicant. We hypothesized that exposure to e-cigarettes during early life stages induce changes in central nervous system (CNS) transcriptome associated with adverse neurobiological outcomes and long-term disease states. To test the hypothesis, pregnant C57BL/6 mice were exposed daily (via whole body inhalation) throughout gestation (3 h/day; 5 days/week) to aerosols produced from e-cigarettes either with nicotine (13-16 mg/mL) or without nicotine; following birth, pups and dams were exposed together to e-cigarette aerosols throughout lactation beginning at postnatal day (PND) 4-6 and using the same exposure conditions employed during gestational exposure. Following exposure, frontal cortex recovered from ~one-month-old male and female offspring were excised and analyzed for gene expression by RNA Sequencing (RNA-Seq). Comparisons between the treatment groups revealed that e-cigarette constituents other than nicotine might be partly responsible for the observed biological effects. Transcriptome alterations in both offspring sexes and treatment groups were all significantly associated with downstream adverse neurobiological outcomes. Results from this study demonstrate that e-cigarette exposure during early life alters CNS development potentially leading to chronic neuropathology.

In search of the functional neuroanatomy of sociality: MRI subdivisions of orbital frontal cortex and social cognition.

PubMed

Nestor, Paul G; Nakamura, Motoaki; Niznikiewicz, Margaret; Thompson, Elizabeth; Levitt, James J; Choate, Victoria; Shenton, Martha E; McCarley, Robert W

2013-04-01

We examined social cognition in a sample of healthy participants who had prior magnetic resonance imaging (MRI) gray matter volume studies of the orbital frontal cortex (OFC) that was parcellated into three regions: gyrus rectus, middle orbital gyrus and lateral orbital gyrus. These subjects also completed a self-report measure of Machiavelli personality traits, along with psychometric tests of social comprehension and declarative episodic memory, all of which we used as proxy measures to examine various features of social cognition. The data pointed to distinct functional-anatomical relationships highlighted by strong correlations of left lateral orbital gyrus and Machiavellian scores and right middle orbital gyrus with social comprehension and declarative episodic memory. In addition, hierarchical regression analyses revealed statistical evidence of a double dissociation between Machiavellian scores and left lateral orbital gyrus on one hand, and social comprehension with right middle orbital gyrus, on the other hand. To our knowledge, these findings are the first to show evidence linking normal variation in OFC subregions and different aspects of social cognition.

In search of the functional neuroanatomy of sociality: MRI subdivisions of orbital frontal cortex and social cognition

PubMed Central

Nakamura, Motoaki; Niznikiewicz, Margaret; Thompson, Elizabeth; Levitt, James J.; Choate, Victoria; Shenton, Martha E.; McCarley, Robert W.

2013-01-01

We examined social cognition in a sample of healthy participants who had prior magnetic resonance imaging (MRI) gray matter volume studies of the orbital frontal cortex (OFC) that was parcellated into three regions: gyrus rectus, middle orbital gyrus and lateral orbital gyrus. These subjects also completed a self-report measure of Machiavelli personality traits, along with psychometric tests of social comprehension and declarative episodic memory, all of which we used as proxy measures to examine various features of social cognition. The data pointed to distinct functional–anatomical relationships highlighted by strong correlations of left lateral orbital gyrus and Machiavellian scores and right middle orbital gyrus with social comprehension and declarative episodic memory. In addition, hierarchical regression analyses revealed statistical evidence of a double dissociation between Machiavellian scores and left lateral orbital gyrus on one hand, and social comprehension with right middle orbital gyrus, on the other hand. To our knowledge, these findings are the first to show evidence linking normal variation in OFC subregions and different aspects of social cognition. PMID:22345366

Reduced dorso-lateral prefrontal cortex in treatment resistant schizophrenia.

PubMed

Zugman, André; Gadelha, Ary; Assunção, Idaiane; Sato, João; Ota, Vanessa K; Rocha, Deyvis L; Mari, Jair J; Belangero, Sintia I; Bressan, Rodrigo A; Brietzke, Elisa; Jackowski, Andrea P

2013-08-01

Treatment resistance affects up to one third of patients with schizophrenia (SCZ). A better understanding of its biological underlying processes could improve treatment. The aim of this study was to compare cortical thickness between non-resistant SCZ (NR-SCZ), treatment-resistant SCZ (TR-SCZ) patients and healthy controls (HC). Structural MRI scans were obtained from 3 groups of individuals: 61 treatment resistant SCZ individuals, 67 non-resistant SCZ and 80 healthy controls. Images were analyzed using cortical surface modelling (implemented in freesurfer package) to identify group differences in cortical thickness. Statistical significant differences were identified using Monte-Carlo simulation method with a corrected p-cluster<0.01. Patients in the TR-SCZ group showed a widespread reduction in cortical thickness in frontal, parietal, temporal and occipital regions bilaterally. NR-SCZ group had reduced cortex in two regions (left superior frontal cortex and left caudal middle frontal cortex). TR-SCZ group also showed decreased thickness in the left dorsolateral prefrontal cortex (DLPFC) when compared with patients from NR-SCZ group. The reduction in cortical thickness in DLPFC indicates a more severe form of the disease or a specific finding for this group. Alterations in this region should be explored as a putative marker for treatment resistance. Prospective studies, with individuals being followed from first episode psychosis until refractoriness is diagnosed, are needed to clarify these hypotheses. Copyright © 2013 Elsevier B.V. All rights reserved.

Lateral prefrontal cortex is organized into parallel dorsal and ventral streams along the rostro-caudal axis.

PubMed

Blumenfeld, Robert S; Nomura, Emi M; Gratton, Caterina; D'Esposito, Mark

2013-10-01

Anatomical connectivity differences between the dorsal and ventral lateral prefrontal cortex (PFC) of the non-human primate strongly suggests that these regions support different functions. However, after years of study, it remains unclear whether these regions are functionally distinct. In contrast, there has been a groundswell of recent studies providing evidence for a rostro-caudal functional organization, along the lateral as well as dorsomedial frontal cortex. Thus, it is not known whether dorsal and ventral regions of lateral PFC form distinct functional networks and how to reconcile any dorso-ventral organization with the medio-lateral and rostro-caudal axes. Here, we used resting-state connectivity data to identify parallel dorsolateral and ventrolateral streams of intrinsic connectivity with the dorsomedial frontal cortex. Moreover, we show that this connectivity follows a rostro-caudal gradient. Our results provide evidence for a novel framework for the intrinsic organization of the frontal cortex that incorporates connections between medio-lateral, dorso-ventral, and rostro-caudal axes.

Oleoylethanolamide prevents neuroimmune HMGB1/TLR4/NF-kB danger signaling in rat frontal cortex and depressive-like behavior induced by ethanol binge administration.

PubMed

Antón, María; Alén, Francisco; Gómez de Heras, Raquel; Serrano, Antonia; Pavón, Francisco Javier; Leza, Juan Carlos; García-Bueno, Borja; Rodríguez de Fonseca, Fernando; Orio, Laura

2017-05-01

Alcohol abuse is frequently characterized by a specific pattern of intake in binge drinking episodes, inducing neuroinflammation and brain damage. Here, we characterized the temporal profile of neuroinflammation in rats exposed to intragastric binge ethanol administrations (3 times/day × 4 days) and tested the anti-inflammatory/neuroprotective properties of the satiety factor oleoylethanolamide (OEA). Pre-treatment with OEA (5 mg/kg, i.p.) previous each alcohol gavage blocked the expression of high mobility group box 1 (HMGB1) danger signal and the innate immunity Toll-like receptors 4 (TLR4) in frontal cortex, and inhibited the nuclear factor-kappa B (NF-kB) proinflammatory cascade induced by alcohol binge administration. OEA reduced the levels of interleukin-1beta (IL-1β), the monocyte chemoattractant protein-1 (MCP-1), and the enzymes cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in ethanol binged animals. Elevations in plasma tumor necrosis factor alpha (TNF-α) and IL-1β after ethanol were also inhibited by OEA. OEA also prevented ethanol-induced lipid peroxidation, caspase-8 and pro-apoptotic caspase-3 activation in frontal cortex. Additionally, OEA blocked the rise in blood corticosterone levels after ethanol with no alteration in blood ethanol levels and may affect ethanol-induced gut permeability for endotoxin. Finally, OEA, administered as a pre-treatment during the ethanol binge, exerted antidepressant-like effects during acute withdrawal. Altogether, results highlight a beneficial profile of OEA as a potent anti-inflammatory, antioxidant, neuroprotective and antidepressant-like compound to treat alcohol abuse. © 2016 Society for the Study of Addiction.

Addition of fornix transection to frontal-temporal disconnection increases the impairment in object-in-place memory in macaque monkeys.

PubMed

Wilson, C R E; Baxter, M G; Easton, A; Gaffan, D

2008-04-01

Both frontal-inferotemporal disconnection and fornix transection (Fx) in the monkey impair object-in-place scene learning, a model of human episodic memory. If the contribution of the fornix to scene learning is via interaction with or modulation of frontal-temporal interaction--that is, if they form a unitary system--then Fx should have no further effect when added to frontal-temporal disconnection. However, if the contribution of the fornix is to some extent distinct, then fornix lesions may produce an additional deficit in scene learning beyond that caused by frontal-temporal disconnection. To distinguish between these possibilities, we trained three male rhesus monkeys on the object-in-place scene-learning task. We tested their learning on the task following frontal-temporal disconnection, achieved by crossed unilateral aspiration of the frontal cortex in one hemisphere and the inferotemporal cortex in the other, and again following the addition of Fx. The monkeys were significantly impaired in scene learning following frontal-temporal disconnection, and furthermore showed a significant increase in this impairment following the addition of Fx, from 32.8% error to 40.5% error (chance = 50%). The increased impairment following the addition of Fx provides evidence that the fornix and frontal-inferotemporal interaction make distinct contributions to episodic memory.

Frontal white matter damage impairs response inhibition in children following traumatic brain injury.

PubMed

Lipszyc, Jonathan; Levin, Harvey; Hanten, Gerri; Hunter, Jill; Dennis, Maureen; Schachar, Russell

2014-05-01

Inhibition, the ability to suppress inappropriate cognitions or behaviors, can be measured using computer tasks and questionnaires. Inhibition depends on the frontal cortex, but the role of the underlying white matter (WM) is unclear. We assessed the specific impact of frontal WM damage on inhibition in 29 children with moderate-to-severe traumatic brain injury (15 with and 14 without frontal WM damage), 21 children with orthopedic injury, and 29 population controls. We used the Stop Signal Task to measure response inhibition, the Behavior Rating Inventory of Executive Function to assess everyday inhibition, and T2 fluid-attenuated inversion recovery magnetic resonance imaging to identify lesions. Children with frontal WM damage had impaired response inhibition compared with all other groups and poorer everyday inhibition than the orthopedic injury group. Frontal WM lesions most often affected the superior frontal gyrus. These results provide evidence for the critical role of frontal WM in inhibition.

Specific impairments of rule induction in different frontal lobe subgroups.

PubMed

Reverberi, Carlo; Lavaroni, Antonio; Gigli, Gian Luigi; Skrap, Miran; Shallice, Tim

2005-01-01

The neural correlates of inductive reasoning are still poorly understood. In order to explore them, we administered a revised version of the Brixton test, a rule attainment task, to a group of 40 patients with a focal frontal brain lesion of mixed aetiology and to 43 control subjects. To interpret an impairment on the test as suggesting an inductive reasoning deficit a number of alternative hypotheses need first to be considered, namely whether the Brixton impairment could be explained by: (i) a working memory deficit; (ii) a monitoring deficit; (iii) a difficulty in applying an already induced rule; (iv) greater impulsivity. The patients with left lateral (LL) frontal lesions were significantly impaired on the Brixton test; more importantly they were the only group in which none of the alternative hypotheses we explored proved able to explain the flawed performance. In sharp contrast, right lateral lesion patients did not make significantly more errors on the Brixton test than controls, but they produced three times more capture errors (a sign of impaired monitoring processes). The results were interpreted as suggesting functional dissociations between inductive reasoning, monitoring and working memory and a localisation of key processes for induction in left lateral frontal cortex and in right lateral cortex for monitoring and checking.

Distinct Neural Activities in Premotor Cortex during Natural Vocal Behaviors in a New World Primate, the Common Marmoset (Callithrix jacchus).

PubMed

Roy, Sabyasachi; Zhao, Lingyun; Wang, Xiaoqin

2016-11-30

Although evidence from human studies has long indicated the crucial role of the frontal cortex in speech production, it has remained uncertain whether the frontal cortex in nonhuman primates plays a similar role in vocal communication. Previous studies of prefrontal and premotor cortices of macaque monkeys have found neural signals associated with cue- and reward-conditioned vocal production, but not with self-initiated or spontaneous vocalizations (Coudé et al., 2011; Hage and Nieder, 2013), which casts doubt on the role of the frontal cortex of the Old World monkeys in vocal communication. A recent study of marmoset frontal cortex observed modulated neural activities associated with self-initiated vocal production (Miller et al., 2015), but it did not delineate whether these neural activities were specifically attributed to vocal production or if they may result from other nonvocal motor activity such as orofacial motor movement. In the present study, we attempted to resolve these issues and examined single neuron activities in premotor cortex during natural vocal exchanges in the common marmoset (Callithrix jacchus), a highly vocal New World primate. Neural activation and suppression were observed both before and during self-initiated vocal production. Furthermore, by comparing neural activities between self-initiated vocal production and nonvocal orofacial motor movement, we identified a subpopulation of neurons in marmoset premotor cortex that was activated or suppressed by vocal production, but not by orofacial movement. These findings provide clear evidence of the premotor cortex's involvement in self-initiated vocal production in natural vocal behaviors of a New World primate. Human frontal cortex plays a crucial role in speech production. However, it has remained unclear whether the frontal cortex of nonhuman primates is involved in the production of self-initiated vocalizations during natural vocal communication. Using a wireless multichannel neural

Frontal and Parietal Cortices Show Different Spatiotemporal Dynamics across Problem-solving Stages.

PubMed

Tschentscher, Nadja; Hauk, Olaf

2016-08-01

Arithmetic problem-solving can be conceptualized as a multistage process ranging from task encoding over rule and strategy selection to step-wise task execution. Previous fMRI research suggested a frontal-parietal network involved in the execution of complex numerical and nonnumerical tasks, but evidence is lacking on the particular contributions of frontal and parietal cortices across time. In an arithmetic task paradigm, we evaluated individual participants' "retrieval" and "multistep procedural" strategies on a trial-by-trial basis and contrasted those in time-resolved analyses using combined EEG and MEG. Retrieval strategies relied on direct retrieval of arithmetic facts (e.g., 2 + 3 = 5). Procedural strategies required multiple solution steps (e.g., 12 + 23 = 12 + 20 + 3 or 23 + 10 + 2). Evoked source analyses revealed independent activation dynamics within the first second of problem-solving in brain areas previously described as one network, such as the frontal-parietal cognitive control network: The right frontal cortex showed earliest effects of strategy selection for multistep procedural strategies around 300 msec, before parietal cortex activated around 700 msec. In time-frequency source power analyses, memory retrieval and multistep procedural strategies were differentially reflected in theta, alpha, and beta frequencies: Stronger beta and alpha desynchronizations emerged for procedural strategies in right frontal, parietal, and temporal regions as function of executive demands. Arithmetic fact retrieval was reflected in right prefrontal increases in theta power. Our results demonstrate differential brain dynamics within frontal-parietal networks across the time course of a problem-solving process, and analyses of different frequency bands allowed us to disentangle cortical regions supporting the underlying memory and executive functions.

Fetal Cerebrovascular Resistance and Neonatal EEG Predict 18-month Neurodevelopmental Outcome in Infants with Congenital Heart Disease

PubMed Central

Williams, Ismee A.; Tarullo, Amanda R.; Grieve, Philip G.; Wilpers, Abigail; Vignola, Emilia F.; Myers, Michael M.; Fifer, William P.

2012-01-01

Objectives The purpose of this study was to investigate early markers of risk for neurobehavioral compromise in congenital heart disease (CHD) survivors. Methods Fetuses < 24 wks gestational age (GA) were enrolled in this prospective pilot study for serial Doppler assessment of the middle cerebral and umbilical artery. The cerebral-to-placental resistance ratio (CPR) and MCA pulsatility index (PI) z-scores for GA were calculated. After birth, subjects underwent high-density (128-lead) electroencephalogram (EEG) and beta frequency (12–24Hz) band EEG power, a measure of local neural synchrony, was analyzed. Neurodevelopment was assessed at 18-months with the Bayley Scales of Infant Development III (BSID). Results 13 subjects were enrolled: 4 with hypoplastic left heart syndrome (HLHS), 4 with transposition of the great arteries (TGA), and 5 with tetralogy of Fallot (TOF). Compared with subjects with normal CPR, those with CPR<1(N=7) had lower mean BSID cognitive scores (91.4±4.8 vs. 99.2±3.8, p=.008). Fetal MCA PI z-score also correlated with BSID cognitive score (r=.589, p=0.044) as did neonatal EEG left frontal polar (r=.58, p=.037) and left frontal (r=.77,p=.002) beta power. Furthermore, fetal Doppler measures were associated with EEG power: fetuses with CPR<1 had lower left frontal polar (t=2.36, p=.038) and left frontal (t=2.85, p=.016) beta power as newborns compared with fetuses with normal CPR, and fetal MCA PI z-score correlated with neonatal EEG left frontal polar (r=.596, p=.04) and left frontal (r=.598, p=.04) beta power. Conclusions In CHD fetuses with HLHS, TGA, and TOF, abnormal cerebrovascular resistance predicted decreased neonatal EEG left frontal beta power and lower 18-mo cognitive development scores. PMID:22351034

Frontal Gamma-Aminobutyric Acid Concentrations Are Associated With Cognitive Performance in Older Adults.

PubMed

Porges, Eric C; Woods, Adam J; Edden, Richard A E; Puts, Nicolaas A J; Harris, Ashley D; Chen, Huaihou; Garcia, Amanda M; Seider, Talia R; Lamb, Damon G; Williamson, John B; Cohen, Ronald A

2017-01-01

Gamma-aminobutyric acid (GABA), the brain's principal inhibitory neurotransmitter, has been associated with perceptual and attentional functioning. Recent application of magnetic resonance spectroscopy (MRS) provides in vivo evidence for decreasing GABA concentrations during adulthood. It is unclear, however, how age-related decrements in cerebral GABA concentrations contribute to cognitive decline, or whether previously reported declines in cerebral GABA concentrations persist during healthy aging. We hypothesized that participants with higher GABA concentrations in the frontal cortex would exhibit superior cognitive function and that previously reported age-related decreases in cortical GABA concentrations continue into old age. We measured GABA concentrations in frontal and posterior midline cerebral regions using a Mescher-Garwood point-resolved spectroscopy (MEGA-PRESS) 1 H-MRS approach in 94 older adults without history or clinical evidence of mild cognitive impairment or dementia (mean age, 73 years). We administered the Montreal Cognitive Assessment to assess cognitive functioning. Greater frontal GABA concentrations were associated with superior cognitive performance. This relation remained significant after controlling for age, years of education, and brain atrophy. GABA concentrations in both frontal and posterior regions decreased as a function of age. These novel findings from a large, healthy, older population indicate that cognitive function is sensitive to cerebral GABA concentrations in the frontal cortex, and GABA concentration in frontal and posterior regions continue to decline in later age. These effects suggest that proton MRS may provide a clinically useful method for the assessment of normal and abnormal age-related cognitive changes and the associated physiological contributors.

Frontal Gamma-Aminobutyric Acid Concentrations Are Associated With Cognitive Performance in Older Adults

PubMed Central

Porges, Eric C.; Woods, Adam J.; Edden, Richard A.E.; Puts, Nicolaas A.J.; Harris, Ashley D.; Chen, Huaihou; Garcia, Amanda M.; Seider, Talia R.; Lamb, Damon G.; Williamson, John B.; Cohen, Ronald A.

2017-01-01

BACKGROUND Gamma-aminobutyric acid (GABA), the brain’s principal inhibitory neurotransmitter, has been associated with perceptual and attentional functioning. Recent application of magnetic resonance spectroscopy (MRS) provides in vivo evidence for decreasing GABA concentrations during adulthood. It is unclear, however, how age-related decrements in cerebral GABA concentrations contribute to cognitive decline, or whether previously reported declines in cerebral GABA concentrations persist during healthy aging. We hypothesized that participants with higher GABA concentrations in the frontal cortex would exhibit superior cognitive function and that previously reported age-related decreases in cortical GABA concentrations continue into old age. METHODS We measured GABA concentrations in frontal and posterior midline cerebral regions using a Mescher-Garwood point-resolved spectroscopy (MEGA-PRESS) 1H-MRS approach in 94 older adults without history or clinical evidence of mild cognitive impairment or dementia (mean age, 73 years). We administered the Montreal Cognitive Assessment to assess cognitive functioning. RESULTS Greater frontal GABA concentrations were associated with superior cognitive performance. This relation remained significant after controlling for age, years of education, and brain atrophy. GABA concentrations in both frontal and posterior regions decreased as a function of age. CONCLUSIONS These novel findings from a large, healthy, older population indicate that cognitive function is sensitive to cerebral GABA concentrations in the frontal cortex, and GABA concentration in frontal and posterior regions continue to decline in later age. These effects suggest that proton MRS may provide a clinically useful method for the assessment of normal and abnormal age-related cognitive changes and the associated physiological contributors. PMID:28217759

"Lipid raft aging" in the human frontal cortex during nonpathological aging: gender influences and potential implications in Alzheimer's disease.

PubMed

Díaz, Mario; Fabelo, Noemí; Ferrer, Isidre; Marín, Raquel

2018-07-01

Lipid rafts are highly dynamic membrane domains featured by distinctive biochemical composition and physicochemical properties compared with the surrounding plasma membrane. These microstructures are associated not only with cellular signaling and communication in normal nerve cells but also with pathological processing of amyloid precursor protein in Alzheimer's disease. Using lipid rafts isolated from human frontal cortex in nondemented subjects aging 24 to 85 years, we demonstrate here that lipid structure of lipid rafts undergo significant alterations of specific lipid classes and phospholipid-bound fatty acids as brain cortex correlating with aging. Main changes affect levels of plasmalogens, polyunsaturated fatty acids (especially docosahexaenoic acid and arachidonic acid), total polar lipids (mainly phosphatidylinositol, sphingomyelin, sulfatides, and cerebrosides), and total neutral lipids (particularly cholesterol and sterol esters). Besides, relevant relationships between main fatty acids and/or lipid classes were altered in an age-related manner. This "lipid raft aging" exhibits clear gender differences and appear to be more pronounced in women than in men, especially in older (postmenopausal) women. The outcomes led us to conclude that human cortical lipid rafts are modified by aging in a gender-dependent fashion. Given the central role of bilayer lipid matrix in lipid rafts functionality and neuronal signaling, we hypothesize that these findings might underlie the higher prevalence of cognitive decline evolving toward Alzheimer's disease in postmenopausal women. Copyright © 2018 Elsevier Inc. All rights reserved.

The effects of fetal and perinatal asphyxia on neuronal cytokine levels and ceramide metabolism in adulthood.

PubMed

Vlassaks, Evi; Gavilanes, Antonio W D; Vles, Johan S H; Deville, Sarah; Kramer, Boris W; Strackx, Eveline; Martinez-Martinez, Pilar

2013-02-15

In a rat model of global fetal and perinatal asphyxia, we investigated if asphyxia and long-lasting brain tolerance to asphyxia (preconditioning) are mediated by modifications in inflammatory cytokines and ceramide metabolism genes in prefrontal cortex, hippocampus and caudate-putamen at the age of 8months. Most significant changes were found in prefrontal cortex, with reduced LAG1 homolog ceramide synthase 1 expression after both types of asphyxia. Additionally, sphingosine kinase 1 was upregulated in those animals that experienced the combination of fetal and perinatal asphyxia (preconditioning), suggesting increased cell proliferation. While cytokine levels are normal, levels of ceramide genes were modulated both after fetal and perinatal asphyxia in the adult prefrontal cortex. Moreover, the combination of two subsequent asphyctic insults provides long-lasting neuroprotection in the prefrontal cortex probably by maintaining normal apoptosis and promoting cell proliferation. Better understanding of the effects of asphyxia on ceramide metabolism will help to understand the changes leading to brain tolerance and will open opportunities for the development of new neuroprotective therapies. Copyright © 2012 Elsevier B.V. All rights reserved.

[3H]MK-801 binding sites in post-mortem human frontal cortex.

PubMed

Kornhuber, J; Mack-Burkhardt, F; Kornhuber, M E; Riederer, P

1989-03-29

The binding of [3H]MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate) was investigated in extensively washed homogenates of post-mortem human frontal cortex. The association of [3H]MK-801 proceeded slowly (t1/2 = 553 min) and reached equilibrium only after a prolonged incubation (greater than 24 h). The dissociation of [3H]MK-801 from the binding site was also slow (t1/2 = 244 min). Glutamate, glycine and magnesium markedly increased the rate of association (t1/2 = 14.8 min) and dissociation (t1/2 = 36.5 min). At equilibrium, the binding was not altered by these substances. Specific binding was linear with protein concentration, was saturable, reversible, stereoselective, heat-labile and was nearly absent in the white matter. Scatchard analysis of the saturation curves obtained at equilibrium indicated that there was a high-affinity (Kd1 1.39 +/- 0.21 nM, Bmax1 0.483 +/- 0.084 pmol/mg protein) and a low-affinity (Kd2 116.25 +/- 50.79 nM, Bmax2 3.251 +/- 0.991 pmol/mg protein) binding site. All competition curves obtained with (+)-MK-801, (-)-MK-801, phencyclidine and ketamine had Hill coefficients of less than unity and were best explained by a two-site model. Thus, our results demonstrate the presence of binding sites for MK-801 in post-mortem human brains and provide evidence for binding site heterogeneity. Furthermore, glutamate, glycine and magnesium accelerate the association and dissociation of [3H]MK-801 to and from its binding sites. The results add support to the hypothesis that MK-801, glutamate, glycine and magnesium all bind to different sites on the NMDA receptor-ion channel complex.

Cognitive Functions and Neurodevelopmental Disorders Involving the Prefrontal Cortex and Mediodorsal Thalamus

PubMed Central

Ouhaz, Zakaria; Fleming, Hugo; Mitchell, Anna S.

2018-01-01

The mediodorsal nucleus of the thalamus (MD) has been implicated in executive functions (such as planning, cognitive control, working memory, and decision-making) because of its significant interconnectivity with the prefrontal cortex (PFC). Yet, whilst the roles of the PFC have been extensively studied, how the MD contributes to these cognitive functions remains relatively unclear. Recently, causal evidence in monkeys has demonstrated that in everyday tasks involving rapid updating (e.g., while learning something new, making decisions, or planning the next move), the MD and frontal cortex are working in close partnership. Furthermore, researchers studying the MD in rodents have been able to probe the underlying mechanisms of this relationship to give greater insights into how the frontal cortex and MD might interact during the performance of these essential tasks. This review summarizes the circuitry and known neuromodulators of the MD, and considers the most recent behavioral, cognitive, and neurophysiological studies conducted in monkeys and rodents; in total, this evidence demonstrates that MD makes a critical contribution to cognitive functions. We propose that communication occurs between the MD and the frontal cortex in an ongoing, fluid manner during rapid cognitive operations, via the means of efference copies of messages passed through transthalamic routes; the conductance of these messages may be modulated by other brain structures interconnected to the MD. This is similar to the way in which other thalamic structures have been suggested to carry out forward modeling associated with rapid motor responding and visual processing. Given this, and the marked thalamic pathophysiology now identified in many neuropsychiatric disorders, we suggest that changes in the different subdivisions of the MD and their interconnections with the cortex could plausibly give rise to a number of the otherwise disparate symptoms (including changes to olfaction and cognitive

The frontal-anatomic specificity of design fluency repetitions and their diagnostic relevance for behavioral variant frontotemporal dementia.

PubMed

Possin, Katherine L; Chester, Serana K; Laluz, Victor; Bostrom, Alan; Rosen, Howard J; Miller, Bruce L; Kramer, Joel H

2012-09-01

On tests of design fluency, an examinee draws as many different designs as possible in a specified time limit while avoiding repetition. The neuroanatomical substrates and diagnostic group differences of design fluency repetition errors and total correct scores were examined in 110 individuals diagnosed with dementia, 53 with mild cognitive impairment (MCI), and 37 neurologically healthy controls. The errors correlated significantly with volumes in the right and left orbitofrontal cortex (OFC), the right and left superior frontal gyrus, the right inferior frontal gyrus, and the right striatum, but did not correlate with volumes in any parietal or temporal lobe regions. Regression analyses indicated that the lateral OFC may be particularly crucial for preventing these errors, even after excluding patients with behavioral variant frontotemporal dementia (bvFTD) from the analysis. Total correct correlated more diffusely with volumes in the right and left frontal and parietal cortex, the right temporal cortex, and the right striatum and thalamus. Patients diagnosed with bvFTD made significantly more repetition errors than patients diagnosed with MCI, Alzheimer's disease, semantic dementia, progressive supranuclear palsy, or corticobasal syndrome. In contrast, total correct design scores did not differentiate the dementia patients. These results highlight the frontal-anatomic specificity of design fluency repetitions. In addition, the results indicate that the propensity to make these errors supports the diagnosis of bvFTD. (JINS, 2012, 18, 1-11).

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

PubMed

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

2016-04-27

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

Updating expected action outcome in the medial frontal cortex involves an evaluation of error type.

PubMed

Maier, Martin E; Steinhauser, Marco

2013-10-02

Forming expectations about the outcome of an action is an important prerequisite for action control and reinforcement learning in the human brain. The medial frontal cortex (MFC) has been shown to play an important role in the representation of outcome expectations, particularly when an update of expected outcome becomes necessary because an error is detected. However, error detection alone is not always sufficient to compute expected outcome because errors can occur in various ways and different types of errors may be associated with different outcomes. In the present study, we therefore investigate whether updating expected outcome in the human MFC is based on an evaluation of error type. Our approach was to consider an electrophysiological correlate of MFC activity on errors, the error-related negativity (Ne/ERN), in a task in which two types of errors could occur. Because the two error types were associated with different amounts of monetary loss, updating expected outcomes on error trials required an evaluation of error type. Our data revealed a pattern of Ne/ERN amplitudes that closely mirrored the amount of monetary loss associated with each error type, suggesting that outcome expectations are updated based on an evaluation of error type. We propose that this is achieved by a proactive evaluation process that anticipates error types by continuously monitoring error sources or by dynamically representing possible response-outcome relations.

Effects of lisdexamfetamine alone and in combination with s-citalopram on acetylcholine and histamine efflux in the rat pre-frontal cortex and ventral hippocampus.

PubMed

Hutson, Peter H; Heins, Mariette S; Folgering, Joost H A

2015-08-01

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by poor attention, impulse control and hyperactivity. A significant proportion of ADHD patients are also co-morbid for other psychiatric problems including mood disorders and these patients may be managed with a combination of psychostimulants and anti-depressants. While it is generally accepted that enhanced catecholamine signalling via the action of psychostimulants is likely responsible for the cognitive improvement in ADHD, other neurotransmitters including acetylcholine and histamine may be involved. In the present study, we have examined the effect of lisdexamfetamine dimesylate (LDX), an amphetamine pro-drug that is approved for the treatment of ADHD on acetylcholine and histamine efflux in pre-frontal cortex and hippocampus alone and in combination with the anti-depressant s-citalopram. LDX increased cortical acetylcholine efflux, an effect that was not significantly altered by co-administration of s-citalopram. Cortical and hippocampal histamine were markedly increased by LDX, an effect that was attenuated in the hippocampus but not in pre-frontal cortex when co-administered with s-citalopram. Taken together, these results suggest that efflux of acetylcholine and histamine may be involved in the therapeutic effects of LDX and are differentially influenced by the co-administration of s-citalopram. Attention deficit hyperactivity disorder (ADHD) is characterized by poor attention, impulse control and hyperactivity. Some ADHD patients are also co-morbid for mood disorders and may be managed with psychostimulants (e.g. lisdexamfetamine, LDX) and anti-depressants (e.g. s-citalopram). LDX increased the efflux of acetylcholine and histamine, neurotransmitters involved in cognitive function, which were differentially influenced when co-administered with s-citalopram. Acetylcholine and histamine may be involved in the therapeutic effects of LDX and are differentially

Charting the Maturation of the Frontal Lobe: An Electrophysiological Strategy

ERIC Educational Resources Information Center

Segalowitz, S. J.; Davies, Patricia L.

