Glenn, Andrea L.; Yang, Yaling; Raine, Adrian; Colletti, Patrick
Functional imaging studies of psychopathy have demonstrated reduced activity in the anterior cingulate, yet it is unclear whether this region is structurally impaired. In this study, we used structural MRI to examine whether volumetric differences exist in the anterior cingulate between psychopathic (n=24) and control (n=24) male participants. We found no group differences in the volume of the anterior cingulate or its dorsal and ventral subregions. Our findings call into question whether the anterior cingulate is impaired in psychopathy, or whether previous findings of reduced activity may result from reduced input from other deficient regions. PMID:20630717
Mirza, Yousha; Tang, Jennifer; Russell, Aileen; Banerjee, S. Preeya; Bhandari, Rashmi; Ivey, Jennifer; Rose, Michelle; Moore, Gregory J.; Rosenberg, David R.
Objective: To examine in vivo glutamatergic neurochemical alterations in the anterior cingulate cortex of children with major depressive disorder (MDD). Method: Single-voxel proton magnetic resonance spectroscopic ([.sup.1]H-MRS) examinations of the anterior cingulate cortex were conducted in 13 psychotropic-naive children and adolescents with MDD…
Nimchinsky, E. A.; Vogt, B. A.; Morrison, J. H.; Hof, P. R.; Bloom, F. E. (Principal Investigator)
The human anterior cingulate cortex is distinguished by the presence of an unusual cell type, a large spindle neuron in layer Vb. This cell has been noted numerous times in the historical literature but has not been studied with modern neuroanatomic techniques. For instance, details regarding the neuronal class to which these cells belong and regarding their precise distribution along both ventrodorsal and anteroposterior axes of the cingulate gyrus are still lacking. In the present study, morphological features and the anatomic distribution of this cell type were studied using computer-assisted mapping and immunocytochemical techniques. Spindle neurons are restricted to the subfields of the anterior cingulate cortex (Brodmann's area 24), exhibiting a greater density in anterior portions of this area than in posterior portions, and tapering off in the transition zone between anterior and posterior cingulate cortex. Furthermore, a majority of the spindle cells at any level is located in subarea 24b on the gyral surface. Immunocytochemical analysis revealed that the neurofilament protein triple was present in a large percentage of these neurons and that they did not contain calcium-binding proteins. Injections of the carbocyanine dye DiI into the cingulum bundle revealed that these cells are projection neurons. Finally, spindle cells were consistently affected in Alzheimer's disease cases, with an overall loss of about 60%. Taken together, these observations indicate that the spindle cells of the human cingulate cortex represent a morphological subpopulation of pyramidal neurons whose restricted distribution may be associated with functionally distinct areas.
Wang, Szu-Han; Tse, Dorothy; Morris, Richard G. M.
In humans and in animals, mental schemas can store information within an associative framework that enables rapid and efficient assimilation of new information. Using a hippocampal-dependent paired-associate task, we now report that the anterior cingulate cortex is part of a neocortical network of schema storage with NMDA receptor-mediated…
Mitchell, Rachel L C
The role of anterior cingulate cortex (ACC) in attention is a matter of debate. One hypothesis suggests that its role is to monitor response-level conflict, but explicit evidence is somewhat lacking. In this study, the activation of ACC was compared in (a) color and number standard Stroop tasks in which response preparation and interference shared modality (response-level conflict) and (b) color and number matching Stroop tasks in which response preparation and interference did not share modality (non-response-level conflict). In the congruent conditions, there was no effect of task type. In the interference conditions, anterior cingulate activity in the matching tasks was less than that in the standard tasks. These results support the hypothesis that ACC specifically mediates generalized modality-independent selection processes invoked by response competition.
Gallagher, Catherine L; Bell, Brian; Palotti, Matthew; Oh, Jen; Christian, Bradley T; Okonkwo, Ozioma; Sojkova, Jitka; Buyan-Dent, Laura; Nickles, Robert J; Harding, Sandra J; Stone, Charles K; Johnson, Sterling C; Holden, James E
Subtle cognitive and behavioral changes are common in early Parkinson's disease. The cause of these symptoms is probably multifactorial but may in part be related to extra-striatal dopamine levels. 6-[(18) F]-Fluoro-L-dopa (FDOPA) positron emission tomography has been widely used to quantify dopamine metabolism in the brain; the most frequently measured kinetic parameter is the tissue uptake rate constant, Ki. However, estimates of dopamine turnover, which also account for the small rate of FDOPA loss from areas of specific trapping, may be more sensitive than Ki for early disease-related changes in dopamine biosynthesis. The purpose of the present study was to compare effective distribution volume ratio (eDVR), a metric for dopamine turnover, to cognitive and behavioral measures in Parkinson's patients. We chose to focus the investigation on anterior cingulate cortex, which shows highest FDOPA uptake within frontal regions and has known roles in executive function. Fifteen non-demented early-stage PD patients were pretreated with carbidopa and tolcapone, a central catechol-O-methyl transferase (COMT) inhibitor, and then underwent extended imaging with FDOPA PET. Anterior cingulate eDVR was compared with composite scores for language, memory, and executive function measured by neuropsychological testing, and behavior change measured using two informant-based questionnaires, the Cambridge Behavioral Inventory and the Behavior Rating Inventory of Executive Function-Adult Version. Lower mean eDVR (thus higher dopamine turnover) in anterior cingulate cortex was related to lower (more impaired) behavior scores. We conclude that subtle changes in anterior cingulate dopamine metabolism may contribute to dysexecutive behaviors in Parkinson's disease.
Kireev, M V; Medvedev, N S; Korotkov, A D; Poliakov, Iu I; Anichkov, A D; Medvedev, S V
In the present article the features of the functional activity of the anterior cingulate cortex (ACC), a key element of neuroanatomical brain system of an error detection, in drug-resistant forms of obsessive-compulsive disorder (OCD) are discussed on a basis of both original and literature data. Available data indicate the presence of functional deficit in the ACC during OCD. This allows to suggest that functions of the ACC in OCD patient are partially redistributed between other brain areas. Thus in contrast to the previously accepted notion, the ACC as the target ofstereotactic surgery for OCD is pathologically altered brain region. Probably this is the reason why stereotactic destruction of ACC does not lead to significant changes in the patient's psyche. The essence of the pathological reorganisation of the functional activity of the brain in OCD remains unclear and requires further investigation.
Holroyd, Clay B; Yeung, Nick
Intense research interest over the past decade has yielded diverse and often discrepant theories about the function of anterior cingulate cortex (ACC). In particular, a dichotomy has emerged between neuropsychological theories suggesting a primary role for ACC in motivating or 'energizing' behavior, and neuroimaging-inspired theories emphasizing its contribution to cognitive control and reinforcement learning. To reconcile these views, we propose that ACC supports the selection and maintenance of 'options' - extended, context-specific sequences of behavior directed toward particular goals - that are learned through a process of hierarchical reinforcement learning. This theory accounts for ACC activity in relation to learning and control while simultaneously explaining the effects of ACC damage as disrupting the motivational context supporting the production of goal-directed action sequences.
Kolling, Nils; Wittmann, Marco K; Behrens, Tim E J; Boorman, Erie D; Mars, Rogier B; Rushworth, Matthew F S
Dorsal anterior cingulate cortex (dACC) carries a wealth of value-related information necessary for regulating behavioral flexibility and persistence. It signals error and reward events informing decisions about switching or staying with current behavior. During decision-making, it encodes the average value of exploring alternative choices (search value), even after controlling for response selection difficulty, and during learning, it encodes the degree to which internal models of the environment and current task must be updated. dACC value signals are derived in part from the history of recent reward integrated simultaneously over multiple time scales, thereby enabling comparison of experience over the recent and extended past. Such ACC signals may instigate attentionally demanding and difficult processes such as behavioral change via interactions with prefrontal cortex. However, the signal in dACC that instigates behavioral change need not itself be a conflict or difficulty signal.
Hillman, Kristin L; Bilkey, David K
In social environments, animals often compete to obtain limited resources. Strategically electing to work against another animal represents a cost-benefit decision. Is the resource worth an investment of competitive effort? The anterior cingulate cortex (ACC) has been implicated in cost-benefit decision-making, but its role in competitive effort has not been examined. We recorded ACC neurons in freely moving rats as they performed a competitive foraging choice task. When at least one of the two choice options demanded competitive effort, the majority of ACC neurons exhibited heightened and differential firing between the goal trajectories. Inter- and intrasession manipulations revealed that differential firing was not attributable to effort or reward in isolation; instead ACC encoding patterns appeared to indicate net utility assessments of available choice options. Our findings suggest that the ACC is important for encoding competitive effort, a cost-benefit domain that has received little neural-level investigation despite its predominance in nature.
Walton, Mark E; Mars, Rogier B
Previous research has identified the anterior cingulate cortex (ACC) as an important node in the neural network underlying decision making in primates. Decision making can, however, be studied under a large variety of circumstances, ranging from the standard well-controlled lab situation to more natural, stochastic settings, in which multiple agents interact. Here, we illustrate how these different varieties of decision making studied can influence theories ofACC function in monkeys. Converging evidence from unit recordings and lesion studies now suggest that the ACC is important for interpreting outcome information according to the current task context to guide future action selection. We then apply this framework to the study of human ACC function and discuss its potential implications.
Yang, Tony T.; Simmons, Alan N.; Matthews, Scott C.; Tapert, Susan F.; Frank, Guido K.; Bischoff-Grethe, Amanda; Lansing, Amy E.; Wu, Jing; Brown, Gregory G.; Paulus, Martin P.
Neuroimaging studies implicate the subgenual anterior cingulate cortex (sgACC) as a critical brain region in adult depression. However, unlike adult depression, little is known about the underlying neural substrates of adolescent depression, and there are no published data examining differences in sgACC activation between depressed and healthy adolescents. This study used functional magnetic resonance imaging to examine sgACC activity in twenty-six depressed and normal 13- to 17-year olds during the performance of a stop-signal task. Significantly greater sgACC activation was found in the depressed adolescents relative to controls. These results establish for the first time abnormal functioning of the sgACC in depressed adolescents and have important implications for understanding the underlying neural correlates and potential treatments of adolescent depression. PMID:19218875
Yang, Tony T.; Simmons, Alan N.; Matthews, Scott C.; Tapert, Susan F.; Frank, Guido K.; Bischoff-Grethe, Amanda; Lansing, Amy E.; Wu, Jing; Paulus, Martin P.
Recent adult studies suggest that the subgenual anterior cingulate cortex (sgACC) is involved in fundamental mental operations such as affective processing and inhibitory control. However, little is known about inhibition-associated sgACC function in adolescents, and there are no published data regarding whether personality characteristics are related to inhibition-associated sgACC brain activity in adolescents. This study examined the relationship between personality and inhibition-associated sgACC response in healthy adolescents. Seventeen adolescents of 13–17 years of age underwent functional magnetic resonance imaging while performing a parametric stop-signal task. Greater harm avoidance levels were significantly associated with increased inhibition-related sgACC activity. These results establish, for the first time, a link between personality and differential sgACC activation in adolescents. PMID:19034055
Winkelman, John W.; Plante, David T.; Schoerning, Laura; Benson, Kathleen; Buxton, Orfeu M.; O'Connor, Shawn P.; Jensen, J. Eric; Renshaw, Perry F.; Gonenc, Atilla
Background: Recent studies document alterations in cortical and subcortical volumes in patients with chronic primary insomnia (PI) in comparison with normal sleepers. We sought to confirm this observation in two previously studied PI cohorts. Methods: Two separate and independent groups of unmedicated patients who met Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition (DSM-IV) criteria for PI were compared with two separate, healthy control groups (Study 1: PI = 20, controls = 15; Study 2: PI = 21, controls = 20). Both studies included 2 weeks of sleep diaries supplemented by wrist actigraphy. The 3.0 T MRI-derived rostral anterior cingulate cortex (rACC) volumes were measured with FreeSurfer image analysis suite (version 5.0) and results normalized to total intracranial volume (ICV). Unpaired t-tests (two-tailed) were used to compare rACC volumes between groups. Post hoc correlations of rACC volumes to insomnia severity measures were performed (uncorrected for multiplicity). Results: Both studies demonstrated increases in normalized rACC volume in PI compared with control patients (Study 1: right side P = 0.05, left side P = 0.03; Study 2: right side P = 0.03, left side P = 0.02). In PI patients from Study 1, right rACC volume was correlated with sleep onset latency (SOL) by both diary (r = 0.51, P = 0.02) and actigraphy (r = 0.50, P = 0.03), and with sleep efficiency by actigraphy (r = -0.57, P = 0.01); left rACC volume was correlated with SOL by diary (r = 0.48, P = 0.04), and wake after sleep onset (WASO) (r = 0.49, P = 0.03) and sleep efficiency (r = -0.49, P = 0.03) by actigraphy. In Study 2, right rACC volume was correlated with SOL by diary (r = 0.44, P = 0.05) in PI patients. Conclusions: Rostral ACC volumes are larger in patients with PI compared with control patients. Clinical severity measures in PI correlate with rACC volumes. These data may reflect a compensatory brain response to chronic insomnia and may represent a marker of
De Ridder, Dirk; Joos, Kathleen; Vanneste, Sven
Tinnitus can be distressful, and tinnitus distress has been linked to increased beta oscillatory activity in the dorsal anterior cingulate cortex (dACC). The amount of distress is linked to alpha activity in the medial temporal lobe (amygdala and parahippocampal area), as well as the subgenual (sg)ACC and insula, and the functional connectivity between the parahippocampal area and the sgACC at 10 and 11.5 Hz. The authors describe 2 patients with very severely distressing intractable tinnitus who underwent transcranial magnetic stimulation (TMS) with a double-cone coil targeting the dACC and subsequent implantation of electrodes on the dACC. One of the patients responded to the implant and one did not, even though phenomenologically they both expressed the same tinnitus loudness and distress. The responder has remained dramatically improved for more than 2 years with 6-Hz burst stimulation of the dACC. The 2 patients differed in functional connectivity between the area of the implant and a tinnitus network consisting of the parahippocampal area as well as the sgACC and insula; that is, the responder had increased functional connectivity between these areas, whereas the nonresponder had decreased functional connectivity between these areas. Only the patient with increased functional connectivity linked to the target area of repetitive TMS or implantation might transmit the stimulation current to the entire tinnitus network and thus clinically improve.
Umemoto, Akina; HajiHosseini, Azadeh; Yates, Michael E; Holroyd, Clay B
The anterior cingulate cortex (ACC) is commonly associated with cognitive control and decision making, but its specific function is highly debated. To explore a recent theory that the ACC learns the reward values of task contexts (Holroyd & McClure in Psychological Review, 122, 54-83, 2015; Holroyd & Yeung in Trends in Cognitive Sciences, 16, 122-128, 2012), we recorded the event-related brain potentials (ERPs) from participants as they played a novel gambling task. The participants were first required to select from among three games in one "virtual casino," and subsequently they were required to select from among three different games in a different virtual casino; unbeknownst to them, the payoffs for the games were higher in one casino than in the other. Analysis of the reward positivity, an ERP component believed to reflect reward-related signals carried to the ACC by the midbrain dopamine system, revealed that the ACC is sensitive to differences in the reward values associated with both the casinos and the games inside the casinos, indicating that participants learned the values of the contexts in which rewards were delivered. These results highlight the importance of the ACC in learning the reward values of task contexts in order to guide action selection.
Lindgren, Lenita; Westling, Göran; Brulin, Christine; Lehtipalo, Stefan; Andersson, Micael; Nyberg, Lars
Touch massage (TM) is a form of pleasant touch stimulation used as treatment in clinical settings and found to improve well-being and decrease anxiety, stress, and pain. Emotional responses reported during and after TM have been studied, but the underlying mechanisms are still largely unexplored. In this study, we used functional magnetic resonance (fMRI) to test the hypothesis that the combination of human touch (i.e. skin-to-skin contact) with movement is eliciting a specific response in brain areas coding for pleasant sensations. The design included four different touch conditions; human touch with or without movement and rubber glove with or without movement. Force (2.5 N) and velocity (1.5 cm/s) were held constant across conditions. The pleasantness of the four different touch stimulations was rated on a visual analog scale (VAS-scale) and human touch was rated as most pleasant, particularly in combination with movement. The fMRI results revealed that TM stimulation most strongly activated the pregenual anterior cingulate cortex (pgACC). These results are consistent with findings showing pgACC activation during various rewarding pleasant stimulations. This area is also known to be activated by both opioid analgesia and placebo. Together with these prior results, our finding furthers the understanding of the basis for positive TM treatment effects.
Lu, Jing-Shan; Yue, Fang; Liu, Xiaoqing; Chen, Tao; Zhuo, Min
The anterior cingulate cortex (ACC) is a key brain region for the perception of pain and emotion. Cellular and molecular mechanisms of the ACC are usually investigated in rodents such as mice and rats. Studies of synaptic mechanisms in primates are limited. To facilitate the translation of basic results from rodents to humans, it is critical to use a primate-like animal model for the investigation of the ACC. The tree shrew presents a great opportunity for this as they have similar genome sequences to primates and are considered to have many similarities to primates. In the present study, by combining anatomy, immunostaining and micro-optical sectioning tomography methods, we examined the morphological properties of the ACC in the tree shrew and compared them with the mouse and rat. We found that the ACC in the tree shrew is significantly larger than those found in the mouse and rat. The sizes of cell bodies of ACC pyramidal cells in tree shrew are also larger than that found in the mouse or rat. Furthermore, there are significantly more apical/basal dendritic branches and apical dendritic spines of ACC pyramidal neurons in tree shrew. These results demonstrate that pyramidal cells of the ACC in tree shrews are more advanced than those found in rodents (mice and rats), indicating that the tree shrew can be used as a useful animal model for studying the cellular mechanism for ACC-related physiological and pathological changes in humans.
Shenhav, Amitai; Cohen, Jonathan D; Botvinick, Matthew M
Debates over the function(s) of dorsal anterior cingulate cortex (dACC) have persisted for decades. So too have demonstrations of the region's association with cognitive control. Researchers have struggled to account for this association and, simultaneously, dACC's involvement in phenomena related to evaluation and motivation. We describe a recent integrative theory that achieves this goal. It proposes that dACC serves to specify the currently optimal allocation of control by determining the overall expected value of control (EVC), thereby licensing the associated cognitive effort. The EVC theory accounts for dACC's sensitivity to a wide array of experimental variables, and their relationship to subsequent control adjustments. Finally, we contrast our theory with a recent theory proposing a primary role for dACC in foraging-like decisions. We describe why the EVC theory offers a more comprehensive and coherent account of dACC function, including dACC's particular involvement in decisions regarding foraging or otherwise altering one's behavior.
Mulert, C; Gallinat, J; Pascual-Marqui, R; Dorn, H; Frick, K; Schlattmann, P; Mientus, S; Herrmann, W M; Winterer, G
There is good evidence from neuroanatomic postmortem and functional imaging studies that dysfunction of the anterior cingulate cortex plays a prominent role in the pathophysiology of schizophrenia. So far, no electrophysiological localization study has been performed to investigate this deficit. We investigated 18 drug-free schizophrenic patients and 25 normal subjects with an auditory choice reaction task and measured event-related activity with 19 electrodes. Estimation of the current source density distribution in Talairach space was performed with low-resolution electromagnetic tomography (LORETA). In normals, we could differentiate between an early event-related potential peak of the N1 (90-100 ms) and a later N1 peak (120-130 ms). Subsequent current-density LORETA analysis in Talairach space showed increased activity in the auditory cortex area during the first N1 peak and increased activity in the anterior cingulate gyrus during the second N1 peak. No activation difference was observed in the auditory cortex between normals and patients with schizophrenia. However, schizophrenics showed significantly less anterior cingulate gyrus activation and slowed reaction times. Our results confirm previous findings of an electrical source in the anterior cingulate and an anterior cingulate dysfunction in schizophrenics. Our data also suggest that anterior cingulate function in schizophrenics is disturbed at a relatively early time point in the information-processing stream (100-140 ms poststimulus).
Woodward, Steven H.; Kuo, Janice R.; Schaer, Marie; Kaloupek, Danny G.; Eliez, Stephan
Objective Childhood and combat trauma have been observed to interact to influence amygdala volume in a sample of U.S. military veterans with and without PTSD. This interaction was assessed in a second, functionally-related fear system component, the pregenual and dorsal anterior cingulate cortex, using the same sample and modeling approach. Method Anterior cingulate cortical tissues (gray + white matter) were manually-delineated in 1.5 T MR images in 87 U.S. military veterans of the Vietnam and Persian Gulf wars. Hierarchical multiple regression modeling was used to assess associations between anterior cingulate volume and the following predictors, trauma prior to age 13, combat exposure, the interaction of early trauma and combat exposure, and PTSD diagnosis. Results As previously observed in the amygdala, unique variance in anterior cingulate cortical volume was associated with both the diagnosis of PTSD and with the interaction of childhood and combat trauma. The pattern of the latter interaction indicated that veterans with childhood trauma exhibited a significant inverse linear relationship between combat trauma and anterior cingulate volume while those without childhood trauma did not. Such associations were not observed in hippocampal or total cerebral tissue volumes. Conclusions In the dorsal anterior cingulate cortex, as in the amygdala, early trauma may confer excess sensitivity to later combat trauma. PMID:24179818
Critchley, Hugo D.
There is now a wealth of evidence that anterior insular and anterior cingulate cortices have a close functional relationship, such that they may be considered together as input and output regions of a functional system. This system is typically engaged across cognitive, affective, and behavioural contexts, suggesting that it is of fundamental importance for mental life. Here, we review the literature and reinforce the case that these brain regions are crucial, firstly, for the production of subjective feelings and, secondly, for co-ordinating appropriate responses to internal and external events. This model seeks to integrate higher-order cortical functions with sensory representation and autonomic control: it is argued that feeling states emerge from the raw data of sensory (including interoceptive) inputs and are integrated through representations in conscious awareness. Correspondingly, autonomic nervous system reactivity is particularly important amongst the responses that accompany conscious experiences. Potential clinical implications are also discussed. PMID:20512367
Chavanon, Mira-Lynn; Wacker, Jan; Stemmler, Gerhard
Recent research using the resting electroencephalogram (EEG) showed that posterior versus anterior theta activity (around 4-8 Hz) is consistently associated with agency, reflecting the dopaminergic core of extraversion (i.e., incentive motivation, positive emotion). Neuroimaging studies using various methodologies and experimental paradigms have converged on the anterior cingulate cortex (ACC) as a neurophysiological correlate of extraversion. The aim of the present study is integrate these lines of research by testing the hypothesis that posterior versus anterior EEG theta is at least partly based on ACC theta activity. Resting EEG data were analyzed in N = 78 healthy, male participants extremely high or low in agentic extraversion (aE). Using the low-resolution electromagnetic tomography algorithm, we localized the sources of aE-dependent intracerebral theta activity within rostral subdivisions of the ACC. The posterior versus anterior index and theta current density within the rostral ACC were significantly correlated (r = -.52), and both displayed high retest stability across 5 hr and were associated with traits from the aE spectrum. These neurophysiological correlates of aE and their possible functional significance are discussed.
Baird, Amee; Dewar, Bonnie-Kate; Critchley, Hugo; Gilbert, Sam J.; Dolan, Raymond J.; Cipolotti, Lisa
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…
García-Cabezas, Miguel Á.; Barbas, Helen
Behavioral and functional studies in humans suggest that attention plays a key role in activating the primary olfactory cortex through an unknown circuit mechanism. We report that a novel pathway from the anterior cingulate cortex, an area which has a key role in attention, projects directly to the primary olfactory cortex in rhesus monkeys, innervating mostly the anterior olfactory nucleus. Axons from the anterior cingulate cortex formed synapses mostly with spines of putative excitatory pyramidal neurons and with a small proportion of a neurochemical class of inhibitory neurons that are thought to have disinhibitory effect on excitatory neurons. This novel pathway from the anterior cingulate is poised to exert a powerful excitatory effect on the anterior olfactory nucleus, which is a critical hub for odorant processing via extensive bilateral connections with primary olfactory cortices and the olfactory bulb. Acting on the anterior olfactory nucleus, the anterior cingulate may activate the entire primary olfactory cortex to mediate the process of rapid attention to olfactory stimuli. PMID:23797208
Liu, Yi; Du, Lian; Li, Yongmei; Liu, Haixia; Zhao, Wenjing; Liu, Dan; Zeng, Jinkun; Li, Xingbao; Fu, Yixiao; Qiu, Haitang; Li, Xirong; Qiu, Tian; Hu, Hua; Meng, Huaqing; Luo, Qinghua
Abstract The mechanisms underlying the effects of electroconvulsive therapy (ECT) in major depressive disorder (MDD) are not fully understood. Resting-state functional magnetic resonance imaging (rs-fMRI) is a new tool to study the effects of brain stimulation interventions, particularly ECT. The authors aim to investigate the mechanisms of ECT in MDD by rs-fMRI. They used rs-fMRI to measure functional changes in the brain of first-episode, treatment-naive MDD patients (n = 23) immediately before and then following 8 ECT sessions (brief-pulse square-wave apparatus, bitemporal). They also computed voxel-wise amplitude of low-frequency fluctuation (ALFF) as a measure of regional brain activity and selected the left subgenual anterior cingulate cortex (sgACC) to evaluate functional connectivity between the sgACC and other brain regions. Increased regional brain activity measured by ALFF mainly in the left sgACC following ECT. Functional connectivity of the left sgACC increased in the ipsilateral parahippocampal gyrus, pregenual ACC, contralateral middle temporal pole, and orbitofrontal cortex. Importantly, reduction in depressive symptoms were negatively correlated with increased ALFF in the left sgACC and left hippocampus, and with distant functional connectivity between the left sgACC and contralateral middle temporal pole. That is, across subjects, as depression improved, regional brain activity in sgACC and its functional connectivity increased in the brain. Eight ECT sessions in MDD patients modulated activity in the sgACC and its networks. The antidepressant effects of ECT were negatively correlated with sgACC brain activity and connectivity. These findings suggest that sgACC-associated prefrontal-limbic structures are associated with the therapeutic effects of ECT in MDD. PMID:26559309
Rosenberg, David R.; Mirza, Yousha; Russell, Aileen; Tang, Jennifer; Smith, Janet M.; Banerjee, Preeya S.; Bhandari, Rashmi; Rose, Michelle; Ivey, Jennifer; Boyd, Courtney; Moore, Gregory J.
Objective: To examine in vivo glutamatergic neurochemical alterations in the anterior cingulate cortex of pediatric patients with obsessive-compulsive disorder (OCD) without major depressive disorder (MDD) versus pediatric patients with MDD without OCD and healthy controls. Method: Single-voxel proton magnetic resonance spectroscopic examinations…
Carr, Joshua K.; Fournier, Neil M.; Lehmann, Hugo
We examined whether increasing retrieval difficulty in a spatial memory task would promote the recruitment of the anterior cingulate cortex (ACC) similar to what is typically observed during remote memory retrieval. Rats were trained on the hidden platform version of the Morris Water Task and tested three or 30 d later. Retrieval difficulty was…
Schweimer, Judith; Hauber, Wolfgang
The anterior cingulate cortex (ACC) plays a critical role in stimulus-reinforcement learning and reward-guided selection of actions. Here we conducted a series of experiments to further elucidate the role of the ACC in instrumental behavior involving effort-based decision-making and instrumental learning guided by reward-predictive stimuli. In…
van Veen, V.; Holroyd, C.B.; Cohen, J.D.; Stenger, V.A.; Carter, C.S.
Recent theories of the neural basis of performance monitoring have emphasized a central role for the anterior cingulate cortex (ACC). Replicating an earlier event-related potential (ERP) study, which showed an error feedback negativity that was modeled as having an ACC generator, we used event-related fMRI to investigate whether the ACC would…
Magno, Elena; Simoes-Franklin, Cristina; Robertson, Ian H.; Garavan, Hugh
Effective goal-directed behavior relies on a network of regions including anterior cingulate cortex and ventral striatum to learn from negative outcomes in order to improve performance. We employed fMRI to determine if this frontal-striatal system is also involved in instances of behavior that do not presume negative circumstances. Participants…
Thakkar, Katharine N.; Polli, Frida E.; Joseph, Robert M.; Tuch, David S.; Hadjikhani, Nouchine; Barton, Jason J. S.; Manoach, Dara S.
Autism spectrum disorders (ASD) are characterized by inflexible and repetitive behaviour. Response monitoring involves evaluating the consequences of behaviour and making adjustments to optimize outcomes. Deficiencies in this function, and abnormalities in the anterior cingulate cortex (ACC) on which it relies, have been reported as contributing…
Dapres, G.; Cadilhac, J.; Passouant, P.
Stimuli of varying strength, frequency and duration were applied to the anterior cingulate gyrus in unanesthetized cats with freedom of movement. The motor, vegetative and electrical effects of these stimuli, although inconstant, lead to a consideration of the role of this structure in the extrapyramidal control of motricity.
Makris, Nikos; Seidman, Larry J.; Valera, Eve M.; Biederman, Joseph; Monuteaux, Michael C.; Kennedy, David N.; Caviness, Verne S., Jr.; Bush, George; Crum, Katherine; Brown, Ariel B.; Faraone, Stephen V.
Objective: We sought to examine preliminary results of brain alterations in anterior cingulate cortex (ACC) in treatment-naive adults with ADHD. The ACC is a central brain node for the integration of cognitive control and allocation of attention, affect and drive. Thus its anatomical alteration may give rise to impulsivity, hyperactivity and…
Posner, Michael I; Rothbart, Mary K; Sheese, Brad E; Tang, Yiyuan
The midfrontal cortex, and particularly the anterior cingulate gyrus, appears active in many studies of functional imaging. Various models have competed to explain the functions of the anterior cingulate in relation to its patterns of activation. We believe that the concept of self-regulation is valuable in considering the role of the cingulate. The sensitivity of the cingulate to both reward and pain, and evidence for cingulate coupling to cognitive and emotional areas during task performance, support this identification. Self-regulation is a very broad concept that does not lend itself very well to specific models or tests, but it does provide a framework for examining development. We trace the role of the midfrontal cortex in evolution and infant development. Both genes and environment influence self-regulation. The presence of both genetic and environmental effects raises the issue of their interaction, which we discuss in relation to the dopamine 4 receptor gene and parenting methods. The role of the midfrontal cortex in self-regulation allows us to consider both brain networks common to all people and network efficiency underlying individual differences in behavior.
Wan, Xiaohong; Cheng, Kang; Tanaka, Keiji
Humans, and animals, often encounter ambiguous situations that require a decision on whether to take an offense or a defense strategy. Behavioral studies suggest that a strategy decision is frequently made before concrete options are evaluated. It remains enigmatic, however, how a strategy is determined without exploration of options. Here we investigated neural correlates of quick offense-versus-defense strategy decision in a board game, shogi. We found that the rostral anterior cingulate cortex and the posterior cingulate cortex complementally encoded the defense and attack strategy values, respectively. The dorsolateral prefrontal cortex compared the two strategy values. Several brain regions were activated during decision of concrete moves under an instructed strategy, whereas none of them showed correlation with defense or attack strategy values in their activities during strategy decision. These findings suggest that values of alternative strategies represented in different parts of the cingulate cortex have essential roles in intuitive strategy decision-making.
Szeszko, P R; Bilder, R M; Lencz, T; Ashtari, M; Goldman, R S; Reiter, G; Wu, H; Lieberman, J A
Although frontal lobe structural and functional abnormalities have been identified in schizophrenia, their relationship remains elusive. Because the frontal lobes are both structurally and functionally heterogeneous, it is possible that some measures of frontal lobe structure may not have accurately identified relevant frontal lobe subregions. The authors hypothesized that the volumes of two dorsal, 'archicortical' subregions (i.e. superior frontal gyrus and anterior cingulate gyrus), but not a ventral, 'paleocortical' subregion (i.e. orbital frontal region) would be significantly and selectively correlated with executive and motor dysfunction in patients with schizophrenia as previously reported for the anterior hippocampal region. Volumes of these frontal lobe subregions were measured from magnetic resonance images based on sulcal anatomy in 20 men and 15 women with first-episode schizophrenia. All patients completed a comprehensive neuropsychological test battery while clinically stabilized that encompassed six domains of functioning: attention, executive, motor, visuospatial, memory and language. Findings indicated that reduced anterior cingulate gyrus volume was significantly correlated with worse executive functioning in men; among women, there were no significant correlations. Among men, anterior cingulate gyrus volume was significantly more strongly correlated with executive functioning than with attention, visuospatial, memory, language and general intellectual functioning. Neither executive nor motor functioning was significantly more strongly correlated with the dorsal 'archicortical' volumes than with orbital frontal volume. These findings suggest a link between executive deficits and dysfunction of the dorsal 'archicortical' system and implicate sex differences in their relationship in first-episode schizophrenia.
Matsuzaki, Yu; Honda, Kenji; Eto, Fumihiro; Furukawa, Tomonori; Migita, Keisuke; Irie, Keiichi; Mishima, Kenichi; Ueno, Shinya
Background Cholinergic systems regulate the synaptic transmission resulting in the contribution of the nociceptive behaviors. Anterior cingulate cortex is a key cortical area to play roles in nociception and chronic pain. However, the effect of the activation of cholinergic system for nociception is still unknown in the cortical area. Here, we tested whether the activation of cholinergic receptors can regulate nociceptive behaviors in adult rat anterior cingulate cortex by integrative methods including behavior, immunohistochemical, and electrophysiological methods. Results We found that muscarinic M1 receptors were clearly expressed in the anterior cingulate cortex. Using behavioral tests, we identified that microinjection of a selective muscarinic M1 receptors agonist McN-A-343 into the anterior cingulate cortex dose dependently increased the mechanical threshold. In contrast, the local injection of McN-A-343 into the anterior cingulate cortex showed normal motor function. The microinjection of a selective M1 receptors antagonist pirenzepine blocked the McN-A-343-induced antinociceptive effect. Pirenzepine alone into the anterior cingulate cortex decreased the mechanical thresholds. The local injection of the GABAA receptors antagonist bicuculline into the anterior cingulate cortex also inhibited the McN-A-343-induced antinociceptive effect and decreased the mechanical threshold. Finally, we further tested whether the activation of M1 receptors could regulate GABAergic transmission using whole-cell patch-clamp recordings. The activation of M1 receptors enhanced the frequency of spontaneous and miniature inhibitory postsynaptic currents as well as the amplitude of spontaneous inhibitory postsynaptic currents in the anterior cingulate cortex. Conclusions These results suggest that the activation of muscarinic M1 receptors in part increased the mechanical threshold by increasing GABAergic transmitter release and facilitating GABAergic transmission in the anterior
Tolomeo, Serenella; Christmas, David; Jentzsch, Ines; Johnston, Blair; Sprengelmeyer, Reiner; Matthews, Keith; Douglas Steele, J
Converging evidence has linked the anterior mid-cingulate cortex to negative affect, pain and cognitive control. It has previously been proposed that this region uses information about punishment to control aversively motivated actions. Studies on the effects of lesions allow causal inferences about brain function; however, naturally occurring lesions in the anterior mid-cingulate cortex are rare. In two studies we therefore recruited 94 volunteers, comprising 15 patients with treatment-resistant depression who had received bilateral anterior cingulotomy, which consists of lesions made within the anterior mid-cingulate cortex, 20 patients with treatment-resistant depression who had not received surgery and 59 healthy control subjects. Using the Ekman 60 faces paradigm and two Stroop paradigms, we tested the hypothesis that patients who received anterior cingulotomy were impaired in recognizing negative facial affect expressions but not positive or neutral facial expressions, and impaired in Stroop cognitive control, with larger lesions being associated with more impairment. Consistent with this hypothesis, we found that larger volume lesions predicted more impairment in recognizing fear, disgust and anger, and no impairment in recognizing facial expressions of surprise or happiness. However, we found no impairment in recognizing expressions of sadness. Also consistent with the hypothesis, we found that larger volume lesions predicted impaired Stroop cognitive control. Notably, this relationship was only present when anterior mid-cingulate cortex lesion volume was defined as the overlap between cingulotomy lesion volume and Shackman's meta-analysis-derived binary masks for negative affect and cognitive control. Given substantial evidence from healthy subjects that the anterior mid-cingulate cortex is part of a network associated with the experience of negative affect and pain, engaging cognitive control processes for optimizing behaviour in the presence of such
Preston, Catherine; Ehrsson, H. Henrik
In today's Western society, concerns regarding body size and negative feelings toward one's body are all too common. However, little is known about the neural mechanisms underlying negative feelings toward the body and how they relate to body perception and eating-disorder pathology. Here, we used multisensory illusions to elicit illusory ownership of obese and slim bodies during functional magnetic resonance imaging. The results implicate the anterior insula and the anterior cingulate cortex in the development of negative feelings toward the body through functional interactions with the posterior parietal cortex, which mediates perceived obesity. Moreover, cingulate neural responses were modulated by nonclinical eating-disorder psychopathology and were attenuated in females. These results reveal how perceptual and affective body representations interact in the human brain and may help explain the neurobiological underpinnings of eating-disorder vulnerability in women. PMID:27733537
Gallagher, Catherine L; Bell, Brian; Palotti, Matthew; Oh, Jen; Christian, Bradley T.; Okonkwo, Ozioma; Sojkova, Jitka; Buyan-Dent, Laura; Nickles, Robert J.; Harding, Sandra J.; Stone, Charles K.; Johnson, Sterling C.; Holden, James E.
Subtle cognitive and behavioral changes are common in early Parkinson’s disease. The cause of these symptoms is probably multifactorial but may in part be related to extra-striatal dopamine levels. 6-[18F]-Fluoro-L-dopa (FDOPA) positron emission tomography has been widely used to quantify dopamine metabolism in the brain; the most frequently measured kinetic parameter is the tissue uptake rate constant, Ki. However, estimates of dopamine turnover, which also account for the small rate of FDOPA loss from areas of specific trapping, may be more sensitive than Ki for early disease-related changes in dopamine biosynthesis. The purpose of the present study was to compare effective distribution volume ratio (eDVR), a metric for dopamine turnover, to cognitive and behavioral measures in Parkinson’s patients. We chose to focus the investigation on anterior cingulate cortex, which shows highest FDOPA uptake within frontal regions and has known roles in executive function. 15 Non-demented early-stage PD patients were pretreated with carbidopa and tolcapone, a central catechol-O-methyl transferase (COMT) inhibitor and then underwent extended imaging with FDOPA PET. Anterior cingulate eDVR was compared with composite scores for language, memory, and executive function measured by neuropsychological testing, and behavior change measured using two informant-based questionnaires, the Cambridge Behavioral Inventory and the Behavior Rating Inventory of Executive Function- Adult Version. Lower mean eDVR (thus higher dopamine turnover) in anterior cingulate cortex was related to lower (more impaired) behavior scores. We conclude that subtle changes in anterior cingulate dopamine metabolism may contribute to dysexecutive behaviors in Parkinson’s disease. PMID:25511521
Allman, J M; Hakeem, A; Erwin, J M; Nimchinsky, E; Hof, P
We propose that the anterior cingulate cortex is a specialization of neocortex rather than a more primitive stage of cortical evolution. Functions central to intelligent behavior, that is, emotional self-control, focused problem solving, error recognition, and adaptive response to changing conditions, are juxtaposed with the emotions in this structure. Evidence of an important role for the anterior cingulate cortex in these functions has accumulated through single-neuron recording, electrical stimulation, EEG, PET, fMRI, and lesion studies. The anterior cingulate cortex contains a class of spindle-shaped neurons that are found only in humans and the great apes, and thus are a recent evolutionary specialization probably related to these functions. The spindle cells appear to be widely connected with diverse parts of the brain and may have a role in the coordination that would be essential in developing the capacity to focus on difficult problems. Furthermore, they emerge postnatally and their survival may be enhanced or reduced by environmental conditions of enrichment or stress, thus potentially influencing adult competence or dysfunction in emotional self-control and problem-solving capacity.
van Steenbergen, H; Haasnoot, E; Bocanegra, B R; Berretty, E W; Hommel, B
The role of mid-cingulate cortex (MCC), also referred to as dorsal anterior cingulate cortex, in regulating cognitive control is a topic of primary importance in cognitive neuroscience. Although many studies have shown that MCC responds to cognitive demands, lesion studies in humans are inconclusive concerning the causal role of the MCC in the adaptation to these demands. By elegantly combining single-cell recordings with behavioural methods, Sheth et al. [Sheth, S. et al. Human dorsal anterior cingulate cortex neurons mediate ongoing behavioural adaptation. Nature 488, 218-22 (2012).] recently were able to show that neurons in MCC encode cognitive demand. Importantly, this study also claimed that focal lesions of the MCC abolished behavioural adaptation to cognitive demands. Here we show that the absence of post-cingulotomy behavioural adaptation reported in this study may have been due to practice effects. We run a control condition where we tested subjects before and after a dummy treatment, which substituted cingulotomy with a filler task (presentation of a documentary). The results revealed abolished behavioural adaptation following the dummy treatment. Our findings suggest that future work using proper experimental designs is needed to advance the understanding of the causal role of the MCC in behavioural adaptation.
Lim, Jonathan W. C.; Donahoo, Amber-Lee S.; Bunt, Jens; Edwards, Timothy J.; Fenlon, Laura R.; Liu, Ying; Zhou, Jing; Moldrich, Randal X.; Piper, Michael; Gobius, Ilan; Bailey, Timothy L.; Wray, Naomi R.; Kessaris, Nicoletta; Poo, Mu-Ming; Rubenstein, John L. R.; Richards, Linda J.
Transcription factors act during cortical development as master regulatory genes that specify cortical arealization and cellular identities. Although numerous transcription factors have been identified as being crucial for cortical development, little is known about their downstream targets and how they mediate the emergence of specific neuronal connections via selective axon guidance. The EMX transcription factors are essential for early patterning of the cerebral cortex, but whether EMX1 mediates interhemispheric connectivity by controlling corpus callosum formation remains unclear. Here, we demonstrate that in mice on the C57Bl/6 background EMX1 plays an essential role in the midline crossing of an axonal subpopulation of the corpus callosum derived from the anterior cingulate cortex. In the absence of EMX1, cingulate axons display reduced expression of the axon guidance receptor NRP1 and form aberrant axonal bundles within the rostral corpus callosum. EMX1 also functions as a transcriptional activator of Nrp1 expression in vitro, and overexpression of this protein in Emx1 knockout mice rescues the midline-crossing phenotype. These findings reveal a novel role for the EMX1 transcription factor in establishing cortical connectivity by regulating the interhemispheric wiring of a subpopulation of neurons within the mouse anterior cingulate cortex. PMID:26534986
Caruana, Fausto; Avanzini, Pietro; Gozzo, Francesca; Francione, Stefano; Cardinale, Francesco; Rizzolatti, Giacomo
Laughter is a complex motor behavior that, typically, expresses mirth. Despite its fundamental role in social life, knowledge about the neural basis of laughter is very limited and mostly based on a few electrical stimulation (ES) studies carried out in epileptic patients. In these studies laughter was elicited from temporal areas where it was accompanied by mirth and from frontal areas plus an anterior cingulate case where laughter without mirth was observed. On the basis of these findings, it has been proposed a dichotomy between temporal lobe areas processing the emotional content of laughter and anterior cingulate cortex (ACC) and motor areas responsible of laughter production. The present study is aimed to understand the role of ACC in laughter. We report the effects of stimulation of 10 rostral, pregenual ACC (pACC) patients in which the ES elicited laughter. In half of the patients ES elicited a clear burst of laughter with mirth, while in the other half mirth was not evident. This large dataset allow us to offer a more reliable picture of the functional contribute of this region in laughter, and to precisely localize it in the cingulate cortex. We conclude that the pACC is involved in both the motor and the affective components of emotions, and challenge the validity of a sharp dichotomy between motor and emotional centers for laughing. Finally, we suggest a possible anatomical network for the production of positive emotional expressions.
Ansell, Emily B.; Rando, Kenneth; Tuit, Keri; Guarnaccia, Joseph; Sinha, Rajita
Background Cumulative adversity and stress are associated with risk of psychiatric disorders. While basic science studies show repeated and chronic stress effects on prefrontal and limbic neurons, human studies examining cumulative stress and effects on brain morphology are rare. Thus, we assessed whether cumulative adversity is associated with differences in gray matter volume, particularly in regions regulating emotion, self-control, and top-down processing in a community sample. Methods One hundred three healthy community participants, aged 18 to 48 and 68% male, completed interview assessment of cumulative adversity and a structural magnetic resonance imaging protocol. Whole-brain voxel-based-morphometry analysis was performed adjusting for age, gender, and total intracranial volume. Results Cumulative adversity was associated with smaller volume in medial prefrontal cortex (PFC), insular cortex, and subgenual anterior cingulate regions (familywise error corrected, p <.001). Recent stressful life events were associated with smaller volume in two clusters: the medial PFC and the right insula. Life trauma was associated with smaller volume in the medial PFC, anterior cingulate, and subgenual regions. The interaction of greater subjective chronic stress and greater cumulative life events was associated with smaller volume in the orbitofrontal cortex, insula, and anterior and subgenual cingulate regions. Conclusions Current results demonstrate that increasing cumulative exposure to adverse life events is associated with smaller gray matter volume in key prefrontal and limbic regions involved in stress, emotion and reward regulation, and impulse control. These differences found in community participants may serve to mediate vulnerability to depression, addiction, and other stress-related psychopathology. PMID:22218286
Wang, Jue; Liu, Dong-Qiang; Zhang, Han; Zhu, Wei-Xuan; Dong, Zhang-Ye; Zang, Yu-Feng
The dorsal anterior cingulate cortex (dACC) has been consistently implicated in cognitive control processes. Many studies have found higher fractional anisotropy (FA) in the left anterior cingulum bundle (aCB) than in the right. However, the asymmetry of gray matter density (GMD) is not clear. Using multiple modalities of MRI, we investigated both FA and GMD in the dACC in two independent groups of healthy participants (50 per group, 18-24 years old, half males and half females). Consistent with previous findings, the mean FA of the left aCB was significantly higher than that of the right. Males showed higher FA in the bilateral aCB than females. Voxel-based analysis of GMD in the dACC presented a region-specific significant asymmetry: right > left in the lower part (around callosal sulcus) but left > right in the upper part (around cingulate sulcus). No significant sex effect was found for GMD in the dACC. All these results were almost the same across the two independent groups. The complex pattern of asymmetry in GMD may imply highly differentiated functions of the dACC. Future fine-scale structural and diffusion MRI studies and a battery of cognitive behavioral measurements are needed to fully elucidate the asymmetry of the dACC.
Baird, Amee; Dewar, Bonnie-Kate; Critchley, Hugo; Gilbert, Sam J; Dolan, Raymond J; Cipolotti, Lisa
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 compared with age and education matched healthy controls. Both patients showed intact intellectual, memory, and language abilities. No clear-cut abnormalities were noted in visuoperceptual functions. Speed of information processing was mildly reduced only in Patient 2 (bilateral ACC lesion). The patients demonstrated weak or impaired performance only on selective executive function tests. Performance on anterior attention tasks was satisfactory. We tentatively suggest that our findings are inconsistent with anterior attention theories of ACC function based on neuroimaging findings. We propose that the data may imply that the ACC does not have a central role in cognition. We speculate that our findings may be compatible with the view that the ACC integrates cognitive processing with autonomic functioning to guide behaviour.
Oemisch, Mariann; Westendorff, Stephanie; Everling, Stefan; Womelsdorf, Thilo
The anterior cingulate cortex (ACC) and prefrontal cortex (PFC) are believed to coactivate during goal-directed behavior to identify, select, and monitor relevant sensory information. Here, we tested whether coactivation of neurons across macaque ACC and PFC would be evident at the level of pairwise neuronal correlations during stimulus selection in a spatial attention task. We found that firing correlations emerged shortly after an attention cue, were evident for 50-200 ms time windows, were strongest for neuron pairs in area 24 (ACC) and areas 8 and 9 (dorsal PFC), and were independent of overall firing rate modulations. For a subset of cell pairs from ACC and dorsal PFC, the observed functional spike-train connectivity carried information about the direction of the attention shift. Reliable firing correlations were evident across area boundaries for neurons with broad spike waveforms (putative excitatory neurons) as well as for pairs of putative excitatory neurons and neurons with narrow spike waveforms (putative interneurons). These findings reveal that stimulus selection is accompanied by slow time scale firing correlations across those ACC/PFC subfields implicated to control and monitor attention. This functional coupling was informative about which stimulus was selected and thus indexed possibly the exchange of task-relevant information. We speculate that interareal, transient firing correlations reflect the transient coordination of larger, reciprocally interacting brain networks at a characteristic 50-200 ms time scale. Significance statement: Our manuscript identifies interareal spike-train correlations between primate anterior cingulate and dorsal prefrontal cortex during a period where attentional stimulus selection is likely controlled by these very same circuits. Interareal correlations emerged during the covert attention shift to one of two peripheral stimuli, proceeded on a slow 50-200 ms time scale, and occurred between putative pyramidal and
Long-term potentiation (LTP) is the key cellular mechanism for physiological learning and pathological chronic pain. In the anterior cingulate cortex (ACC), postsynaptic recruitment or modification of AMPA receptor (AMPAR) GluA1 contribute to the expression of LTP. Here we report that pyramidal cells in the deep layers of the ACC send direct descending projecting terminals to the dorsal horn of the spinal cord (lamina I-III). After peripheral nerve injury, these projection cells are activated, and postsynaptic excitatory responses of these descending projecting neurons were significantly enhanced. Newly recruited AMPARs contribute to the potentiated synaptic transmission of cingulate neurons. PKA-dependent phosphorylation of GluA1 is important, since enhanced synaptic transmission was abolished in GluA1 phosphorylation site serine-845 mutant mice. Our findings provide strong evidence that peripheral nerve injury induce long-term enhancement of cortical-spinal projecting cells in the ACC. Direct top-down projection system provides rapid and profound modulation of spinal sensory transmission, including painful information. Inhibiting cortical top-down descending facilitation may serve as a novel target for treating neuropathic pain. PMID:24890933
Amemori, Ken-ichi; Amemori, Satoko
The judgment of whether to accept or to reject an offer is determined by positive and negative affect related to the offer, but affect also induces motivational responses. Rewarding and aversive cues influence the firing rates of many neurons in primate prefrontal and cingulate neocortical regions, but it still is unclear whether neurons in these regions are related to affective judgment or to motivation. To address this issue, we recorded simultaneously the neuronal spike activities of single units in the dorsolateral prefrontal cortex (dlPFC) and the anterior cingulate cortex (ACC) of macaque monkeys as they performed approach–avoidance (Ap–Av) and approach–approach (Ap–Ap) decision-making tasks that can behaviorally dissociate affective judgment and motivation. Notably, neurons having activity correlated with motivational condition could be distinguished from neurons having activity related to affective judgment, especially in the Ap–Av task. Although many neurons in both regions exhibited similar, selective patterns of task-related activity, we found a larger proportion of neurons activated in low motivational conditions in the dlPFC than in the ACC, and the onset of this activity was significantly earlier in the dlPFC than in the ACC. Furthermore, the temporal onsets of affective judgment represented by neuronal activities were significantly slower in the low motivational conditions than in the other conditions. These findings suggest that motivation and affective judgment both recruit dlPFC and ACC neurons but with differential degrees of involvement and timing. PMID:25653353
Shenhav, Amitai; Botvinick, Matthew M.; Cohen, Jonathan D.
Summary The dorsal anterior cingulate cortex (dACC) has a near-ubiquitous presence in the neuroscience of cognitive control. It has been implicated in a diversity of functions, from reward processing and performance monitoring to the execution of control and action selection. Here, we propose that this diversity can be understood in terms of a single underlying function: allocation of control based on an evaluation of the expected value of control (EVC). We present a normative model of EVC that integrates three critical factors: the expected payoff from a controlled process, the amount of control that must be invested to achieve that payoff, and the cost in terms of cognitive effort. We propose that dACC integrates this information, using it to determine whether, where and how much control to allocate. We then consider how the EVC model can explain the diverse array of findings concerning dACC function. PMID:23889930
Hill, Michael R.; Boorman, Erie D.; Fried, Itzhak
When learning from direct experience, neurons in the primate brain have been shown to encode a teaching signal used by algorithms in artificial intelligence: the reward prediction error (PE)—the difference between how rewarding an event is, and how rewarding it was expected to be. However, in humans and other species learning often takes place by observing other individuals. Here, we show that, when humans observe other players in a card game, neurons in their rostral anterior cingulate cortex (rACC) encode both the expected value of an observed choice, and the PE after the outcome was revealed. Notably, during the same task neurons recorded in the amygdala (AMY) and the rostromedial prefrontal cortex (rmPFC) do not exhibit this type of encoding. Our results suggest that humans learn by observing others, at least in part through the encoding of observational PEs in single neurons in the rACC. PMID:27598687
Mohanty, Aprajita; Engels, Anna S; Herrington, John D; Heller, Wendy; Ho, Moon-Ho Ringo; Banich, Marie T; Webb, Andrew G; Warren, Stacie L; Miller, Gregory A
Functional differentiation of dorsal (dACC) and rostral (rACC) anterior cingulate cortex for cognitive and emotional function has received considerable indirect support. Using fMRI, parallel tasks, and within-subject analysis, the present study directly tested the proposed specialization of ACC subdivisions. A Task x Region interaction confirmed more dACC activation during color-word distractors and more rACC activation during emotion-word distractors. Activity in ACC subdivisions differentially predicted behavioral performance. Connectivity with prefrontal and limbic regions also supported distinct dACC and rACC roles. Findings provide direct evidence for differential engagement of ACC subdivisions in cognitive and emotional processing and for differential functional connectivity in the implementation of cognitive control and emotion regulation. Results point to an anatomical and functional continuum rather than segregated operations.