2004-01-01

Tracking the functional development of specific regions of the prefrontal cortex in children using event-related potentials (ERPs) is challenging for both technical and conceptual reasons. In this paper we outline our strategy for studying frontal lobe development and present preliminary results from children aged 7-17 years and young adults using…

Ventromedial Frontal Cortex Is Critical for Guiding Attention to Reward-Predictive Visual Features in Humans.

PubMed

Vaidya, Avinash R; Fellows, Lesley K

2015-09-16

Adaptively interacting with our environment requires extracting information that will allow us to successfully predict reward. This can be a challenge, particularly when there are many candidate cues, and when rewards are probabilistic. Recent work has demonstrated that visual attention is allocated to stimulus features that have been associated with reward on previous trials. The ventromedial frontal lobe (VMF) has been implicated in learning in dynamic environments of this kind, but the mechanism by which this region influences this process is not clear. Here, we hypothesized that the VMF plays a critical role in guiding attention to reward-predictive stimulus features based on feedback. We tested the effects of VMF damage in human subjects on a visual search task in which subjects were primed to attend to task-irrelevant colors associated with different levels of reward, incidental to the search task. Consistent with previous work, we found that distractors had a greater influence on reaction time when they appeared in colors associated with high reward in the previous trial compared with colors associated with low reward in healthy control subjects and patients with prefrontal damage sparing the VMF. However, this reward modulation of attentional priming was absent in patients with VMF damage. Thus, an intact VMF is necessary for directing attention based on experience with cue-reward associations. We suggest that this region plays a role in selecting reward-predictive cues to facilitate future learning. There has been a swell of interest recently in the ventromedial frontal cortex (VMF), a brain region critical to associative learning. However, the underlying mechanism by which this region guides learning is not well understood. Here, we tested the effects of damage to this region in humans on a task in which rewards were linked incidentally to visual features, resulting in trial-by-trial attentional priming. Controls and subjects with prefrontal damage

Frontal glutamate and reward processing in adolescence and adulthood.

PubMed

Gleich, Tobias; Lorenz, Robert C; Pöhland, Lydia; Raufelder, Diana; Deserno, Lorenz; Beck, Anne; Heinz, Andreas; Kühn, Simone; Gallinat, Jürgen

2015-11-01

The fronto-limbic network interaction, driven by glutamatergic and dopaminergic neurotransmission, represents a core mechanism of motivated behavior and personality traits. Reward seeking behavior undergoes tremendous changes in adolescence paralleled by neurobiological changes of this network including the prefrontal cortex, striatum and amygdala. Since fronto-limbic dysfunctions also underlie major psychiatric diseases beginning in adolescence, this investigation focuses on network characteristics separating adolescents from adults. To investigate differences in network interactions, the brain reward system activity (slot machine task) together with frontal glutamate concentration (anterior cingulate cortex, ACC) was measured in 28 adolescents and 26 adults employing functional magnetic resonance imaging and magnetic resonance spectroscopy, respectively. An inverse coupling of glutamate concentrations in the ACC and activation of the ventral striatum was observed in adolescents. Further, amygdala response in adolescents was negatively correlated with the personality trait impulsivity. For adults, no significant associations of network components or correlations with impulsivity were found. The inverse association between frontal glutamate concentration and striatal activation in adolescents is in line with the triadic model of motivated behavior stressing the important role of frontal top-down inhibition on limbic structures. Our data identified glutamate as the mediating neurotransmitter of this inhibitory process and demonstrates the relevance of glutamate on the reward system and related behavioral traits like impulsivity. This fronto-limbic coupling may represent a vulnerability factor for psychiatric disorders starting in adolescence but not in adulthood.

Functional roles of the cingulo-frontal network in performance on working memory.

PubMed

Kondo, Hirohito; Morishita, Masanao; Osaka, Naoyuki; Osaka, Mariko; Fukuyama, Hidenao; Shibasaki, Hiroshi

2004-01-01

We examined the relationship between brain activities and task performance on working memory. A large-scale study was initially administered to identify good and poor performers using the operation span and reading span tasks. On the basis of those span scores, we divided 20 consenting participants into high- and low-span groups. In an fMRI study, the participants performed verification of arithmetic problems and retention of target words either concurrently or separately. The behavioral results showed that performance was better in the high-span group than in the low-span group under a dual-task condition, but not under two single-task conditions. The anterior cingulate cortex (ACC), left prefrontal cortex (PFC), left inferior frontal cortex, and bilateral parietal cortex were primarily activated for both span groups. We found that signal changes in the ACC were greater in the high-span group than in the low-span group under the dual-task condition, but not under the single-task conditions. Structural equation modeling indicated that an estimate of effective connectivity from the ACC to the left PFC was positive for the high-span group and negative for the-low span group, suggesting that closer cooperation between the two brain regions was strongly related to working memory performance. We conclude that central executive functioning for attention shifting is modulated by the cingulo-frontal network.

Evidence for parallel activation of the pre-supplementary motor area and inferior frontal cortex during response inhibition: a combined MEG and TMS study

PubMed Central

Singh, Krish D.; Verbruggen, Frederick

2018-01-01

This pre-registered experiment sought to uncover the temporal relationship between the inferior frontal cortex (IFC) and the pre-supplementary motor area (pre-SMA) during stopping of an ongoing action. Both regions have previously been highlighted as being central to cognitive control of actions, particularly response inhibition. Here we tested which area is activated first during the stopping process using magnetoencephalography, before assessing the relative chronometry of each region using functionally localized transcranial magnetic stimulation. Both lines of evidence pointed towards simultaneous activity across both regions, suggesting that parallel, mutually interdependent processing may form the cortical basis of stopping. Additional exploratory analysis, however, provided weak evidence in support of previous suggestions that the pre-SMA may provide an ongoing drive of activity to the IFC. PMID:29515852

Comparison of functional and morphological deficits in the rat after gestational exposure to ionizing radiation

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

Norton, S.; Kimler, B.F.

1988-07-01

Ionizing radiation is a precise tool for altering formation of the developing cerebral cortex of the fetal rat. Whole body exposure of the pregnant rat on gestational day 13, 15 or 17 to 1.0 Gy of gamma radiation resulted in maximum thinning of the cortex on days 15 and 17. In the preweaning period, functional tests (negative geotaxis, reflex suspension, continuous corridor and gait) were most affected by irradiation gestational day 15, as was body weight. When a lower dose of radiation (0.75 Gy) was used on gestational day 15, the damage to the cortex was much less but behavioralmore » changes were still present. Frontal, parietal and occipital areas of the cortex were approximately equally affected. Using stepwise multiple regression analysis, the linkage of functional tests and cortical thickness was examined. Functional variables which were most commonly included as predictors of frontal and parietal cortex were negative geotaxis and continuous corridor. Occipital cortical layers were not predicted by behavioral variables. In predicting function using cortical variables, frontal cortex was better than parietal and occipital cortex was the poorest predictor.« less

Inactivation of Primate Prefrontal Cortex Impairs Auditory and Audiovisual Working Memory.

PubMed

Plakke, Bethany; Hwang, Jaewon; Romanski, Lizabeth M

2015-07-01

The prefrontal cortex is associated with cognitive functions that include planning, reasoning, decision-making, working memory, and communication. Neurophysiology and neuropsychology studies have established that dorsolateral prefrontal cortex is essential in spatial working memory while the ventral frontal lobe processes language and communication signals. Single-unit recordings in nonhuman primates has shown that ventral prefrontal (VLPFC) neurons integrate face and vocal information and are active during audiovisual working memory. However, whether VLPFC is essential in remembering face and voice information is unknown. We therefore trained nonhuman primates in an audiovisual working memory paradigm using naturalistic face-vocalization movies as memoranda. We inactivated VLPFC, with reversible cortical cooling, and examined performance when faces, vocalizations or both faces and vocalization had to be remembered. We found that VLPFC inactivation impaired subjects' performance in audiovisual and auditory-alone versions of the task. In contrast, VLPFC inactivation did not disrupt visual working memory. Our studies demonstrate the importance of VLPFC in auditory and audiovisual working memory for social stimuli but suggest a different role for VLPFC in unimodal visual processing. The ventral frontal lobe, or inferior frontal gyrus, plays an important role in audiovisual communication in the human brain. Studies with nonhuman primates have found that neurons within ventral prefrontal cortex (VLPFC) encode both faces and vocalizations and that VLPFC is active when animals need to remember these social stimuli. In the present study, we temporarily inactivated VLPFC by cooling the cortex while nonhuman primates performed a working memory task. This impaired the ability of subjects to remember a face and vocalization pair or just the vocalization alone. Our work highlights the importance of the primate VLPFC in the processing of faces and vocalizations in a manner that

Decision Making and Reward in Frontal Cortex

PubMed Central

Kennerley, Steven W.; Walton, Mark E.

2011-01-01

Patients with damage to the prefrontal cortex (PFC)—especially the ventral and medial parts of PFC—often show a marked inability to make choices that meet their needs and goals. These decision-making impairments often reflect both a deficit in learning concerning the consequences of a choice, as well as deficits in the ability to adapt future choices based on experienced value of the current choice. Thus, areas of PFC must support some value computations that are necessary for optimal choice. However, recent frameworks of decision making have highlighted that optimal and adaptive decision making does not simply rest on a single computation, but a number of different value computations may be necessary. Using this framework as a guide, we summarize evidence from both lesion studies and single-neuron physiology for the representation of different value computations across PFC areas. PMID:21534649

Primary cultures of astrocytes from fetal bovine brain.

PubMed

Ballarin, Cristina; Peruffo, Antonella

2012-01-01

We describe here a method to obtain primary cell cultures from the cerebral cortex and the hypothalamus of bovine fetuses. We report how tissue origin, developmental stages, and culture medium conditions influence cell differentiation and the prevalence of glial cells vs. neurons. We compare explants from early, middle, and late stages of development and two different fetal calf serum concentrations (1 and 10%) to identify the best conditions to obtain and grow viable astrocytes in culture. In addition, we describe how to cryopreserve and obtain viable cortical astrocytes from frozen fetal bovine brain samples.

Agrammatic Comprehension Caused by a Glioma in the Left Frontal Cortex

ERIC Educational Resources Information Center

Kinno, Ryuta; Muragaki, Yoshihiro; Hori, Tomokatsu; Maruyama, Takashi; Kawamura, Mitsuru; Sakai, Kuniyoshi L.

2009-01-01

It has been known that lesions in the left inferior frontal gyrus (L. IFG) do not always cause Broca's aphasia, casting doubt upon the specificity of this region. We have previously devised a picture-sentence matching task for a functional magnetic resonance imaging (fMRI) study, and observed that both pars triangularis (L. F3t) of L. IFG…

Upward gaze and head deviation with frontal eye field stimulation.

PubMed

Kaiboriboon, Kitti; Lüders, Hans O; Miller, Jonathan P; Leigh, R John

2012-03-01

Using electrical stimulation to the deep, most caudal part of the right frontal eye field (FEF), we demonstrate a novel pattern of vertical (upward) eye movement that was previously only thought possible by stimulating both frontal eye fields simultaneously. If stimulation was started when the subject looked laterally, the initial eye movement was back to the midline, followed by upward deviation. Our finding challenges current view of topological organisation in the human FEF and may have general implications for concepts of topological organisation of the motor cortex, since sustained stimulation also induced upward head movements as a component of the vertical gaze shift. [Published with video sequences].

A Combined Metabonomic and Proteomic Approach Identifies Frontal Cortex Changes in a Chronic Phencyclidine Rat Model in Relation to Human Schizophrenia Brain Pathology

PubMed Central

Wesseling, Hendrik; Chan, Man K; Tsang, T M; Ernst, Agnes; Peters, Fabian; Guest, Paul C; Holmes, Elaine; Bahn, Sabine

2013-01-01

Current schizophrenia (SCZ) treatments fail to treat the broad range of manifestations associated with this devastating disorder. Thus, new translational models that reproduce the core pathological features are urgently needed to facilitate novel drug discovery efforts. Here, we report findings from the first comprehensive label-free liquid-mass spectrometry proteomic- and proton nuclear magnetic resonance-based metabonomic profiling of the rat frontal cortex after chronic phencyclidine (PCP) intervention, which induces SCZ-like symptoms. The findings were compared with results from a proteomic profiling of post-mortem prefrontal cortex from SCZ patients and with relevant findings in the literature. Through this approach, we identified proteomic alterations in glutamate-mediated Ca2+ signaling (Ca2+/calmodulin-dependent protein kinase II, PPP3CA, and VISL1), mitochondrial function (GOT2 and PKLR), and cytoskeletal remodeling (ARP3). Metabonomic profiling revealed changes in the levels of glutamate, glutamine, glycine, pyruvate, and the Ca2+ regulator taurine. Effects on similar pathways were also identified in the prefrontal cortex tissue from human SCZ subjects. The discovery of similar but not identical proteomic and metabonomic alterations in the chronic PCP rat model and human brain indicates that this model recapitulates only some of the molecular alterations of the disease. This knowledge may be helpful in understanding mechanisms underlying psychosis, which, in turn, can facilitate improved therapy and drug discovery for SCZ and other psychiatric diseases. Most importantly, these molecular findings suggest that the combined use of multiple models may be required for more effective translation to studies of human SCZ. PMID:23942359

A Postmortem Study of Frontal and Temporal Gyri Thickness and Cell Number in Human Obesity.

PubMed

Gómez-Apo, Erick; García-Sierra, Adrián; Silva-Pereyra, Juan; Soto-Abraham, Virgilia; Mondragón-Maya, Alejandra; Velasco-Vales, Verónica; Pescatello, Linda S

2018-01-01

This study aimed to compare cortex thickness and neuronal cell density in postmortem brain tissue from people with overweight or obesity and normal weight. The cortex thickness and neuron density of eight donors with overweight or obesity (mean = 31.6 kg/m 2 ; SD = 4.35; n = 8; 6 male) and eight donors with normal weight (mean = 21.8 kg/m 2 ; SD = 1.5; n = 8; 5 male) were compared. All participants were Mexican and lived in Mexico City. Randomly selected thickness measures of different cortex areas from the frontal and temporal lobes were analyzed based on high-resolution real-size photographs. A histological analysis of systematic-random fields was used to quantify the number of neurons in postmortem left and right of the first, second, and third gyri of frontal and temporal lobe brain samples. No statistical difference was found in cortical thickness between donors with overweight or obesity and individuals with normal weight. A smaller number of neurons was found among the donors with overweight or obesity than the donors with normal weight at different frontal and temporal areas. A lower density of neurons is associated with overweight or obesity. The morphological basis for structural brain changes in obesity requires further investigation. © 2017 The Obesity Society.

Dissociating medial frontal and posterior cingulate activity during self-reflection.

PubMed

Johnson, Marcia K; Raye, Carol L; Mitchell, Karen J; Touryan, Sharon R; Greene, Erich J; Nolen-Hoeksema, Susan

2006-06-01

Motivationally significant agendas guide perception, thought and behaviour, helping one to define a 'self' and to regulate interactions with the environment. To investigate neural correlates of thinking about such agendas, we asked participants to think about their hopes and aspirations (promotion focus) or their duties and obligations (prevention focus) during functional magnetic resonance imaging and compared these self-reflection conditions with a distraction condition in which participants thought about non-self-relevant items. Self-reflection resulted in greater activity than distraction in dorsomedial frontal/anterior cingulate cortex and posterior cingulate cortex/precuneus, consistent with previous findings of activity in these areas during self-relevant thought. For additional medial areas, we report new evidence of a double dissociation of function between medial prefrontal/anterior cingulate cortex, which showed relatively greater activity to thinking about hopes and aspirations, and posterior cingulate cortex/precuneus, which showed relatively greater activity to thinking about duties and obligations. One possibility is that activity in medial prefrontal cortex is associated with instrumental or agentic self-reflection, whereas posterior medial cortex is associated with experiential self-reflection. Another, not necessarily mutually exclusive, possibility is that medial prefrontal cortex is associated with a more inward-directed focus, while posterior cingulate is associated with a more outward-directed, social or contextual focus.

Dissociating medial frontal and posterior cingulate activity during self-reflection

PubMed Central

Johnson, Marcia K.; Raye, Carol L.; Mitchell, Karen J.; Touryan, Sharon R.; Greene, Erich J.; Nolen-Hoeksema, Susan

2006-01-01

Motivationally significant agendas guide perception, thought and behaviour, helping one to define a ‘self’ and to regulate interactions with the environment. To investigate neural correlates of thinking about such agendas, we asked participants to think about their hopes and aspirations (promotion focus) or their duties and obligations (prevention focus) during functional magnetic resonance imaging and compared these self-reflection conditions with a distraction condition in which participants thought about non-self-relevant items. Self-reflection resulted in greater activity than distraction in dorsomedial frontal/anterior cingulate cortex and posterior cingulate cortex/precuneus, consistent with previous findings of activity in these areas during self-relevant thought. For additional medial areas, we report new evidence of a double dissociation of function between medial prefrontal/anterior cingulate cortex, which showed relatively greater activity to thinking about hopes and aspirations, and posterior cingulate cortex/precuneus, which showed relatively greater activity to thinking about duties and obligations. One possibility is that activity in medial prefrontal cortex is associated with instrumental or agentic self-reflection, whereas posterior medial cortex is associated with experiential self-reflection. Another, not necessarily mutually exclusive, possibility is that medial prefrontal cortex is associated with a more inward-directed focus, while posterior cingulate is associated with a more outward-directed, social or contextual focus. PMID:18574518

Damage to Left Frontal Regulatory Circuits Produces Greater Positive Emotional Reactivity in Frontotemporal Dementia

PubMed Central

Sturm, Virginia E.; Yokoyama, Jennifer S.; Eckart, Janet A.; Zakrzewski, Jessica; Rosen, Howard J.; Miller, Bruce L.; Seeley, William W.; Levenson, Robert W.

2015-01-01

Positive emotions foster social relationships and motivate thought and action. Dysregulation of positive emotion may give rise to debilitating clinical symptomatology such as mania, risk-taking, and disinhibition. Neuroanatomically, there is extensive evidence that the left hemisphere of the brain, and the left frontal lobe in particular, plays an important role in positive emotion generation. Although prior studies have found that left frontal injury decreases positive emotion, it is not clear whether selective damage to left frontal emotion regulatory systems can actually increase positive emotion. We measured happiness reactivity in 96 patients with frontotemporal dementia, a neurodegenerative disease that targets emotion-relevant neural systems and causes alterations in positive emotion (i.e., euphoria and jocularity), and in 34 healthy controls. Participants watched a film clip designed to elicit happiness and a comparison film clip designed to elicit sadness while their facial behavior, physiological reactivity, and self-reported emotional experience were monitored. Whole-brain voxel-based morphometry analyses revealed that atrophy in predominantly left hemisphere fronto-striatal emotion regulation systems including left ventrolateral prefrontal cortex, orbitofrontal cortex, anterior insula, and striatum (pFWE < .05) was associated with greater happiness facial behavior during the film. Atrophy in left anterior insula and bilateral frontopolar cortex was also associated with higher cardiovascular reactivity (i.e., heart rate and blood pressure) but not self-reported positive emotional experience during the happy film (p< .005, uncorrected). No regions emerged as being associated with greater sadness reactivity, which suggests that left-lateralized fronto-striatal atrophy is selectively associated with happiness dysregulation. Whereas previous models have proposed that left frontal injury decreases positive emotional responding, we argue that selective

Extinction-induced "despair" in aged and adult rats: links to neurotrophins in frontal cortex and hippocampus.

PubMed

Topic, Bianca; Huston, Joseph P; Namestkova, Katerina; Zhu, Shun-Wei; Mohammed, Abdul H; Schulz, Daniela

2008-10-01

In the search for animal models of human geriatric depression, we found that operant extinction of escape from water results in the expression of immobility in different age groups, indicative of behavioral "despair", which was also associated with the resistance-to-extinction (RTE) expressed by these animals. With respect to the neurotrophin hypothesis of depression, nerve-growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) protein levels in frontal cortex (FC) and hippocampus (HP) were examined and related to behavioral immobility and RTE in the water maze in aged and adult Wistar rats. Age-related increases in levels of NGF were found in HP and of NT-3 in FC. Indices of immobility showed relationships in the aged with NGF and, in adults, with BDNF, pointing to a dissociation of neurotrophic involvement in extinction trial-induced "despair" in aged and adult rats. The present results support the hypothesis, that extinction-induced immobility in the water maze reflects a state akin to behavioral despair and point to age-related differences of neurotrophic involvement in depressive-like symptoms. The concept of extinction-induced behavioral "despair" in the aged subsumes several aspects of human geriatric depression, such as co-morbidity of learning impairment and anxiety, and, thus could represent a useful paradigm to examine the neuronal mechanisms underlying depression, especially in aged rodents.

Ictal visual hallucinations due to frontal lobe epilepsy in a patient with bipolar disorder☆

PubMed Central

Manfioli, Valeria; Saladini, Marina; Cagnin, Annachiara

2013-01-01

In ictal psychosis with complex visual hallucinations (VHs), widespread functional changes of cortical networks have been suggested. We describe the clinical and EEG findings of a patient with bipolar disorder who manifested complex VHs associated with intense emotional symptoms caused by frontal epileptic seizures. This description highlights the challenges of diagnosing the epileptic nature of new psychotic phenomena in patients with previous psychiatric disorders and shines light into the role of the frontal cortex in the genesis of complex VHs. PMID:25667849

The relation of hedonic hunger and restrained eating to lateralized frontal activation.

PubMed

Winter, S R; Feig, E H; Kounios, J; Erickson, B; Berkowitz, S; Lowe, M R

2016-09-01

Asymmetrical alpha activation in the prefrontal cortex (frontal asymmetry) in electroencephalography (EEG) has been related to eating behavior. Prior studies linked dietary restraint with right frontal asymmetry [1] and disinhibition with left frontal asymmetry [2]. The current study simultaneously assessed restrained eating and hedonic hunger (drive for food reward in the absence of hunger) in relation to frontal asymmetry. Resting-state EEG and measures of restrained eating (Revised Restraint Scale; RRS) and hedonic hunger (Power of Food Scale; PFS) were assessed in 61 non-obese adults. Individually, hedonic hunger predicted left asymmetry. However, PFS and RRS were correlated (r=0.48, p<0.05) and there was a significant interaction between PFS and RRS on frontal asymmetry, p<0.01. Results indicated that those high in hedonic hunger exhibited left asymmetry irrespective of RRS scores; among those low in PFS, only those high in RRS showed right asymmetry. Results were consistent with literature linking avoidant behaviors (restraint) with right-frontal asymmetry and approach behaviors (binge eating) with left-frontal asymmetry. It appears that a strong drive toward palatable foods predominates at a neural level even when restraint is high. Findings suggest that lateralized frontal activity is an indicator of motivation both to consume and to avoid consuming highly palatable foods. Copyright © 2016 Elsevier Inc. All rights reserved.

Opposing Effects of Acute versus Chronic Blockade of Frontal Cortex Somatostatin-Positive Inhibitory Neurons on Behavioral Emotionality in Mice

PubMed Central

Soumier, Amelie; Sibille, Etienne

2014-01-01

Reduced expression of somatostatin (SST) is reported across chronic brain conditions including major depression and normal aging. SST is a signaling neuropeptide and marker of gamma-amino butyric acid (GABA) neurons, which specifically inhibit pyramidal neuron dendrites. Studies in auditory cortex suggest that chronic reduction in dendritic inhibition induces compensatory homeostatic adaptations that oppose the effects of acute inhibition. Whether such mechanisms occur in frontal cortex (FC) and affect behavioral outcome is not known. Here, we used two complementary viral vector strategies to examine the effects of acute vs chronic inhibition of SST-positive neurons on behavioral emotionality in adult mice. SST-IRES-Cre mice were injected in FC (prelimbic/precingulate) with CRE-dependent adeno-associated viral (AAV) vector encoding the engineered Gi/o-coupled human muscarinic M4 designer receptor exclusively activated by a designer drug (DREADD-hM4Di) or a control reporter (AAV-DIO-mCherry) for acute or chronic cellular inhibition. A separate cohort was injected with CRE-dependent AAV vectors expressing diphtheria toxin (DTA) to selectively ablate FC SST neurons. Mice were assessed for anxiety- and depressive-like behaviors (defined as emotionality). Results indicate that acute inhibition of FC SST neurons increased behavioral emotionality, whereas chronic inhibition decreased behavioral emotionality. Furthermore, ablation of FC SST neurons also decreased behavioral emotionality under baseline condition and after chronic stress. Together, our results reveal opposite effects of acute and chronic inhibition of FC SST neurons on behavioral emotionality and suggest the recruitment of homeostatic plasticity mechanisms that have implications for understanding the neurobiology of chronic brain conditions affecting dendritic-targeting inhibitory neurons. PMID:24690741

Opposing effects of acute versus chronic blockade of frontal cortex somatostatin-positive inhibitory neurons on behavioral emotionality in mice.

PubMed

Soumier, Amelie; Sibille, Etienne

2014-08-01

Reduced expression of somatostatin (SST) is reported across chronic brain conditions including major depression and normal aging. SST is a signaling neuropeptide and marker of gamma-amino butyric acid (GABA) neurons, which specifically inhibit pyramidal neuron dendrites. Studies in auditory cortex suggest that chronic reduction in dendritic inhibition induces compensatory homeostatic adaptations that oppose the effects of acute inhibition. Whether such mechanisms occur in frontal cortex (FC) and affect behavioral outcome is not known. Here, we used two complementary viral vector strategies to examine the effects of acute vs chronic inhibition of SST-positive neurons on behavioral emotionality in adult mice. SST-IRES-Cre mice were injected in FC (prelimbic/precingulate) with CRE-dependent adeno-associated viral (AAV) vector encoding the engineered Gi/o-coupled human muscarinic M4 designer receptor exclusively activated by a designer drug (DREADD-hM4Di) or a control reporter (AAV-DIO-mCherry) for acute or chronic cellular inhibition. A separate cohort was injected with CRE-dependent AAV vectors expressing diphtheria toxin (DTA) to selectively ablate FC SST neurons. Mice were assessed for anxiety- and depressive-like behaviors (defined as emotionality). Results indicate that acute inhibition of FC SST neurons increased behavioral emotionality, whereas chronic inhibition decreased behavioral emotionality. Furthermore, ablation of FC SST neurons also decreased behavioral emotionality under baseline condition and after chronic stress. Together, our results reveal opposite effects of acute and chronic inhibition of FC SST neurons on behavioral emotionality and suggest the recruitment of homeostatic plasticity mechanisms that have implications for understanding the neurobiology of chronic brain conditions affecting dendritic-targeting inhibitory neurons.

The 5-HT6 receptor antagonist idalopirdine potentiates the effects of donepezil on gamma oscillations in the frontal cortex of anesthetized and awake rats without affecting sleep-wake architecture.

PubMed

Amat-Foraster, Maria; Leiser, Steven C; Herrik, Kjartan F; Richard, Nelly; Agerskov, Claus; Bundgaard, Christoffer; Bastlund, Jesper F; de Jong, Inge E M

2017-02-01

The 5-HT 6 receptor is a promising target for cognitive disorders, in particular for Alzheimer's disease (AD). The high affinity and selective 5-HT 6 receptor antagonist idalopirdine (Lu AE58054) is currently in development for mild-moderate AD as adjunct therapy to acetylcholinesterase inhibitors (AChEIs). We studied the effects of idalopirdine alone and in combination with the AChEI donepezil on cortical function using two in vivo electrophysiological methods. Neuronal network oscillations in the frontal cortex were measured during electrical stimulation of the brainstem nucleus pontis oralis (nPO) in the anesthetized rat and by an electroencephalogram (EEG) in the awake, freely moving rat. In conjunction with the EEG study, we investigated the effects of idalopirdine and donepezil on sleep-wake architecture using telemetric polysomnography. Idalopirdine (2 mg/kg i.v.) increased gamma power in the medial prefrontal cortex (mPFC) during nPO stimulation. Donepezil (0.3 and 1 mg/kg i.v.) also increased cortical gamma power and pretreatment with idalopirdine (2 mg/kg i.v.) potentiated and prolonged the effects of donepezil. Similarly, donepezil (1 and 3 mg/kg s.c.) dose-dependently increased frontal cortical gamma power in the freely moving rat and pretreatment with idalopirdine (10 mg/kg p.o.) augmented the effect of donepezil 1 mg/kg. Analysis of the sleep-wake architecture showed that donepezil (1 and 3 mg/kg s.c.) dose-dependently delayed sleep onset and decreased the time spent in both REM and non REM sleep stages. In contrast, idalopirdine (10 mg/kg p.o.) did not affect sleep-wake architecture nor the effects of donepezil. In summary, we show that idalopirdine potentiates the effects of donepezil on frontal cortical gamma oscillations, a pharmacodynamic biomarker associated with cognition, without modifying the effects of donepezil on sleep. The increased cortical excitability may contribute to the procognitive effects of idalopirdine in donepezil

Frontal lobe activation during object permanence: data from near-infrared spectroscopy.

PubMed

Baird, Abigail A; Kagan, Jerome; Gaudette, Thomas; Walz, Kathryn A; Hershlag, Natalie; Boas, David A

2002-08-01

The ability to create and hold a mental schema of an object is one of the milestones in cognitive development. Developmental scientists have named the behavioral manifestation of this competence object permanence. Convergent evidence indicates that frontal lobe maturation plays a critical role in the display of object permanence, but methodological and ethical constrains have made it difficult to collect neurophysiological evidence from awake, behaving infants. Near-infrared spectroscopy provides a noninvasive assessment of changes in oxy- and deoxyhemoglobin and total hemoglobin concentration within a prescribed region. The evidence described in this report reveals that the emergence of object permanence is related to an increase in hemoglobin concentration in frontal cortex.

Temporal Lobe and Frontal-Subcortical Dissociations in Non-Demented Parkinson's Disease with Verbal Memory Impairment.

PubMed

Tanner, Jared J; Mareci, Thomas H; Okun, Michael S; Bowers, Dawn; Libon, David J; Price, Catherine C

2015-01-01

The current investigation examined verbal memory in idiopathic non-dementia Parkinson's disease and the significance of the left entorhinal cortex and left entorhinal-retrosplenial region connections (via temporal cingulum) on memory impairment in Parkinson's disease. Forty non-demented Parkinson's disease patients and forty non-Parkinson's disease controls completed two verbal memory tests--a wordlist measure (Philadelphia repeatable Verbal Memory Test) and a story measure (Logical Memory). All participants received T1-weighted and diffusion magnetic resonance imaging (3T; Siemens) sequences. Left entorhinal volume and left entorhinal-retrosplenial connectivity (temporal cingulum edge weight) were the primary imaging variables of interest with frontal lobe thickness and subcortical structure volumes as dissociating variables. Individuals with Parkinson's disease showed worse verbal memory, smaller entorhinal volumes, but did not differ in entorhinal-retrosplenial connectivity. For Parkinson's disease entorhinal-retrosplenial edge weight had the strongest associations with verbal memory. A subset of Parkinson's disease patients (23%) had deficits (z-scores < -1.5) across both memory measures. Relative to non-impaired Parkinson's peers, this memory-impaired group had smaller entorhinal volumes. Although entorhinal cortex volume was significantly reduced in Parkinson's disease patients relative to non-Parkinson's peers, only white matter connections associated with the entorhinal cortex were significantly associated with verbal memory performance in our sample. There was also no suggestion of contribution from frontal-subcortical gray or frontal white matter regions. These findings argue for additional investigation into medial temporal lobe gray and white matter connectivity for understanding memory in Parkinson's disease.

Factors influencing frontal cortex development and recovery from early frontal injury.

PubMed

Halliwell, Celeste; Comeau, Wendy; Gibb, Robbin; Frost, Douglas O; Kolb, Bryan

2009-01-01

Neocortical development represents more than a simple unfolding of a genetic blueprint but rather represents a complex dance of genetic and environmental events that interact to adapt the brain to fit a particular environmental context. Although most cortical regions are sensitive to a wide range of experiential factors during development and later in life, the prefrontal cortex appears to be unusually sensitive to perinatal experiences and relatively immune to many adulthood experiences relative to other neocortical regions. One way to examine experience-dependent prefrontal development is to conduct studies in which experiential perturbations are related neuronal morphology. This review of the research reveals both pre- and post-natal factors have important effects on prefrontal development and behaviour. Such factors include psychoactive drugs, including both illicit drugs and prescription drugs, stress, gonadal hormones and sensory and motor stimulation. A second method of study is to examine both the effects of perinatal prefrontal injury on the development of the remaining cerebral mantle and correlated behaviours as well as the effects of post-injury rehabilitation programmes on the anatomical and behavioural measures. Prefrontal injury alters cerebral development in a developmental-stage dependent manner with perinatal injuries having far more deleterious effects than similar injuries later in infancy. The outcome of perinatal injuries can be modified, however, by rehabilitation with many of the factors shown to influence prefrontal development in the otherwise normal brain.

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

Distinct frontal regions subserve evaluation of linguistic and emotional aspects of speech intonation.

PubMed

Wildgruber, D; Hertrich, I; Riecker, A; Erb, M; Anders, S; Grodd, W; Ackermann, H

2004-12-01

In addition to the propositional content of verbal utterances, significant linguistic and emotional information is conveyed by the tone of speech. To differentiate brain regions subserving processing of linguistic and affective aspects of intonation, discrimination of sentences differing in linguistic accentuation and emotional expressiveness was evaluated by functional magnetic resonance imaging. Both tasks yielded rightward lateralization of hemodynamic responses at the level of the dorsolateral frontal cortex as well as bilateral thalamic and temporal activation. Processing of linguistic and affective intonation, thus, seems to be supported by overlapping neural networks comprising partially right-sided brain regions. Comparison of hemodynamic activation during the two different tasks, however, revealed bilateral orbito-frontal responses restricted to the affective condition as opposed to activation of the left lateral inferior frontal gyrus confined to evaluation of linguistic intonation. These findings indicate that distinct frontal regions contribute to higher level processing of intonational information depending on its communicational function. In line with other components of language processing, discrimination of linguistic accentuation seems to be lateralized to the left inferior-lateral frontal region whereas bilateral orbito-frontal areas subserve evaluation of emotional expressiveness.

Functional Connectivity Between Superior Parietal Lobule and Primary Visual Cortex "at Rest" Predicts Visual Search Efficiency.

PubMed

Bueichekú, Elisenda; Ventura-Campos, Noelia; Palomar-García, María-Ángeles; Miró-Padilla, Anna; Parcet, María-Antonia; Ávila, César

2015-10-01

Spatiotemporal activity that emerges spontaneously "at rest" has been proposed to reflect individual a priori biases in cognitive processing. This research focused on testing neurocognitive models of visual attention by studying the functional connectivity (FC) of the superior parietal lobule (SPL), given its central role in establishing priority maps during visual search tasks. Twenty-three human participants completed a functional magnetic resonance imaging session that featured a resting-state scan, followed by a visual search task based on the alphanumeric category effect. As expected, the behavioral results showed longer reaction times and more errors for the within-category (i.e., searching a target letter among letters) than the between-category search (i.e., searching a target letter among numbers). The within-category condition was related to greater activation of the superior and inferior parietal lobules, occipital cortex, inferior frontal cortex, dorsal anterior cingulate cortex, and the superior colliculus than the between-category search. The resting-state FC analysis of the SPL revealed a broad network that included connections with the inferotemporal cortex, dorsolateral prefrontal cortex, and dorsal frontal areas like the supplementary motor area and frontal eye field. Noteworthy, the regression analysis revealed that the more efficient participants in the visual search showed stronger FC between the SPL and areas of primary visual cortex (V1) related to the search task. We shed some light on how the SPL establishes a priority map of the environment during visual attention tasks and how FC is a valuable tool for assessing individual differences while performing cognitive tasks.

Subspecialization in the human posterior medial cortex

PubMed Central

Bzdok, Danilo; Heeger, Adrian; Langner, Robert; Laird, Angela R.; Fox, Peter T.; Palomero-Gallagher, Nicola; Vogt, Brent A.; Zilles, Karl; Eickhoff, Simon B.

2014-01-01

The posterior medial cortex (PMC) is particularly poorly understood. Its neural activity changes have been related to highly disparate mental processes. We therefore investigated PMC properties with a data-driven exploratory approach. First, we subdivided the PMC by whole-brain coactivation profiles. Second, functional connectivity of the ensuing PMC regions was compared by task-constrained meta-analytic coactivation mapping (MACM) and task-unconstrained resting-state correlations (RSFC). Third, PMC regions were functionally described by forward/reverse functional inference. A precuneal cluster was mostly connected to the intraparietal sulcus, frontal eye fields, and right temporo-parietal junction; associated with attention and motor tasks. A ventral posterior cingulate cortex (PCC) cluster was mostly connected to the ventromedial prefrontal cortex and middle left inferior parietal cortex (IPC); associated with facial appraisal and language tasks. A dorsal PCC cluster was mostly connected to the dorsomedial prefrontal cortex, anterior/posterior IPC, posterior midcingulate cortex, and left dorsolateral prefrontal cortex; associated with delay discounting. A cluster in the retrosplenial cortex was mostly connected to the anterior thalamus and hippocampus. Furthermore, all PMC clusters were congruently coupled with the default mode network according to task-constrained but not task-unconstrained connectivity. We thus identified distinct regions in the PMC and characterized their neural networks and functional implications. PMID:25462801

Learning of spatial relationships between observed and imitated actions allows invariant inverse computation in the frontal mirror neuron system.

PubMed

Oh, Hyuk; Gentili, Rodolphe J; Reggia, James A; Contreras-Vidal, José L

2011-01-01

It has been suggested that the human mirror neuron system can facilitate learning by imitation through coupling of observation and action execution. During imitation of observed actions, the functional relationship between and within the inferior frontal cortex, the posterior parietal cortex, and the superior temporal sulcus can be modeled within the internal model framework. The proposed biologically plausible mirror neuron system model extends currently available models by explicitly modeling the intraparietal sulcus and the superior parietal lobule in implementing the function of a frame of reference transformation during imitation. Moreover, the model posits the ventral premotor cortex as performing an inverse computation. The simulations reveal that: i) the transformation system can learn and represent the changes in extrinsic to intrinsic coordinates when an imitator observes a demonstrator; ii) the inverse model of the imitator's frontal mirror neuron system can be trained to provide the motor plans for the imitated actions.

Perseverative Interference with Object-in-Place Scene Learning in Rhesus Monkeys with Bilateral Ablation of Ventrolateral Prefrontal Cortex

ERIC Educational Resources Information Center

Baxter, Mark G.; Browning, Philip G. F.; Mitchell, Anna S.

2008-01-01

Surgical disconnection of the frontal cortex and inferotemporal cortex severely impairs many aspects of visual learning and memory, including learning of new object-in-place scene memory problems, a monkey model of episodic memory. As part of a study of specialization within prefrontal cortex in visual learning and memory, we tested monkeys with…

Neural Tuning to Low-Level Features of Speech throughout the Perisylvian Cortex.

PubMed

Berezutskaya, Julia; Freudenburg, Zachary V; Güçlü, Umut; van Gerven, Marcel A J; Ramsey, Nick F

2017-08-16

Despite a large body of research, we continue to lack a detailed account of how auditory processing of continuous speech unfolds in the human brain. Previous research showed the propagation of low-level acoustic features of speech from posterior superior temporal gyrus toward anterior superior temporal gyrus in the human brain (Hullett et al., 2016). In this study, we investigate what happens to these neural representations past the superior temporal gyrus and how they engage higher-level language processing areas such as inferior frontal gyrus. We used low-level sound features to model neural responses to speech outside of the primary auditory cortex. Two complementary imaging techniques were used with human participants (both males and females): electrocorticography (ECoG) and fMRI. Both imaging techniques showed tuning of the perisylvian cortex to low-level speech features. With ECoG, we found evidence of propagation of the temporal features of speech sounds along the ventral pathway of language processing in the brain toward inferior frontal gyrus. Increasingly coarse temporal features of speech spreading from posterior superior temporal cortex toward inferior frontal gyrus were associated with linguistic features such as voice onset time, duration of the formant transitions, and phoneme, syllable, and word boundaries. The present findings provide the groundwork for a comprehensive bottom-up account of speech comprehension in the human brain. SIGNIFICANCE STATEMENT We know that, during natural speech comprehension, a broad network of perisylvian cortical regions is involved in sound and language processing. Here, we investigated the tuning to low-level sound features within these regions using neural responses to a short feature film. We also looked at whether the tuning organization along these brain regions showed any parallel to the hierarchy of language structures in continuous speech. Our results show that low-level speech features propagate throughout the

High density scalp EEG in frontal lobe epilepsy.

PubMed

Feyissa, Anteneh M; Britton, Jeffrey W; Van Gompel, Jamie; Lagerlund, Terrance L; So, Elson; Wong-Kisiel, Lilly C; Cascino, Gregory C; Brinkman, Benjamin H; Nelson, Cindy L; Watson, Robert; Worrell, Gregory A

2017-01-01

Localization of seizures in frontal lobe epilepsy using the 10-20 system scalp EEG is often challenging because neocortical seizure can spread rapidly, significant muscle artifact, and the suboptimal spatial resolution for seizure generators involving mesial frontal lobe cortex. Our aim in this study was to determine the value of visual interpretation of 76 channel high density EEG (hdEEG) monitoring (10-10 system) in patients with suspected frontal lobe epilepsy, and to evaluate concordance with MRI, subtraction ictal SPECT co-registered to MRI (SISCOM), conventional EEG, and intracranial EEG (iEEG). We performed a retrospective cohort study of 14 consecutive patients who underwent hdEEG monitoring for suspected frontal lobe seizures. The gold standard for localization was considered to be iEEG. Concordance of hdEEG findings with MRI, subtraction ictal SPECT co-registered to MRI (SISCOM), conventional 10-20 EEG, and iEEG as well as correlation of hdEEG localization with surgical outcome were examined. hdEEG localization was concordant with iEEG in 12/14 and was superior to conventional EEG 3/14 (p<0.01) and SISCOM 3/12 (p<0.01). hdEEG correctly lateralized seizure onset in 14/14 cases, compared to 9/14 (p=0.04) cases with conventional EEG. Seven patients underwent surgical resection, of whom five were seizure free. hdEEG monitoring should be considered in patients with suspected frontal epilepsy requiring localization of epileptogenic brain. hdEEG may assist in developing a hypothesis for iEEG monitoring and could potentially augment EEG source localization. Published by Elsevier B.V.

High Working Memory Load Increases Intracortical Inhibition in Primary Motor Cortex and Diminishes the Motor Affordance Effect.

PubMed

Freeman, Scott M; Itthipuripat, Sirawaj; Aron, Adam R

2016-05-18

Motor affordances occur when the visual properties of an object elicit behaviorally relevant motor representations. Typically, motor affordances only produce subtle effects on response time or on motor activity indexed by neuroimaging/neuroelectrophysiology, but sometimes they can trigger action itself. This is apparent in "utilization behavior," where individuals with frontal cortex damage inappropriately grasp affording objects. This raises the possibility that, in healthy-functioning individuals, frontal cortex helps ensure that irrelevant affordance provocations remain below the threshold for actual movement. In Experiment 1, we tested this "frontal control" hypothesis by "loading" the frontal cortex with an effortful working memory (WM) task (which ostensibly consumes frontal resources) and examined whether this increased EEG measures of motor affordances to irrelevant affording objects. Under low WM load, there were typical motor affordance signatures: an event-related desynchronization in the mu frequency and an increased P300 amplitude for affording (vs nonaffording) objects over centroparietal electrodes. Contrary to our prediction, however, these affordance measures were diminished under high WM load. In Experiment 2, we tested competing mechanisms responsible for the diminished affordance in Experiment 1. We used paired-pulse transcranial magnetic stimulation over primary motor cortex to measure long-interval cortical inhibition. We found greater long-interval cortical inhibition for high versus low load both before and after the affording object, suggesting that a tonic inhibition state in primary motor cortex could prevent the affordance from provoking the motor system. Overall, our results suggest that a high WM load "sets" the motor system into a suppressed state that mitigates motor affordances. Is an irrelevant motor affordance more likely to be triggered when you are under low or high cognitive load? We examined this using physiological measures

Neural network underlying ictal pouting ("chapeau de gendarme") in frontal lobe epilepsy.

PubMed

Souirti, Zouhayr; Landré, Elisabeth; Mellerio, Charles; Devaux, Bertrand; Chassoux, Francine

2014-08-01

In order to determine the anatomical neural network underlying ictal pouting (IP), with the mouth turned down like a "chapeau de gendarme", in frontal lobe epilepsy (FLE), we reviewed the video-EEG recordings of 36 patients with FLE who became seizure-free after surgery. We selected the cases presenting IP, defined as a symmetrical and sustained (>5s) lowering of labial commissures with contraction of chin, mimicking an expression of fear, disgust, or menace. Ictal pouting was identified in 11 patients (8 males; 16-48 years old). We analyzed the clinical semiology, imaging, and electrophysiological data associated with IP, including FDG-PET in 10 and SEEG in 9 cases. In 37 analyzed seizures (2-7/patient), IP was an early symptom, occurring during the first 10s in 9 cases. The main associated features consisted of fear, anguish, vegetative disturbances, behavioral disorders (sudden agitation, insults, and fighting), tonic posturing, and complex motor activities. The epileptogenic zone assessed by SEEG involved the mesial frontal areas, especially the anterior cingulate cortex (ACC) in 8 patients, whereas lateral frontal onset with an early spread to the ACC was seen in the other patient. Ictal pouting associated with emotional changes and hypermotor behavior had high localizing value for rostroventral "affective" ACC, whereas less intense facial expressions were related to the dorsal "cognitive" ACC. Fluorodeoxyglucose positron emission tomography demonstrated the involvement of both the ACC and lateral cortex including the anterior insula in all cases. We propose that IP is sustained by reciprocal mesial and lateral frontal interactions involved in emotional and cognitive processes, in which the ACC plays a pivotal role. Copyright © 2014 Elsevier Inc. All rights reserved.

Insight in psychotic disorder: relation with psychopathology and frontal lobe function.

PubMed

Kumar, Atmesh; Sharma, Pranjal; Das, Shyamanta; Nath, Kamal; Talukdar, Uddip; Bhagabati, Dipesh

2014-01-01

Through conceptualising poor insight in psychotic disorders as a form of anosognosia, frontal lobe dysfunction is often ascribed a vital role in its pathogenesis. The objective of this study was to compare the relation of insight in patients with psychotic illness to that of psychopathology and frontal lobe function. Forty patients with psychotic disorder were selected from those attending the Department of Psychiatry in a tertiary care teaching hospital. The evaluation of insight was carried out using the Schedule for Assessment of Insight (SAI), that of frontal lobe function by the Frontal Assessment Battery (FAB) and psychopathology by the Brief Psychiatric Rating Scale (BPRS). The correlation coefficients were determined. A negative correlation between SAI and BPRS scores means that the BPRS score is opposite to SAI scores. When the SAI total score was compared with the FAB total score, the correlation coefficient demonstrated a positive correlation. Better insight predicted lesser psychopathology and also that poor insight would exist with greater psychopathology. Better insight predicted a higher functional status of frontal lobes and prefrontal cortex in particular. Insight deficits in schizophrenia and other psychotic illnesses are multidimensional. Integration of different aetiological factors like biological, psychopathological, environmental ones and others are necessary for a better understanding of insight in psychosis. Copyright © 2013 S. Karger AG, Basel.

A computational model of cerebral cortex folding.

PubMed

Nie, Jingxin; Guo, Lei; Li, Gang; Faraco, Carlos; Stephen Miller, L; Liu, Tianming

2010-05-21

The geometric complexity and variability of the human cerebral cortex have long intrigued the scientific community. As a result, quantitative description of cortical folding patterns and the understanding of underlying folding mechanisms have emerged as important research goals. This paper presents a computational 3D geometric model of cerebral cortex folding initialized by MRI data of a human fetal brain and deformed under the governance of a partial differential equation modeling cortical growth. By applying different simulation parameters, our model is able to generate folding convolutions and shape dynamics of the cerebral cortex. The simulations of this 3D geometric model provide computational experimental support to the following hypotheses: (1) Mechanical constraints of the skull regulate the cortical folding process. (2) The cortical folding pattern is dependent on the global cell growth rate of the whole cortex. (3) The cortical folding pattern is dependent on relative rates of cell growth in different cortical areas. (4) The cortical folding pattern is dependent on the initial geometry of the cortex. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Frontal activations associated with accessing and evaluating information in working memory: an fMRI study.

PubMed

Zhang, John X; Leung, Hoi-Chung; Johnson, Marcia K

2003-11-01

To investigate the involvement of frontal cortex in accessing and evaluating information in working memory, we used a variant of a Sternberg paradigm and compared brain activations between positive and negative responses (known to differentially tax access/evaluation processes). Participants remembered two trigrams in each trial and were then cued to discard one of them and maintain the other one as the target set. After a delay, a probe letter was presented and participants made decisions about whether or not it was in the target set. Several frontal areas--anterior cingulate (BA32), middle frontal gyrus (bilateral BA9, right BA10, and right BA46), and left inferior frontal gyrus (BA44/45)--showed increased activity when participants made correct negative responses relative to when they made correct positive responses. No areas activated significantly more for the positive responses than for the negative responses. It is suggested that the multiple frontal areas involved in the test phase of this task may reflect several component processes that underlie more general frontal functions.

Task-dependent and distinct roles of the temporoparietal junction and inferior frontal cortex in the control of imitation

PubMed Central

Obhi, Sukhvinder S.; Banissy, Michael J.; Santiesteban, Idalmis; Press, Clare; Catmur, Caroline; Bird, Geoffrey

2015-01-01

The control of neurological networks supporting social cognition is crucially important for social interaction. In particular, the control of imitation is directly linked to interaction quality, with impairments associated with disorders characterized by social difficulties. Previous work suggests inferior frontal cortex (IFC) and the temporoparietal junction (TPJ) are involved in controlling imitation, but the functional roles of these areas remain unclear. Here, transcranial direct current stimulation (tDCS) was used to enhance cortical excitability at IFC and the TPJ prior to the completion of three tasks: (i) a naturalistic social interaction during which increased imitation is known to improve rapport, (ii) a choice reaction time task in which imitation needs to be inhibited for successful performance and (iii) a non-imitative control task. Relative to sham stimulation, stimulating IFC improved the context-dependent control of imitation—participants imitated more during the social interaction and less during the imitation inhibition task. In contrast, stimulating the TPJ reduced imitation in the inhibition task without affecting imitation during social interaction. Neither stimulation site affected the non-imitative control task. These data support a model in which IFC modulates imitation directly according to task demands, whereas TPJ controls task-appropriate shifts in attention toward representation of the self or the other, indirectly impacting upon imitation. PMID:25481003

Resting-state functional connectivity between right anterior insula and right orbital frontal cortex correlate with insight level in obsessive-compulsive disorder.

PubMed

Fan, Jie; Zhong, Mingtian; Zhu, Xiongzhao; Gan, Jun; Liu, Wanting; Niu, Chaoyang; Liao, Haiyan; Zhang, Hongchun; Yi, Jinyao; Tan, Changlian

2017-01-01

Few studies have explored the neurobiological basis of insight level in obsessive-compulsive disorder (OCD), though the salience network (SN) has been implicated in insight deficits in schizophrenia. This study was then designed to investigate whether resting-state (rs) functional connectivity (FC) of SN was associated with insight level in OCD patients. We analyzed rs-functional magnetic resonance imaging (fMRI) data from 21 OCD patients with good insight (OCD-GI), 19 OCD patients with poor insight (OCD-PI), and 24 healthy controls (HCs). Seed-based whole-brain FC and ROI (region of interest)-wise connectivity analyses were performed with seeds/ROIs in the bilateral anterior insula (AI) and dorsal anterior cingulate cortex (dACC). The right AI-right medial orbital frontal cortex (mOFC) connectivity was found to be uniquely decreased in the OCD-PI group, and the value of this aberrant connectivity correlated with insight level in OCD patients. In addition, we found that the OCD-GI group had significantly increased right AI-left dACC connectivity within the SN, relative to HCs (overall trend for groups: OCD-GI > OCD-PI > HC). Our findings suggest that abnormal right AI-right mOFC FC may mediate insight deficits in OCD, perhaps due to impaired encoding and integration of self-evaluative information about OCD-related beliefs and behaviors. Our findings indicate a SN connectivity dissociation between OCD-GI and OCD-PI patients and support the notion of considering OCD-GI and OCD-PI as two distinct disorder subtypes.

Reduced gamma frequency in the medial frontal cortex of aged rats during behavior and rest: implications for age-related behavioral slowing.

PubMed

Insel, Nathan; Patron, Lilian A; Hoang, Lan T; Nematollahi, Saman; Schimanski, Lesley A; Lipa, Peter; Barnes, Carol A

2012-11-14

Age-related cognitive and behavioral slowing may be caused by changes in the speed of neural signaling or by changes in the number of signaling steps necessary to achieve a given function. In the mammalian cortex, neural communication is organized by a 30-100 Hz "gamma" oscillation. There is a putative link between the gamma frequency and the speed of processing in a neural network: the dynamics of pyramidal neuron membrane time constants suggest that synaptic integration is framed by the gamma cycle, and pharmacological slowing of gamma also slows reaction times on behavioral tasks. The present experiments identify reductions in a robust 40-70 Hz gamma oscillation in the aged rat medial frontal cortex. The reductions were observed in the form of local field potentials, later peaks in fast-spiking neuron autocorrelations, and delays in the spiking of inhibitory neurons following local excitatory signals. Gamma frequency did not vary with movement speed, but rats with slower gamma also moved more slowly. Gamma frequency age differences were not observed in hippocampus. Hippocampal CA1 fast-spiking neurons exhibited interspike intervals consistent with a fast (70-100 Hz) gamma frequency, a pattern maintained across theta phases and theta frequencies independent of fluctuations in the average firing rates of the neurons. We propose that an average lengthening of the cortical 15-25 ms gamma cycle is one factor contributing to age-related slowing and that future attempts to offset cognitive declines will find a target in the response of fast-spiking inhibitory neurons to excitatory inputs.

Reduced gamma frequency in the medial frontal cortex of aged rats during behavior and rest: implications for age-related behavioral slowing

PubMed Central

Insel, Nathan; Patron, Lilian A.; Hoang, Lan T.; Nematollahi, Saman; Schimanski, Lesley A.; Lipa, Peter; Barnes, Carol A.

2012-01-01

Age-related cognitive and behavioral slowing may be caused by changes in the speed of neural signaling or by changes in the number of signaling steps necessary to achieve a given function. In the mammalian cortex, neural communication is organized by a 30–100 Hz “gamma” oscillation. There is a putative link between the gamma frequency and the speed of processing in a neural network: the dynamics of pyramidal neuron membrane time constants suggest that synaptic integration is framed by the gamma cycle, and pharmacological slowing of gamma also slows reaction times on behavioral tasks. The present experiments identify reductions in a robust 40–70 Hz gamma oscillation in the aged rat medial frontal cortex. The reductions were observed in the form of local field potentials (LFPs), later peaks in fast-spiking neuron autocorrelations, and delays in the spiking of inhibitory neurons following local excitatory signals. Gamma frequency did not vary with movement speed, but rats with slower gamma also moved more slowly. Gamma frequency age differences were not observed in hippocampus. Hippocampal CA1 fast-spiking neurons exhibited inter-spike intervals consistent with a fast (70–100 Hz) gamma frequency, a pattern maintained across theta phases and theta frequencies independent of fluctuations in the neurons’ average firing rates. We propose that an average lengthening of the cortical 15–25 ms gamma cycle is one factor contributing to age-related slowing, and that future attempts to offset cognitive declines will find a target in the response of fast-spiking inhibitory neurons to excitatory inputs. PMID:23152616

Betaine prevents homocysteine-induced memory impairment via matrix metalloproteinase-9 in the frontal cortex.

PubMed

Kunisawa, K; Nakashima, N; Nagao, M; Nomura, T; Kinoshita, S; Hiramatsu, M

2015-10-01

Betaine plays important roles that include acting as a methyl donor and converting homocysteine (Hcy) to methionine. Elevated plasma Hcy levels are known as hyperhomocysteinemia (HHcy) and contribute to impairments of learning and memory. Although it is commonly known that betaine plays an important role in Hcy metabolism, the effects of betaine on Hcy-induced memory impairment have not been investigated. Previously, we demonstrated the beneficial effects of betaine on acute stress and lipopolysaccharide-induced memory impairment. In the present study, we investigated whether betaine ameliorates Hcy-induced memory impairment and the underlying mechanisms of this putative effect. Mice were treated with Hcy (0.162mg/kg, s.c.) twice a day for nine days, and betaine (25mg/kg, s.c.) was administered 30min before the Hcy injections. The memory functions were evaluated using a spontaneous alternation performance test (Y-maze) at seven days and a step-down type passive avoidance test (SD) at nine and ten days after Hcy injection. We found that betaine suppressed the memory impairment induced by repeated Hcy injections. However, the blood concentrations of Hcy were significantly increased in the Hcy-treated mice immediately after the passive avoidance test, and betaine did not prevent this increase. Furthermore, Hcy induces redox stress in part by activating matrix metalloproteinase-9 (MMP-9), which leads to BBB dysfunction. Therefore, we tested whether betaine affected MMP-9 activity. Interestingly, treatment with betaine significantly inhibited Hcy-induced MMP-9 activity in the frontal cortex but not in the hippocampus after acute Hcy injection. These results suggest that the changes in MMP-9 activity after betaine treatment might have been partially responsible for the amelioration of the memory deficits and that MMP-9 might be a candidate therapeutic target for HHcy. Copyright © 2015 Elsevier B.V. All rights reserved.

Dissociable contribution of the parietal and frontal cortex to coding movement direction and amplitude

PubMed Central

Davare, Marco; Zénon, Alexandre; Desmurget, Michel; Olivier, Etienne

2015-01-01

To reach for an object, we must convert its spatial location into an appropriate motor command, merging movement direction and amplitude. In humans, it has been suggested that this visuo-motor transformation occurs in a dorsomedial parieto-frontal pathway, although the causal contribution of the areas constituting the “reaching circuit” remains unknown. Here we used transcranial magnetic stimulation (TMS) in healthy volunteers to disrupt the function of either the medial intraparietal area (mIPS) or dorsal premotor cortex (PMd), in each hemisphere. The task consisted in performing step-tracking movements with the right wrist towards targets located in different directions and eccentricities; targets were either visible for the whole trial (Target-ON) or flashed for 200 ms (Target-OFF). Left and right mIPS disruption led to errors in the initial direction of movements performed towards contralateral targets. These errors were corrected online in the Target-ON condition but when the target was flashed for 200 ms, mIPS TMS manifested as a larger endpoint spreading. In contrast, left PMd virtual lesions led to higher acceleration and velocity peaks—two parameters typically used to probe the planned movement amplitude—irrespective of the target position, hemifield and presentation condition; in the Target-OFF condition, left PMd TMS induced overshooting and increased the endpoint dispersion along the axis of the target direction. These results indicate that left PMd intervenes in coding amplitude during movement preparation. The critical TMS timings leading to errors in direction and amplitude were different, namely 160–100 ms before movement onset for mIPS and 100–40 ms for left PMd. TMS applied over right PMd had no significant effect. These results demonstrate that, during motor preparation, direction and amplitude of goal-directed movements are processed by different cortical areas, at distinct timings, and according to a specific hemispheric

Persistently active neurons in human medial frontal and medial temporal lobe support working memory

PubMed Central

Kamiński, J; Sullivan, S; Chung, JM; Ross, IB; Mamelak, AN; Rutishauser, U

2017-01-01

Persistent neural activity is a putative mechanism for the maintenance of working memories. Persistent activity relies on the activity of a distributed network of areas, but the differential contribution of each area remains unclear. We recorded single neurons in the human medial frontal cortex and the medial temporal lobe while subjects held up to three items in memory. We found persistently active neurons in both areas. Persistent activity of hippocampal and amygdala neurons was stimulus-specific, formed stable attractors, and was predictive of memory content. Medial frontal cortex persistent activity, on the other hand, was modulated by memory load and task set but was not stimulus-specific. Trial-by-trial variability in persistent activity in both areas was related to memory strength, because it predicted the speed and accuracy by which stimuli were remembered. This work reveals, in humans, direct evidence for a distributed network of persistently active neurons supporting working memory maintenance. PMID:28218914

Frontal Theta Dynamics during Response Conflict in Long-Term Mindfulness Meditators

PubMed Central

Jo, Han-Gue; Malinowski, Peter; Schmidt, Stefan

2017-01-01

Mindfulness meditators often show greater efficiency in resolving response conflicts than non-meditators. However, the neural mechanisms underlying the improved behavioral efficiency are unclear. Here, we investigated frontal theta dynamics—a neural mechanism involved in cognitive control processes—in long-term mindfulness meditators. The dynamics of EEG theta oscillations (4–8 Hz) recorded over the medial frontal cortex (MFC) were examined in terms of their power (MFC theta power) and their functional connectivity with other brain areas (the MFC-centered theta network). Using a flanker-type paradigm, EEG data were obtained from 22 long-term mindfulness meditators and compared to those from 23 matched controls without meditation experience. Meditators showed more efficient cognitive control after conflicts, evidenced by fewer error responses irrespective of response timing. Furthermore, meditators exhibited enhanced conflict modulations of the MFC-centered theta network shortly before the response, in particular for the functional connection between the MFC and the motor cortex. In contrast, MFC theta power was comparable between groups. These results suggest that the higher behavioral efficiency after conflicts in mindfulness meditators could be a function of increased engagement to control the motor system in association with the MFC-centered theta network. PMID:28638334

Frontal Midline Theta Reflects Anxiety and Cognitive Control: Meta-Analytic Evidence

PubMed Central

Cavanagh, James F.; Shackman, Alexander J.

2014-01-01

Evidence from imaging and anatomical studies suggests that the midcingulate cortex (MCC) is a dynamic hub lying at the interface of affect and cognition. In particular, this neural system appears to integrate information about conflict and punishment in order to optimize behavior in the face of action-outcome uncertainty. In a series of meta-analyses, we show how recent human electrophysiological research provides compelling evidence that frontal-midline theta signals reflecting MCC activity are moderated by anxiety and predict adaptive behavioral adjustments. These findings underscore the importance of frontal theta activity to a broad spectrum of control operations. We argue that frontal-midline theta provides a neurophysiologically plausible mechanism for optimally adjusting behavior to uncertainty, a hallmark of situations that elicit anxiety and demand cognitive control. These observations compel a new perspective on the mechanisms guiding motivated learning and behavior and provide a framework for understanding the role of the MCC in temperament and psychopathology. PMID:24787485

Genetic and Environmental Influences on Frontal EEG Asymmetry and Alpha Power in 9–10 Year Old Twins

PubMed Central

Gao, Yu; Tuvblad, Catherine; Raine, Adrian; Lozano, Dora I.; Baker, Laura A.

2008-01-01

Modest genetic influences on frontal EEG asymmetry have been found in adults, but little is known about its genetic origins in children. Resting frontal asymmetry and alpha power were examined in 951 9–10-year-old twins. Results showed that in both males and females: (1) a modest but significant amount of variance in frontal asymmetry was accounted for by genetic factors (11–27%) with the remainder accounted for by non-shared environmental influences, and (2) alpha power were highly heritable, with 70–85% of the variance accounted for by genetic factors. Results suggest that the genetic architecture of frontal asymmetry and alpha power in late childhood are similar to that in adulthood and that the high non-shared environmental influences on frontal asymmetry may reflect environmentally-influenced individual differences in the maturation of frontal cortex as well as state-dependent influences on specific measurements. PMID:19386046

Computational Architecture of the Parieto-Frontal Network Underlying Cognitive-Motor Control in Monkeys

PubMed Central

Borra, Elena; Visco-Comandini, Federica; Averbeck, Bruno B.