Shenhav, Amitai; Botvinick, Matthew M; Cohen, Jonathan D
The dorsal anterior cingulate cortex (dACC) has a near-ubiquitous presence in the neuroscience of cognitive control. It has been implicated in a diversity of functions, from reward processing and performance monitoring to the execution of control and action selection. Here, we propose that this diversity can be understood in terms of a single underlying function: allocation of control based on an evaluation of the expected value of control (EVC). We present a normative model of EVC that integrates three critical factors: the expected payoff from a controlled process, the amount of control that must be invested to achieve that payoff, and the cost in terms of cognitive effort. We propose that dACC integrates this information, using it to determine whether, where and how much control to allocate. We then consider how the EVC model can explain the diverse array of findings concerning dACC function.
Widerström-Noga, Eva; Pattany, Pradip M; Cruz-Almeida, Yenisel; Felix, Elizabeth R; Perez, Salome; Cardenas, Diana D; Martinez-Arizala, Alberto
Persistent pain is a common reason for reduced quality of life after a spinal cord injury (SCI). Biomarkers of neuropathic pain may facilitate translational research and the understanding of underlying mechanisms. Research suggests that pain and affective distress are anatomically and functionally integrated in the anterior cingulate cortex and can modulate sensory and affective aspects of pain. We hypothesized that severe neuropathic pain with a significant psychosocial impact would be associated with metabolite concentrations (obtained by magnetic resonance spectroscopy) in the anterior cingulate cortex, indicating neuronal and/or glial dysfunction. Participants with SCI and severe, high-impact neuropathic pain (SCI-HPI; n=16), SCI and moderate, low-impact neuropathic pain (SCI-LPI; n=24), SCI without neuropathic pain (SCI-noNP; n=14), and able-bodied, pain-free control subjects (A-B; n=22) underwent a 3-T magnetic resonance imaging brain scan. Analyses revealed that the SCI-HPI group had significantly higher levels of myoinositol (Ins) (P<.000), creatine (P=.007), and choline (P=.014), and significantly lower levels of N-acetyl aspartate/Ins (P=.024) and glutamate-glutamine (Glx)/Ins (P=.003) ratios than the SCI-LPI group. The lower Glx/Ins ratio significantly discriminated between SCI-HPI and the A-B (P=.006) and SCI-noNP (P=.026) groups, displayed excellent test-retest reliability, and was significantly related to greater pain severity, interference, and affective distress. This suggests that the combination of lower glutamatergic metabolism and proliferation of glia and glial activation are underlying mechanisms contributing to the maintenance of severe neuropathic pain with significant psychosocial impact in chronic SCI. These findings indicate that the Glx/Ins ratio may be a useful biomarker for severe SCI-related neuropathic pain with significant psychosocial impact.
Allman, John M; Tetreault, Nicole A; Hakeem, Atiya Y; Manaye, Kebreten F; Semendeferi, Katerina; Erwin, Joseph M; Park, Soyoung; Goubert, Virginie; Hof, Patrick R
The von Economo neurons (VENs) are large bipolar neurons located in frontoinsular (FI) and anterior cingulate cortex in great apes and humans, but not other primates. We performed stereological counts of the VENs in FI and LA (limbic anterior, a component of anterior cingulate cortex) in great apes and in humans. The VENs are more numerous in humans than in apes, although one gorilla approached the lower end of the human range. We also examined the ontological development of the VENs in FI and LA in humans. The VENs first appear in small numbers in the 36th week post-conception, are rare at birth, and increase in number during the first 8 months after birth. There are significantly more VENs in the right hemisphere than in the left in FI and LA in postnatal brains of apes and humans. This asymmetry in VEN numbers may be related to asymmetries in the autonomic nervous system. The activity of the inferior anterior insula, which contains FI, is related to physiological changes in the body, decision-making, error recognition, and awareness. The VENs appear to be projection neurons, although their targets are unknown. We made a preliminary study of the connections of FI cortex based on diffusion tensor imaging in the brain of a gorilla. The VEN-containing regions connect to the frontal pole as well as to other parts of frontal and insular cortex, the septum, and the amygdala. It is likely that the VENs in FI are projecting to some or all of these structures and relaying information related to autonomic control, decision-making, or awareness. The VENs selectively express the bombesin peptides neuromedin B (NMB) and gastrin releasing peptide (GRP) which are also expressed in another population of closely related neurons, the fork cells. NMB and GRP signal satiety. The genes for NMB and GRP are expressed selectively in small populations of neurons in the insular cortex in mice. These populations may be related to the VEN and fork cells and may be involved in the regulation
Jonkman, Sietse; Everitt, Barry J.
The integrity of the rodent anterior cingulate cortex (ACC) is essential for various aspects of instrumental behavior, but it is not clear if the ACC is important for the acquisition of a simple instrumental response. Here, it was demonstrated that post-session infusions of anisomycin into the rat ACC completely prevented the acquisition of…
Einarsson, Einar O.; Nader, Karim
It has been suggested that memories become more stable and less susceptible to the disruption of reconsolidation over weeks after learning. Here, we test this by targeting the anterior cingulate cortex (ACC) and test its involvement in the formation, consolidation, and reconsolidation of recent and remote contextual fear memory. We found that…
Salas, Manuel; Torrero, Carmen; Regalado, Mirelta; Rubio, Lorena
In altricial species, early pre- and neonatal undernutrition interferes with the neuronal organization of several brain structures that have critical time windows for synaptic organization, including the prefrontal cortex. In Golgi-Cox stained tissue the basilar dendritic arbor of pyramidal neurons in the anterior cingulate cortex of early underfed adult lactating dams was evaluated. The anterior cingulate of the rat plays a major role in the execution of sexual, maternal and visual attentional control and other cognitive responses. The effects of neonatal undernutrition on the basilar dendritic tree and perikaryon measurements in layer II/III pyramidal neurons of the anterior cingulate were examined in lactating dams at postpartum days 8 and 12. In the underfed dams the distal portions of the basilar dendrites had fewer branches and a lower dendritic density of dendrites, and neurons had perikarya with reduced perimeter and cross-sectional area. Thus, the neuronal alterations may interfere the plastic synaptic activity and with maternal cognitive performance of rats subjected to early underfeeding. These anatomical alterations of the anterior cingulate may help to understand the disruption of long-term cognitive processes associated with perinatal food restriction.
Polli, Frida E.; Barton, Jason J. S.; Thakkar, Katharine N.; Greve, Douglas N.; Goff, Donald C.; Rauch, Scott L.; Manoach, Dara S.
To perform well on any challenging task, it is necessary to evaluate your performance so that you can learn from errors. Recent theoretical and experimental work suggests that the neural sequellae of error commission in a dorsal anterior cingulate circuit index a type of contingency- or reinforcement-based learning, while activation in a rostral…
Lovstad, M.; Funderud, I.; Meling, T.; Kramer, U. M.; Voytek, B.; Due-Tonnessen, P.; Endestad, T.; Lindgren, M.; Knight, R. T.; Solbakk, A. K.
Whereas neuroimaging studies of healthy subjects have demonstrated an association between the anterior cingulate cortex (ACC) and cognitive control functions, including response monitoring and error detection, lesion studies are sparse and have produced mixed results. Due to largely normal behavioral test results in two patients with medial…
Bledsoe, Jesse C; Semrud-Clikeman, Margaret; Pliszka, Steven R
The cause of attention-deficit/hyperactivity disorder (ADHD) has been linked to abnormalities in prefrontal-striatal-cerebellar networks, but the brain-behavioral correlates are relatively equivocal. Children with ADHD and healthy controls underwent MRI and neuropsychological testing. Brain cortical thickness was analyzed for the bilateral rostral and caudal anterior cingulate cortex (ACC). Inhibitory control was assessed with the Stroop Inhibition test, and ADHD symptom severity was assessed with parent and teacher behavioral questionnaires. Brain-behavior relationships were calculated between cortical thickness and behavioral measures with regression models. Children with ADHD had significant cortical thinning in the right rostral ACC but nonsignificant thinning in right caudal, left caudal, or left rostral ACC compared with healthy control children after statistical correction for multiple comparisons. Further, right rostral ACC thickness predicted a significant amount of the variance in parent- and teacher-reported symptoms of ADHD. Exploratory analysis showed that cortical thickness was not related to psychostimulant medication history. Symptoms of ADHD may be related to reductions in cortical thickness in the right anterior attention network, a region implicated in behavioral error detection, impulsivity, and inhibitory control.
Rotge, Jean-Yves; Lemogne, Cedric; Hinfray, Sophie; Huguet, Pascal; Grynszpan, Ouriel; Tartour, Eric; George, Nathalie; Fossati, Philippe
Many functional magnetic resonance imaging studies have explored the neural correlates of social pain that results from social threat, exclusion, rejection, loss or negative evaluation. Although activations have consistently been reported within the anterior cingulate cortex (ACC), it remains unclear which ACC subdivision is particularly involved. To provide a quantitative estimation of the specific involvement of ACC subdivisions in social pain, we conducted a voxel-based meta-analysis. The literature search identified 46 articles that included 940 subjects, the majority of which used the cyberball task. Significant likelihoods of activation were found in both the ventral and dorsal ACC for both social pain elicitation and self-reported distress during social pain. Self-reported distress involved more specifically the subgenual and pregenual ACC than social pain-related contrasts. The cyberball task involved the anterior midcingulate cortex to a lesser extent than other experimental tasks. During social pain, children exhibited subgenual activations to a greater extent than adults. Finally, the ventro-dorsal gradient of ACC activations in cyberball studies was related to the length of exclusion phases. The present meta-analysis contributes to a better understanding of the role of ACC subdivisions in social pain, and it could be of particular importance for guiding future studies of social pain and its neural underpinnings.
Lemogne, Cedric; Hinfray, Sophie; Huguet, Pascal; Grynszpan, Ouriel; Tartour, Eric; George, Nathalie; Fossati, Philippe
Many functional magnetic resonance imaging studies have explored the neural correlates of social pain that results from social threat, exclusion, rejection, loss or negative evaluation. Although activations have consistently been reported within the anterior cingulate cortex (ACC), it remains unclear which ACC subdivision is particularly involved. To provide a quantitative estimation of the specific involvement of ACC subdivisions in social pain, we conducted a voxel-based meta-analysis. The literature search identified 46 articles that included 940 subjects, the majority of which used the cyberball task. Significant likelihoods of activation were found in both the ventral and dorsal ACC for both social pain elicitation and self-reported distress during social pain. Self-reported distress involved more specifically the subgenual and pregenual ACC than social pain-related contrasts. The cyberball task involved the anterior midcingulate cortex to a lesser extent than other experimental tasks. During social pain, children exhibited subgenual activations to a greater extent than adults. Finally, the ventro-dorsal gradient of ACC activations in cyberball studies was related to the length of exclusion phases. The present meta-analysis contributes to a better understanding of the role of ACC subdivisions in social pain, and it could be of particular importance for guiding future studies of social pain and its neural underpinnings. PMID:25140048
Cao, Weifang; Luo, Cheng; Zhu, Bin; Zhang, Dan; Dong, Li; Gong, Jinnan; Gong, Diankun; He, Hui; Tu, Shipeng; Yin, Wenjie; Li, Jianfu; Chen, Huafu; Yao, Dezhong
Growing evidence suggests that normal aging is associated with cognitive decline and well-maintained emotional well-being. The anterior cingulate cortex (ACC) is an important brain region involved in emotional and cognitive processing. We investigated resting-state functional connectivity (FC) of two ACC subregions in 30 healthy older adults vs. 33 healthy younger adults, by parcellating into rostral (rACC) and dorsal (dACC) ACC based on clustering of FC profiles. Compared with younger adults, older adults demonstrated greater connection between rACC and anterior insula, suggesting that older adults recruit more proximal dACC brain regions connected with insula to maintain a salient response. Older adults also demonstrated increased FC between rACC and superior temporal gyrus and inferior frontal gyrus, decreased integration between rACC and default mode, and decreased dACC-hippocampal and dACC-thalamic connectivity. These altered FCs reflected rACC and dACC reorganization, and might be related to well emotion regulation and cognitive decline in older adults. Our findings provide further insight into potential functional substrates of emotional and cognitive alterations in the aging brain. PMID:25400578
Chan, Agnes S.; Cheung, Mei-chun; Sze, Sophia L.; Leung, Winnie W.; Shi, Dejian
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
Lutz, Pierre-Eric; Zhou, Yi; Labbe, Aurélie; Mechawar, Naguib; Turecki, Gustavo
The nociceptin/orphanin FQ (N/OFQ)-Nociceptin Opiod-like Peptide (NOP) receptor system is a critical mediator of physiological and pathological processes involved in emotional regulation and drug addiction. As such, this system may be an important biological substrate underlying psychiatric conditions that contribute to the risk of suicide. Thus, the goal of the present study was to characterize changes in human N/OFQ and NOP signaling as a function of depression, addiction and suicide. We quantified the expression of N/OFQ and NOP by RT-PCR in the anterior insula, the mediodorsal thalamus, and the dorsal anterior cingulate cortex (dACC) from a large sample of individuals who died by suicide and matched psychiatrically-healthy controls. Suicides displayed an 18% decrease in the expression of N/OFQ in the dACC that was not accounted for by current depressive or substance use disorders at the time of death. Therefore, our results suggest that dysregulation of the N/OFQ-NOP system may contribute to the neurobiology of suicide, a hypothesis that warrants further exploration.
Lutz, Pierre-Eric; Zhou, Yi; Labbe, Aurélie; Mechawar, Naguib; Turecki, Gustavo
The nociceptin/orphanin FQ (N/OFQ) – Nociceptin Opiod-like Peptide (NOP) receptor system is a critical mediator of physiological and pathological processes involved in emotional regulation and drug addiction. As such, this system may be an important biological substrate underlying psychiatric conditions that contribute to the risk of suicide. Thus, the goal of the present study was to characterize changes in human N/OFQ and NOP signaling as a function of depression, addiction and suicide. We quantified the expression of N/OFQ and NOP by RT-PCR in the anterior insula, the mediodorsal thalamus, and the dorsal anterior cingulate cortex (dACC) from a large sample of individuals who died by suicide and matched psychiatrically-healthy controls. Suicides displayed an 18% decrease in the expression of N/OFQ in the dACC that was not accounted for by current depressive or substance use disorders at the time of death. Therefore, our results suggest that dysregulation of the N/OFQ-NOP system may contribute to the neurobiology of suicide, a hypothesis that warrants further exploration. PMID:26349406
Hamilton, J. Paul; Glover, Gary H.; Hsu, Jung-Jiin; Johnson, Rebecca F.; Gotlib, Ian H.
The advent of real-time neurofeedback techniques has allowed us to begin to map the controllability of sensory and cognitive and, more recently, affective centers in the brain. The subgenual anterior cingulate cortex (sACC) is thought to be involved in generation of affective states and has been implicated in psychopathology. In this study, we examined whether individuals could use realtime fMRI neurofeedback to modulate sACC activity. Following a localizer task used to identify an sACC region of interest, an experimental group of eight women participated in four scans: (1) a pretraining scan in which they were asked to decrease activity in the sACC without neurofeedback; (2) two training scans in which sACC neurofeedback was presented along with instructions to decrease sACC activity; and (3) a neurofeedback-free post-training scan. An additional nine women in a yoked feedback control group saw sACC activity from the participants in the experimental group. Activity in the sACC was significantly reduced during neurofeedback training in the experimental group, but not in the control group. This training effect in the experimental group, however, did not generalize to the neurofeedback-free post-training scan. A psychophysiological interaction analysis showed decreased correlation in the experimental group relative to the sham control group between activity in the sACC and the posterior cingulate cortex during neurofeedback training relative to neurofeedback-free scans. The finding that individuals can down-modulate the sACC shows that a primary emotion center in which functional abnormality has been strongly implicated in affective disorders can be controlled with the aid of neurofeedback. PMID:21157877
Duffy, Shantel L.; Lagopoulos, Jim; Terpening, Zoe; Lewis, Simon J.G.; Grunstein, Ron; Mowszowski, Loren; Cross, Nathan; Hermens, Daniel F.; Hickie, Ian B.; Naismith, Sharon L.
Study Objectives: Sleep disordered breathing (SDB) is common in older adults and is strongly associated with cognitive decline, with increasing evidence suggesting that it may represent a risk factor for dementia. Given that SDB is characterized by intermittent episodes of hypoxemia during sleep, it is possible that cognitive impairment may relate to cerebral oxidative stress. This study aimed to examine the relationship between nocturnal markers of hypoxemia and proton magnetic resonance spectroscopy (1H-MRS) markers of oxidative stress within the anterior cingulate cortex (ACC) of the brain. Methods: Twenty-four older adults (mean age = 67.9 y) at-risk for dementia were recruited from our Healthy Brain Ageing Research Clinic. At-risk was defined as participants seeking help for assessment and/or intervention for cognitive decline, including those with subjective and/or objective cognitive complaints. This could occur in the context of prior depression or risk factors (e.g., vascular) for dementia. All participants underwent psychiatric, medical and neuropsychological assessment followed by overnight polysomnography. In addition, participants underwent 1H-MRS to derive levels of ACC metabolite glutathione (GSH) reported as a ratio to creatine (GSH/Cr). Results: Increased levels of GSH/Cr were associated with lower oxygen desaturation (r = −0.54, P = 0.007) and more severe apnea-hypopnea index scores during rapid eye movement sleep (r = 0.42, P = 0.050). In addition, ACC GSH/Cr correlated with poorer executive functioning (i.e., response inhibition: r = −0.49, P = 0.015; set shifting: r = −0.43, P = 0.037). Conclusions: Markers of nocturnal hypoxemia and SDB are associated with cerebral oxidative stress in older people at-risk for dementia, suggesting a potential mechanism by which SDB may contribute to brain degeneration, cognitive decline, and dementia. Further work focused on utilizing this biomarker for the early identification and treatment of this
Hippocampal–cortical interaction during sleep promotes transformation of memory for long-term storage in the cortex. In particular, hippocampal sharp-wave ripple-associated neural activation is important for this transformation during slow-wave sleep. The anterior cingulate cortex (ACC) has been shown to be crucial for expression and likely storage of long-term memory. However, little is known about how ACC activity is influenced by hippocampal ripple activity during sleep. We report here about coordinated interactions between hippocampal ripple activity and ACC neural firings. By recording from the ACC and hippocampal CA1 simultaneously in mice, we found that almost all ACC neurons showed increased activity before hippocampal ripple activity; moreover, a subpopulation (17%) displayed a further activation immediately after ripple activity. This postripple activation of ACC neurons correlated positively with ripple amplitude, and the same neurons were excited upon electrical stimulation of the CA1. Interestingly, the preripple activation of ACC neurons was present during the sleep state, but not during the awake state. These results suggest intimate interactions between hippocampal sharp-wave ripples and ACC neurons in a state-dependent manner. Importantly, sharp-wave ripples and associated activation appear to regulate activity of a small population of ACC neurons, a process that may play a critical role in memory consolidation. SIGNIFICANCE STATEMENT The hippocampus communicates with the cortex for memory transformation. Memories of previous experiences become less dependent on the hippocampus and increasingly dependent on cortical areas, such as the anterior cingulate cortex (ACC). However, little evidence is available to directly support this hippocampus-to-cortex information transduction hypothesis of memory consolidation. Here we show that a subpopulation of ACC neurons becomes active just after hippocampal ripple activity, and that electrical stimulation of
Apps, Matthew A.J.; Roiser, Jonathan P.; Viding, Essi
Empathy—the capacity to understand and resonate with the experiences of others—can depend on the ability to predict when others are likely to receive rewards. However, although a plethora of research has examined the neural basis of predictions about the likelihood of receiving rewards ourselves, very little is known about the mechanisms that underpin variability in vicarious reward prediction. Human neuroimaging and nonhuman primate studies suggest that a subregion of the anterior cingulate cortex in the gyrus (ACCg) is engaged when others receive rewards. Does the ACCg show specialization for processing predictions about others' rewards and not one's own and does this specialization vary with empathic abilities? We examined hemodynamic responses in the human brain time-locked to cues that were predictive of a high or low probability of a reward either for the subject themselves or another person. We found that the ACCg robustly signaled the likelihood of a reward being delivered to another. In addition, ACCg response significantly covaried with trait emotion contagion, a necessary foundation for empathizing with other individuals. In individuals high in emotion contagion, the ACCg was specialized for processing others' rewards exclusively, but for those low in emotion contagion, this region also responded to information about the subject's own rewards. Our results are the first to show that the ACCg signals probabilistic predictions about rewards for other people and that the substantial individual variability in the degree to which the ACCg is specialized for processing others' rewards is related to trait empathy. SIGNIFICANCE STATEMENT Successfully cooperating, competing, or empathizing with others can depend on our ability to predict when others are going to get something rewarding. Although many studies have examined how the brain processes rewards we will get ourselves, very little is known about vicarious reward processing. Here, we show that a
Hof, P R; Nimchinsky, E A; Perl, D P; Erwin, J M
In the context of an on-going comparative analysis of primate neocortex evolution, we describe the occurrence and distribution of a previously unrecognized group of pyramidal neurons, restricted to the superficial part of layer V in the anterior cingulate cortex of hominids and characterized by immunoreactivity to the calcium-binding protein, calretinin. These neurons were rare in orangutans, more numerous in gorillas and common chimpanzees, while humans had the highest numbers. These calretinin-containing pyramidal cells were not observed in the cingulate cortex of any other primate or mammalian species. This finding, together with other recent observations on the hominoid cingulate cortex, is interesting when considering primate neocortical evolution, as it indicates possible adaptive and anatomical modifications in a cortical region critical for the integration of many aspects of autonomic function, vocalization, and cognitive processes.
Mutschler, Isabella; Ball, Tonio; Kirmse, Ursula; Wieckhorst, Birgit; Pluess, Michael; Klarhöfer, Markus; Meyer, Andrea H.; Wilhelm, Frank H.; Seifritz, Erich
Newborns and infants communicate their needs and physiological states through crying and emotional facial expressions. Little is known about individual differences in responding to infant crying. Several theories suggest that people vary in their environmental sensitivity with some responding generally more and some generally less to environmental stimuli. Such differences in environmental sensitivity have been associated with personality traits, including neuroticism. This study investigated whether neuroticism impacts neuronal, physiological, and emotional responses to infant crying by investigating blood-oxygenation-level dependent (BOLD) responses using functional magnetic resonance imaging (fMRI) in a large sample of healthy women (N = 102) with simultaneous skin conductance recordings. Participants were repeatedly exposed to a video clip that showed crying infants and emotional responses (valence, arousal, and irritation) were assessed after every video clip presentation. Increased BOLD signal during the perception of crying infants was found in brain regions that are associated with emotional responding, the amygdala and anterior insula. Significant BOLD signal decrements (i.e., habituation) were found in the fusiform gyrus, middle temporal gyrus, superior temporal gyrus, Broca’s homologue on the right hemisphere, (laterobasal) amygdala, and hippocampus. Individuals with high neuroticism showed stronger activation in the amygdala and subgenual anterior cingulate cortex (sgACC) when exposed to infant crying compared to individuals with low neuroticism. In contrast to our prediction we found no evidence that neuroticism impacts fMRI-based measures of habituation. Individuals with high neuroticism showed elevated skin conductance responses, experienced more irritation, and perceived infant crying as more unpleasant. The results support the hypothesis that individuals high in neuroticism are more emotionally responsive, experience more negative emotions, and
Nelissen, Natalie; Stagg, Charlotte J
Dorsal anterior cingulate cortex (dACC) mediates updating and maintenance of cognitive models of the world used to drive adaptive reward-guided behavior. We investigated the neurochemical underpinnings of this process. We used magnetic resonance spectroscopy in humans, to measure levels of glutamate and GABA in dACC. We examined their relationship to neural signals in dACC, measured with fMRI, and cognitive task performance. Both inhibitory and excitatory neurotransmitters in dACC were predictive of the strength of neural signals in dACC and behavioral adaptation. Glutamate levels were correlated, first, with stronger neural activity representing information to be learnt about the tasks’ costs and benefits and, second, greater use of this information in the guidance of behavior. GABA levels were negatively correlated with the same neural signals and the same indices of behavioral influence. Our results suggest that glutamate and GABA in dACC affect the encoding and use of past experiences to guide behavior. DOI: http://dx.doi.org/10.7554/eLife.20365.001 PMID:28055824
Graham, Devon L; Durai, Heather H; Garden, Jamie D; Cohen, Evan L; Echevarria, Franklin D; Stanwood, Gregg D
Disruption to dopamine homeostasis during brain development has been implicated in a variety of neuropsychiatric disorders, including depression and schizophrenia. Inappropriate expression or activity of GABAergic interneurons are common features of many of these disorders. We discovered a persistent upregulation of GAD67+ and parvalbumin+ neurons within the anterior cingulate cortex of dopamine D2 receptor knockout mice, while other GABAergic interneuron markers were unaffected. Interneuron distribution and number were not altered in the striatum or in the dopamine-poor somatosensory cortex. The changes were already present by postnatal day 14, indicating a developmental etiology. D2eGFP BAC transgenic mice demonstrated the presence of D2 receptor expression within a subset of parvalbumin-expressing cortical interneurons, suggesting the possibility of a direct cellular mechanism through which D2 receptor stimulation regulates interneuron differentiation or survival. D2 receptor knockout mice also exhibited decreased depressive-like behavior compared with wild-type controls in the tail suspension test. These data indicate that dopamine signaling modulates interneuron number and emotional behavior and that developmental D2 receptor loss or blockade could reveal a potential mechanism for the prodromal basis of neuropsychiatric disorders.
Darvish-Ghane, Soroush; Yamanaka, Manabu; Zhuo, Min
Dopamine (DA) possesses potent neuromodulatory properties in the central nervous system. In the anterior cingulate cortex, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPAR) are key ion channels in mediating nerve injury induced long-term potentiation (LTP) and chronic pain phenotype. In the present study, we reported the effects of DA on glutamate mediated excitatory post-synaptic currents (EPSCs) in pyramidal neurons of layer II/III of the ACC in adult mice. Bath application of DA (50 μM) caused a significant, rapid and reversible inhibition of evoked EPSCs (eEPSC). This inhibitory effect is dose-related and was absent in lower concentration of DA (5 μM). Furthermore, selective postsynaptic application of GDP-β-S (1.6 mM) in the internal solution completely abolished the inhibitory effects of DA (50 μM). We also investigated modulation of spontaneous EPSCs (sEPSCs) and TTX sensitive, miniature EPSCs (mEPSCs) by DA. Our results indicated mixed effects of potentiation and inhibition of frequency and amplitude for sEPSCs and mEPSCs. Furthermore, high doses of SCH23390 (100 μM) and sulpiride (100 μM) revealed that, inhibition of eEPSCs is mediated by postsynaptic D2-receptors (D2R). Our finding posits a pre- and postsynaptic mode of pyramidal neuron EPSC modulation in mice ACC by DA.
Fornito, Alex; Yücel, Murat; Dean, Brian; Wood, Stephen J.; Pantelis, Christos
The anterior cingulate cortex (ACC) is a functionally heterogeneous region involved in diverse cognitive and emotional processes that support goal-directed behaviour. Structural magnetic resonance imaging (MRI) and neuropathological findings over the past two decades have converged to suggest abnormalities in the region may represent a neurobiological basis for many of the clinical manifestations of schizophrenia. However, while each approach offers complimentary information that can provide clues regarding underlying patholophysiological processes, the findings from these 2 fields are seldom integrated. In this article, we review structural neuroimaging and neuropathological studies of the ACC, focusing on the unique information they provide. The available imaging data suggest grey matter reductions in the ACC precede psychosis onset in some categories of high-risk individuals, show sub-regional specificity, and may progress with illness duration. The available post-mortem findings indicate these imaging-related changes are accompanied by reductions in neuronal, synaptic, and dendritic density, as well as increased afferent input, suggesting the grey matter differences observed with MRI arise from alterations in both neuronal and non-neuronal tissue compartments. We discuss the potential mechanisms that might facilitate integration of these findings and consider strategies for future research. PMID:18436528
Krill, Austen; Platek, Steven M.
Functional magnetic resonance imaging was employed to examine sensitivity to social exclusion in three conditions: same-race, other-race, and self-resembling faces. The anterior cingulate cortex (ACC), specifically the dorsal ACC, has been targeted as a key substrate in the physical and social pain matrix and was hypothesized to regulate activation response to various facial conditions. We show that participants demonstrated greatest ACC activation when being excluded by self-resembling and same-race faces, relative to other-race faces. Additionally, participants expressed greater distress and showed increased ACC activation as a result of exclusion in the same-race condition relative to the other-race condition. A positive correlation between implicit racial bias and activation in the amygdala was also evident. Implicit attitude about other-race faces partly explains levels of concern about exclusion by out-group individuals. These findings suggest that individuals are more distressed and their brain (i.e. neural alarm system) responds with greater activation when being excluded by individuals whom they are more likely to share group membership with. PMID:19597546
Lapish, Christopher C.; Durstewitz, Daniel; Chandler, L. Judson; Seamans, Jeremy K.
Successful decision making requires an ability to monitor contexts, actions, and outcomes. The anterior cingulate cortex (ACC) is thought to be critical for these functions, monitoring and guiding decisions especially in challenging situations involving conflict and errors. A number of different single-unit correlates have been observed in the ACC that reflect the diverse cognitive components involved. Yet how ACC neurons function as an integrated network is poorly understood. Here we show, using advanced population analysis of multiple single-unit recordings from the rat ACC during performance of an ecologically valid decision-making task, that ensembles of neurons move through different coherent and dissociable states as the cognitive requirements of the task change. This organization into distinct network patterns with respect to both firing-rate changes and correlations among units broke down during trials with numerous behavioral errors, especially at choice points of the task. These results point to an underlying functional organization into cell assemblies in the ACC that may monitor choices, outcomes, and task contexts, thus tracking the animal's progression through “task space.” PMID:18708525
Zhang, Xuying; Sullivan, Chelsea S; Kratz, Megan B; Kasten, Michael R; Maness, Patricia F; Manis, Paul B
The neural cell adhesion molecule (NCAM), has been shown to be an obligate regulator of synaptic stability and pruning during critical periods of cortical maturation. However, the functional consequences of NCAM deletion on the organization of inhibitory circuits in cortex are not known. In vesicular gamma-amino butyric acid (GABA) transporter (VGAT)-channelrhodopsin2 (ChR2)-enhanced yellow fluorescent protein (EYFP) transgenic mice, NCAM is expressed postnatally at perisomatic synaptic puncta of EYFP-labeled parvalbumin, somatostatin and calretinin-positive interneurons, and in the neuropil in the anterior cingulate cortex (ACC). To investigate how NCAM deletion affects the spatial organization of inhibitory inputs to pyramidal cells, we used laser scanning photostimulation in brain slices of VGAT-ChR2-EYFP transgenic mice crossed to either NCAM-null or wild type (WT) mice. Laser scanning photostimulation revealed that NCAM deletion increased the strength of close-in inhibitory connections to layer 2/3 pyramidal cells of the ACC. In addition, in NCAM-null mice, the intrinsic excitability of pyramidal cells increased, whereas the intrinsic excitability of GABAergic interneurons did not change. The increase in inhibitory tone onto pyramidal cells, and the increased pyramidal cell excitability in NCAM-null mice will alter the delicate coordination of excitation and inhibition (E/I coordination) in the ACC, and may be a factor contributing to circuit dysfunction in diseases such as schizophrenia and bipolar disorder, in which NCAM has been implicated.
Pannekoek, Justine Nienke; van der Werff, Steven J.A.; van den Bulk, Bianca G.; van Lang, Natasja D.J.; Rombouts, Serge A.R.B.; van Buchem, Mark A.; Vermeiren, Robert R.J.M.; van der Wee, Nic J.A.
Adolescent depression is associated with increased risk for suicidality, social and educational impairment, smoking, substance use, obesity, and depression in adulthood. It is of relevance to further our insight in the neurobiological mechanisms underlying this disorder in the developing brain, as this may be essential to optimize treatment and prevention of adolescent depression and its negative clinical trajectories. The equivocal findings of the limited number of studies on neural abnormalities in depressed youth stress the need for further neurobiological investigation of adolescent depression. We therefore performed a voxel-based morphometry study of the hippocampus, amygdala, superior temporal gyrus, and anterior cingulate cortex (ACC) in 26 treatment-naïve, clinically depressed adolescents and 26 pair-wise matched healthy controls. Additionally, an exploratory whole-brain analysis was performed. Clinically depressed adolescents showed a volume reduction of the bilateral dorsal ACC compared to healthy controls. However, no association was found between gray matter volume of the ACC and clinical severity scores for depression or anxiety. Our finding of a smaller ACC in clinically depressed adolescents is consistent with literature on depressed adults. Future research is needed to investigate if gray matter abnormalities precede or follow clinical depression in adolescents. PMID:24501702
Maier, Martin E.; Di Gregorio, Francesco; Muricchio, Teresa; Di Pellegrino, Giuseppe
Detecting one’s own errors and appropriately correcting behavior are crucial for efficient goal-directed performance. A correlate of rapid evaluation of behavioral outcomes is the error-related negativity (Ne/ERN) which emerges at the time of the erroneous response over frontal brain areas. However, whether the error monitoring system’s ability to distinguish between errors and correct responses at this early time point is a necessary precondition for the subsequent emergence of error awareness remains unclear. The present study investigated this question using error-related brain activity and vocal error signaling responses in seven human patients with lesions in the rostral anterior cingulate cortex (rACC) and adjoining ventromedial prefrontal cortex, while they performed a flanker task. The difference between errors and correct responses was severely attenuated in these patients indicating impaired rapid error monitong, but they showed no impairment in error signaling. However, impaired rapid error monitoring coincided with a failure to increase response accuracy on trials following errors. These results demonstrate that the error monitoring system’s ability to distinguish between errors and correct responses at the time of the response is crucial for adaptive post-error adjustments, but not a necessary precondition for error awareness. PMID:26136674
Pezze, M A; Marshall, H J; Domonkos, A; Cassaday, H J
The anterior cingulate cortex (AC) component of the medial prefrontal cortex (mPFC) has been implicated in attention and working memory as measured by trace conditioning. Since dopamine (DA) is a key modulator of mPFC function, the present study evaluated the role of DA receptor agents in rat AC, using trace fear conditioning. A conditioned stimulus (CS, noise) was followed by an unconditioned stimulus (US, shock) with or without a 10s trace interval interposed between these events in a between-subjects design. Conditioned suppression of drinking was assessed in response to presentation of the CS or an experimental background stimulus (flashing lights, previously presented for the duration of the conditioning session). The selective D1 agonist SKF81297 (0.05μg/side) or D1 antagonist SCH23390 (0.5μg/side) was administered by intra-cerebral microinfusion directly into AC. It was predicted that either of these manipulations should be sufficient to impair trace (but not delay) conditioning. Counter to expectation, there was no effect of DA D1 modulation on trace conditioning as measured by suppression to the noise CS. However, rats infused with SKF81297 acquired stronger conditioned suppression to the experimental background stimulus than those infused with SCH23390 or saline. Thus, the DA D1 agonist SKF81297 increased conditioned suppression to the contextual background light stimulus but was otherwise without effect on fear conditioning.
López-Avila, Alberto; Coffeen, Ulises; Ortega-Legaspi, J Manuel; del Angel, Rosendo; Pellicer, Francisco
The anterior cingulate cortex (ACC) plays a key role in pain processing. It has been reported that increased activity of glutamatergic projections into the ACC intensifies nociception; whereas dopaminergic projections inhibit it. The aim of this study was to evaluate the role of dopaminergic and NMDA systems of the ACC in the modulation of long-term nociception elicited by sciatic denervation in the rat. Score, onset and incidence of long-term nociception were measured by the autotomy behavior. The effects of a single microinjection into the ACC of different doses of dopamine (100 nM, 100 microM and 100 mM), a NMDA receptor antagonist (MK801 200 nM and 9.34 mM) and amantadine, a dopamine agonist and NMDA receptor antagonist (10, 100 and 1000 microM) were tested on long-term nociception. Dopamine diminished autotomy behavior in an inverse dose-dependent manner, with dopamine 100 nM as most effective concentration. MK801 and amantadine elicited a significant reduction on autotomy score. Prior injections of D1 and D2 receptor antagonists blocked the antinociceptive effects of amantadine on long-term nociceptive behavior. The present study suggests an interaction between dopaminergic and glutamatergic systems within the ACC in the genesis and maintenance of long-term nociception.
Gasquoine, Philip Gerard
Early localizationists linked anterior cingulate cortex (ACC: Brodmann's area 24 and adjacent regions) with emotional behavior, paving the way for bilateral cingulotomy psychosurgery in severe, treatment resistant, cases of obsessive-compulsive disorder, chronic pain, depression, and substance abuse. Neuropsychological follow-up of such cases demonstrated executive function impairment. Abnormal neuroimaged activity in ACC has been found in many psychiatric conditions, including obsessive-compulsive disorder, chronic pain, substance abuse, and schizophrenia. With healthy participants, increased neuroimaged activity in ACC has been linked with challenging executive function tasks, homeostatically incongruous physical states, and the encoding of the pleasant/averseness of stimuli. There is disagreement on the cortical substrate subsumed by the term ACC, the existence of functionally distinct ACC subregions (e.g., dorsal: cognitive vs. ventral: emotion), and the interpretation of functional neuroimaging studies. Synthesis of neuropsychological and functional neuroimaging studies suggests ACC contributes to behavior by modifying responses especially in reaction to challenging cognitive and physical states that require additional effortful cognitive control. This is accomplished by monitoring the emotional salience of stimuli, exerting control over the autonomic nervous system, and modulating cognitive activity.
Demers, Lauren A.; Olson, Elizabeth A.; Crowley, David J.; Rauch, Scott L.; Rosso, Isabelle M.
Alexithymia, or “no words for feelings”, is highly prevalent in samples with childhood maltreatment and posttraumatic stress disorder (PTSD). The dorsal anterior cingulate cortex (dACC) has been identified as a key region involved in alexithymia, early life trauma, and PTSD. Functional alterations in the dACC also have been associated with alexithymia in PTSD. This study examined whether dACC morphology is a neural correlate of alexithymia in child maltreatment-related PTSD. Sixteen adults with PTSD and a history of childhood sexual abuse, physical abuse, or exposure to domestic violence, and 24 healthy controls (HC) completed the Toronto Alexithymia Scale 20 (TAS–20) and underwent magnetic resonance imaging. Cortical thickness of the dACC was measured using FreeSurfer, and values were correlated with TAS–20 scores, controlling for sex and age, in both groups. Average TAS–20 score was significantly higher in the PTSD than the HC group. TAS–20 scores were significantly positively associated with dACC thickness only in the PTSD group. This association was strongest in the left hemisphere and for TAS–20 subscales that assess difficulty identifying and describing feelings. We found that increasing dACC gray matter thickness is a neural correlate of greater alexithymia in the context of PTSD with childhood maltreatment. While findings are correlational, they motivate further inquiry into the relationships between childhood adversity, emotional awareness and expression, and dACC morphologic development in trauma-related psychopathology. PMID:26439117
Roberts, RC; Barksdale, KA; Roche, JK; Lahti, AC
Schizophrenia (SZ) is a mental illness characterized by psychosis, negative symptoms, and cognitive deficits. The anterior cingulate cortex (ACC), a structurally and functionally diverse region, is one of several brain regions that is abnormal in SZ. The present study compared synaptic organization and mitochondrial number and morphology in postmortem ACC in SZ versus normal control (NC). Total synaptic density in the combined ACC was decreased in SZ, to 72% of normal controls (NCs), due to selective decreases in axospinous synapses, both asymmetric (excitatory) and symmetric (inhibitory). These changes were present in layers 3 and 5/6. The density of mitochondria in all axon terminals combined in SZ was decreased to 64% of NC. In layer 3, mitochondrial density was decreased only in terminals forming asymmetric synapses with spines, while in layers 5/6 mitochondrial density was decreased in terminals forming symmetric synapses with spines and dendrites. The proportion of terminals making symmetric synapses that contained mitochondria was significantly lower in SZ than in NCs, especially for symmetric axospinous synapses. The number of mitochondria per neuronal somata was decreased in the ACC in SZ compared to NCs; this finding was present in layers 5-6. The size of mitochondria in neuronal somata and throughout the neuropil was similar in SZ and NCs. Our results, though preliminary, are well supported by the literature, and support an anatomical substrate for some of the altered executive functions found in SZ. PMID:26210550
Haas, Brian W; Omura, Kazufumi; Constable, R Todd; Canli, Turhan
The amygdala and subgenual anterior cingulate (AC) have been associated with anxiety and mood disorders, for which trait neuroticism is a risk factor. Prior work has not related individual differences in amygdala or subgenual AC activation with neuroticism. Functional magnetic resonance imaging was used to investigate changes in blood oxygen level-dependent signal within the amygdala and subgenual AC associated with trait neuroticism in a nonclinical sample of 36 volunteers during an emotional conflict task. Neuroticism correlated positively with amygdala and subgenual AC activation during trials of high emotional conflict, compared with trials of low emotional conflict. The subscale of neuroticism that reflected the anxious form of neuroticism (N1) explained a greater proportion of variance within the observed clusters than the subscale of neuroticism that reflected the depressive form of neuroticism (N3). Using a task that is sensitive to individual differences in the detection of emotional conflict, the authors have provided a neural correlate of the link between neuroticism and anxiety and mood disorders. This effect was driven to a greater extent by the anxious relative to the depressive characteristics of neuroticism and may constitute vulnerability markers for anxiety-related disorders.
Pezze, M.A.; Marshall, H.J.; Domonkos, A.; Cassaday, H.J.
The anterior cingulate cortex (AC) component of the medial prefrontal cortex (mPFC) has been implicated in attention and working memory as measured by trace conditioning. Since dopamine (DA) is a key modulator of mPFC function, the present study evaluated the role of DA receptor agents in rat AC, using trace fear conditioning. A conditioned stimulus (CS, noise) was followed by an unconditioned stimulus (US, shock) with or without a 10 s trace interval interposed between these events in a between-subjects design. Conditioned suppression of drinking was assessed in response to presentation of the CS or an experimental background stimulus (flashing lights, previously presented for the duration of the conditioning session). The selective D1 agonist SKF81297 (0.05 μg/side) or D1 antagonist SCH23390 (0.5 μg/side) was administered by intra-cerebral microinfusion directly into AC. It was predicted that either of these manipulations should be sufficient to impair trace (but not delay) conditioning. Counter to expectation, there was no effect of DA D1 modulation on trace conditioning as measured by suppression to the noise CS. However, rats infused with SKF81297 acquired stronger conditioned suppression to the experimental background stimulus than those infused with SCH23390 or saline. Thus, the DA D1 agonist SKF81297 increased conditioned suppression to the contextual background light stimulus but was otherwise without effect on fear conditioning. PMID:26343307
Emeric, Erik E.; Brown, Joshua W.; Leslie, Melanie; Pouget, Pierre; Stuphorn, Veit; Schall, Jeffrey D.
We describe intracranial local field potentials (LFP) recorded in the anterior cingulate cortex (ACC) of macaque monkeys performing a saccade countermanding task. The most prominent feature at ∼70% of sites was greater negative polarity after errors than after rewarded correct trials. This negative polarity was also evoked in unrewarded correct trials. The LFP evoked by the visual target was much less polarized, and the weak presaccadic modulation was insufficient to control the initiation of saccades. When saccades were cancelled, LFP modulation decreased slightly with the magnitude of response conflict that corresponds to the coactivation of gaze-shifting and -holding neurons estimated from the probability of canceling. However, response time adjustments on subsequent trials were not correlated with LFP polarity on individual trials. The results provide clear evidence that error- and feedback-related, but not conflict-related, signals are carried by the LFP in the macaque ACC. Finding performance monitoring field potentials in the ACC of macaque monkeys establishes a bridge between event-related potential and functional brain-imaging studies in humans and neurophysiology studies in non-human primates. PMID:18077665
Alexander, William H.; Brown, Joshua W.
The anterior cingulate cortex (ACC) is implicated in performance monitoring and cognitive control. Non-human primate studies of ACC show prominent reward signals, but these are elusive in human studies, which instead show mainly conflict and error effects. Here we demonstrate distinct appetitive and aversive activity in human ACC. The error likelihood hypothesis suggests that ACC activity increases in proportion to the likelihood of an error, and ACC is also sensitive to the consequence magnitude of the predicted error. Previous work further showed that error likelihood effects reach a ceiling as the potential consequences of an error increase, possibly due to reductions in the average reward. We explored this issue by independently manipulating reward magnitude of task responses and error likelihood while controlling for potential error consequences in an incentive change signal task. The fMRI results ruled out a modulatory effect of expected reward on error likelihood effects in favor of a competition effect between expected reward and error likelihood. Dynamic causal modeling showed that error likelihood and expected reward signals are intrinsic to the ACC rather than received from elsewhere. These findings agree with interpretations of ACC activity as signaling both perceptions of risk and predicted reward. PMID:19961940
Brown, Joshua W.
The error likelihood computational model of anterior cingulate cortex (ACC) (Brown & Braver, 2005) has successfully predicted error likelihood effects, risk prediction effects, and how individual differences in conflict and error likelihood effects vary with trait differences in risk aversion. The same computational model now makes a further prediction that apparent conflict effects in ACC may result in part from an increasing number of simultaneously active responses, regardless of whether or not the cued responses are mutually incompatible. In Experiment 1, the model prediction was tested with a modification of the Eriksen flanker task, in which some task conditions require two otherwise mutually incompatible responses to be generated simultaneously. In that case, the two response processes are no longer in conflict with each other. The results showed small but significant medial PFC effects in the incongruent vs. congruent contrast, despite the absence of response conflict, consistent with model predictions. This is the multiple response effect. Nonetheless, actual response conflict led to greater ACC activation, suggesting that conflict effects are specific to particular task contexts. In Experiment 2, results from a change signal task suggested that the context dependence of conflict signals does not depend on error likelihood effects. Instead, inputs to ACC may reflect complex and task specific representations of motor acts, such as bimanual responses. Overall, the results suggest the existence of a richer set of motor signals monitored by medial PFC and are consistent with distinct effects of multiple responses, conflict, and error likelihood in medial PFC. PMID:19375509
Brown, Joshua W.; Braver, Todd S.
The error likelihood effect in anterior cingulate cortex (ACC) has recently been shown to be a special case of an even more general risk prediction effect, which signals both the likelihood of an error and the potential severity of its consequences. Surprisingly, these error likelihood and anticipated consequence effects are strikingly absent in risk-taking individuals. Conversely, conflict effects in ACC were found to be stronger in these same individuals. Here we show that the error likelihood computational model can account for individual differences in error likelihood, predicted error consequence, and conflict effects in ACC with no changes from the published version of the model. In particular, the model accounts for the counter-intuitive inverse relationship between conflict and error likelihood effects as a function of the ACC learning rate in response to errors. As the learning rate increases, ACC learns more effectively from mistakes, which increases risk prediction effects at the expense of conflict effects. Thus, the model predicts that individuals with faster error-based learning in ACC will be more risk averse and show greater ACC error likelihood effects but smaller ACC conflict effects. Furthermore, the model suggests that apparent response conflict effects in ACC may actually consist of two related effects: increased error likelihood and a greater number of simultaneously cued responses, whether or not the responses are mutually incompatible. The results clarify the basic computational mechanisms of learned risk aversion and may have broad implications for predicting and managing risky behavior in healthy and clinical populations. PMID:17707352
Russo, Jennifer F; Sheth, Sameer A
Chronic neuropathic pain is estimated to affect 3%-4.5% of the worldwide population. It is associated with significant loss of productive time, withdrawal from the workforce, development of mood disorders such as depression and anxiety, and disruption of family and social life. Current medical therapeutics often fail to adequately treat chronic neuropathic pain. Deep brain stimulation (DBS) targeting subcortical structures such as the periaqueductal gray, the ventral posterior lateral and medial thalamic nuclei, and the internal capsule has been investigated for the relief of refractory neuropathic pain over the past 3 decades. Recent work has identified the dorsal anterior cingulate cortex (dACC) as a new potential neuromodulation target given its central role in cognitive and affective processing. In this review, the authors briefly discuss the history of DBS for chronic neuropathic pain in the United States and present evidence supporting dACC DBS for this indication. They review existent literature on dACC DBS and summarize important findings from imaging and neurophysiological studies supporting a central role for the dACC in the processing of chronic neuropathic pain. The available neurophysiological and empirical clinical evidence suggests that dACC DBS is a viable therapeutic option for the treatment of chronic neuropathic pain and warrants further investigation.
Jaworska, Natalia; Blier, Pierre; Fusee, Wendy; Knott, Verner
Left fronto-cortical hypoactivity, thought to reflect reduced activity in approach-related systems, and right parietal hypoactivity, associated with emotional under-arousal, have been noted in major depressive disorder (MDD). Altered theta activity in the anterior cingulate cortex (ACC) has also been associated with the disorder. We assessed resting frontal and parietal alpha asymmetry and power in non-medicated MDD (N = 53; 29 females) and control (N = 43; 23 females) individuals. Theta activity was examined using standardized low-resolution electromagnetic tomography (sLORETA) in the ACC [BA24ab and BA32 comprising the rostral ACC and BA25/subgenual (sg) ACC]. The MDD group, and particularly depressed males, displayed increased overall frontal and parietal alpha power and left midfrontal hypoactivity (alpha(2)-indexed). They also exhibited increased sgACC theta(2) activity. MDD females had increased right parietal activity, suggesting increased emotive arousal. Thus, unmedicated depressed adults were characterized by lower activity in regions implicated in approach/positive affective tendencies as well as diffuse cortical hypoarousal, though sex specific modulations emerged. Altered theta in the sgACC may reflect emotion regulation abnormalities in MDD.
Pissiota, Anna; Frans, Orjan; Michelgård, Asa; Appel, Lieuwe; Långström, Bengt; Flaten, Magne Arve; Fredrikson, Mats
The human startle response is modulated by emotional experiences, with startle potentiation associated with negative affect. We used positron emission tomography with 15O-water to study neural networks associated with startle modulation by phobic fear in a group of subjects with specific snake or spider phobia, but not both, during exposure to pictures of their feared and non-feared objects, paired and unpaired with acoustic startle stimuli. Measurement of eye electromyographic activity confirmed startle potentiation during the phobic as compared with the non-phobic condition. Employing a factorial design, we evaluated brain correlates of startle modulation as the interaction between startle and affect, using the double subtraction contrast (phobic startle vs. phobic alone) vs. (non-phobic startle vs. non-phobic alone). As a result of startle potentiation, a significant increase in regional cerebral blood flow was found in the left amygdaloid-hippocampal region, and medially in the affective division of the anterior cingulate cortex (ACC). These results provide evidence from functional brain imaging for a modulatory role of the amygdaloid complex on startle reactions in humans. They also point to the involvement of the affective ACC in the processing of startle stimuli during emotionally aversive experiences. The co-activation of these areas may reflect increased attention to fear-relevant stimuli. Thus, we suggest that the amygdaloid area and the ACC form part of a neural system dedicated to attention and orientation to danger, and that this network modulates startle during negative affect.
Boes, Aaron D; Tranel, Daniel; Anderson, Steven W; Nopoulos, Peg
Variation in emotional processes may contribute to aggressive and defiant behavior. This study assessed these problem behaviors in a large sample of children and adolescents in relation to the volume of two cortical regions with prominent roles in emotion processing, the anterior cingulate cortex (ACC) and ventromedial prefrontal cortex (vmPFC). One hundred seventeen participants (61 boys, 56 girls), ages 7-17, were recruited from the community. Aggressive and defiant behavior was measured using the parent- and teacher-reported Pediatric Behavior Scale and volumetric measures were generated using structural MRI. Regression analyses indicated a significant sex X ACC volume interaction in predicting aggressive and defiant behavior, without significant results for the vmPFC. Follow-up analyses showed that aggressive and defiant behavior is associated with decreased right ACC volume in boys and a nonsignificant reduction in left ACC volume in girls. These results are consistent with the notion that the right ACC acts as a neuroanatomical correlate of aggression and defiance in boys. The authors discuss this finding in light of its implications for understanding the neural correlates of antisocial behavior.
Koike, Hiroyuki; Demars, Michael P; Short, Jennifer A; Nabel, Elisa M; Akbarian, Schahram; Baxter, Mark G; Morishita, Hirofumi
Attention is disrupted commonly in psychiatric disorders, yet mechanistic insight remains limited. Deficits in this function are associated with dorsal anterior cingulate cortex (dACC) excitotoxic lesions and pharmacological disinhibition; however, a causal relationship has not been established at the cellular level. Moreover, this association has not yet been examined in a genetically tractable species such as mice. Here, we reveal that dACC neurons causally contribute to attention processing by combining a chemogenetic approach that reversibly suppresses neural activity with a translational, touchscreen-based attention task in mice. We virally expressed inhibitory hM4Di DREADD (designer receptor exclusively activated by a designer drug) in dACC neurons, and examined the effects of this inhibitory action with the attention-based five-choice serial reaction time task. DREADD inactivation of the dACC neurons during the task significantly increased omission and correct response latencies, indicating that the neuronal activities of dACC contribute to attention and processing speed. Selective inactivation of excitatory neurons in the dACC not only increased omission, but also decreased accuracy. The effect of inactivating dACC neurons was selective to attention as response control, motivation, and locomotion remain normal. This finding suggests that dACC excitatory neurons play a principal role in modulating attention to task-relevant stimuli. This study establishes a foundation to chemogenetically dissect specific cell-type and circuit mechanisms underlying attentional behaviors in a genetically tractable species. PMID:26224620
Jackson, Stacey A. W.; Horst, Nicole K.; Pears, Andrew; Robbins, Trevor W.; Roberts, Angela C.
Two learning mechanisms contribute to decision-making: goal-directed actions and the “habit” system, by which action-outcome and stimulus-response associations are formed, respectively. Rodent lesion studies and human neuroimaging have implicated both the medial prefrontal cortex (mPFC) and the orbitofrontal cortex (OFC) in the neural basis of contingency learning, a critical component of goal-directed actions, though some published findings are conflicting. We sought to reconcile the existing literature by comparing the effects of excitotoxic lesions of the perigenual anterior cingulate cortex (pgACC), a region of the mPFC, and OFC on contingency learning in the marmoset monkey using a touchscreen-based paradigm, in which the contingent relationship between one of a pair of actions and its outcome was degraded selectively. Both the pgACC and OFC lesion groups were insensitive to the contingency degradation, whereas the control group demonstrated selectively higher performance of the nondegraded action when compared with the degraded action. These findings suggest the pgACC and OFC are both necessary for normal contingency learning and therefore goal-directed behavior. PMID:27130662
Geisler, Daniel; Ritschel, Franziska; King, Joseph A.; Bernardoni, Fabio; Seidel, Maria; Boehm, Ilka; Runge, Franziska; Goschke, Thomas; Roessner, Veit; Smolka, Michael N.; Ehrlich, Stefan
Patients with anorexia nervosa (AN) are characterised by increased self-control, cognitive rigidity and impairments in set-shifting, but the underlying neural mechanisms are poorly understood. Here we used functional magnetic resonance imaging (fMRI) to elucidate the neural correlates of behavioural adaptation to changes in reward contingencies in young acutely ill AN patients. Thirty-six adolescent/young adult, non-chronic female AN patients and 36 age-matched healthy females completed a well-established probabilistic reversal learning task during fMRI. We analysed hemodynamic responses in empirically-defined regions of interest during positive feedback and negative feedback not followed/followed by behavioural adaptation and conducted functional connectivity analyses. Although overall task performance was comparable between groups, AN showed increased shifting after receiving negative feedback (lose-shift behaviour) and altered dorsal anterior cingulate cortex (dACC) responses as a function of feedback. Specifically, patients had increased dACC responses (which correlated with perfectionism) and task-related coupling with amygdala preceding behavioural adaption. Given the generally preserved task performance in young AN, elevated dACC responses specifically during behavioural adaption is suggestive of increased monitoring for the need to adjust performance strategies. Higher dACC-amygdala coupling and increased adaptation after negative feedback underlines this interpretation and could be related to intolerance of uncertainty which has been suggested for AN. PMID:28198813
Dorrepaal, Ethy; Draijer, Nel; de Ruiter, Michiel B.; Elzinga, Bernet M.; Sjoerds, Zsuzsika; van Balkom, Anton J.; Smit, Johannes H.; Veltman, Dick J.
Post-traumatic stress disorder (PTSD) is associated with impaired memory performance coupled with functional changes in brain areas involved in declarative memory and emotion regulation. It is not yet clear how symptom severity and comorbidity affect neurocognitive functioning in PTSD. We performed a functional magnetic resonance imaging (fMRI) study with an emotional declarative memory task in 28 Complex PTSD patients with comorbid depressive and personality disorders, and 21 healthy non-trauma-exposed controls. In Complex PTSD patients—compared to controls—encoding of later remembered negative words vs baseline was associated with increased blood oxygenation level dependent (BOLD) response in the left ventral anterior cingulate cortex (ACC) and dorsal ACC extending to the dorsomedial prefrontal cortex (dmPFC) together with a trend for increased left hippocampus activation. Patients tended to commit more False Alarms to negative words compared to controls, which was associated with enhanced left ventrolateral prefrontal and orbitofrontal cortex (vlPFC/OFC) responses. Severity of child abuse was positively correlated with left ventral ACC activity and severity of depression with (para) hippocampal and ventral ACC activity. Presented results demonstrate functional abnormalities in Complex PTSD in the frontolimbic brain circuit also implicated in fear conditioning models, but generally in the opposite direction, which may be explained by severity of the trauma and severity of comorbid depression in Complex PTSD. PMID:22156722
Geisler, Daniel; Ritschel, Franziska; King, Joseph A; Bernardoni, Fabio; Seidel, Maria; Boehm, Ilka; Runge, Franziska; Goschke, Thomas; Roessner, Veit; Smolka, Michael N; Ehrlich, Stefan
Patients with anorexia nervosa (AN) are characterised by increased self-control, cognitive rigidity and impairments in set-shifting, but the underlying neural mechanisms are poorly understood. Here we used functional magnetic resonance imaging (fMRI) to elucidate the neural correlates of behavioural adaptation to changes in reward contingencies in young acutely ill AN patients. Thirty-six adolescent/young adult, non-chronic female AN patients and 36 age-matched healthy females completed a well-established probabilistic reversal learning task during fMRI. We analysed hemodynamic responses in empirically-defined regions of interest during positive feedback and negative feedback not followed/followed by behavioural adaptation and conducted functional connectivity analyses. Although overall task performance was comparable between groups, AN showed increased shifting after receiving negative feedback (lose-shift behaviour) and altered dorsal anterior cingulate cortex (dACC) responses as a function of feedback. Specifically, patients had increased dACC responses (which correlated with perfectionism) and task-related coupling with amygdala preceding behavioural adaption. Given the generally preserved task performance in young AN, elevated dACC responses specifically during behavioural adaption is suggestive of increased monitoring for the need to adjust performance strategies. Higher dACC-amygdala coupling and increased adaptation after negative feedback underlines this interpretation and could be related to intolerance of uncertainty which has been suggested for AN.
Zhang, Xuying; Sullivan, Chelsea S.; Kratz, Megan B.; Kasten, Michael R.; Maness, Patricia F.; Manis, Paul B.
The neural cell adhesion molecule (NCAM), has been shown to be an obligate regulator of synaptic stability and pruning during critical periods of cortical maturation. However, the functional consequences of NCAM deletion on the organization of inhibitory circuits in cortex are not known. In vesicular gamma-amino butyric acid (GABA) transporter (VGAT)-channelrhodopsin2 (ChR2)-enhanced yellow fluorescent protein (EYFP) transgenic mice, NCAM is expressed postnatally at perisomatic synaptic puncta of EYFP-labeled parvalbumin, somatostatin and calretinin-positive interneurons, and in the neuropil in the anterior cingulate cortex (ACC). To investigate how NCAM deletion affects the spatial organization of inhibitory inputs to pyramidal cells, we used laser scanning photostimulation in brain slices of VGAT-ChR2-EYFP transgenic mice crossed to either NCAM-null or wild type (WT) mice. Laser scanning photostimulation revealed that NCAM deletion increased the strength of close-in inhibitory connections to layer 2/3 pyramidal cells of the ACC. In addition, in NCAM-null mice, the intrinsic excitability of pyramidal cells increased, whereas the intrinsic excitability of GABAergic interneurons did not change. The increase in inhibitory tone onto pyramidal cells, and the increased pyramidal cell excitability in NCAM-null mice will alter the delicate coordination of excitation and inhibition (E/I coordination) in the ACC, and may be a factor contributing to circuit dysfunction in diseases such as schizophrenia and bipolar disorder, in which NCAM has been implicated. PMID:28386219
Wu, Huawang; Sun, Hui; Xu, Jinping; Wu, Yan; Wang, Chao; Xiao, Jing; She, Shenglin; Huang, Jianwei; Zou, Wenjin; Peng, Hongjun; Lu, Xiaobing; Huang, Guimao; Jiang, Tianzi; Ning, Yuping; Wang, Jiaojian
Major depressive disorder (MDD) is one of the most prevalent mental disorders. In the brain, the hubs of the brain network play a key role in integrating and transferring information between different functional modules. However, whether the changed pattern in functional network hubs contributes to the onset of MDD remains unclear. Using resting-state functional magnetic resonance imaging (rs-fMRI) and graph theory methods, we investigated whether alterations of hubs can be detected in MDD. First, we constructed the whole-brain voxel-wise functional networks and calculated a functional connectivity strength (FCS) map in each subject in 34 MDD patients and 34 gender-, age- and education level-matched healthy controls (HCs). Next, the two-sample t-test was applied to compare the FCS maps between HC and MDD patients and identified significant decrease of FCS in subgenual anterior cingulate cortex (sgACC) in MDD patients. Subsequent functional connectivity analyses of sgACC showed disruptions in functional connectivity with posterior insula, middle and inferior temporal gyrus, lingual gyrus and cerebellum in MDD patients. Furthermore, the changed FCS of sgACC and functional connections to sgACC were significantly correlated with the Hamilton Depression Rating Scale (HDRS) scores in MDD patients. The results of the present study revealed the abnormal hub of sgACC and its corresponding disrupted frontal-limbic-visual cognitive-cerebellum functional networks in MDD. These findings may provide a new insight for the diagnosis and treatment of MDD. PMID:28018183
Jahn, Andrew; Nee, Derek Evan; Alexander, William H; Brown, Joshua W
A number of theories have been proposed to account for the role of anterior cingulate cortex (ACC) and the broader medial prefrontal cortex (mPFC) in cognition. The recent Prediction of Response Outcome (PRO) computational model casts the mPFC in part as performing two theoretically distinct functions: learning to predict the various possible outcomes of actions, and then evaluating those predictions against the actual outcomes. Simulations have shown that this new model can account for an unprecedented range of known mPFC effects, but the central theory of distinct prediction and evaluation mechanisms within ACC remains untested. Using combined computational neural modeling and fMRI, we show here that prediction and evaluation signals are indeed each represented in the ACC, and furthermore, they are represented in distinct regions within ACC. Our task independently manipulated both the number of predicted outcomes and the degree to which outcomes violated expectancies, the former providing assessment of regions sensitive to prediction and the latter providing assessment of regions sensitive to evaluation. Using quantitative regressors derived from the PRO computational model, we show that prediction-based model signals load on a network including the posterior and perigenual ACC, but outcome evaluation model signals load on the mid-dorsal ACC. These findings are consistent with distinct prediction and evaluation signals as posited by the PRO model and provide new perspective on a large set of known effects within ACC.
Wu, Huawang; Sun, Hui; Xu, Jinping; Wu, Yan; Wang, Chao; Xiao, Jing; She, Shenglin; Huang, Jianwei; Zou, Wenjin; Peng, Hongjun; Lu, Xiaobing; Huang, Guimao; Jiang, Tianzi; Ning, Yuping; Wang, Jiaojian
Major depressive disorder (MDD) is one of the most prevalent mental disorders. In the brain, the hubs of the brain network play a key role in integrating and transferring information between different functional modules. However, whether the changed pattern in functional network hubs contributes to the onset of MDD remains unclear. Using resting-state functional magnetic resonance imaging (rs-fMRI) and graph theory methods, we investigated whether alterations of hubs can be detected in MDD. First, we constructed the whole-brain voxel-wise functional networks and calculated a functional connectivity strength (FCS) map in each subject in 34 MDD patients and 34 gender-, age- and education level-matched healthy controls (HCs). Next, the two-sample t-test was applied to compare the FCS maps between HC and MDD patients and identified significant decrease of FCS in subgenual anterior cingulate cortex (sgACC) in MDD patients. Subsequent functional connectivity analyses of sgACC showed disruptions in functional connectivity with posterior insula, middle and inferior temporal gyrus, lingual gyrus and cerebellum in MDD patients. Furthermore, the changed FCS of sgACC and functional connections to sgACC were significantly correlated with the Hamilton Depression Rating Scale (HDRS) scores in MDD patients. The results of the present study revealed the abnormal hub of sgACC and its corresponding disrupted frontal-limbic-visual cognitive-cerebellum functional networks in MDD. These findings may provide a new insight for the diagnosis and treatment of MDD.
Kim, Jangjin; Wasserman, Edward A.; Castro, Leyre; Freeman, John H.
Previous studies showed that the anterior cingulate cortex (ACC) plays a role in selective visual attention. The current study further examined the role of the ACC in attention using a visual cuing task with task-relevant and task-irrelevant stimuli. On every trial, two stimuli were presented on the touchscreen; one was task-relevant and the other was task-irrelevant. Rats were trained to attend to the task-relevant stimulus over the task-irrelevant stimulus to determine which side of the touchscreen should be selected for reward. After the rats were well-trained, cannulae targeting the ACC were implanted bilaterally for infusions of PBS or muscimol. When the ACC was functionally intact, high task performance was correlated with the anticipatory touches toward the reward; rats touched the stimulus proximal to the correct side more often, regardless of its task-relevancy. Analysis of the pre-surgery training data showed that rats developed anticipatory touches during training. Linear discriminant analyses of the touches also showed that the touches predict rats’ choices in trials. With muscimol infusions, choice accuracy was impaired and the anticipatory touches toward the correct response location were less frequent. A control experiment, in which there were no irrelevant stimuli, showed no effects of ACC inactivation on choice accuracy or anticipatory touches. These results indicate that the rat ACC plays a critical role in reducing distraction from irrelevant stimuli as well as in guiding attention toward the goal locations. PMID:26692448
Shenhav, Amitai; Straccia, Mark A; Cohen, Jonathan D; Botvinick, Matthew M
Previous theories predict that human dorsal anterior cingulate (dACC) should respond to decision difficulty. An alternative theory has been recently advanced that proposes that dACC evolved to represent the value of 'non-default', foraging behavior, calling into question its role in choice difficulty. However, this new theory does not take into account that choosing whether or not to pursue foraging-like behavior can also be more difficult than simply resorting to a default. The results of two neuroimaging experiments show that dACC is only associated with foraging value when foraging value is confounded with choice difficulty; when the two are dissociated, dACC engagement is only explained by choice difficulty, and not the value of foraging. In addition to refuting this new theory, our studies help to formalize a fundamental connection between choice difficulty and foraging-like decisions, while also prescribing a solution for a common pitfall in studies of reward-based decision making.
van Veen, Vincent; Holroyd, Clay B; Cohen, Jonathan D; Stenger, V Andrew; Carter, Cameron S
Recent theories of the neural basis of performance monitoring have emphasized a central role for the anterior cingulate cortex (ACC). Replicating an earlier event-related potential (ERP) study, which showed an error feedback negativity that was modeled as having an ACC generator, we used event-related fMRI to investigate whether the ACC would differentiate between correct and incorrect feedback stimuli in a time estimation task. The design controlled for response conflict and frequency and expectancy effects. Although participants in the current study adjusted their performance following error feedback, we did not observe error feedback-evoked ACC activity. In contrast, we did observe ACC activity while the same subjects performed the Stroop task, in which an area of the ACC activated during both conflict and error trials. These findings are inconsistent with previous dipole models of the error feedback negativity, and suggest the ACC may not be involved in the generation of this ERP component. These results question involvement of the ACC in the detection of errors per se when controlling for conflict.
Wittmann, Marco K.; Kolling, Nils; Akaishi, Rei; Chau, Bolton K. H.; Brown, Joshua W.; Nelissen, Natalie; Rushworth, Matthew F. S.
In many natural environments the value of a choice gradually gets better or worse as circumstances change. Discerning such trends makes predicting future choice values possible. We show that humans track such trends by comparing estimates of recent and past reward rates, which they are able to hold simultaneously in the dorsal anterior cingulate cortex (dACC). Comparison of recent and past reward rates with positive and negative decision weights is reflected by opposing dACC signals indexing these quantities. The relative strengths of time-linked reward representations in dACC predict whether subjects persist in their current behaviour or switch to an alternative. Computationally, trend-guided choice can be modelled by using a reinforcement-learning mechanism that computes a longer-term estimate (or expectation) of prediction errors. Using such a model, we find a relative predominance of expected prediction errors in dACC, instantaneous prediction errors in the ventral striatum and choice signals in the ventromedial prefrontal cortex. PMID:27477632
Frye, Mark A; Hinton, David J; Karpyak, Victor M; Biernacka, Joanna M; Gunderson, Lee J; Feeder, Scott E; Choi, Doo-Sup; Port, John D
Although the precise drug mechanism of action of acamprosate remains unclear, its antidipsotropic effect is mediated in part through glutamatergic neurotransmission. We evaluated the effect of 4 weeks of acamprosate treatment in a cohort of 13 subjects with alcohol dependence (confirmed by a structured interview, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision) on proton magnetic resonance spectroscopy glutamate levels in the midline anterior cingulate cortex (MACC). We compared levels of metabolites with a group of 16 healthy controls. The Pennsylvania Alcohol Craving Scale was used to assess craving intensity. At baseline, before treatment, the mean cerebrospinal fluid-corrected MACC glutamate (Glu) level was significantly elevated in subjects with alcohol dependence compared with controls (P = 0.004). Four weeks of acamprosate treatment reduced glutamate levels (P = 0.025), an effect that was not observed in subjects who did not take acamprosate. At baseline, there was a significant positive correlation between cravings, measured by the Pennsylvania Alcohol Craving Scale, and MACC (Glu) levels (P = 0.019). Overall, these data would suggest a normalizing effect of acamprosate on a hyperglutamatergic state observed in recently withdrawn patients with alcohol dependence and a positive association between MACC glutamate levels and craving intensity in early abstinence. Further research is needed to evaluate the use of these findings for clinical practice, including monitoring of craving intensity and individualized selection of treatment with antidipsotropic medications in subjects with alcohol dependence.
Xie, Kun; Kuang, Hui; Tsien, Joe Z
There is a general interest in understanding of whether and how exposure to emotionally traumatizing events can alter memory function and anxiety behaviors. Here we have developed a novel laboratory-version of mild blast exposure comprised of high decibel bomb explosion sound coupled with strong air blast to mice. This model allows us to isolate the effects of emotionally fearful components from those of traumatic brain injury or bodily injury typical associated with bomb blasts. We demonstrate that this mild blast exposure is capable of impairing object recognition memory, increasing anxiety in elevated O-maze test, and resulting contextual generalization. Our in vivo neural ensemble recording reveal that such mild blast exposures produced diverse firing changes in the anterior cingulate cortex, a region processing emotional memory and inhibitory control. Moreover, we show that these real-time neural ensemble patterns underwent post-event reverberations, indicating rapid consolidation of those fearful experiences. Identification of blast-induced neural activity changes in the frontal brain may allow us to better understand how mild blast experiences result in abnormal changes in memory functions and excessive fear generalization related to post-traumatic stress disorder.
Hayden, Benjamin Y.
We frequently need to commit to a choice to achieve our goals; however, the neural processes that keep us motivated in pursuit of delayed goals remain obscure. We examined ensemble responses of neurons in macaque dorsal anterior cingulate cortex (dACC), an area previously implicated in self-control and persistence, in a task that requires commitment to a choice to obtain a reward. After reward receipt, dACC neurons signaled reward amount with characteristic ensemble firing rate patterns; during the delay in anticipation of the reward, ensemble activity smoothly and gradually came to resemble the postreward pattern. On the subset of risky trials, in which a reward was anticipated with 50% certainty, ramping ensemble activity evolved to the pattern associated with the anticipated reward (and not with the anticipated loss) and then, on loss trials, took on an inverted form anticorrelated with the form associated with a win. These findings enrich our knowledge of reward processing in dACC and may have broader implications for our understanding of persistence and self-control. PMID:26334016
Steullet, Pascal; Cabungcal, Jan-Harry; Cuénod, Michel; Do, Kim Q.
Dopamine release in the prefrontal cortex plays a critical role in cognitive function such as working memory, attention and planning. Dopamine exerts complex modulation on excitability of pyramidal neurons and interneurons, and regulates excitatory and inhibitory synaptic transmission. Because of the complexity of this modulation, it is difficult to fully comprehend the effect of dopamine on neuronal network activity. In this study, we investigated the effect of dopamine on local high-frequency oscillatory neuronal activity (in β band) in slices of the mouse anterior cingulate cortex (ACC). We found that dopamine enhanced the power of these oscillations induced by kainate and carbachol, but did not affect their peak frequency. Activation of D2R and in a lesser degree D1R increased the oscillation power, while activation of D4R had no effect. These high-frequency oscillations in the ACC relied on both phasic inhibitory and excitatory transmission and functional gap junctions. Thus, dopamine released in the ACC promotes high-frequency synchronized local cortical activity which is known to favor information transfer, fast selection and binding of distributed neuronal responses. Finally, the power of these oscillations was significantly enhanced after degradation of the perineuronal nets (PNNs) enwrapping most parvalbumin interneurons. This study provides new insights for a better understanding of the abnormal prefrontal gamma activity in schizophrenia (SZ) patients who display prefrontal anomalies of both the dopaminergic system and the PNNs. PMID:25191228
Matsunaga, Masahiro; Kawamichi, Hiroaki; Koike, Takahiko; Yoshihara, Kazufumi; Yoshida, Yumiko; Takahashi, Haruka K; Nakagawa, Eri; Sadato, Norihiro
Happiness is one of the most fundamental human goals, which has led researchers to examine the source of individual happiness. Happiness has usually been discussed regarding two aspects (a temporary positive emotion and a trait-like long-term sense of being happy) that are interrelated; for example, individuals with a high level of trait-like subjective happiness tend to rate events as more pleasant. In this study, we hypothesized that the interaction between the two aspects of happiness could be explained by the interaction between structure and function in certain brain regions. Thus, we first assessed the association between gray matter density (GMD) of healthy participants and trait-like subjective happiness using voxel-based morphometry (VBM). Further, to assess the association between the GMD and brain function, we conducted functional magnetic resonance imaging (MRI) using the task of positive emotion induction (imagination of several emotional life events). VBM indicated that the subjective happiness was positively correlated with the GMD of the rostral anterior cingulate cortex (rACC). Functional MRI demonstrated that experimentally induced temporal happy feelings were positively correlated with subjective happiness level and rACC activity. The rACC response to positive events was also positively correlated with its GMD. These results provide convergent structural and functional evidence that the rACC is related to happiness and suggest that the interaction between structure and function in the rACC may explain the trait-state interaction in happiness.
Disruption to dopamine homeostasis during brain development has been implicated in a variety of neuropsychiatric disorders, including depression and schizophrenia. Inappropriate expression or activity of GABAergic interneurons are common features of many of these disorders. We discovered a persistent upregulation of GAD67+ and parvalbumin+ neurons within the anterior cingulate cortex of dopamine D2 receptor knockout mice, while other GABAergic interneuron markers were unaffected. Interneuron distribution and number were not altered in the striatum or in the dopamine-poor somatosensory cortex. The changes were already present by postnatal day 14, indicating a developmental etiology. D2eGFP BAC transgenic mice demonstrated the presence of D2 receptor expression within a subset of parvalbumin-expressing cortical interneurons, suggesting the possibility of a direct cellular mechanism through which D2 receptor stimulation regulates interneuron differentiation or survival. D2 receptor knockout mice also exhibited decreased depressive-like behavior compared with wild-type controls in the tail suspension test. These data indicate that dopamine signaling modulates interneuron number and emotional behavior and that developmental D2 receptor loss or blockade could reveal a potential mechanism for the prodromal basis of neuropsychiatric disorders. PMID:25393953
Iseger, Tabitha A; Korgaonkar, Mayuresh S; Kenemans, J Leon; Grieve, Stuart M; Baeken, Chris; Fitzgerald, Paul B; Arns, Martijn
Antidepressant medication is the most common treatment for major depressive disorder (MDD), however, the precise working mechanism underlying these treatments remains unclear. Recent neuromodulation treatments demonstrate that direct stimulation of the dorsolateral prefrontal cortex (DLPFC), dorsomedial prefrontal cortex (DMPFC), and subgenual anterior cingulate (sgACC) relate to clinical improvement, suggesting connectivity alterations of the DLPFC-DMPFC-sgACC network to mediate antidepressant response. The international Study to Predict Optimized Treatment in Depression (iSPOT-D) is an international multicentre study that collected EEG data for 1008 MDD patients, randomized to 3 different antidepressant medications (N=447 MDD with complete pre- and post-treatment data and N=336 non-MDD). Treatment response was defined by a decline of >50% on the Hamilton Rating Score for Depression (HRSD17). We investigated whether connectivity in alpha and theta frequencies of the DLPFC-DMPFC-sgACC network changed from pre- to post-treatment between: (i) patients and controls, and (ii) responders (R) and non-responders (NR). Women exhibited higher alpha and theta connectivity compared to males, both pre- and post-treatment. Furthermore, theta, but not alpha, hypo-connectivity was found for MDD patients. A decreased alpha connectivity after treatment was found only for male responders, while non-responders and females exhibited no changes in alpha connectivity. Decreasing alpha connectivity could potentially serve as a treatment emergent biomarker, in males only. Furthermore, it could be useful to a priori stratify by gender for future MDD studies.
Babapoor-Farrokhran, Sahand; Vinck, Martin; Womelsdorf, Thilo; Everling, Stefan
The frontal eye fields (FEFs) and the anterior cingulate cortex (ACC) are commonly coactivated for cognitive saccade tasks, but whether this joined activation indexes coordinated activity underlying successful guidance of sensorimotor mapping is unknown. Here we test whether ACC and FEF circuits coordinate through phase synchronization of local field potential and neural spiking activity in macaque monkeys performing memory-guided and pro- and anti-saccades. We find that FEF and ACC showed prominent synchronization at a 3–9 Hz theta and a 12–30 Hz beta frequency band during the delay and preparation periods with a strong Granger-causal influence from ACC to FEF. The strength of theta- and beta-band coherence between ACC and FEF but not variations in power predict correct task performance. Taken together, the results support a role of ACC in cognitive control of frontoparietal networks and suggest that narrow-band theta and to some extent beta rhythmic activity indexes the coordination of relevant information during periods of enhanced control demands. PMID:28169987
Brennan, Brian P; Tkachenko, Olga; Schwab, Zachary J; Juelich, Richard J; Ryan, Erin M; Athey, Alison J; Pope, Harrison G; Jenike, Michael A; Baker, Justin T; Killgore, William DS; Hudson, James I; Jensen, J Eric; Rauch, Scott L
The anterior cingulate cortex is implicated in the neurobiology of obsessive–compulsive disorder (OCD). However, few studies have examined functional and neurochemical abnormalities specifically in the rostral subdivision of the ACC (rACC) in OCD patients. We used functional magnetic resonance imaging (fMRI) during an emotional counting Stroop task and single-voxel J-resolved proton magnetic resonance spectroscopy (1H-MRS) in the rACC to examine the function and neurochemistry of the rACC in individuals with OCD and comparison individuals without OCD. Between-group differences in rACC activation and glutamine/glutamate ratio (Gln/Glu), Glu, and Gln levels, as well as associations between rACC activation, Gln/Glu, Glu, Gln, behavioral, and clinical measures were examined using linear regression. In a sample of 30 participants with OCD and 29 age- and sex-matched participants without OCD, participants with OCD displayed significantly reduced rACC deactivation compared with those without OCD in response to OCD-specific words versus neutral words on the emotional counting Stroop task. However, Gln/Glu, Glu, and Gln in the rACC did not differ between groups nor was there an association between reduced rACC deactivation and Gln/Glu, Glu, or Gln in the OCD group. Taken together, these findings strengthen the evidence for rACC dysfunction in OCD, but weigh against an underlying association with abnormal rACC glutamatergic neurotransmission. PMID:25662837
Michelet, Thomas; Bioulac, Bernard; Langbour, Nicolas; Goillandeau, Michel; Guehl, Dominique; Burbaud, Pierre
When a subject faces conflicting situations, decision-making becomes uncertain. The human dorsal anterior cingulate cortex (dACC) has been repeatedly implicated in the monitoring of such situations, and its neural activity is thought to be involved in behavioral adjustment. However, this hypothesis is mainly based on neuroimaging results and is challenged by animal studies that failed to report any neuronal correlates of conflict monitoring. This discrepancy is thought be due either to methodological or more fundamental cross-species differences. In this study, we eliminated methodological biases and recorded single-neuron activity in monkeys performing a Stroop-like task. We found specific changes in dACC activity during incongruent trials but only in a small subpopulation of cells. Critically, these changes were not related to reaction time and were absent before any incorrect action was taken. A larger fraction of neurons exhibited sustained activity during the whole decision period, whereas another subpopulation of neurons was modulated by reaction time, with a gradual increase in their firing rate that peaked at movement onset. Most of the neurons found in these subpopulations exhibited activity after the delivery of an external negative feedback stimulus that indicated an error had been made. These findings, which are consistent with an executive control role, reconcile various theories of prefrontal cortex function and support the homology between human and monkey cognitive architectures.
Sollberger, Marc; Seeley, William W.; Rankin, Katherine P.; Ascher, Elizabeth A.; Rosen, Howard J.; Miller, Bruce L.; Levenson, Robert W.
Self-conscious emotions such as embarrassment arise when one’s actions fail to meet salient social expectations and are accompanied by marked physiological and behavioral activation. We investigated the neural correlates of self-conscious emotional reactivity in 27 patients with behavioral variant frontotemporal dementia (bvFTD), a neurodegenerative disease that disrupts self-conscious emotion and targets brain regions critical for emotional functioning early in the disease course, and in 33 healthy older controls. Subjects participated in an embarrassing karaoke task in which they watched a video clip of themselves singing. They also watched a sad film clip; these data were used to control for non-self-conscious emotional reactivity in response to audiovisual stimuli. Using Freesurfer to quantify regional brain volumes from structural magnetic resonance imaging, right pregenual anterior cingulate cortex (pACC) gray matter volume was the only brain region that was a significant predictor of self-conscious emotion. Smaller pACC volume was associated with attenuated physiological and behavioral self-conscious emotional reactivity, and this relationship was not specific to diagnosis. We argue that these results reflect the significant role that right pACC plays in the visceromotor responding that accompanies self-conscious emotion and that neurodegeneration in this region may underlie the self-conscious emotional decline seen in bvFTD. PMID:22345371
Suzuki, Tadashi; Itoh, Shouichi; Hayashi, Mototaka; Kouno, Masako; Takeda, Katsuhiko
We report the case of a 69-year-old woman with cerebral infarction in the left anterior cingulate cortex and corpus callosum. She showed hyperlexia, which was a distinctive reading phenomenon, as well as ambient echolalia. Clinical features also included complex disorders such as visual groping, compulsive manipulation of tools, and callosal disconnection syndrome. She read words written on the cover of a book and repeated words emanating from unrelated conversations around her or from hospital announcements. The combination of these two features due to a focal lesion has never been reported previously. The supplementary motor area may control the execution of established subroutines according to external and internal inputs. Hyperlexia as well as the compulsive manipulation of tools could be interpreted as faulty inhibition of preexisting essentially intact motor subroutines by damage to the anterior cingulate cortex reciprocally interconnected with the supplementary motor area.
Zavitsanou, K; Huang, X F
Abnormalities in the anterior cingulate cortex have been reported in patients with schizophrenia, and have been implicated in the pathophysiology of this disorder. In the present study, we have examined antipsychotic-sensitive binding sites in the left anterior cingulate cortex of schizophrenia patients and controls. Using quantitative autoradiography and [(3)H]spiperone as a ligand, both saturation and competition experiments were performed in post-mortem brain tissue obtained from six schizophrenia and six control cases. Saturation experiments revealed that the maximum number of [(3)H]spiperone binding sites was significantly reduced by 31% in the schizophrenia group as compared to the control group (65.3+/-5.6 fmol/mg tissue versus 94.2+/-7.3 fmol/mg tissue). Increased dissociation constant was also observed in the schizophrenia group (2.2+/-0.4 nM versus 1.3+/-0.2 nM), but was not statistically significant (P=0.07). Competition experiments were performed in order to examine the pharmacological profile of [(3)H]spiperone binding, and revealed that: (i) displacement of [(3)H]spiperone binding by clozapine and mianserin was significantly reduced in the schizophrenia group as compared to the control group (-26% and -16% respectively); (ii) the order of displacement potency of the drugs tested was: haloperidol>mianserin>butaclamol approximately risperidone>clozapine>2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene. Our results suggest a reduction of antipsychotic-sensitive binding sites in the anterior cingulate cortex of patients with schizophrenia. Such abnormality could lead to an imbalance in neurotransmitter regulation in the anterior cingulate cortex which may contribute to the emergence of some symptoms of schizophrenia.
Onoda, Keiichi; Yamaguchi, Shuhei
Apathy is defined as a mental state characterized by a lack of goal-directed behavior. However, the underlying mechanisms of apathy remain to be fully understood. Apathy shares certain symptoms with depression and both these affective disorders are known to be associated with dysfunctions of the frontal cortex-basal ganglia circuits. It is expected that clarifying differences in neural mechanisms between the two conditions would lead to an improved understanding of apathy. The present study was designed to investigate whether apathy and depression depend on different network properties of the frontal cortex-basal ganglia circuits, by using resting state fMRI. Resting-state fMRI measurement and neuropsychological testing were conducted on middle-aged and older adults (N=392). Based on graph theory, we estimated nodal efficiency (functional integration), local efficiency (functional segregation), and betweenness centrality. We conducted multiple regression analyses for the network parameters using age, sex, apathy, and depression as predictors. Interestingly, results indicated that the anterior cingulate cortex showed lower nodal efficiency, local efficiency, and betweenness centrality in apathy, whereas in depression, it showed higher nodal efficiency and betweenness centrality. The anterior cingulate cortex constitutes the so-called "salience network", which detects salient experiences. Our results indicate that apathy is characterized by decreased salience-related processing in the anterior cingulate cortex, whereas depression is characterized by increased salience-related processing.
Silva, Elizabeth; Quiñones, Belkis; Páez, Ximena; Hernández, Luis
The aim of this research was to find out the effects of ip morphine pretreatment in the extracellular content of the arginine, glutamate, aspartate and GABA levels in the anterior cingulate cortex in rats, during the formalin test (phase I). A combination of micro dialysis and Capillary Electrophoresis Zone and laser-induced fluorescence detection (CZE-LIFD) technique was used to measure the extracellular levels of amino acids in microdialized zones. The microdialysis probes were unilaterally implanted in the left anterior cingulate cortex of freely moving rats. The samples were collected every 30 seconds and derivatized with fluorescein isothiocianate. The arginine, glutamate, aspartate and GABA levels were measured in the CZE-LIFD device. Arginine (p<0.001) and glutamate levels (p<0.012) were significantly increased in the first few minutes following the formalin test (phase 1). Pretreatment with morphine suppressed the glutamate increase. A transient GABA level increase (p<0.001) was also detected. These experiments suggest that rapid changes in neurotransmitters levels were detected in the first few minutes of acute pain as revealed by the glutamate and arginine level increases in the anterior cingulate cortex. These changes could be related to the emotion of pain processing (fear and aversion). Morphine pretreatment produced an increase in GABA levels and a decrease in glutamate levels in the first few minutes. These findings may be related to euphoria and/or analgesia.
Albert, Jacobo; López-Martín, Sara; Tapia, Manuel; Montoya, Daniel; Carretié, Luis
Although the involvement of the anterior cingulate cortex (ACC) in emotional response inhibition is well established, there are several outstanding issues about the nature of this involvement that are not well understood. The present study aimed to examine the precise contribution of the ACC to emotion-modulated response inhibition by capitalizing on fine temporal resolution of the event-related potentials (ERPs) and the recent advances in source localization. To this end, participants (N = 30) performed an indirect affective Go/Nogo task (i.e., unrelated to the emotional content of stimulation) that required the inhibition of a motor response to three types of visual stimuli: arousing negative (A-), neutral (N), and arousing positive (A+). Behavioral data revealed that participants made more commission errors to A+ than to N and A-. Electrophysiological data showed that a specific region of the ACC at the intersection of its dorsal and rostral subdivisions was significantly involved in the interaction between emotional processing and motor inhibition. Specifically, activity reflecting this interaction was observed in the P3 (but not in the N2) time range, and was greater during the inhibition of responses to A+ than to N and A-. Additionally, regression analyses showed that inhibition-related activity within this ACC region was associated with the emotional content of the stimuli (its activity increased as stimulus valence was more positive), and also with behavioral performance (both with reaction times and commission errors). The present results provide additional data for understanding how, when, and where emotion interacts with response inhibition within the ACC.
Kim, Jieun E; Kim, Geon Ha; Hwang, Jaeuk; Kim, Jung Yoon; Renshaw, Perry F; Yurgelun-Todd, Deborah A; Kim, Binna; Kang, Ilhyang; Jeon, Saerom; Ma, Jiyoung; Lyoo, In Kyoon; Yoon, Sujung
The adolescent brain, with ongoing prefrontal maturation, may be more vulnerable to drug use-related neurotoxic changes as compared to the adult brain. We investigated whether the use of methamphetamine (MA), a highly addictive psychostimulant, during adolescence affect metabolic and cognitive functions of the anterior cingulate cortex (ACC). In adolescent MA users (n = 44) and healthy adolescents (n = 53), the levels of N-acetyl aspartate (NAA), a neuronal marker, were examined in the ACC using proton magnetic resonance spectroscopy. The Stroop color-word task was used to assess Stroop interference, which may reflect cognitive functions of behavior monitoring and response selection that are mediated by the ACC. Adolescent MA users had lower NAA levels in the ACC (t = -2.88, P = 0.005) and relatively higher interference scores (t = 2.03, P = 0.045) than healthy adolescents. Moreover, there were significant relationships between lower NAA levels in the ACC and worse interference scores in adolescent MA users (r = -0.61, P < 0.001). Interestingly, early onset of MA use, as compared to late onset, was related to both lower NAA levels in the ACC (t = -2.24, P = 0.03) as well as lower performance on interference measure of the Stroop color-word task (t = 2.25, P = 0.03). The current findings suggest that metabolic dysfunction in the ACC and its related cognitive impairment may play an important role in adolescent-onset addiction, particularly during early adolescence.
Yan, Ni; Cao, Bing; Xu, Jiahe; Hao, Chun; Zhang, Xu; Li, Ying
Studies of both humans and animals suggest that anterior cingulate cortex (ACC) is important for processing pain perception. We identified that perigenul ACC (pACC) sensitization and enhanced visceral pain in a visceral hypersensitive rat in previous studies. Pain contains both sensory and affective dimensions. Teasing apart the mechanisms that control the neural pathways mediating pain affect and sensation in nociceptive behavioral response is a challenge. In this study, using a rodent visceral pain assay that combines the colorectal distension (CRD)-induced visceromotor response (VMR) with the conditioning place avoidance (CPA), we measured a learned behavior that directly reflects the affective component of visceral pain. When CRD was paired with a distinct environment context, the rats spent significantly less time in this compartment on the post-conditioning test days as compared with the pre-conditioning day. Effects were lasted for 14 days. Bilateral pACC lesion significantly reduced CPA scores without reducing acute visceral pain behaviors (CRD-induced VMR). Bilateral administration of non-NMDA receptor antagonist CNQX or NMDA receptor antagonist AP5 into the pACC decreased the CPA scores. AP5 or CNQX at dose of 400 mM produced about 70% inhibition of CRD-CPA in the day 1, 4 and 7, and completely abolished the CPA in the day 14 after conditioning. We concluded that neurons in the pACC are necessary for the "aversiveness" of visceral nociceptor stimulation. pACC activation is critical for the memory processing involved in long-term negative affective state and prediction of aversive stimuli by contextual cue.
Navratilova, Edita; Xie, Jennifer Yanhua; Meske, Diana; Qu, Chaoling; Morimura, Kozo; Okun, Alec; Arakawa, Naohisa; Ossipov, Michael; Fields, Howard L.
Pain is aversive, and its relief elicits reward mediated by dopaminergic signaling in the nucleus accumbens (NAc), a part of the mesolimbic reward motivation pathway. How the reward pathway is engaged by pain-relieving treatments is not known. Endogenous opioid signaling in the anterior cingulate cortex (ACC), an area encoding pain aversiveness, contributes to pain modulation. We examined whether endogenous ACC opioid neurotransmission is required for relief of pain and subsequent downstream activation of NAc dopamine signaling. Conditioned place preference (CPP) and in vivo microdialysis were used to assess negative reinforcement and NAc dopaminergic transmission. In rats with postsurgical or neuropathic pain, blockade of opioid signaling in the rostral ACC (rACC) inhibited CPP and NAc dopamine release resulting from non-opioid pain-relieving treatments, including peripheral nerve block or spinal clonidine, an α2-adrenergic agonist. Conversely, pharmacological activation of rACC opioid receptors of injured, but not pain-free, animals was sufficient to stimulate dopamine release in the NAc and produce CPP. In neuropathic, but not sham-operated, rats, systemic doses of morphine that did not affect withdrawal thresholds elicited CPP and NAc dopamine release, effects that were prevented by blockade of ACC opioid receptors. The data provide a neural explanation for the preferential effects of opioids on pain affect and demonstrate that engagement of NAc dopaminergic transmission by non-opioid pain-relieving treatments depends on upstream ACC opioid circuits. Endogenous opioid signaling in the ACC appears to be both necessary and sufficient for relief of pain aversiveness. PMID:25948274
Drummond, Jana B; Tucholski, Janusz; Haroutunian, Vahram; Meador-Woodruff, James H
The glutamate hypothesis of schizophrenia proposes that abnormal glutamatergic neurotransmission occurs in this illness, and a major contribution may involve dysregulation of the AMPA subtype of ionotropic glutamate receptor (AMPAR). Transmembrane AMPAR regulatory proteins (TARPs) form direct associations with AMPARs to modulate the trafficking and biophysical functions of these receptors, and their dysregulation may alter the localization and activity of AMPARs, thus having a potential role in the pathophysiology of schizophrenia. We performed comparative quantitative real-time PCR and Western blot analysis to measure transcript (schizophrenia, N=25; comparison subjects, N=25) and protein (schizophrenia, N=36; comparison subjects, N=33) expression of TARPs (γ subunits 1-8) in the anterior cingulate cortex (ACC) in schizophrenia and a comparison group. TARP expression was also measured in frontal cortex of rats chronically treated with haloperidol decanoate (28.5mg/kg every three weeks for nine months) to determine the effect of antipsychotic treatment on the expression of these molecules. We found decreased transcript expression of TARP γ-8 in schizophrenia. At the protein level, γ-3 and γ-5 were increased, while γ-4, γ-7 and γ-8 were decreased in schizophrenia. No changes in any of the molecules were noted in the frontal cortex of haloperidol-treated rats. TARPs are abnormally expressed at transcript and protein levels in ACC in schizophrenia, and these changes are likely due to the illness and not to the antipsychotic treatment. Alterations in the expression of TARPs may contribute to the pathophysiology of schizophrenia, and represent a potential mechanism of glutamatergic dysregulation in this illness.
Shenhav, Amitai; Straccia, Mark A; Botvinick, Matthew M; Cohen, Jonathan D
Recent research has highlighted a distinction between sequential foraging choices and traditional economic choices between simultaneously presented options. This was partly motivated by observations in Kolling, Behrens, Mars, and Rushworth, Science, 336(6077), 95-98 (2012) (hereafter, KBMR) that these choice types are subserved by different circuits, with dorsal anterior cingulate (dACC) preferentially involved in foraging and ventromedial prefrontal cortex (vmPFC) preferentially involved in economic choice. To support this account, KBMR used fMRI to scan human subjects making either a foraging choice (between exploiting a current offer or swapping for potentially better rewards) or an economic choice (between two reward-probability pairs). This study found that dACC better tracked values pertaining to foraging, whereas vmPFC better tracked values pertaining to economic choice. We recently showed that dACC's role in these foraging choices is better described by the difficulty of choosing than by foraging value, when correcting for choice biases and testing a sufficiently broad set of foraging values (Shenhav, Straccia, Cohen, & Botvinick Nature Neuroscience, 17(9), 1249-1254, 2014). Here, we extend these findings in 3 ways. First, we replicate our original finding with a larger sample and a task modified to address remaining methodological gaps between our previous experiments and that of KBMR. Second, we show that dACC activity is best accounted for by choice difficulty alone (rather than in combination with foraging value) during both foraging and economic choices. Third, we show that patterns of vmPFC activity, inverted relative to dACC, also suggest a common function across both choice types. Overall, we conclude that both regions are similarly engaged by foraging-like and economic choice.
Cullen, Patrick K; Gilman, T Lee; Winiecki, Patrick; Riccio, David C; Jasnow, Aaron M
Memories for context become less specific with time resulting in animals generalizing fear from training contexts to novel contexts. Though much attention has been given to the neural structures that underlie the long-term consolidation of a context fear memory, very little is known about the mechanisms responsible for the increase in fear generalization that occurs as the memory ages. Here, we examine the neural pattern of activation underlying the expression of a generalized context fear memory in male C57BL/6J mice. Animals were context fear conditioned and tested for fear in either the training context or a novel context at recent and remote time points. Animals were sacrificed and fluorescent in situ hybridization was performed to assay neural activation. Our results demonstrate activity of the prelimbic, infralimbic, and anterior cingulate (ACC) cortices as well as the ventral hippocampus (vHPC) underlie expression of a generalized fear memory. To verify the involvement of the ACC and vHPC in the expression of a generalized fear memory, animals were context fear conditioned and infused with 4% lidocaine into the ACC, dHPC, or vHPC prior to retrieval to temporarily inactivate these structures. The results demonstrate that activity of the ACC and vHPC is required for the expression of a generalized fear memory, as inactivation of these regions returned the memory to a contextually precise form. Current theories of time-dependent generalization of contextual memories do not predict involvement of the vHPC. Our data suggest a novel role of this region in generalized memory, which should be incorporated into current theories of time-dependent memory generalization. We also show that the dorsal hippocampus plays a prolonged role in contextually precise memories. Our findings suggest a possible interaction between the ACC and vHPC controls the expression of fear generalization.
Motomura, Yuki; Kitamura, Shingo; Oba, Kentaro; Terasawa, Yuri; Enomoto, Minori; Katayose, Yasuko; Hida, Akiko; Moriguchi, Yoshiya; Higuchi, Shigekazu; Mishima, Kazuo
Objectives Sleep debt reportedly increases emotional instability, such as anxiety and confusion, in addition to sleepiness and psychomotor impairment. However, the neural basis of emotional instability due to sleep debt has yet to be elucidated. This study investigated changes in emotional responses that are elicited by the simulation of short-term sleep loss and the brain regions responsible for these changes. Subjects and Methods Fourteen healthy adult men aged 24.1±3.3 years (range, 20–32 years) participated in a within-subject crossover study consisting of 5-day sessions of both sleep debt (4 h for time in bed) and sleep control (8 h for time in bed). On the last day of each session, participants underwent polysomnography and completed the State-Trait Anxiety Inventory and Profile of Mood States questionnaires. In addition, functional magnetic resonance imaging was conducted while performing an emotional face viewing task. Results Restricted sleep over the 5-day period increased the activity of the left amygdala in response to the facial expression of fear, whereas a happy facial expression did not change the activity. Restricted sleep also resulted in a significant decrease in the functional connectivity between the amygdala and the ventral anterior cingulate cortex (vACC) in proportion to the degree of sleep debt (as indicated by the percentage of slow wave sleep and δ wave power). This decrease was significantly correlated with activation of the left amygdala and deterioration of subjective mood state. Conclusion The results of this study suggest that continuous and accumulating sleep debt that can be experienced in everyday life can downregulate the functional suppression of the amygdala by the vACC and consequently enhance the response of the amygdala to negative emotional stimuli. Such functional alteration in emotional control may, in part, be attributed to the neural basis of emotional instability during sleep debt. PMID:23418586
Apps, Matthew A J; Ramnani, Narender
Evaluating the costs and benefits of our own choices is central to most forms of decision-making and its mechanisms in the brain are becoming increasingly well understood. To interact successfully in social environments, it is also essential to monitor the rewards that others receive. Previous studies in nonhuman primates have found neurons in the anterior cingulate cortex (ACC) that signal the net value (benefit minus cost) of rewards that will be received oneself and also neurons that signal when a reward will be received by someone else. However, little is understood about the way in which the human brain engages in cost-benefit analyses during social interactions. Does the ACC signal the net value (the benefits minus the costs) of rewards that others will receive? Here, using fMRI, we examined activity time locked to cues that signaled the anticipated reward magnitude (benefit) to be gained and the level of effort (cost) to be incurred either by a subject themselves or by a social confederate. We investigated whether activity in the ACC covaries with the net value of rewards that someone else will receive when that person is required to exert effort for the reward. We show that, although activation in the sulcus of the ACC signaled the costs on all trials, gyral ACC (ACC(g)) activity varied parametrically only with the net value of rewards gained by others. These results suggest that the ACC(g) plays an important role in signaling cost-benefit information by signaling the value of others' rewards during social interactions.
Zhang, Xu; Cao, Bing; Wang, Jun; Liu, Jin; Tung, Vivian Oi Vian; Lam, Paul Kwan Sing; Chan, Leo Lai; Li, Ying
Ciguatoxins (CTXs) cause long-term disturbance of cerebral functions. The primary mechanism of neurotoxicity is related to their interaction with voltage-gated sodium channels. However, until now, the neurological targets for CTXs in the brain of intact animals have not been described. In our study, 1 day following oral exposure to 0.26 ng/g of Pacific ciguatoxin 1 (P-CTX-1), we performed in vivo electrophysiological recordings in the rat anterior cingulate cortex (ACC) and identified the increase in spontaneous firings and enhanced responses to visceral noxious stimulation. Local field recordings characterized the P-CTX-1-induced synaptic potentiation and blockage of the induction of electrical stimulation-induced long-term potentiation in the medial thalamus (MT)-ACC pathway. Furthermore, intracerebroventricular administration of P-CTX-1 at doses of 1.0, 5.0, and 10 nM produced a dose-dependent increase in ACC neuronal firings and MT-ACC synaptic transmission. Further studies showed upregulated Na(+) channel expression in astrocytes under pathological conditions. We hypothesized that the astrocytes might have been activated in the ciguatera poisoning in vivo. Increases in glial fibrillary acid protein expression were detected in reactive astrocytes in the rat ACC. The activation of astroglia was further indicated by activation of the gap junction protein connexin 43 and upregulation of excitatory amino acid transporter 2 expression suggesting that glutamate was normally rapidly cleared from the synaptic cleft during acute ciguatera poisoning. However, neurotoxicity and reactive astrogliosis were not detected in the ACC after 7 days of P-CTX-1 exposure. The present results are the first characterization of P-CTX-1-invoked brain cortex neuronal excitotoxicity in vivo and supported the theme that neuron and astroglia signals might play roles in acute ciguatera poisoning.
Shibata, Hideshi; Naito, Jumpei
The retrosplenial cortex (areas 29a-d), which plays an important role in spatial memory and navigation, is known to provide massive projections to frontal association and motor cortices, which are also essential for spatial behavior. The reciprocal projections originating from these frontal cortices to areas 29a-d, however, have been analyzed to only a limited extent. Here, we report an analysis of the anatomical organization of projections from anterior cingulate area 24 and motor and prefrontal cortices to areas 29a-d in the rat, using the axonal transport of cholera toxin B subunit and biotinylated dextran amine. Area 29a receives projections from rostral area 24a, area 24b, the ventral orbital area, and the caudal secondary motor area. Rostral area 29b receives projections from caudal area 24a, whereas caudal area 29b receives projections from rostral area 24a. Area 29b also receives projections from area 24b and the ventral orbital area. Areas 29c and 29d receive projections from areas 24a and 24b and the secondary motor area in a topographic manner such that the rostrocaudal axis of areas 29c and 29d corresponds to the caudorostral axis of areas 24a and 24b and the secondary motor area. Rostral areas 29c and 29d also receive projections from the caudal primary motor area, and area 29d receives projections from the ventral, lateral, and medial orbital areas. These differential frontal cortical projections to each area of the retrosplenial cortex suggest that each area may contribute to different aspects of retrosplenial cortical function such as spatial memory and behavior.
Asemi, Avisa; Ramaseshan, Karthik; Burgess, Ashley; Diwadkar, Vaibhav A.; Bressler, Steven L.
Motor control is integral to all types of human behavior, and the dorsal Anterior Cingulate Cortex (dACC) is thought to play an important role in the brain network underlying motor control. Yet the role of the dACC in motor control is under-characterized. Here we aimed to characterize the dACC’s role in adolescent brain network interactions during a simple motor control task involving visually coordinated unimanual finger movements. Network interactions were assessed using both undirected and directed functional connectivity analysis of functional Magnetic Resonance Imaging (fMRI) Blood-Oxygen-Level-Dependent (BOLD) signals, comparing the task with a rest condition. The relation between the dACC and Supplementary Motor Area (SMA) was compared to that between the dACC and Primary Motor Cortex (M1). The directed signal from dACC to SMA was significantly elevated during motor control in the task. By contrast, the directed signal from SMA to dACC, both directed signals between dACC and M1, and the undirected functional connections of dACC with SMA and M1, all did not differ between task and rest. Undirected coupling of dACC with both SMA and dACC, and only the dACC-to-SMA directed signal, were significantly greater for a proactive than a reactive task condition, suggesting that dACC plays a role in motor control by maintaining stimulus timing expectancy. Overall, these results suggest that the dACC selectively modulates the SMA during visually coordinated unimanual behavior in adolescence. The role of the dACC as an important brain area for the mediation of task-related motor control may be in place in adolescence, continuing into adulthood. The task and analytic approach described here should be extended to the study of healthy adults to examine network profiles of the dACC during basic motor behavior. PMID:26089783
Blom, Sigrid Marie; Pfister, Jean-Pascal; Santello, Mirko; Senn, Walter; Nevian, Thomas
Neuropathic pain caused by peripheral nerve injury is a debilitating neurological condition of high clinical relevance. On the cellular level, the elevated pain sensitivity is induced by plasticity of neuronal function along the pain pathway. Changes in cortical areas involved in pain processing contribute to the development of neuropathic pain. Yet, it remains elusive which plasticity mechanisms occur in cortical circuits. We investigated the properties of neural networks in the anterior cingulate cortex (ACC), a brain region mediating affective responses to noxious stimuli. We performed multiple whole-cell recordings from neurons in layer 5 (L5) of the ACC of adult mice after chronic constriction injury of the sciatic nerve of the left hindpaw and observed a striking loss of connections between excitatory and inhibitory neurons in both directions. In contrast, no significant changes in synaptic efficacy in the remaining connected pairs were found. These changes were reflected on the network level by a decrease in the mEPSC and mIPSC frequency. Additionally, nerve injury resulted in a potentiation of the intrinsic excitability of pyramidal neurons, whereas the cellular properties of interneurons were unchanged. Our set of experimental parameters allowed constructing a neuronal network model of L5 in the ACC, revealing that the modification of inhibitory connectivity had the most profound effect on increased network activity. Thus, our combined experimental and modeling approach suggests that cortical disinhibition is a fundamental pathological modification associated with peripheral nerve damage. These changes at the cortical network level might therefore contribute to the neuropathic pain condition.