2017-01-01

The statistical structure of intrinsic parietal and parieto-frontal connectivity in monkeys was studied through hierarchical cluster analysis. Based on their inputs, parietal and frontal areas were grouped into different clusters, including a variable number of areas that in most instances occupied contiguous architectonic fields. Connectivity tended to be stronger locally: that is, within areas of the same cluster. Distant frontal and parietal areas were targeted through connections that in most instances were reciprocal and often of different strength. These connections linked parietal and frontal clusters formed by areas sharing basic functional properties. This led to five different medio-laterally oriented pillar domains spanning the entire extent of the parieto-frontal system, in the posterior parietal, anterior parietal, cingulate, frontal, and prefrontal cortex. Different information processing streams could be identified thanks to inter-domain connectivity. These streams encode fast hand reaching and its control, complex visuomotor action spaces, hand grasping, action/intention recognition, oculomotor intention and visual attention, behavioral goals and strategies, and reward and decision value outcome. Most of these streams converge on the cingulate domain, the main hub of the system. All of them are embedded within a larger eye–hand coordination network, from which they can be selectively set in motion by task demands. PMID:28275714

Frontal top-down signals increase coupling of auditory low-frequency oscillations to continuous speech in human listeners.

PubMed

Park, Hyojin; Ince, Robin A A; Schyns, Philippe G; Thut, Gregor; Gross, Joachim

2015-06-15

Humans show a remarkable ability to understand continuous speech even under adverse listening conditions. This ability critically relies on dynamically updated predictions of incoming sensory information, but exactly how top-down predictions improve speech processing is still unclear. Brain oscillations are a likely mechanism for these top-down predictions [1, 2]. Quasi-rhythmic components in speech are known to entrain low-frequency oscillations in auditory areas [3, 4], and this entrainment increases with intelligibility [5]. We hypothesize that top-down signals from frontal brain areas causally modulate the phase of brain oscillations in auditory cortex. We use magnetoencephalography (MEG) to monitor brain oscillations in 22 participants during continuous speech perception. We characterize prominent spectral components of speech-brain coupling in auditory cortex and use causal connectivity analysis (transfer entropy) to identify the top-down signals driving this coupling more strongly during intelligible speech than during unintelligible speech. We report three main findings. First, frontal and motor cortices significantly modulate the phase of speech-coupled low-frequency oscillations in auditory cortex, and this effect depends on intelligibility of speech. Second, top-down signals are significantly stronger for left auditory cortex than for right auditory cortex. Third, speech-auditory cortex coupling is enhanced as a function of stronger top-down signals. Together, our results suggest that low-frequency brain oscillations play a role in implementing predictive top-down control during continuous speech perception and that top-down control is largely directed at left auditory cortex. This suggests a close relationship between (left-lateralized) speech production areas and the implementation of top-down control in continuous speech perception. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Frontal Top-Down Signals Increase Coupling of Auditory Low-Frequency Oscillations to Continuous Speech in Human Listeners

PubMed Central

Park, Hyojin; Ince, Robin A.A.; Schyns, Philippe G.; Thut, Gregor; Gross, Joachim

2015-01-01

Summary Humans show a remarkable ability to understand continuous speech even under adverse listening conditions. This ability critically relies on dynamically updated predictions of incoming sensory information, but exactly how top-down predictions improve speech processing is still unclear. Brain oscillations are a likely mechanism for these top-down predictions [1, 2]. Quasi-rhythmic components in speech are known to entrain low-frequency oscillations in auditory areas [3, 4], and this entrainment increases with intelligibility [5]. We hypothesize that top-down signals from frontal brain areas causally modulate the phase of brain oscillations in auditory cortex. We use magnetoencephalography (MEG) to monitor brain oscillations in 22 participants during continuous speech perception. We characterize prominent spectral components of speech-brain coupling in auditory cortex and use causal connectivity analysis (transfer entropy) to identify the top-down signals driving this coupling more strongly during intelligible speech than during unintelligible speech. We report three main findings. First, frontal and motor cortices significantly modulate the phase of speech-coupled low-frequency oscillations in auditory cortex, and this effect depends on intelligibility of speech. Second, top-down signals are significantly stronger for left auditory cortex than for right auditory cortex. Third, speech-auditory cortex coupling is enhanced as a function of stronger top-down signals. Together, our results suggest that low-frequency brain oscillations play a role in implementing predictive top-down control during continuous speech perception and that top-down control is largely directed at left auditory cortex. This suggests a close relationship between (left-lateralized) speech production areas and the implementation of top-down control in continuous speech perception. PMID:26028433

Effects of hypercapnia and hypoxemia on fetal breathing after decortication.

PubMed

Ioffe, S; Jansen, A H; Chernick, V

1986-09-01

The effects of hypercapnia and hypoxemia on breathing movements were studied in 12 chronically decorticated fetal sheep, 127-140 days gestation. The fetal state of consciousness was defined in terms of activity of the lateral rectus and nuchal muscles. Arterial blood pressure was monitored. Fetal breathing was determined by integrated diaphragmatic electromyogram (EMG) and analyzed in terms of inspiratory time (TI), expiratory time (TE), electrical equivalent of tidal volume (EVT), breath interval (TT), duty cycle (TI/TT), mean inspiratory flow equivalent (EVT/TI), and instantaneous ventilation equivalent (EVT/TT). Fetal breathing occurred only during episodes of rapid-eye movements, and the response to hypercapnia consisted of an increase in EVT, TI, EVE, and EVT/TI and a decrease in the coefficient of variation of all measured parameters. Induction of hypoxia during episodes of spontaneous fetal breathing produced a decrease in the rate of breathing and an increase in EVT and TI with no change in the variability of all parameters studied. Since similar responses to hypercapnia and hypoxemia are seen in the intact fetus, we conclude that the cerebral cortex has no obvious effect on the chemical control of fetal breathing.

Optogenetic stimulation of cortex to map evoked whisker movements in awake head-restrained mice.

PubMed

Auffret, Matthieu; Ravano, Veronica L; Rossi, Giulia M C; Hankov, Nicolas; Petersen, Merissa F A; Petersen, Carl C H

2018-01-01

Whisker movements are used by rodents to touch objects in order to extract spatial and textural tactile information about their immediate surroundings. To understand the mechanisms of such active sensorimotor processing it is important to investigate whisker motor control. The activity of neurons in the neocortex affects whisker movements, but many aspects of the organization of cortical whisker motor control remain unknown. Here, we filmed whisker movements evoked by sequential optogenetic stimulation of different locations across the left dorsal sensorimotor cortex of awake head-restrained mice. Whisker movements were evoked by optogenetic stimulation of many regions in the dorsal sensorimotor cortex. Optogenetic stimulation of whisker sensory barrel cortex evoked retraction of the contralateral whisker after a short latency, and a delayed rhythmic protraction of the ipsilateral whisker. Optogenetic stimulation of frontal cortex evoked rhythmic bilateral whisker protraction with a longer latency compared to stimulation of sensory cortex. Compared to frontal cortex stimulation, larger amplitude bilateral rhythmic whisking in a less protracted position was evoked at a similar latency by stimulating a cortical region posterior to Bregma and close to the midline. These data suggest that whisker motor control might be broadly distributed across the dorsal mouse sensorimotor cortex. Future experiments must investigate the complex neuronal circuits connecting specific cell-types in various cortical regions with the whisker motor neurons located in the facial nucleus. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Reduced frontal theta oscillations indicate altered crossmodal prediction error processing in schizophrenia

PubMed Central

Keil, Julian; Balz, Johanna; Gallinat, Jürgen; Senkowski, Daniel

2016-01-01

Our brain generates predictions about forthcoming stimuli and compares predicted with incoming input. Failures in predicting events might contribute to hallucinations and delusions in schizophrenia (SZ). When a stimulus violates prediction, neural activity that reflects prediction error (PE) processing is found. While PE processing deficits have been reported in unisensory paradigms, it is unknown whether SZ patients (SZP) show altered crossmodal PE processing. We measured high-density electroencephalography and applied source estimation approaches to investigate crossmodal PE processing generated by audiovisual speech. In SZP and healthy control participants (HC), we used an established paradigm in which high- and low-predictive visual syllables were paired with congruent or incongruent auditory syllables. We examined crossmodal PE processing in SZP and HC by comparing differences in event-related potentials and neural oscillations between incongruent and congruent high- and low-predictive audiovisual syllables. In both groups event-related potentials between 206 and 250 ms were larger in high- compared with low-predictive syllables, suggesting intact audiovisual incongruence detection in the auditory cortex of SZP. The analysis of oscillatory responses revealed theta-band (4–7 Hz) power enhancement in high- compared with low-predictive syllables between 230 and 370 ms in the frontal cortex of HC but not SZP. Thus aberrant frontal theta-band oscillations reflect crossmodal PE processing deficits in SZ. The present study suggests a top-down multisensory processing deficit and highlights the role of dysfunctional frontal oscillations for the SZ psychopathology. PMID:27358314

Chronic Mild Stress Alters Kynurenine Pathways Changing the Glutamate Neurotransmission in Frontal Cortex of Rats.

PubMed

Martín-Hernández, David; Tendilla-Beltrán, Hiram; Madrigal, José L M; García-Bueno, Borja; Leza, Juan C; Caso, Javier R

2018-05-03

Immune stimulation might be involved in the pathophysiology of major depressive disorder (MDD). This stimulation induces indoleamine 2,3-dioxygenase (IDO), an enzyme that reduces the tryptophan bioavailability to synthesize serotonin. IDO products, kynurenine metabolites, exert neurotoxic/neuroprotective actions through glutamate receptors. Thus, we study elements of these pathways linked to kynurenine metabolite activity examining whether antidepressants (ADs) can modulate them. Male Wistar rats were exposed to chronic mild stress (CMS), and some of them were treated with ADs. The expression of elements of the IDO pathway, including kynurenine metabolites, and their possible modulation by ADs was studied in the frontal cortex (FC). CMS increased IDO expression in FC compared to control group, and ADs restored the IDO expression levels to control values. CMS-induced IDO expression led to increased levels of the excitotoxic quinolinic acid (QUINA) compared to control, and ADs prevented the rise in such levels. Neither CMS nor ADs changed significantly the antiexcitotoxic kynurenic acid (KYNA) levels. The QUINA/KYNA ratio, calculated as excitotoxicity risk indicator, increased after CMS and ADs prevented this increase. CMS lowered excitatory amino acid transporter (EAAT)-1 and EAAT-4 expression, and some ADs restored their expression levels. Furthermore, CMS decreased N-methyl-D-aspartate receptor (NMDAR)-2A and 2B protein expression, and ADs mitigated this decrease. Our research examines the link between CMS-induced pro-inflammatory cytokines and the kynurenine pathway; it shows that CMS alters the kynurenine pathway in rat FC. Importantly, it also reveals the ability of classic ADs to prevent potentially harmful situations related to the brain scenario caused by CMS.

Receptor subtypes involved in callosally-induced postsynaptic potentials in rat frontal agranular cortex in vitro.

PubMed

Kawaguchi, Y

1992-01-01

A slice preparation of rat frontal agranular cortex preserving commissural inputs has been used for intracellular recording from layer V pyramidal cells, in order to characterize the synaptic potentials induced by stimulation of the corpus callosum and to reveal the subtypes of amino acid receptors involved. Stimulation of the corpus callosum induced EPSPs followed by early IPSPs with a peak latency of 30 +/- 2 ms and late IPSPs with a peak latency of 185 +/- 18 ms. Reversal potentials for early and late IPSPs were -75 +/- 5 mV (early) and -96 +/- 5 mV (late). Late IPSPs were more dependent on extracellular K+ concentration. The early IPSPs were blocked by GABAA antagonists, bicuculline and picrotoxin, whereas the late IPSPs were reduced by the GABAB antagonist, phaclofen. CNQX (6-cyano-7-nitroquinoxaline-2,3-dione), an antagonist of non-NMDA (N-methyl-D-aspartate) receptors, suppressed both EPSPs and late IPSPs at 5 microM. Early IPSPs remained at this concentration but were suppressed by 20 microM CNQX. In Mg(2+)-free solution, EPSPs were larger and more prolonged than in control solution. These enhanced EPSPs persisted after 5 to 20 microM CNQX, but were reduced in amplitude, and their onset was delayed by 3.6 +/- 0.8 ms. The remaining EPSPs were suppressed by 50 microM APV (DL-2-amino-5-phosphono-valeric acid), an antagonist of NMDA receptors. In Mg(2+)-free solution containing 5 to 20 microM CNQX, the late IPSPs were not diminished. The remaining late IPSPs were suppressed by APV or by phaclofen.(ABSTRACT TRUNCATED AT 250 WORDS)

New Model of Action for Mood Stabilizers: Phosphoproteome from Rat Pre-Frontal Cortex Synaptoneurosomal Preparations

PubMed Central

Corena-McLeod, Maria; Walss-Bass, Consuelo; Oliveros, Alfredo; Gordillo Villegas, Andres; Ceballos, Carolina; Charlesworth, Cristine M.; Madden, Benjamin; Linser, Paul J.; Van Ekeris, Leslie; Smith, Kristin; Richelson, Elliott

2013-01-01

Background Mitochondrial short and long-range movements are necessary to generate the energy needed for synaptic signaling and plasticity. Therefore, an effective mechanism to transport and anchor mitochondria to pre- and post-synaptic terminals is as important as functional mitochondria in neuronal firing. Mitochondrial movement range is regulated by phosphorylation of cytoskeletal and motor proteins in addition to changes in mitochondrial membrane potential. Movement direction is regulated by serotonin and dopamine levels. However, data on mitochondrial movement defects and their involvement in defective signaling and neuroplasticity in relationship with mood disorders is scarce. We have previously reported the effects of lithium, valproate and a new antipsychotic, paliperidone on protein expression levels at the synaptic level. Hypothesis Mitochondrial function defects have recently been implicated in schizophrenia and bipolar disorder. We postulate that mood stabilizer treatment has a profound effect on mitochondrial function, synaptic plasticity, mitochondrial migration and direction of movement. Methods Synaptoneurosomal preparations from rat pre-frontal cortex were obtained after 28 daily intraperitoneal injections of lithium, valproate and paliperidone. Phosphorylated proteins were identified using 2D-DIGE and nano LC-ESI tandem mass spectrometry. Results Lithium, valproate and paliperidone had a substantial and common effect on the phosphorylation state of specific actin, tubulin and myosin isoforms as well as other proteins associated with neurofilaments. Furthermore, different subunits from complex III and V of the electron transfer chain were heavily phosphorylated by treatment with these drugs indicating selective phosphorylation. Conclusions Mood stabilizers have an effect on mitochondrial function, mitochondrial movement and the direction of this movement. The implications of these findings will contribute to novel insights regarding clinical

Representation of Cognitive Reappraisal Goals in Frontal Gamma Oscillations

PubMed Central

Kang, Jae-Hwan; Jeong, Ji Woon; Kim, Hyun Taek; Kim, Sang Hee; Kim, Sung-Phil

2014-01-01

Recently, numerous efforts have been made to understand the neural mechanisms underlying cognitive regulation of emotion, such as cognitive reappraisal. Many studies have reported that cognitive control of emotion induces increases in neural activity of the control system, including the prefrontal cortex and the dorsal anterior cingulate cortex, and increases or decreases (depending upon the regulation goal) in neural activity of the appraisal system, including the amygdala and the insula. It has been hypothesized that information about regulation goals needs to be processed through interactions between the control and appraisal systems in order to support cognitive reappraisal. However, how this information is represented in the dynamics of cortical activity remains largely unknown. To address this, we investigated temporal changes in gamma band activity (35–55 Hz) in human electroencephalograms during a cognitive reappraisal task that was comprised of three reappraisal goals: to decease, maintain, or increase emotional responses modulated by affect-laden pictures. We examined how the characteristics of gamma oscillations, such as spectral power and large-scale phase synchronization, represented cognitive reappraisal goals. We found that left frontal gamma power decreased, was sustained, or increased when the participants suppressed, maintained, or amplified their emotions, respectively. This change in left frontal gamma power appeared during an interval of 1926 to 2453 ms after stimulus onset. We also found that the number of phase-synchronized pairs of gamma oscillations over the entire brain increased when participants regulated their emotions compared to when they maintained their emotions. These results suggest that left frontal gamma power may reflect cortical representation of emotional states modulated by cognitive reappraisal goals and gamma phase synchronization across whole brain regions may reflect emotional regulatory efforts to achieve these goals

Representation of cognitive reappraisal goals in frontal gamma oscillations.

PubMed

Kang, Jae-Hwan; Jeong, Ji Woon; Kim, Hyun Taek; Kim, Sang Hee; Kim, Sung-Phil

2014-01-01

Recently, numerous efforts have been made to understand the neural mechanisms underlying cognitive regulation of emotion, such as cognitive reappraisal. Many studies have reported that cognitive control of emotion induces increases in neural activity of the control system, including the prefrontal cortex and the dorsal anterior cingulate cortex, and increases or decreases (depending upon the regulation goal) in neural activity of the appraisal system, including the amygdala and the insula. It has been hypothesized that information about regulation goals needs to be processed through interactions between the control and appraisal systems in order to support cognitive reappraisal. However, how this information is represented in the dynamics of cortical activity remains largely unknown. To address this, we investigated temporal changes in gamma band activity (35-55 Hz) in human electroencephalograms during a cognitive reappraisal task that was comprised of three reappraisal goals: to decease, maintain, or increase emotional responses modulated by affect-laden pictures. We examined how the characteristics of gamma oscillations, such as spectral power and large-scale phase synchronization, represented cognitive reappraisal goals. We found that left frontal gamma power decreased, was sustained, or increased when the participants suppressed, maintained, or amplified their emotions, respectively. This change in left frontal gamma power appeared during an interval of 1926 to 2453 ms after stimulus onset. We also found that the number of phase-synchronized pairs of gamma oscillations over the entire brain increased when participants regulated their emotions compared to when they maintained their emotions. These results suggest that left frontal gamma power may reflect cortical representation of emotional states modulated by cognitive reappraisal goals and gamma phase synchronization across whole brain regions may reflect emotional regulatory efforts to achieve these goals

Energy metabolism of rat cerebral cortex, hypothalamus and hypophysis during ageing.

PubMed

Villa, R F; Ferrari, F; Gorini, A

2012-12-27

Ageing is one of the main risk factors for brain disorders. According to the neuroendocrine theory, ageing modifies the sensitivity of hypothalamus-pituitary-adrenal axis to homoeostatic signals coming from the cerebral cortex. The relationships between the energy metabolism of these areas have not been considered yet, in particular with respect to ageing. For these reasons, this study was undertaken to systematically investigate in female Sprague-Dawley rats aged 4, 6, 12, 18, 24, 28 months and in 4-month-old male ones, the catalytic properties of energy-linked enzymes of the Krebs' cycle, electron transport chain, glutamate and related amino acids on different mitochondrial subpopulations, i.e. non-synaptic perikaryal and intra-synaptic (two types) mitochondria. The biochemical enzymatic pattern of these mitochondria shows different expression of the above-mentioned enzymatic activities in the investigated brain areas, including frontal cerebral cortex, hippocampus, striatum, hypothalamus and hypophysis. The study shows that: (i) the energy metabolism of the frontal cerebral cortex is poorly affected by physiological ageing; (ii) the biochemical machinery of non-synaptic perikaryal mitochondria is differently expressed in the considered brain areas; (iii) at 4-6 months, hypothalamus and hypophysis possess lower oxidative metabolism with respect to the frontal cerebral cortex while (iv), during ageing, the opposite situation occurs. We hypothesised that these metabolic modifications likely try to grant HPA functionality in response to the incoming external stress stimuli increased during ageing. It is particularly notable that age-related changes in brain bioenergetics and in mitochondrial functionality may be considered as remarkable factors during physiological ageing and should play important roles in predisposing the brain to physiopathological events, tightly related to molecular mechanisms evoked for pharmacological treatments. Copyright © 2012 IBRO

Prefrontal Cortex Contributions to Episodic Retrieval Monitoring and Evaluation

ERIC Educational Resources Information Center

Cruse, Damian; Wilding, Edward L.

2009-01-01

Although the prefrontal cortex (PFC) plays roles in episodic memory judgments, the specific processes it supports are not understood fully. Event-related potential (ERP) studies of episodic retrieval have revealed an electrophysiological modulation--the right-frontal ERP old/new effect--which is thought to reflect activity in PFC. The functional…

Dysfunctional frontal lobe activity during inhibitory tasks in individuals with childhood trauma: An event-related potential study.

PubMed

Kim, Sungkean; Kim, Ji Sun; Jin, Min Jin; Im, Chang-Hwan; Lee, Seung-Hwan

2018-01-01

Individuals who experience childhood trauma are vulnerable to various psychological and behavioral problems throughout their lifetime. This study aimed to investigate whether individuals with childhood trauma show altered frontal lobe activity during response inhibition tasks. In total, 157 healthy individuals were recruited and instructed to perform a Go/Nogo task during electroencephalography recording. Source activities of N2 and P3 of Nogo event-related potentials (ERP) were analyzed. The Childhood Trauma Questionnaire (CTQ) and Barratt Impulsivity Scale (BIS) were applied. Individuals were divided into three groups based on their total CTQ score: low CTQ, middle CTQ, and high CTQ groups. The high CTQ group exhibited significantly higher BIS scores than the low CTQ group. P3 amplitudes of the differences between Nogo and Go ERP waves exhibited higher mean values in the low CTQ than the high CTQ group, with trending effects. In Nogo-P3, the source activities of the right anterior cingulate cortex, bilateral medial frontal cortex (MFC), bilateral superior frontal gyrus (SFG), and right precentral gyrus were significantly lower in the high CTQ than the low CTQ group. Motor impulsivity showed a significant negative correlation with activities of the bilateral MFC and SFG in Nogo-P3 conditions. Our study revealed that individuals with childhood trauma have inhibitory failure and frontal lobe dysfunction in regions related to Nogo-P3.

Activation of sensory cortex by imagined genital stimulation: an fMRI analysis

PubMed Central

Wise, Nan J.; Frangos, Eleni; Komisaruk, Barry R.

2016-01-01

Background During the course of a previous study, our laboratory made a serendipitous finding that just thinking about genital stimulation resulted in brain activations that overlapped with, and differed from, those generated by physical genital stimulation. Objective This study extends our previous findings by further characterizing how the brain differentially processes physical ‘touch’ stimulation and ‘imagined’ stimulation. Design Eleven healthy women (age range 29–74) participated in an fMRI study of the brain response to imagined or actual tactile stimulation of the nipple and clitoris. Two additional conditions – imagined dildo self-stimulation and imagined speculum stimulation – were included to characterize the effects of erotic versus non-erotic imagery. Results Imagined and tactile self-stimulation of the nipple and clitoris each activated the paracentral lobule (the genital region of the primary sensory cortex) and the secondary somatosensory cortex. Imagined self-stimulation of the clitoris and nipple resulted in greater activation of the frontal pole and orbital frontal cortex compared to tactile self-stimulation of these two bodily regions. Tactile self-stimulation of the clitoris and nipple activated the cerebellum, primary somatosensory cortex (hand region), and premotor cortex more than the imagined stimulation of these body regions. Imagining dildo stimulation generated extensive brain activation in the genital sensory cortex, secondary somatosensory cortex, hippocampus, amygdala, insula, nucleus accumbens, and medial prefrontal cortex, whereas imagining speculum stimulation generated only minimal activation. Conclusion The present findings provide evidence of the potency of imagined stimulation of the genitals and that the following brain regions may participate in erogenous experience: primary and secondary sensory cortices, sensory-motor integration areas, limbic structures, and components of the ‘reward system’. In addition

Activation of sensory cortex by imagined genital stimulation: an fMRI analysis.

PubMed

Wise, Nan J; Frangos, Eleni; Komisaruk, Barry R

2016-01-01

During the course of a previous study, our laboratory made a serendipitous finding that just thinking about genital stimulation resulted in brain activations that overlapped with, and differed from, those generated by physical genital stimulation. This study extends our previous findings by further characterizing how the brain differentially processes physical 'touch' stimulation and 'imagined' stimulation. Eleven healthy women (age range 29-74) participated in an fMRI study of the brain response to imagined or actual tactile stimulation of the nipple and clitoris. Two additional conditions - imagined dildo self-stimulation and imagined speculum stimulation - were included to characterize the effects of erotic versus non-erotic imagery. Imagined and tactile self-stimulation of the nipple and clitoris each activated the paracentral lobule (the genital region of the primary sensory cortex) and the secondary somatosensory cortex. Imagined self-stimulation of the clitoris and nipple resulted in greater activation of the frontal pole and orbital frontal cortex compared to tactile self-stimulation of these two bodily regions. Tactile self-stimulation of the clitoris and nipple activated the cerebellum, primary somatosensory cortex (hand region), and premotor cortex more than the imagined stimulation of these body regions. Imagining dildo stimulation generated extensive brain activation in the genital sensory cortex, secondary somatosensory cortex, hippocampus, amygdala, insula, nucleus accumbens, and medial prefrontal cortex, whereas imagining speculum stimulation generated only minimal activation. The present findings provide evidence of the potency of imagined stimulation of the genitals and that the following brain regions may participate in erogenous experience: primary and secondary sensory cortices, sensory-motor integration areas, limbic structures, and components of the 'reward system'. In addition, these results suggest a mechanism by which some individuals may

Orienting Auditory Spatial Attention Engages Frontal Eye Fields and Medial Occipital Cortex in Congenitally Blind Humans

PubMed Central

Garg, Arun; Schwartz, Daniel; Stevens, Alexander A.

2007-01-01

What happens in vision related cortical areas when congenitally blind (CB) individuals orient attention to spatial locations? Previous neuroimaging of sighted individuals has found overlapping activation in a network of frontoparietal areas including frontal eye-fields (FEF), during both overt (with eye movement) and covert (without eye movement) shifts of spatial attention. Since voluntary eye movement planning seems irrelevant in CB, their FEF neurons should be recruited for alternative functions if their attentional role in sighted individuals is only due to eye movement planning. Recent neuroimaging of the blind has also reported activation in medial occipital areas, normally associated with visual processing, during a diverse set of non-visual tasks, but their response to attentional shifts remains poorly understood. Here, we used event-related fMRI to explore FEF and medial occipital areas in CB individuals and sighted controls with eyes closed (SC) performing a covert attention orienting task, using endogenous verbal cues and spatialized auditory targets. We found robust stimulus-locked FEF activation of all CB subjects, similar but stronger than in SC, suggesting that FEF plays a role in endogenous orienting of covert spatial attention even in individuals in whom voluntary eye movements are irrelevant. We also found robust activation in bilateral medial occipital cortex in CB but not in SC subjects. The response decreased below baseline following endogenous verbal cues but increased following auditory targets, suggesting that the medial occipital area in CB does not directly engage during cued orienting of attention but may be recruited for processing of spatialized auditory targets. PMID:17397882

Reduced functional connectivity to the frontal cortex during processing of social cues in autism spectrum disorder.

PubMed

Hoffmann, Elgin; Brück, Carolin; Kreifelts, Benjamin; Ethofer, Thomas; Wildgruber, Dirk

2016-08-01

People diagnosed with autism spectrum disorder (ASD) characteristically present with severe difficulties in interpreting every-day social signals. Currently it is assumed that these difficulties might have neurobiological correlates in alterations in activation as well as in connectivity in and between regions of the social perception network suggested to govern the processing of social cues. In this study, we conducted functional magnetic resonance imaging (fMRI)-based activation and connectivity analyses focusing on face-, voice-, and audiovisual-processing brain regions as the most important subareas of the social perception network. Results revealed alterations in connectivity among regions involved in the processing of social stimuli in ASD subjects compared to typically developed (TD) controls-specifically, a reduced connectivity between the left temporal voice area (TVA) and the superior and medial frontal gyrus. Alterations in connectivity, moreover, were correlated with the severity of autistic traits: correlation analysis indicated that the connectivity between the left TVA and the limbic lobe, anterior cingulate and the medial frontal gyrus as well as between the right TVA and the frontal lobe, anterior cingulate, limbic lobe and the caudate decreased with increasing symptom severity. As these frontal regions are understood to play an important role in interpreting and mentalizing social signals, the observed underconnectivity might be construed as playing a role in social impairments in ASD.

Diffusion-weighted magnetic resonance imaging of the fetal brain in intrauterine growth restriction.

PubMed

Arthurs, O J; Rega, A; Guimiot, F; Belarbi, N; Rosenblatt, J; Biran, V; Elmaleh, M; Sebag, G; Alison, M

2017-07-01

Diffusion-weighted magnetic resonance imaging (DWI) is a sensitive method for assessing brain maturation and detecting brain lesions, providing apparent diffusion coefficient (ADC) values as a measure of water diffusion. Abnormal ADC values are seen in ischemic brain lesions, such as those associated with acute or chronic hypoxia. The aim of this study was to assess whether ADC values in the fetal brain were different in fetuses with severe intrauterine growth restriction (IUGR) compared with normal controls. Brain magnetic resonance imaging (MRI) with single-shot axial DWI (b = 0 and b = 700 s/mm 2 ) was performed in 30 fetuses with severe IUGR (estimated fetal weight < 3 rd centile with absent or reversed umbilical artery Doppler flow) and in 24 normal controls of similar gestational age. Brain morphology and biometry were analyzed. ADC values were measured in frontal and occipital white matter, centrum semiovale, thalami, cerebellar hemisphere and pons. Frontal-occipital and frontal-cerebellar ADC ratios were calculated, and values were compared between IUGR fetuses and controls. There was no difference in gestational age at MRI between IUGR and control fetuses (IUGR, 30.2 ± 1.6 weeks vs controls, 30.7 ± 1.4 weeks). Fetal brain morphology and signals were normal in all fetuses. Brain dimensions (supratentorial ± infratentorial) were decreased (Z-score, < -2) in 20 (66.7%) IUGR fetuses. Compared with controls, IUGR fetuses had significantly lower ADC values in frontal white matter (1.97 ± 0.23 vs 2.17 ± 0.22 × 10 -3 mm 2 /s; P < 0.0001), thalami (1.04 ± 0.15 vs 1.13 ± 0.10 ×10 -3 mm 2 /s; P = 0.0002), centrum semiovale (1.86 ± 0.22 vs 1.97 ± 0.23 ×10 -3 mm 2 /s; P = 0.01) and pons (0.85 ± 0.19 vs 0.94 ± 0.12 ×10 -3 mm 2 /s; P = 0.043). IUGR fetuses had a lower frontal-occipital ADC ratio than did normal fetuses (1.00 ± 0.11 vs 1.08 ± 0.05; P = 0.003). ADC values in IUGR fetuses were significantly lower than in

Measurements of evoked electroencephalograph by transcranial magnetic stimulation applied to motor cortex and posterior parietal cortex

NASA Astrophysics Data System (ADS)

Iwahashi, Masakuni; Koyama, Yohei; Hyodo, Akira; Hayami, Takehito; Ueno, Shoogo; Iramina, Keiji

2009-04-01

To investigate the functional connectivity, the evoked potentials by stimulating at the motor cortex, the posterior parietal cortex, and the cerebellum by transcranial magnetic stimulation (TMS) were measured. It is difficult to measure the evoked electroencephalograph (EEG) by the magnetic stimulation because of the large artifact induced by the magnetic pulse. We used an EEG measurement system with sample-and-hold circuit and an independent component analysis to eliminate the electromagnetic interaction emitted from TMS. It was possible to measure EEG signals from all electrodes over the head within 10 ms after applying the TMS. When the motor area was stimulated by TMS, the spread of evoked electrical activity to the contralateral hemisphere was observed at 20 ms after stimulation. However, when the posterior parietal cortex was stimulated, the evoked electrical activity to the contralateral hemisphere was not observed. When the cerebellum was stimulated, the cortical activity propagated from the stimulated point to the frontal area and the contralateral hemisphere at around 20 ms after stimulation. These results suggest that the motor area has a strong interhemispheric connection and the posterior parietal cortex has no interhemispheric connection.

The Involvement of Occipital and Inferior Frontal Cortex in the Phonological Learning of Chinese Characters

PubMed Central

Deng, Yuan; Chou, Tai-li; Ding, Guo-sheng; Peng, Dan-ling; Booth, James R.