O’Reilly, Jill X.; Schüffelgen, Urs; Cuell, Steven F.; Behrens, Timothy E. J.; Mars, Rogier B.; Rushworth, Matthew F. S.
Brains use predictive models to facilitate the processing of expected stimuli or planned actions. Under a predictive model, surprising (low probability) stimuli or actions necessitate the immediate reallocation of processing resources, but they can also signal the need to update the underlying predictive model to reflect changes in the environment. Surprise and updating are often correlated in experimental paradigms but are, in fact, distinct constructs that can be formally defined as the Shannon information (IS) and Kullback–Leibler divergence (DKL) associated with an observation. In a saccadic planning task, we observed that distinct behaviors and brain regions are associated with surprise/IS and updating/DKL. Although surprise/IS was associated with behavioral reprogramming as indexed by slower reaction times, as well as with activity in the posterior parietal cortex [human lateral intraparietal area (LIP)], the anterior cingulate cortex (ACC) was specifically activated during updating of the predictive model (DKL). A second saccade-sensitive region in the inferior posterior parietal cortex (human 7a), which has connections to both LIP and ACC, was activated by surprise and modulated by updating. Pupillometry revealed a further dissociation between surprise and updating with an early positive effect of surprise and late negative effect of updating on pupil area. These results give a computational account of the roles of the ACC and two parietal saccade regions, LIP and 7a, by which their involvement in diverse tasks can be understood mechanistically. The dissociation of functional roles between regions within the reorienting/reprogramming network may also inform models of neurological phenomena, such as extinction and Balint syndrome, and neglect. PMID:23986499
Kaping, Daniel; Vinck, Martin; Hutchison, R Matthew; Everling, Stefan; Womelsdorf, Thilo
Attentional control ensures that neuronal processes prioritize the most relevant stimulus in a given environment. Controlling which stimulus is attended thus originates from neurons encoding the relevance of stimuli, i.e. their expected value, in hand with neurons encoding contextual information about stimulus locations, features, and rules that guide the conditional allocation of attention. Here, we examined how these distinct processes are encoded and integrated in macaque prefrontal cortex (PFC) by mapping their functional topographies at the time of attentional stimulus selection. We find confined clusters of neurons in ventromedial PFC (vmPFC) that predominantly convey stimulus valuation information during attention shifts. These valuation signals were topographically largely separated from neurons predicting the stimulus location to which attention covertly shifted, and which were evident across the complete medial-to-lateral extent of the PFC, encompassing anterior cingulate cortex (ACC), and lateral PFC (LPFC). LPFC responses showed particularly early-onset selectivity and primarily facilitated attention shifts to contralateral targets. Spatial selectivity within ACC was delayed and heterogeneous, with similar proportions of facilitated and suppressed responses during contralateral attention shifts. The integration of spatial and valuation signals about attentional target stimuli was observed in a confined cluster of neurons at the intersection of vmPFC, ACC, and LPFC. These results suggest that valuation processes reflecting stimulus-specific outcome predictions are recruited during covert attentional control. Value predictions and the spatial identification of attentional targets were conveyed by largely separate neuronal populations, but were integrated locally at the intersection of three major prefrontal areas, which may constitute a functional hub within the larger attentional control network.
Holroyd, Clay B; Coles, Michael G H
Two competing types of theory have been proposed about the function of dorsal anterior cingulate cortex (dACC): evaluative theories hold that dACC monitors ongoing behavior to detect errors or conflict, whereas response selection theories hold that dACC is directly involved in the decision making process. In particular, one response selection theory proposes that dACC utilizes reward prediction error signals carried by the midbrain dopamine system to decide which of several competing motor control systems should be given control over the motor system (Holroyd and Coles, 2002). The theory further proposes that the impact of these dopamine signals on dACC determines the amplitude of a component of the event-related brain potential called the error-related negativity (ERN). In the present study, we applied this theory to a decision making problem that requires participants to select between two response options in which an erroneous choice is not clearly defined. Rather, the reward received for a particular response evolves in relation to the individual's previous behavior. We adapted a computational model associated with the theory to simulate human performance and the ERN in the task, and tested the predictions of the model against empirical ERP data. Our results indicate that ERN amplitude reflects the subjective value attributed by each participant to their response options as derived from their recent reward history. This finding is consistent with the position that dACC integrates the recent history of reinforcements to guide voluntary choice behavior, as opposed to evaluating behaviors per se.
Drummond, Jana B.; Tucholski, Janusz; Haroutunian, Vahram; Meador-Woodruff, James H.
The glutamate hypothesis of schizophrenia proposes that abnormal glutamatergic neurotransmission occurs in this illness, and a major contribution may involve dysregulation of the AMPA subtype of ionotropic glutamate receptor (AMPAR). Transmembrane AMPAR regulatory proteins (TARPs) form direct associations with AMPARs to modulate the trafficking and biophysical functions of these receptors, and their dysregulation may alter the localization and activity of AMPARs, thus having a potential role in the pathophysiology of schizophrenia. We performed comparative quantitative real-time PCR and Western blot analysis to measure transcript (schizophrenia, N = 25; comparison subjects, N = 25) and protein (schizophrenia, N = 36; comparison subjects, N = 33) expression of TARPs (γ subunits 1-8) in the anterior cingulate cortex (ACC) in schizophrenia and a comparison group. TARP expression was also measured in frontal cortex of rats chronically treated with haloperidol decanoate (28.5 mg/kg every three weeks for nine months) to determine the effect of antipsychotic treatment on the expression of these molecules. We found decreased transcript expression of TARP γ-8 in schizophrenia. At the protein level, γ-3 and γ-5 were increased, while γ-4, γ-7 and γ-8 were decreased in schizophrenia. No changes in any of the molecules were noted in the frontal cortex of haloperidol-treated rats. TARPs are abnormally expressed at transcript and protein levels in ACC in schizophrenia, and these changes are likely due to the illness and not antipsychotic treatment. Alterations in the expression of TARPs may contribute to the pathophysiology of schizophrenia, and represent a potential mechanism of glutamatergic dysregulation in this illness. PMID:23566497
Toda, Koji; Sugase-Miyamoto, Yasuko; Mizuhiki, Takashi; Inaba, Kiyonori; Richmond, Barry J.; Shidara, Munetaka
Background The value of a predicted reward can be estimated based on the conjunction of both the intrinsic reward value and the length of time to obtain it. The question we addressed is how the two aspects, reward size and proximity to reward, influence the responses of neurons in rostral anterior cingulate cortex (rACC), a brain region thought to play an important role in reward processing. Methods and Findings We recorded from single neurons while two monkeys performed a multi-trial reward schedule task. The monkeys performed 1–4 sequential color discrimination trials to obtain a reward of 1–3 liquid drops. There were two task conditions, a valid cue condition, where the number of trials and reward amount were associated with visual cues, and a random cue condition, where the cue was picked from the cue set at random. In the valid cue condition, the neuronal firing is strongly modulated by the predicted reward proximity during the trials. Information about the predicted reward amount is almost absent at those times. In substantial subpopulations, the neuronal responses decreased or increased gradually through schedule progress to the predicted outcome. These two gradually modulating signals could be used to calculate the effect of time on the perception of reward value. In the random cue condition, little information about the reward proximity or reward amount is encoded during the course of the trial before reward delivery, but when the reward is actually delivered the responses reflect both the reward proximity and reward amount. Conclusions Our results suggest that the rACC neurons encode information about reward proximity and amount in a manner that is dependent on utility of reward information. The manner in which the information is represented could be used in the moment-to-moment calculation of the effect of time and amount on predicted outcome value. PMID:22279569
Reser, David H; Majka, Piotr; Snell, Shakira; Chan, Jonathan M H; Watkins, Kirsty; Worthy, Katrina; Quiroga, Maria Del Mar; Rosa, Marcello G P
The claustrum has been the subject of intense research interest in recent years, driven in large part by its extensive connections with various regions of the cerebral cortex and by hypotheses surrounding its possible role in multimodal sensory and/or sensory-emotional integration. Here we employed neuroanatomical tracers to map projections from the claustrum-insular region to the medial prefrontal and anterior cingulate cortex of the common marmoset (Callithrx jacchus). These areas were selected based on their identification as "hub" areas of the default mode and cortical salience networks, respectively. Microinjections of fluorescent tracers, along with gold-nanoparticle-conjugated cholera toxin B-subunit and biotinylated dextran amine, were placed in subdivisions of the anterior cingulate area 24b/c and in medial prefrontal areas 32 and 32V. The resulting distribution of transported label showed rostral-caudal and dorsal-ventral topographic arrangement of claustrum connections and clear rostral-caudal topography of insular projections. Medial prefrontal connections were restricted mainly to a ventromedial strip located in the rostral half of the claustrum, with a second, smaller patch of cells in the caudal, ventrolateral portion. In contrast, injections into area 24 yielded dense, widespread connections from the dorsal claustrum, extending along its entire rostral-caudal length. Projections from the "classical" agranular, disgranular, and granular insular areas were sparse or nonexistent in areas 32 and 32V, with progressively increasing connections observed in more caudal tracer injections (i.e., in subdivisions of area 24). Transported label was observed in rostral peri-insular areas orbital periallocortex, orbital proisocortex, and insular proisocortex following all prefrontal injections. These data provide a structural connectivity foundation for interpretation of functional imaging studies, which often indicate activity in the "anterior insula" that may
Thakkar, Katharine N; Polli, Frida E; Joseph, Robert M; Tuch, David S; Hadjikhani, Nouchine; Barton, Jason J S; Manoach, Dara S
Autism spectrum disorders (ASD) are characterized by inflexible and repetitive behaviour. Response monitoring involves evaluating the consequences of behaviour and making adjustments to optimize outcomes. Deficiencies in this function, and abnormalities in the anterior cingulate cortex (ACC) on which it relies, have been reported as contributing factors to autistic disorders. We investigated whether ACC structure and function during response monitoring were associated with repetitive behaviour in ASD. We compared ACC activation to correct and erroneous antisaccades using rapid presentation event-related functional MRI in 14 control and ten ASD participants. Because response monitoring is the product of coordinated activity in ACC networks, we also examined the microstructural integrity of the white matter (WM) underlying this brain region using diffusion tensor imaging (DTI) measures of fractional anisotropy (FA) in 12 control and 12 adult ASD participants. ACC activation and FA were examined in relation to Autism Diagnostic Interview-Revised ratings of restricted and repetitive behaviour. Relative to controls, ASD participants: (i) made more antisaccade errors and responded more quickly on correct trials; (ii) showed reduced discrimination between error and correct responses in rostral ACC (rACC), which was primarily due to (iii) abnormally increased activation on correct trials and (iv) showed reduced FA in WM underlying ACC. Finally, in ASD (v) increased activation on correct trials and reduced FA in rACC WM were related to higher ratings of repetitive behaviour. These findings demonstrate functional and structural abnormalities of the ACC in ASD that may contribute to repetitive behaviour. rACC activity following errors is thought to reflect affective appraisal of the error. Thus, the hyperactive rACC response to correct trials can be interpreted as a misleading affective signal that something is awry, which may trigger repetitive attempts at correction
Alkawadri, Rafeed; So, Norman K.; Van Ness, Paul C.; Alexopoulos, Andreas V.
IMPORTANCE The literature on cingulate gyrus epilepsy in the magnetic resonance imaging era is limited to case reports and small case series. To our knowledge, this is the largest study of surgically confirmed epilepsy arising from the anterior or posterior cingulate region. OBJECTIVE To characterize the clinical and electrophysiological findings of epilepsies arising from the anterior and posterior cingulate gyrus. DESIGN, SETTING, AND PARTICIPANTS We studied consecutive cingulate gyrus epilepsy cases identified retrospectively from the Cleveland Clinic and University of Texas Southwestern Medical Center epilepsy databases from 1992 to 2009. Participants included 14 consecutive cases of cingulate gyrus epilepsies confirmed by restricted magnetic resonance image lesions and seizure freedom or marked improvement following lesionectomy. MAIN OUTCOMES AND MEASURES The main outcome measure was improvement in seizure frequency following surgery. The clinical, video electroencephalography, neuroimaging, pathology, and surgical outcome data were reviewed. RESULTS All 14 patients had cingulate epilepsy confirmed by restricted magnetic resonance image lesions and seizure freedom or marked improvement following lesionectomy. They were divided into 3 groups based on anatomical location of the lesion and corresponding seizure semiology. In the posterior cingulate group, all 4 patients had electroclinical findings suggestive of temporal origin of the epilepsy. The anterior cingulate cases were divided into a typical (Bancaud) group (6 cases with hypermotor seizures and infrequent generalization with the presence of fear, laughter, or severe interictal personality changes) and an atypical group (4 cases presenting with simple motor seizures and a tendency for more frequent generalization and less-favorable long-term surgical outcome). All atypical cases were associated with an underlying infiltrative astrocytoma. CONCLUSIONS AND RELEVANCE Posterior cingulate gyrus epilepsy may
Zamroziewicz, Marta K.; Paul, Erick J.; Rubin, Rachael D.; Barbey, Aron K.
Introduction: Although diet has a substantial influence on the aging brain, the relationship between biomarkers of diet and aspects of brain health remains unclear. This study examines the neural mechanisms that mediate the relationship between omega-3 polyunsaturated fatty acids (O3PUFAs) and executive functions in at-risk (APOE e4 carriers), cognitively intact older adults. We hypothesized that higher levels of O3PUFAs are associated with better performance in a particular component of the executive functions, namely cognitive flexibility, and that this relationship is mediated by gray matter volume of a specific region thought to be important for cognitive flexibility, the anterior cingulate cortex. Methods: We examined 40 cognitively intact adults between the ages of 65 and 75 with the APOE e4 polymorphism to investigate the relationship between biomarkers of O3PUFAs, tests of cognitive flexibility (measured by the Delis-Kaplan Executive Function System Trail Making Test), and gray matter volume within regions of the prefrontal cortex (PFC). Results: A mediation analysis revealed that gray matter volume within the left rostral anterior cingulate cortex partially mediates the relationship between O3PUFA biomarkers and cognitive flexibility. Conclusion: These results suggest that the anterior cingulate cortex acts as a mediator of the relationship between O3PUFAs and cognitive flexibility in cognitively intact adults thought to be at risk for cognitive decline. Through their link to executive functions and neuronal measures of PFC volume, O3PUFAs show potential as a nutritional therapy to prevent dysfunction in the aging brain. PMID:26052283
Gulick, Danielle; Gould, Thomas J
The current study examines the role of the dorsal and ventral hippocampus, and anterior cingulate in the interactive effects of ethanol and nicotine on learning, anxiety and locomotion in the plus-maze discriminative avoidance task, which allows dissociation of drug effects on each behaviour. At training, time spent in each of the arms of the elevated plus-maze was recorded for 5 minutes. Each time that the mouse entered the aversive enclosed arm, a light and white noise were turned on. At testing, no cues were turned on and time spent in each arm was recorded for 3 minutes. The effects of systemic ethanol (1.0 or 1.4 g/kg) and nicotine (0.35 µg/0.50 µl/side) infused into the anterior cingulate, dorsal and ventral hippocampus were examined, as were the interactive effects of systemic ethanol (1.0 g/kg) and nicotine (0.09 mg/kg) with the high-affinity nicotinic receptor antagonist dihydro-beta-erythroidine (DHβE) (18.0 µg/0.50 µl/side) infused into the anterior cingulate. Ethanol dose dependently decreased anxiety, increased locomotion, and decreased learning. Anterior cingulate-infused nicotine decreased anxiety and reversed ethanol-associated learning deficits. Anterior cingulate-infused DHβE blocked reversal of ethanol-induced learning deficits by systemic nicotine. Dorsal hippocampus-infused nicotine reversed ethanol-induced anxiolysis and hyper-locomotion (1.4 g/kg) but produced no behavioural changes in ethanol-naïve mice. Ventral hippocampus-infused nicotine enhanced anxiolysis associated with 1.4 g/kg ethanol, but had no other effects. The anterior cingulate is necessary and sufficient for nicotine reversal of ethanol-induced learning deficits. In addition, the anterior cingulate, dorsal hippocampus and ventral hippocampus may mediate drug-induced changes in anxiety.
Huang, Wei; King, Jean A; Ursprung, W W Sanouri; Zheng, Shaokuan; Zhang, Nanyin; Kennedy, David N; Ziedonis, Douglas; DiFranza, Joseph R
Introduction Perturbations in neural function provoked by a drug are thought to induce neural adaptations, which, in the absence of the drug, give rise to withdrawal symptoms. Previously published structural data from this study indicated that the progressive development of physical dependence is associated with increasing density of white matter tracts between the anterior cingulum bundle and the precuneus. Methods Using functional magnetic resonance imaging, we compared 11 smokers after 11 h of abstinence from nicotine and after satiation, with 10 nonsmoking controls, using independent component analysis for brain network comparisons as well as a whole brain resting-state functional connectivity analysis using the anterior cingulate cortex as a seed. Results Independent component analysis demonstrated increased functional connectivity in brain networks such as the default mode network associated with the withdrawal state in multiple brain regions. In seed-based analysis, smokers in the withdrawal state showed stronger functional connectivity than nonsmoking controls between the anterior cingulate cortex and the precuneus, caudate, putamen, and frontal cortex (P < 0.05). Among smokers, compared to the satiated state, nicotine withdrawal was associated with increased connectivity between the anterior cingulate cortex and the precuneus, insula, orbital frontal gyrus, superior frontal gyrus, posterior cingulate cortex, superior temporal, and inferior temporal lobe (P < 0.02). The intensity of withdrawal-induced craving correlated with the strength of connectivity between the anterior cingulate cortex and the precuneus, insula, caudate, putamen, middle cingulate gyrus, and precentral gyrus (r = 0.60–0.76; P < 0.05). Conclusions In concordance with our previous report that structural neural connectivity between the anterior cingulate area and the precuneus increased in proportion to the progression of physical dependence, resting-state functional connectivity in this
Rosso, Isabelle M.; Weiner, Melissa R.; Crowley, Davidan J; Silveri, Marisa M.; Rauch, Scott L.; Jensen, J. Eric
Background Increased reactivity of the insular cortex and decreased activity of the dorsal anterior cingulate (ACC) are seen in functional imaging studies of post-traumatic stress disorder (PTSD), and may partly explain the persistent fear- and anxiety-proneness that characterize the disorder. A possible neurochemical correlate is altered function of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). We report results from what we believe is the first study applying proton magnetic resonance spectroscopy (1H-MRS) to measure brain GABA in PTSD. Methods Thirteen adults with DSM-IV PTSD and 13 matched healthy control subjects underwent single voxel 1H-MRS at 4 Tesla. GABA was measured in the right anterior insula and dorsal anterior cingulate, using MEGAPRESS spectral editing. Subjects were interviewed with the Structured Clinical Interview for DSM-IV and the Clinician Administered PTSD Scale, and also completed the State and Trait Anxiety Inventory. Results Insula GABA was significantly lower in PTSD subjects than in controls, and dorsal ACC GABA did not differ significantly between the groups. Insula GABA was not significantly associated with severity of PTSD symptoms. However, lower insula GABA was associated with significantly higher state and trait anxiety in the subject sample as a whole. Conclusions PTSD is associated with reduced GABA in the right anterior insula. This preliminary evidence of the 1H-MRS GABA metabolite as a possible biomarker of PTSD encourages replication in larger samples and examination of relations with symptom dimensions. Future studies also should examine whether insula GABA is a marker of anxiety proneness, cutting across clinical diagnostic categories. PMID:23861191
Pastorello, Bruno F.; Leite, Cláudia da Costa; Henning, Anke; Moreno, Ricardo A.; Garcia Otaduy, Maria Concepción
Objective: Oxidative stress and mitochondrial dysfunction are 2 closely integrated processes implicated in the physiopathology of bipolar disorder. Advanced proton magnetic resonance spectroscopy techniques enable the measurement of levels of lactate, the main marker of mitochondrial dysfunction, and glutathione, the predominant brain antioxidant. The objective of this study was to measure brain lactate and glutathione levels in bipolar disorder and healthy controls. Methods: Eighty-eight individuals (50 bipolar disorder and 38 healthy controls) underwent 3T proton magnetic resonance spectroscopy in the dorsal anterior cingulate cortex (2x2x4.5cm3) using a 2-D JPRESS sequence. Lactate and glutathione were quantified using the ProFit software program. Results: Bipolar disorder patients had higher dorsal anterior cingulate cortex lactate levels compared with controls. Glutathione levels did not differ between euthymic bipolar disorder and controls. There was a positive correlation between lactate and glutathione levels specific to bipolar disorder. No influence of medications on metabolites was observed. Conclusion: This is the most extensive magnetic resonance spectroscopy study of lactate and glutathione in bipolar disorder to date, and results indicated that euthymic bipolar disorder patients had higher levels of lactate, which might be an indication of altered mitochondrial function. Moreover, lactate levels correlated with glutathione levels, indicating a compensatory mechanism regardless of bipolar disorder diagnosis. PMID:27207914
Akanuma, Kyoko; Meguro, Kenichi; Meguro, Mitsue; Sasaki, Eriko; Chiba, Kentaro; Ishii, Hiroshi; Tanaka, Naofumi
A group reminiscence approach (GRA) with reality orientation (RO) is widely used as a psychosocial intervention for dementia. Since clinical effectiveness was reported for the intervention, interest has been directed toward areas of the neuronal network that might be being stimulated. We hypothesized that the frontal lobe associated with social interaction was being stimulated. To test this hypothesis, we studied 24 patients with vascular dementia. In addition to conventional care, a 1-h session of GRA with RO was provided once a week for 3 months in the GRA-RO arm (n=12). Only supportive care was provided in the control arm (n=12). Before and after the interventions, cognitive function, depressive state, and social activities were assessed. Since glucose metabolism is associated with brain function, cerebral glucose metabolism was measured by positron emission tomography (PET). Regarding behavioral improvement, 10 patients in the GRA-RO arm showed improvement compared with only two patients in the control arm, a significant difference. PET demonstrated that metabolism in the anterior cingulate was increased in the GRA-RO arm, whereas no significant changes were observed in the control arm. These results suggest that GRA-RO stimulates the anterior cingulate and has a positive effect on social interaction.
Xi, Yi-Bin; Li, Chen; Cui, Long-Biao; Liu, Jian; Guo, Fan; Li, Liang; Liu, Ting-Ting; Liu, Kang; Chen, Gang; Xi, Min; Wang, Hua-Ning; Yin, Hong
Familial risk plays a significant role in the etiology of schizophrenia (SZ). Many studies using neuroimaging have demonstrated structural and functional alterations in relatives of SZ patients, with significant results found in diverse brain regions involving the anterior cingulate cortex (ACC), caudate, dorsolateral prefrontal cortex (DLPFC), and hippocampus. This study investigated whether unaffected relatives of first episode SZ differ from healthy controls (HCs) in effective connectivity measures among these regions. Forty-six unaffected first-degree relatives of first episode SZ patients—according to the DSM-IV—were studied. Fifty HCs were included for comparison. All subjects underwent resting state functional magnetic resonance imaging (fMRI). We used stochastic dynamic causal modeling (sDCM) to estimate the directed connections between the left ACC, right ACC, left caudate, right caudate, left DLPFC, left hippocampus, and right hippocampus. We used Bayesian parameter averaging (BPA) to characterize the differences. The BPA results showed hyperconnectivity from the left ACC to right hippocampus and hypoconnectivity from the right ACC to right hippocampus in SZ relatives compared to HCs. The pattern of anterior cingulate cortico-hippocampal connectivity in SZ relatives may be a familial feature of SZ risk, appearing to reflect familial susceptibility for SZ. PMID:27512370
McGovern, Robert A; Ratneswaren, Tarini; Smith, Elliot H; Russo, Jennifer F; Jongeling, Amy C; Bateman, Lisa M; Schevon, Catherine A; Feldstein, Neil A; McKhann, Guy M; Sheth, Sameer
Stereotactic Electroencephalography (SEEG) is a technique used to localize seizure foci in patients with medically intractable epilepsy. This procedure involves the chronic placement of multiple depth electrodes into regions of the brain typically inaccessible via subdural grid electrode placement. SEEG thus provides a unique opportunity to investigate brain function. In this paper we demonstrate how SEEG can be used to investigate the role of the dorsal anterior cingulate cortex (dACC) in cognitive control. We include a description of the SEEG procedure, demonstrating the surgical placement of the electrodes. We describe the components and process required to record local field potential (LFP) data from consenting subjects while they are engaged in a behavioral task. In the example provided, subjects play a cognitive interference task, and we demonstrate how signals are recorded and analyzed from electrodes in the dorsal anterior cingulate cortex, an area intimately involved in decision-making. We conclude with further suggestions of ways in which this method can be used for investigating human cognitive processes.
Aydın, Adem; Atmaca, Halil; Müezzinoğlu, Ümit Sefa
Traumatic dislocation of the knee joint is an uncommon complex, multiple ligamentous injury resulting from a high-energy trauma. Significant lack of functions can be seen because of both early and late complications of these injuries such as popliteal artery disruption, peroneal nerve injury, persistent instability and posttraumatic arthritis. Therefore, the emergency surgery is necessary due to possibility of neurovascular compromise and limb loss. Controversies over operative versus closed immobilization of traumatic complex, multiple ligamentous knee injury are still debated. We report a case of traumatic anterior dislocation of the right knee with an ipsilateral tibial shaft fracture in association with right popliteal artery occlusion of a professional athlete who was returned to his sports activity by surgical treated tibia fracture and conservative treatment of the knee dislocation.
Kumar, Sunil; Rathi, Akhilesh; Sehrawat, Sunil; Gupta, Vikas; Talwar, Jatin; Arora, Sumit
Open anterior dislocation of the hip is a very rare injury, especially in adults. It is a hyperabduction, external rotation and extension injury. Its combination with open posterior dislocation of the elbow has not been described in English language-based medical literature. Primary resuscitation, debridement, urgent reduction of dislocation, and adequate antibiotic support resulted in good clinical outcome in our patient. At 18 months follow-up, no signs of avascular necrosis of the femoral head or infection were observed.
Shu, I-Wei; Onton, Julie A; O'Connell, Ryan M; Simmons, Alan N; Matthews, Scott C
Posttraumatic stress disorder (PTSD) is common among combat personnel with mild traumatic brain injury (mTBI). While patients with either PTSD or mTBI share abnormal activation of multiple frontal brain areas, anterior cingulate cortex (ACC) activity during inhibitory processing may be particularly affected by PTSD. To further test this hypothesis, we recorded electroencephalography from 32 combat veterans with mTBI-17 of whom were also comorbid for PTSD (mTBI+PTSD) and 15 without PTSD (mTBI-only). Subjects performed the Stop Task, a validated inhibitory control task requiring inhibition of initiated motor responses. We observed a larger inhibitory processing eventrelated potential (ERP) in veterans with mTBI+PTSD, including greater N200 negativity. Furthermore, greater N200 negativity correlated with greater PTSD severity. This correlation was most dependent on contributions from the dorsal ACC. Support vector machine analysis demonstrated that N200 and P300 amplitudes objectively classified veterans into mTBI-only or mTBI+PTSD groups with 79.4% accuracy. Our results support a model where, in combat veterans with mTBI, larger ERPs from cingulate areas are associated with greater PTSD severity and likely related to difficulty controlling ongoing brain processes, including trauma-related thoughts and feelings.
Caseras, Xavier; Murphy, Kevin; Mataix-Cols, David; López-Solà, Marina; Soriano-Mas, Carles; Ortriz, Hector; Pujol, Jesus; Torrubia, Rafael
The anterior insula and the dorsal anterior cingulate cortex (ACC) are regarded as key brain structures associated with the integration of perceived phobic characteristics of external stimuli and the perception of ones own body responses that leads to emotional feelings. To test to what extent the activity in these two brain structures anatomically and functionally overlap during phobic reactions and interoception, we submitted the same group of phobic participants (n = 29; either spider or blood-injection-injury (BII) phobics) and controls (n = 17) to both type of experimental paradigms. Results showed that there was a clear anatomical overlap in the Blood Oxygen Level-Dependent (BOLD) responses within the anterior insula and ACC elicited during phobic symptom provocation and during interoceptive awareness. The activity within these two brain structures also showed to be correlated in the spider phobia group, but not in the BII phobic participants. Our results seem to support the idea that the activity within these two brain areas would be associated with the integration of perceived stimuli characteristics and bodily responses that lead to what we label as "fear." However, that seems not to be the case in BII phobia, where more research is needed in order to clarify to what extent that could be associated with the idiosyncratic physiological response that these patients present in front of phobic stimuli (i.e., drop in heart rate and blood pressure).
Ebitz, R Becket; Platt, Michael L
Whether driving a car, shopping for food, or paying attention in a classroom of boisterous teenagers, it's often hard to maintain focus on goals in the face of distraction. Brain imaging studies in humans implicate the dorsal anterior cingulate cortex (dACC) in regulating the conflict between goals and distractors. Here we show that single dACC neurons signal conflict between task goals and distractors in the rhesus macaque, particularly for biologically relevant social stimuli. For some neurons, task conflict signals predicted subsequent changes in pupil size-a peripheral index of arousal linked to noradrenergic tone-associated with reduced distractor interference. dACC neurons also responded to errors, and these signals predicted adjustments in pupil size. These findings provide the first neurophysiological endorsement of the hypothesis that dACC regulates conflict, in part, via modulation of pupil-linked processes such as arousal.
Wu, Dingcheng; Deng, Hanfei; Xiao, Xiong; Zuo, Yanfang; Sun, Jingjing; Wang, Zuoren
The anterior cingulate cortex (ACC) has long been thought to regulate conflict between an object of attention and distractors during goal-directed sustained attention. However, it is unclear whether ACC serves to sustained attention itself. Here, we developed a task in which the time course of sustained attention could be controlled in rats. Then, using pharmacological lesion experiments, we employed it to assess function of ACC in sustained attention. We then recorded neuronal activity in ACC using multichannel extracellular recording techniques and identified specific ACC neurons persistently activated during the period of attention. Further experiments showed that target modality had minimal influence on the neuronal activity, and distracting external sensory input during the attention period did not perturb persistent neuronal activity. Additionally, minimal trial-to-trial variability in neuronal activity observed during sustained attention supports a role for ACC neurons in that behavior. Therefore, we conclude that the ACC neuronal activity correlates with sustained attention. PMID:28230158
Mao, Can Van; Araujo, Mariana F. P.; Nishimaru, Hiroshi; Matsumoto, Jumpei; Tran, Ahn Hai; Hori, Etsuro; Ono, Taketoshi; Nishijo, Hisao
The anterior cingulate cortex (ACC) has been implicated in different aspects of cognition and decision making, including social cognition. Several studies suggest that this region is actually formed by sub-regions concerned with distinct cognitive functions. The ACC is usually divided in its rostro-caudal axis, with the caudal ACC playing a major role in processing own actions, and the rostral ACC being related to social cognition. Recently, it has been suggested that the ACC can also be functionally divided in its dorso-ventral axis into ACC gyrus (ACCg) and ACC sulcus (ACCs), with the ACCg having a central role in processing social information. In this context, we propose that the pregenual ACCg might be especially important for engaging in social interactions. We discuss previous findings that support this hypothesis and present evidence suggesting that the activity of pregenual ACCg neurons is modulated during spontaneous social interactions. PMID:28203143
Anderson, John R.; Anderson, John F.; Ferris, Jennifer L.; Fincham, Jon M.; Jung, Kwan-Jin
Two studies used puzzles that required participants to find a word that satisfied a set of constraints. The first study used a remote-association task, where participants had to find a word that would form compound words with 3 other words. The second study required participants to complete a word fragment with an associate of another word. Both studies produced distinct patterns of activity in the lateral inferior prefrontal cortex (LIPFC) and the anterior cingulate cortex (ACC). Activation in the LIPFC rose only as long as the participants were trying to retrieve the solution and dropped off as soon as the solution was obtained. However, activation in the ACC increased upon the retrieval of a solution, reflecting the need to process that solution. The data of the second experiment are fit by an information-processing model that interprets the activity in the LIPFC as reflecting retrieval operations and the activity in the ACC as reflecting subgoal setting. PMID:19541657
Kanske, Philipp; Kotz, Sonja A
Coherent behavior depends on attentional control that detects and resolves conflict between opposing actions. The current functional magnetic resonance imaging study tested the hypothesis that emotion triggers attentional control to speed up conflict processing in particularly salient situations. Therefore, we presented emotionally negative and neutral words in a version of the flanker task. In response to conflict, we found activation of the dorsal anterior cingulate cortex (ACC) and of the amygdala for emotional stimuli. When emotion and conflict coincided, a region in the ventral ACC was activated, which resulted in faster conflict processing in reaction times. Emotion also increased functional connectivity between the ventral ACC and activation of the dorsal ACC and the amygdala in conflict trials. These data suggest that the ventral ACC integrates emotion and conflict and prioritizes the processing of conflict in emotional trials. This adaptive mechanism ensures rapid detection and resolution of conflict in potentially threatening situations signaled by emotional stimuli.
Ebitz, R. Becket; Platt, Michael L.
Summary Whether driving a car, shopping for food, or paying attention in a classroom of boisterous teenagers, it’s often hard to maintain focus on goals in the face of distraction. Brain imaging studies in humans implicate the dorsal anterior cingulate cortex (dACC) in regulating the conflict between goals and distractors. Here we show for the first time that single dACC neurons signal conflict between task goals and distractors in the rhesus macaque, particularly for biologically-relevant social stimuli. For some neurons, task conflict signals predicted subsequent changes in pupil size—a peripheral index of arousal linked to noradrenergic tone—associated with reduced distractor interference. dACC neurons also responded to errors and these signals predicted adjustments in pupil size. These findings provide the first neurophysiological endorsement of the hypothesis that dACC regulates conflict, in part, via modulation of pupil-linked processes such as arousal. PMID:25654259
Ito, Takahiro; Tanaka-Mizuno, Sachiko; Iwashita, Narihito; Tooyama, Ikuo; Shiino, Akihiko; Miura, Katsuyuki; Fukui, Sei
Background Chronic pain is a common cause of reduced quality of life. Recent studies suggest that chronic pain patients have a different brain neurometabolic status to healthy people. Proton magnetic resonance spectroscopy (1H-MRS) can determine the concentrations of metabolites in a specific region of the brain without being invasive. Patients and methods We recruited 56 chronic pain patients and 60 healthy controls to compare brain metabolic characteristics. The concentrations of glutamic acid (Glu), myo-inositol (Ins), N-acetylaspartate (NAA), Glu + glutamine (Glx), and creatine + phosphocreatine (total creatine [tCr]) in the anterior cingulate cortex of participants were measured using 1H-MRS. We used age- and gender-adjusted general linear models and receiver-operating characteristic analyses for this investigation. Patients were also assessed using the Hospital Anxiety and Depression Scale (HADS) to reveal the existence of any mental health issues. Results Our analysis indicates that pain patients have statistically significantly higher levels of Glu/tCr (p=0.039) and Glx/tCr (p<0.001) and lower levels of NAA/tCr than controls, although this did not reach statistical significance (p=0.052). Receiver-operating characteristic analysis performed on the combination of Glx/tCr, Ins/tCr, and NAA/tCr effectively discriminated chronic pain patients from healthy controls. Patients with higher HADS-Depression scores had increased Glx/rCr levels (p=0.015), and those with higher HADS-Anxiety scores had increased NAA/tCr levels (p=0.018). Conclusion Chronic pain patients have a different metabolite status in the anterior cingulate cortex to controls. Within the pain patient group, HADS scores had a positive relationship with NAA/tCr and Glx/tCr levels. 1H-MRS successfully detected metabolic changes in patients’ brains in a noninvasive manner, revealing its potential as a superior diagnostic tool for pain patients. PMID:28203104
Jia, Fujun; Guo, Guangquan; Quan, Dongming; Li, Gang; Wu, Huawang; Zhang, Bin; Fan, Changhe; He, Xiajun; Huang, Huiyan
Background: Cognitive impairment is a key feature of treatment-resistant depression (TRD) and can be related to the anterior cingulate cortex (ACC) function. Repetitive transcranial magnetic stimulation (rTMS) as an antidepressant intervention has increasingly been investigated in the last two decades. However, no studies to date have investigated the association between neurobiochemical changes within the anterior cingulate and executive dysfunction measured in TRD being treated with rTMS. Methods: Thirty-two young depressed patients with treatment-resistant unipolar depression were enrolled in a double-blind, randomized study [active (n=18) vs. sham (n=14)]. ACC metabolism was investigated before and after high-frequency (15Hz) rTMS using 3-tesla proton magnetic resonance spectroscopy (1H-MRS). The results were compared with 28 age- and gender-matched healthy controls. Executive functioning was measured with the Wisconsin Card Sorting Test (WCST) among 34 subjects with TRD and 28 healthy subjects. Results: Significant reductions in N-acetylaspartate (NAA) and choline-containing Compound levels in the left ACC were found in subjects with TRD pre-rTMS when compared with healthy controls. After successful treatment, NAA levels increased significantly in the left ACC of subjects and were not different from those of age-matched controls. In the WCST, more perseverative errors and fewer correct numbers were observed in TRD subjects at baseline. Improvements in both perseverative errors and correct numbers occurred after active rTMS. In addition, improvement of perseverative errors was positively correlated with enhancement of NAA levels in the left ACC in the active rTMS group. Conclusions: Our results suggest that the NAA concentration in the left ACC is associated with an improvement in cognitive functioning among subjects with TRD response to active rTMS. PMID:26025780
De Ridder, Dirk; Vanneste, Sven; Kovacs, Silvia; Sunaert, Stefan; Dom, Geert
It has recently become clear that alcohol addiction might be related to a brain dysfunction, in which a genetic background and environmental factors shape brain mechanisms involved with alcohol consumption. Craving, a major component determining relapses in alcohol abuse has been linked to abnormal activity in the orbitofrontal cortex, dorsal anterior cingulated cortex (dACC) and amygdala. We report the results of a patient who underwent rTMS targeting the dACC using a double cone coil in an attempt to suppress very severe intractable alcohol craving. Functional imaging studies consisting of fMRI and resting state EEG were performed before rTMS, after successful rTMS and after unsuccessful rTMS with relapse. Craving was associated with EEG beta activity and connectivity between the dACC and PCC in the patient in comparison to a healthy population, which disappeared after successful rTMS. Cue induced worsening of craving pre-rTMS activated the ACC-vmPFC and PCC on fMRI, as well as the nucleus accumbens area, and lateral frontoparietal areas. The nucleus accumbens, ACC-vmPFC and PCC activation disappeared on fMRI following successful rTMS. Relapse was associated with recurrence of ACC and PCC EEG activity, but in gamma band, in comparison to a healthy population. On fMRI nucleus accumbens, ACC and PCC activation returned to the initial activation pattern. A pathophysiological approach is described to suppress alcohol craving temporarily by rTMS directed at the anterior cingulate. Linking functional imaging changes to craving intensity suggests this approach warrants further exploration.
Sibille, François-Xavier; Duprez, Thierry; van Pesch, Vincent; Giglioli, Simone
We report on two cases of transient akinetic mutism after massive subarachnoid haemorrhage due to the rupture of an intracranial aneurysm of the anterior cerebral artery (ACA). In the two cases, vasospasm could not be demonstrated by imaging studies throughout the clinical course. Both patients shared common radiological features: a hydrocephalus due to haemorrhagic contamination of the ventricular system and a mass effect of a subpial hematoma on the borders of the corpus callosum. Patients were also investigated using auditory event-related evoked potentials at acute stage. In contrast to previous observations of akinetic mutism, P300 wave could not be recorded. Both patients had good recovery and we hypothesized that this unexpectedly favourable outcome was due to the absence of permanent structural damage to the ACA territory, with only transient dysfunction due to a reversible mass effect on cingulate gyri. PMID:27418987
Moore, Constance M.; Frazier, Jean A.; Glod, Carol A.; Breeze, Janis L.; Dieterich, Megan; Finn, Chelsea T.; deB. Frederick, Blaise; Renshaw, Perry F.
Objective: The purpose of this study was to use proton magnetic resonance spectroscopy, at 4.0 T, to explore the glutamine and glutamate levels in the anterior cingulate cortex of children and adolescents with bipolar disorder (BPD; medicated and unmedicated) and healthy comparison subjects (HCSs). We hypothesized that unmedicated children with…
Smith, Anna B.; Taylor, Eric; Brammer, Michael; Halari, Rozmin; Rubia, Katya
Background: Patients with attention deficit hyperactivity disorder (ADHD) under-perform when discriminating between durations differing by several hundred milliseconds. This function involves right prefrontal and anterior cingulate (AC) brain regions, which are structurally and functionally compromised in this patient group during executive tasks.…
Griffin, Amy L.; Berry, Stephen D.
Although past research has highlighted the involvement of limbic structures such as the anterior cingulate cortex (ACC) and hippocampus in learning, few have addressed the nature of their interaction. The current study of rabbit jaw movement conditioning used a combination of reversible lesions and electrophysiology to examine the involvement of…
Chan, Agnes S.; Han, Yvonne M. Y.; Leung, Winnie Wing-man; Leung, Connie; Wong, Virginia C. N.; Cheung, Mei-chun
Previous studies showed that the anterior cingulate cortex (ACC) is activated when individuals engage in attention and inhibitory control tasks. The present study examined whether ACC activity is associated with behavioral performance of the two tasks. Twenty normal and 20 children with autism spectrum disorders (ASDs) were subjected to…
Chin, Kingsley R.; Seale, Jason; Butron, Veronica
Hematoma alone is the most common vascular complication reported after anterior cervical decompression and fusion (ACDF). We present this case to report the occurrence of postoperative cervical hematoma complicated by ipsilateral carotid thrombosis and aphasia after an uncomplicated C4–6 ACDF. This is a case of a 65-year-old woman who underwent revision fusions of the C4-5 and C6-7 levels complicated by postoperative cervical hematoma and carotid thrombosis. The patient's history, clinical examination, imaging findings, and treatment are reported. The revision fusions were performed and deemed routine. Approximately eight hours later 200 mL of blood was evacuated from a postoperative cervical hematoma. The patient became unresponsive and disoriented a few hours after evacuating the hematoma. Computed tomography and magnetic resonance imaging of the brain were normal, but magnetic resonance angiography demonstrated total occlusion of the left carotid artery. Thrombectomy was performed and the patient was discharged without residual deficits. At the latest followup she is fully functional and asymptomatic in her neck. We suggest, after evacuating a cervical hematoma, an evaluation of the carotids be made with MRA or cerebral angiography, as this may demonstrate a clot before the patient develops symptoms. PMID:23533432
Scheck, Simon M; Pannek, Kerstin; Raffelt, David A; Fiori, Simona; Boyd, Roslyn N; Rose, Stephen E
In this work we investigate the structural connectivity of the anterior cingulate cortex (ACC) and its link with impaired executive function in children with unilateral cerebral palsy (UCP) due to periventricular white matter lesions. Fifty two children with UCP and 17 children with typical development participated in the study, and underwent diffusion and structural MRI. Five brain regions were identified for their high connectivity with the ACC using diffusion MRI fibre tractography: the superior frontal gyrus, medial orbitofrontal cortex, rostral middle frontal gyrus, precuneus and isthmus cingulate. Structural connectivity was assessed in pathways connecting these regions to the ACC using three diffusion MRI derived measures: fractional anisotropy (FA), mean diffusivity (MD) and apparent fibre density (AFD), and compared between participant groups. Furthermore we investigated correlations of these measures with executive function as assessed by the Flanker task. The ACC-precuneus tract had significantly different MD (p < 0.0001) and AFD (p = 0.0072) between groups, with post-hoc analysis showing significantly increased MD in the right hemisphere of children with left hemiparesis compared with controls. The ACC-superior frontal gyrus tract had significantly different FA (p = 0.0049) and MD (p = 0.0031) between groups. AFD in this tract (contralateral to side of hemiparesis; right hemisphere in controls) showed a significant relationship with Flanker task performance (p = 0.0045, β = -0.5856), suggesting that reduced connectivity correlates with executive dysfunction. Reduced structural integrity of ACC tracts appears to be important in UCP, in particular the connection to the superior frontal gyrus. Although damage to this area is heterogeneous it may be important in early identification of children with impaired executive function.
Vogt, B.A.; Gabriel, M.; Vogt, L.J.; Poremba, A.; Jensen, E.L.; Kubota, Y.; Kang, E. )
Training-induced neuronal activity develops in the mammalian limbic system during discriminative avoidance conditioning. This study explores behaviorally relevant changes in muscarinic ACh receptor binding in 52 rabbits that were trained to one of five stages of conditioned response acquisition. Sixteen naive and 10 animals yoked to criterion performance served as control cases. Upon reaching a particular stage of training, the brains were removed and autoradiographically assayed for 3H-oxotremorine-M binding with 50 nM pirenzepine (OxO-M/PZ) or for 3H-pirenzepine binding in nine limbic thalamic nuclei and cingulate cortex. Specific OxO-M/PZ binding increased in the parvocellular division of the anterodorsal nucleus early in training when the animals were first exposed to pairing of the conditional and unconditional stimuli. Elevated binding in this nucleus was maintained throughout subsequent training. In the parvocellular division of the anteroventral nucleus (AVp), OxO-M/PZ binding progressively increased throughout training, reached a peak at the criterion stage of performance, and returned to control values during extinction sessions. Peak OxO-M/PZ binding in AVp was significantly elevated over that for cases yoked to criterion performance. In the magnocellular division of the anteroventral nucleus (AVm), OxO-M/PZ binding was elevated only during criterion performance of the task, and it was unaltered in any other limbic thalamic nuclei. Specific OxO-M/PZ binding was also elevated in most layers in rostral area 29c when subjects first performed a significant behavioral discrimination. Training-induced alterations in OxO-M/PZ binding in AVp and layer Ia of area 29c were similar and highly correlated.
Linares, I M P; Jackowski, A P; Trzesniak, C M F; Arrais, K C; Chagas, M H N; Sato, J R; Santos, A C; Hallak, J E C; Zuardi, A W; Nardi, A E; Coimbra, N C; Crippa, J A S
There a lack of consistent neuroimaging data on specific phobia (SP) and a need to assess volumetric and metabolic differences in structures implicated in this condition. The aim of this study is investigate possible metabolic (via (1)H MRS) and cortical thickness abnormalities in spider-phobic patients compared to healthy volunteers. Participants were recruited via public advertisement and underwent clinical evaluations and MRI scans. The study started in 2010 and the investigators involved were not blind in respect to patient groupings. The study was conducted at the Ribeirão Preto Medical School University Hospital of the University of São Paulo, Brazil. Patients with spider phobia (n=19) were matched to 17 healthy volunteers with respect to age, education and socio-economic status. The spider SP group fulfilled the diagnostic criteria for spider phobia according to the Structured Clinical Interview for DSM-IV. None of the participants had a history of neurological, psychiatric or other relevant organic diseases, use of prescribed psychotropic medication or substance abuse. All imaging and spectroscopy data were collected with a 3 T MRI scanner equipped with 25 mT gradient coils in 30-minute scans. The Freesurfer image analysis package and LC Model software were used to analyze data. The hypothesis being tested was formulated before the data collection (neural correlates of SP would include the amygdala, insula, anterior cingulate gyrus and others). The results indicated the absence of metabolic alterations, but thinning of the right anterior cingulate cortex (ACC) in the SP group when compared to the healthy control group (mean cortical thickness±SD: SP=2.11±0.45 mm; HC=2.16±0.42 mm; t (34)=3.19, p=0.001 [-35.45, 71.00, -23.82]). In spectroscopy, the ratios between N-acetylaspartate and creatine and choline levels were measured. No significant effect or correlation was found between MRS metabolites and scores in the Spider Phobia Questionnaire and Beck
McGovern, Robert A; Sheth, Sameer A
OBJECTIVE Advances in understanding the neurobiological basis of psychiatric disorders will improve the ability to refine neuromodulatory procedures for treatment-refractory patients. One of the core dysfunctions in obsessive-compulsive disorder (OCD) is a deficit in cognitive control, especially involving the dorsal anterior cingulate cortex (dACC). The authors' aim was to derive a neurobiological understanding of the successful treatment of refractory OCD with psychiatric neurosurgical procedures targeting the dACC. METHODS First, the authors systematically conducted a review of the literature on the role of the dACC in OCD by using the search terms "obsessive compulsive disorder" and "anterior cingulate." The neuroscience literature on cognitive control mechanisms in the dACC was then combined with the literature on psychiatric neurosurgical procedures targeting the dACC for the treatment of refractory OCD. RESULTS The authors reviewed 89 studies covering topics that included structural and functional neuroimaging and electrophysiology. The majority of resting-state functional neuroimaging studies demonstrated dACC hyperactivity in patients with OCD relative to that in controls, while task-based studies were more variable. Electrophysiological studies showed altered dACC-related biomarkers of cognitive control, such as error-related negativity in OCD patients. These studies were combined with the cognitive control neurophysiology literature, including the recently elaborated expected value of control theory of dACC function. The authors suggest that a central feature of OCD pathophysiology involves the generation of mis-specified cognitive control signals by the dACC, and they elaborate on this theory and provide suggestions for further study. CONCLUSIONS Although abnormalities in brain structure and function in OCD are distributed across a wide network, the dACC plays a central role. The authors propose a theory of cognitive control dysfunction in OCD that
Ortega-Legaspi, J Manuel; López-Avila, Alberto; Coffeen, Ulises; del Angel, Rosendo; Pellicer, Francisco
The cingulate cortex plays a key role in the affective component related to pain perception. This structure receives cholinergic projections and also plays a role in memory processing. Therefore, we propose that the cholinergic system in the anterior cingulate cortex is involved in the nociceptive memory process. We used scopolamine (10 microg in 0.25 mircrol/saline) microinjected into the anterior cingulate cortex, either before thermonociception followed by a sciatic denervation, between thermonociception and denervation or after both procedures (n=10 each). The vehicle group (saline solution 0.9%, n=14) was microinjected before thermonociception. Chronic nociception was measured by the autotomy score, which onset and incidence were also determined. Group scopolamine-thermonociception-denervation (STD) presented the lowest autotomy score as compared to vehicle and group thermonociception-denervation-scopolamine (TDS) (vehicle vs. STD, p=0.002, STD vs. TDS, p=0.001). Group thermonociception-scopolamine-denervation (TSD) showed a diminished autotomy score when compared to TDS (p=0.053). STD group showed a delay in the onset of AB as compared to the rest of the groups. Group TSD presented a significative delay (p=0.048) in AB onset when compared to group TDS. There were no differences in the incidence between groups. The results show that nociception-related memory processed in the anterior cingulate cortex is susceptible of being modified by the cholinergic transmission blockade. When scopolamine is microinjected prior to the nociceptive stimuli, nociception-related memory acquisition is prevented. The evidence obtained in this study shows the role of the anterior cingulate cortex in the acquisition of nociception-related memory.
Emmert, Kirsten; Breimhorst, Markus; Bauermann, Thomas; Birklein, Frank; Van De Ville, Dimitri; Haller, Sven
Real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback allows learning voluntary control over specific brain areas by means of operant conditioning and has been shown to decrease pain perception. To further increase the effect of rt-fMRI neurofeedback on pain, we directly compared two different target regions of the pain network, notably the anterior insular cortex (AIC) and the anterior cingulate cortex (ACC). Participants for this prospective study were randomly assigned to two age-matched groups of 14 participants each (7 females per group) for AIC and ACC feedback. First, a functional localizer using block-design heat pain stimulation was performed to define the pain-sensitive target region within the AIC or ACC. Second, subjects were asked to down-regulate the BOLD activation in four neurofeedback runs during identical pain stimulation. Data analysis included task-related and functional connectivity analysis. At the behavioral level, pain ratings significantly decreased during feedback vs. localizer runs, but there was no difference between AIC and ACC groups. Concerning neuroimaging, ACC and AIC showed consistent involvement of the caudate nucleus for subjects that learned down-regulation (17/28) in both task-related and functional connectivity analysis. The functional connectivity toward the caudate nucleus is stronger for the ACC while the AIC is more heavily connected to the ventrolateral prefrontal cortex. Consequently, the ACC and AIC are suitable targets for real-time fMRI neurofeedback during pain perception as they both affect the caudate nucleus, although functional connectivity indicates that the direct connection seems to be stronger with the ACC. Additionally, the caudate, an important area involved in pain perception and suppression, could be a good rt-fMRI target itself. Future studies are needed to identify parameters characterizing successful regulators and to assess the effect of repeated rt-fMRI neurofeedback on pain
Hayden, Benjamin Y.; Heilbronner, Sarah R.; Pearson, John M.; Platt, Michael L.