2016-01-01

Neural changes related to the learning of the pronunciation of Chinese characters in English speakers were examined using fMRI. We examined the item-specific learning effects for trained characters and the generalization of phonetic knowledge to novel transfer characters that shared a phonetic radical (part of a character that gives a clue to the whole character’s pronunciation) with trained characters. Behavioral results showed that shared phonetic information improved performance for transfer characters. Neuroimaging results for trained characters over learning found increased activation in the right lingual gyrus, and greater activation enhancement in the left inferior frontal gyrus (Brodmann’s area 44) was correlated with higher accuracy improvement. Moreover, greater activation for transfer characters in these two regions at the late stage of training was correlated with better knowledge of the phonetic radical in a delayed recall test. The current study suggests that the right lingual gyrus and the left inferior frontal gyrus are crucial for the learning of Chinese characters and the generalization of that knowledge to novel characters. Left inferior frontal gyrus is likely involved in phonological segmentation, whereas right lingual gyrus may subserve processing visual–orthographic information. PMID:20807053

Analysis of haptic information in the cerebral cortex

PubMed Central

2016-01-01

Haptic sensing of objects acquires information about a number of properties. This review summarizes current understanding about how these properties are processed in the cerebral cortex of macaques and humans. Nonnoxious somatosensory inputs, after initial processing in primary somatosensory cortex, are partially segregated into different pathways. A ventrally directed pathway carries information about surface texture into parietal opercular cortex and thence to medial occipital cortex. A dorsally directed pathway transmits information regarding the location of features on objects to the intraparietal sulcus and frontal eye fields. Shape processing occurs mainly in the intraparietal sulcus and lateral occipital complex, while orientation processing is distributed across primary somatosensory cortex, the parietal operculum, the anterior intraparietal sulcus, and a parieto-occipital region. For each of these properties, the respective areas outside primary somatosensory cortex also process corresponding visual information and are thus multisensory. Consistent with the distributed neural processing of haptic object properties, tactile spatial acuity depends on interaction between bottom-up tactile inputs and top-down attentional signals in a distributed neural network. Future work should clarify the roles of the various brain regions and how they interact at the network level. PMID:27440247

Material-dependent and material-independent selection processes in the frontal and parietal lobes: an event-related fMRI investigation of response competition

NASA Technical Reports Server (NTRS)

Hazeltine, Eliot; Bunge, Silvia A.; Scanlon, Michael D.; Gabrieli, John D E.

2003-01-01

The present study used the flanker task [Percept. Psychophys. 16 (1974) 143] to identify neural structures that support response selection processes, and to determine which of these structures respond differently depending on the type of stimulus material associated with the response. Participants performed two versions of the flanker task while undergoing event-related functional magnetic resonance imaging (fMRI). Both versions of the task required participants to respond to a central stimulus regardless of the responses associated with simultaneously presented flanking stimuli, but one used colored circle stimuli and the other used letter stimuli. Competition-related activation was identified by comparing Incongruent trials, in which the flanker stimuli indicated a different response than the central stimulus, to Neutral stimuli, in which the flanker stimuli indicated no response. A region within the right inferior frontal gyrus exhibited significantly more competition-related activation for the color stimuli, whereas regions within the middle frontal gyri of both hemispheres exhibited more competition-related activation for the letter stimuli. The border of the right middle frontal and inferior frontal gyri and the anterior cingulate cortex (ACC) were significantly activated by competition for both types of stimulus materials. Posterior foci demonstrated a similar pattern: left inferior parietal cortex showed greater competition-related activation for the letters, whereas right parietal cortex was significantly activated by competition for both materials. These findings indicate that the resolution of response competition invokes both material-dependent and material-independent processes.

Increased premotor cortex activation in high functioning autism during action observation.

PubMed

Perkins, Tom J; Bittar, Richard G; McGillivray, Jane A; Cox, Ivanna I; Stokes, Mark A

2015-04-01

The mirror neuron (MN) hypothesis of autism has received considerable attention, but to date has produced inconsistent findings. Using functional MRI, participants with high functioning autism or Asperger's syndrome were compared to typically developing individuals (n=12 in each group). Participants passively observed hand gestures that included waving, pointing, and grasping. Concerning the MN network, both groups activated similar regions including prefrontal, inferior parietal and superior temporal regions, with the autism group demonstrating significantly greater activation in the dorsal premotor cortex. Concerning other regions, participants with autism demonstrated increased activity in the anterior cingulate and medial frontal gyrus, and reduced activation in calcarine, cuneus, and middle temporal gyrus. These results suggest that during observation of hand gestures, frontal cortex activation is affected in autism, which we suggest may be linked to abnormal functioning of the MN system. Copyright © 2014 Elsevier Ltd. All rights reserved.

Localization of dysfunction in major depressive disorder: Prefrontal cortex and amygdala

PubMed Central

Murray, Elisabeth A.; Wise, Steven P.; Drevets, Wayne C.

2010-01-01

Despite considerable effort, the localization of dysfunction in major depressive disorder (MDD) remains poorly understood. We present a hypothesis about its localization that builds on recent findings from primate neuropsychology. The hypothesis has four key components: a deficit in the valuation of ‘self’ underlies the core disorder in MDD; the medial frontal cortex represents ‘self’; interactions between the amygdala and cortical representations update their valuation; and inefficiency in using positive feedback by orbital prefrontal cortex contributes to MDD. PMID:21111403

Task-dependent and distinct roles of the temporoparietal junction and inferior frontal cortex in the control of imitation.

PubMed

Hogeveen, Jeremy; Obhi, Sukhvinder S; Banissy, Michael J; Santiesteban, Idalmis; Press, Clare; Catmur, Caroline; Bird, Geoffrey

2015-07-01

The control of neurological networks supporting social cognition is crucially important for social interaction. In particular, the control of imitation is directly linked to interaction quality, with impairments associated with disorders characterized by social difficulties. Previous work suggests inferior frontal cortex (IFC) and the temporoparietal junction (TPJ) are involved in controlling imitation, but the functional roles of these areas remain unclear. Here, transcranial direct current stimulation (tDCS) was used to enhance cortical excitability at IFC and the TPJ prior to the completion of three tasks: (i) a naturalistic social interaction during which increased imitation is known to improve rapport, (ii) a choice reaction time task in which imitation needs to be inhibited for successful performance and (iii) a non-imitative control task. Relative to sham stimulation, stimulating IFC improved the context-dependent control of imitation-participants imitated more during the social interaction and less during the imitation inhibition task. In contrast, stimulating the TPJ reduced imitation in the inhibition task without affecting imitation during social interaction. Neither stimulation site affected the non-imitative control task. These data support a model in which IFC modulates imitation directly according to task demands, whereas TPJ controls task-appropriate shifts in attention toward representation of the self or the other, indirectly impacting upon imitation. © The Author (2014). Published by Oxford University Press.

Attention enhances multi-voxel representation of novel objects in frontal, parietal and visual cortices.

PubMed

Woolgar, Alexandra; Williams, Mark A; Rich, Anina N

2015-04-01

Selective attention is fundamental for human activity, but the details of its neural implementation remain elusive. One influential theory, the adaptive coding hypothesis (Duncan, 2001, An adaptive coding model of neural function in prefrontal cortex, Nature Reviews Neuroscience 2:820-829), proposes that single neurons in certain frontal and parietal regions dynamically adjust their responses to selectively encode relevant information. This selective representation may in turn support selective processing in more specialized brain regions such as the visual cortices. Here, we use multi-voxel decoding of functional magnetic resonance images to demonstrate selective representation of attended--and not distractor--objects in frontal, parietal, and visual cortices. In addition, we highlight a critical role for task demands in determining which brain regions exhibit selective coding. Strikingly, representation of attended objects in frontoparietal cortex was highest under conditions of high perceptual demand, when stimuli were hard to perceive and coding in early visual cortex was weak. Coding in early visual cortex varied as a function of attention and perceptual demand, while coding in higher visual areas was sensitive to the allocation of attention but robust to changes in perceptual difficulty. Consistent with high-profile reports, peripherally presented objects could also be decoded from activity at the occipital pole, a region which corresponds to the fovea. Our results emphasize the flexibility of frontoparietal and visual systems. They support the hypothesis that attention enhances the multi-voxel representation of information in the brain, and suggest that the engagement of this attentional mechanism depends critically on current task demands. Copyright © 2015 Elsevier Inc. All rights reserved.

Statistically based splicing detection reveals neural enrichment and tissue-specific induction of circular RNA during human fetal development.

PubMed

Szabo, Linda; Morey, Robert; Palpant, Nathan J; Wang, Peter L; Afari, Nastaran; Jiang, Chuan; Parast, Mana M; Murry, Charles E; Laurent, Louise C; Salzman, Julia

2015-06-16

The pervasive expression of circular RNA is a recently discovered feature of gene expression in highly diverged eukaryotes, but the functions of most circular RNAs are still unknown. Computational methods to discover and quantify circular RNA are essential. Moreover, discovering biological contexts where circular RNAs are regulated will shed light on potential functional roles they may play. We present a new algorithm that increases the sensitivity and specificity of circular RNA detection by discovering and quantifying circular and linear RNA splicing events at both annotated and un-annotated exon boundaries, including intergenic regions of the genome, with high statistical confidence. Unlike approaches that rely on read count and exon homology to determine confidence in prediction of circular RNA expression, our algorithm uses a statistical approach. Using our algorithm, we unveiled striking induction of general and tissue-specific circular RNAs, including in the heart and lung, during human fetal development. We discover regions of the human fetal brain, such as the frontal cortex, with marked enrichment for genes where circular RNA isoforms are dominant. The vast majority of circular RNA production occurs at major spliceosome splice sites; however, we find the first examples of developmentally induced circular RNAs processed by the minor spliceosome, and an enriched propensity of minor spliceosome donors to splice into circular RNA at un-annotated, rather than annotated, exons. Together, these results suggest a potentially significant role for circular RNA in human development.

Stimulus-response incompatibility activates cortex proximate to three eye fields

NASA Technical Reports Server (NTRS)

Merriam, E. P.; Colby, C. L.; Thulborn, K. R.; Luna, B.; Olson, C. R.; Sweeney, J. A.

2001-01-01

We used functional magnetic resonance imaging (fMRI) to investigate cortical activation during the performance of three oculomotor tasks that impose increasing levels of cognitive demand. (1) In a visually guided saccade (VGS) task, subjects made saccades to flashed targets. (2) In a compatible task, subjects made leftward and rightward saccades in response to foveal presentation of the uppercase words "LEFT" or "RIGHT." (3) In a mixed task, subjects made rightward saccades in response to the lowercase word "left" and leftward saccades in response to the lowercase word "right" on incompatible trials (60%). The remaining 40% of trials required compatible responses to uppercase words. The VGS and compatible tasks, when compared to fixation, activated the three cortical eye fields: the supplementary eye field (SEF), the frontal eye field (FEF), and the parietal eye field (PEF). The mixed task, when compared to the compatible task, activated three additional cortical regions proximate to the three eye fields: (1) rostral to the SEF in medial frontal cortex; (2) rostral to the FEF in dorsolateral prefrontal cortex (DLPFC); (3) rostral and lateral to the PEF in posterior parietal cortex. These areas may contribute to the suppression of prepotent responses and in holding novel visuomotor associations in working memory. Copyright 2001 Academic Press.

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.

Frontal alpha asymmetry predicts inhibitory processing in youth with attention deficit/hyperactivity disorder.

PubMed

Ellis, Alissa J; Kinzel, Chantelle; Salgari, Giulia C; Loo, Sandra K

2017-07-28

Atypical asymmetry in brain activity has been implicated in the behavioral and attentional dysregulation observed in ADHD. Specifically, asymmetry in neural activity in the right versus left frontal regions has been linked to ADHD, as well as to symptoms often associated with ADHD such as heightened approach behaviors, impulsivity and difficulties with inhibition. Clarifying the role of frontal asymmetry in ADHD-like traits, such as disinhibition, may provide information on the neurophysiological processes underlying these behaviors. ADHD youth (ADHD: n = 25) and healthy, typically developing controls (TD: n = 25) underwent an electroencephalography (EEG) recording while completing a go/no-go task-a commonly used test measuring behavioral inhibition. In addition, advanced signal processing for source localization estimated the location of signal generators underlying frontal alpha asymmetry (FA) during correct and incorrect trials. This is the first study in ADHD to demonstrate that the dorsal-lateral prefrontal cortex (DLPFC) may be responsible for generating frontal alpha. During failed inhibition trials, ADHD youth displayed greater FA than TD youth. In addition, within the ADHD group, frontal asymmetry during later processing stages (i.e., 400-800ms after stimulus) predicted a higher number of commission errors throughout the task. These results suggest that frontal alpha asymmetry may be a specific biomarker of cognitive disinhibition among youth with ADHD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Loss of Sleep Affects the Ultrastructure of Pyramidal Neurons in the Adolescent Mouse Frontal Cortex.

PubMed

de Vivo, Luisa; Nelson, Aaron B; Bellesi, Michele; Noguti, Juliana; Tononi, Giulio; Cirelli, Chiara

2016-04-01

The adolescent brain may be uniquely affected by acute sleep deprivation (ASD) and chronic sleep restriction (CSR), but direct evidence is lacking. We used electron microscopy to examine how ASD and CSR affect pyramidal neurons in the frontal cortex of adolescent mice, focusing on mitochondria, endosomes, and lysosomes that together perform most basic cellular functions, from nutrient intake to prevention of cellular stress. Adolescent (1-mo-old) mice slept (S) or were sleep deprived (ASD, with novel objects and running wheels) during the first 6-8 h of the light period, chronically sleep restricted (CSR) for > 4 days (using novel objects, running wheels, social interaction, forced locomotion, caffeinated water), or allowed to recover sleep (RS) for ∼32 h after CSR. Ultrastructural analysis of 350 pyramidal neurons was performed (S = 82; ASD = 86; CSR = 103; RS = 79; 4 to 5 mice/group). Several ultrastructural parameters differed in S versus ASD, S versus CSR, CSR versus RS, and S versus RS, although the different methods used to enforce wake may have contributed to some of the differences between short and long sleep loss. Differences included larger cytoplasmic area occupied by mitochondria in CSR versus S, and higher number of secondary lysosomes in CSR versus S and RS. We also found that sleep loss may unmask interindividual differences not obvious during baseline sleep. Moreover, using a combination of 11 ultrastructural parameters, we could predict in up to 80% of cases whether sleep or wake occurred at the single cell level. Ultrastructural analysis may be a powerful tool to identify which cellular organelles, and thus which cellular functions, are most affected by sleep and sleep loss. © 2016 Associated Professional Sleep Societies, LLC.

Transcranial Direct Current Stimulation of Frontal Cortex Decreases Performance on the WAIS-IV Intelligence Test

PubMed Central

Sellers, Kristin K.; Mellin, Juliann M.; Lustenberger, Caroline M.; Boyle, Michael R.; Lee, Won Hee; Peterchev, Angel V.; Frohlich, Flavio

2015-01-01

Transcranial direct current stimulation (tDCS) modulates excitability of motor cortex. However, there is conflicting evidence about the efficacy of this non-invasive brain stimulation modality to modulate performance on cognitive tasks. Previous work has tested the effect of tDCS on specific facets of cognition and executive processing. However, no randomized, double-blind, sham-controlled study has looked at the effects of tDCS on a comprehensive battery of cognitive processes. The objective of this study was to test if tDCS had an effect on performance on a comprehensive assay of cognitive processes, a standardized intelligence quotient (IQ) test. The study consisted of two substudies and followed a double-blind, between-subjects, sham-controlled design. In total, 41 healthy adult participants completed the Wechsler Adult Intelligence Scale, Fourth Edition (WAIS-IV) as a baseline measure. At least one week later, participants in substudy 1 received either bilateral tDCS (anodes over both F4 and F3, cathode over Cz, 2mA at each anode for 20 minutes) or active sham tDCS (2mA for 40 seconds), and participants in substudy 2 received either right or left tDCS (anode over either F4 or F3, cathode over Cz, 2mA for 20 minutes). In both studies, the WAIS-IV was immediately administered following stimulation to assess for performance differences induced by bilateral and unilateral tDCS. Compared to sham stimulation, right, left, and bilateral tDCS reduced improvement between sessions on Full Scale IQ and the Perceptual Reasoning Index. This demonstration that frontal tDCS selectively degraded improvement on specific metrics of the WAIS-IV raises important questions about the often proposed role of tDCS in cognitive enhancement. PMID:25934490

Dissociating frontal regions that co-lateralize with different ventral occipitotemporal regions during word processing☆

PubMed Central

Seghier, Mohamed L.; Price, Cathy J.

2013-01-01

The ventral occipitotemporal sulcus (vOT) sustains strong interactions with the inferior frontal cortex during word processing. Consequently, activation in both regions co-lateralize towards the same hemisphere in healthy subjects. Because the determinants of lateralisation differ across posterior, middle and anterior vOT subregions, we investigated whether lateralisation in different inferior frontal regions would co-vary with lateralisation in the three different vOT subregions. A whole brain analysis found that, during semantic decisions on written words, laterality covaried in (1) posterior vOT and the precentral gyrus; (2) middle vOT and the pars opercularis, pars triangularis, and supramarginal gyrus; and (3) anterior vOT and the pars orbitalis, middle frontal gyrus and thalamus. These findings increase the spatial resolution of our understanding of how vOT interacts with other brain areas during semantic categorisation on words. PMID:23728081

[The treatment principles of frontal sinus tract after the frontal approach craniotomy].

PubMed

Yu, Huanxin; Li, Haiyan; Liu, Gang

2015-12-01

To investigate the causes, clinical manifestation and treatment principles of frontal sinus tract after the frontal approach craniotomy. The clinic data of 13 patients with frontal skin sinus tract after the frontal approach craniotomy were retrospectively analyzed. All of them were described in the clinical record to have undergone frontal sinus mucosa pushing down or shaving and bone wax filling in the frontal sinus during the surgery, of whom 3 cases had history of frontal abscess incision drainage. All patients were performed endoscopic frontal sinus surgery and forehead skin sinus tract excision and suture. All of the patients successfully recovered after one-stage operation, and the frontal skin sinus tract was healed. The frontal approach craniotomy with postoperative frontal sinus tract was related with the improper use of bone wax tamponade and sealing of frontal sinus. The treatment principles were to remove bone wax, remove inflammatory granulation tissue around the sinus tract, and to open frontal sinus and promote frontal sinus drainage.

Distributed task coding throughout the multiple demand network of the human frontal-insular cortex.

PubMed

Stiers, Peter; Mennes, Maarten; Sunaert, Stefan

2010-08-01

The large variety of tasks that humans can perform is governed by a small number of key frontal-insular regions that are commonly active during task performance. Little is known about how this network distinguishes different tasks. We report on fMRI data in twelve participants while they performed four cognitive tasks. Of 20 commonly active frontal-insular regions in each hemisphere, five showed a BOLD response increase with increased task demands, regardless of the task. Although active in all tasks, each task invoked a unique response pattern across the voxels in each area that proved reliable in split-half multi-voxel correlation analysis. Consequently, voxels differed in their preference for one or more of the tasks. Voxel-based functional connectivity analyses revealed that same preference voxels distributed across all areas of the network constituted functional sub-networks that characterized the task being executed. Copyright 2010 Elsevier Inc. All rights reserved.

Methamphetamine Induces Anhedonic-Like Behavior and Impairs Frontal Cortical Energetics in Mice.

PubMed

Fonseca, Raquel; Carvalho, Rui A; Lemos, Cristina; Sequeira, Ana C; Pita, Inês R; Carvalho, Fábio; Silva, Carlos D; Prediger, Rui D S; Jarak, Ivana; Cunha, Rodrigo A; Fontes Ribeiro, Carlos A; Köfalvi, Attila; Pereira, Frederico C

2017-02-01

We recently showed that a single high dose of methamphetamine (METH) induces a persistent frontal cortical monoamine depletion that is accompanied by helpless-like behavior in mice. However, brain metabolic alterations underlying both neurochemical and mood alterations remain unknown. Herein, we aimed at characterizing frontal cortical metabolic alterations associated with early negative mood behavior triggered by METH. Adult C57BL/6 mice were injected with METH (30 mg/kg, i.p.), and their frontal cortical metabolic status was characterized after probing their mood and anxiety-related phenotypes 3 days postinjection. Methamphetamine induced depressive-like behavior, as indicated by the decreased grooming time in the splash test and by a transient decrease in sucrose preference. At this time, METH did not alter anxiety-like behavior or motor functions. Depolarization-induced glucose uptake was reduced in frontocortical slices from METH-treated mice compared to controls. Consistently, astrocytic glucose transporter (GluT1) density was lower in the METH group. A proton high rotation magic angle spinning (HRMAS) spectroscopic approach revealed that METH induced a significant decrease in N-acetyl aspartate (NAA) and glutamate levels, suggesting that METH decreased neuronal glutamatergic function in frontal cortex. We report, for the first time, that a single METH injection triggers early self-care and hedonic deficits and impairs frontal cortical energetics in mice. © 2016 John Wiley & Sons Ltd.

Deviance detection by a P3-like response in rat posterior parietal cortex

PubMed Central

Imada, Allicia; Morris, Allyn; Wiest, Michael C.

2013-01-01

To better understand sensory processing in frontal and parietal cortex of the rat, and to further assess the rat as a model of human frontal-parietal processing, we recorded local field potentials (LFPs) from microelectrode arrays implanted in medio-dorsal frontal, and posterior parietal cortex of awake rats as they were presented with a succession of frequent “standard” tones and infrequent “oddball” tones. Extending previous results from surface recordings we found, after controlling for the frequencies of the standard and oddball tones, that rat frontal and parietal-evoked LFPs (eLFPs) exhibit significantly larger N1 (~40 ms latency), P2 (~100 ms), N2 (~160 ms), P3E (~200–240 ms), and P3L (~300–500 ms) amplitudes after an oddball tone. These neural oddball effects could contribute to the automatic allocation of attention to rare stimuli. To determine whether these enhanced responses to rare stimuli could be accounted for in terms of stimulus-specific neural adaptation (SSA), we also recorded during single-tone control sessions involving frequent standard, or infrequent oddball beeps alone. We compared the difference between rare-tone and frequent-tone response amplitudes in the two-tone context (oddball effect) or single-tone context which isolates the contribution of SSA (SSA effect). An analysis of variance (ANOVA) revealed a significant main effect of tone context on rare-tone response enhancements, showing that the rare-tone enhancements were stronger in the two-tone context than the single-tone context. This difference between tone contexts was greatest at the early P3E peak (200–240 ms post-beep) in parietal cortex, suggesting true deviance detection by this evoked response component, which cannot be accounted for in terms of simple models of SSA. PMID:23316147

Thyroid Hormone Economy in the Perinatal Mouse Brain: Implications for Cerebral Cortex Development.

PubMed

Bárez-López, Soledad; Obregon, Maria Jesus; Bernal, Juan; Guadaño-Ferraz, Ana

2018-05-01

Thyroid hormones (THs, T4 and the transcriptionally active hormone T3) play an essential role in neurodevelopment; however, the mechanisms underlying T3 brain delivery during mice fetal development are not well known. This work has explored the sources of brain T3 during mice fetal development using biochemical, anatomical, and molecular approaches. The findings revealed that during late gestation, a large amount of fetal brain T4 is of maternal origin. Also, in the developing mouse brain, fetal T3 content is regulated through the conversion of T4 into T3 by type-2 deiodinase (D2) activity, which is present from earlier prenatal stages. Additionally, D2 activity was found to be essential to mediate expression of T3-dependent genes in the cerebral cortex, and also necessary to generate the transient cerebral cortex hyperthyroidism present in mice lacking the TH transporter Monocarboxylate transporter 8. Notably, the gene encoding for D2 (Dio2) was mainly expressed at the blood-cerebrospinal fluid barrier (BCSFB). Overall, these data signify that T4 deiodinated by D2 may be the only source of T3 during neocortical development. We therefore propose that D2 activity at the BCSFB converts the T4 transported across the choroid plexus into T3, thus supplying the brain with active hormone to maintain TH homeostasis.

Role of Frontal Alpha Oscillations in Creativity

PubMed Central

Lustenberger, Caroline; Boyle, Michael R.; Foulser, A. Alban; Mellin, Juliann M.; Fröhlich, Flavio

2015-01-01

Creativity, the ability to produce innovative ideas, is a key higher-order cognitive function that is poorly understood. At the level of macroscopic cortical network dynamics, recent EEG data suggests that cortical oscillations in the alpha frequency band (8 – 12 Hz) are correlated with creative thinking. However, whether alpha oscillations play a fundamental role in creativity has remained unknown. Here we show that creativity is increased by enhancing alpha power using 10 Hz transcranial alternating current stimulation (10Hz-tACS) of the frontal cortex. In a study of 20 healthy participants with a randomized, balanced cross-over design, we found a significant improvement of 7.4% in the Creativity Index measured by the Torrance Test of Creative Thinking, a comprehensive and most frequently used assay of creative potential and strengths. In a second similar study with 20 subjects, 40Hz-tACS was used in instead of 10Hz-tACS to rule out a general “electrical stimulation” effect. No significant change in the Creativity Index was found for such frontal gamma stimulation. Our results suggest that alpha activity in frontal brain areas is selectively involved in creativity; this enhancement represents the first demonstration of specific neuronal dynamics that drive creativity and can be modulated by non-invasive brain stimulation. Our findings agree with the model that alpha recruitment increases with internal processing demands and is involved in inhibitory top-down control, which is an important requirement for creative ideation. PMID:25913062

Modulation of the release of norepinephrine by gamma-aminobutyric acid and morphine in the frontal cerebral cortex of the rat

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

Peoples, R.W.

1989-01-01

Agents that enhance gamma-aminobutyric acid, or GABA, neurotransmission modulate certain effects of opioids, such as analgesia. Opioid analgesia is mediated in part by norepinephrine in the forebrain. In this study, the interactions between morphine and GABAergic agents on release of ({sup 3}H) norepinephrine from rat frontal cerebral cortical slices were examined. GABA, 5 {times} 10{sup {minus}5}-10{sup {minus}3} M, enhanced potassium stimulated ({sup 3}H) norepinephrine release and reversed the inhibitory effect of morphine in a noncompetitive manner. GABA did not enhance release of ({sup 3}H) norepinephrine stimulated by the calcium ionophore A23187. The effect of GABA was reduced by the GABA{submore » A} receptor antagonists bicuculline methiodide or picrotoxin, and by the selective inhibitor of GABA uptake SKF 89976A, but was blocked completely only when bicuculline methiodide and SKF 89976A were used in combination. The GABA{sub A} agonist muscimol, 10{sup {minus}4} M, mimicked the effect of GABA, but the GABA{sub B} agonist ({plus minus})baclofen, 10{sup {minus}4} M, did not affect the release of ({sup 3}H) norepinephrine in the absence or the presence of morphine. Thus GABA appears to produce this effect by stimulating GABA uptake and GABA{sub A}, but not GABA{sub B}, receptors. In contrast to the results that would be predicted for an event involving GABA{sub A} receptors, however, the effect of GABA did not desensitize, and benzodiazepine agonists did not enhance the effect of GABA at any concentration tested between 10{sup {minus}8} and 10{sup {minus}4} M. Thus these receptors may constitute a subclass of GABA{sub A} receptors. These results support a role of GABA uptake and GABA{sub A} receptors in enhancing the release of norepinephrine and modulating its inhibition by opioids in the frontal cortex of the rat.« less

Aging is associated with altered inflammatory, arachidonic acid cascade and synaptic markers, influenced by epigenetic modifications, in the human frontal cortex

PubMed Central

Keleshian, Vasken L.; Modi, Hiren R.; Rapoport, Stanley I.; Rao, Jagadeesh S.

2013-01-01

Aging is a risk factor for Alzheimer’s disease (AD) and is associated with cognitive decline. However, underlying molecular mechanisms of brain aging are not clear. Recent studies suggest epigenetic influences on gene expression in AD, since DNA methylation levels influence protein and mRNA expression in postmortem AD brain. We hypothesized that some of these changes occur with normal aging. To test this hypothesis, we measured markers of the arachidonic acid (AA) cascade, neuroinflammation, pro- and anti-apoptosis factors, and gene specific epigenetic modifications in postmortem frontal cortex from nine middle-aged (41 ± 1 (SEM) years) and ten aged subjects (70 ± 3 years). The aged compared with middle-aged brain showed elevated levels of neuroinflammatory and AA cascade markers, altered pro and anti-apoptosis factors and loss of synaptophysin. Some of these changes correlated with promoter hypermethylation of BDNF, CREB, and synaptophysin and hypomethylation of BAX. These molecular alterations in aging are different from or more subtle than changes associated with AD pathology. The degree to which they are related to changes in cognition or behavior during normal aging remains to be evaluated. PMID:23336521

The time course of ventrolateral prefrontal cortex involvement in memory formation.

PubMed

Machizawa, Maro G; Kalla, Roger; Walsh, Vincent; Otten, Leun J

2010-03-01

Human neuroimaging studies have implicated a number of brain regions in long-term memory formation. Foremost among these is ventrolateral prefrontal cortex. Here, we used double-pulse transcranial magnetic stimulation (TMS) to assess whether the contribution of this part of cortex is crucial for laying down new memories and, if so, to examine the time course of this process. Healthy adult volunteers performed an incidental encoding task (living/nonliving judgments) on sequences of words. In separate series, the task was performed either on its own or while TMS was applied to one of two sites of experimental interest (left/right anterior inferior frontal gyrus) or a control site (vertex). TMS pulses were delivered at 350, 750, or 1,150 ms following word onset. After a delay of 15 min, memory for the items was probed with a recognition memory test including confidence judgments. TMS to all three sites nonspecifically affected the speed and accuracy with which judgments were made during the encoding task. However, only TMS to prefrontal cortex affected later memory performance. Stimulation of left or right inferior frontal gyrus at all three time points reduced the likelihood that a word would later be recognized by a small, but significant, amount (approximately 4%). These findings indicate that bilateral ventrolateral prefrontal cortex plays an essential role in memory formation, exerting its influence between > or = 350 and 1,150 ms after an event is encountered.

Fatty acid composition of the postmortem prefrontal cortex of patients with schizophrenia, bipolar disorder, and major depressive disorder.

PubMed

Hamazaki, Kei; Maekawa, Motoko; Toyota, Tomoko; Dean, Brian; Hamazaki, Tomohito; Yoshikawa, Takeo

2015-06-30

Postmortem brain studies have shown abnormal levels of n-3 polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid, in the frontal cortex (particularly the orbitofrontal cortex) of patients with depression, schizophrenia, or bipolar disorder. However, the results from regions in the frontal cortex other than the orbitofrontal cortex are inconsistent. In this study we investigated whether patients with schizophrenia, bipolar disorder, or major depressive disorder have abnormalities in PUFA levels in the prefrontal cortex [Brodmann area (BA) 8]. In postmortem studies, fatty acids in the phospholipids of the prefrontal cortex (BA8) were evaluated by thin layer chromatography and gas chromatography. Specimens were evaluated for patients with schizophrenia (n=15), bipolar disorder (n=15), or major depressive disorder (n=15) and compared with unaffected controls (n=15). In contrast to previous studies, we found no significant differences in the levels of PUFAs or other fatty acids in the prefrontal cortex (BA8) between patients and controls. Subanalysis by sex also showed no significant differences. No significant differences were found in any individual fatty acids between suicide and non-suicide cases. These psychiatric disorders might be characterized by very specific fatty acid compositions in certain areas of the brain, and BA8 might not be involved in abnormalities of PUFA metabolism. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Frontal mucocele with intracranial extension causing frontal lobe syndrome.

PubMed

Weidmayer, Sara

2015-06-01

Mucoceles are mucus-containing cysts that form in paranasal sinuses; although mucoceles themselves are benign, this case report highlights the extensive damage they can cause as their expansion may lead to bony erosion and extension of the mucocele into the orbit and cranium; it also presents a rarely reported instance of frontal sinus mucocele leading to frontal lobe syndrome. A thorough discussion and review of mucoceles is included. A 68-year-old white man presented with intermittent diplopia and a pressure sensation in the right eye. He had a history of chronic sinusitis and had had endoscopic sinus surgery 5 years prior. A maxillofacial computed tomography scan revealed a large right frontal sinus mucocele, which had caused erosion along the medial wall of the right orbit and the outer and inner tables of the right frontal sinus. The mucocele had protruded both into the right orbit and intracranially, causing mass effect on the frontal lobe, which led to frontal lobe syndrome. The patient was successfully treated with endoscopic right ethmoidectomy, radial frontal sinusotomy, marsupialization of the mucocele, and transcutaneous irrigation. Paranasal sinus mucoceles may expand and lead to bony erosion and can become very invasive in surrounding structures such as the orbit and cranium. This case not only exhibits a very rare presentation of frontal sinus mucocele with intracranial extension and frontal lobe mass effect causing a frontal lobe syndrome but also demonstrates many of the ocular and visual complications commonly associated with paranasal sinus mucoceles. Early identification and surgical intervention is vital for preventing and reducing morbidity associated with invasive mucoceles, and the patient must be followed regularly to monitor for recurrence.