In attentional models of learning, associations between actions and subsequent rewards are stronger when outcomes are surprising, regardless of their valence. Despite the behavioral evidence that surprising outcomes drive learning, neural correlates of unsigned reward prediction errors remain elusive. Here we show that in a probabilistic choice task, trial-to-trial variations in preference track outcome surprisingness. Concordant with this behavioral pattern, responses of neurons in macaque (Macaca mulatta) dorsal anterior cingulate cortex (dACC) to both large and small rewards were enhanced when the outcome was surprising. Moreover, when, on some trials, probabilities were hidden, neuronal responses to rewards were reduced, consistent with the idea that the absence of clear expectations diminishes surprise. These patterns are inconsistent with the idea that dACC neurons track signed errors in reward prediction, as dopamine neurons do. Our results also indicate that dACC neurons do not signal conflict. In the context of other studies of dACC function, these results suggest a link between reward-related modulations in dACC activity and attention and motor control processes involved in behavioral adjustment. More speculatively, these data point to a harmonious integration between reward and learning accounts of ACC function on one hand, and attention and cognitive control accounts on the other. PMID:21411658
Jonkman, Sietse; Everitt, Barry J
The integrity of the rodent anterior cingulate cortex (ACC) is essential for various aspects of instrumental behavior, but it is not clear if the ACC is important for the acquisition of a simple instrumental response. Here, it was demonstrated that post-session infusions of anisomycin into the rat ACC completely prevented the acquisition of instrumental responding. The experimental use of post-session intracranial infusions of plasticity inhibitors is assumed to affect local consolidation of plasticity, but not behavioral task performance. However, in associative appetitive conditioning, post-session intracranial infusion of pharmaco-active compounds could actually interfere with subsequent task performance indirectly through retrospective effects on the valuation of ingested rewards. Thus, it was subsequently demonstrated that the intracranial infusion of anisomycin into the ACC after sucrose pellet consumption significantly reduced subsequent pellet consumption, suggesting that the infusion of anisomycin into the ACC produced conditioned taste avoidance. In the third experiment, an innovative procedure was introduced that dissociated the effects of intracranial infusions after conditioning sessions on task-learning and unconditioned stimulus valuation. With this procedure, the infusion of anisomycin into the ACC after instrumental sessions did not affect instrumental reinforcer valuation or the acquisition of instrumental responding, suggesting that plasticity in the ACC is not necessary for the acquisition of instrumental behavior.
Caracheo, Barak F.; Emberly, Eldon; Hadizadeh, Shirin; Hyman, James M.; Seamans, Jeremy K.
Foraging typically involves two distinct phases, an exploration phase where an organism explores its local environment in search of needed resources and an exploitation phase where a discovered resource is consumed. The behavior and cognitive requirements of exploration and exploitation are quite different and yet organisms can quickly and efficiently switch between them many times during a foraging bout. The present study investigated neural activity state dynamics in the anterior cingulate sub-region of the rat medial prefrontal cortex (mPFC) when a reliable food source was introduced into an environment. Distinct and largely independent states were detected using a Hidden Markov Model (HMM) when food was present or absent in the environment. Measures of neural entropy or complexity decreased when rats went from exploring the environment to exploiting a reliable food source. Exploration in the absence of food was associated with many weak activity states, while bouts of food consumption were characterized by fewer stronger states. Widespread activity state changes in the mPFC may help to inform foraging decisions and focus behavior on what is currently most prominent or valuable in the environment. PMID:23745102
Aulická, Stefania Rusnáková; Jurák, Pavel; Chládek, Jan; Daniel, Pavel; Halámek, Josef; Baláž, Marek; Bočková, Martina; Chrastina, Jan; Rektor, Ivan
We studied the appearance of broadband oscillatory changes (ranging 2-45 Hz) induced by a cognitive task with two levels of complexity. The event-related de/synchronizations (ERD/S) in the subthalamic nucleus (STN) and in the anterior cingulate cortex (ACC) were evaluated in an executive function test. Four epilepsy surgery candidates with intracerebral electrodes implanted in the ACC and three Parkinson's disease patients with externalized deep brain stimulation electrodes implanted in the STN participated in the study. A Flanker test (FT) with visual stimuli (arrows) was performed. Subjects reacted to four types of stimuli presented on the monitor by pushing the right or left button: congruent arrows to the right or left side (simple task) and incongruent arrows to the right or left side (more difficult complex task). We explored the activation of STN and the activation of the ACC while processing the FT. Both conditions, i.e. congruent and incongruent, induced oscillatory changes in the ACC and also STN with significantly higher activation during incongruent trial. At variance with the ACC, in the STN not only the ERD beta but also the ERD alpha activity was significantly more activated by the incongruent condition. In line with our earlier studies, the STN appears to be involved in activities linked with increased cognitive load. The specificity and complexity of task-related activation of the STN might indicate the involvement of the STN in processes controlling human behaviour, e.g. in the selection and inhibition of competing alternatives.
Lueken, Ulrike; Straube, Benjamin; Wittchen, Hans-Ulrich; Konrad, Carsten; Ströhle, Andreas; Wittmann, André; Pfleiderer, Bettina; Arolt, Volker; Kircher, Tilo; Deckert, Jürgen; Reif, Andreas
Variation in the 5'-flanking promoter region of the serotonin transporter gene SLC6A4, the 5-HTT-linked polymorphic region (5-HTTLPR) has been inconclusively associated with response to cognitive-behavioural therapy (CBT). As genomic functions are stronger related to neural than to behavioural markers, we investigated the association of treatment response, 5-HTTLPR and functional brain connectivity in patients with panic disorder with agoraphobia (PD/AG). Within the national research network PANIC-NET 231 PD/AG patients who provided genetic information underwent a manualized exposure-based CBT. A subset of 41 patients participated in a functional magnetic resonance imaging (fMRI) add-on study prior to treatment applying a differential fear conditioning task. Neither the treatment nor the reduced fMRI sample showed a direct effect of 5-HTTLPR on treatment response as defined by a reduction in the Hamilton Anxiety Scale score ≥50 % from baseline to post assessment. On a neural level, inhibitory anterior cingulate cortex (ACC)-amygdala coupling during fear conditioning that had previously been shown to characterize treatment response in this sample was driven by responders with the L/L genotype. Building upon conclusive evidence from basic and preclinical findings on the association of the 5-HTTLPR polymorphism with emotion regulation and related brain connectivity patterns, present findings translate these to a clinical sample of PD/AG patients and point towards a potential intermediate connectivity phenotype modulating response to exposure-based CBT.
Colla, Michael; Ende, Gabriele; Alm, Barbara; Deuschle, Michael; Heuser, Isabella; Kronenberg, Golo
The anterior cingulate cortex (ACC) plays a major role in modulating executive control of attention. Here, 15 medication-nai ve patients with attention deficit/hyperactivity disorder (ADHD) and 10 carefully matched healthy controls were studied with 2D (1)H-magnetic resonance spectroscopic imaging (MRSI) of the ACC [Brodmann areas 24b'-c' and 32']. Attentional skills were assessed using the identical pairs version of the continuous performance task (CPT-IP). Analysis of regional brain spectra revealed a significantly increased signal of choline-containing compounds (Ch) in the ACC of ADHD patients (p<0.05). Across and within groups, the Ch signal showed high correlations with slowed hit reaction times on the CPT-IP. No group differences in N-acetyl-aspartate (NAA) and creatine (tCr) were detectable. The combination of performance deficits and elevated Ch levels in the ACC supports the hypothesis that subtle structural abnormalities underlie the functional alterations in ACC activation previously observed in ADHD patients.
Kreuzer, Peter M.; Lehner, Astrid; Schlee, Winfried; Vielsmeier, Veronika; Schecklmann, Martin; Poeppl, Timm B.; Landgrebe, Michael; Rupprecht, Rainer; Langguth, Berthold
Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a tinnitus treatment option. Promising results have been obtained by consecutive stimulation of lateral frontal and auditory brain regions. We investigated a combined stimulation paradigm targeting the anterior cingulate cortex (ACC) with double cone coil rTMS, followed by stimulation of the temporo-parietal junction area with a figure-of-eight coil. The study was conducted as a randomized, double-blind pilot trial in 40 patients suffering from chronic tinnitus. We compared mediofrontal stimulation with double-cone-coil, (2000 stimuli, 10 Hz) followed by left temporo-parietal stimulation with figure-of-eight-coil (2000 stimuli, 1 Hz) to left dorsolateral-prefrontal-cortex stimulation with figure-of-eight-coil (2000 stimuli, 10 Hz) followed by temporo-parietal stimulation with figure-of-eight-coil (2000 stimuli, 1 Hz). The stimulation was feasible with comparable dropout rates in both study arms; no severe adverse events were registered. Responder rates did not differ in both study arms. There was a significant main effect of time for the change in the TQ score, but no significant time x group interaction. This pilot study demonstrated the feasibility of combined mediofrontal/temporoparietal-rTMS-stimulation with double cone coil in tinnitus patients but failed to show better outcome compared to an actively rTMS treated control group. PMID:26667790
Zuo, Gong Cheng; Yang, Jing Yu; Hao, Yue; Dong, Ying Xu; Wu, Chun Fu
It is controversial regarding to the roles of acetaldehyde and ethanol in the central nervous system. In the present study, the effects of acetaldehyde and ethanol on extracellular levels of glutamate, taurine and GABA in the anterior cingulate cortex (ACC) of freely moving rats were investigated by using the microdialysis technique coupled to high performance liquid chromatography (HPLC) with fluorescent detection. The result showed that glutamate levels were significantly decreased after acute administration of acetaldehyde (AcH, 20 and 100 mg/kg, i.p.), while taurine levels were significantly increased after the higher dose of acetaldehyde (100 mg/kg, i.p.). GABA levels had no changes at any doses of acetaldehyde tested. Interestingly, similar changes of these amino acids were induced by ethanol (EtOH, 3 g/kg, i.p.) when sodium azide (NaN3, 10 mg/kg, i.p.), a catalase inhibitor that can reduce brain ethanol metabolism, was used simultaneously. These findings suggest that acetaldehyde and ethanol have the similar effects on the extracellular output of glutamate, taurine and GABA in the ACC.
Nelson, Brady D.; Bjorkquist, Olivia A.; Olsen, Emily K.; Herbener, Ellen S.
Schizophrenia is a chronic mental illness characterized by distinct positive and negative symptoms and functional impairment. The anterior cingulate cortex (ACC) is a region of the brain’s limbic system that is hypoactive during emotion processing in schizophrenia. Recent evidence suggests the hypoactive ACC in schizophrenia is due to negative (and not positive) symptoms. However, this finding has not been replicated and the functional significance of this relationship remains unclear. The present study examined the association between positive and negative symptoms, ACC activation to emotional images, and functional outcome in schizophrenia. Specifically, 16 schizophrenia/schizoaffective disorder (SZ/SZAF) and 15 control (CON) participants underwent an fMRI scan while completing an emotional picture-rating task. SZ/SZAF participants also completed clinician-rated measures of positive and negative symptoms and functional abilities. SZ/SZAF participants with high negative symptoms had reduced ACC activation to pleasant images relative to those with low negative symptoms and CON, who did not differ. Furthermore, amongst all SZ/SZAF participants poorer social functioning was associated with decreased ACC activation to pleasant images. Finally, ACC activation partially mediated the relationship between negative symptoms and social dysfunction. These results provide evidence of the functional significance of the relationship between negative symptoms and ACC dysfunction in schizophrenia. PMID:26596521
Xu, Xiaoxiang; Cao, Bing; Wang, Jun; Yu, Tianran; Li, Ying
Human studies have shown that multiple teeth loss was significantly associated with cognitive impairment, dementia and Alzheimer's disease. However, the causal relationship between tooth loss and cognitive deficits has not been clarified. Rodents demonstrate human-like cognitive faculties. In this study by performing rat gambling task (RGT), we reported that prolonged tooth loss condition by extracting all left molars in the rats led to an increase in the proportion of poor decision-makers, and decrease in the proportion of good decision-makers compared with controls. No influence was detected on the general activity and motivation after tooth loss. Recent experiments have shown that decision-making performances in the RGT rely on the functional integrity of the amygdala and anterior cingulate cortex (ACC). The theta band brain oscillation has been acknowledged for extensive cognitive functions. Here, we performed multiple-electrode array recordings of local field potential (LFP) in anesthetized rats. The results exhibited an increase in accumulative power of the theta frequency of LFP in the basolateral amygdala (BLA) and decrease of theta power in the ACC in tooth loss rats. Furthermore, cross-correlation analysis displayed that tooth loss suppressed the synchronization of theta frequency of LFP between the BLA and ACC, indicating reduced neuronal communications between these two regions. In conclusion, we demonstrate for the first time that tooth loss leads to higher-order cognitive deficits accompanied by the alteration of theta frequency of LFP in brain circuitries and disruption of neural network integrity.
Woodcock, Eric A.; Wadehra, Sunali; Diwadkar, Vaibhav A.
Schizophrenia is a disorder characterized by brain network dysfunction, particularly during behavioral tasks that depend on frontal and hippocampal mechanisms. Here, we investigated network profiles of the regions of the frontal cortex during memory encoding and retrieval, phases of processing essential to associative memory. Schizophrenia patients (n = 12) and healthy control (HC) subjects (n = 10) participated in an established object-location associative memory paradigm that drives frontal-hippocampal interactions. Network profiles were modeled of both the dorsal prefrontal (dPFC) and the dorsal anterior cingulate cortex (dACC) as seeds using psychophysiological interaction analyses, a robust framework for investigating seed-based connectivity in specific task contexts. The choice of seeds was motivated by previous evidence of involvement of these regions during associative memory. Differences between patients and controls were evaluated using second-level analyses of variance (ANOVA) with seed (dPFC vs. dACC), group (patients vs. controls), and memory process (encoding and retrieval) as factors. Patients showed a pattern of exaggerated modulation by each of the dACC and the dPFC during memory encoding and retrieval. Furthermore, group by memory process interactions were observed within regions of the hippocampus. In schizophrenia patients, relatively diminished modulation during encoding was associated with increased modulation during retrieval. These results suggest a pattern of complex dysfunctional network signatures of critical forebrain regions in schizophrenia. Evidence of dysfunctional frontal-medial temporal lobe network signatures in schizophrenia is consistent with the illness’ characterization as a disconnection syndrome. PMID:27092063
Woodcock, Eric A; Wadehra, Sunali; Diwadkar, Vaibhav A
Schizophrenia is a disorder characterized by brain network dysfunction, particularly during behavioral tasks that depend on frontal and hippocampal mechanisms. Here, we investigated network profiles of the regions of the frontal cortex during memory encoding and retrieval, phases of processing essential to associative memory. Schizophrenia patients (n = 12) and healthy control (HC) subjects (n = 10) participated in an established object-location associative memory paradigm that drives frontal-hippocampal interactions. Network profiles were modeled of both the dorsal prefrontal (dPFC) and the dorsal anterior cingulate cortex (dACC) as seeds using psychophysiological interaction analyses, a robust framework for investigating seed-based connectivity in specific task contexts. The choice of seeds was motivated by previous evidence of involvement of these regions during associative memory. Differences between patients and controls were evaluated using second-level analyses of variance (ANOVA) with seed (dPFC vs. dACC), group (patients vs. controls), and memory process (encoding and retrieval) as factors. Patients showed a pattern of exaggerated modulation by each of the dACC and the dPFC during memory encoding and retrieval. Furthermore, group by memory process interactions were observed within regions of the hippocampus. In schizophrenia patients, relatively diminished modulation during encoding was associated with increased modulation during retrieval. These results suggest a pattern of complex dysfunctional network signatures of critical forebrain regions in schizophrenia. Evidence of dysfunctional frontal-medial temporal lobe network signatures in schizophrenia is consistent with the illness' characterization as a disconnection syndrome.
Kawamoto, Taishi; Onoda, Keiichi; Nakashima, Ken'ichiro; Nittono, Hiroshi; Yamaguchi, Shuhei; Ura, Mitsuhiro
People are typically quite sensitive about being accepted or excluded by others. Previous studies have suggested that the dorsal anterior cingulate cortex (dACC) is a key brain region involved in the detection of social exclusion. However, this region has also been shown to be sensitive to non-social expectancy violations. We often expect other people to follow an unwritten rule in which they include us as they would expect to be included, such that social exclusion likely involves some degree of expectancy violation. The present event-related functional magnetic resonance imaging (fMRI) study sought to separate the effects of expectancy violation from those of social exclusion, such that we employed an “overinclusion” condition in which a player was unexpectedly overincluded in the game by the other players. With this modification, we found that the dACC and right ventrolateral prefrontal cortex (rVLPFC) were activated by exclusion, relative to overinclusion. In addition, we identified a negative correlation between exclusion-evoked brain activity and self-rated social pain in the rVLPFC, but not in the dACC. These findings suggest that the rVLPFC is critical for regulating social pain, whereas the dACC plays an important role in the detection of exclusion. The neurobiological basis of social exclusion is different from that of mere expectancy violation. PMID:22866035
Schlund, Michael W.; Brewer, Adam T.; Richman, David M.; Magee, Sandy K.; Dymond, Simon
The dorsal anterior cingulate (adACC) and dorsal medial prefrontal cortex (dmPFC) play a central role in the discrimination and appraisal of threatening stimuli. Yet, little is known about what specific features of threatening situations recruit these regions and how avoidance may modulate appraisal and activation through prevention of aversive events. In this investigation, 30 healthy adults underwent functional neuroimaging while completing an avoidance task in which responses to an Avoidable CS+ threat prevented delivery of an aversive stimulus, but not to an Unavoidable CS+ threat. Extinction testing was also completed where CSs were presented without aversive stimulus delivery and an opportunity to avoid. The Avoidable CS+ relative to the Unavoidable CS+ was associated with reductions in ratings of negative valence, fear, and US expectancy and activation. Greater regional activation was consistently observed to the Unavoidable CS+ during avoidance, which declined during extinction. Individuals exhibiting greater aversive discounting—that is, those more avoidant of immediate monetary loss compared to a larger delayed loss—also displayed greater activation to the Unavoidable CS+, highlighting aversive discounting as a significant individual difference variable. These are the first results linking adACC/dmPFC reactivity to avoidance-based reductions of aversive events and modulation of activation by individual differences in aversive discounting. PMID:26113813
Cao, Bing; Wang, Jun; Shahed, Mahadi; Jelfs, Beth; Chan, Rosa H. M.; Li, Ying
Vagus nerve stimulation (VNS) can enhance memory and cognitive functions in both rats and humans. Studies have shown that VNS influenced decision-making in epileptic patients. However, the sites of action involved in the cognitive-enhancement are poorly understood. By employing a conscious rat model equipped with vagus nerve cuff electrode, we assess the role of chronic VNS on decision-making in rat gambling task (RGT). Simultaneous multichannel-recordings offer an ideal setup to test the hypothesis that VNS may induce alterations of in both spike-field-coherence and synchronization of theta oscillations across brain areas in the anterior cingulate cortex (ACC) and basolateral amygdala (BLA). Daily VNS, administered immediately following training sessions of RGT, caused an increase in ‘good decision-maker’ rats. Neural spikes in the ACC became synchronized with the ongoing theta oscillations of local field potential (LFP) in BLA following VNS. Moreover, cross-correlation analysis revealed synchronization between the ACC and BLA. Our results provide specific evidence that VNS facilitates decision-making and unveils several important roles for VNS in regulating LFP and spike phases, as well as enhancing spike-phase coherence between key brain areas involved in cognitive performance. These data may serve to provide fundamental notions regarding neurophysiological biomarkers for therapeutic VNS in cognitive impairment. PMID:27731403
Alkozei, Anna; Smith, Ryan; Killgore, William D S
Blue wavelength light has been used as an effective treatment for some types of mood disorders and circadian rhythm related sleep problems. We hypothesized that acute exposure to blue wavelength light would directly affect the functioning of neurocircuity implicated in emotion regulation (i.e., ventromedial prefrontal cortex, amygdala, insula, and anterior cingulate cortex [ACC]) during 'certain' and 'uncertain' anticipation of negative and positive stimuli. Thirty-five healthy adults were randomized to receive a thirty-minute exposure to either blue (active) or amber (placebo) light, immediately followed by an emotional anticipation task during functional magnetic resonance imaging (fMRI). In contrast to placebo, participants in the blue light group showed significantly reduced activation within the rostral ACC during 'uncertain' anticipation (i.e., uncertainty regarding whether a positive or negative stimulus would be shown) in comparison to 'certain' anticipation of a positive stimulus. These findings may be explicable in terms of interactions between blue light exposure and the influence of specific neuromodulators on ACC-mediated decision-making mechanisms.
Aggleton, John P; Saunders, Richard C; Wright, Nicholas F; Vann, Seralynne D
Interactions between the posterior cingulate cortex (areas 23 and 31) and the retrosplenial cortex (areas 29 and 30) with the anterior, laterodorsal and dorsal medial thalamic nuclei are thought to support various aspects of cognition, including memory and spatial processing. To detail these interactions better, the present study used retrograde tracers to reveal the origins of the corticothalamic projections in two closely related monkey species (Macaca mulatta, Macaca fascicularis). The medial dorsal thalamic nucleus received only light cortical inputs, which predominantly arose from area 23. Efferents to the anterior medial thalamic nucleus also arose principally from area 23, but these projections proved more numerous than those to the medial dorsal nucleus and also involved additional inputs from areas 29 and 30. The anterior ventral and laterodorsal thalamic nuclei had similar sources of inputs from the posterior cingulate and retrosplenial cortices. For both nuclei, the densest projections arose from areas 29 and 30, with numbers of thalamic inputs often decreasing when going dorsal from area 23a to 23c and to area 31. In all cases, the corticothalamic projections almost always arose from the deepest cortical layer. The different profiles of inputs to the anterior medial and anterior ventral thalamic nuclei reinforce other anatomical and electrophysiological findings suggesting that these adjacent thalamic nuclei serve different, but complementary, functions supporting memory. While the lack of retrosplenial connections singled out the medial dorsal nucleus, the very similar connection patterns shown by the anterior ventral and laterodorsal nuclei point to common roles in cognition.
Rance, Mariela; Ruttorf, Michaela; Nees, Frauke; Schad, Lothar Rudi; Flor, Herta
Self-regulation of brain activation using real-time functional magnetic resonance imaging has been used to train subjects to modulate activation in various brain areas and has been associated with behavioral changes such as altered pain perception. The aim of this study was to assess the comparability of upregulation versus downregulation of activation in the rostral anterior cingulate cortex (rACC) and left posterior insula (pInsL) and its effect on pain intensity and unpleasantness. In a first study, we trained 10 healthy subjects to separately upregulate and downregulate the blood oxygenation level-dependent response in the rACC or pInsL (six trials on 4 days) in response to painful electrical stimulation. The participants learned to significantly downregulate activation in pInsL and rACC and upregulate pInsL but not rACC. Success in the modulation of one region and direction of the modulation was not significantly correlated with success in another condition, indicating that the ability to control pain-related brain activation is site-specific. Less covariation between the areas in response to the nociceptive stimulus was positively correlated with learning success. Upregulation or downregulation of either region was unrelated to pain intensity or unpleasantness; however, our subjects did not learn rACC upregulation, which might be important for pain control. A significant increase in pain unpleasantness was found during upregulation of pInsL when covariation with the rACC was low. These initial results suggest that the state of the network involved in the processing of pain needs to be considered in the modulation of pain-evoked activation and its behavioral effects.
Goji, Aya; Ito, Hiromichi; Mori, Kenji; Harada, Masafumi; Hisaoka, Sonoka; Toda, Yoshihiro; Mori, Tatsuo; Abe, Yoko; Miyazaki, Masahito; Kagami, Shoji
Purpose Proton magnetic resonance spectroscopy (1H MRS) is a noninvasive neuroimaging method to quantify biochemical metabolites in vivo and it can serve as a powerful tool to monitor neurobiochemical profiles in the brain. Asperger’s syndrome (AS) is a type of autism spectrum disorder, which is characterized by impaired social skills and restrictive, repetitive patterns of interest and activities, while intellectual levels and language skills are relatively preserved. Despite clinical aspects have been well-characterized, neurometabolic profiling in the brain of AS remains to be clear. The present study used proton magnetic resonance spectroscopy (1H MRS) to investigate whether pediatric AS is associated with measurable neurometabolic abnormalities that can contribute new information on the neurobiological underpinnings of the disorder. Methods Study participants consisted of 34 children with AS (2–12 years old; mean age 5.2 (±2.0); 28 boys) and 19 typically developed children (2–11 years old; mean age 5.6 (±2.6); 12 boys) who served as the normal control group. The 1H MRS data were obtained from two regions of interest: the anterior cingulate cortex (ACC) and left cerebellum. Results In the ACC, levels of N-acetylaspartate (NAA), total creatine (tCr), total choline-containing compounds (tCho) and myo-Inositol (mI) were significantly decreased in children with AS compared to controls. On the other hand, no significant group differences in any of the metabolites were found in the left cerebellum. Neither age nor sex accounted for the metabolic findings in the regions. Conclusion The finding of decreased levels of NAA, tCr, tCho, and mI in the ACC but not in left cerebellar voxels in the AS, suggests a lower ACC neuronal density in the present AS cohort compared to controls. PMID:28060873
Nakagawa, Jun; Takahashi, Muneyoshi; Okada, Rieko; Matsushima, Eisuke; Matsuda, Tetsuya
Men, like the male of many animal species, use gifts to build satisfactory relationships with a desired woman. From the woman’s perspective, all gifts are not always equally rewarding; the reward value of a gift depends on two factors: (1) the giver and (2) the type of the gift (the gift’s social meaning). In this study, we investigated how these two factors interactively determine the reward value of a gift. Specifically, we examined how the neural processing for understanding a gift’s social meaning is modulated by preferences for the giver. We performed a functional magnetic resonance imaging (fMRI) study in which a female participant was asked to judge a gift from a male she was acquainted with in real life. We examined the interactive effects between (1) the female participant’s attitude toward the male acquaintance (liked vs. uninteresting) and (2) the type of the gift (romantic [e.g., bouquet, earrings, and perfumes] vs. non-romantic [e.g., pencils, memo pad, and moneybox]). We found that preference for an acquaintance selectively modulated activity in the anterior cingulate cortex (ACC) in response to romantic gifts, compared to non-romantic gifts. In contrast, if the woman was indifferent toward an acquaintance, no activity modulation was observed in this area for the same gifts. In addition, the ACC showed functional connectivity with the supplementary motor area/dorsal ACC (SMA/dACC), an area within the dorsal mediofrontal cortex, suggesting that it integrates action monitoring and emotional and cognitive processing in decision-making. These results suggest that attitude toward an opposite sex member has a modulatory role in recognizing the social meaning of material goods—preference for the member is a powerful modulator of social reward processing. PMID:26301954
Mazgaj, Robert; Tal, Assaf; Goetz, Raymond; Lazar, Mariana; Rothman, Karen; Messinger, Julie Walsh; Malaspina, Dolores; Gonen, Oded
Working memory (Work-Mem), the capacity to hold and manipulate information, activates the anterior cingulate cortex (ACC), especially its caudal subregion. Impaired Work-Mem and structural and functional abnormalities of the ACC are reported in schizophrenia. This study aims to elucidate the pathogenesis of Work-Mem dysfunction in schizophrenia by comparing metabolite concentrations across ACC subregions. This retrospective study of 18 schizophrenia cases and 10 matched controls used proton magnetic resonance spectroscopic imaging ((1)H-MRSI, TR/TE = 1800/35 ms, 0.5 cm(3) spatial resolution) to test whether the Work-Mem Index of the Wechsler Adult Intelligence Scale, third edition is associated with differences in the rostral to caudal ACC ratios of N-acetylaspartate (NAA) and creatine (Cr). Higher caudal:rostral ACC Cr (but not NAA) concentrations were associated with decreased Work-Mem Index in cases (r = -0.6, p = 0.02), with a similar trend in controls (r = -0.56, p = 0.10), although caudal:rostral ACC Cr correlated with NAA in cases and controls (r = 0.67 and 0.62, p < 0.05 for both). NAA and Cr ratios did not correlate with myo-inositol, excluding gliosis as the underlying process. Subjects' sex and age had no effects on these relationships. The findings suggest that rostral ACC energy hypo-metabolism, possibly arising from neurodevelopmental processes, is associated with working memory impairment in schizophrenia. Changes in the rostral (not the expected caudal) subregion underscore the interconnections between the ACC subregions and may offer laboratory markers for treatment trials, etiology studies, and perhaps even enhanced identification of prodromal "at risk" subjects.
Tikàsz, Andràs; Potvin, Stéphane; Lungu, Ovidiu; Joyal, Christian C; Hodgins, Sheilagh; Mendrek, Adrianna; Dumais, Alexandre
Background Evidence suggests a 2.1–4.6 times increase in the risk of violent behavior in schizophrenia compared to the general population. Current theories propose that the processing of negative emotions is defective in violent individuals and that dysfunctions within the neural circuits involved in emotion processing are implicated in violence. Although schizophrenia patients show enhanced sensitivity to negative stimuli, there are only few functional neuroimaging studies that have examined emotion processing among men with schizophrenia and a history of violence. Objective The present study aimed to identify the brain regions with greater neurofunctional alterations, as detected by functional magnetic resonance imaging during an emotion processing task, of men with schizophrenia who had engaged in violent behavior compared with those who had not. Methods Sixty men were studied; 20 with schizophrenia and a history of violence, 19 with schizophrenia and no violence, and 21 healthy men were scanned while viewing positive, negative, and neutral images. Results Negative images elicited hyperactivations in the anterior cingulate cortex (ACC), left and right lingual gyrus, and the left precentral gyrus in violent men with schizophrenia, compared to nonviolent men with schizophrenia and healthy men. Neutral images elicited hyperactivations in the right and left middle occipital gyrus, left lingual gyrus, and the left fusiform gyrus in violent men with schizophrenia, compared to the other two groups. Discussion Violent men with schizophrenia displayed specific increases in ACC in response to negative images. Given the role of the ACC in information integration, these results indicate a specific dysfunction in the processing of negative emotions that may trigger violent behavior in men with schizophrenia. PMID:27366072
Helmbold, K; Zvyagintsev, M; Dahmen, B; Bubenzer-Busch, S; Gaber, T J; Crockett, M J; Klasen, M; Sánchez, C L; Eisert, A; Konrad, K; Habel, U; Herpertz-Dahlmann, B; Zepf, F D
Diminished synthesis of the neurotransmitter serotonin (5-HT) has been linked to disrupted impulse control in aversive contexts. However, the neural correlates underlying a serotonergic modulation of female impulsivity remain unclear. The present study investigated punishment-induced inhibition in healthy young women. Eighteen healthy female subjects (aged 20-31) participated in a double-blinded, counterbalanced, placebo-controlled, within subjects, repeated measures study. They were assessed on two randomly assigned occasions that were controlled for menstrual cycle phase. In a randomized order, one day, acute tryptophan depletion (ATD) was used to reduce 5-HT synthesis in the brain. On the other day, participants received a tryptophan-balanced amino acid load (BAL) as a control condition. Three hours after administration of ATD/BAL, neural activity was recorded during a modified Go/No-Go task implementing reward or punishment processes using functional magnetic resonance imaging (fMRI). Neural activation during No-Go trials in punishment conditions after BAL versus ATD administration correlated positively with the magnitude of central 5-HT depletion in the ventral and subgenual anterior cingulate cortices (ACC). Furthermore, neural activation in the medial orbitofrontal cortex (mOFC) and the dorsal ACC correlated positively with trait impulsivity. The results indicate reduced neural sensitivity to punishment after short-term depletion of 5-HT in brain areas related to emotion regulation (subgenual ACC) increasing with depletion magnitude and in brain areas related to appraisal and expression of emotions (mOFC and dorsal ACC), increasing with trait impulsivity. This suggests a serotonergic modulation of neural circuits related to emotion regulation, impulsive behavior, and punishment processing in females.
Spinal astrocyte activation contributes to the pathogenesis of paclitaxel-induced neuropathic pain (PINP) in animal models. We examined glial fibrillary acidic protein (GFAP; an astrocyte marker) immunoreactivity and gene expression of GFAP, glutamate transporters and receptor subunits by real time PCR in the anterior cingulate cortex (ACC) at 7 days post first administration of paclitaxel, a time point when mice had developed thermal hyperalgesia. The ACC, an area in the brain involved in pain perception and modulation, was chosen because changes in this area might contribute to the pathophysiology of PINP. GFAP transcripts levels were elevated by more than fivefold and GFAP immunoreactivity increased in the ACC of paclitaxel-treated mice. The 6 glutamate transporters (GLAST, GLT-1 EAAC1, EAAT4, VGLUT-1 and VGLUT-2) quantified were not significantly altered by paclitaxel treatment. Of the 12 ionotropic glutamate receptor subunits transcripts analysed 6 (GLuA1, GLuA3, GLuK2, GLuK3, GLuK5 and GLuN1) were significantly up-regulated, whereas GLuA2, GLuK1, GLuK4, GLuN2A and GLuN2B were not significantly altered and GLuA4 was lowly expressed. Amongst the 8 metabotropic receptor subunits analysed only mGLuR8 was significantly elevated. In conclusion, during PINP there is astrocyte activation, with no change in glutamate transporter expression and differential up-regulation of glutamate receptor subunits in the ACC. Thus, targeting astrocyte activation and the glutamatergic system might be another therapeutic avenue for management of PINP. PMID:26528412
Zhan, Chenyang; Liu, Yuhong; Wu, Kai; Gao, Yu; Li, Xiaobo
Attention-deficit/hyperactivity disorder (ADHD), characterized by developmentally inappropriate inattention, hyperactivity/impulsivity, or a combination of both, is a major public health problem. Neuroimaging studies have revealed associations of these cognitive impairments with structural and functional deficits all over the brain. Existing findings are not fully consistent because of the heterogeneity of study samples and diversity of research techniques. In this study, we propose to utilize a multimodal magnetic resonance imaging (MRI) approach to study the structural and functional brain networks in children with ADHD-combined type (ADHD-C) with a focus on the subgenual anterior cingulate cortex (sgACC). Diffusion tensor imaging (DTI) and resting-state functional MRI (rs-fMRI) data from 32 children with ADHD-C and 32 group-matched controls were involved. Network-based statistic analysis of the rs-fMRI data revealed a disconnected functional network between the sgACC and multiple regions in the occipital lobe and cerebellum, whereas the DTI data showed disrupted white matter integrity in the subgenual cingulum bundle (sgCB). Post hoc region of interest (ROI)-based analyses showed significantly increased fluctuation of the spontaneous brain activity in the sgACC and higher radial diffusivity in the sgCB in the ADHD group. Both the rs-fMRI and DTI ROI-based measures were significantly correlated with clinical measures that examine behavioral capacities of attention and inhibitory control. Findings of this study suggest that functional alterations in the sgACC and white matter under development in the sgCB may impact each other, and together contribute to impaired attention and inhibitory control function in children with ADHD.
Cordes, Julia S.; Mathiak, Krystyna A.; Dyck, Miriam; Alawi, Eliza M.; Gaber, Tilman J.; Zepf, Florian D.; Klasen, Martin; Zvyagintsev, Mikhail; Gur, Ruben C.; Mathiak, Klaus
Cognitive functioning is impaired in patients with schizophrenia, leading to significant disabilities in everyday functioning. Its improvement is an important treatment target. Neurofeedback (NF) seems a promising method to address the neural dysfunctions underlying those cognitive impairments. The anterior cingulate cortex (ACC), a central hub for cognitive processing, is one of the brain regions known to be dysfunctional in schizophrenia. Here we conducted NF training based on real-time functional magnetic resonance imaging (fMRI) in patients with schizophrenia to enable them to control their ACC activity. Training was performed over 3 days in a group of 11 patients with schizophrenia and 11 healthy controls. Social feedback was provided in accordance with the evoked activity in the selected region of interest (ROI). Neural and cognitive strategies were examined off-line. Both groups learned to control the activity of their ACC but used different neural strategies: patients activated the dorsal and healthy controls the rostral subdivision. Patients mainly used imagination of music to elicit activity and the control group imagination of sports. In a stepwise regression analysis, the difference in neural control did not result from the differences in cognitive strategies but from diagnosis alone. Based on social reinforcers, patients with schizophrenia can learn to regulate localized brain activity. However, cognitive strategies and neural network location differ from healthy controls. These data emphasize that for therapeutic interventions in patients with schizophrenia compensatory strategies may emerge. Specific cognitive skills or specific dysfunctional networks should be addressed to train impaired skills. Social NF based on fMRI may be one method to accomplish precise learning targets. PMID:26161073
López-Cruz, Laura; Carbó-Gas, Maria; Pardo, Marta; Bayarri, Pilar; Valverde, Olga; Ledent, Catherine; Salamone, John D; Correa, Mercè
Blockade of adenosine A2A receptors can potentiate motivation to work for natural reinforcers such as food. Conspecific interaction is a potent natural reinforcer in social animals that can be manifested as preference for social exploration versus other sources of novel stimulation. Deficiencies in this type of motivated behavior (social withdrawal) have been seen in several pathologies such as autism and depression. However, the role of A2A receptors in motivation for social interaction has not been widely explored. Social interaction paradigms evaluate the natural preference of animals for exploring other conspecifics, and the ability to differentiate between familiar versus novel ones. Anxiety is one of the factors that can induce avoidance of social interaction. In the present study, adenosine A2A knockout (A2AKO) and wild-type (WT) mice were assessed for social and anxiety-related behaviors. c-Fos immunoreactivity was evaluated as a measure of neuronal activation in brain areas involved in different aspects of motivation and emotional processes. Although A2AKO mice showed an anxious profile, they displayed higher levels of sociability and were less sensitive to social novelty. WT mice displayed a typical pattern of social recognition 24h later, but not A2AKO mice, which explored equally both conspecifics. There were no differences between strains in aggressiveness, perseverance or social odor preferences. c-Fos immunoreactivity in A2AKO mice was higher in anterior cingulate and amygdala compared to WT mice. Thus, A2A receptors appear to be potential targets for the improvement of pathologies related to social function.
Woodcock, Eric A; White, Richard; Diwadkar, Vaibhav A
Cognitive control includes processes that facilitate execution of effortful cognitive tasks, including associative memory. Regions implicated in cognitive control during associative memory include the dorsal prefrontal (dPFC) and dorsal anterior cingulate cortex (dACC). Here we investigated the relative degrees of network-related interactions originating in the dPFC and dACC during oscillating phases of associative memory: encoding and cued retrieval. Volunteers completed an established object-location associative memory paradigm during fMRI. Psychophysiological interactions modeled modulatory network interactions from the dPFC and dACC during memory encoding and retrieval. Results were evaluated in second level analyses of variance with seed region and memory process as factors. Each seed exerted differentiable modulatory effects during encoding and retrieval. The dACC exhibited greater modulation (than the dPFC) on the fusiform and parahippocampal gyrus during encoding, while the dPFC exhibited greater modulation (than the dACC) on the fusiform, hippocampus, dPFC and basal ganglia. During retrieval, the dPFC exhibited greater modulation (than the dACC) on the parahippocampal gyrus, hippocampus, superior parietal lobule, and dPFC. The most notable finding was a seed by process interaction indicating that the dACC and the dPFC exerted complementary modulatory control on the hippocampus during each of the associative memory processes. These results provide evidence for differentiable, yet complementary, control-related modulation by the dACC and dPFC, while establishing the primacy of dPFC in exerting network control during both associative memory phases. Our approach and findings are relevant for understanding basic processes in human memory and psychiatric disorders that impact associative memory-related networks.
Ducharme, Simon; Hudziak, James J; Botteron, Kelly N; Ganjavi, Hooman; Lepage, Claude; Collins, D Louis; Albaugh, Matthew D.; Evans, Alan C; Karama, Sherif
Background The anterior cingulate cortex (ACC), orbito-frontal cortex (OFC) and basal ganglia have been implicated in pathological aggression. This study aimed at identifying neuroanatomical correlates of impulsive aggression in healthy children. Methods Data from 193 representative 6–18 year-old healthy children were obtained from the NIH MRI Study of Normal Brain Development after a blinded quality control (1). Cortical thickness and subcortical volumes were obtained with automated software. Aggression levels were measured with the Aggressive Behavior scale (AGG) of the Child Behavior Checklist (CBCL). AGG scores were regressed against cortical thickness and basal ganglia volumes using first and second-order linear models while controlling for age, gender, scanner site and total brain volume. ‘Gender by AGG’ interactions were analyzed. Results There were positive associations between bilateral striatal volumes and AGG scores (right: r=0.238, p=0.001; left: r=0.188, p=0.01). A significant association was found with right ACC and subgenual ACC cortical thickness in a second-order linear model (p<0.05, corrected). High AGG scores were associated with a relatively thin right ACC cortex. An ‘AGG by gender’ interaction trend was found in bilateral OFC and ACC associations with AGG scores. Conclusion This study shows the existence of relationships between impulsive aggression in healthy children and the structure of the striatum and right ACC. It also suggests the existence of gender specific patterns of association in OFC/ACC grey matter. These results may guide research on oppositional-defiant and conduct disorders. PMID:21531391
Gittins, Rebecca; Harrison, Paul J
There are an increasing number of quantitative morphometric studies of the human cerebral cortex, especially as part of comparative investigations of major psychiatric disorders. In this context, the present study had two aims. First, to provide quantitative data regarding key neuronal morphometric parameters in the anterior cingulate cortex. Second, to compare the results of conventional Nissl staining with those observed after immunostaining with NeuN, an antibody becoming widely used as a selective neuronal marker. We stained adjacent sections of area 24b from 16 adult brains with cresyl violet or NeuN. We measured the density of pyramidal and non-pyramidal neurons, and the size and shape of pyramidal neurons, in laminae II, III, Va, Vb and VI, using two-dimensional counting methods. Strong correlations between the two modes of staining were seen for all variables. However, NeuN gave slightly higher estimates of neuronal density and size, and a more circular perikaryal shape. Brain pH was correlated with neuronal size, measured with both methods, and with neuronal shape. Age and post-mortem interval showed no correlations with any parameter. These data confirm the value of NeuN as a tool for quantitative neuronal morphometric studies in routinely processed human brain tissue. Absolute values are highly correlated between NeuN and cresyl violet stains, but cannot be interchanged. NeuN may be particularly useful when it is important to distinguish small neurons from glia, such as in cytoarchitectural studies of the cerebral cortex in depression and schizophrenia.
Minzenberg, Michael J; Lesh, Tyler; Niendam, Tara; Yoon, Jong H; Cheng, Yaoan; Rhoades, Remy; Carter, Cameron S
Suicide is highly prevalent in schizophrenia (SZ), yet it remains unclear how suicide risk factors such as past suicidal ideation or behavior relate to brain function. Circuits modulated by the prefrontal cortex (PFC) are altered in SZ, including in dorsal anterior cingulate cortex (dACC) during conflict-monitoring (an important component of cognitive control), and dACC changes are observed in post-mortem studies of heterogeneous suicide victims. We tested whether conflict-related dACC functional connectivity is associated with past suicidal ideation and behavior in SZ. 32 patients with recent-onset of DSM-IV-TR-defined SZ were evaluated with the Columbia Suicide Severity Rating Scale and functional MRI during cognitive control (AX-CPT) task performance. Group-level regression models relating past history of suicidal ideation or behavior to dACC-seeded functional connectivity during conflict-monitoring controlled for severity of depression, psychosis and impulsivity. Past suicidal ideation was associated with relatively higher functional connectivity of the dACC with the precuneus during conflict-monitoring. Intensity of worst-point past suicidal ideation was associated with relatively higher dACC functional connectivity in medial parietal lobe and striato-thalamic nuclei. In contrast, among those with past suicidal ideation (n = 17), past suicidal behavior was associated with lower conflict-related dACC connectivity with multiple lateral and medial PFC regions, parietal and temporal cortical regions. This study provides unique evidence that recent-onset schizophrenia patients with past suicidal ideation or behavior show altered dACC-based circuit function during conflict-monitoring. Suicidal ideation and suicidal behavior have divergent patterns of associated dACC functional connectivity, suggesting a differing pattern of conflict-related brain dysfunction with these two distinct features of suicide phenomenology.
Wartman, Brianne C.; Gabel, Jennifer; Holahan, Matthew R.
One system consolidation model suggests that as time passes, ensembles of cortical neurons form strong connections to represent remote memories. In this model, the anterior cingulate cortex (ACC) serves as a cortical region that represents remote memories. However, there is debate as to whether remote spatial memories go through this systems consolidation process and come to rely on the ACC. The present experiment examined whether increasing the processing demand on the hippocampus, by sequential training on two spatial tasks, would more fully engage the ACC during retrieval of a remote spatial memory. In this scenario, inactivation of the ACC at a remote time point was hypothesized to produce a severe memory deficit if rats had been trained on two, sequential spatial tasks. Rats were trained on a water maze (WM) task only or a WM task followed by a radial arm maze task. A WM probe test was given recently or remotely to all rats. Prior to the probe test, rats received an injection of saline or muscimol into the ACC. A subtle deficit in probe performance was found at the remote time point in the group trained on only one spatial task and treated with muscimol. In the group trained on two spatial tasks and treated with muscimol, a subtle deficit in probe performance was noted at the recent time point and a substantial deficit in probe performance was observed at the remote time point. c-Fos labeling in the hippocampus revealed more labeling in the CA1 region in all remotely tested groups than recently tested groups. Findings suggest that spatial remote memories come to rely more fully on the ACC when hippocampal processing requirements are increased. Results also suggest continued involvement of the hippocampus in spatial memory retrieval along with a progressive strengthening of cortical connections as time progresses. PMID:25279556
Barch, D M; Braver, T S; Sabb, F W; Noll, D C
Studies of a range of higher cognitive functions consistently activate a region of anterior cingulate cortex (ACC), typically posterior to the genu and superior to the corpus collosum. In particular, this ACC region appears to be active in task situations where there is a need to override a prepotent response tendency, when responding is underdetermined, and when errors are made. We have hypothesized that the function of this ACC region is to monitor for the presence of "crosstalk" or competition between incompatible responses. In prior work, we provided initial support for this hypothesis, demonstrating ACC activity in the same region both during error trials and during correct trials in task conditions designed to elicit greater response competition. In the present study, we extend our testing of this hypothesis to task situations involving underdetermined responding. Specifically, 14 healthy control subjects performed a verb-generation task during event-related functional magnetic resonance imaging (fMRI), with the on-line acquisition of overt verbal responses. The results demonstrated that the ACC, and only the ACC, was more active in a series of task conditions that elicited competition among alternative responses. These conditions included a greater ACC response to: (1) Nouns categorized as low vs. high constraint (i.e., during a norming study, multiple verbs were produced with equal frequency vs. a single verb that produced much more frequently than any other); (2) the production of verbs that were weak associates, rather than, strong associates of particular nouns; and (3) the production of verbs that were weak associates for nouns categorized as high constraint. We discuss the implication of these results for understanding the role that the ACC plays in human cognition.
Weissman, D H; Giesbrecht, B; Song, A W; Mangun, G R; Woldorff, M G
Parallel processing affords the brain many advantages, but processing multiple bits of information simultaneously presents formidable challenges. For example, while one is listening to a speaker at a noisy social gathering, processing irrelevant conversations may lead to the activation of irrelevant perceptual, semantic, and response representations that conflict with those evoked by the speaker. In these situations, specialized brain systems may be recruited to detect and resolve conflict before it leads to incorrect perception and/or behavior. Consistent with this view, recent findings indicate that dorsal/caudal anterior cingulate cortex (dACC), on the medial walls of the frontal lobes, detects conflict between competing motor responses primed by relevant versus irrelevant stimuli. Here, we used a cued global/local selective attention task to investigate whether the dACC plays a general role in conflict detection that includes monitoring for conflicting perceptual or semantic representations. Using event-related functional magnetic resonance imaging (fMRI), we found that the dACC was activated by response conflict in both the global and the local task, consistent with results from prior studies. However, dACC was also activated by perceptual and semantic conflict arising from global distracters during the local task. The results from the local task have implications for recent theories of attentional control in which the dACC's contribution to conflict monitoring is limited to response stages of processing, as well as for our understanding of clinical disorders in which disruptions of attention are associated with dACC dysfunction.
Feroz, Farah Shahnaz; Leicht, Gregor; Steinmann, Saskia; Andreou, Christina; Mulert, Christoph
Growing evidence from neuroimaging studies suggest that emotional and cognitive processes are interrelated. Anatomical key structures in this context are the dorsal and rostral-ventral anterior cingulate cortex (dACC and rvACC). However, up to now, the time course of activations within these regions during emotion-cognition interactions has not been disentangled. In the present study, we used event-related potentials (ERP) and standardized low-resolution electromagnetic tomography (sLORETA) region of interest (ROI) source localization analyses to explore the time course of neural activations within the dACC and rvACC using a modified emotional Stroop paradigm. ERP components related to Stroop conflict (N200, N450 and late negativity) were analyzed. The time course of brain activations in the dACC and rvACC was strikingly different with more pronounced initial responses in the rvACC followed by increased dACC activity mainly at the late negativity window. Moreover, emotional valence modulated the earlier N450 stage within the rvACC region with higher neural activations in the positive compared to the negative and neutral conditions. Emotional arousal modulated the late negativity stage; firstly in the significant arousal × congruence ERP effect and then the significant higher current density in the low arousal condition within the dACC. Using sLORETA source localization, substantial differences in the activation time courses in the dACC and rvACC could be found during the emotional Stroop task. We suggest that during late negativity, within the dACC, emotional arousal modulated the processing of response conflict, reflected in the correlation between the ex-Gaussian µ and the current density in the dACC.
Holec, Victoria; Pirot, Heather L.; Euston, David R.
The rat anterior cingulate cortex (ACC) mediates effort-based decision making when the task requires the physical effort of climbing a ramp. Normal rats will readily climb a barrier leading to high reward whereas rats with ACC lesions will opt instead for an easily obtained small reward. The present study explored whether the role of ACC in cost-benefit decisions extends beyond climbing by testing its role in ramp climbing as well as two novel cost-benefit decision tasks, one involving the physical effort of lifting weights and the other the emotional cost of overcoming fear (i.e., “courage”). As expected, rats with extensive ACC lesions tested on a ramp-climbing task were less likely to choose a high-reward/high-effort arm than sham controls. However, during the first few trials, lesioned rats were as likely as controls to initially turn into the high-reward arm (HRA) but far less likely to actually climb the barrier, suggesting that the role of the ACC is not in deciding which course of action to pursue, but rather in maintaining a course of action in the face of countervailing forces. In the effort-reward decision task involving weight lifting, some lesion animals behaved like controls while others avoided the HRA. However, the results were not statistically significant and a follow-up study using incremental increasing effort failed to show any difference between lesion and control groups. The results suggest that the ACC is not needed for effort-reward decisions involving weight lifting but may affect motor abilities. Finally, a courage task explored the willingness of rats to overcome the fear of crossing an open, exposed arm to obtain a high reward. Both sham and ACC-lesioned animals exhibited equal tendencies to enter the open arm. However, whereas sham animals gradually improved on the task, ACC-lesioned rats did not. Taken together, the results suggest that the role of the ACC in effort-reward decisions may be limited to certain tasks. PMID:24478659
Dedovic, Katarina; Slavich, George M.; Muscatell, Keely A.; Irwin, Michael R.; Eisenberger, Naomi I.
The dorsal anterior cingulate cortex (dACC) is recruited when a person is socially rejected or negatively evaluated. However, it remains to be fully understood how this region responds to repeated exposure to personally-relevant social evaluation, in both healthy populations and those vulnerable to Major Depressive Disorder (MDD), as well as how responding in these regions is associated with subsequent clinical functioning. To address this gap in the literature, we recruited 17 young women with past history of MDD (previously depressed) and 31 healthy controls and exposed them to a social evaluative session in a neuroimaging environment. In two bouts, participants received an equal amount of positive, negative, and neutral feedback from a confederate. All participants reported increases in feelings of social evaluation in response to the evaluative task. However, compared to healthy controls, previously depressed participants tended to show greater increases in depressed mood following the task. At the neural level, in response to negative (vs. positive) feedback, no main effect of group or evaluation periods was observed. However, a significant interaction between group and evaluation periods was found. Specifically, over the two bouts of evaluation, activity in the dACC decreased among healthy participants while it increased among previously depressed individuals. Interestingly and unexpectedly, in the previously depressed group specifically, this increased activity in dACC over time was associated with lower levels of depressive symptoms at baseline and at 6-months following the evaluation session (controlling for baseline levels). Thus, the subset of previously depressed participants who showed increases in the recruitment of the dACC over time in response to the negative evaluation seemed to fair better emotionally. These findings suggest that examining how the dACC responds to repeated bouts of negative evaluation reveals a new dimension to the role of the d
Onoda, Keiichi; Okamoto, Yasumasa; Nakashima, Ken'ichiro; Nittono, Hiroshi; Yoshimura, Shinpei; Yamawaki, Sigeto; Yamaguchi, Shuhei; Ura, Mitsuhiro
According to sociometer theory, self-esteem serves as a barometer of the extent to which individuals are socially included or excluded by others. We hypothesized that trait self-esteem would be related to social pain responsiveness, and we used functional magnetic resonance imaging to experimentally investigate this potential relationship. Participants (n = 26) performed a cyberball task, a computerized game of catch during which the participants were excluded from the game. Participants then rated the degree of social pain experienced during both inclusion in and exclusion from the game. Individuals with lower trait self-esteem reported increased social pain relative to individuals with higher trait self-esteem, and such individuals also demonstrated a greater degree of dorsal anterior cingulate cortex activation. A psychophysiological interaction analysis revealed a positive connectivity between the dorsal anterior cingulate and prefrontal cortices for the lower trait self-esteem group, and a corresponding negative connectivity for the higher trait self-esteem group. Heightened dorsal anterior cortex activity and a corresponding connection with the prefrontal cortex might be one possible explanation for the greater levels of social pain observed experienced by individuals with low trait self-esteem.
Bejjani, Anthony; O'Neill, Joseph; Kim, John A.; Frew, Andrew J.; Yee, Victor W.; Ly, Ronald; Kitchen, Christina; Salamon, Noriko; McCracken, James T.; Toga, Arthur W.; Alger, Jeffry R.; Levitt, Jennifer G.
Recent research in autism spectrum disorder (ASD) has aroused interest in anterior cingulate cortex and in the neurometabolite glutamate. We report two studies of pregenual anterior cingulate cortex (pACC) in pediatric ASD. First, we acquired in vivo single-voxel proton magnetic resonance spectroscopy (1H MRS) in 8 children with ASD and 10 typically developing controls who were well matched for age, but with fewer males and higher IQ. In the ASD group in midline pACC, we found mean 17.7% elevation of glutamate + glutamine (Glx) (p<0.05) and 21.2% (p<0.001) decrement in creatine + phosphocreatine (Cr). We then performed a larger (26 subjects with ASD, 16 controls) follow-up study in samples now matched for age, gender, and IQ using proton magnetic resonance spectroscopic imaging (1H MRSI). Higher spatial resolution enabled bilateral pACC acquisition. Significant effects were restricted to right pACC where Glx (9.5%, p<0.05), Cr (6.7%, p<0.05), and N-acetyl-aspartate + N-acetyl-aspartyl-glutamate (10.2%, p<0.01) in the ASD sample were elevated above control. These two independent studies suggest hyperglutamatergia and other neurometabolic abnormalities in pACC in ASD, with possible right-lateralization. The hyperglutamatergic state may reflect an imbalance of excitation over inhibition in the brain as proposed in recent neurodevelopmental models of ASD. PMID:22848344
Passamonti, Luca; Rowe, James B.; Ewbank, Michael; Hampshire, Adam; Keane, Jill; Calder, Andrew J.
For some people facial expressions of aggression are intimidating, for others they are perceived as provocative, evoking an aggressive response. Identifying the key neurobiological factors that underlie this variation is fundamental to our understanding of aggressive behaviour. The amygdala and the ventral anterior cingulate cortex (ACC) have been implicated in aggression. Using functional magnetic resonance imaging (fMRI), we studied how the interaction between these regions is influenced by the drive to obtain reward (reward–drive or appetitive motivation), a personality trait consistently associated with aggression. Two distinct techniques showed that the connectivity between the ventral ACC and the amygdala was strongly correlated with personality, with high reward–drive participants displaying reduced negative connectivity. Furthermore, the direction of this effect was restricted from ventral ACC to the amygdala but not vice versa. The personality-mediated variation in the pathway from the ventral anterior cingulate cortex to the amygdala provides an account of why signals of aggression are interpreted as provocative by some individuals more than others. PMID:18722533
Brocki, K; Clerkin, S M; Guise, K G; Fan, Jin; Fossella, J A
It is well known that children show gradual and protracted improvement in an array of behaviors involved in the conscious control of thought and emotion. Non-invasive neuroimaging in developing populations has revealed many neural correlates of behavior, particularly in the developing cingulate cortex and frontostriatal circuits. These brain regions, themselves, undergo protracted molecular and cellular change in the first two decades of human development and, as such, are ideal regions of interest for cognitive- and imaging-genetic studies that seek to link processes at the biochemical and synaptic levels to brain activity and behavior. We review our research to date that employs both adult and child-friendly versions of the attention network task (ANT) in an effort to begin to describe the role of specific genes in the assembly of a functional attention system. Presently, we constrain our predictions for genetic association studies by focusing on the role of the anterior cingulate cortex (ACC) and of dopamine in the development of executive attention.
Fukunaga, Rena; Brown, Joshua W.; Bogg, Tim
The inferior frontal gyrus/anterior insula (IFG/AI) and anterior cingulate cortex (ACC) are key regions involved in risk appraisal during decision making, but accounts of how these regions contribute to decision-making under risk remain contested. To help clarify the roles of these and other related regions, we used a modified version of the Balloon Analogue Risk Task (Lejuez et al., 2002) to distinguish between decision-making and feedback-related processes when participants decided to pursue a gain as the probability of loss increased parametrically. Specifically, we set out to test whether ACC and IFG/AI regions correspond to loss-aversion at the time of decision making in a way that is not confounded with either reward-seeking or infrequency effects. When participants chose to discontinue inflating the balloon (win option), we observed greater ACC and mainly bilateral IFG/AI activity at the time of decision as the probability of explosion increased, consistent with increased loss-aversion but inconsistent with an infrequency effect. In contrast, we found robust vmPFC activity when participants chose to continue inflating the balloon (risky option), consistent with reward-seeking. However, in the cingulate and mainly bilateral IFG regions, BOLD activation decreased when participants chose to inflate the balloon as the probability of explosion increased, findings consistent with a reduced loss-aversion signal. Our results highlight the existence of distinct reward-seeking and loss-averse signals during decision-making, as well as the importance of distinguishing decision and feedback signals. PMID:22707378
Helmeke, C; Poeggel, G; Braun, K
It appears likely that, in analogy to the synaptic development of sensory and motor cortices, which critically depends on sensory or motor stimulation (Rosenzweig and Bennett, 1996), the synaptic development of limbic cortical regions are modulated by early postnatal cognitive and emotional experiences. The very first postnatal experience, which takes place in a confined and stable familial environment, is the interaction of the newborn individual with the parents and siblings (Gray, 1958). The aim of this quantitative morphological study was to analyze the impact of different degrees of juvenile emotional experience on the synaptic development in a limbic cortical area, the dorsal anterior cingulate cortex, a region which is involved in the perception and regulation of emotions. We study the precocious trumpet-tailed rat (Octodon degus) as the animal model, because, like human babies, this species is born with functional visual and acoustic systems and the pups are therefore capable of detecting even subtle environmental changes immediately after birth (Reynolds and Wright, 1979; Poeggel and Braun, 1996; Braun et al., 2000; Ovtscharoff and Braun, 2001). The results demonstrate that already a subtle disturbance of the familial environment such as handling induced significantly elevated spine densities on the basal dendrites of layer III cortical pyramidal neurons. More severe disturbances of the emotional environment, such as periodic parental deprivation with or without subsequent chronic social isolation, resulted in an elevation of spine densities of similar magnitude as seen after handling and in addition, altered spine densities confined to specific dendritic segments were observed in these groups. These observations unveil the remarkable sensitivity of the dorsal anterior cingulate cortex towards environmental influences and behavioral experiences during phases of postnatal development. The behavioral consequences of these experience-induced synaptic changes
Cui, Long-Biao; Liu, Jian; Wang, Liu-Xian; Li, Chen; Xi, Yi-Bin; Guo, Fan; Wang, Hua-Ning; Zhang, Lin-Chuan; Liu, Wen-Ming; He, Hong; Tian, Ping; Yin, Hong; Lu, Hongbing
Understanding the neural basis of schizophrenia (SZ) is important for shedding light on the neurobiological mechanisms underlying this mental disorder. Structural and functional alterations in the anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), hippocampus, and medial prefrontal cortex (MPFC) have been implicated in the neurobiology of SZ. However, the effective connectivity among them in SZ remains unclear. The current study investigated how neuronal pathways involving these regions were affected in first-episode SZ using functional magnetic resonance imaging (fMRI). Forty-nine patients with a first-episode of psychosis and diagnosis of SZ—according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision—were studied. Fifty healthy controls (HCs) were included for comparison. All subjects underwent resting state fMRI. We used spectral dynamic causal modeling (DCM) to estimate directed connections among the bilateral ACC, DLPFC, hippocampus, and MPFC. We characterized the differences using Bayesian parameter averaging (BPA) in addition to classical inference (t-test). In addition to common effective connectivity in these two groups, HCs displayed widespread significant connections predominantly involved in ACC not detected in SZ patients, but SZ showed few connections. Based on BPA results, SZ patients exhibited anterior cingulate cortico-prefrontal-hippocampal hyperconnectivity, as well as ACC-related and hippocampal-dorsolateral prefrontal-medial prefrontal hypoconnectivity. In summary, spectral DCM revealed the pattern of effective connectivity involving ACC in patients with first-episode SZ. This study provides a potential link between SZ and dysfunction of ACC, creating an ideal situation to associate mechanisms behind SZ with aberrant connectivity among these cognition and emotion-related regions. PMID:26578933
Albrechet-Souza, Lucas; Carvalho, Milene Cristina; Brandão, Marcus Lira
Although dopamine-related circuits are best known for their roles in appetitive motivation, consistent data have implicated this catecholamine in some forms of response to stressful situations. In fact, projection areas of the ventral tegmental area, such as the amygdala and hippocampus, are well established to be involved in the acquisition and expression of fear conditioning, while less is known about the role of the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) in these processes. In the present study, we initially investigated the involvement of the mPFC and NAc in the expression of conditioned fear, assessing freezing behaviour and Fos protein expression in the brains of rats exposed to a context, light or tone previously paired with footshocks. Contextual and cued stimuli were able to increase the time of the freezing response while only the contextual fear promoted a significant increase in Fos protein expression in the mPFC and caudal NAc. We then examined the effects of specific dopaminergic agonists and antagonists injected bilaterally into the posterior medioventral shell subregion of the NAc (NAcSh) on the expression of contextual fear. SKF38393, quinpirole and sulpiride induced no behavioural changes, but the D1-like receptor antagonist SCH23390 increased the freezing response of the rats and selectively reduced Fos protein expression in the anterior cingulate cortex and rostral NAcSh. These findings confirm the involvement of the NAcSh in the expression of contextual fear memories and indicate the selective role of NAcSh D1-like receptors and anterior cingulate cortex in this process.
Krause-Utz, Annegret; Elzinga, Bernet M.; Oei, Nicole Y. L.; Paret, Christian; Niedtfeld, Inga; Spinhoven, Philip; Bohus, Martin; Schmahl, Christian
Working memory is critically involved in ignoring emotional distraction while maintaining goal-directed behavior. Antagonistic interactions between brain regions implicated in emotion processing, e.g., amygdala, and brain regions involved in cognitive control, e.g., dorsolateral and dorsomedial prefrontal cortex (dlPFC, dmPFC), may play an important role in coping with emotional distraction. We previously reported prolonged reaction times associated with amygdala hyperreactivity during emotional distraction in interpersonally traumatized borderline personality disorder (BPD) patients compared to healthy controls (HC): Participants performed a working memory task, while neutral versus negative distractors (interpersonal scenes from the International Affective Picture System) were presented. Here, we re-analyzed data from this study using psychophysiological interaction analysis. The bilateral amygdala and bilateral dorsal anterior cingulate cortex (dACC) were defined as seed regions of interest. Whole-brain regression analyses with reaction times and self-reported increase of dissociation were performed. During emotional distraction, reduced amygdala connectivity with clusters in the left dorsolateral and ventrolateral PFC was observed in the whole group. Compared to HC, BPD patients showed a stronger coupling of both seeds with a cluster in the right dmPFC and stronger positive amygdala connectivity with bilateral (para)hippocampus. Patients further demonstrated stronger positive dACC connectivity with left posterior cingulate, insula, and frontoparietal regions during emotional distraction. Reaction times positively predicted amygdala connectivity with right dmPFC and (para)hippocampus, while dissociation positively predicted amygdala connectivity with right ACC during emotional distraction in patients. Our findings suggest increased attention to task-irrelevant (emotional) social information during a working memory task in interpersonally traumatized patients
Corcoran, Kevin A; Frick, Brendan J; Radulovic, Jelena; Kay, Leslie M
Memory for contextual fear conditioning relies upon the retrosplenial cortex (RSC) regardless of how long ago conditioning occurred, whereas areas connected to the RSC, such as the dorsal hippocampus (DH) and anterior cingulate cortex (ACC) appear to play time-limited roles. To better understand whether these brain regions functionally interact during memory processing and how the passage of time affects these interactions, we simultaneously recorded local field potentials (LFPs) from these three regions as well as anterior dorsal thalamus (ADT), which provides one of the strongest inputs to RSC, and measured coherence of oscillatory activity within the theta (4-12Hz) and gamma (30-80Hz) frequency bands. We identified changes of theta coherence related to encoding, retrieval, and extinction of context fear, whereas changes in gamma coherence were restricted to fear extinction. Specifically, exposure to a novel context and retrieval of recently acquired fear conditioning memory were associated with increased theta coherence between RSC and all three other structures. In contrast, RSC-DH and RSC-ADT theta coherence were decreased in mice that successfully retrieved, relative to mice that failed to retrieve, remote memory. Greater RSC-ADT theta and gamma coherence were observed during recent, compared to remote, extinction of freezing responses. Thus, the degree of coherence between RSC and connected brain areas may predict and contribute to context memory retrieval and retrieval-related phenomena such as fear extinction. Importantly, although theta coherence in this circuit increases during memory encoding and retrieval of recent memory, failure to decrease RSC-DH theta coherence might be linked to retrieval deficit in the long term, and possibly contribute to aberrant memory processing characteristic of neuropsychiatric disorders.
Gaudio, Santino; Piervincenzi, Claudia; Beomonte Zobel, Bruno; Romana Montecchi, Francesca; Riva, Giuseppe; Carducci, Filippo; Cosimo Quattrocchi, Carlo
Previous Resting-State Functional Connectivity (RSFC) studies have shown several functional alterations in adults with or recovered from long Anorexia Nervosa (AN). The aim of this paper was to investigate whole brain RSFC in adolescents with AN in the earliest stages, less than 6 months, of the disorder. Sixteen drug-naïve outpatient female adolescents with AN-restrictive type (AN-r) (mean age: 15,8; SD 1,7) were compared to 16 age-matched healthy female (mean age: 16,3; SD 1,4). Relevant resting state networks (RSNs) were identified using independent component analysis (ICA) from functional magnetic resonance imaging data; a dual regression technique was used to detect between-group differences in the RSNs. Between-group differences of the functional connectivity maps were found in the executive control network (ECN). Particularly, decreased temporal correlation was observed in AN-r patients relative to healthy controls between the ECN functional connectivity maps and the anterior cingulate cortex (p < 0.05 corrected). Our results in AN adolescents may represent an early trait-related biomarker of the disease. Considering that the above mentioned network and its area are mainly involved in cognitive control and emotional processing, our findings could explain the impaired cognitive flexibility in relation to body image and appetite in AN patients. PMID:26043139
Shen, Zui; Sun, Jing; Liu, Boyi; Jiang, Yongliang; Wu, Yuanyuan; Wang, Jialing; Shao, Xiaomei; Fang, Jianqiao
BACKGROUND The rostral anterior cingulate cortex (rACC) is important in pain expectation. Previous studies demonstrated that mechanical stimulus-induced withdrawal behaviors are spinally-mediated nocifensive reflexes in rats, but it is not known whether pain expectation is influenced by withdrawal behaviors. MATERIAL AND METHODS We reanalyzed previous mechanosensitivity measurements of 244 rats measured 5 times in succession. To study neural oscillation in the rACC, 1 recording microwire array was surgically implanted. Then, we simultaneously recorded the local field potential (LFP) of the rACC over the course of multiple withdrawal behaviors in unanesthetized rats. RESULTS From our previous withdrawal behavioral data in 244 rats, we observed that the distributions of paw withdrawal thresholds (PWTs) were denser and more concentrated after the first withdrawal behavior. Compared to the first mechanical stimulus, increased neuronal synchrony and a stronger delta band component existed in each pre-stimulus LFP in the rACC during subsequent stimuli. CONCLUSIONS Pain expectation could be involved in withdrawal behaviors, which is related to increased total power and delta band power of the subsequent pre-stimulus LFPs in the rACC.
Hosking, Jay G; Cocker, Paul J; Winstanley, Catharine A
Personal success often requires the choice to expend greater effort for larger rewards, and deficits in such effortful decision making accompany a number of illnesses including depression, schizophrenia, and attention-deficit/hyperactivity disorder. Animal models have implicated brain regions such as the basolateral amygdala (BLA) and anterior cingulate cortex (ACC) in physical effort-based choice, but disentangling the unique contributions of these two regions has proven difficult, and effort demands in industrialized society are predominantly cognitive in nature. Here we utilize the rodent cognitive effort task (rCET), a modification of the five-choice serial reaction-time task, wherein animals can choose to expend greater visuospatial attention to obtain larger sucrose rewards. Temporary inactivation (via baclofen-muscimol) of BLA and ACC showed dissociable effects: BLA inactivation caused hard-working rats to 'slack off' and 'slacker' rats to work harder, whereas ACC inactivation caused all animals to reduce willingness to expend mental effort. Furthermore, BLA inactivation increased the time needed to make choices, whereas ACC inactivation increased motor impulsivity. These data illuminate unique contributions of BLA and ACC to effort-based decision making, and imply overlapping yet distinct circuitry for cognitive vs physical effort. Our understanding of effortful decision making may therefore require expanding our models beyond purely physical costs.
Adams, Natalie E; Sherfey, Jason S; Kopell, Nancy J; Whittington, Miles A; LeBeau, Fiona E N
The anterior cingulate cortex (ACC) is vital for a range of brain functions requiring cognitive control and has highly divergent inputs and outputs, thus manifesting as a hub in connectomic analyses. Studies show diverse functional interactions within the ACC are associated with network oscillations in the β (20-30 Hz) and γ (30-80 Hz) frequency range. Oscillations permit dynamic routing of information within cortex, a function that depends on bandpass filter-like behavior to selectively respond to specific inputs. However, a putative hub region such as ACC needs to be able to combine inputs from multiple sources rather than select a single input at the expense of others. To address this potential functional dichotomy, we modeled local ACC network dynamics in the rat in vitro. Modal peak oscillation frequencies in the β- and γ-frequency band corresponded to GABAAergic synaptic kinetics as seen in other regions; however, the intrinsic properties of ACC principal neurons were highly diverse. Computational modeling predicted that this neuronal response diversity broadened the bandwidth for filtering rhythmic inputs and supported combination-rather than selection-of different frequencies within the canonical γ and β electroencephalograph bands. These findings suggest that oscillating neuronal populations can support either response selection (routing) or combination, depending on the interplay between the kinetics of synaptic inhibition and the degree of heterogeneity of principal cell intrinsic conductances.
Cohen-Gilbert, Julia E; Sneider, Jennifer T; Crowley, David J; Rosso, Isabelle M; Jensen, J Eric; Silveri, Marisa M
Neuroimaging studies of individuals with family histories of alcoholism provide evidence suggesting neurobiological risk factors for alcoholism. Youth family history positive (FH+) for alcoholism exhibit increased impulsivity compared to family history negative (FH-) peers in conjunction with altered functional activation in prefrontal cortex, including anterior cingulate cortex (ACC). This study examined glutamate (Glu) and glutamine (Gln), amino acids vital to protein synthesis, cellular metabolism and neurotransmission, acquired from ACC and parieto-occipital cortex (POC) using magnetic resonance spectroscopy (MRS) at 4T. Participants were 28 adolescents (13 male, 12-14 yrs) and 31 emerging adults (16 male, 18-25 yrs), stratified into FH- and FH+ groups. Significantly higher ACC Gln/Glu was observed in emerging adults versus adolescents in FH- but not FH+ groups. In FH- adolescents, higher impulsivity was significantly associated with higher ACC Gln/Glu. In FH+ emerging adults, higher impulsivity was negatively associated with ACC Gln/Glu. No differences or associations were observed for POC. These findings provide preliminary evidence that family history of alcoholism is associated with a neurochemical profile that may influence normative age differences in glutamatergic metabolites and their association with impulse control, which together could confer greater genetic risk of addiction later in life.
Reis, Fernando M C V; Albrechet-Souza, Lucas; Franci, Celso R; Brandão, Marcus L
The extent to which the hypothalamic-pituitary-adrenal axis is activated by short-term and long-term consequences of stress is still open to investigation. This study aimed to determine (i) the correlation between plasma corticosterone and exploratory behavior exhibited by rats subjected to the elevated plus maze (EPM) following different periods of social isolation, (ii) the effects of the corticosterone synthesis blocker, metyrapone, on the behavioral consequences of isolation, and (iii) whether corticosterone produces its effects through an action on the anterior cingulate cortex, area 1 (Cg1). Rats were subjected to 30-min, 2-h, 24-h, or 7-day isolation periods before EPM exposure and plasma corticosterone assessments. Isolation for longer periods of time produced greater anxiogenic-like effects on the EPM. However, stretched attend posture (SAP) and plasma corticosterone concentrations were increased significantly after 30 min of isolation. Among all of the behavioral categories measured in the EPM, only SAP positively correlated with plasma corticosterone. Metyrapone injected prior to the 24 h isolation period reversed the anxiogenic effects of isolation. Moreover, corticosterone injected into the Cg1 produced a selective increase in SAP. These findings indicate that risk assessment behavior induced by the action of corticosterone on Cg1 neurons initiates a cascade of defensive responses during exposure to stressors.
Sun, Jing; Liu, Bo-Yi; Shen, Zui; Fang, Fang; Wang, Jia-Ling
Pain memory is considered as endopathic factor underlying stubborn chronic pain. Our previous study demonstrated that electroacupuncture (EA) can alleviate retrieval of pain memory. This study was designed to observe the different effects between EA and indomethacin (a kind of nonsteroid anti-inflammatory drugs, NSAIDs) in a rat pain memory model. To explore the critical role of protein kinase A (PKA) in pain memory, a PKA inhibitor was microinjected into anterior cingulate cortex (ACC) in model rats. We further investigated the roles of the cyclic adenosine monophosphate (cAMP), PKA, cAMP response element-binding protein (CREB), and cAMP/PKA/CREB pathway in pain memory to explore the potential molecular mechanism. The results showed that EA alleviates the retrieval of pain memory while indomethacin failed. Intra-ACC microinjection of a PKA inhibitor blocked the occurrence of pain memory. EA reduced the activation of cAMP, PKA, and CREB and the coexpression levels of cAMP/PKA and PKA/CREB in the ACC of pain memory model rats, but indomethacin failed. The present findings identified a critical role of PKA in ACC in retrieval of pain memory. We propose that the proper mechanism of EA on pain memory is possibly due to the partial inhibition of cAMP/PKA/CREB signaling pathway by EA. PMID:28090359
Friedman, Amy L; Burgess, Ashley; Ramaseshan, Karthik; Easter, Phil; Khatib, Dalal; Chowdury, Asadur; Arnold, Paul D; Hanna, Gregory L; Rosenberg, David R; Diwadkar, Vaibhav A
In an effort to elucidate differences in functioning brain networks between youth with obsessive-compulsive disorder and controls, we used fMRI signals to analyze brain network interactions of the dorsal anterior cingulate cortex (dACC) during visually coordinated motor responses. Subjects made a uni-manual response to briefly presented probes, at periodic (allowing participants to maintain a "motor set") or random intervals (demanding reactive responses). Network interactions were assessed using psycho-physiological interaction (PPI), a basic model of functional connectivity evaluating modulatory effects of the dACC in the context of each task condition. Across conditions, OCD were characterized by hyper-modulation by the dACC, with loci alternatively observed as both condition-general and condition-specific. Thus, dynamically driven task demands during simple uni-manual motor control induce compensatory network interactions in cortical-thalamic regions in OCD. These findings support previous research in OCD showing compensatory network interactions during complex memory tasks, but establish that these network effects are observed during basic sensorimotor processing. Thus, these patterns of network dysfunction may in fact be independent of the complexity of tasks used to induce brain network activity. Hypothesis-driven approaches coupled with sophisticated network analyses are a highly valuable approach in using fMRI to uncover mechanisms in disorders like OCD.
Toyoda, Hiroki; Zhao, Ming-Gao; Ulzhöfer, Bettina; Wu, Long-Jun; Xu, Hui; Seeburg, Peter H; Sprengel, Rolf; Kuner, Rohini; Zhuo, Min
Cortical areas including the anterior cingulate cortex (ACC) are important for pain and pleasure. Recent studies using genetic and physiological approaches have demonstrated that the investigation of basic mechanism for long-term potentiation (LTP) in the ACC may reveal key cellular and molecular mechanisms for chronic pain in the cortex. Glutamate N-methyl D-aspartate (NMDA) receptors in the ACC are critical for the induction of LTP, including both NR2A and NR2B subunits. However, cellular and molecular mechanisms for the expression of ACC LTP have been less investigated. Here, we report that the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit, GluA1 but not GluA2 contributes to LTP in the ACC using genetic manipulated mice lacking GluA1 or GluA2 gene. Furthermore, GluA1 knockout mice showed decreased extracellular signal-regulated kinase (ERK) phosphorylation in the ACC in inflammatory pain models in vivo. Our results demonstrate that AMPA receptor subunit GluA1 is a key mechanism for the expression of ACC LTP and inflammation-induced long-term plastic changes in the ACC.
Friedman, Amy L.; Burgess, Ashley; Ramaseshan, Karthik; Easter, Phil; Khatib, Dalal; Chowdury, Asadur; Arnold, Paul D.; Hanna, Gregory L.; Rosenberg, David R.; Diwadkar, Vaibhav A.
In an effort to elucidate differences in functioning brain networks between youth with obsessive-compulsive disorder and controls, we used fMRI signals to analyze brain network interactions of the dorsal anterior cingulate cortex (dACC) during visually coordinated motor responses. Subjects made a uni-manual response to briefly presented probes, at periodic (allowing participants to maintain a “motor set”) or random intervals (demanding reactive responses). Network interactions were assessed using psycho-physiological interaction (PPI), a basic model of functional connectivity evaluating modulatory effects of the dACC in the context of each task condition. Across conditions, OCD were characterized by hyper-modulation by the dACC, with loci alternatively observed as both condition-general and condition-specific. Thus, dynamically driven task demands during simple uni-manual motor control induce compensatory network interactions in cortical-thalamic regions in OCD. These findings support previous research in OCD showing compensatory network interactions during complex memory tasks, but establish that these network effects are observed during basic sensorimotor processing. Thus, these patterns of network dysfunction may in fact be independent of the complexity of tasks used to induce brain network activity. Hypothesis-driven approaches coupled with sophisticated network analyses are a highly valuable approach in using fMRI to uncover mechanisms in disorders like OCD. PMID:27992792
Diwadkar, Vaibhav A.; Burgess, Ashley; Hong, Ella; Rix, Carrie; Arnold, Paul D.; Hanna, Gregory L.; Rosenberg, David R.
Brain network dysfunction is emerging as a central biomarker of interest in psychiatry, in large part, because psychiatric conditions are increasingly seen as disconnection syndromes. Understanding dysfunctional brain network profiles in task-active states provides important information on network engagement in an experimental context. This in turn may be predictive of many of the cognitive and behavioral deficits associated with complex behavioral phenotypes. Here we investigated brain network profiles in youth with obsessive-compulsive disorder (OCD), contrasting them with a group of age-comparable controls. Network interactions were assessed during simple working memory: in particular, we focused on the modulation by the dorsal anterior cingulate cortex (dACC) of cortical, striatal, and thalamic regions. The focus on the dACC was motivated by its hypothesized role in the pathophysiology of OCD. However, its task-active network signatures have not been investigated before. Network interactions were modeled using psychophysiological interaction, a simple directional model of seed to target brain interactions. Our results indicate that OCD is characterized by significantly increased dACC modulation of cortical, striatal, and thalamic targets during working memory, and that this aberrant increase in OCD patients is maintained regardless of working memory demand. The results constitute compelling evidence of dysfunctional brain network interactions in OCD and suggest that these interactions may be related to a combination of network inefficiencies and dACC hyper-activity that has been associated with the phenotype. PMID:25852529
Watanabe, Hiroyuki; Fitting, Sylvia; Hussain, Muhammad Z.; Kononenko, Olga; Iatsyshyna, Anna; Yoshitake, Takashi; Kehr, Jan; Alkass, Kanar; Druid, Henrik; Wadensten, Henrik; Andren, Per E.; Nylander, Ingrid; Wedell, Douglas H.; Krishtal, Oleg; Hauser, Kurt F.; Nyberg, Fred; Karpyak, Victor M.; Yakovleva, Tatjana; Bakalkin, Georgy
Lateralization of the processing of positive and negative emotions and pain suggests an asymmetric distribution of the neurotransmitter systems regulating these functions between the left and right brain hemispheres. By virtue of their ability to selectively mediate euphoria, dysphoria, and pain, the μ-, δ-, and κ-opioid receptors and their endogenous ligands may subserve these lateralized functions. We addressed this hypothesis by comparing the levels of the opioid receptors and peptides in the left and right anterior cingulate cortex (ACC), a key area for emotion and pain processing. Opioid mRNAs and peptides and 5 “classical” neurotransmitters were analyzed in postmortem tissues from 20 human subjects. Leu-enkephalin-Arg (LER) and Met-enkephalin-Arg-Phe, preferential δ-/μ- and κ-/μ-opioid agonists, demonstrated marked lateralization to the left and right ACC, respectively. Dynorphin B (Dyn B) strongly correlated with LER in the left, but not in the right ACC suggesting different mechanisms of the conversion of this κ-opioid agonist to δ-/μ-opioid ligand in the 2 hemispheres; in the right ACC, Dyn B may be cleaved by PACE4, a proprotein convertase regulating left–right asymmetry formation. These findings suggest that region-specific lateralization of neuronal networks expressing opioid peptides underlies in part lateralization of higher functions, including positive and negative emotions and pain in the human brain. PMID:23960211
Kühn, Simone; Schubert, Florian; Mekle, Ralf; Wenger, Elisabeth; Ittermann, Bernd; Lindenberger, Ulman; Gallinat, Jürgen
Neural activity as indirectly observed in blood oxygenation level-dependent (BOLD) response is thought to reflect changes in neurotransmitter flux. In this study, we used fMRI-guided functional magnetic resonance spectroscopy (MRS) to measure metabolite/BOLD associations during a cognitive task at 3 T. GABA and glutamate concentration in anterior cingulate cortex (ACC) were determined by means of MRS using the SPECIAL pulse sequence before, during and after the performance of a manual Stroop task. MRS voxel positions were centred around individuals' BOLD activity during Stroop performance. Levels of GABA and glutamate showed inverted U-shape patterns across measurement time points (before, during, and after task), glutamine increased linearly and total creatine did not change. The GABA increase during task performance was associated with ACC BOLD signal changes in both congruent and incongruent Stroop conditions. Using an fMRI-guided MRS approach, an association between induced inhibitory neurotransmitter increase and BOLD changes was observed. The proposed procedure might allow the in vivo investigation of normal and dysfunctional associations between neurotransmitters and BOLD signal crucial for cerebral functioning.
Zhang, Meng-Lin; Wang, Hong-Bo; Fu, Feng-Hua; Yu, Long-Chuan
The present study was performed to explore the role of galanin and galanin receptor 2 in nociceptive modulation in anterior cingulate cortex (ACC) of normal rats and rats with mononeuropathy. Intra-ACC injection of galanin induced significant increases in hindpaw withdrawal latencies (HWLs) to thermal and mechanical stimulations in both normal rats and rats with mononeuropathy, the increased HWLs were attenuated significantly by intra-ACC injection of galanin receptor 2 antagonist M871, indicating an involvement of galanin receptor 2 in nociceptive modulation in ACC. Interestingly, the galanin-induced HWL was significant higher in rats with mononeuropathy than that in normal rats tested by Randall Selitto test. Furthermore, both the galanin mRNA expression and galanin content increased significantly in ACC in rats with mononeuropathy than that in normal rats. Moreover, both the mRNA levels of galanin receptor 2 and the content of galanin receptor 2 in ACC increased significantly in rats with mononeuropathy than that in normal rats. These results found that galanin induced antinociception in ACC in both normal rats and rats with mononeuropathy. And there may be plastic changes in the expression of galanin and galanin receptor 2 in rats with mononeuropathy, as well as in the galanin-induced antinociception. PMID:28378856
Abstract The anterior cingulate cortex (ACC) is vital for a range of brain functions requiring cognitive control and has highly divergent inputs and outputs, thus manifesting as a hub in connectomic analyses. Studies show diverse functional interactions within the ACC are associated with network oscillations in the β (20–30 Hz) and γ (30-80 Hz) frequency range. Oscillations permit dynamic routing of information within cortex, a function that depends on bandpass filter–like behavior to selectively respond to specific inputs. However, a putative hub region such as ACC needs to be able to combine inputs from multiple sources rather than select a single input at the expense of others. To address this potential functional dichotomy, we modeled local ACC network dynamics in the rat in vitro. Modal peak oscillation frequencies in the β- and γ-frequency band corresponded to GABAAergic synaptic kinetics as seen in other regions; however, the intrinsic properties of ACC principal neurons were highly diverse. Computational modeling predicted that this neuronal response diversity broadened the bandwidth for filtering rhythmic inputs and supported combination—rather than selection—of different frequencies within the canonical γ and β electroencephalograph bands. These findings suggest that oscillating neuronal populations can support either response selection (routing) or combination, depending on the interplay between the kinetics of synaptic inhibition and the degree of heterogeneity of principal cell intrinsic conductances. PMID:28275720
Xu, Lei; Zhang, Xue-Han
Dopamine plays an important role in cognitive functions including decision making, attention, learning and memory in the anterior cingulate cortex (ACC). However, little is known about dopamine receptors (DAR) expression patterns in ACC neurons, especially GABAergic interneurons. The aim of the present study was to investigate the expression of the most abundant DAR subtypes, D1 receptors (D1Rs) and D2 receptors (D2Rs), in major types of GABAergic interneurons in rat ACC, including parvalbumin (PV)-, calretinin (CR)-, and calbindin D-28k (CB)-containing interneurons. Double immunofluorescence staining and confocal scanning were used to detect protein expression in rat brain sections. The results showed a high proportion of PV-containing interneurons express D1Rs and D2Rs, while a low proportion of CR-positive interneurons express D1Rs and D2Rs. D1R- and D2R-expressing PV interneurons are more prevalently distributed in deep layers than superficial layers of ACC. Moreover, we found the proportion of D2Rs expressed in CR cells is much greater than that of D1Rs. These regional and interneuron type-specific differences of D1Rs and D2Rs indicate functionally distinct roles for dopamine in modulating ACC activities via stimulating D1Rs and D2Rs.
Watanabe, Hiroyuki; Fitting, Sylvia; Hussain, Muhammad Z; Kononenko, Olga; Iatsyshyna, Anna; Yoshitake, Takashi; Kehr, Jan; Alkass, Kanar; Druid, Henrik; Wadensten, Henrik; Andren, Per E; Nylander, Ingrid; Wedell, Douglas H; Krishtal, Oleg; Hauser, Kurt F; Nyberg, Fred; Karpyak, Victor M; Yakovleva, Tatjana; Bakalkin, Georgy
Lateralization of the processing of positive and negative emotions and pain suggests an asymmetric distribution of the neurotransmitter systems regulating these functions between the left and right brain hemispheres. By virtue of their ability to selectively mediate euphoria, dysphoria, and pain, the μ-, δ-, and κ-opioid receptors and their endogenous ligands may subserve these lateralized functions. We addressed this hypothesis by comparing the levels of the opioid receptors and peptides in the left and right anterior cingulate cortex (ACC), a key area for emotion and pain processing. Opioid mRNAs and peptides and 5 "classical" neurotransmitters were analyzed in postmortem tissues from 20 human subjects. Leu-enkephalin-Arg (LER) and Met-enkephalin-Arg-Phe, preferential δ-/μ- and κ-/μ-opioid agonists, demonstrated marked lateralization to the left and right ACC, respectively. Dynorphin B (Dyn B) strongly correlated with LER in the left, but not in the right ACC suggesting different mechanisms of the conversion of this κ-opioid agonist to δ-/μ-opioid ligand in the 2 hemispheres; in the right ACC, Dyn B may be cleaved by PACE4, a proprotein convertase regulating left-right asymmetry formation. These findings suggest that region-specific lateralization of neuronal networks expressing opioid peptides underlies in part lateralization of higher functions, including positive and negative emotions and pain in the human brain.
Shen, Zui; Sun, Jing; Liu, Boyi; Jiang, Yongliang; Wu, Yuanyuan; Wang, Jialing; Shao, Xiaomei; Fang, Jianqiao
Background The rostral anterior cingulate cortex (rACC) is important in pain expectation. Previous studies demonstrated that mechanical stimulus-induced withdrawal behaviors are spinally-mediated nocifensive reflexes in rats, but it is not known whether pain expectation is influenced by withdrawal behaviors. Material/Methods We reanalyzed previous mechanosensitivity measurements of 244 rats measured 5 times in succession. To study neural oscillation in the rACC, 1 recording microwire array was surgically implanted. Then, we simultaneously recorded the local field potential (LFP) of the rACC over the course of multiple withdrawal behaviors in unanesthetized rats. Results From our previous withdrawal behavioral data in 244 rats, we observed that the distributions of paw withdrawal thresholds (PWTs) were denser and more concentrated after the first withdrawal behavior. Compared to the first mechanical stimulus, increased neuronal synchrony and a stronger delta band component existed in each pre-stimulus LFP in the rACC during subsequent stimuli. Conclusions Pain expectation could be involved in withdrawal behaviors, which is related to increased total power and delta band power of the subsequent pre-stimulus LFPs in the rACC. PMID:28250407
Li, Xiang-Yao; Wang, Ning; Wang, Yong-Jie; Zuo, Zhen-Xing; Koga, Kohei; Luo, Fei
Temporal properties of spike firing in the central nervous system (CNS) are critical for neuronal coding and the precision of information storage. Chronic pain has been reported to affect cognitive and emotional functions, in addition to trigger long-term plasticity in sensory synapses and behavioral sensitization. Less is known about the possible changes in temporal precision of cortical neurons in chronic pain conditions. In the present study, we investigated the temporal precision of action potential firing in the anterior cingulate cortex (ACC) by using both in vivo and in vitro electrophysiological approaches. We found that peripheral inflammation caused by complete Freund's adjuvant (CFA) increased the standard deviation (SD) of spikes latency (also called jitter) of ∼51% of recorded neurons in the ACC of adult rats in vivo. Similar increases in jitter were found in ACC neurons using in vitro brain slices from adult mice with peripheral inflammation or nerve injury. Bath application of glutamate receptor antagonists CNQX and AP5 abolished the enhancement of jitter induced by CFA injection or nerve injury, suggesting that the increased jitter depends on the glutamatergic synaptic transmission. Activation of adenylyl cyclases (ACs) by bath application of forskolin increased jitter, whereas genetic deletion of AC1 abolished the change of jitter caused by CFA inflammation. Our study provides strong evidence for long-term changes of temporal precision of information coding in cortical neurons after peripheral injuries and explains neuronal mechanism for chronic pain caused cognitive and emotional impairment. PMID:25100600
Bijanki, Kelly R.; Matsui, Joy T.; Mayberg, Helen S.; Magnotta, Vincent A.; Arndt, Stephan; Johnson, Hans J.; Nopoulos, Peg; Paradiso, Sergio; McCormick, Laurie M.; Fiedorowicz, Jess G.; Epping, Eric A.; Moser, David J.
We sought to characterize the relationship between integrity of the white matter underlying the ventral anterior cingulate (vAC) and depressive symptoms in older adults with atherosclerotic vascular disease (AVD), a condition associated with preferential degeneration of the white matter. The vAC was defined as including white matter underlying ventral Brodmann Area 24 and Brodmann Area 25, corresponding with the “subcallosal” and “subgenual” cingulate respectively. This region of interest was chosen based on the preponderance of evidence that the white matter in the region plays a critical role in the manifestation of depressive symptoms. Participants had current unequivocal diagnoses of AVD and were between 55 and 90 years-old. Fractional anisotropy (FA) was used as an index of white matter integrity and organization. Whole-brain mean diffusivity (MD) was used as an index of global white matter lesion burden. Depressive symptoms were measured using the Symptom Checklist-90-Revised (SCL-90-R) Depression Scale. Depressive symptoms were significantly related to low FA in the right vAC (r = -0.356, df = 30, p = 0.045) but not the left vAC (r = 0.024, df = 30, p = 0.896) after controlling for total brain MD (a statistical control for global white matter lesion burden). Further, depressive symptoms were significantly related to low FA in the right vAC (r = -0.361, df = 31, p = 0.039), but not the left vAC (r = 0.259, df = 31, p = 0.145) when controlled for the contralateral vAC FA. The correlation coefficients for this follow-up analysis were found to be significantly different between left and right vAC (Z = 2.310, p = 0.021). Poor white matter health in the vAC may be a biological mechanism for depressive symptoms in older adults with vascular disease. Further studies may corroborate that the right vAC plays a unique role in depressive symptom manifestation in cases where the white matter is preferentially affected, as is the case in AVD. This could lead to
Sierra, Rodrigo O; Pedraza, Lizeth K; Zanona, Querusche K; Santana, Fabiana; Boos, Flávia Z; Crestani, Ana P; Haubrich, Josué; de Oliveira Alvares, Lucas; Calcagnotto, Maria Elisa; Quillfeldt, Jorge A
Systems consolidation is a time-dependent reorganization process involving neocortical and hippocampal networks underlying memory storage and retrieval. The involvement of the hippocampus during acquisition is well described; however we know much less about the concomitant contribution of cortical activity levels to the formation of stable remote memories. Here, after a reversible pharmacological inhibition of the anterior cingulate cortex (ACC) during the acquisition of a contextual fear conditioning, retrieval of both recent and remote memories were impaired, an effect that was reverted by a single memory reactivation session 48 h after training, through a destabilization-dependent mechanism interpreted as reconsolidation, that restored the normal course of systems consolidation in order to rescue a remote memory. Next we have shown that the integrity of both the anterior cingulate cortex and the thalamic nucleus reuniens (RE) were required for this reactivation-induced memory rescue. Because lidocaine infused into the RE inhibited LTP induction in the CA1-anterior cingulate cortex pathways, it seems that RE is a necessary component of the circuit underlying systems consolidation, mediating communication between dorsal hippocampus and cortical areas. To our notice, this is the first demonstration of the rescue of remote memories disrupted by ACC inhibition during acquisition, via a reconsolidation-driven mechanism. We have also shown the importance of RE to ensure the interconnection among brain areas that collectively seem to control the natural course of systems consolidation and allow the persistence of relevant emotional engrams. © 2017 Wiley Periodicals, Inc.
Chen, Tao; O'Den, Gerile; Song, Qian; Koga, Kohei; Zhang, Ming-Ming; Zhuo, Min
Long-term potentiation (LTP) is a key cellular mechanism for pathological pain in the central nervous system. LTP contains at least two different phases: early-phase LTP (E-LTP) and late-phase LTP (L-LTP). Among several major cortical areas, the anterior cingulate cortex (ACC) is a critical brain region for pain perception and its related emotional changes. Periphery tissue or nerve injuries cause LTP of excitatory synaptic transmission in the ACC. Our previous studies have demonstrated that genetic deletion of calcium-stimulated adenylyl cyclase 1 (AC1) or pharmacological application of a selective AC1 inhibitor NB001 blocked E-LTP in the ACC. However, the effect of AC1 on L-LTP, which requires new protein synthesis and is important for the process of chronic pain, has not been investigated. Here we tested the effects of NB001 on the ACC L-LTP and found that bath application of NB001 (0.1 μM) totally blocked the induction of L-LTP and recruitment of cortical circuitry without affecting basal excitatory transmission. In contrast, gabapentin, a widely used analgesic drug for neuropathic pain, did not block the induction of L-LTP and circuitry recruitment even at a high concentration (100 μM). Gabapentin non-selectively decreased basal synaptic transmission. Our results provide strong evidence that the selective AC1 inhibitor NB001 can be used to inhibit pain-related cortical L-LTP without affecting basal synaptic transmission. It also provides basic mechanisms for possible side effects of gabapentin in the central nervous system and its ineffectiveness in some patients with neuropathic pain.
Slaats-Willemse, Dorine; Kan, Cornelis C.; Goebel, Rainer; Buitelaar, Jan K.
Attention Deficit Hyperactivity Disorder (ADHD) is characterized by poor cognitive control/attention and hypofunctioning of the dorsal anterior cingulate cortex (dACC). In the current study, we investigated for the first time whether real-time fMRI neurofeedback (rt-fMRI) training targeted at increasing activation levels within dACC in adults with ADHD leads to a reduction of clinical symptoms and improved cognitive functioning. An exploratory randomized controlled treatment study with blinding of the participants was conducted. Participants with ADHD (n = 7 in the neurofeedback group, and n = 6 in the control group) attended four weekly MRI training sessions (60-min training time/session), during which they performed a mental calculation task at varying levels of difficulty, in order to learn how to up-regulate dACC activation. Only neurofeedback participants received continuous feedback information on actual brain activation levels within dACC. Before and after the training, ADHD symptoms and relevant cognitive functioning was assessed. Results showed that both groups achieved a significant increase in dACC activation levels over sessions. While there was no significant difference between the neurofeedback and control group in clinical outcome, neurofeedback participants showed stronger improvement on cognitive functioning. The current study demonstrates the general feasibility of the suggested rt-fMRI neurofeedback training approach as a potential novel treatment option for ADHD patients. Due to the study’s small sample size, potential clinical benefits need to be further investigated in future studies. Trial Registration: ISRCTN12390961 PMID:28125735
Geliebter, Allan; Benson, Leora; Pantazatos, Spiro P.; Hirsch, Joy; Carnell, Susan
Obese individuals show altered neural responses to high-calorie food cues. Individuals with binge eating [BE], who exhibit heightened impulsivity and emotionality, may show a related but distinct pattern of irregular neural responses. However, few neuroimaging studies have compared BE and non-BE groups. To examine neural responses to food cues in BE, 10 women with BE and 10 women without BE (non-BE) who were matched for obesity (5 obese and 5 lean in each group) underwent fMRI scanning during presentation of visual (picture) and auditory (spoken word) cues representing high energy density (ED) foods, low-ED foods, and non-foods. We then compared regional brain activation in BE vs. non-BE groups for high-ED vs. low-ED foods. To explore differences in functional connectivity, we also compared psychophysiologic interactions [PPI] with dorsal anterior cingulate cortex [dACC] for BE vs. non-BE groups. Region of interest (ROI) analyses revealed that the BE group showed more activation than the non-BE group in the dACC, with no activation differences in the striatum or OFC. Exploratory PPI analyses revealed a trend towards greater functional connectivity with dACC in the insula, cerebellum, and supramarginal gyrus in the BE vs. non-BE group. Our results suggest that women with BE show hyper-responsivity in the dACC as well as increased coupling with other brain regions when presented with high-ED cues. These differences are independent of body weight, and appear to be associated with the BE phenotype. PMID:26275334
Cocker, P J; Hosking, J G; Murch, W S; Clark, L; Winstanley, C A
Using a rodent slot machine task (rSMT), we have previously shown that rats, like humans, are susceptible to the reinforcing effects of winning signals presented within a compound stimulus array, even when the pattern generated predicts a negative rather than a positive outcome such as during a "near-miss". The dopamine D4 receptor critically mediates the erroneous reward expectancy generated on such trials. D4 receptors are particularly enriched within frontal and limbic areas activated during slot machine play, such as the anterior cingulate cortex (ACC). We therefore selectively inactivated the ACC to confirm involvement of this region in rSMT performance, and subsequently examined the specific contribution of local D4 receptors. ACC inactivations generally impaired animals' ability to optimally differentiate winning from losing outcomes. Local administration of the D4 agonist PD168077 had a qualitatively similar effect, but increased reward expectancy was only evident on archetypal "near-miss" trials i.e. when the first two of three stimuli in the array were concordant with a rewarding outcome, and only the last stimulus critically signalled a non-win. These data indicate that the ACC is critically involved in parsing the appropriate response when competing stimulus-outcome associations are activated, and that signalling via D4 receptors may play a particularly important role in gating the temporal and spatial summation of salient events. Such findings provide novel insights into the mechanism underlying the erroneous expectations of reward generated when playing slot machines, and suggest a mechanism by which D4 receptor antagonists may be effective in treating gambling disorder.
Marusak, H A; Thomason, M E; Peters, C; Zundel, C; Elrahal, F; Rabinak, C A
Connections between the amygdala and medial prefrontal cortex (mPFC) are considered critical for the expression and regulation of emotional behavior. Abnormalities in frontoamygdala circuitry are reported across several internalizing conditions and associated risk factors (for example, childhood trauma), which may underlie the strong phenotypic overlap and co-occurrence of internalizing conditions. However, it is unclear if these findings converge on the same localized areas of mPFC or adjacent anterior cingulate cortex (ACC). Examining 46 resting-state functional connectivity magnetic resonance imaging studies of internalizing conditions or risk factors (for example, early adversity and family history), we conducted an activation likelihood estimation meta-analysis of frontoamygdala circuitry. We included all reported amygdala to frontal coordinate locations that fell within a liberal anatomically defined frontal mask. Peak effects across studies were centered in two focal subareas of the ACC: pregenual (pgACC) and subgenual (sgACC). Using publicly available maps and databases of healthy individuals, we found that observed subareas have unique connectivity profiles, patterns of neural co-activation across a range of neuropsychological tasks, and distribution of tasks spanning various behavioral domains within peak regions, also known as ‘functional fingerprints'. These results suggest disruptions in unique amygdala–ACC subcircuits across internalizing, genetic and environmental risk studies. Based on functional characterizations and the studies contributing to each peak, observed amygdala–ACC subcircuits may reflect separate transdiagnostic neural signatures. In particular, they may reflect common neurobiological substrates involved in developmental risk (sgACC), or the broad expression of emotional psychopathology (pgACC) across disease boundaries. PMID:27824358
Martinelli, Pénélope; Sperduti, Marco; Devauchelle, Anne-Dominique; Kalenzaga, Sandrine; Gallarda, Thierry; Lion, Stéphanie; Delhommeau, Marion; Anssens, Adèle; Amado, Isabelle; Meder, Jean François; Krebs, Marie-Odile; Oppenheim, Catherine; Piolino, Pascale
Age-related changes in autobiographical memory (AM) recall are characterized by a decline in episodic details, while semantic aspects are spared. This deleterious effect is supposed to be mediated by an inefficient recruitment of executive processes during AM retrieval. To date, contrasting evidence has been reported on the neural underpinning of this decline, and none of the previous studies has directly compared the episodic and semantic aspects of AM in elderly. We asked 20 young and 17 older participants to recall specific and general autobiographical events (i.e., episodic and semantic AM) elicited by personalized cues while recording their brain activity by means of fMRI. At the behavioral level, we confirmed that the richness of episodic AM retrieval is specifically impoverished in aging and that this decline is related to the reduction of executive functions. At the neural level, in both age groups, we showed the recruitment of a large network during episodic AM retrieval encompassing prefrontal, cortical midline and posterior regions, and medial temporal structures, including the hippocampus. This network was very similar, but less extended, during semantic AM retrieval. Nevertheless, a greater activity was evidenced in the dorsal anterior cingulate cortex (dACC) during episodic, compared to semantic AM retrieval in young participants, and a reversed pattern in the elderly. Moreover, activity in dACC during episodic AM retrieval was correlated with inhibition and richness of memories in both groups. Our findings shed light on the direct link between episodic AM retrieval, executive control, and their decline in aging, proposing a possible neuronal signature. They also suggest that increased activity in dACC during semantic AM retrieval in the elderly could be seen as a compensatory mechanism underpinning successful AM performance observed in aging. These results are discussed in the framework of recently proposed models of neural reorganization in aging
Gresch, Paul J; Barrett, Robert J; Sanders-Bush, Elaine; Smith, Randy L
d-Lysergic acid diethylamide (LSD), an indoleamine hallucinogen, produces profound alterations in mood, thought, and perception in humans. The brain site(s) that mediates the effects of LSD is currently unknown. In this study, we combine the drug discrimination paradigm with intracerebral microinjections to investigate the anatomical localization of the discriminative stimulus of LSD in rats. Based on our previous findings, we targeted the anterior cingulate cortex (ACC) to test its involvement in mediating the discriminative stimulus properties of LSD. Rats were trained to discriminate systemically administered LSD (0.085 mg/kg s.c.) from saline. Following acquisition of the discrimination, bilateral cannulae were implanted into the ACC (AP, +1.2 mm; ML, +/-1.0 mm; DV, -2.0 mm relative to bregma). Rats were tested for their ability to discriminate varying doses of locally infused LSD (0.1875, 0.375, and 0.75 microg/side) or artificial cerebrospinal fluid (n = 3-7). LSD locally infused into ACC dose-dependently substituted for systemically administered LSD, with 0.75 microg/side LSD substituting completely (89% correct). Systemic administration of the selective 5-hydroxytryptamine (serotonin) (5-HT)(2A) receptor antagonist R-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidine-methanol (M100907; 0.4 mg/kg) blocked the discriminative cue of LSD (0.375 microg/side) infused into ACC (from 68 to 16% drug lever responding). Furthermore, M100907 (0.5 microg/microl/side) locally infused into ACC completely blocked the stimulus effects of systemic LSD (0.04 mg/kg; from 80 to 12% on the LSD lever). Taken together, these data indicate that 5-HT(2A) receptors in the ACC are a primary target mediating the discriminative stimulus properties of LSD.
Mortensen, Jørgen Assar; Evensmoen, Hallvard Røe; Klensmeden, Gunilla; Håberg, Asta Kristine
Uncertainty is recognized as an important component in distress, which may elicit impulsive behavior in patients with borderline personality disorder (BPD). These patients are known to be both impulsive and distress intolerant. The present study explored the connection between outcome uncertainty and impulsivity in BPD. The prediction was that cue primes, which provide incomplete information of subsequent target stimuli, led BPD patients to overrate the predictive value of these cues in order to reduce distress related to outcome uncertainty. This would yield dysfunctional impulsive behavior detected as commission errors to incorrectly primed targets. We hypothesized that dysfunctional impulsivity would be accompanied by aberrant brain activity in the right insula and anterior cingulate cortex (ACC), previously described to be involved in uncertainty processing, attention-/cognitive control and BPD pathology. 14 female BPD patients and 14 healthy matched controls (HCs) for comparison completed a Posner task during fMRI at 3T. The task was modified to limit the effect of spatial orientation and enhance the effect of conscious expectations. Brain activity was monitored in the priming phase where the effects of cue primes and neutral primes were compared. As predicted, the BPD group made significantly more commission errors to incorrectly primed targets than HCs. Also, the patients had faster reaction times to correctly primed targets relative to targets preceded by neutral primes. The BPD group had decreased activity in the right mid insula and increased activity in bilateral dorsal ACC during cue primes. The results indicate that strong expectations induced by cue primes led to reduced uncertainty, increased response readiness, and ultimately, dysfunctional impulsivity in BPD patients. We suggest that outcome uncertainty may be an important component in distress related impulsivity in BPD. PMID:27199724
Conklin, Sarah M; Runyan, Caroline A; Leonard, Sherry; Reddy, Ravinder D; Muldoon, Matthew F; Yao, Jeffrey K
Accumulating evidence finds a relative deficiency of peripheral membrane fatty acids in persons with affective disorders such as unipolar and bipolar depression. Here we sought to investigate whether postmortem brain fatty acids within the anterior cingulate cortex (BA-24) varied according to the presence of major depression at the time of death. Using capillary gas chromatography we measured fatty acids in a depressed group (n=12), and in a control group without lifetime history of psychiatric diagnosis (n=14). Compared to the control group, the depressed group showed significantly lower concentrations of numerous saturated and polyunsaturated fatty acids including both the n-3 and n-6 fatty acids. Additionally, significant correlations between age at death and precursor (or metabolites) in the n-3 fatty acid pathway were demonstrated in the depressed group but not in control subjects. In the n-6 fatty acid family, the ratio of 20:3(n-6)/18:2(n-6) was higher in patients than in control groups, whereas the ratio of 20:4(n-6)/20:3(n-6) was relatively decreased in patients. Lastly, a significant negative correlation between age and the ratio of 20:4(n-6) to 22:6(n-3) was found in patients, but not in controls. Taken together, decreases in 22:6(n-3) may be caused, at least in part, by the diminished formation of 20:5(n-3), which is derived from 20:4(n-3) through a Delta5 desaturase reaction. The present findings from postmortem brain tissue raise the possibility that an increased ratio of 20:4(n-6) to 22:6(n-3) may provide us with a biomarker for depression. Future research should further investigate these relationships.