Inactivation of the prelimbic or infralimbic cortex impairs decision-making in the rat gambling task.

PubMed

Zeeb, Fiona D; Baarendse, P J J; Vanderschuren, L J M J; Winstanley, Catharine A

2015-12-01

Studies employing the Iowa Gambling Task (IGT) demonstrated that areas of the frontal cortex, including the ventromedial prefrontal cortex, orbitofrontal cortex (OFC), dorsolateral prefrontal cortex, and anterior cingulate cortex (ACC), are involved in the decision-making process. However, the precise role of these regions in maintaining optimal choice is not clear. We used the rat gambling task (rGT), a rodent analogue of the IGT, to determine whether inactivation of or altered dopamine signalling within discrete cortical sub-regions disrupts decision-making. Following training on the rGT, animals were implanted with guide cannulae aimed at the prelimbic (PrL) or infralimbic (IL) cortices, the OFC, or the ACC. Prior to testing, rats received an infusion of saline or a combination of baclofen and muscimol (0.125 μg of each/side) to inactivate the region and an infusion of a dopamine D2 receptor antagonist (0, 0.1, 0.3, and 1.0 μg/side). Rats tended to increase their choice of a disadvantageous option and decrease their choice of the optimal option following inactivation of either the IL or PrL cortex. In contrast, OFC or ACC inactivation did not affect decision-making. Infusion of a dopamine D2 receptor antagonist into any sub-region did not alter choice preference. Online activity of the IL or PrL cortex is important for maintaining an optimal decision-making strategy, but optimal performance on the rGT does not require frontal cortex dopamine D2 receptor activation. Additionally, these results demonstrate that the roles of different cortical regions in cost-benefit decision-making may be dissociated using the rGT.

Dissociating frontal regions that co-lateralize with different ventral occipitotemporal regions during word processing.

PubMed

Seghier, Mohamed L; Price, Cathy J

2013-08-01

The ventral occipitotemporal sulcus (vOT) sustains strong interactions with the inferior frontal cortex during word processing. Consequently, activation in both regions co-lateralize towards the same hemisphere in healthy subjects. Because the determinants of lateralisation differ across posterior, middle and anterior vOT subregions, we investigated whether lateralisation in different inferior frontal regions would co-vary with lateralisation in the three different vOT subregions. A whole brain analysis found that, during semantic decisions on written words, laterality covaried in (1) posterior vOT and the precentral gyrus; (2) middle vOT and the pars opercularis, pars triangularis, and supramarginal gyrus; and (3) anterior vOT and the pars orbitalis, middle frontal gyrus and thalamus. These findings increase the spatial resolution of our understanding of how vOT interacts with other brain areas during semantic categorisation on words. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Differential Gene Expression in the Nucleus Accumbens and Frontal Cortex of Lewis and Fischer 344 Rats Relevant to Drug Addiction

PubMed Central

Higuera-Matas, A; Montoya, G. L; Coria, S.M; Miguéns, M; García-Lecumberri, C; Ambrosio, E

2011-01-01

Drug addiction results from the interplay between social and biological factors. Among these, genetic variables play a major role. The use of genetically related inbred rat strains that differ in their preference for drugs of abuse is one approach of great importance to explore genetic determinants. Lewis and Fischer 344 rats have been extensively studied and it has been shown that the Lewis strain is especially vulnerable to the addictive properties of several drugs when compared with the Fischer 344 strain. Here, we have used microarrays to analyze gene expression profiles in the frontal cortex and nucleus accumbens of Lewis and Fischer 344 rats. Our results show that only a very limited group of genes were differentially expressed in Lewis rats when compared with the Fischer 344 strain. The genes that were induced in the Lewis strain were related to oxygen transport, neurotransmitter processing and fatty acid metabolism. On the contrary genes that were repressed in Lewis rats were involved in physiological functions such as drug and proton transport, oligodendrocyte survival and lipid catabolism. These data might be useful for the identification of genes which could be potential markers of the vulnerability to the addictive properties of drugs of abuse. PMID:21886580

Left inferior frontal cortex and syntax: function, structure and behaviour in patients with left hemisphere damage

PubMed Central

Marslen-Wilson, William D.; Randall, Billi; Wright, Paul; Devereux, Barry J.; Zhuang, Jie; Papoutsi, Marina; Stamatakis, Emmanuel A.

2011-01-01

For the past 150 years, neurobiological models of language have debated the role of key brain regions in language function. One consistently debated set of issues concern the role of the left inferior frontal gyrus in syntactic processing. Here we combine measures of functional activity, grey matter integrity and performance in patients with left hemisphere damage and healthy participants to ask whether the left inferior frontal gyrus is essential for syntactic processing. In a functional neuroimaging study, participants listened to spoken sentences that either contained a syntactically ambiguous or matched unambiguous phrase. Behavioural data on three tests of syntactic processing were subsequently collected. In controls, syntactic processing co-activated left hemisphere Brodmann areas 45/47 and posterior middle temporal gyrus. Activity in a left parietal cluster was sensitive to working memory demands in both patients and controls. Exploiting the variability in lesion location and performance in the patients, voxel-based correlational analyses showed that tissue integrity and neural activity—primarily in left Brodmann area 45 and posterior middle temporal gyrus—were correlated with preserved syntactic performance, but unlike the controls, patients were insensitive to syntactic preferences, reflecting their syntactic deficit. These results argue for the essential contribution of the left inferior frontal gyrus in syntactic analysis and highlight the functional relationship between left Brodmann area 45 and the left posterior middle temporal gyrus, suggesting that when this relationship breaks down, through damage to either region or to the connections between them, syntactic processing is impaired. On this view, the left inferior frontal gyrus may not itself be specialized for syntactic processing, but plays an essential role in the neural network that carries out syntactic computations. PMID:21278407

Perceived ownership impacts reward evaluation within medial-frontal cortex.

PubMed

Krigolson, Olave E; Hassall, Cameron D; Balcom, Lynsey; Turk, David

2013-06-01

Ownership is a powerful construct. Indeed, in a series of recent studies, perceived ownership has been shown to increase attentional capacity, facilitate a memorial advantage, and elicit positive attitudes. Here, we sought to determine whether self-relevance would bias reward evaluation systems within the brain. To accomplish this, we had participants complete a simple gambling task during which they could "win" or "lose" prizes for themselves or for someone else, while electroencephalographic data were recorded. Our results indicated that the amplitude of the feedback error-related negativity, a component of the event-related brain potential sensitive to reward evaluation, was diminished when participants were not gambling for themselves. Furthermore, our data suggest that the ownership cues that indicated who would win or lose a given gamble either were processed as a potential for an increase in utility (i.e., gain: self-gambles) or were processed in a nonutilitarian manner (other-gambles). Importantly, our results suggest that the medial-frontal reward system is sensitive to perceived ownership, to the extent that it may not process changes in utility when they are not directly relevant to self.

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

Inefficiency in Self-organized Attentional Switching in the Normal Aging Population is Associated with Decreased Activity in the Ventrolateral Prefrontal Cortex

PubMed Central

Hampshire, Adam; Gruszka, Aleksandra; Fallon, Sean J.; Owen, Adrian M.

2010-01-01

Studies of the aging brain have demonstrated that areas of the frontal cortex, along with their associated top–down executive control processes, are particularly prone to the neurodegenerative effects of age. Here, we investigate the effects of aging on brain and behavior using a novel task, which allows us to examine separate components of an individual's chosen strategy during routine problem solving. Our findings reveal that, contrary to previous suggestions of a specific decrease in cognitive flexibility, older participants show no increased level of perseveration to either the recently rewarded object or the recently relevant object category. In line with this lack of perseveration, lateral and medial regions of the orbito-frontal cortex, which are associated with inhibitory control and reward processing, appear to be functionally intact. Instead, a general loss of efficient problem-solving strategy is apparent with a concomitant decrease in neural activity in the ventrolateral prefrontal cortex and the posterior parietal cortex. The dorsolateral prefrontal cortex is also affected during problem solving, but age-related decline within this region appears to occur at a later stage. PMID:18345987

Functional Connectivity Bias in the Prefrontal Cortex of Psychopaths.

PubMed

Contreras-Rodríguez, Oren; Pujol, Jesus; Batalla, Iolanda; Harrison, Ben J; Soriano-Mas, Carles; Deus, Joan; López-Solà, Marina; Macià, Dídac; Pera, Vanessa; Hernández-Ribas, Rosa; Pifarré, Josep; Menchón, José M; Cardoner, Narcís

2015-11-01

Psychopathy is characterized by a distinctive interpersonal style that combines callous-unemotional traits with inflexible and antisocial behavior. Traditional emotion-based perspectives link emotional impairment mostly to alterations in amygdala-ventromedial frontal circuits. However, these models alone cannot explain why individuals with psychopathy can regularly benefit from emotional information when placed on their focus of attention and why they are more resistant to interference from nonaffective contextual cues. The present study aimed to identify abnormal or distinctive functional links between and within emotional and cognitive brain systems in the psychopathic brain to characterize further the neural bases of psychopathy. High-resolution anatomic magnetic resonance imaging with a functional sequence acquired in the resting state was used to assess 22 subjects with psychopathy and 22 control subjects. Anatomic and functional connectivity alterations were investigated first using a whole-brain analysis. Brain regions showing overlapping anatomic and functional changes were examined further using seed-based functional connectivity mapping. Subjects with psychopathy showed gray matter reduction involving prefrontal cortex, paralimbic, and limbic structures. Anatomic changes overlapped with areas showing increased degree of functional connectivity at the medial-dorsal frontal cortex. Subsequent functional seed-based connectivity mapping revealed a pattern of reduced functional connectivity of prefrontal areas with limbic-paralimbic structures and enhanced connectivity within the dorsal frontal lobe in subjects with psychopathy. Our results suggest that a weakened link between emotional and cognitive domains in the psychopathic brain may combine with enhanced functional connections within frontal executive areas. The identified functional alterations are discussed in the context of potential contributors to the inflexible behavior displayed by individuals with

Let's inhibit our excitement: the relationships between Stroop, behavioral disinhibition, and the frontal lobes.

PubMed

Heflin, Lara H; Laluz, Victor; Jang, Jung; Ketelle, Robin; Miller, Bruce L; Kramer, Joel H

2011-09-01

The Stroop (Stroop, 1935) is a frequently used neuropsychological test, with poor performance typically interpreted as indicative of disinhibition and frontal lobe damage. This study tested those interpretations by examining relationships between Stroop performance, behavioral disinhibition, and frontal lobe atrophy. Participants were 112 patients with mild cognitive impairment or dementia, recruited through UCSF's Memory and Aging Center. Participants received comprehensive dementia evaluations including structural MRI, neuropsychological testing, and informant interviews. Freesurfer, a semiautomated parcellation program, was used to analyze 1.5T MRI scans. Behavioral disinhibition was measured using the Neuropsychiatric Inventory (Cummings, 1997; Cummings et al., 1994) Disinhibition Scale. The sample (n = 112) mean age was 65.40 (SD = 8.60) years, education was 16.64 (SD = 2.54) years, and Mini-Mental State Examination (MMSE; Folstein et al., 1975) was 26.63 (SD = 3.32). Hierarchical linear regressions were used for data analysis. Controlling for age, MMSE, and color naming, Stroop performance was not significantly associated with disinhibition (β = 0.01, ΔR² = 0.01, p = .29). Hierarchical regressions controlling for age, MMSE, color naming, intracranial volume, and temporal and parietal lobes, examined whether left or right hemisphere regions predict Stroop performance. Bilaterally, parietal lobe atrophy best predicted poorer Stroop (left: β = 0.0004, ΔR² = 0.02, p = .002; right: β = 0.0004, ΔR² = 0.02, p = .002). Of frontal regions, only dorsolateral prefrontal cortex atrophy predicted poorer Stroop (β = 0.001, ΔR² = 0.01, p = .03); left and right anterior cingulate cortex atrophy predicted better Stroop (left: β = -0.003, ΔR² = 0.01, p = .02; right: β = -0.004, ΔR² = 0.01, p = .02). These findings suggest Stroop performance is a poor measure of behavioral disinhibition and frontal lobe atrophy even among a relatively high-risk population

Wada testing reveals frontal lateralization for the memorization of words and faces.

PubMed

Kelley, W M; Ojemann, J G; Wetzel, R D; Derdeyn, C P; Moran, C J; Cross, D T; Dowling, J L; Miller, J W; Petersen, S E

2002-01-01

Neuroimaging studies have suggested that specific regions of the frontal and medial temporal cortex are engaged during memory formation. Further, there is specialization across these regions such that verbal materials appear to preferentially engage the left regions while nonverbal materials primarily engage the right regions. An open question, however, has been to what extent frontal regions contribute to successful memory formation. The present study investigates this question using a reversible lesion technique known as the Wada test. Patients memorized words and unfamiliar faces while portions of their left and right hemispheres were temporarily anesthetized with sodium amytal. Subsequent memory tests revealed that faces were remembered better than words following left-hemisphere anesthesia, whereas words were remembered better than faces following right-hemisphere anesthesia. Importantly, inspection of the circulation affected by the amytal further suggests that these memory impairments did not result from direct anesthetization of the medial temporal regions. Taken in the context of the imaging findings, these results suggest that frontal regions may also contribute to memory formation in normal performance.

Prefrontal cortex volume reductions and tic inhibition are unrelated in uncomplicated GTS adults.

PubMed

Ganos, Christos; Kühn, Simone; Kahl, Ursula; Schunke, Odette; Brandt, Valerie; Bäumer, Tobias; Thomalla, Götz; Haggard, Patrick; Münchau, Alexander

2014-01-01

Tics in Gilles de la Tourette syndrome (GTS) are repetitive patterned movements, resembling spontaneous motor behaviour, but escaping voluntary control. Previous studies hypothesised relations between structural alterations in prefrontal cortex of GTS adults and tic severity using voxel-based morphometry (VBM), but could not demonstrate a significant association. The relation between prefrontal cortex structure and tic inhibition has not been investigated. Here, we used VBM to examine 14 GTS adults without associated comorbidities, and 15 healthy controls. We related structural alterations in GTS to clinical measures of tic severity and tic control. Grey matter volumes in the right inferior frontal gyrus and the left frontal pole were reduced in patients relative to healthy controls. These changes were not related to tic severity and tic inhibition. Prefrontal grey matter volume reductions in GTS adults are not related to state measures of tic phenomenology. © 2013.

Frontal Preparatory Neural Oscillations Associated with Cognitive Control: A Developmental Study Comparing Young Adults and Adolescents

PubMed Central

Hwang, Kai; Ghuman, Avniel S.; Manoach, Dara S.; Jones, Stephanie R.; Luna, Beatriz

2016-01-01

Functional magnetic resonance imaging (fMRI) studies suggest that age-related changes in the frontal cortex may underlie developmental improvements in cognitive control. In the present study we used magnetoencephalography (MEG) to identify frontal oscillatory neurodynamics that support age-related improvements in cognitive control during adolescence. We characterized the differences in neural oscillations in adolescents and adults during the preparation to suppress a prepotent saccade (antisaccade trials – AS) compared to preparing to generate a more automatic saccade (prosaccade trials – PS). We found that for adults, AS were associated with increased beta-band (16–38 Hz) power in the dorsal lateral prefrontal cortex (DLPFC), enhanced alpha- to low beta-band (10–18 Hz) power in the frontal eye field (FEF) that predicted performance, and increased cross-frequency alpha-beta (10–26 Hz) amplitude coupling between the DLPFC and the FEF. Developmental comparisons between adults and adolescents revealed similar engagement of DLPFC beta-band power but weaker FEF alpha-band power, and lower cross-frequency coupling between the DLPFC and the FEF in adolescents. These results suggest that lateral prefrontal neural activity associated with cognitive control is adult-like by adolescence; the development of cognitive control from adolescence to adulthood is instead associated with increases in prefrontal connectivity and strengthening of inhibition signaling for suppressing task-incompatible processes. PMID:27173759

Altered local spontaneous activity in frontal lobe epilepsy: a resting-state functional magnetic resonance imaging study.

PubMed

Dong, Li; Li, Hechun; He, Zhongqiong; Jiang, Sisi; Klugah-Brown, Benjamin; Chen, Lin; Wang, Pu; Tan, Song; Luo, Cheng; Yao, Dezhong

2016-11-01

The purpose of this study was to investigate the local spatiotemporal consistency of spontaneous brain activity in patients with frontal lobe epilepsy (FLE). Eyes closed resting-state functional magnetic resonance imaging (fMRI) data were collected from 19 FLE patients and 19 age- and gender-matched healthy controls. A novel measure, named FOur-dimensional (spatiotemporal) Consistency of local neural Activities (FOCA) was used to assess the spatiotemporal consistency of local spontaneous activity (emphasizing both local temporal homogeneity and regional stability of brain activity states). Then, two-sample t test was performed to detect the FOCA differences between two groups. Partial correlations between the FOCA values and durations of epilepsy were further analyzed. Compared with controls, FLE patients demonstrated increased FOCA in distant brain regions including the frontal and parietal cortices, as well as the basal ganglia. The decreased FOCA was located in the temporal cortex, posterior default model regions, and cerebellum. In addition, the FOCA measure was linked to the duration of epilepsy in basal ganglia. Our study suggested that alterations of local spontaneous activity in frontoparietal cortex and basal ganglia was associated with the pathophysiology of FLE; and the abnormality in frontal and default model regions might account for the potential cognitive impairment in FLE. We also presumed that the FOCA measure had potential to provide important insights into understanding epilepsy such as FLE.

Reduced frontal cortical thickness and increased caudate volume within fronto-striatal circuits in young adult smokers.

PubMed

Li, Yangding; Yuan, Kai; Cai, Chenxi; Feng, Dan; Yin, Junsen; Bi, Yanzhi; Shi, Sha; Yu, Dahua; Jin, Chenwang; von Deneen, Karen M; Qin, Wei; Tian, Jie

2015-06-01

Smoking during early adulthood results in neurophysiological and brain structural changes that may promote nicotine dependence later in life. Previous studies have revealed the important roles of fronto-striatal circuits in the pathology of nicotine dependence; however, few studies have focused on both cortical thickness and subcortical striatal volume differences between young adult smokers and nonsmokers. Twenty-seven young male adult smokers and 22 age-, education- and gender-matched nonsmokers were recruited in the present study. The cortical thickness and striatal volume differences of young adult smokers and age-matched nonsmokers were investigated in the present study and then correlated with pack-years and Fagerström Test for Nicotine Dependence (FTND). The following results were obtained: (1) young adult smokers showed significant cortical thinning in the frontal cortex (left caudal anterior cingulate cortex (ACC), right lateral orbitofrontal cortex (OFC)), left insula, left middle temporal gyrus, right inferior parietal lobule, and right parahippocampus; (2) in regards to subcortical striatal volume, the volume of the right caudate was larger in young adult smokers than nonsmokers; and (3) the cortical thickness of the right dorsolateral prefrontal cortex (DLPFC) and OFC were associated with nicotine dependence severity (FTND) and cumulative amount of nicotine intake (pack-years) in smokers, respectively. This study revealed reduced frontal cortical thickness and increased caudate volume in the fronto-striatal circuits in young adult smokers compared to nonsmokers. These deficits suggest an imbalance between cognitive control (reduced protection factors) and reward drive behaviours (increased risk factors) associated with nicotine addiction and relapse. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Interfering with the neural activity of mirror-related frontal areas impairs mentalistic inferences.

PubMed

Herbet, Guillaume; Lafargue, Gilles; Moritz-Gasser, Sylvie; Bonnetblanc, François; Duffau, Hugues

2015-07-01

According to recently proposed interactive dual-process theories, mentalizing abilities emerge from the coherent interaction between two physically distinct neural systems: (1) the mirror network, coding for the low-level embodied representations involved in pre-reflective sociocognitive processes and (2) the mentalizing network per se, which codes for higher level representations subtending the reflective attribution of psychological states. However, although the latest studies have shown that the core areas forming these two neurocognitive systems do indeed maintain effective connectivity during mentalizing, it is unclear whether an intact mirror system (and, more specifically, its anterior node, namely the posterior inferior frontal cortex) is a prerequisite for accurate mentalistic inferences. Intraoperative brain mapping via direct electrical stimulation offers a unique opportunity to address this issue. Electrical stimulation of the brain creates a "virtual" lesion, which provides functional information on well-defined parts of the cerebral cortex. In the present study, five patients were mapped in real time while they performed a mentalizing task. We found six responsive sites: four in the lateral part of the right pars opercularis and two in the dorsal part of the right pars triangularis. On the subcortical level, two additional sites were located within the white matter connectivity of the pars opercularis. Taken as a whole, our results suggest that the right inferior frontal cortex and its underlying axonal connectivity have a key role in mentalizing. Specifically, our findings support the hypothesis whereby transient, functional disruption of the mirror network influences higher order mentalistic inferences.

The frontal cortex and the criminal justice system.

PubMed

Sapolsky, Robert M

2004-11-29

In recent decades, the general trend in the criminal justice system in the USA has been to narrow the range of insanity defences available, with an increasing dependence solely on the M'Naghten rule. This states that innocence by reason of insanity requires that the perpetrator could not understand the nature of their criminal act, or did not know that the act was wrong, by reason of a mental illness. In this essay, I question the appropriateness of this, in light of contemporary neuroscience. Specifically, I focus on the role of the prefrontal cortex (PFC) in cognition, emotional regulation, control of impulsive behaviour and moral reasoning. I review the consequences of PFC damage on these endpoints, the capacity for factors such as alcohol and stress to transiently impair PFC function, and the remarkably late development of the PFC (in which full myelination may not occur until early adulthood). I also consider how individual variation in PFC function and anatomy, within the normative range, covaries with some of these endpoints. This literature is reviewed because of its relevance to issues of criminal insanity; specifically, damage can produce an individual capable of differentiating right from wrong but who, nonetheless, is organically incapable of appropriately regulating their behaviour.

Deep serotonergic and dopaminergic structures in fetal alcoholic syndrome: a study with nor-beta-CIT-single-photon emission computed tomography and magnetic resonance imaging volumetry.

PubMed

Riikonen, Raili S; Nokelainen, Pekka; Valkonen, Kirsi; Kolehmainen, Anni I; Kumpulainen, Kirsti I; Könönen, Mervi; Vanninen, Ritva-Liisa S; Kuikka, Jyrki T

2005-06-15

In prenatally alcohol exposed children, the relationship between brain structure and function is highlighted to be important to study. We studied 12 children with fetal alcoholic syndrome (FAS) and fetal alcoholic effects (FAE) by magnetic resonance imaging volumetry and by single-photon emission computed tomography with iodine-123 labeled 2beta-carbomethoxy-3beta-(4-iodophenyl) ([123I]nor-beta-CIT) and related these findings to those from neuropsychological and psychiatric tests. The absolute volumes of studied nuclei, including the brain volume, were significantly smaller in FAS/FAE children than in control patients. After normalization of volumes, significant differences were not found. Left hippocampus was smaller than the right (p<.003) but did not significantly differ from the control subjects. The children with FAS/FAE showed reduced serotonin (p=.02) in the medial frontal cortex and slightly increased striatal dopamine transporter binding. All FAS/FAE children had attention-deficit/hyperkinetic disorder (ADHD). None had depression. The internalization scores correlated with dopamine transporter binding (r=-.65; p=.03). The results indicate that the serotonin (5-HT) system may be vulnerable to the effects of ethanol in utero. The high dopamine transporter levels may correlate with the ADHD findings. Reduced serotonin and increased binding of dopamine transporter are also seen in type 2 alcoholism. Some behavioral problems of FAS/FAE might be preventable by early intervention and treatment.

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

PubMed

Jäncke, Lutz; Brunner, Béatrice; Esslen, Michaela

2008-07-16

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

Frontal lobe functioning during a simple response conflict task in first-episode psychosis and its relationship to treatment response.

PubMed

Shafritz, Keith M; Ikuta, Toshikazu; Greene, Allison; Robinson, Delbert G; Gallego, Juan; Lencz, Todd; DeRosse, Pamela; Kingsley, Peter B; Szeszko, Philip R

2018-05-09

Prior functional magnetic resonance imaging (fMRI) studies have investigated the neural mechanisms underlying cognitive control in patients with psychosis with findings of both hypo- and hyperfrontality. One factor that may contribute to inconsistent findings is the use of complex and polyfactorial tasks to investigate frontal lobe functioning. In the current study we employed a simple response conflict task during fMRI to examine differences in brain activation between patients experiencing their first-episode of psychosis (n = 33) and age- and sex-matched healthy volunteers (n = 33). We further investigated whether baseline brain activation among patients predicted changes in symptom severity and treatment response following 12 weeks of controlled antipsychotic treatment. During the task subjects were instructed to press a response button on the same side or opposite side of a circle that appeared on either side of a central fixation point. Imaging data revealed that for the contrast of opposite-side vs. same-side, patients showed significantly greater activation compared with healthy volunteers in the anterior cingulate cortex and intraparietal sulcus. Among patients, greater baseline anterior cingulate cortex, temporal-parietal junction, and superior temporal cortex activation predicted greater symptom reduction and therapeutic response following treatment. All findings remained significant after covarying for task performance. Intact performance on this relatively parsimonious task was associated with frontal hyperactivity suggesting the need for patients to utilize greater neural resources to achieve task performance comparable to healthy individuals. Moreover, frontal hyperactivity observed using a simple fMRI task may provide a biomarker for predicting treatment response in first-episode psychosis.

Frontal lobe neurology and the creative mind

PubMed Central

de Souza, Leonardo C.; Guimarães, Henrique C.; Teixeira, Antônio L.; Caramelli, Paulo; Levy, Richard; Dubois, Bruno; Volle, Emmanuelle

2014-01-01

Concepts from cognitive neuroscience strongly suggest that the prefrontal cortex (PFC) plays a crucial role in the cognitive functions necessary for creative thinking. Functional imaging studies have repeatedly demonstrated the involvement of PFC in creativity tasks. Patient studies have demonstrated that frontal damage due to focal lesions or neurodegenerative diseases are associated with impairments in various creativity tasks. However, against all odds, a series of clinical observations has reported the facilitation of artistic production in patients with neurodegenerative diseases affecting PFC, such as frontotemporal dementia (FTD). An exacerbation of creativity in frontal diseases would challenge neuroimaging findings in controls and patients, as well as the theoretical role of prefrontal functions in creativity processes. To explore this paradox, we reported the history of a FTD patient who exhibited the emergence of visual artistic productions during the course of the disease. The patient produced a large amount of drawings, which have been evaluated by a group of professional artists who were blind to the diagnosis. We also reviewed the published clinical cases reporting a change in the artistic abilities in patients with neurological diseases. We attempted to reconcile these clinical observations to previous experimental findings by addressing several questions raised by our review. For instance, to what extent can the cognitive, conative, and affective changes following frontal damage explain changes in artistic abilities? Does artistic exacerbation truly reflect increased creative capacities? These considerations could help to clarify the place of creativity—as it has been defined and explored by cognitive neuroscience—in artistic creation and may provide leads for future lesion studies. PMID:25101029

Frontal lobe neurology and the creative mind.

PubMed

de Souza, Leonardo C; Guimarães, Henrique C; Teixeira, Antônio L; Caramelli, Paulo; Levy, Richard; Dubois, Bruno; Volle, Emmanuelle

2014-01-01

Concepts from cognitive neuroscience strongly suggest that the prefrontal cortex (PFC) plays a crucial role in the cognitive functions necessary for creative thinking. Functional imaging studies have repeatedly demonstrated the involvement of PFC in creativity tasks. Patient studies have demonstrated that frontal damage due to focal lesions or neurodegenerative diseases are associated with impairments in various creativity tasks. However, against all odds, a series of clinical observations has reported the facilitation of artistic production in patients with neurodegenerative diseases affecting PFC, such as frontotemporal dementia (FTD). An exacerbation of creativity in frontal diseases would challenge neuroimaging findings in controls and patients, as well as the theoretical role of prefrontal functions in creativity processes. To explore this paradox, we reported the history of a FTD patient who exhibited the emergence of visual artistic productions during the course of the disease. The patient produced a large amount of drawings, which have been evaluated by a group of professional artists who were blind to the diagnosis. We also reviewed the published clinical cases reporting a change in the artistic abilities in patients with neurological diseases. We attempted to reconcile these clinical observations to previous experimental findings by addressing several questions raised by our review. For instance, to what extent can the cognitive, conative, and affective changes following frontal damage explain changes in artistic abilities? Does artistic exacerbation truly reflect increased creative capacities? These considerations could help to clarify the place of creativity-as it has been defined and explored by cognitive neuroscience-in artistic creation and may provide leads for future lesion studies.

Human cerebral organoids recapitulate gene expression programs of fetal neocortex development

PubMed Central

Camp, J. Gray; Badsha, Farhath; Florio, Marta; Kanton, Sabina; Gerber, Tobias; Wilsch-Bräuninger, Michaela; Lewitus, Eric; Sykes, Alex; Hevers, Wulf; Lancaster, Madeline; Knoblich, Juergen A.; Lachmann, Robert; Pääbo, Svante; Huttner, Wieland B.; Treutlein, Barbara

2015-01-01

Cerebral organoids—3D cultures of human cerebral tissue derived from pluripotent stem cells—have emerged as models of human cortical development. However, the extent to which in vitro organoid systems recapitulate neural progenitor cell proliferation and neuronal differentiation programs observed in vivo remains unclear. Here we use single-cell RNA sequencing (scRNA-seq) to dissect and compare cell composition and progenitor-to-neuron lineage relationships in human cerebral organoids and fetal neocortex. Covariation network analysis using the fetal neocortex data reveals known and previously unidentified interactions among genes central to neural progenitor proliferation and neuronal differentiation. In the organoid, we detect diverse progenitors and differentiated cell types of neuronal and mesenchymal lineages and identify cells that derived from regions resembling the fetal neocortex. We find that these organoid cortical cells use gene expression programs remarkably similar to those of the fetal tissue to organize into cerebral cortex-like regions. Our comparison of in vivo and in vitro cortical single-cell transcriptomes illuminates the genetic features underlying human cortical development that can be studied in organoid cultures. PMID:26644564

Postmenopausal frontal fibrosing alopecia: a frontal variant of lichen planopilaris.

PubMed

Kossard, S; Lee, M S; Wilkinson, B

1997-01-01

Lichen planopilaris usually produces multifocal areas of scarring alopecia. Recently, a condition in postmenopausal women characterized by progressive frontal hairline recession associated with scarring has been described. Our purpose was to study the clinical and histopathologic features and results of treatment in a group of women with the frontal variant of lichen planopilaris and to compare the immunohistochemical profile of scalp biopsy specimens from this subset with that found in the multifocal variant of lichen planopilaris. The clinical data as well as the histopathologic findings in 16 women with frontal fibrosing alopecia were collated. The immunohistochemical profile of six scalp biopsy specimens from the frontal hairline were compared with six specimens from women with multifocal lichen planopilaris. In addition to the progressive frontal fibrosing alopecia in all 16 women, total loss or a marked decrease of the eyebrows was observed in 13. No evidence of lichen planus was observed at other sites. In one patient multifocal areas of lichen planopilaris developed in the scalp. The frontal fibrosing alopecia was slowly progressive but has stabilized in five patients. Biopsy specimens from the frontal hairline showed histologic changes identical to lichen planopilaris. Immunophenotyping failed to reveal any significant differences between the frontal and multifocal variants. No effective treatments emerged although oral steroids and antimalarials may temporarily slow the course. Hormone replacement therapy did not appear to influence the course of the alopecia. Progressive frontal fibrosing alopecia is a clinically distinct variant of lichen planopilaris that affects in particular elderly women and frequently involves the eyebrows. The basis for this lichenoid tissue reaction targeting frontal scalp follicles and eyebrows is unknown.