Li, Ying; Zhang, Xu; Liu, Haiyan; Cao, Zhijun; Chen, Shengliang; Cao, Bing; Liu, Jin
The NR2B subunit of NMDA receptor in the anterior cingulate cortex (ACC) is up-regulated in viscerally hypersensitive (VH) rats induced by colonic anaphylaxis. It plays a critical role in modulation of ACC sensitization and visceral pain responses. Given the key role of calcium/calmodulin-dependent protein kinase II (CaMKII) in synaptic plasticity and behavior learning and memory, we hypothesize that phosphorylation of CaMKII binding to NR2B mediates visceral pain in VH states. We performed in vivo electroporation of CaMKII siRNA produced inhibition of colorectal distension-induced visceromotor response in the VH rats. The NR2B, CaMKII and P-CaMKII-Thr²⁸⁶ protein levels were increased in 180%, 220% and 304% fold in the post-synaptic density (PSD) fraction in VH rats separately. Western blotting following co-immunoprecipitation showed that P-CaMKII-Thr²⁸⁶ bound to NR2B in the PSD, which was increased to 267% of control in VH rats. Administration of CaMKII antagonist Antennapedia-CaMKIINtide suppressed visceromotor response in VH rats in parallel with decrease of NR2B levels and reduction of the NR2B-P-CaMKII-Thr²⁸⁶ protein complex in PSD. In conclusion, CaMKII is a critical signaling molecule in the ACC glutamatergic synaptic transmission and phosphorylation of CaMKII at Thr286, which binds to NR2B subunit at post-synaptic site, modulates visceral pain in viscerally hypersensitive state.
Mulert, Christoph; Seifert, Christian; Leicht, Gregor; Kirsch, Valerie; Ertl, Matthias; Karch, Susanne; Moosmann, Matthias; Lutz, Jürgen; Möller, Hans-Jürgen; Hegerl, Ulrich; Pogarell, Oliver; Jäger, Lorenz
While the precise role of the anterior cingulate cortex (ACC) is still being discussed, it has been suggested that ACC activity might reflect the amount of mental effort associated with cognitive processing. So far, not much is known about the temporal dynamics of ACC activity in effort-related decision making or auditory attention, because fMRI is limited concerning its temporal resolution and electroencephalography (EEG) is limited concerning its spatial resolution. Single-trial coupling of EEG and fMRI can be used to predict the BOLD signal specifically related to amplitude variations of electrophysiological components. The striking feature of single-trial coupling is its ability to separate different aspects of the BOLD signal according to their specific relationship to a distinct neural process. In the present study we investigated 10 healthy subjects with a forced choice reaction task under both low and high effort conditions and a control condition (passive listening) using simultaneous EEG and fMRI. We detected a significant effect of mental effort only for the N1 potential, but not for the P300 potential. In the fMRI analysis, ACC activation was present only in the high effort condition. We used single-trial coupling of EEG and fMRI in order to separate information specific to N1-amplitude variations from the unrelated BOLD response. Under high effort conditions we were able to detect circumscribed BOLD activations specific to the N1 potential in the ACC (t=4.7) and the auditory cortex (t=6.1). Comparing the N1-specific BOLD activity of the high effort condition versus the control condition we found only activation of the ACC (random effects analysis, corrected for multiple comparisons, t=4.4). These findings suggest a role of early ACC activation in effort-related decision making and provide a direct link between the N1 component and its corresponding BOLD signal.
Åhs, Fredrik; Savic, Ivanka
Multiple chemical sensitivity (MCS) is a common condition, characterized by somatic distress upon exposure to odors. As in other idiopathic environmental intolerances, the underlying mechanisms are unknown. Contrary to the expectations it was recently found that persons with MCS activate the odor-processing brain regions less than controls, while their activation of the anterior cingulate cortex (ACC) is increased. The present follow-up study was designed to test the hypotheses that MCS subjects have increased harm avoidance and deviations in the serotonin system, which could render them intolerant to environmental odors. Twelve MCS and 11 control subjects, age 22–44, all working or studying females, were included in a PET study where 5-HT1A receptor binding potential (BP) was assessed after bolus injection of [11C]WAY100635. Psychological profiles were assessed by the Temperament and Character Inventory and the Swedish universities Scales of Personality. All MCS and 12 control subjects were also tested for emotional startle modulation in an acoustic startle test. MCS subjects exhibited significantly increased harm avoidance, and anxiety compared to controls. They also had a reduced 5-HT1A receptor BP in amygdala (p = 0.029), ACC (p = 0.005) (planned comparisons, significance level 0.05), and insular cortex (p = 0.003; significance level p<0.005 with Bonferroni correction), and showed an inverse correlation between degree of anxiety and the BP in the amygdala (planned comparison). No group by emotional category difference was found in the startle test. Increased harm avoidance and the observed changes in the 5-HT1A receptor BP in the regions processing harm avoidance provides a plausible pathophysiological ground for the symptoms described in MCS, and yields valuable information for our general understanding of idiopathic environmental intolerances. PMID:23349968
Cao, Hong; Zang, Kai-Kai; Han, Mei; Zhao, Zhi-Qi; Wu, Gen-Cheng; Zhang, Yu-Qiu
The emotional components of pain are far less studied than the sensory components. Previous studies have indicated that the rostral anterior cingulate cortex (rACC) is implicated in the affective response to noxious stimuli. Activation of p38 mitogen-activated protein kinase (MAPK) in the spinal cord has been documented to play an important role in diverse kinds of pathological pain states. We used formalin-induced conditioned place aversion (F-CPA) in rats, an animal model believed to reflect the emotional response to pain, to investigate the involvement of p38 MAPK in the rACC after the induction of affective pain. Intraplantar formalin injection produced a significant activation of p38 MAPK, as well as mitogen-activated kinase kinase (MKK) 3 and MKK6, its upstream activators, in the bilateral rACC. p38 MAPK was elevated in both NeuN-positive neurons and Iba1-positive microglia in the rACC, but not GFAP-positive cells. Blocking p38 MAPK activation in the bilateral rACC using its specific inhibitor SB203580 or SB239063 dose-dependently suppressed the formation of F-CPA. Inhibiting p38 MAPK activation did not affect formalin-induced two-phase spontaneous nociceptive response and low intensity electric foot-shock induced CPA. The present study demonstrated that p38 MAPK signaling pathway in the rACC contributes to pain-related negative emotion. Thus, a new pharmacological strategy targeted at the p38 MAPK cascade may be useful in treating pain-related emotional disorders.
Mohila, Carrie Ann; Onn, Shao-Pii
We previously reported synchronization of pyramidal neurons within prefrontal cortex of rats repeatedly exposed to amphetamine (AMPH). To test the hypothesis that cortical synchronization may be related to changes in local GABA signaling, we used antibodies specific for parvalbumin (PV), calbindin D28k (CB) and calretinin (CR) as selective labels for three distinct GABA interneuron classes in the anterior cingulate cortex (ACC) of similarly treated rats. We observed a selective increase in the density of PV-immunoreactive (ir), but not CB-ir or CR-ir, neurons in the ACC of AMPH-treated rats at both 1 day and 7 day withdrawal. Increased density of PV-ir GABA interneurons in the ACC at 1 day withdrawal was reproduced in rats repeatedly injected with apomorphine or with SKF-38393. Thus, the critical role of DA receptors during AMPH exposure is evident. However, DA receptor activation did not appear to account for the PV up-regulation in AMPH-treated rats at 7 day withdrawal. Significantly higher numbers of pericellular basket-like puncta immunoreactive for corticotropin-releasing factor (CRF) were observed in the ACC of AMPH rats at 7 day withdrawal. Combined dual immunofluorescence and confocal microscopy further revealed that CRF-ir puncta made possible pericellular contacts on PV-ir (not CB-, CR- or glutamate-ir) cell bodies. A potential cellular mechanism seems to emerge that CRF-ir terminals, that may be underdetected under normal conditions due to low activity levels, may be functionally activated during psychostimulant withdrawal, thereby altering local GABAergic signaling.
Prisciandaro, James J.; Schacht, Joseph P.; Prescot, Andrew P.; Renshaw, Perry F.; Brown, Truman R.; Anton, Raymond F.
Background Proton magnetic resonance spectroscopy (1H-MRS) studies have consistently found abnormal brain concentrations of N-acetylaspartate (NAA) and glutamate in individuals with alcohol use disorders (AUD) relative to light drinkers. However, most such studies have focused on individuals in treatment for severe alcohol dependence and few studies have investigated associations between neurochemical concentrations and recent alcohol consumption. The present study focused on associations between recent drinking and prefrontal neurometabolite concentrations in non-severe, non-treatment seeking individuals with AUD. Methods Nineteen treatment naïve alcohol-dependent individuals aged 21–40 completed a 1H-MRS scan. Single-voxel 1H-MRS spectra were acquired in dorsal anterior cingulate (dACC) using a Two-dimensional J-resolved Point Resolved Spectroscopy (2D J-PRESS) sequence. Associations between recent heavy drinking, assessed using the Timeline FollowBack, and dACC metabolite concentrations were estimated via regression controlling for within-voxel tissue composition. Results Participants provided a negative breathalyzer reading and reported between 1 and 5 days (M = 2.45, SD = 1.23) since their last drink. Number of heavy drinking days in the 14 days preceding the scan (M = 4.84, SD = 3.32) was significantly inversely associated with both glutamate/water (β = −0.63, t(17) = −3.37, p = 0.004) and NAA/water concentrations (β = −0.59, t(17) = −2.98, p = 0.008). Conclusions The present study extends the literature by demonstrating inverse associations between recent heavy drinking and dACC glutamate and NAA concentrations in a sample of non-severe, non-treatment seeking individuals with AD. These findings may support the hypothesis that amount of recent alcohol consumption may account for differences in neuronal metabolism, even in non-severe, non-treatment seeking alcoholics. PMID:26853538
Ishikawa, Kozo; Yasuda, Seiko; Fukuhara, Kayoko; Iwanaga, Yasutake; Ida, Yuika; Ishikawa, Junko; Yamagata, Hirotaka; Ono, Midori; Kakeda, Takahiro; Ishikawa, Toshizo
Chronic pain with mood disorder, resulting from a peripheral nerve injury, is a serious clinical problem affecting the quality of life. A lack of brain-derived neurotrophic factor (BDNF) and abnormal intercellular signaling in the brain can mediate this symptom. BDNF is induced in cultured neurons by 4-methylcatechol (4-MC), but little is known about its role in pain-emotion. Thus, we characterized the actions of 4-MC on TrkB receptor-related pERK and BDNF mRNA in discreet brain regions related to pain-emotion after chronic pain in rat. Rats implanted with a stainless steel cannula into the lateral ventricular were subjected to chronic constriction injury (CCI). Pain was assessed by changes in paw withdrawal latency (PWL) to heat stimuli after CCI. Immobility time during the forced swimming testing was measured for depression-like behavior. Analgesic and antidepression modulations with 4-MC were examined by an anti-BDNF antibody (K252a, a TrkB receptor inhibitor). The animals were perfused and fixed (4% paraformaldehyde) for immunohistochemistry analysis (c-FOS/pERK). BDNF mRNA expression (anterior cingulate cortex) was determined using reverse transcription-PCR. Rats showed a sustained decrease in PWL, associated with a prolonged immobility time after CCI. 4-MC reduced decreases in PWL and increased immobility time. 4-MC reduced increases in pERK immunoreactivity and decreases in BDNF mRNA expression in regions related to pain and the limbic system. Anti-BDNF blocked effects induced by 4-MC. We suggest that a lack of BDNF associated with activated extracellular signal-regulated kinase in the pain-emotion network may be involved in depression-like behavior during chronic pain. 4-MC ameliorates pain-emotion symptoms by inducing BDNF and normalizing pERK activities.
Cano-Ramírez, Hugo; Hoffman, Kurt L
We propose that maternal nest building in the female laboratory rabbit is a useful model for compulsions in obsessive-compulsive disorder (OCD). This repetitive behavior comprises collecting straw, depositing it into the nest box, and then returning to collect more straw. We reasoned that if "straw carrying" behavior is homologous to compulsive behavior, then it should be associated with activation of prefrontal regions associated with OCD, namely, the orbitofrontal and anterior cingulate cortices (OFC and ACC, respectively). In the present study, we quantified c-FOS immunoreactivity in the ACC, OFC, premotor (PM), infralimbic (IL), prelimbic (PL), and piriform (PI) cortices of: (1) pregnant female rabbits that were given straw (PREG+STRAW); (2) pregnant rabbits that were not given straw (PREG); (3) estrous rabbits that were given straw (ESTROUS+STRAW); (4) estrous rabbits that were not given straw (ESTROUS). After 1h, all females were sacrificed and processed for brain c-FOS immunoreactivity. We found that pregnant rabbits showed lower latencies to interact with the straw than estrous rabbits, and that pregnant rabbits displayed straw carrying, while estrous rabbits did not. c-FOS expression was increased in the OFC, ACC, and PI in the PREG+STRAW compared to all other groups. By contrast, c-FOS expression in all other regions was greater in PREG+STRAW compared to PREG, but not different from ESTROUS+STRAW. These results point to an important role for the OFC, ACC, and PI in initiating repetitive straw-carrying behavior, and further support the proposal that this behavior can serve as a model for compulsions in OCD.
Wartman, Brianne C.; Holahan, Matthew R.
Consolidation processes, involving synaptic and systems level changes, are suggested to stabilize memories once they are formed. At the synaptic level, dendritic structural changes are associated with long-term memory storage. At the systems level, memory storage dynamics between the hippocampus and anterior cingulate cortex (ACC) may be influenced by the number of sequentially encoded memories. The present experiment utilized Golgi-Cox staining and neuron reconstruction to examine recent and remote structural changes in the hippocampus and ACC following training on three different behavioral procedures. Rats were trained on one hippocampal-dependent task only (a water maze task), two hippocampal-dependent tasks (a water maze task followed by a radial arm maze task), or one hippocampal-dependent and one non-hippocampal-dependent task (a water maze task followed by an operant conditioning task). Rats were euthanized recently or remotely. Brains underwent Golgi-Cox processing and neurons were reconstructed using Neurolucida software (MicroBrightField, Williston, VT, USA). Rats trained on two hippocampal-dependent tasks displayed increased dendritic complexity compared to control rats, in neurons examined in both the ACC and hippocampus at recent and remote time points. Importantly, this behavioral group showed consistent, significant structural differences in the ACC compared to the control group at the recent time point. These findings suggest that taxing the demand placed upon the hippocampus, by training rats on two hippocampal-dependent tasks, engages synaptic and systems consolidation processes in the ACC at an accelerated rate for recent and remote storage of spatial memories. PMID:24795581
Bauer, Jochen; Pedersen, Anya; Scherbaum, Norbert; Bening, Johanna; Patschke, Johanna; Kugel, Harald; Heindel, Walter; Arolt, Volker; Ohrmann, Patricia
The upregulation of glutamatergic excitatory neurotransmission is thought to be partly responsible for the acute withdrawal symptoms and craving experienced by alcohol-dependent patients. Most physiological evidence supporting this hypothesis is based on data from animal studies. In addition, clinical data show that GABAergic and anti-glutamatergic drugs ameliorate withdrawal symptoms, offering indirect evidence indicative of glutamatergic hyperexcitability in alcohol-dependent subjects. We used proton magnetic resonance spectroscopy to quantify the glutamate (Glu) levels in healthy control subjects and in alcohol-dependent patients immediately after detoxification. The volumes of interest were located in the nucleus accumbens (NAcc) and the anterior cingulate cortex (ACC), which are two brain areas that have important functions in reward circuitry. In addition to Glu, we quantified the levels of combined Glu and glutamine (Gln), N-acetylaspartate, choline-containing compounds, and creatine. The Glu levels in the NAcc were significantly higher in patients than in controls. Craving, which was measured using the Obsessive Compulsive Drinking Scale, correlated positively with levels of combined Glu and Gln in the NAcc and in the ACC. The levels of all other metabolites were not significantly different between patients and controls. The increased Glu levels in the NAcc in alcohol-dependent patients shortly after detoxification confirm the animal data and suggest that striatal glutamatergic dysfunction is related to ethanol withdrawal. The positive correlation between craving and glutamatergic metabolism in both key reward circuitry areas support the hypothesis that the glutamatergic system has an important role in the later course of alcohol dependence with respect to abstinence and relapse. PMID:23403696
Li, Xingbao; Hartwell, Karen J; Borckardt, Jeffery; Prisciandaro, James J; Saladin, Michael E; Morgan, Paul S; Johnson, Kevin A; Lematty, Todd; Brady, Kathleen T; George, Mark S
Numerous research groups are now using analysis of blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) results and relaying back information about regional activity in their brains to participants in the scanner in 'real time'. In this study, we explored the feasibility of self-regulation of frontal cortical activation using real-time fMRI (rtfMRI) neurofeedback in nicotine-dependent cigarette smokers during exposure to smoking cues. Ten cigarette smokers were shown smoking-related visual cues in a 3 Tesla MRI scanner to induce their nicotine craving. Participants were instructed to modify their craving using rtfMRI feedback with two different approaches. In a 'reduce craving' paradigm, participants were instructed to 'reduce' their craving, and decrease the anterior cingulate cortex (ACC) activity. In a separate 'increase resistance' paradigm, participants were asked to increase their resistance to craving and to increase middle prefrontal cortex (mPFC) activity. We found that participants were able to significantly reduce the BOLD signal in the ACC during the 'reduce craving' task (P=0.028). There was a significant correlation between decreased ACC activation and reduced craving ratings during the 'reduce craving' session (P=0.011). In contrast, there was no modulation of the BOLD signal in mPFC during the 'increase resistance' session. These preliminary results suggest that some smokers may be able to use neurofeedback via rtfMRI to voluntarily regulate ACC activation and temporarily reduce smoking cue-induced craving. Further research is needed to determine the optimal parameters of neurofeedback rtfMRI, and whether it might eventually become a therapeutic tool for nicotine dependence.
Geliebter, Allan; Benson, Leora; Pantazatos, Spiro P; Hirsch, Joy; Carnell, Susan
Obese individuals show altered neural responses to high-calorie food cues. Individuals with binge eating [BE], who exhibit heightened impulsivity and emotionality, may show a related but distinct pattern of irregular neural responses. However, few neuroimaging studies have compared BE and non-BE groups. To examine neural responses to food cues in BE, 10 women with BE and 10 women without BE (non-BE) who were matched for obesity (5 obese and 5 lean in each group) underwent fMRI scanning during presentation of visual (picture) and auditory (spoken word) cues representing high energy density (ED) foods, low-ED foods, and non-foods. We then compared regional brain activation in BE vs. non-BE groups for high-ED vs. low-ED foods. To explore differences in functional connectivity, we also compared psychophysiologic interactions [PPI] with dorsal anterior cingulate cortex [dACC] for BE vs. non-BE groups. Region of interest (ROI) analyses revealed that the BE group showed more activation than the non-BE group in the dACC, with no activation differences in the striatum or orbitofrontal cortex [OFC]. Exploratory PPI analyses revealed a trend towards greater functional connectivity with dACC in the insula, cerebellum, and supramarginal gyrus in the BE vs. non-BE group. Our results suggest that women with BE show hyper-responsivity in the dACC as well as increased coupling with other brain regions when presented with high-ED cues. These differences are independent of body weight, and appear to be associated with the BE phenotype.
Kremer, Heidemarie; Lutz, Franz P C; McIntosh, Roger C; Dévieux, Jessy G; Ironson, Gail
Resting EEGs of 40 people living with HIV (PLWH) on long-term antiretroviral treatment were examined for z-scored deviations from a healthy control (normative database) to examine the main and interaction effects of depression and gender. Regions of interest were frontal (alpha) and central (all bands) for interhemispheric asymmetries in quantitative EEGs and theta in the rostral anterior cingulate cortex (rACC) in low-resolution electromagnetic tomography (LORETA). Z-scored normed deviations of depressed PLWH, compared with nondepressed, showed right-dominant interhemispheric asymmetries in all regions. However, after adjusting for multiple testing, significance remained only central for theta, alpha, and beta. Reversed (left-dominant) frontal alpha asymmetry is a potential EEG marker of depression in the HIV negative population that was not reversed in depressive PLWH; however, corresponding with extant literature, gender had an effect on the size of frontal alpha asymmetry. The LORETA analysis revealed a trending interactional effect of depression and gender on theta activity in the rACC in Brodmann area 32. We found that compared to men, women had greater right-dominant frontal alpha-asymmetry and elevated theta activity in voxels of the rACC, which may indicate less likelihood of depression and a higher likelihood of response to antidepressants. In conclusion, subtle EEG deviations, such as right-dominant central theta, alpha, and beta asymmetries and theta activity in the rACC may mark HIV-related depressive symptoms and may predict the likelihood of response to antidepressants but gender effects need to be taken into account. Although this study introduced the use of LORETA to examine the neurophysiological correlates of negative affect in PLWH, further research is needed to assess the utility of this tool in diagnostics and treatment monitoring of depression in PLWH.
Rance, Mariela; Ruttorf, Michaela; Nees, Frauke; Schad, Lothar R; Flor, Herta
The aim of this study was the analysis of the effect of a learned increase in the dissociation between the rostral anterior cingulate cortex (rACC) and the left posterior insula (pInsL) on pain intensity and unpleasantness and the contribution of each region to the effect, exploring the possibility to influence the perception of pain with neurofeedback methods. We trained ten healthy subjects to increase the difference in the blood oxygenation level-dependent response between the rACC and pInsL to painful electric stimuli. Subjects learned to increase the dissociation with either the rACC (state 1) or the pInsL (state 2) being higher. For feedback we subtracted the signal of one region from the other and provided feedback in four conditions with six trials each yielding two different states: [rACC-pInsL increase (state 1), rACC-pInsL decrease (state 2), pInsL-rACC increase (state 2), pInsL-rACC decrease (state 1)]. Significant changes in the dissociation from trial one to six were seen in all conditions. There were significant changes from trial one to six in the pInsL in three of the four conditions, the rACC showed no significant change. Pain intensity or unpleasantness ratings were unrelated to the dissociation between the regions and the activation in each region. Learning success in the conditions did not significantly correlate and there was no significant correlation between the two respective conditions of one state, i.e., learning to achieve a specific state is not a stable ability. The pInsL seems to be the driving force behind changes in the learned dissociation between the regions. Despite successful differential modulation of activation in areas responsive to the painful stimulus, no corresponding changes in the perception of pain intensity or unpleasantness emerged. Learning to induce different states of dissociation between the areas is not a stable ability since success did not correlate overall or between two conditions of the the same state.
Shaped magnetic field pulses by multi-coil repetitive transcranial magnetic stimulation (rTMS) differentially modulate anterior cingulate cortex responses and pain in volunteers and fibromyalgia patients
Background Repetitive transcranial magnetic stimulation (rTMS) has shown promise in the alleviation of acute and chronic pain by altering the activity of cortical areas involved in pain sensation. However, current single-coil rTMS technology only allows for effects in surface cortical structures. The ability to affect activity in certain deep brain structures may however, allow for a better efficacy, safety, and tolerability. This study used PET imaging to determine whether a novel multi-coil rTMS would allow for preferential targeting of the dorsal anterior cingulate cortex (dACC), an area always activated with pain, and to provide preliminary evidence as to whether this targeted approach would allow for efficacious, safe, and tolerable analgesia both in a volunteer/acute pain model as well as in fibromyalgia chronic pain patients. Methods Part 1: Different coil configurations were tested in a placebo-controlled crossover design in volunteers (N = 16). Tonic pain was induced using a capsaicin/thermal pain model and functional brain imaging was performed by means of H215O positron emission tomography – computed tomography (PET/CT) scans. Differences in NRS pain ratings between TMS and sham treatment (NRSTMS-NRSplacebo) which were recorded each minute during the 10 minute PET scans. Part 2: 16 fibromyalgia patients were subjected to 20 multi-coil rTMS treatments over 4 weeks and effects on standard pain scales (Brief Pain Inventory, item 5, i.e. average pain NRS over the last 24 hours) were recorded. Results A single 30 minute session using one of 3 tested rTMS coil configurations operated at 1 Hz consistently produced robust reduction (mean 70% on NRS scale) in evoked pain in volunteers. In fibromyalgia patients, the 20 rTMS sessions also produced a significant pain inhibition (43% reduction in NRS pain over last 24 hours), but only when operated at 10 Hz. This degree of pain control was maintained for at least 4 weeks after the final session
Paclitaxel, a chemotherapeutic agent, causes neuropathic pain whose supraspinal pathophysiology is not fully understood. Dysregulation of sodium channel expression, studied mainly in the periphery and spinal cord level, contributes to the pathogenesis of neuropathic pain. We examined gene expression of sodium channel (Nav) subunits by real time polymerase chain reaction (PCR) in the anterior cingulate cortex (ACC) at day 7 post first administration of paclitaxel, when mice had developed paclitaxel-induced thermal hyperalgesia. The ACC was chosen because increased activity in the ACC has been observed during neuropathic pain. In the ACC of vehicle-treated animals the threshold cycle (Ct) values for Nav1.4, Nav1.5, Nav1.7, Nav1.8 and Nav1.9 were above 30 and/or not detectable in some samples. Thus, comparison in mRNA expression between untreated control, vehicle-treated and paclitaxel treated animals was done for Nav1.1, Nav1.2, Nav1.3, Nav1.6, Nax as well as Navβ1–Navβ4. There were no differences in the transcript levels of Nav1.1–Nav1.3, Nav1.6, Nax, Navβ1–Navβ3 between untreated and vehicle-treated mice, however, vehicle treatment increased Navβ4 expression. Paclitaxel treatment significantly increased the mRNA expression of Nav1.1, Nav1.2, Nav1.6 and Nax, but not Nav1.3, sodium channel alpha subunits compared to vehicle-treated animals. Treatment with paclitaxel significantly increased the expression of Navβ1 and Navβ3, but not Navβ2 and Navβ4, sodium channel beta subunits compared to vehicle-treated animals. These findings suggest that during paclitaxel-induced neuropathic pain (PINP) there is differential upregulation of sodium channels in the ACC, which might contribute to the increased neuronal activity observed in the area during neuropathic pain. PMID:27896032
Hakamata, Yuko; Iwase, Mikio; Kato, Takashi; Senda, Kohei; Inada, Toshiya
Background Human personality consists of two fundamental elements character and temperament. Character allays automatic and preconceptual emotional responses determined by temperament. However, the neurobiological basis of character and its interplay with temperament remain elusive. Here, we examined character-temperament interplay and explored the neural basis of character, with a particular focus on the subgenual anterior cingulate cortex extending to a ventromedial portion of the prefrontal cortex (sgACC/vmPFC). Methods Resting brain glucose metabolism (GM) was measured using [18F] fluorodeoxyglucose positron emission tomography in 140 healthy adults. Personality traits were assessed using the Temperament and Character Inventory. Regions of interest (ROI) analysis and whole-brain analysis were performed to examine a combination effect of temperament and character on the sgACC/vmPFC and to explore the neural correlates of character, respectively. Results Harm avoidance (HA), a temperament trait (i.e., depressive, anxious, vulnerable), showed a significant negative impact on the sgACC/vmPFC GM, whereas self-transcendence (ST), a character trait (i.e., intuitive, judicious, spiritual), exhibited a significant positive effect on GM in the same region (HA β = −0.248, p = 0.003; ST: β = 0.250, p = 0.003). In addition, when coupled with strong ST, individuals with strong HA maintained the sgACC/vmPFC GM level comparable to the level of those with low scores on both HA and ST. Furthermore, exploratory whole-brain analysis revealed a significant positive relationship between ST and sgACC/vmPFC GM (peak voxel at x = −8, y = 32, z = −8, k = 423, Z = 4.41, corrected pFDR = 0.030). Conclusion The current findings indicate that the sgACC/vmPFC might play a critical role in mindful awareness to something beyond as well as in emotional regulation. Developing a sense of mindfulness may temper exaggerated emotional responses in
Nimchinsky, E. A.; Hof, P. R.; Young, W. G.; Morrison, J. H.; Bloom, F. E. (Principal Investigator)
The primate cingulate gyrus contains multiple cortical areas that can be distinguished by several neurochemical features, including the distribution of neurofilament protein-enriched pyramidal neurons. In addition, connectivity and functional properties indicate that there are multiple motor areas in the cortex lining the cingulate sulcus. These motor areas were targeted for analysis of potential interactions among regional specialization, connectivity, and cellular characteristics such as neurochemical profile and morphology. Specifically, intracortical injections of retrogradely transported dyes and intracellular injection were combined with immunocytochemistry to investigate neurons projecting from the cingulate motor areas to the putative forelimb region of the primary motor cortex, area M1. Two separate groups of neurons projecting to area M1 emanated from the cingulate sulcus, one anterior and one posterior, both of which furnished commissural and ipsilateral connections with area M1. The primary difference between the two populations was laminar origin, with the anterior projection originating largely in deep layers, and the posterior projection taking origin equally in superficial and deep layers. With regard to cellular morphology, the anterior projection exhibited more morphologic diversity than the posterior projection. Commissural projections from both anterior and posterior fields originated largely in layer VI. Neurofilament protein distribution was a reliable tool for localizing the two projections and for discriminating between them. Comparable proportions of the two sets of projection neurons contained neurofilament protein, although the density and distribution of the total population of neurofilament protein-enriched neurons was very different in the two subareas of origin. Within a projection, the participating neurons exhibited a high degree of morphologic heterogeneity, and no correlation was observed between somatodendritic morphology and
Pourtois, Gilles; Vocat, Roland; N'Diaye, Karim; Spinelli, Laurent; Seeck, Margitta; Vuilleumier, Patrik
We studied error monitoring in a human patient with unique implantation of depth electrodes in both the left dorsal cingulate gyrus and medial temporal lobe prior to surgery. The patient performed a speeded go/nogo task and made a substantial number of commission errors (false alarms). As predicted, intracranial Local Field Potentials (iLFPs) in…
Halari, Rozmin; Simic, Mima; Pariante, Carmine M.; Papadopoulos, Andrew; Cleare, Anthony; Brammer, Michael; Fombonne, Eric; Rubia, Katya
Background: There is increasing recognition of major depressive disorder (MDD) in adolescence. In adult MDD, abnormalities of fronto-striatal and fronto-cingulate circuitries mediating cognitive control functions have been implicated in the pathogenesis and been related to problems with controlling negative thoughts. No neuroimaging studies of…
Killing two birds with one stone: the potential role of aripiprazole for patients with comorbid major depressive disorder and nicotine dependence via altering brain activity in the anterior cingulate cortex.
Chu, Che-Sheng; Tzeng, Nian-Sheng; Chang, Hsin-An; Chang, Chuan-Chia; Chen, Tien-Yu
The high comorbidity between major depressive disorder (MDD) and nicotine dependence (ND) is well recognized. Patients with comorbid MDD and ND often have increased suicidal risk and poor outcomes. A dysfunctional dopaminergic brain reward system might be a neurobiological link between MDD and ND. Aripiprazole has been considered as a dopamine stabilizer and was the first atypical antipsychotic agent approved by the US Food and Drug Administration as an adjunctive to the treatment of unipolar MDD. Bupropion is well known as a dual norepinephrine and dopamine reuptake inhibitor, and has been shown to be effective in smoking cessation. One reason bupropion is useful in treating ND is that it enhances the level of dopamine in the brain. Aripiprazole might act as a dopamine agonist similar to the way that bupropion does because of its partial dopamine D2 agonist and 30% intrinsic dopaminergic activity. Several recent studies have applied the unique pharmacodynamic characteristics of aripiprazole to treat patients with ND. Based on neuroimaging findings, aripiprazole can reduce substance cravings by altering brain activity, particularly in the brain regions of the anterior cingulate cortex. Therefore, we hypothesize that adjunctive aripiprazole with antidepressant may be an effective treatment for patients with MDD and ND comorbidity. A new drug invention that combines an antidepressant with an adequate dose of aripiprazole thus should be considered. The neurobiological basis for this combination to treat patients with MDD and ND comorbidity deserves further study.
Webb, William M; Sanchez, Richard G; Perez, Gabriella; Butler, Anderson A; Hauser, Rebecca M; Rich, Megan C; O'Bierne, Aidan L; Jarome, Timothy J; Lubin, Farah D
Epigenetic mechanisms such as DNA methylation and histone methylation are critical regulators of gene transcription changes during memory consolidation. However, it is unknown how these epigenetic modifications coordinate control of gene expression following reactivation of a previously consolidated memory. Here, we found that retrieval of a recent contextual fear conditioned memory increased global levels of H3 lysine 4-trimethylation (H3K4me3) and DNA 5-hydroxymethylation (5hmC) in area CA1 of the dorsal hippocampus. Further experiments revealed increased levels of H3K4me3 and DNA 5hmC within a CpG-enriched coding region of the Npas4, but not c-fos, gene. Intriguingly, retrieval of a 30-day old memory increased H3K4me3 and DNA 5hmC levels at a CpG-enriched coding region of c-fos, but not Npas4, in the anterior cingulate cortex, suggesting that while these two epigenetic mechanisms co-occur following the retrieval of a recent or remote memory, their gene targets differ depending on the brain region. Additionally, we found that in vivo siRNA-mediated knockdown of the H3K4me3 methyltransferase Mll1 in CA1 abolished retrieval-induced increases in DNA 5hmC levels at the Npas4 gene, suggesting that H3K4me3 couples to DNA 5hmC mechanisms. Consistent with this, loss of Mll1 prevented retrieval-induced increases in Npas4 mRNA levels in CA1 and impaired fear memory. Collectively, these findings suggest an important link between histone methylation and DNA hydroxymethylation mechanisms in the epigenetic control of de novo gene transcription triggered by memory retrieval.
Metabotropic glutamate receptor mGluR2/3 and mGluR5 binding in the anterior cingulate cortex in psychotic and nonpsychotic depression, bipolar disorder and schizophrenia: implications for novel mGluR-based therapeutics
Matosin, Natalie; Fernandez-Enright, Francesca; Frank, Elisabeth; Deng, Chao; Wong, Jenny; Huang, Xu-Feng; Newell, Kelly A.
Background Metabotropic glutamate receptors 2/3 (mGluR2/3) and 5 (mGluR5) are novel therapeutic targets for major depression (MD), bipolar disorder (BD) and schizophrenia. We aimed to determine whether mGluR2/3 and mGluR5 binding in the anterior cingulate cortex (ACC), a brain region essential for the regulation of mood, cognition and emotion, were differentially altered in these pathologies. Methods Using postmortem human brains derived from 2 cohorts, [3H]LY341495 binding to mGluR2/3 and [3H]MPEP binding to mGluR5 were measured by receptor autoradiography in the ACC. The first cohort comprised samples from individuals who had MD with psychosis (MDP), MD without psychosis (MDNP) and matched controls (n = 11–12 per group). The second cohort comprised samples from individuals who had MDNP, BD, schizophrenia and matched controls (n = 15 per group). Results No differences in mGluR2/3 or mGluR5 binding were observed in the MDP, MDNP, BD or schizophrenia groups compared with the control group (all p > 0.05). Importantly, there were also no differences in binding densities between the psychiatric disorders (p > 0.05). We did, however, observe age-related effects, with consistent negative associations between mGluR2/3 and age in the control group (r < −0.575, p < 0.025) and the psychotic disorder groups (MDP and schizophrenia: r = −0.765 to −0.515, p < 0.05), but not in the mood disorder groups (MDNP, BD). Limitations Replication in larger independent cohorts and medication-naive individuals would strengthen these findings. Conclusion Our findings suggest that mGluRs are unaltered in the ACC; however, the presence of altered receptor function cannot be discounted and requires further investigation. Taken together with previous studies, which report differential changes in mGluR2, 3 and 5 across these disorders, we suggest mGluRs may be affected in a brain region–specific manner. PMID:24949866
Fujiwara, Juri; Tobler, Philippe N; Taira, Masato; Iijima, Toshio; Tsutsui, Ken-Ichiro
Reward and punishment have opposite affective value but are both processed by the cingulate cortex. However, it is unclear whether the positive and negative affective values of monetary reward and punishment are processed by separate or common subregions of the cingulate cortex. We performed a functional magnetic resonance imaging study using a free-choice task and compared cingulate activations for different levels of monetary gain and loss. Gain-specific activation (increasing activation for increasing gain, but no activation change in relation to loss) occurred mainly in the anterior part of the anterior cingulate and in the posterior cingulate cortex. Conversely, loss-specific activation (increasing activation for increasing loss, but no activation change in relation to gain) occurred between these areas, in the middle and posterior part of the anterior cingulate. Integrated coding of gain and loss (increasing activation throughout the full range, from biggest loss to biggest gain) occurred in the dorsal part of the anterior cingulate, at the border with the medial prefrontal cortex. Finally, unspecific activation increases to both gains and losses (increasing activation to increasing gains and increasing losses, possibly reflecting attention) occurred in dorsal and middle regions of the cingulate cortex. Together, these results suggest separate and common coding of monetary reward and punishment in distinct subregions of the cingulate cortex. Further meta-analysis suggested that the presently found reward- and punishment-specific areas overlapped with those processing positive and negative emotions, respectively.
Vogt, Brent A; Paxinos, George
A gulf exists between cingulate area designations in human neurocytology and those used in rodent brain atlases with a major underpinning of the former being midcingulate cortex (MCC). The present study used images extracted from the Franklin and Paxinos mouse atlas and Paxinos and Watson rat atlas to demonstrate areas comprising MCC and modifications of anterior cingulate (ACC) and retrosplenial cortices. The laminar architecture not available in the atlases is also provided for each cingulate area. Both mouse and rat have a MCC with neurons in all layers that are larger than in ACC and layer Va has particularly prominent neurons and reduced neuron densities. An undifferentiated ACC area 33 lies along the rostral callosal sulcus in rat but not in mouse and area 32 has dorsal and ventral subdivisions with the former having particularly large pyramidal neurons in layer Vb. Both mouse and rat have anterior and posterior divisions of retrosplenial areas 29c and 30, although their cytology is different in rat and mouse. Maps of the rodent cingulate cortices provide for direct comparisons with each region in the human including MCC and it is significant that rodents do not have a posterior cingulate region composed of areas 23 and 31 like the human. It is concluded that rodents and primates, including humans, possess a MCC and this homology along with those in ACC and retrosplenial cortices permit scientists inspired by human considerations to test hypotheses on rodent models of human diseases.
Gu, Xiaosi; Gao, Zhixian; Wang, Xingchao; Liu, Xun; Knight, Robert T.; Hof, Patrick R.
Empathy refers to the ability to perceive and share another person’s affective state. Much neuroimaging evidence suggests that observing others’ suffering and pain elicits activations of the anterior insular and the anterior cingulate cortices associated with subjective empathetic responses in the observer. However, these observations do not provide causal evidence for the respective roles of anterior insular and anterior cingulate cortices in empathetic pain. Therefore, whether these regions are ‘necessary’ for empathetic pain remains unknown. Herein, we examined the perception of others’ pain in patients with anterior insular cortex or anterior cingulate cortex lesions whose locations matched with the anterior insular cortex or anterior cingulate cortex clusters identified by a meta-analysis on neuroimaging studies of empathetic pain perception. Patients with focal anterior insular cortex lesions displayed decreased discrimination accuracy and prolonged reaction time when processing others’ pain explicitly and lacked a typical interference effect of empathetic pain on the performance of a pain-irrelevant task. In contrast, these deficits were not observed in patients with anterior cingulate cortex lesions. These findings reveal that only discrete anterior insular cortex lesions, but not anterior cingulate cortex lesions, result in deficits in explicit and implicit pain perception, supporting a critical role of anterior insular cortex in empathetic pain processing. Our findings have implications for a wide range of neuropsychiatric illnesses characterized by prominent deficits in higher-level social functioning. PMID:22961548
Behr, Ian; Blint, Andy; Trenhaile, Scott
Ipsilateral dislocation of the shoulder and elbow is an uncommon injury. A literature review identified nine previously described cases. We are reporting a unique case of ipsilateral posterior shoulder dislocation and anterior elbow dislocation along with concomitant intra-articular fractures of both joints. This is the first report describing this combination of injuries. Successful treatment generally occurs with closed reduction of ipsilateral shoulder and elbow dislocations, usually reducing the elbow first. When combined with a fracture at one or both locations, closed reduction of the dislocations in conjunction with appropriate fracture management can result in a positive functional outcome.
Behr, Ian; Blint, Andy; Trenhaile, Scott
Ipsilateral dislocation of the shoulder and elbow is an uncommon injury. A literature review identified nine previously described cases. We are reporting a unique case of ipsilateral posterior shoulder dislocation and anterior elbow dislocation along with concomitant intra-articular fractures of both joints. This is the first report describing this combination of injuries. Successful treatment generally occurs with closed reduction of ipsilateral shoulder and elbow dislocations, usually reducing the elbow first. When combined with a fracture at one or both locations, closed reduction of the dislocations in conjunction with appropriate fracture management can result in a positive functional outcome. PMID:26403884
Shi, Dong-liang; Li, Jing-long; Zhai, Hua; Wang, Hui-fang; Meng, Han; Wang, Yu-bin
The incidence of anterior cruciate ligament injury has continued to increase over the last two decades. This injury is associated with abnormal gait patterns and osteoarthritis of the knee. In order to accelerate recovery, the introduction of core stability exercises into the rehabilitation program is proposed. The theory underlying the use of core stability exercise relates to the neuroplasticity that follows anterior cruciate ligament injury. Neuroplasticity in lumbar, thoracic, cervical and brain regions diminish activation in the contralateral thalamus, postparietal cortex, SM1, basal ganglia-external globus pallidus, SII, cingulated motor area, premotor cortex, and in the ipsilateral cerebellum and SM1 and increase activation in pre-SMA, SIIp, and pITG, indicating modifications of the CNS. In addition, the neuroplasticity can regulate the movement of trunk muscles, for example, sternocleidomastoid and lower trapezius muscles. Core stability also demonstrates a negative correlation with the incidence of anterior cruciate ligament injury. Therefore, we propose that core stability exercises may improve the rehabilitation of anterior cruciate ligament injuries by increasing core motor control. Specialized core stability exercises aimed at rectifying biomechanical problems associated with gait and core stability may play a key role in the management of anterior cruciate ligament injury.
Vanopdenbosch, L J; Verhoeven, K; Casselman, J W
Bell's palsy is an idiopathic facial palsy of the peripheral type. A herpes virus is the most likely mechanism. We report a patient with the often encountered combination of a facial palsy with ipsilateral sensory changes. Magnetic resonance imaging showed had contrast enhancement in the greater petrosal nerve. Viral spread through anatomical connections could be an explanation for the association of facial palsy with numbness.
Rovira, Víctor; Geijo-Barrientos, Emilio
Disinhibition of the cortex (e.g., by GABA -receptor blockade) generates synchronous and oscillatory electrophysiological activity that propagates along the cortex. We have studied, in brain slices of the cingulate cortex of mice (postnatal age 14–20 days), the propagation along layer 2/3 as well as the interhemispheric propagation through the corpus callosum of synchronous discharges recorded extracellularly and evoked in the presence of 10 μM bicuculline by electrical stimulation of layer 1. The latency of the responses obtained at the same distance from the stimulus electrode was longer in anterior cingulate cortex (ACC: 39.53 ± 2.83 ms, n = 7) than in retrosplenial cortex slices (RSC: 21.99 ± 2.75 ms, n = 5; p<0.05), which is equivalent to a lower propagation velocity in the dorso-ventral direction in ACC than in RSC slices (43.0 mm/s vs 72.9 mm/s). We studied the modulation of this propagation by serotonin. Serotonin significantly increased the latency of the intracortical synchronous discharges (18.9% in the ipsilateral hemisphere and 40.2% in the contralateral hemisphere), and also increased the interhemispheric propagation time by 86.4%. These actions of serotonin were mimicked by the activation of either 5-HT1B or 5-HT2A receptors, but not by the activation of the 5-HT1A subtype. These findings provide further knowledge about the propagation of synchronic electrical activity in the cerebral cortex, including its modulation by serotonin, and suggest the presence of deep differences between the ACC and RSC in the structure of the local cortical microcircuits underlying the propagation of synchronous discharges. PMID:26930051
Rovira, Víctor; Geijo-Barrientos, Emilio
Disinhibition of the cortex (e.g., by GABA -receptor blockade) generates synchronous and oscillatory electrophysiological activity that propagates along the cortex. We have studied, in brain slices of the cingulate cortex of mice (postnatal age 14-20 days), the propagation along layer 2/3 as well as the interhemispheric propagation through the corpus callosum of synchronous discharges recorded extracellularly and evoked in the presence of 10 μM bicuculline by electrical stimulation of layer 1. The latency of the responses obtained at the same distance from the stimulus electrode was longer in anterior cingulate cortex (ACC: 39.53 ± 2.83 ms, n = 7) than in retrosplenial cortex slices (RSC: 21.99 ± 2.75 ms, n = 5; p<0.05), which is equivalent to a lower propagation velocity in the dorso-ventral direction in ACC than in RSC slices (43.0 mm/s vs 72.9 mm/s). We studied the modulation of this propagation by serotonin. Serotonin significantly increased the latency of the intracortical synchronous discharges (18.9% in the ipsilateral hemisphere and 40.2% in the contralateral hemisphere), and also increased the interhemispheric propagation time by 86.4%. These actions of serotonin were mimicked by the activation of either 5-HT1B or 5-HT2A receptors, but not by the activation of the 5-HT1A subtype. These findings provide further knowledge about the propagation of synchronic electrical activity in the cerebral cortex, including its modulation by serotonin, and suggest the presence of deep differences between the ACC and RSC in the structure of the local cortical microcircuits underlying the propagation of synchronous discharges.
Tootell, Roger B. H.; Mendola, Janine D.; Hadjikhani, Nouchine K.; Liu, Arthur K.; Dale, Anders M.
Previous studies of cortical retinotopy focused on influences from the contralateral visual field, because ascending inputs to cortex are known to be crossed. Here, functional magnetic resonance imaging was used to demonstrate and analyze an ipsilateral representation in human visual cortex. Moving stimuli, in a range of ipsilateral visual field locations, revealed activity: (i) along the vertical meridian in retinotopic (presumably lower-tier) areas; and (ii) in two large branches anterior to that, in presumptive higher-tier areas. One branch shares the anterior vertical meridian representation in human V3A, extending superiorly toward parietal cortex. The second branch runs antero-posteriorly along lateral visual cortex, overlying motion-selective area MT. Ipsilateral stimuli sparing the region around the vertical meridian representation also produced signal reductions (perhaps reflecting neural inhibition) in areas showing contralaterally driven retinotopy. Systematic sampling across a range of ipsilateral visual field extents revealed significant increases in ipsilateral activation in V3A and V4v, compared with immediately posterior areas V3 and VP. Finally, comparisons between ipsilateral stimuli of different types but equal retinotopic extent showed clear stimulus specificity, consistent with earlier suggestions of a functional segregation of motion vs. form processing in parietal vs. temporal cortex, respectively. PMID:9448246
Goehre, Felix; Jahromi, Behnam Rezai; Elsharkawy, Ahmed; Lehto, Hanna; Shekhtman, Oleg; Andrade-Barazarte, Hugo; Munoz, Francisco; Hijazy, Ferzat; Makhkamov, Makhkam; Hernesniemi, Juha
Background: Aneurysms of the posterior cerebral artery (PCA) are rare and often associated with anterior circulation aneurysms. The lateral supraorbital approach allows for a very fast and safe approach to the ipsilateral lesions Circle of Willis. A technical note on the successful clip occlusion of two aneurysms in the anterior and posterior Circle of Willis via this less invasive approach has not been published before. The objective of this technical note is to describe the simultaneous microsurgical clip occlusion of an ipsilateral PCA-P1 and an internal carotid artery - posterior communicating artery (ICA-PCoA) aneurysm via the lateral supraorbital approach. Case Description: The authors present a technical report of successful clip occlusions of ipsilateral located PCA-P1 and ICA-PCoA aneurysms. A 59-year-old female patient was diagnosed with a PCA-P1 and an ipsilateral ICA-PCoA aneurysm by computed tomography angiography (CTA) after an ischemic stroke secondary to a contralateral ICA dissection. The patient underwent microsurgical clipping after a lateral supraorbital craniotomy. The intraoperative indocyanine green (ICG) videoangiography and the postoperative CTA showed a complete occlusion of both aneurysms; the parent vessels (ICA and PCA) were patent. The patient presents postoperative no new neurologic deficit. Conclusion: The lateral supraorbital approach is suitable for the simultaneous microsurgical treatment of proximal anterior circulation and ipsilateral proximal PCA aneurysms. Compared to endovascular treatment, direct visual control of brainstem perforators is possible. PMID:26060600
O'Neill, Joseph; Lai, Tsz M; Sheen, Courtney; Salgari, Giulia C; Ly, Ronald; Armstrong, Casey; Chang, Susanna; Levitt, Jennifer G; Salamon, Noriko; Alger, Jeffry R; Feusner, Jamie D
Focal brain metabolic effects detected by proton magnetic resonance spectroscopy (MRS) in obsessive-compulsive disorder (OCD) represent prospective indices of clinical status and guides to treatment design. Sampling bilateral pregenual anterior cingulate cortex (pACC), anterior middle cingulate cortex (aMCC), and thalamus in 40 adult patients and 16 healthy controls, we examined relationships of the neurometabolites glutamate+glutamine (Glx), creatine+phosphocreatine (Cr), and choline-compounds (Cho) with OCD diagnosis and multiple symptom types. The latter included OC core symptoms (Yale-Brown Obsessive-Compulsive Scale - YBOCS), depressive symptoms (Montgomery-Åsberg Depression Rating Scale - MADRS), and general functioning (Global Assessment Scale - GAS). pACC Glx was 9.7% higher in patients than controls. Within patients, Cr and Cho correlated negatively with YBOCS and MADRS, while Cr correlated positively with the GAS. In aMCC, Cr and Cho correlated negatively with MADRS, while Cr in thalamus correlated positively with GAS. These findings present moderate support for glutamatergic and cingulocentric perspectives on OCD. Based on our prior metabolic model of OCD, we offer one possible interpretation of these group and correlational effects as consequences of a corticothalamic state of elevated glutamatergic receptor activity alongside below-normal glutamatergic transporter activity.
Mohamed, Ismail S; Otsubo, Hiroshi; Shroff, Manohar; Donner, Elizabeth; Drake, James; Snead, O Carter
Gelastic seizures are relatively uncommon and rarely observed secondary to frontal lobe lesions. This report presents magnetoencephalography (MEG) and diffusion tensor imaging (DTI) findings in an adolescent with gelastic seizures secondary to a left anterior cingulate gyrus lesion. Ictal scalp video EEG showed bilateral frontal 4 Hz theta discharges. Interictal EEG showed left fronto-temporal spikes or sharp waves. Interictal MEG showed spike sources over bilateral temporal regions. DTI and tractography delineated slightly shifted corpus callosum posterior to the lesion, unaffected uncinate and inferior longitudinal fasciculi. The patient became seizure free for 12 months after surgical excision of a pleomorphic xanthoastrocytoma in the left anterior cingulate region. In our patient, MEG and EEG did not localize the deep-seated epileptogenic zone. The combination of DTI and neurophysiologic studies, however, possibly disclosed neuronal connections within the epileptic network and indicated that epileptic discharges propagated via the uncinate fibers from the primary epileptogenic zone in the anterior cingulate region to the mesial temporal region in this case with gelastic seizures secondary to a cingulate lesion.