Modeling ADHD-type arousal with unilateral frontal cortex damage in rats and beneficial effects of play therapy.

PubMed

Panksepp, Jaak; Burgdorf, Jeff; Turner, Cortney; Gordon, Nakia

2003-06-01

It has been recently shown that human adolescents with Attention Deficit/Hyperactivity Disorder (ADHD) have frontal lobe deficits, especially on the right sides of their brains (). ADHD is commonly treated with psychostimulants which may have adverse consequences. Hence, less invasive therapies need to be developed. In the present work, we tested the ability of right frontal lesions to induce hyperactivity in rats. We also evaluated the effects of chronic play therapy during early adolescence to reduce both hyperactivity and the elevated playfulness later in development. Play therapy was able to reduce both hyperactivity and excessive playfulness. In additional work, we found that access to rough-and-tumble play in normal animals could enhance subsequent behavioral indices of behavioral inhibition (i.e., freezing in response to a startle stimulus) that appeared to be independent of increased fearfulness and fatigue. Overall, these results suggest that (1) neonatal frontal lobe lesions can be used as an animal model of the overactivity in ADHD and (2) rough-and-tumble play therapy may be a new useful treatment for ADHD.

Lateral Prefrontal Cortex Mediates the Cognitive Modification of Attentional Bias

PubMed Central

Browning, Michael; Holmes, Emily A.; Murphy, Susannah E.; Goodwin, Guy M.; Harmer, Catherine J.

2010-01-01

Background A tendency to orient attention toward threatening stimuli may be involved in the etiology of anxiety disorders. In keeping with this, both psychological and pharmacological treatments of anxiety reduce this negative attentional bias. It has been hypothesized, but not proved, that psychological interventions may alter the function of prefrontal regions supervising the allocation of attentional resources. Methods The current study examined the effects of a cognitive training regime on attention. Participants were randomly assigned to one of two training conditions: “attend-threat” training, which increases negative attentional bias, or “avoid-threat” training, which reduces it. The behavioral effects of training were assessed using a sample of 24 healthy participants. Functional magnetic resonance imaging data were collected in a further 29 healthy volunteers using a protocol that allowed the influence of both stimuli valence and attention to be discriminated. Results Cognitive training induced the expected attentional biases in healthy volunteers. Further, the training altered lateral frontal activation to emotional stimuli, with these areas responding specifically to violations of the behavioral rules learned during training. Connectivity analysis confirmed that the identified lateral frontal regions were influencing attention as indexed by activity in visual association cortex. Conclusions Our results indicate that frontal control over the processing of emotional stimuli may be tuned by psychological interventions in a manner predicted to regulate levels of anxiety. This directly supports the proposal that psychological interventions may influence attention via an effect on the prefrontal cortex. PMID:20034617

Widespread heterogeneous neuronal loss across the cerebral cortex in Huntington's disease.

PubMed

Nana, Alissa L; Kim, Eric H; Thu, Doris C V; Oorschot, Dorothy E; Tippett, Lynette J; Hogg, Virginia M; Synek, Beth J; Roxburgh, Richard; Waldvogel, Henry J; Faull, Richard L M

2014-01-01

Huntington's disease is an autosomal dominant neurodegenerative disease characterized by neuronal degeneration in the basal ganglia and cerebral cortex, and a variable symptom profile. Although progressive striatal degeneration is known to occur and is related to symptom profile, little is known about the cellular basis of symptom heterogeneity across the entire cerebral cortex. To investigate this, we have undertaken a double blind study using unbiased stereological cell counting techniques to determine the pattern of cell loss in six representative cortical regions from the frontal, parietal, temporal, and occipital lobes in the brains of 14 Huntington's disease cases and 15 controls. The results clearly demonstrate a widespread loss of total neurons and pyramidal cells across all cortical regions studied, except for the primary visual cortex. Importantly, the results show that cell loss is remarkably variable both within and between Huntington's disease cases. The results also show that neuronal loss in the primary sensory and secondary visual cortices relate to Huntington's disease motor symptom profiles, and neuronal loss across the associational cortices in the frontal, parietal and temporal lobes is related to both Huntington's disease motor and to mood symptom profiles. This finding considerably extends a previous study (Thu et al., Brain, 2010; 133:1094-1110) which showed that neuronal loss in the primary motor cortex was related specifically to the motor symptom profiles while neuronal loss in the anterior cingulate cortex was related specifically to mood symptom profiles. The extent of cortical cell loss in the current study was generally related to the striatal neuropathological grade, but not to CAG repeat length on the HTT gene. Overall our findings show that Huntington's disease is characterized by a heterogeneous pattern of neuronal cell loss across the entire cerebrum which varies with symptom profile.

Dissociable Changes of Frontal and Parietal Cortices in Inherent Functional Flexibility across the Human Life Span.

PubMed

Yin, Dazhi; Liu, Wenjing; Zeljic, Kristina; Wang, Zhiwei; Lv, Qian; Fan, Mingxia; Cheng, Wenhong; Wang, Zheng

2016-09-28

Extensive evidence suggests that frontoparietal regions can dynamically update their pattern of functional connectivity, supporting cognitive control and adaptive implementation of task demands. However, it is largely unknown whether this flexibly functional reconfiguration is intrinsic and occurs even in the absence of overt tasks. Based on recent advances in dynamics of resting-state functional resonance imaging (fMRI), we propose a probabilistic framework in which dynamic reconfiguration of intrinsic functional connectivity between each brain region and others can be represented as a probability distribution. A complexity measurement (i.e., entropy) was used to quantify functional flexibility, which characterizes heterogeneous connectivity between a particular region and others over time. Following this framework, we identified both functionally flexible and specialized regions over the human life span (112 healthy subjects from 13 to 76 years old). Across brainwide regions, we found regions showing high flexibility mainly in the higher-order association cortex, such as the lateral prefrontal cortex (LPFC), lateral parietal cortex, and lateral temporal lobules. In contrast, visual, auditory, and sensory areas exhibited low flexibility. Furthermore, we observed that flexibility of the right LPFC improved during maturation and reduced due to normal aging, with the opposite occurring for the left lateral parietal cortex. Our findings reveal dissociable changes of frontal and parietal cortices over the life span in terms of inherent functional flexibility. This study not only provides a new framework to quantify the spatiotemporal behavior of spontaneous brain activity, but also sheds light on the organizational principle behind changes in brain function across the human life span. Recent neuroscientific research has demonstrated that the human capability of adaptive task control is primarily the result of the flexible operation of frontal brain networks. However

Insights in spatio-temporal characterization of human fetal neural stem cells.

PubMed

Martín-Ibáñez, Raquel; Guardia, Inés; Pardo, Mónica; Herranz, Cristina; Zietlow, Rike; Vinh, Ngoc-Nga; Rosser, Anne; Canals, Josep M

2017-05-01

Primary human fetal cells have been used in clinical trials of cell replacement therapy for the treatment of neurodegenerative disorders such as Huntington's disease (HD). However, human fetal primary cells are scarce and difficult to work with and so a renewable source of cells is sought. Human fetal neural stem cells (hfNSCs) can be generated from human fetal tissue, but little is known about the differences between hfNSCs obtained from different developmental stages and brain areas. In the present work we characterized hfNSCs, grown as neurospheres, obtained from three developmental stages: 4-5, 6-7 and 8-9weeks post conception (wpc) and four brain areas: forebrain, cortex, whole ganglionic eminence (WGE) and cerebellum. We observed that, as fetal brain development proceeds, the number of neural precursors is diminished and post-mitotic cells are increased. In turn, primary cells obtained from older embryos are more sensitive to the dissociation process, their viability is diminished and they present lower proliferation ratios compared to younger embryos. However, independently of the developmental stage of derivation proliferation ratios were very low in all cases. Improvements in the expansion rates were achieved by mechanical, instead of enzymatic, dissociation of neurospheres but not by changes in the seeding densities. Regardless of the developmental stage, neurosphere cultures presented large variability in the viability and proliferation rates during the initial 3-4 passages, but stabilized achieving significant expansion rates at passage 5 to 6. This was true also for all brain regions except cerebellar derived cultures that did not expand. Interestingly, the brain region of hfNSC derivation influences the expansion potential, being forebrain, cortex and WGE derived cells the most expandable compared to cerebellar. Short term expansion partially compromised the regional identity of cortical but not WGE cultures. Nevertheless, both expanded cultures were

The impact of different aetiologies on the cognitive performance of frontal patients

PubMed Central

Cipolotti, Lisa; Healy, Colm; Chan, Edgar; Bolsover, Fay; Lecce, Francesca; White, Mark; Spanò, Barbara; Shallice, Tim; Bozzali, Marco

2015-01-01

Neuropsychological group study methodology is considered one of the primary methods to further understanding of the organisation of frontal ‘executive’ functions. Typically, patients with frontal lesions caused by stroke or tumours have been grouped together to obtain sufficient power. However, it has been debated whether it is methodologically appropriate to group together patients with neurological lesions of different aetiologies. Despite this debate, very few studies have directly compared the performance of patients with different neurological aetiologies on neuropsychological measures. The few that did included patients with both anterior and posterior lesions. We present the first comprehensive retrospective comparison of the impact of lesions of different aetiologies on neuropsychological performance in a large number of patients whose lesion solely affects the frontal cortex. We investigated patients who had a cerebrovascular accident (CVA), high (HGT) or low grade (LGT) tumour, or meningioma, all at the post-operative stage. The same frontal ‘executive’ (Raven's Advanced Progressive Matrices, Stroop Colour-Word Test, Letter Fluency-S; Trail Making Test Part B) and nominal (Graded Naming Test) tasks were compared. Patients' performance was compared across aetiologies controlling for age and NART IQ scores. Assessments of focal frontal lesion location, lesion volume, global brain atrophy and non-specific white matter (WM) changes were undertaken and compared across the four aetiology. We found no significant difference in performance between the four aetiology subgroups on the ‘frontal’ executive and nominal tasks. However, we found strong effects of premorbid IQ on all cognitive tasks and robust effects of age only on the frontal tasks. We also compared specific aetiology subgroups directly, as previously reported in the literature. Overall we found no significant differences in the performance of CVA and tumour patients, or LGT and HGT

When anger leads to aggression: induction of relative left frontal cortical activity with transcranial direct current stimulation increases the anger–aggression relationship

PubMed Central

Hortensius, Ruud; Schutter, Dennis J. L. G.

2012-01-01

The relationship between anger and aggression is imperfect. Based on work on the neuroscience of anger, we predicted that anger associated with greater relative left frontal cortical activation would be more likely to result in aggression. To test this hypothesis, we combined transcranial direct current stimulation (tDCS) over the frontal cortex with interpersonal provocation. Participants received insulting feedback after 15 min of tDCS and were able to aggress by administering noise blasts to the insulting participant. Individuals who received tDCS to increase relative left frontal cortical activity behaved more aggressively when they were angry. No relation between anger and aggression was observed in the increase relative right frontal cortical activity or sham condition. These results concur with the motivational direction model of frontal asymmetry, in which left frontal activity is associated with anger. We propose that anger with approach motivational tendencies is more likely to result in aggression. PMID:21421731

Pediatric frontal mucocele secondary to a bifid frontal sinus septum.

PubMed

Plikaitis, Christina M; Purzycki, Adam R; Couture, Daniel; David, Lisa R

2010-09-01

A mucocele is a mucus-containing sac lined with epithelium that arises within a sinus when its drainage is compromised. The frontal sinus is the most common location, with frontal mucocele development occurring when the nasofrontal duct becomes obstructed because of polyps, bone tumors, prior surgery, sinusitis, trauma, or anatomic variation. We report an unusual case of a sterile pediatric frontal mucocele presenting as a slowly enlarging forehead mass due to a bifid frontal sinus septum. A 9-year-old girl presented to the craniofacial clinic for evaluation of a right frontal mass that had been slowly growing over the past year. She was otherwise healthy and had no history of previous trauma or sinus infections. Computed tomography (CT) scan results revealed a localized frontal fluid collection with protrusion and thinning of the anterior frontal bone between 2 midline bony septii. Surgical cranialization of the frontal sinus was performed. The anatomy of her lesion seen both on CT scan and intraoperatively likely explains this unusual case presentation. Instead of the usual inciting event of an intact frontal sinus drainage system becoming blocked, this patient seemed to have a primary developmental lack of any drainage system that led to her mucocele. During formation of her frontal sinus, she developed a bifid septum within the midline that excluded a portion of her frontal sinus from the lateral nasofrontal ducts. With mucus-producing epithelium trapped within these bony confines, pressure began to mount with expansion and thinning of the bone both anteriorly and posteriorly. The lack of any infectious symptoms and sterile culture results may support that this space developed primarily and was never in continuity with the external drainage system. Only 4 other patients have been reported with asymptomatic forehead swelling as the only presenting symptom, with the age ranging from 33 to 79 years. This patient represents the first clinical report of a congenital

New aids for the non-invasive prenatal diagnosis of achondroplasia: dysmorphic features, charts of fetal size and molecular confirmation using cell-free fetal DNA in maternal plasma.

PubMed

Chitty, L S; Griffin, D R; Meaney, C; Barrett, A; Khalil, A; Pajkrt, E; Cole, T J

2011-03-01

To improve the prenatal diagnosis of achondroplasia by constructing charts of fetal size, defining frequency of sonographic features and exploring the role of non-invasive molecular diagnosis based on cell-free fetal deoxyribonucleic acid (DNA) in maternal plasma. Data on fetuses with a confirmed diagnosis of achondroplasia were obtained from our databases, records reviewed, sonographic features and measurements determined and charts of fetal size constructed using the LMS (lambda-mu-sigma) method and compared with charts used in normal pregnancies. Cases referred to our regional genetics laboratory for molecular diagnosis using cell-free fetal DNA were identified and results reviewed. Twenty-six cases were scanned in our unit. Fetal size charts showed that femur length was usually on or below the 3(rd) centile by 25 weeks' gestation, and always below the 3(rd) by 30 weeks. Head circumference was above the 50(th) centile, increasing to above the 95(th) when compared with normal for the majority of fetuses. The abdominal circumference was also increased but to a lesser extent. Commonly reported sonographic features were bowing of the femora, frontal bossing, short fingers, a small chest and polyhydramnios. Analysis of cell-free fetal DNA in six pregnancies confirmed the presence of the c.1138G > A mutation in the FGRF3 gene in four cases with achondroplasia, but not the two subsequently found to be growth restricted. These data should improve the accuracy of diagnosis of achondroplasia based on sonographic findings, and have implications for targeted molecular confirmation that can reliably and safely be carried out using cell-free fetal DNA. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.

Neuronal basis of covert spatial attention in the frontal eye field.

PubMed

Thompson, Kirk G; Biscoe, Keri L; Sato, Takashi R

2005-10-12

The influential "premotor theory of attention" proposes that developing oculomotor commands mediate covert visual spatial attention. A likely source of this attentional bias is the frontal eye field (FEF), an area of the frontal cortex involved in converting visual information into saccade commands. We investigated the link between FEF activity and covert spatial attention by recording from FEF visual and saccade-related neurons in monkeys performing covert visual search tasks without eye movements. Here we show that the source of attention signals in the FEF is enhanced activity of visually responsive neurons. At the time attention is allocated to the visual search target, nonvisually responsive saccade-related movement neurons are inhibited. Therefore, in the FEF, spatial attention signals are independent of explicit saccade command signals. We propose that spatially selective activity in FEF visually responsive neurons corresponds to the mental spotlight of attention via modulation of ongoing visual processing.

Proteomic Analysis of Zika Virus Infected Primary Human Fetal Neural Progenitors Suggests a Role for Doublecortin in the Pathological Consequences of Infection in the Cortex.

PubMed

Jiang, Xuan; Dong, Xiao; Li, Shi-Hua; Zhou, Yue-Peng; Rayner, Simon; Xia, Hui-Min; Gao, George F; Yuan, Hui; Tang, Ya-Ping; Luo, Min-Hua

2018-01-01

Zika virus (ZIKV) infection is associated with severe neurological defects in fetuses and newborns, such as microcephaly. However, the underlying mechanisms remain to be elucidated. In this study, proteomic analysis on ZIKV-infected primary human fetal neural progenitor cells (NPCs) revealed that virus infection altered levels of cellular proteins involved in NPC proliferation, differentiation and migration. The transcriptional levels of some of the altered targets were also confirmed by qRT-PCR. Among the altered proteins, doublecortin (DCX) plays an important role in NPC differentiation and migration. Results showed that ZIKV infection downregulated DCX, at both mRNA and protein levels, as early as 1 day post infection (1 dpi), and lasted throughout the virus replication cycle (4 days). The downregulation of DCX was also observed in a ZIKV-infected fetal mouse brain model, which displayed decreased body weight, brain size and weight, as well as defective cortex structure. By screening the ten viral proteins of ZIKV, we found that both the expression of NS4A and NS5 were correlated with the downregulation of both mRNA and protein levels of DCX in NPCs. These data suggest that DCX is modulated following infection of the brain by ZIKV. How these observed changes of DCX expression translate in the pathological consequences of ZIKV infection and if other cellular proteins are equally involved remains to be investigated.

Frontal D2/3 Receptor Availability in Schizophrenia Patients Before and After Their First Antipsychotic Treatment: Relation to Cognitive Functions and Psychopathology.

PubMed

Nørbak-Emig, Henrik; Ebdrup, Bjørn H; Fagerlund, Birgitte; Svarer, Claus; Rasmussen, Hans; Friberg, Lars; Allerup, Peter N; Rostrup, Egill; Pinborg, Lars H; Glenthøj, Birte Y

2016-05-01

We have previously reported associations between frontal D2/3 receptor binding potential positive symptoms and cognitive deficits in antipsychotic-naïve schizophrenia patients. Here, we examined the effect of dopamine D2/3 receptor blockade on cognition. Additionally, we explored the relation between frontal D2/3 receptor availability and treatment effect on positive symptoms. Twenty-five antipsychotic-naïve first-episode schizophrenia patients were examined with the Positive and Negative Syndrome Scale, tested with the cognitive test battery Cambridge Neuropsychological Test Automated Battery, scanned with single-photon emission computerized tomography using the dopamine D2/3 receptor ligand [(123)I]epidepride, and scanned with MRI. After 3 months of treatment with either risperidone (n=13) or zuclopenthixol (n=9), 22 patients were reexamined. Blockade of extrastriatal dopamine D2/3 receptors was correlated with decreased attentional focus (r = -0.615, P=.003) and planning time (r = -0.436, P=.048). Moreover, baseline frontal dopamine D2/3 binding potential and positive symptom reduction correlated positively (D2/3 receptor binding potential left frontal cortex rho = 0.56, P=.003; D2/3 receptor binding potential right frontal cortex rho = 0.48, P=.016). Our data support the hypothesis of a negative influence of D2/3 receptor blockade on specific cognitive functions in schizophrenia. This is highly clinically relevant given the well-established association between severity of cognitive disturbances and a poor functional outcome in schizophrenia. Additionally, the findings support associations between frontal D2/3 receptor binding potential at baseline and the effect of antipsychotic treatment on positive symptoms. © The Author 2016. Published by Oxford University Press on behalf of CINP.

How can we explain the frontal presentation of insular lobe epilepsy? The impact of non-linear analysis of insular seizures.

PubMed

Hagiwara, Koichi; Jung, Julien; Bouet, Romain; Abdallah, Chifaou; Guénot, Marc; Garcia-Larrea, Luis; Mauguière, François; Rheims, Sylvain; Isnard, Jean

2017-05-01

For a decade it has been known that the insular lobe epilepsy can mimic frontal lobe epilepsy. We aimed to clarify the pattern of functional coupling occurring during the frontal presentation. We analyzed five insular lobe epilepsy patients. Frontal semiology was predominant for three of them, whereas insular semiology was predominant for the two others. We applied the non-linear regression analysis to stereoelectroencephalography-recorded seizures. A directed functional coupling index was calculated during clonic discharge periods that were accompanied either with frontal or insular semiology. We found significant functional coupling between the insula and mesial frontal/cingulate regions, with the former being a leader region for seizures propagation. Extra-insular regions showed significantly less or even no coupling with the mesial hemispheric regions. The three patients with frontal semiology showed strong couplings with the mesial frontal as well as cingulate regions, including the medial orbitofrontal cortex, pre-SMA/SMA, and the anterior to posterior cingulate. The two patients with the insular semiology only showed couplings between the insula and cingulate regions. The frontal semiology was expressed by strong functional couplings between the insula and mesial frontal regions. The insular origin of seizure should be considered in cryptogenic mesial frontal epilepsies. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Detection of basal acetylcholine release in the microdialysis of rat frontal cortex by high-performance liquid chromatography using a horseradish peroxidase-osmium redox polymer electrode with pre-enzyme reactor.

PubMed

Kato, T; Liu, J K; Yamamoto, K; Osborne, P G; Niwa, O

1996-06-28

To determine the basal acetylcholine level in the dialysate of rat frontal cortex, a horseradish peroxidase-osmium redox polymer-modified glassy carbon electrode (HRP-GCE) was employed instead of the conventional platinum electrode used in high-performance liquid chromatography-electrochemical detection (HPLC-ED). In initial experiments, an oxidizable unknown compound interfered with the detection of basal acetylcholine release on HPLC-HRP-GCE. An immobilized peroxidase-choline oxidase precolumn (pre-reactor) was included in the HPLC system, to eliminate the interference from the unknown compound. This combination could detect less than 10 fmol of standard acetylcholine and basal acetylcholine levels in the dialysate from a conventional concentric design microdialysis probe, without the use of cholinesterase inhibitor, and may facilitate physiological investigation of cholinergic neuronal activity in the central nervous system.

Mitochondrial dysfunction and lipid peroxidation in rat frontal cortex by chronic NMDA administration can be partially prevented by lithium treatment.

PubMed

Kim, Helena K; Isaacs-Trepanier, Cameron; Elmi, Nika; Rapoport, Stanley I; Andreazza, Ana C

2016-05-01

Chronic N-methyl-d-aspartate (NMDA) administration to rats may be a model to investigate excitotoxicity mediated by glutamatergic hyperactivity, and lithium has been reported to be neuroprotective. We hypothesized that glutamatergic hyperactivity in chronic NMDA injected rats would cause mitochondrial dysfunction and lipid peroxidation in the brain, and that chronic lithium treatment would ameliorate some of these NMDA-induced alterations. Rats treated with lithium for 6 weeks were injected i.p. 25 mg/kg NMDA on a daily basis for the last 21 days of lithium treatment. Brain was removed and frontal cortex was analyzed. Chronic NMDA decreased brain levels of mitochondrial complex I and III, and increased levels of the lipid oxidation products, 8-isoprostane and 4-hydroxynonenal, compared with non-NMDA injected rats. Lithium treatment prevented the NMDA-induced increments in 8-isoprostane and 4-hydroxynonenal. Our findings suggest that increased chronic activation of NMDA receptors can induce alterations in electron transport chain complexes I and III and in lipid peroxidation in brain. The NMDA-induced changes may contribute to glutamate-mediated excitotoxicity, which plays a role in brain diseases such as bipolar disorder. Lithium treatment prevented changes in 8-isoprostane and 4-hydroxynonenal, which may contribute to lithium's reported neuroprotective effect and efficacy in bipolar disorder. Copyright © 2016 Elsevier Ltd. All rights reserved.

Adolescent engagement in dangerous behaviors is associated with increased white matter maturity of frontal cortex.

PubMed

Berns, Gregory S; Moore, Sara; Capra, C Monica

2009-08-26

Myelination of white matter in the brain continues throughout adolescence and early adulthood. This cortical immaturity has been suggested as a potential cause of dangerous and impulsive behaviors in adolescence. We tested this hypothesis in a group of healthy adolescents, age 12-18 (N = 91), who underwent diffusion tensor imaging (DTI) to delineate cortical white matter tracts. As a measure of real-world risk taking, participants completed the Adolescent Risk Questionnaire (ARQ) which measures engagement in dangerous activities. After adjusting for age-related changes in both DTI and ARQ, engagement in dangerous behaviors was found to be positively correlated with fractional anisotropy and negatively correlated with transverse diffusivity in frontal white matter tracts, indicative of increased myelination and/or density of fibers (ages 14-18, N = 60). The direction of correlation suggests that rather than having immature cortices, adolescents who engage in dangerous activities have frontal white matter tracts that are more adult in form than their more conservative peers.

Frontal lobe damage impairs process and content in semantic memory: evidence from category-specific effects in progressive non-fluent aphasia.

PubMed

Reilly, Jamie; Rodriguez, Amy D; Peelle, Jonathan E; Grossman, Murray

2011-06-01

Portions of left inferior frontal cortex have been linked to semantic memory both in terms of the content of conceptual representation (e.g., motor aspects in an embodied semantics framework) and the cognitive processes used to access these representations (e.g., response selection). Progressive non-fluent aphasia (PNFA) is a neurodegenerative condition characterized by progressive atrophy of left inferior frontal cortex. PNFA can, therefore, provide a lesion model for examining the impact of frontal lobe damage on semantic processing and content. In the current study we examined picture naming in a cohort of PNFA patients across a variety of semantic categories. An embodied approach to semantic memory holds that sensorimotor features such as self-initiated action may assume differential importance for the representation of manufactured artifacts (e.g., naming hand tools). Embodiment theories might therefore predict that patients with frontal damage would be differentially impaired on manufactured artifacts relative to natural kinds, and this prediction was borne out. We also examined patterns of naming errors across a wide range of semantic categories and found that naming error distributions were heterogeneous. Although PNFA patients performed worse overall on naming manufactured artifacts, there was no reliable relationship between anomia and manipulability across semantic categories. These results add to a growing body of research arguing against a purely sensorimotor account of semantic memory, suggesting instead a more nuanced balance of process and content in how the brain represents conceptual knowledge. Copyright © 2010 Elsevier Srl. All rights reserved.

Accelerated aging-related transcriptome changes in the female prefrontal cortex

PubMed Central

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

2012-01-01

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

Longitudinal progression of frontal and temporal lobe changes in schizophrenia

PubMed Central

Cobia, Derin J.; Smith, Matthew J.; Wang, Lei; Csernansky, John G.

2012-01-01

Cortical abnormalities are considered a neurobiological characteristic of schizophrenia. However, the pattern of such deficits as they progress over the illness remains poorly understood. The goal of this project was to assess the progression of cortical thinning in frontal and temporal cortical regions in schizophrenia, and determine whether relationships exist between them and neuropsychological and clinical symptom profiles. As part of a larger longitudinal 2-year follow-up study, schizophrenia (n=20) and healthy participants (n=20) group-matched for age, gender, and recent-alcohol use, were selected. Using MRI, estimates of gray matter thickness were derived from primary anatomical gyri of the frontal and temporal lobes using surface-based algorithms. These values were entered into repeated-measures analysis of variance models to determine group status and time effects. Change values in cortical regions were correlated with changes in neuropsychological functioning and clinical symptomatology. Results revealed exaggerated cortical thinning of the middle frontal, superior temporal, and middle temporal gyri in schizophrenia participants. These thickness changes strongly influenced volumetric reductions, but were not related to shrinking surface area. Neuropsychological and clinical symptom profiles were stable in the schizophrenia participants despite these neuroanatomic changes. Overall it appears ongoing abnormalities in the cerebral cortex continue after initial onset of schizophrenia, particularly the lateral aspects of frontal and temporal regions, and do not relate to neuropsychological or clinical measures over time. Maintenance of neuropsychological performance and clinical stability in the face of changing neuroanatomical structure suggests the involvement of alternative compensatory mechanisms. PMID:22647883

Longitudinal progression of frontal and temporal lobe changes in schizophrenia.

PubMed

Cobia, Derin J; Smith, Matthew J; Wang, Lei; Csernansky, John G

2012-08-01

Cortical abnormalities are considered a neurobiological characteristic of schizophrenia. However, the pattern of such deficits as they progress over the illness remains poorly understood. The goal of this project was to assess the progression of cortical thinning in frontal and temporal cortical regions in schizophrenia, and determine whether relationships exist between them and neuropsychological and clinical symptom profiles. As part of a larger longitudinal 2-year follow-up study, schizophrenia (n=20) and healthy participants (n=20) group-matched for age, gender, and recent-alcohol use, were selected. Using MRI, estimates of gray matter thickness were derived from primary anatomical gyri of the frontal and temporal lobes using surface-based algorithms. These values were entered into repeated-measures analysis of variance models to determine group status and time effects. Change values in cortical regions were correlated with changes in neuropsychological functioning and clinical symptomatology. Results revealed exaggerated cortical thinning of the middle frontal, superior temporal, and middle temporal gyri in schizophrenia participants. These thickness changes strongly influenced volumetric reductions, but were not related to shrinking surface area. Neuropsychological and clinical symptom profiles were stable in the schizophrenia participants despite these neuroanatomic changes. Overall it appears that ongoing abnormalities in the cerebral cortex continue after initial onset of schizophrenia, particularly the lateral aspects of frontal and temporal regions, and do not relate to neuropsychological or clinical measures over time. Maintenance of neuropsychological performance and clinical stability in the face of changing neuroanatomical structure suggests the involvement of alternative compensatory mechanisms. Copyright © 2012 Elsevier B.V. All rights reserved.

Frontal Theta Links Prediction Errors to Behavioral Adaptation in Reinforcement Learning

PubMed Central

Cavanagh, James F.; Frank, Michael J.; Klein, Theresa J.; Allen, John J.B.

2009-01-01

Investigations into action monitoring have consistently detailed a fronto-central voltage deflection in the Event-Related Potential (ERP) following the presentation of negatively valenced feedback, sometimes termed the Feedback Related Negativity (FRN). The FRN has been proposed to reflect a neural response to prediction errors during reinforcement learning, yet the single trial relationship between neural activity and the quanta of expectation violation remains untested. Although ERP methods are not well suited to single trial analyses, the FRN has been associated with theta band oscillatory perturbations in the medial prefrontal cortex. Medio-frontal theta oscillations have been previously associated with expectation violation and behavioral adaptation and are well suited to single trial analysis. Here, we recorded EEG activity during a probabilistic reinforcement learning task and fit the performance data to an abstract computational model (Q-learning) for calculation of single-trial reward prediction errors. Single-trial theta oscillatory activities following feedback were investigated within the context of expectation (prediction error) and adaptation (subsequent reaction time change). Results indicate that interactive medial and lateral frontal theta activities reflect the degree of negative and positive reward prediction error in the service of behavioral adaptation. These different brain areas use prediction error calculations for different behavioral adaptations: with medial frontal theta reflecting the utilization of prediction errors for reaction time slowing (specifically following errors), but lateral frontal theta reflecting prediction errors leading to working memory-related reaction time speeding for the correct choice. PMID:19969093

Attenuated frontal and sensory inputs to the basal ganglia in cannabis users.

PubMed

Blanco-Hinojo, Laura; Pujol, Jesus; Harrison, Ben J; Macià, Dídac; Batalla, Albert; Nogué, Santiago; Torrens, Marta; Farré, Magí; Deus, Joan; Martín-Santos, Rocío

2017-07-01

Heavy cannabis use is associated with reduced motivation. The basal ganglia, central in the motivation system, have the brain's highest cannabinoid receptor density. The frontal lobe is functionally coupled to the basal ganglia via segregated frontal-subcortical circuits conveying information from internal, self-generated activity. The basal ganglia, however, receive additional influence from the sensory system to further modulate purposeful behaviors according to the context. We postulated that cannabis use would impact functional connectivity between the basal ganglia and both internal (frontal cortex) and external (sensory cortices) sources of influence. Resting-state functional connectivity was measured in 28 chronic cannabis users and 29 controls. Selected behavioral tests included reaction time, verbal fluency and exposition to affective pictures. Assessments were repeated after one month of abstinence. Cannabis exposure was associated with (1) attenuation of the positive correlation between the striatum and areas pertaining to the 'limbic' frontal-basal ganglia circuit, and (2) attenuation of the negative correlation between the striatum and the fusiform gyrus, which is critical in recognizing significant visual features. Connectivity alterations were associated with lower arousal in response to affective pictures. Functional connectivity changes had a tendency to normalize after abstinence. The results overall indicate that frontal and sensory inputs to the basal ganglia are attenuated after chronic exposure to cannabis. This effect is consistent with the common behavioral consequences of chronic cannabis use concerning diminished responsiveness to both internal and external motivation signals. Such an impairment of the fine-tuning in the motivation system notably reverts after abstinence. © 2016 Society for the Study of Addiction.

Gonadotropin-releasing hormone immunoreactivity in the adult and fetal human olfactory system.

PubMed

Kim, K H; Patel, L; Tobet, S A; King, J C; Rubin, B S; Stopa, E G

1999-05-01

Studies in fetal brain tissue of rodents, nonhuman primates and birds have demonstrated that cells containing gonadotropin-releasing hormone (GnRH) migrate from the olfactory placode across the nasal septum into the forebrain. The purpose of this study was to examine GnRH neurons in components of the adult and fetal human olfactory system. In the adult human brain (n=4), immunoreactive GnRH was evident within diffusely scattered cell bodies and processes in the olfactory bulb, olfactory nerve, olfactory cortex, and nervus terminalis located on the anterior surface of the gyrus rectus. GnRH-immunoreactive structures showed a similar distribution in 20-week human fetal brains (n=2), indicating that the migration of GnRH neurons is complete at this time. In 10-11-week fetal brains (n=2), more cells were noted in the nasal cavity than in the brain. Our data are consistent with observations made in other species, confirming olfactory derivation and migration of GnRH neurons into the brain from the olfactory placode. Copyright 1999 Elsevier Science B.V.

Frontal networks associated with command following after hemorrhagic stroke.

PubMed

Mikell, Charles B; Banks, Garrett P; Frey, Hans-Peter; Youngerman, Brett E; Nelp, Taylor B; Karas, Patrick J; Chan, Andrew K; Voss, Henning U; Connolly, E Sander; Claassen, Jan

2015-01-01

Level of consciousness is frequently assessed by command-following ability in the clinical setting. However, it is unclear what brain circuits are needed to follow commands. We sought to determine what networks differentiate command following from noncommand following patients after hemorrhagic stroke. Structural MRI, resting-state functional MRI, and electroencephalography were performed on 25 awake and unresponsive patients with acute intracerebral and subarachnoid hemorrhage. Structural injury was assessed via volumetric T1-weighted MRI analysis. Functional connectivity differences were analyzed against a template of standard resting-state networks. The default mode network (DMN) and the task-positive network were investigated using seed-based functional connectivity. Networks were interrogated by pairwise coherence of electroencephalograph leads in regions of interest defined by functional MRI. Functional imaging of unresponsive patients identified significant differences in 6 of 16 standard resting-state networks. Significant voxels were found in premotor cortex, dorsal anterior cingulate gyrus, and supplementary motor area. Direct interrogation of the DMN and task-positive network revealed loss of connectivity between the DMN and the orbitofrontal cortex and new connections between the task-positive network and DMN. Coherence between electrodes corresponding to right executive network and visual networks was also decreased in unresponsive patients. Resting-state functional MRI and electroencephalography coherence data support a model in which multiple, chiefly frontal networks are required for command following. Loss of DMN anticorrelation with task-positive network may reflect a loss of inhibitory control of the DMN by motor-executive regions. Frontal networks should thus be a target for future investigations into the mechanism of responsiveness in the intensive care unit environment. © 2014 American Heart Association, Inc.

Transcranial direct current stimulation (tDCS) of the inferior frontal cortex affects the "social scaling" of extrapersonal space depending on perspective-taking ability.

PubMed

Fini, Chiara; Bardi, Lara; Epifanio, Alessandra; Committeri, Giorgia; Moors, Agnes; Brass, Marcel

2017-03-01

When we have to judge the distance between another person and an object (social condition), we judge this distance as being smaller compared to judging the distance between two objects (nonsocial condition). It has been suggested that this compression is mediated by the attribution of a motor potential to the reference frame (other person vs. object). In order to explore the neural basis of this effect, we investigated whether the modulation of activity in the inferior frontal cortex (IFC) of the left hemisphere (recruited during visuospatial processes with a social component) changes the way we categorize space in a social compared with a nonsocial condition. We applied transcranial direct current stimulation to the left IFC, with different polarities (anodal, cathodal, and sham) while subjects performed an extrapersonal space categorization task. Interestingly, anodal stimulation of IFC induced an higher compression of space in the social compared to nonsocial condition. By contrast, cathodal stimulation induced the opposite effect. Furthermore, we found that this effect is modulated by interindividual differences in cognitive perspective taking. Our data support the idea that IFC is recruited during the social categorization of space.

Impaired Activation of Visual Attention Network for Motion Salience Is Accompanied by Reduced Functional Connectivity between Frontal Eye Fields and Visual Cortex in Strabismic Amblyopia

PubMed Central

Wang, Hao; Crewther, Sheila G.; Liang, Minglong; Laycock, Robin; Yu, Tao; Alexander, Bonnie; Crewther, David P.; Wang, Jian; Yin, Zhengqin

2017-01-01

Strabismic amblyopia is now acknowledged to be more than a simple loss of acuity and to involve alterations in visually driven attention, though whether this applies to both stimulus-driven and goal-directed attention has not been explored. Hence we investigated monocular threshold performance during a motion salience-driven attention task involving detection of a coherent dot motion target in one of four quadrants in adult controls and those with strabismic amblyopia. Psychophysical motion thresholds were impaired for the strabismic amblyopic eye, requiring longer inspection time and consequently slower target speed for detection compared to the fellow eye or control eyes. We compared fMRI activation and functional connectivity between four ROIs of the occipital-parieto-frontal visual attention network [primary visual cortex (V1), motion sensitive area V5, intraparietal sulcus (IPS) and frontal eye fields (FEF)], during a suprathreshold version of the motion-driven attention task, and also a simple goal-directed task, requiring voluntary saccades to targets randomly appearing along a horizontal line. Activation was compared when viewed monocularly by controls and the amblyopic and its fellow eye in strabismics. BOLD activation was weaker in IPS, FEF and V5 for both tasks when viewing through the amblyopic eye compared to viewing through the fellow eye or control participants' non-dominant eye. No difference in V1 activation was seen between the amblyopic and fellow eye, nor between the two eyes of control participants during the motion salience task, though V1 activation was significantly less through the amblyopic eye than through the fellow eye and control group non-dominant eye viewing during the voluntary saccade task. Functional correlations of ROIs within the attention network were impaired through the amblyopic eye during the motion salience task, whereas this was not the case during the voluntary saccade task. Specifically, FEF showed reduced functional

Top-down modulation from inferior frontal junction to FEFs and intraparietal sulcus during short-term memory for visual features.

PubMed

Sneve, Markus H; Magnussen, Svein; Alnæs, Dag; Endestad, Tor; D'Esposito, Mark

2013-11-01

Visual STM of simple features is achieved through interactions between retinotopic visual cortex and a set of frontal and parietal regions. In the present fMRI study, we investigated effective connectivity between central nodes in this network during the different task epochs of a modified delayed orientation discrimination task. Our univariate analyses demonstrate that the inferior frontal junction (IFJ) is preferentially involved in memory encoding, whereas activity in the putative FEFs and anterior intraparietal sulcus (aIPS) remains elevated throughout periods of memory maintenance. We have earlier reported, using the same task, that areas in visual cortex sustain information about task-relevant stimulus properties during delay intervals [Sneve, M. H., Alnæs, D., Endestad, T., Greenlee, M. W., & Magnussen, S. Visual short-term memory: Activity supporting encoding and maintenance in retinotopic visual cortex. Neuroimage, 63, 166-178, 2012]. To elucidate the temporal dynamics of the IFJ-FEF-aIPS-visual cortex network during memory operations, we estimated Granger causality effects between these regions with fMRI data representing memory encoding/maintenance as well as during memory retrieval. We also investigated a set of control conditions involving active processing of stimuli not associated with a memory task and passive viewing. In line with the developing understanding of IFJ as a region critical for control processes with a possible initiating role in visual STM operations, we observed influence from IFJ to FEF and aIPS during memory encoding. Furthermore, FEF predicted activity in a set of higher-order visual areas during memory retrieval, a finding consistent with its suggested role in top-down biasing of sensory cortex.

Dissociable Roles of Right Inferior Frontal Cortex and Anterior Insula in Inhibitory Control: Evidence from Intrinsic and Task-Related Functional Parcellation, Connectivity, and Response Profile Analyses across Multiple Datasets

PubMed Central

Ryali, Srikanth; Chen, Tianwen; Li, Chiang-Shan R.

2014-01-01

The right inferior frontal cortex (rIFC) and the right anterior insula (rAI) have been implicated consistently in inhibitory control, but their differential roles are poorly understood. Here we use multiple quantitative techniques to dissociate the functional organization and roles of the rAI and rIFC. We first conducted a meta-analysis of 70 published inhibitory control studies to generate a commonly activated right fronto-opercular cortex volume of interest (VOI). We then segmented this VOI using two types of features: (1) intrinsic brain activity; and (2) stop-signal task-evoked hemodynamic response profiles. In both cases, segmentation algorithms identified two stable and distinct clusters encompassing the rAI and rIFC. The rAI and rIFC clusters exhibited several distinct functional characteristics. First, the rAI showed stronger intrinsic and task-evoked functional connectivity with the anterior cingulate cortex, whereas the rIFC had stronger intrinsic and task-evoked functional connectivity with dorsomedial prefrontal and lateral fronto-parietal cortices. Second, the rAI showed greater activation than the rIFC during Unsuccessful, but not Successful, Stop trials, and multivoxel response profiles in the rAI, but not the rIFC, accurately differentiated between Successful and Unsuccessful Stop trials. Third, activation in the rIFC, but not rAI, predicted individual differences in inhibitory control abilities. Crucially, these findings were replicated in two independent cohorts of human participants. Together, our findings provide novel quantitative evidence for the dissociable roles of the rAI and rIFC in inhibitory control. We suggest that the rAI is particularly important for detecting behaviorally salient events, whereas the rIFC is more involved in implementing inhibitory control. PMID:25355218

Frontal headache induced by osteoma of frontal recess.

PubMed

Kim, Kyung Soo

2013-01-01

We reported a case of osteoma involving the frontal recess, which presented as frontal headache and reviewed literatures. Also, this case highlights that sinunasal osteomas can cause pain by local mass effects, referred pain, or prostaglandin E2-mediated mechanisms. © 2012 American Headache Society.

Parietal and superior frontal visuospatial maps activated by pointing and saccades

PubMed Central

Hagler, D.J.; Riecke, L.; Sereno, M.I.

2009-01-01

A recent study from our laboratory demonstrated that parietal cortex contains a map of visual space related to saccades and spatial attention and identified this area as the likely human homologue of the lateral intraparietal (LIP). A human homologue for the parietal reach region (PRR), thought to preferentially encode planned hand movements, has also been recently proposed. Both of these areas, originally identified in the macaque monkey, have been shown to encode space with eye-centered coordinates. Functional magnetic resonance imaging (fMRI) of humans was used to test the hypothesis that the putative human PRR contains a retinotopic map recruited by finger pointing but not saccades and to test more generally for differences in the visuospatial maps recruited by pointing and saccades. We identified multiple maps in both posterior parietal cortex and superior frontal cortex recruited for eye and hand movements, including maps not observed in previous mapping studies. Pointing and saccade maps were generally consistent within single subjects. We have developed new group analysis methods for phase-encoded data, which revealed subtle differences between pointing and saccades, including hemispheric asymmetries, but we did not find evidence of pointing-specific maps of visual space. PMID:17376706

Conceptual control across modalities: graded specialisation for pictures and words in inferior frontal and posterior temporal cortex.

PubMed

Krieger-Redwood, Katya; Teige, Catarina; Davey, James; Hymers, Mark; Jefferies, Elizabeth

2015-09-01

Controlled semantic retrieval to words elicits co-activation of inferior frontal (IFG) and left posterior temporal cortex (pMTG), but research has not yet established (i) the distinct contributions of these regions or (ii) whether the same processes are recruited for non-verbal stimuli. Words have relatively flexible meanings - as a consequence, identifying the context that links two specific words is relatively demanding. In contrast, pictures are richer stimuli and their precise meaning is better specified by their visible features - however, not all of these features will be relevant to uncovering a given association, tapping selection/inhibition processes. To explore potential differences across modalities, we took a commonly-used manipulation of controlled retrieval demands, namely the identification of weak vs. strong associations, and compared word and picture versions. There were 4 key findings: (1) Regions of interest (ROIs) in posterior IFG (BA44) showed graded effects of modality (e.g., words>pictures in left BA44; pictures>words in right BA44). (2) An equivalent response was observed in left mid-IFG (BA45) across modalities, consistent with the multimodal semantic control deficits that typically follow LIFG lesions. (3) The anterior IFG (BA47) ROI showed a stronger response to verbal than pictorial associations, potentially reflecting a role for this region in establishing a meaningful context that can be used to direct semantic retrieval. (4) The left pMTG ROI also responded to difficulty across modalities yet showed a stronger response overall to verbal stimuli, helping to reconcile two distinct literatures that have implicated this site in semantic control and lexical-semantic access respectively. We propose that left anterior IFG and pMTG work together to maintain a meaningful context that shapes ongoing semantic processing, and that this process is more strongly taxed by word than picture associations. Copyright © 2015 The Authors. Published by

Conceptual control across modalities: graded specialisation for pictures and words in inferior frontal and posterior temporal cortex

PubMed Central

Krieger-Redwood, Katya; Teige, Catarina; Davey, James; Hymers, Mark; Jefferies, Elizabeth

2015-01-01

Controlled semantic retrieval to words elicits co-activation of inferior frontal (IFG) and left posterior temporal cortex (pMTG), but research has not yet established (i) the distinct contributions of these regions or (ii) whether the same processes are recruited for non-verbal stimuli. Words have relatively flexible meanings – as a consequence, identifying the context that links two specific words is relatively demanding. In contrast, pictures are richer stimuli and their precise meaning is better specified by their visible features – however, not all of these features will be relevant to uncovering a given association, tapping selection/inhibition processes. To explore potential differences across modalities, we took a commonly-used manipulation of controlled retrieval demands, namely the identification of weak vs. strong associations, and compared word and picture versions. There were 4 key findings: (1) Regions of interest (ROIs) in posterior IFG (BA44) showed graded effects of modality (e.g., words>pictures in left BA44; pictures>words in right BA44). (2) An equivalent response was observed in left mid-IFG (BA45) across modalities, consistent with the multimodal semantic control deficits that typically follow LIFG lesions. (3) The anterior IFG (BA47) ROI showed a stronger response to verbal than pictorial associations, potentially reflecting a role for this region in establishing a meaningful context that can be used to direct semantic retrieval. (4) The left pMTG ROI also responded to difficulty across modalities yet showed a stronger response overall to verbal stimuli, helping to reconcile two distinct literatures that have implicated this site in semantic control and lexical-semantic access respectively. We propose that left anterior IFG and pMTG work together to maintain a meaningful context that shapes ongoing semantic processing, and that this process is more strongly taxed by word than picture associations. PMID:25726898

Transcranial direct current stimulation (tDCS) of frontal cortex decreases performance on the WAIS-IV intelligence test.

PubMed

Sellers, Kristin K; Mellin, Juliann M; Lustenberger, Caroline M; Boyle, Michael R; Lee, Won Hee; Peterchev, Angel V; Fröhlich, Flavio

2015-09-01

Transcranial direct current stimulation (tDCS) modulates excitability of motor cortex. However, there is conflicting evidence about the efficacy of this non-invasive brain stimulation modality to modulate performance on cognitive tasks. Previous work has tested the effect of tDCS on specific facets of cognition and executive processing. However, no randomized, double-blind, sham-controlled study has looked at the effects of tDCS on a comprehensive battery of cognitive processes. The objective of this study was to test if tDCS had an effect on performance on a comprehensive assay of cognitive processes, a standardized intelligence quotient (IQ) test. The study consisted of two substudies and followed a double-blind, between-subjects, sham-controlled design. In total, 41 healthy adult participants were included in the final analysis. These participants completed the Wechsler Adult Intelligence Scale, Fourth Edition (WAIS-IV) as a baseline measure. At least one week later, participants in substudy 1 received either bilateral tDCS (anodes over both F4 and F3, cathode over Cz, 2 mA at each anode for 20 min) or active sham tDCS (2 mA for 40 s), and participants in substudy 2 received either right or left tDCS (anode over either F4 or F3, cathode over Cz, 2 mA for 20 min). In both studies, the WAIS-IV was immediately administered following stimulation to assess for performance differences induced by bilateral and unilateral tDCS. Compared to sham stimulation, right, left, and bilateral tDCS reduced improvement between sessions on Full Scale IQ and the Perceptual Reasoning Index. This demonstration that frontal tDCS selectively degraded improvement on specific metrics of the WAIS-IV raises important questions about the often proposed role of tDCS in cognitive enhancement. Copyright © 2015 Elsevier B.V. All rights reserved.

Non-invasive Prefrontal/Frontal Brain Stimulation Is Not Effective in Modulating Food Reappraisal Abilities or Calorie Consumption in Obese Females

PubMed Central

Grundeis, Felicitas; Brand, Cristin; Kumar, Saurabh; Rullmann, Michael; Mehnert, Jan; Pleger, Burkhard

2017-01-01

Background/Objectives: Previous studies suggest that non-invasive transcranial direct current stimulation (tDCS) applied to the prefrontal cortex modulates food choices and calorie intake in obese humans. Participants/Methods: In the present fully randomized, placebo-controlled, within-subject and double-blinded study, we applied single sessions of anodal, cathodal, and sham tDCS to the left dorsolateral prefrontal cortex (DLPFC) and contralateral frontal operculum in 25 hungry obese women and investigated possible influences on food reappraisal abilities as well as calorie intake. We hypothesized that tDCS, (i) improves the ability to regulate the desire for visually presented foods and, (ii) reduces their consumption. Results: We could not confirm an effect of anodal or cathodal tDCS, neither on the ability to modulate the desire for visually presented foods, nor on calorie consumption. Conclusions: The present findings do not support the notion of prefrontal/frontal tDCS as a promising treatment option for obesity. PMID:28676735

Let's Inhibit Our Excitement: The Relationships Between Stroop, Behavioral Disinhibition, and the Frontal Lobes

PubMed Central

Heflin, Lara H.; Laluz, Victor; Jang, Jung; Ketelle, Robin; Miller, Bruce L.; Kramer, Joel H.

2011-01-01

Objective The Stroop is a frequently used neuropsychological test, with poor performance typically interpreted as indicative of disinhibition and frontal lobe damage. This study tested those interpretations by examining relationships between Stroop performance, behavioral disinhibition, and frontal lobe atrophy. Method Participants were 112 well-characterized patients with mild cognitive impairment or dementia, recruited through UCSF's Memory and Aging Center. Participants received comprehensive dementia evaluations including structural MRI, neuropsychological testing, and informant interviews. Freesurfer, a semi-automated parcellation program, was used to analyze 1.5T MRI scans. Behavioral disinhibition was measured using the Disinhibition scale of the Neuropsychiatric Inventory. The sample (n=112) mean age was 65.40 (SD=8.60) years, education was 16.64 (SD=2.54) years, and MMSE was 26.63 (SD=3.32). Hierarchical linear regressions were used for data analysis. Results Controlling for age, MMSE, and Color Naming performance, Stroop performance was not significantly associated with behavioral disinhibition (β=0.01, ΔR2=0.01, p=0.29). Hierarchical regressions controlling for age, MMSE, Color Naming, intracranial volume, and temporal and parietal lobes, examined whether left hemisphere or right hemisphere regions predict Interference speed. Bilaterally, parietal lobes were the brain region in which atrophy best predicted poorer Stroop (left: β=0.0004, ΔR2=0.02, p=0.002; right: β=0.0004, ΔR2=0.02, p=0.002). Of frontal regions, only dorsolateral prefrontal cortex atrophy predicted poorer Stroop (β=0.001, ΔR2=0.01, p=0.03); left and right anterior cingulate cortex (ACC) atrophy predicted better Stroop (left: β=−0.003, ΔR2=0.01, p=0.02; right: β=−0.004, ΔR2=0.01, p=0.02). Conclusions These findings suggest Stroop performance is a poor measure of behavioral disinhibition and frontal lobe atrophy even among a relatively high-risk population. PMID:21574716

Measurement of frontal lobe volume and thalamic volume in fetuses with congenital heart disease at different gestational weeks using three dimensional ultra sonography and its clinical value.

PubMed

Li-Fei, Zhu; Hong-Xiong, Liu; Ying, H E

2016-11-01

Our study aimed to investigate the measurement of frontal lobe volume and thalamic volume in fetuses with congenital heart disease (CHD) at different gestational weeks using three dimensional (3-D) ultrasonography and its clinical value. Then, 238 pregnant women who received obstetric ultrasonography in ultrasound department of Internal Medicine of our hospital were enrolled between March 2013 to April 2014. In this study, 85 fetuses were diagnosed to develop CHD by prenatal fetal echocardiography, and the other 153 fetuses were normal. Frontal lobe volume, thalamic volume and cerebral blood flow was determined by color Doppler ultrasonic diagnostic apparatus (type: GE Voluson E8). The level of MCA-PI and CPR in CHD fetus group performed significantly lower than that in normal fetus group (P<0.05), but the level of UA-PI performed significantly higher than that in normal fetus group (P<0.05). When gestational age <30 weeks, there was no significant difference in thalamic volume and frontal lobe volume between the two groups (P<0.05); when gestational age <30 weeks, the level of CHD fetus group performed significantly lower thalamic volume and frontal lobe volume than that in normal fetus group (P<0.05). When gestational age <30 weeks, there was no significant difference in BPD, HC, and GA between the two groups (P<0.05); when gestational age <30 weeks, the level of BPD, HC and GA in CHD fetus group performed significantly lower than that in normal fetus group (P<0.05). If gestational age <30 weeks, CHD performed a small impact on fetal frontal lobe volume and thalamic volume; if gestational age <30 weeks, the level of frontal lobe volume and thalamic volume in fetuses with CHD performed significantly lower than that in normal fetuses.

Functional role of frontal alpha oscillations in creativity.

PubMed

Lustenberger, Caroline; Boyle, Michael R; Foulser, A Alban; Mellin, Juliann M; Fröhlich, Flavio

2015-06-01

Creativity, the ability to produce innovative ideas, is a key higher-order cognitive function that is poorly understood. At the level of macroscopic cortical network dynamics, recent electroencephalography (EEG) data suggests that cortical oscillations in the alpha frequency band (8-12 Hz) are correlated with creative thinking. However, whether alpha oscillations play a functional role in creativity has remained unknown. Here we show that creativity is increased by enhancing alpha power using 10 Hz transcranial alternating current stimulation (10 Hz-tACS) of the frontal cortex. In a study of 20 healthy participants with a randomized, balanced cross-over design, we found a significant improvement of 7.4% in the Creativity Index measured by the Torrance Test of Creative Thinking (TTCT), a comprehensive and most frequently used assay of creative potential and strengths. In a second similar study with 20 subjects, 40 Hz-tACS was used instead of 10 Hz-tACS to rule out a general "electrical stimulation" effect. No significant change in the Creativity Index was found for such frontal 40 Hz stimulation. Our results suggest that alpha activity in frontal brain areas is selectively involved in creativity; this enhancement represents the first demonstration of specific neuronal dynamics that drive creativity and can be modulated by non-invasive brain stimulation. Our findings agree with the model that alpha recruitment increases with internal processing demands and is involved in inhibitory top-down control, which is an important requirement for creative ideation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Whole-brain MRI phenotyping in dysplasia-related frontal lobe epilepsy.

PubMed

Hong, Seok-Jun; Bernhardt, Boris C; Schrader, Dewi S; Bernasconi, Neda; Bernasconi, Andrea

2016-02-16

To perform whole-brain morphometry in patients with frontal lobe epilepsy and evaluate the utility of group-level patterns for individualized diagnosis and prognosis. We compared MRI-based cortical thickness and folding complexity between 2 frontal lobe epilepsy cohorts with histologically verified focal cortical dysplasia (FCD) (13 type I; 28 type II) and 41 closely matched controls. Pattern learning algorithms evaluated the utility of group-level findings to predict histologic FCD subtype, the side of the seizure focus, and postsurgical seizure outcome in single individuals. Relative to controls, FCD type I displayed multilobar cortical thinning that was most marked in ipsilateral frontal cortices. Conversely, type II showed thickening in temporal and postcentral cortices. Cortical folding also diverged, with increased complexity in prefrontal cortices in type I and decreases in type II. Group-level findings successfully guided automated FCD subtype classification (type I: 100%; type II: 96%), seizure focus lateralization (type I: 92%; type II: 86%), and outcome prediction (type I: 92%; type II: 82%). FCD subtypes relate to diverse whole-brain structural phenotypes. While cortical thickening in type II may indicate delayed pruning, a thin cortex in type I likely results from combined effects of seizure excitotoxicity and the primary malformation. Group-level patterns have a high translational value in guiding individualized diagnostics. © 2016 American Academy of Neurology.

Evolution of posterior parietal cortex and parietal-frontal networks for specific actions in primates.

PubMed

Kaas, Jon H; Stepniewska, Iwona

2016-02-15

Posterior parietal cortex (PPC) is an extensive region of the human brain that develops relatively late and is proportionally large compared with that of monkeys and prosimian primates. Our ongoing comparative studies have led to several conclusions about the evolution of this posterior parietal region. In early placental mammals, PPC likely was a small multisensory region much like PPC of extant rodents and tree shrews. In early primates, PPC likely resembled that of prosimian galagos, in which caudal PPC (PPCc) is visual and rostral PPC (PPCr) has eight or more multisensory domains where electrical stimulation evokes different complex motor behaviors, including reaching, hand-to-mouth, looking, protecting the face or body, and grasping. These evoked behaviors depend on connections with functionally matched domains in premotor cortex (PMC) and motor cortex (M1). Domains in each region compete with each other, and a serial arrangement of domains allows different factors to influence motor outcomes successively. Similar arrangements of domains have been retained in New and Old World monkeys, and humans appear to have at least some of these domains. The great expansion and prolonged development of PPC in humans suggest the addition of functionally distinct territories. We propose that, across primates, PMC and M1 domains are second and third levels in a number of parallel, interacting networks for mediating and selecting one type of action over others. © 2015 Wiley Periodicals, Inc.

Monkey cortex through fMRI glasses

PubMed Central

Vanduffel, Wim; Zhu, Qi; Orban, Guy A.

2015-01-01

In 1998 several groups reported the feasibility of functional magnetic resonance imaging (fMRI) experiments in monkeys, with the goal to bridge the gap between invasive nonhuman primate studies and human functional imaging. These studies yielded critical insights in the neuronal underpinnings of the BOLD signal. Furthermore, the technology has been successful in guiding electrophysiological recordings and identifying focal perturbation targets. Finally, invaluable information was obtained concerning human brain evolution. We here provide a comprehensive overview of awake monkey fMRI studies mainly confined to the visual system. We review the latest insights about the topographic organization of monkey visual cortex and discuss the spatial relationships between retinotopy and category and feature selective clusters. We briefly discuss the functional layout of parietal and frontal cortex and continue with a summary of some fascinating functional and effective connectivity studies. Finally, we review recent comparative fMRI experiments and speculate about the future of nonhuman primate imaging. PMID:25102559

Monkey cortex through fMRI glasses.

PubMed

Vanduffel, Wim; Zhu, Qi; Orban, Guy A

2014-08-06

In 1998 several groups reported the feasibility of fMRI experiments in monkeys, with the goal to bridge the gap between invasive nonhuman primate studies and human functional imaging. These studies yielded critical insights in the neuronal underpinnings of the BOLD signal. Furthermore, the technology has been successful in guiding electrophysiological recordings and identifying focal perturbation targets. Finally, invaluable information was obtained concerning human brain evolution. We here provide a comprehensive overview of awake monkey fMRI studies mainly confined to the visual system. We review the latest insights about the topographic organization of monkey visual cortex and discuss the spatial relationships between retinotopy and category- and feature-selective clusters. We briefly discuss the functional layout of parietal and frontal cortex and continue with a summary of some fascinating functional and effective connectivity studies. Finally, we review recent comparative fMRI experiments and speculate about the future of nonhuman primate imaging. Copyright © 2014 Elsevier Inc. All rights reserved.

Fetal Cortical Transplants in Adult Rats Subjected to Experimental Brain Injury

PubMed Central

Soares, Holly; McIntosh, Tracy K.

1991-01-01

Fetal cortical tissue was injected into injured adult rat brains following concussive fluid percussion (FP) brain injury. Rats subjected to moderate FP injury received E16 cortex transplant injections into lesioned motor cortex 2 days, 1 week, 2 weeks, and 4 weeks post injury. Histological assessment of transplant survival and integration was based upon Nissl staining, glial fibrillary acidic protein (GFAP) immunocytochemistry, and staining for acetylcholinesterase. In addition to histological analysis, the ability of the transplants to attenuate neurological motor deficits associated with concussive FP brain injury was also tested. Three subgroups of rats receiving transplant 1 week, 2 weeks, and 4 weeks post injury Were chosen for evaluation of neurological motor function. Fetal cortical tissue injected into the injury site 4 weeks post injury failed to incorporate with injured host brain, did not affect glial scar formation, and exhibited extensive GFAP immunoreactivity. No improvement in neurological motor function was observed in animals receiving transplants 4 weeks post injury. Conversely, transplants injected 2 days, 1 week, or 2 weeks post injury survived, incorporated with host brain, exhibited little GFAP immunoreactivity, and successfully attenuated glial scarring. However, no significant improvement in motor function was observed at the one week or two week time points. The inability of the transplants to attenuate motor function may indicate inappropriate host/transplant interaction. Our results demonstrate that there exists a temporal window in which fetal cortical transplants can attenuate glial scarring as well as be successfully incorporated into host brains following FP injury. PMID:1782253

Specializations for reward-guided decision-making in the primate ventral prefrontal cortex.

PubMed

Murray, Elisabeth A; Rudebeck, Peter H

2018-05-23

The estimated values of choices, and therefore decision-making based on those values, are influenced by both the chance that the chosen items or goods can be obtained (availability) and their current worth (desirability) as well as by the ability to link the estimated values to choices (a process sometimes called credit assignment). In primates, the prefrontal cortex (PFC) has been thought to contribute to each of these processes; however, causal relationships between particular subdivisions of the PFC and specific functions have been difficult to establish. Recent lesion-based research studies have defined the roles of two different parts of the primate PFC - the orbitofrontal cortex (OFC) and the ventral lateral frontal cortex (VLFC) - and their subdivisions in evaluating each of these factors and in mediating credit assignment during reward-based decision-making.

Interference effects of transcranial direct current stimulation over the right frontal cortex and adrenergic system on conditioned fear.

PubMed

Nasehi, Mohammad; Soltanpour, Reyhaneh; Ebrahimi-Ghiri, Mohaddeseh; Zarrabian, Shahram; Zarrindast, Mohammad-Reza

2017-11-01

The effects of pharmacological interventions on fear memory have widely been studied, but there are very few studies about the effects of brain electrical stimulation on fear memory function. Therefore, our aim was to determine whether anodal/cathodal transcranial direct current stimulation (tDCS) over the right frontal cortex would modify propranolol-induced contextual and auditory fear memory deficits, before or after training. The adult NMRI male mice were randomly assigned into three groups: the sham group, the anodal tDCS group, and the cathodal tDCS group. Fear memories were evaluated using a classical fear conditioning apparatus. While the anodal stimulation did not affect fear retrieval, post-training cathodal stimulation improved fear memory retrieval. Regardless of when propranolol (0.1 mg/kg) was administered, it impaired fear memory retrieval. However, when anodal stimulation and propranolol were applied prior to the training, contextual fear memory retrieval was increased and auditory fear memory was reversed. An enhanced contextual retrieval was also observed when propranolol was administered prior to the training and stimulation occurred after the training. Only when the stimulation occurred prior to the training and propranolol was administered after the training was there a selective improvement in contextual fear memory retrieval, leaving the auditory fear memory retrieval impaired. Interestingly, cathodal stimulation improved the effects of propranolol on auditory fear memory only when it occurred prior to the training. The results highlight possible improving effects for anodal/cathodal tDCS on propranolol-induced deficits on fear memories. The timing of the interventions related to the specific phases of memory formation is important in modulating fear behaviors.