Vandenberg, Angela; Piekarski, David J.; Caporale, Natalia; Munoz-Cuevas, Francisco Javier; Wilbrecht, Linda
The maturation of inhibitory circuits during adolescence may be tied to the onset of mental health disorders such as schizophrenia. Neurotrophin signaling likely plays a critical role in supporting inhibitory circuit development and is also implicated in psychiatric disease. Within the neocortex, subcircuits may mature at different times and show differential sensitivity to neurotrophin signaling. We measured miniature inhibitory and excitatory postsynaptic currents (mIPSCs and mEPSCs) in Layer 5 cell-types in the mouse anterior cingulate (Cg) across the periadolescent period. We differentiated cell-types mainly by Thy1 YFP transgene expression and also retrobead injection labeling in the contralateral Cg and ipsilateral pons. We found that YFP− neurons and commissural projecting neurons had lower frequency of mIPSCs than neighboring YFP+ neurons or pons projecting neurons in juvenile mice (P21–25). YFP− neurons and to a lesser extent commissural projecting neurons also showed a significant increase in mIPSC amplitude during the periadolescent period (P21–25 vs. P40–50), which was not seen in YFP+ neurons or pons projecting neurons. Systemic disruption of tyrosine kinase receptor B (TrkB) signaling during P23–50 in TrkBF616A mice blocked developmental changes in mIPSC amplitude, without affecting miniature excitatory post synaptic currents (mEPSCs). Our data suggest that the maturation of inhibitory inputs onto Layer 5 pyramidal neurons is cell-type specific. These data may inform our understanding of adolescent brain development across species and aid in identifying candidate subcircuits that may show greater vulnerability in mental illness. PMID:25762898
Vanneste, Sven; De Ridder, Dirk
The question arises whether functional connectivity (FC) changes between the distress and tinnitus loudness network during resting state depends on the amount of distress tinnitus patients' experience. Fifty-five patients with constant chronic tinnitus were included in this study. Electroencephalography (EEG) recordings were performed and seed-based (at the auditory cortex) source localized FC (lagged phase synchronization) was computed for the different EEG frequency bands. Results initially demonstrate that the correlation between loudness and distress is nonlinear. Loudness correlates with beta3 and gamma band activity in the auditory cortices, and distress with alpha1 and beta3 changes in the subgenual, dorsal anterior, and posterior cingulate cortex. In comparison to nontinnitus controls, seed-based FC differed between the left auditory cortices for the alpha1 and beta3 bands in a network encompassing the posterior cingulate cortex extending into the parahippocampal area, the anterior cingulate, and insula. Furthermore, distress changes the FC between the auditory cortex, encoding loudness, and different parts of the cingulate, encoding distress: the subgenual anterior, the dorsal anterior, and the posterior cingulate. These changes are specific for the alpha1 and beta3 frequency bands. These results fit with a recently proposed model that states that tinnitus is generated by multiple dynamically active separable but overlapping networks, each characterizing a specific aspect of the unified tinnitus percept, but adds to this concept that the interaction between these networks is a complex interplay of correlations and anti-correlations between areas involved in distress and loudness depending on the distress state of the tinnitus patient.
Meena, Sanjay; Trikha, Vivek; Kumar, Rakesh; Saini, Pramod; Sambharia, Abhishek Kumar
Elbow dislocation associated with ipsilateral distal radius fracture is a rare pattern of injury, although it is common for elbow dislocation and forearm fractures to occur separately. We report a rare case of a 20-year-old male who had a posterior elbow dislocation and ipsilateral distal radius fracture. Elbow dislocation was first reduced in extension and distal radius fracture was then reduced in flexion. Both the injuries were conservatively managed. At 6 months follow-up, the patient had no pain in his elbow and minimal pain in his wrist on heavy lifting and had resumed his work as a laborer. PMID:24082758
Meena, Sanjay; Trikha, Vivek; Kumar, Rakesh; Saini, Pramod; Sambharia, Abhishek Kumar
Elbow dislocation associated with ipsilateral distal radius fracture is a rare pattern of injury, although it is common for elbow dislocation and forearm fractures to occur separately. We report a rare case of a 20-year-old male who had a posterior elbow dislocation and ipsilateral distal radius fracture. Elbow dislocation was first reduced in extension and distal radius fracture was then reduced in flexion. Both the injuries were conservatively managed. At 6 months follow-up, the patient had no pain in his elbow and minimal pain in his wrist on heavy lifting and had resumed his work as a laborer.
Blackford, Jennifer Urbano; Clauss, Jacqueline A.; Avery, Suzanne N.; Cowan, Ronald L.; Benningfield, Margaret M.; VanDerKlok, Ross M.
The tendency to approach or avoid novel people is a fundamental human behavior and is a core dimension of social anxiety. Resting state fMRI was used to test for an association between social inhibition and intrinsic connectivity in 40 young adults ranging from low to high in social inhibition. Higher levels of social inhibition were associated with specific patterns of reduced amygdala-cingulate cortex connectivity. Connectivity was reduced between the superficial amygdala and the rostral cingulate cortex and between the centromedial amygdala and the dorsal anterior cingulate cortex. Social inhibition also modulated connectivity in several well-established intrinsic networks; higher social inhibition correlated with reduced connectivity with default mode and dorsal attention networks and enhanced connectivity in salience and executive control networks. These findings provide important preliminary evidence that social inhibition reflects differences in the underlying intrinsic connectivity of the brain in the absence of social stimuli or stressors. PMID:24534162
Yu, Chunshui; Zhou, Yuan; Liu, Yong; Jiang, Tianzi; Dong, Haiwei; Zhang, Yunting; Walter, Martin
The four-region model with 7 specified subregions represents a theoretical construct of functionally segregated divisions of the cingulate cortex based on integrated neurobiological assessments. Under this framework, we aimed to investigate the functional specialization of the human cingulate cortex by analyzing the resting-state functional connectivity (FC) of each subregion from a network perspective. In 20 healthy subjects we systematically investigated the FC patterns of the bilateral subgenual (sACC) and pregenual (pACC) anterior cingulate cortices, anterior (aMCC) and posterior (pMCC) midcingulate cortices, dorsal (dPCC) and ventral (vPCC) posterior cingulate cortices and retrosplenial cortices (RSC). We found that each cingulate subregion was specifically integrated in the predescribed functional networks and showed anti-correlated resting-state fluctuations. The sACC and pACC were involved in an affective network and anti-correlated with the sensorimotor and cognitive networks, while the pACC also correlated with the default-mode network and anti-correlated with the visual network. In the midcingulate cortex, however, the aMCC was correlated with the cognitive and sensorimotor networks and anti-correlated with the visual, affective and default-mode networks, whereas the pMCC only correlated with the sensorimotor network and anti-correlated with the cognitive and visual networks. The dPCC and vPCC involved in the default-mode network and anti-correlated with the sensorimotor, cognitive and visual networks, in contrast, the RSC was mainly correlated with the PCC and thalamus. Based on a strong hypothesis driven approach of anatomical partitions of the cingulate cortex, we could confirm their segregation in terms of functional neuroanatomy, as suggested earlier by task studies or exploratory multi-seed investigations.
Cole, Michael W; Yeung, Nick; Freiwald, Winrich A; Botvinick, Matthew
Cognitive neuroscience research relies, in part, on homologies between the brains of human and non-human primates. A quandary therefore arises when presumed anatomical homologues exhibit different functional properties. Such a situation has recently arisen in the case of the anterior cingulate cortex (ACC). In humans, numerous studies suggest a role for ACC in detecting conflicts in information processing. Studies of macaque monkey ACC, in contrast, have failed to find conflict-related responses. We consider several interpretations of this discrepancy, including differences in research methodology and cross-species differences in functional neuroanatomy. New directions for future research are outlined, emphasizing the importance of distinguishing illusory cross-species differences from the true evolutionary differences that make our species unique.
Korkmaz, Bariş; Benbir, Gülçin; Demirbilek, Veysi
Autism, characterized by an impairment in communication, including language, narrowly focused interests, and poor sociability, is a neurodevelopmental disorder of still largely unknown pathogenesis. In children with autistic symptomatology, the most consistent functional or anatomic abnormalities are found in the cingulate gyrus, particularly in the anterior regions. Neuronal migration malformations caused by incomplete neuronal migration and characterized by loss of the normal gyral patterns in the cerebral hemispheres and prominent disorganization of the cerebral cortical cytoarchitecture are generally associated with profound neurologic deficits, epilepsy, and autism. In this report, we present a case with an isolated migration abnormality located in the anterior part of the left cingulate gyrus who was admitted with the complaints of epileptic seizures and autism. In addition, the role of the localization of the migration abnormality in the appearance of autistic symptomatology is discussed.
Limongi, Roberto; Sutherland, Steven C; Zhu, Jian; Young, Michael E; Habib, Reza
Prediction error (i.e., the difference between the expected and the actual event's outcome) mediates adaptive behavior. Activity in the anterior mid-cingulate cortex (aMCC) and in the anterior insula (aINS) is associated with the commission of prediction errors under uncertainty. We propose a dynamic causal model of effective connectivity (i.e., neuronal coupling) between the aMCC, the aINS, and the striatum in which the task context drives activity in the aINS and the temporal prediction errors modulate extrinsic cingulate-insular connections. With functional magnetic resonance imaging, we scanned 15 participants when they performed a temporal prediction task. They observed visual animations and predicted when a stationary ball began moving after being contacted by another moving ball. To induced uncertainty-driven prediction errors, we introduced spatial gaps and temporal delays between the balls. Classical and Bayesian fMRI analyses provided evidence to support that the aMCC-aINS system along with the striatum not only responds when humans predict whether a dynamic event occurs but also when it occurs. Our results reveal that the insula is the entry port of a three-region pathway involved in the processing of temporal predictions. Moreover, prediction errors rather than attentional demands, task difficulty, or task duration exert an influence in the aMCC-aINS system. Prediction errors debilitate the effect of the aMCC on the aINS. Finally, our computational model provides a way forward to characterize the physiological parallel of temporal prediction errors elicited in dynamic tasks.
Philpot, Stephen J; Archer, John S
A 74-year-old woman developed vertigo and jerk nystagmus to the left with normal cerebral imaging. Three days later she developed fever, altered mental state and left medial temporal lobe hypodensity, confirmed on lumbar puncture to be due to herpes simplex type 1 encephalitis. We propose that the patient had vestibular neuronitis caused by HSV-1 that progressed to ipsilateral temporal lobe encephalitis.
Walter, Susanna A.; Forsgren, Mikael; Lundengård, Karin; Simon, Rozalyn; Torkildsen Nilsson, Maritha; Söderfeldt, Birgitta; Lundberg, Peter; Engström, Maria
Knowledge about the neural underpinnings of the negative blood oxygen level dependent (BOLD) responses in functional magnetic resonance imaging (fMRI) is still limited. We hypothesized that pharmacological GABAergic modulation attenuates BOLD responses, and that blood concentrations of a positive allosteric modulator of GABA correlate inversely with BOLD responses in the cingulate cortex. We investigated whether or not pure task-related negative BOLD responses were co-localized with pharmacologically modulated BOLD responses. Twenty healthy adults received either 5 mg diazepam or placebo in a double blind, randomized design. During fMRI the subjects performed a working memory task. Results showed that BOLD responses in the cingulate cortex were inversely correlated with diazepam blood concentrations; that is, the higher the blood diazepam concentration, the lower the BOLD response. This inverse correlation was most pronounced in the pregenual anterior cingulate cortex and the anterior mid-cingulate cortex. For subjects with diazepam plasma concentration > 0.1 mg/L we observed negative BOLD responses with respect to fixation baseline. There was minor overlap between cingulate regions with task-related negative BOLD responses and regions where the BOLD responses were inversely correlated with diazepam concentration. We interpret that the inverse correlation between the BOLD response and diazepam was caused by GABA-related neural inhibition. Thus, this study supports the hypothesis that GABA attenuates BOLD responses in fMRI. The minimal overlap between task-related negative BOLD responses and responses attenuated by diazepam suggests that these responses might be caused by different mechanisms. PMID:26930498
Ryan, John P; Sheu, Lei K; Gianaros, Peter J
Exaggerated cardiovascular reactivity to stress is a risk factor for cardiovascular disease. Further, individual differences in stressor-evoked cardiovascular reactivity covary with the functionality of corticolimbic brain systems, particularly areas of the cingulate cortex. What remains unclear, however, is how individual differences in personality traits interact with cingulate functionality in the prediction of stressor-evoked cardiovascular reactivity. Accordingly, we tested the associations between (i) a particular personality trait, Agreeableness, which is associated with emotional reactions to conflict, (ii) resting state functional connectivity within the cingulate cortex, and (iii) stressor-evoked blood pressure (BP) reactivity. Participants (N=39, 19 men, aged 20-37 years) completed a resting functional connectivity MRI protocol, followed by two standardized stressor tasks that engaged conflict processing and evoked BP reactivity. Agreeableness covaried positively with BP reactivity across individuals. Moreover, connectivity analyses demonstrated that a more positive functional connectivity between the posterior cingulate (BA31) and the perigenual anterior cingulate (BA32) covaried positively with Agreeableness and with BP reactivity. Finally, statistical mediation analyses demonstrated that BA31-BA32 connectivity mediated the covariation between Agreeableness and BP reactivity. Functional connectivity within the cingulate appears to link Agreeableness and a risk factor for cardiovascular disease, stressor-evoked BP reactivity.
Na, D L; Adair, J C; Kim, G M; Seo, D W; Hong, S B; Heilman, K M
Neglect usually occurs in the space contralateral to brain injury. Recent studies describe ipsilateral neglect (IN) whereby patients with right hemisphere injury misbisect lines to the left of midpoint. IN usually develops after contralateral neglect (CN) resolves. We observed whether IN occurs during intracarotid amobarbital infusion. After clinical testing but before resolution of barbiturate effect, 20 right-handed subjects bisected lines until baseline performance returned. More than half (12 of 20) showed transient CN. IN occurred in 40% (8 of 20) of patients, always during the recovery stage of anesthesia, and most frequently followed initial CN.
Wang, Tom Kai Ming; Bhamidipaty, Venu; MacCormick, Murray
First bite syndrome (FBS) is characterized by unilateral pain in the parotid region after the first bite of each meal, usually following ipsilateral neck surgery. The proposed mechanism is sympathetic denervation of the parotid gland, from iatrogenic injury to the sympathetic trunk supplying this gland. Local botulinum toxin injection has emerged as a promising treatment option with favorable results. To date, there are 3 published cases in the literature describing FBS after carotid endarterectomy. We present a case of a 75-year-old gentleman who developed FBS after carotid endarterectomy, to raise the awareness of this unusual and uncommon complication.
Klug, A; Bauer, E E; Pollak, G D
The central nucleus of the inferior colliculus (ICc) receives a large number of convergent inputs that are both excitatory and inhibitory. Although excitatory inputs typically are evoked by stimulation of the contralateral ear, inhibitory inputs can be recruited by either ear. Here we evaluate ipsilaterally evoked inhibition in single ICc cells in awake Mexican free-tailed bats. The principal question we addressed concerns the degree to which ipsilateral inhibition at the ICc suppresses contralaterally evoked discharges and thus creates the excitatory-inhibitory (EI) properties of ICc neurons. To study ipsilaterally evoked inhibition, we iontophoretically applied excitatory neurotransmitters and visualized the ipsilateral inhibition as a gap in the carpet of background activity evoked by the transmitters. Ipsilateral inhibition was seen in 86% of ICc cells. The inhibition in most cells had both glycinergic and GABAergic components that could be blocked by the iontophoretic application of bicuculline and strychnine. In 80% of the cells that were inhibited, the ipsilateral inhibition and contralateral excitation were temporally coincident. In many of these cells, the ipsilateral inhibition suppressed contralateral discharges and thus generated the cell's EI property in the ICc. In other cells, the ipsilateral inhibition was coincident with the initial portion of the excitation, but the inhibition was only 2-4 ms in duration and suppressed only the first few contralaterally evoked discharges. The suppression was so slight that it often could not be detected as a decrease in the spike count generated by increasing ipsilateral intensities. Twenty percent of the cells that expressed inhibition, however, had inhibitory latencies that were longer than the excitatory latencies. In these neurons, the inhibition arrived too late to suppress most or any of the discharges. Finally, in the majority of cells, the ipsilateral inhibition persisted for tens of milliseconds beyond
Sharma, Mohit; Gaona, Charles; Roland, Jarod; Anderson, Nick; Freudenberg, Zachary; Leuthardt, Eric C
The majority of Brain Computer Interfaces have relied on signals related to primary motor cortex and the operation of the contralateral limb. Recently, the physiology associated with same-sided (ipsilateral) motor movements has been found to have a unique cortical physiology. This study sets out to assess whether more complex motor movements can be discerned utilizing ipsilateral cortical signals. In this study, three invasively monitored human subjects were recorded while performing a center out joystick task with the hand ipsilateral to the hemispheric subdural grid array. It was found that directional tuning was present in ipsilateral cortex. This information was encoded in both distinct anatomic populations and spectral distributions. These findings support the notion that ipsilateral signals may provide added information for BCI operation in the future.
van Steenbergen, Henk; Band, Guido P H; Hommel, Bernhard; Rombouts, Serge A R B; Nieuwenhuis, Sander
Positive hedonic states are known to attenuate the impact of demanding events on our body and brain, supporting adaptive behavior in response to changes in the environment. We used functional magnetic resonance imaging to examine the neural mechanism of this hedonic regulation. The effect of hedonic state (as induced by funny vs. neutral cartoons) on flexible behavioral and neural adaptation to cognitive demands was assessed in a flanker task in female volunteers. Behavioral results showed that humor reduced the compensatory adjustments to cognitive demands, as observed in sequential adaptations. This modulation was also reflected in midcingulate cortex (MCC; also known as the dorsal anterior cingulate cortex, ACC) activation. Furthermore, hedonic context increased activation in ventral striatum (VS) and ventral pallidum (VP). These hedonic hotspots attenuated the medial prefrontal cortex response to the cognitive demands in the ACC (also known as the rostral ACC). Activity in the ACC proved predictive of subsequent behavioral adaptation. Moreover, psychophysiological interaction analyses revealed that the MCC and the ACC were functionally connected with VS and VP, respectively. These observations reveal how MCC-VS and VP-ACC interactions are involved in the detection and hedonic modulation of behavioral adaptations to cognitive demands, which supports behavioral flexibility.
van Beilen, M; Vogt, B A; Leenders, K L
Conversion disorder is one of the terms used to describe various psychosomatic neurological symptoms that are thought to originate from a psychological conflict. Psychological stressors can usually be identified but appear to be almost similar to the severity of psychological stress in non-psychosomatic neurological disorders. Recent neuroimaging research provides one rather robust finding of increased activation in the anterior cingulate gyrus. This activation has been explained as a reflection of 'active inhibition' or 'self-monitoring' but its meaning in conversion disorder still remains mysterious. In this paper, current theories are re-examined from a neuroanatomical point of view.
Adanır, Oktay; Yüksel, Serdar; Beytemur, Ozan; Güleç, M Akif
Combination of the Galeazzi fracture and dislocation of the elbow joint in same extremity is very rare. In this article, we report a 26-year-old male patient with a posterolateral dislocation of the elbow and ipsilateral volar type Galeazzi fracture. We performed closed reduction for the elbow dislocation during admission to the emergency department. Patient was taken to the operating room in the sixth hour of his application to emergency department and open wound on the ulnovolar region of the wrist was closed primarily after irrigation and debridement. We performed open reduction and internal fixation of the radial fracture with a dynamic compression plate. After fixation, we evaluated the stability of the elbow joint and distal radioulnar joint. Distal radioulnar joint was unstable under fluoroscopic examination and fixed with one 1.8 mm Kirschner wire in a pronated position. Then, elbow joint was stable. One year after surgery, patient had no pain or sings of instability. At the last follow-up, range of motion of the elbow was 10°-135° and forearm pronation and supination were 70°.
Kannepalli, Narasinga Rao V. L.; Yadav, Ravi; Vazhayil, Vikas; Somanna, Sampath; Pal, Pramod Kumar
Background Ipsilateral hemiballismus refers to the rare occurrence of hemiballism developing on the same side of a brain lesion. Case report We describe a rare case of postoperative ipsilateral hemiballism in a patient who underwent pituitary adenoma resection and experienced a right internal cerebral artery territory infarct. We review the literature on hemichorea hemiballismus (HCHB) and explore various mechanisms for its occurrence. Discussion Only three cases of ipsilateral hemiballism have been described, and the exact pathophysiology remains unknown. A dominant left hemisphere with corpus callosal connections to the right basal ganglia is the most probable explanation for this unusual event. PMID:27127720
Luttrell, Andrew; Stillman, Paul E; Hasinski, Adam E; Cunningham, William A
People's behaviors are often guided by valenced responses to objects in the environment. Beyond positive and negative evaluations, attitudes research has documented the importance of attitude strength--qualities of an attitude that enhance or attenuate its impact and durability. Although neuroscience research has extensively investigated valence, little work exists on other related variables like metacognitive judgments about one's attitudes. It remains unclear, then, whether the various indicators of attitude strength represent a single underlying neural process or whether they reflect independent processes. To examine this, we used functional MRI (fMRI) to identify the neural correlates of attitude strength. Specifically, we focus on ambivalence and certainty, which represent metacognitive judgments that people can make about their evaluations. Although often correlated, prior neuroscience research suggests that these 2 attributes may have distinct neural underpinnings. We investigate this by having participants make evaluative judgments of visually presented words while undergoing fMRI. After scanning, participants rated the degree of ambivalence and certainty they felt regarding their attitudes toward each word. We found that these 2 judgments corresponded to distinct brain regions' activity during the process of evaluation. Ambivalence corresponded to activation in anterior cingulate cortex, dorsomedial prefrontal cortex, and posterior cingulate cortex. Certainty, however, corresponded to activation in unique areas of the precuneus/posterior cingulate cortex. These results support a model treating ambivalence and certainty as distinct, though related, attitude strength variables, and we discuss implications for both attitudes and neuroscience research.
The anterior cingulate cortex (ACC) is important for cognitive and sensory functions including memory and chronic pain. Glutamatergic excitatory synaptic transmission undergo long-term potentiation in ACC pyramidal cells after peripheral injury. Less information is available for the possible long-term changes in neuronal action potentials or intrinsic properties. In the present study, we characterized cingulate pyramidal cells in the layer II/III of the ACC in adult mice. We then examined possible long-term changes in intrinsic properties of the ACC pyramidal cells after peripheral nerve injury. In the control mice, we found that there are three major types of pyramidal cells according to their action potential firing pattern: (i) regular spiking (RS) cells (24.7%), intrinsic bursting (IB) cells (30.9%), and intermediate (IM) cells (44.4%). In a state of neuropathic pain, the population distribution (RS: 21.3%; IB: 31.2%; IM: 47.5%) and the single action potential properties of these three groups were indistinguishable from those in control mice. However, for repetitive action potentials, IM cells from neuropathic pain animals showed higher initial firing frequency with no change for the properties of RS and IB neurons from neuropathic pain mice. The present results provide the first evidence that, in addition to synaptic potentiation reported previously, peripheral nerve injury produces long-term plastic changes in the action potentials of cingulate pyramidal neurons in a cell type-specific manner. PMID:20015370
Parvizi, Josef; Rangarajan, Vinitha; Shirer, William R; Desai, Nikita; Greicius, Michael D
Anterior cingulate cortex (ACC) is known to be involved in functions such as emotion, pain, and cognitive control. While studies in humans and nonhuman mammals have advanced our understanding of ACC function, the subjective correlates of ACC activity have remained largely unexplored. In the current study, we show that electrical charge delivery in the anterior midcingulate cortex (aMCC) elicits autonomic changes and the expectation of an imminent challenge coupled with a determined attitude to overcome it. Seed-based, resting-state connectivity analysis revealed that the site of stimulation in both patients was at the core of a large-scale distributed network linking aMCC to the frontoinsular and frontopolar as well as some subcortical regions. This report provides compelling, first-person accounts of electrical stimulation of this brain network and suggests its possible involvement in psychopathological conditions that are characterized by a reduced capacity to endure psychological or physical distress.
Erika, Comasco; Andreas, Hahn; Sebastian, Ganger; Malin, Gingnell; Elin, Bannbers; Lars, Oreland; Johan, Wikström; Neill, Epperson C.; Rupert, Lanzenberger; Inger, Sundström-Poromaa
Premenstrual dysphoric disorder (PMDD) is the prototypical sex-specific disorder in which symptom onset and offset require a particular hormonal milieu and for which there is moderate heritability. The present study investigated brain emotion processing in PMDD and healthy controls, as well as functional polymorphisms in two candidate genes for PMDD, the serotonin transporter (5-HTT) and brain derived neurotrophic factor (BDNF). The 5-HTT linked polymorphic region (5-HTTLPR) and BDNF Val66Met polymorphisms were genotyped in 31 patients with PMDD and 31 healthy controls. A subset of 16 patients and 15 controls participated in two functional magnetic resonance imaging-sessions performing an emotion processing task; once in the mid-follicular, and once in the late luteal phase which corresponds with maximum severity of mood symptoms. Genotypes were not directly associated with PMDD. A main effect of group was found in the whole brain analysis, with patients having lower activation of the pre-genual anterior cingulate and ventro-medial prefrontal cortex, independent of menstrual cycle phase. Post-hoc functional ROI analyses in the fronto-cingulate cluster showed no effect of 5-HTTLPR genotype but a genotype-by-group-by-phase interaction effect of BDNF Val66Met. Women with PMDD who were carriers of the Met-allele had lower fronto-cingulate cortex activation in the luteal phase compared to Met-allele carrying controls. The results provide suggestive evidence of impaired emotion-induced fronto-cingulate cortex activation in PMDD patients. Although limited by a small sample, the potential influence of BDNF Val66Met in PMDD is in line with preclinical research. PMID:24615932
Zhang, Haosu; Dai, Rui; Qin, Pengmin; Tang, Weijun; Hu, Jin; Weng, Xuchu; Wu, Xing; Mao, Ying; Wu, Xuehai; Northoff, Georg
Previous studies have demonstrated that altered states of consciousness are related to changes in resting state activity in the default-mode network (DMN). Anatomically, the DMN can be divided into anterior and posterior regions. The anterior DMN includes the perigenual anterior cingulate cortex and other medial prefrontal cortical regions, whereas the posterior DMN includes regions such as the posterior cingulate cortex (PCC) and the temporal parietal junction (TPJ). Although differential roles have been attributed to the anterior and posterior DMN regions, their exact contributions to consciousness levels remain unclear. To investigate the specific role of the posterior DMN in consciousness levels, we investigated 20 healthy controls (7 females, mean age = 33.6 years old) and 20 traumatic brain injury (TBI) patients (5 females, mean age = 43 years old) whose brain lesions were mainly restricted to the bilateral frontal cortex but retained a well-preserved posterior DMN (e.g., the PCC and the TPJ) and who exhibited varying levels of consciousness. We investigated the intra- and cross-functional connectivity strengths (FCSs) between the right/left PCC and the right/left TPJ and their correlation with consciousness levels. Significant reductions in both the intra- and cross-hemispheric FCSs were observed in patients compared with controls. A significant correlation with consciousness levels was observed only for the cross-hemispheric PCC-TPJ FCS but not for the intra-hemispheric PCC-TPJ FCS. Taken together, our results show that the cross-hemispheric posterior DMN is related to consciousness levels in a specific group of patients without posterior structural lesions. We therefore propose that the PCC may be central in maintaining consciousness through its cross-hemispheric FC with the TPJ.
Pruitt, David T; Schmid, Ariel N; Danaphongse, Tanya T; Flanagan, Kate E; Morrison, Robert A; Kilgard, Michael P; Rennaker, Robert L; Hays, Seth A
Skilled motor training results in reorganization of contralateral motor cortex movement representations. The ipsilateral motor cortex is believed to play a role in skilled motor control, but little is known about how training influences reorganization of ipsilateral motor representations of the trained limb. To determine whether training results in reorganization of ipsilateral motor cortex maps, rats were trained to perform the isometric pull task, an automated motor task that requires skilled forelimb use. After either 3 or 6 months of training, intracortical microstimulation (ICMS) mapping was performed to document motor representations of the trained forelimb in the hemisphere ipsilateral to that limb. Motor training for 3 months resulted in a robust expansion of right forelimb representation in the right motor cortex, demonstrating that skilled motor training drives map plasticity ipsilateral to the trained limb. After 6 months of training, the right forelimb representation in the right motor cortex was significantly smaller than the representation observed in rats trained for 3 months and similar to untrained controls, consistent with a normalization of motor cortex maps. Forelimb map area was not correlated with performance on the trained task, suggesting that task performance is maintained despite normalization of cortical maps. This study provides new insights into how the ipsilateral cortex changes in response to skilled learning and may inform rehabilitative strategies to enhance cortical plasticity to support recovery after brain injury.
Nagamitsu, Shinichiro; Sakurai, Rieko; Matsuoka, Michiko; Chiba, Hiromi; Ozono, Shuichi; Tanigawa, Hitoshi; Yamashita, Yushiro; Kaida, Hayato; Ishibashi, Masatoshi; Kakuma, Tatsuki; Croarkin, Paul E.; Matsuishi, Toyojiro
Several lines of evidence suggest that anxiety plays a key role in the development and maintenance of anorexia nervosa (AN) in children. The purpose of this study was to examine cortical GABA(A)-benzodiazepine receptor binding before and after treatment in children beginning intensive AN treatment. Brain single-photon emission computed tomography (SPECT) measurements using 123I-iomazenil, which binds to GABA(A)-benzodiazepine receptors, was performed in 26 participants with AN who were enrolled in a multimodal treatment program. Sixteen of the 26 participants underwent a repeat SPECT scan immediately before discharge at conclusion of the intensive treatment program. Eating behavior and mood disturbances were assessed using Eating Attitudes Test with 26 items (EAT-26) and the short form of the Profile of Mood States (POMS). Clinical outcome scores were evaluated after a 1-year period. We examined association between relative iomazenil-binding activity in cortical regions of interest and psychometric profiles and determined which psychometric profiles show interaction effects with brain regions. Further, we determined if binding activity could predict clinical outcome and treatment changes. Higher EAT-26 scores were significantly associated with lower iomazenil-binding activity in the anterior and posterior cingulate cortex. Higher POMS subscale scores were significantly associated with lower iomazenil-binding activity in the left frontal, parietal cortex, and posterior cingulate cortex (PCC). “Depression–Dejection” and “Confusion” POMS subscale scores, and total POMS score showed interaction effects with brain regions in iomazenil-binding activity. Decreased binding in the anterior cingulate cortex and left parietal cortex was associated with poor clinical outcomes. Relative binding increases throughout the PCC and occipital gyrus were observed after weight gain in children with AN. These findings suggest that cortical GABAergic receptor binding is altered
Takeuchi, Hikaru; Taki, Yasuyuki; Sekiguchi, Atsushi; Nouchi, Rui; Kotozaki, Yuka; Nakagawa, Seishu; Miyauchi, Carlos Makoto; Iizuka, Kunio; Yokoyama, Ryoichi; Shinada, Takamitsu; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Hashizume, Hiroshi; Kunitoki, Keiko; Sassa, Yuko; Kawashima, Ryuta
Sex-role egalitarianism (SRE) is the belief that the sex of an individual should not influence the perception of his or her rights, abilities, obligations, and opportunities. Thus, low SRE reflects a more conservative stereotypical view on sex-role. Here we investigated anatomical correlates of individual differences in SRE in the present study. We used voxel-based morphometry, a questionnaire to determine an individual’s SRE and associated psychological measures, and determined the association of SRE with gray matter structures and their cognitive nature in healthy individuals (375 men and 306 women; age, 20.6 ± 1.8 years). We demonstrated that higher SRE was associated with smaller regional gray matter density (rGMD) in the anterior part of the posterior cingulate cortex (PCC) and higher rGMD in the right amygdala. Post-hoc analyses revealed psychological measures characterized by contentious interpersonal orientations, such as contentious achievement motivation, were associated with lower SRE and higher rGMD in the anterior part of PCC. Depressive tendencies were associated with lower SRE and higher rGMD in the right amygdala. These findings suggest that variations in stereotype on sex role have roots in the limbic brain structures linked to contentious interpersonal orientation (cingulate) and negative mood (amygdala). PMID:26420574
Sharma, Aseem; Ray, Rahul; Sridhar, Jandhyala; Trehan, Arti; Khandare, Manish
Eosinophilic fasciitis, also known as Shulman's syndrome, is a fibrosing scleroderma-like syndrome, which is a distinct entity. A 55-year-old man, presented with progressive skin darkening, thickening, and tightening over the left lower limb since 6 months. Dermatological examination revealed a hyperpigmented indurated area on the left thigh, extending to the anterior aspect of the left leg. A well-defined hypopigmented indurated plaque was present over the left iliac region. Histopathology and imaging studies confirmed the diagnosis of eosinophilic fasciitis and lichen sclerosus. The indurated lesion on the left lower limb responded dramatically well to oral corticosteroids. This is a rare case of unilateral eosinophilic fasciitis associated with ipsilateral extragenital lichen sclerosus. PMID:27730034
Sharma, Aseem; Ray, Rahul; Sridhar, Jandhyala; Trehan, Arti; Khandare, Manish
Eosinophilic fasciitis, also known as Shulman's syndrome, is a fibrosing scleroderma-like syndrome, which is a distinct entity. A 55-year-old man, presented with progressive skin darkening, thickening, and tightening over the left lower limb since 6 months. Dermatological examination revealed a hyperpigmented indurated area on the left thigh, extending to the anterior aspect of the left leg. A well-defined hypopigmented indurated plaque was present over the left iliac region. Histopathology and imaging studies confirmed the diagnosis of eosinophilic fasciitis and lichen sclerosus. The indurated lesion on the left lower limb responded dramatically well to oral corticosteroids. This is a rare case of unilateral eosinophilic fasciitis associated with ipsilateral extragenital lichen sclerosus.
Suárez, M; Perassi, N I
The influence of extrahypothalamic limbic structures on adrenocortical activity was investigated in female adult rats. Bilateral lesions on the anteromedial thalami nucleus (AMTN), anteroventral thalami nucleus (AVTN) or the posterior cingulate cortex (PCC) all elicited a significant decrease on plasma corticosterone, while their electrochemical stimulation produced a significant increase with respect to animals with sham lesions or sham stimulation. In contrast, after lesions of the dorsomedial thalami nucleus (DMTN), medial mammillary nucleus (pars lateralis) (MMN) or retrosplenial cortex (RC), values of plasma corticosterone were significantly higher than those found in controls, whereas following their stimulation plasma corticosterone levels were lower than in controls. Bilateral lesions or stimulations of anterior cingulate cortex had no significant effect upon corticosterone secretion. These findings may be interpreted as indicative of the existence of excitatory (AMTN, AVTN, and PCC) and inhibitory (DMTN, MMN and RC) central nervous structures for the control of corticoadrenal secretion besides those already known.
Olsen, S; Osterhammel, P A; Rasmussen, A N; Nielsen, L H
Pure-tone Reference Equivalent Threshold Sound Pressure Level (RETSPL) of the ipsilateral stimulus receiver for acoustic reflex measurements on Madsen Electronics type Zodiac 901 impedance audiometer is provided. The results, obtained from 20 normal-hearing subjects, are achieved by comparing hearing threshold levels measured using a TDH 39 telephone (calibrated to ISO 389) with thresholds recorded using the ipsilateral stimulus insert phone. The calibration is referenced to an IEC-711 ear simulator and comprises the following frequencies: 125, 250, 500, 750, 1000, 1500, 2000, 3000, 4000, 6000, 8000 Hz.
Matsumoto, Hideyuki; Shimizu, Takahiro; Igeta, Yukifusa; Hashida, Hideji
This report describes the rare case of a 27-year-old female patient with conversion disorder who presented unilateral ptosis with ipsilateral muscle spasm of orbicular oculi. The co-existing of ptosis and muscle spasm of orbicular oculi indicates that, in accord with prior reports, the overactivity of orbicular oculi is essential in psychogenic pseudoptosis. The co-existing of unilateral ptosis and ipsilateral muscle spasm of orbicular oculi in the present case leads us to the conclusion that the overactivity of orbicular oculi is essential in psychogenic pseudoptosis.
Yesudas, Esther H.; Lee, Tatia M. C.
Vicarious pain is defined as the observation of individuals in pain. There is growing neuroimaging evidence suggesting that the cingulate cortex plays a significant role in self-experienced pain processing. Yet, very few studies have directly tested the distinct functions of the cingulate cortex for vicarious pain. In this review, one EEG and eighteen neuroimaging studies reporting cingulate cortex activity during pain observation were discussed. The data indicate that there is overlapping neural activity in the cingulate cortex during self- and vicarious pain. Such activity may contribute to shared neural pain representations that permit inference of the affective state of individuals in pain, facilitating empathy. However, the exact location of neuronal populations in which activity overlaps or differs for self- and observed pain processing requires further confirmation. This review also discusses evidence suggesting differential functions of the cingulate cortex in cognitive, affective, and motor processing during empathy induction. While affective processing in the cingulate cortex during pain observation has been explored relatively more often, its attention and motor roles remain underresearched. Shedding light on the neural correlates of vicarious pain and corresponding empathy in healthy populations can provide neurobiological markers and intervention targets for empathic deficits found in various clinical disorders. PMID:25815331
Vogt, Brent A.; Laureys, Steven
Neuronal aggregates involved in conscious awareness are not evenly distributed throughout the CNS but are comprised of key components referred to as the neural network correlates of consciousness (NNCC). A critical node in this network is the retrosplenial, posterior cingulate, and precuneal cortices (RSC/PCC/PrCC). The cytological and neurochemical composition of this region is reviewed in relation to the Brodmann map. This region has the highest level of brain glucose metabolism and cytochrome c oxidase activity. Monkey studies suggest that the anterior thalamic projection likely drives RSC and PCC metabolism and that the midbrain projection to the anteroventral thalamic nucleus is a key coupling site between the brainstem system for arousal and cortical systems for cognitive processing and awareness. The pivotal role of RSC/PCC/PrCC in consciousness is demonstrated with posterior cingulate epilepsy cases, midcingulate lesions that de-afferent this region and are associated with unilateral sensory neglect, observations from stroke and vegetative state patients, alterations in blood flow during sleep, and the actions of anesthetics. Since this region is critically involved in self reflection, it is not surprising that it is similarly a site for the NNCC. Interestingly, information processing during complex cognitive tasks and during aversive sensations such as pain induces efforts to terminate self reflection and result in decreased processing in PCC/PrCC. Finally, anatomical relations between the neural correlates of mind and NNCC in the cingulate gyrus do not appear to overlap and suggests that mental function and conscious awareness may be mediated by two neural networks. PMID:16186025
Zakiniaeiz, Yasmin; Scheinost, Dustin; Seo, Dongju; Sinha, Rajita; Constable, R Todd
Alcohol dependence is a chronic relapsing illness. Alcohol and stress cues have consistently been shown to increase craving and relapse risk in recovering alcohol dependent (AUD) patients. However, differences in functional connectivity in response to these cues have not been studied using data-driven approaches. Here, voxel-wise connectivity is used in a whole-brain investigation of functional connectivity differences associated with alcohol and stress cues and to examine whether these differences are related to subsequent relapse. In Study 1, 45, 4- to 8-week abstinent, recovering AUD patients underwent functional magnetic resonance imaging during individualized imagery of alcohol, stress, and neutral cues. Relapse measures were collected prospectively for 90 days post-discharge from inpatient treatment. AUD patients showed blunted anterior (ACC), mid (MCC) and posterior cingulate cortex (PCC), voxel-wise connectivity responses to stress compared to neutral cues and blunted PCC response to alcohol compared to neutral cues. Using Cox proportional hazard regression, weaker connectivity in ACC and MCC during neutral exposure was associated with longer time to relapse (better recovery outcome). Similarly, greater connectivity in PCC during alcohol-cue compared to stress cue was associated with longer time to relapse. In Study 2, a sub-group of 30 AUD patients were demographically-matched to 30 healthy control (HC) participants for group comparisons. AUD compared to HC participants showed reduced cingulate connectivity during alcohol and stress cues. Using novel data-driven approaches, the cingulate cortex emerged as a key region in the disruption of functional connectivity during alcohol and stress-cue processing in AUD patients and as a marker of subsequent alcohol relapse.
Chen, Peii; Erdahl, Lillian; Barrett, Anna M.
Spatial bias is an asymmetry of perception and/or representation of spatial information —“where” bias —, or of spatially directed actions — “aiming” bias. A monocular patch may induce contralateral “where” spatial bias (the Sprague effect; Sprague (1966) Science, 153, 1544–1547). However, an ipsilateral patch-induced spatial bias may be observed if visual occlusion results in top-down, compensatory re-allocation of spatial perceptual or representational resources toward the region of visual deprivation. Tactile distraction from a monocular patch may also contribute to an ipsilateral bias. To examine these hypotheses, neurologically normal adults bisected horizontal lines at baseline without a patch, while wearing a monocular patch, and while wearing tactile-only and visual-only monocular occlusion. We fractionated “where” and “aiming” spatial bias components using a video apparatus to reverse visual feedback for half of the test trials. The results support monocular patch-induced ipsilateral “where” spatial errors, which are not consistent with the Sprague effect. Further, the present findings suggested that the induced ipsilateral bias may be primarily induced by visual deprivation, consistent with compensatory “where” resource re-allocation. PMID:19100274
Jeong, Min; Shin, Sung Jin; Kang, Byoung Youl
Insufficiency fracture of the calcaneus is a rare entity. In the absence of trauma, evaluating a painful ankle in an elderly patient can be difficult and also it might be overlook the insufficiency fracture. We experienced a case of insufficiency calcaneus fracture that occurred after ipsilateral total knee arthroplasty. Here, we report our case with a review of literatures. PMID:26981521
Chase, Henry W; Segreti, Anna Maria; Keller, Timothy A; Cherkassky, Vladimir L; Just, Marcel A; Pan, Lisa A; Brent, David A
The 'default mode network' (DMN), a collection of brain regions including the posterior cingulate cortex (PCC), shows reliable inter-regional functional connectivity at rest. It has been implicated in rumination and other negative affective states, but its role in suicidal ideation is not well understood. We employed seed based functional connectivity methods to analyze resting state fMRI data in 34 suicidal ideators and 40 healthy control participants. Whole-brain connectivity with dorsal PCC or ventral PCC was broadly intact between the two groups, but while the control participants showed greater coupling between the dorsal anterior cingulate cortex (dACC) and dorsal PCC, compared to the dACC and ventral PCC, this difference was reversed in the ideators. Furthermore, ongoing low frequency BOLD signal in these three regions (dorsal, ventral PCC, dACC) was reduced in the ideators. The structural integrity of the cingulum bundle, as measured using diffusion tensor imaging (DTI), also explained variation in the functional connectivity measures but did not abolish the group differences. Together, these findings provide evidence of abnormalities in the DMN underlying the tendency towards suicidal ideation.
Strikwerda-Brown, Cherie; Davey, Christopher G.; Whittle, Sarah; Allen, Nicholas B.; Byrne, Michelle L.; Schwartz, Orli S.; Simmons, Julian G.; Dwyer, Dominic
Changes in the functional connectivity of the subgenual anterior cingulate cortex (SGC) have been linked with depressive symptoms. The aim of this study was to map this relationship across mid to late adolescence. Employing a longitudinal functional magnetic resonance imaging (fMRI) design, associations between patterns of resting-state SGC functional connectivity and symptoms of depression were examined at two time points in an initial sample of 72 adolescents. Using a region-of-interest approach, these associations were evaluated cross-sectionally and longitudinally. Cross-sectionally, weaker SGC functional connectivity with the posterior cingulate cortex (PCC), angular gyrus and dorsal prefrontal cortex at baseline, and weaker SGC connectivity with the dorsomedial prefrontal cortex (DMPFC) and ventromedial prefrontal cortex at follow-up, were associated with higher depressive symptoms. Longitudinally, a decrease in SGC functional connectivity with DMPFC, PCC, angular gyrus and middle temporal gyrus was associated with higher depressive symptoms at follow-up. The observation of weaker SGC connectivity predicting increased symptoms contrasts with the majority of resting-state fMRI studies in clinically depressed populations. Taken together with these past studies, our findings suggest depression-related changes in SGC functional connectivity may differ across developmental and illness stages. PMID:25416726
Zhao, Weihua; Kendrick, Keith M; Chen, Fei; Li, Hong; Feng, Tingyong
The more times people fail the more likely they are to give up, however little is known about the neural mechanisms underlying this impact of repeated failure on decision making. Here we have used a visual shape discrimination task with computer-controlled feedback combined with functional magnetic resonance imaging (fMRI) to investigate the neural circuits involved. The behavioral task confirmed that the more times subjects experienced failure the more likely they were to give up, with three successive failures being the key threshold and the majority of subjects reaching the point where they decided to quit and try a new stimulus set after three or four failures. The fMRI analysis revealed activity changes in frontal, parietal, temporal, limbic and striatal regions, especially anterior cingulate cortex (ACC), posterior cingulate cortex (PCC) and temporal parietal junction (TPJ) associated with the number of previous failures experienced. Furthermore, their parameter estimates were predictive of subjects’ quitting rate. Thus, subjects reach the point where they decide to quit after three/four failures and this is associated with differential changes in brain regions involved in error monitoring and reward which regulate both failure detection and changes in decision-making strategy. PMID:27097529
Kaçar, Emre; Nas, Ömer Fatih; Erdoğan, Cüneyt; Hakyemez, Bahattin
PURPOSE We aimed to evaluate the safety and effectiveness of single-stage endovascular treatment in patients with severe extracranial large vessel stenosis and concomitant ipsilateral unruptured intracranial aneurysm. METHODS Hospital database was screened for patients who underwent single-stage endovascular treatment between February 2008 and June 2013 and seven patients were identified. The procedures included unilateral carotid artery stenting (CAS) (n=4), bilateral CAS (n=2), and proximal left subclavian artery stenting (n=1) along with ipsilateral intracranial aneurysm treatment (n=7). The mean internal carotid artery stenosis was 81.6% (range, 70%–95%), and the subclavian artery stenosis was 90%. All aneurysms were unruptured. The mean aneurysm diameter was 7.7 mm (range, 5–13 mm). The aneurysms were ipsilateral to the internal carotid artery stenosis (internal carotid artery aneurysm) in five patients, and in the anterior communicating artery in one patient. The patient with subclavian artery stenosis had a fenestration aneurysm in the proximal basilar artery. Stenting of the extracranial large vessel stenosis was performed before aneurysm treatment in all patients. In two patients who underwent bilateral CAS, the contralateral carotid artery stenosis, which had no aneurysm distally, was treated initially. RESULTS There were no procedure-related complications or technical failure. The mean clinical follow-up period was 18 months (range, 9–34 months). One patient who underwent unilateral CAS experienced contralateral transient ischemic attack during the clinical follow-up. There was no restenosis on six-month follow-up angiograms, and all aneurysms were adequately occluded. CONCLUSION A single-stage procedure appears to be feasible for treatment of patients with severe extracranial large vessel stenosis and concomitant ipsilateral intracranial aneurysm. PMID:26359875
Gibbs, Terrell T.; Blatt, Gene J.
Autism is a behaviorally defined neurodevelopmental disorder and among its symptoms are disturbances in face and emotional processing. Emerging evidence demonstrates abnormalities in the GABAergic (gamma-aminobutyric acid) system in autism, which likely contributes to these deficits. GABAB receptors play an important role in modulating synapses and maintaining the balance of excitation-inhibition in the brain. The density of GABAB receptors in subjects with autism and matched controls was quantified in the anterior and posterior cingulate cortex, important for socio-emotional and cognitive processing, and the fusiform gyrus, important for identification of faces and facial expressions. Significant reductions in GABAB receptor density were demonstrated in all three regions examined suggesting that alterations in this key inhibitory receptor subtype may contribute to the functional deficits in individuals with autism. Interestingly, the presence of seizure in a subset of autism cases did not have a significant effect on the density of GABAB receptors in any of the three regions. PMID:20557420
Joshi, Siddhartha; Li, Yin; Kalwani, Rishi; Gold, Joshua I.
SUMMARY Changes in pupil diameter that reflect effort and other cognitive factors are often interpreted in terms of the activity of norepinephrine-containing neurons in the brainstem nucleus locus coeruleus (LC), but there is little direct evidence for such a relationship. Here we show that LC activation reliably anticipates changes in pupil diameter that either fluctuate naturally or are driven by external events during near fixation, as in many psychophysical tasks. This relationship occurs on as fine a temporal and spatial scale as single spikes from single units. However, this relationship is not specific to the LC. Similar relationships, albeit with delayed timing and different reliabilities across sites, are evident in the inferior and superior colliculus and anterior and posterior cingulate cortex. Because these regions are interconnected with the LC, the results suggest that non-luminance-mediated changes in pupil diameter might reflect LC-mediated coordination of neuronal activity throughout some parts of the brain. PMID:26711118
Golchert, Johannes; Smallwood, Jonathan; Jefferies, Elizabeth; Liem, Franziskus; Huntenburg, Julia M; Falkiewicz, Marcel; Lauckner, Mark E; Oligschläger, Sabine; Villringer, Arno; Margulies, Daniel S
Impulsive behavior often occurs without forethought and can be driven by strong emotions or sudden impulses, leading to problems in cognition and behavior across a wide range of situations. Although neuroimaging studies have explored the neurocognitive indicators of impulsivity, the large-scale functional networks that contribute to different aspects of impulsive cognition remain unclear. In particular, we lack a coherent account of why impulsivity is associated with such a broad range of different psychological features. Here, we use resting state functional connectivity, acquired in two independent samples, to investigate the neural substrates underlying different aspects of self-reported impulsivity. Based on the involvement of the anterior cingulate cortex (ACC) in cognitive but also affective processes, five seed regions were placed along the caudal to rostral gradient of the ACC. We found that positive urgency was related to functional connectivity between subgenual ACC and bilateral parietal regions such as retrosplenial cortex potentially highlighting this connection as being important in the modulation of the non-prospective, hastiness - related aspects of impulsivity. Further, two impulsivity dimensions were associated with significant alterations in functional connectivity of the supragenual ACC: (i) lack of perseverance was positively correlated to connectivity with the bilateral dorsolateral prefrontal cortex and right inferior frontal gyrus and (ii) lack of premeditation was inversely associated with functional connectivity with clusters within bilateral occipital cortex. Further analysis revealed that these connectivity patterns overlapped with bilateral dorsolateral prefrontal and bilateral occipital regions of the multiple demand network, a large-scale neural system implicated in the general control of thought and action. Together these results demonstrate that different forms of impulsivity have different neural correlates, which are linked to the
Jessup, Ryan K.; Busemeyer, Jerome R.; Brown, Joshua W.
Strong error-related activity in medial prefrontal cortex (mPFC) has been shown repeatedly with neuroimaging and event-related potential studies for the last several decades. Multiple theories have been proposed to account for error effects, including comparator models and conflict detection models, but the neural mechanisms that generate error signals remain in dispute. Typical studies use relatively low error rates, confounding the expectedness and the desirability of an error. Here we show with a gambling task and fMRI that when losses are more frequent than wins, the mPFC error effect disappears, and moreover, exhibits the opposite pattern by responding more strongly to unexpected wins than losses. These findings provide perspective on recent ERP studies and suggest that mPFC error effects result from a comparison between actual and expected outcomes. PMID:20203206
Rodriguez, Paul F.
Memory systems are known to be influenced by feedback and error processing, but it is not well known what aspects of outcome contingencies are related to different memory systems. Here we use the Rescorla-Wagner model to estimate prediction errors in an fMRI study of stimulus-outcome association learning. The conditional probabilities of outcomes…
Pedersen, Anya; Wilmsmeier, Andreas; Wiedl, Karl H.; Bauer, Jochen; Kueppers, Kerstin; Koelkebeck, Katja; Kohl, Waldemar; Kugel, Harald; Arolt, Volker; Ohrmann, Patricia
The remediation of executive function in patients with schizophrenia is important in rehabilitation because these skills affect the patient's capacity to function in the community. There is evidence that instructional techniques can improve deficits in the Wisconsin Card Sorting Test (WCST) in some schizophrenia patients. We used a standard…
Marsh, Abigail A.; Finger, Elizabeth C.; Fowler, Katherine A.; Adalio, Christopher J.; Jurkowitz, Ilana T. N.; Schechter, Julia C.; Pine, Daniel S.; Decety, Jean; Blair, R. J. R.
Background: Psychopathic traits are associated with increases in antisocial behaviors such as aggression and are characterized by reduced empathy for others' distress. This suggests that psychopathic traits may also impair empathic pain sensitivity. However, whether psychopathic traits affect responses to the pain of others versus the self…
Yoshimura, Shinpei; Ueda, Kazutaka; Suzuki, Shin-ichi; Onoda, Keiichi; Okamoto, Yasumasa; Yamawaki, Shigeto
Neural activity associated with self-referential processing of emotional stimuli was investigated using whole brain functional magnetic resonance imaging (fMRI). Fifteen healthy subjects underwent fMRI scanning while making judgments about positive and negative trait words in four conditions (self-reference, other-reference, semantic processing,…
in diabetes neuropathy  in which ACC NAA concentrations were no different in subjects with neuropathic pain compared with pain-free control...brain regions in patients with diabetes and painful neuropathy . Diabetes Care. 2008; 31:980–1. [PubMed: 18299445] 46. Spielberger, CD.; Garsuch, RC... diabetes  and after SCI . Basic research suggests that glial activation is an important mechanism underlying neuropathic pain after SCI [22,23
Udagawa, Jun; Nimura, Masayuki; Kagohashi, Yukiko; Otani, Hiroki
Leptin is an obese gene product, and leptin-deficient ob/ob mice develop hyperphagia and reduced locomotor activity. Leptin is thought to be related to brain development, because leptin receptors are widely expressed in the brain, and because brain weight as well as brain protein and DNA contents were reduced in adult ob/ob mice. In this study, we investigated the effect of leptin on the fetal cingulate cortex, since the leptin receptor is expressed in the neurons of the cingulate cortex, which is involved in emotion as well as in sensory, motor, and cognitive processes. The ob/ob fetuses had more pycnotic cells than wild-type fetuses in the cingulate cortex at embryonic day (E) 18. Many pycnotic cells were observed in the intermediate zone of the cingulate cortex. Most cells observed in this area were neuronal lineage cells, while few undifferentiated cells and oligodendrocyte precursor cells were found. At E18 there was no significant difference in the rostrocaudal length of the corpus callosum, which contains the neuronal projection from the cingulate cortex, between ob/ob and wild-type fetuses. We also showed that the length of the cerebrum was greater and the width of the cerebrum and cerebellum were lesser in ob/ob fetuses than in wild-type at E16. These results suggest an increased cell death in neuronal lineage cells in the intermediate zone of the cingulate cortex in leptin-deficient ob/ob mice. Leptin deficiency may also alter the gross morphology of the brain in development, but not the formation of the corpus callosum.
Sarmiento, Fernanda; Atehortúa, Angélica; Martínez, Fabio; Romero, Eduardo
A reliable diagnosis of the Parkinson Disease lies on the objective evaluation of different motor sub-systems. Discovering specific motor patterns associated to the disease is fundamental for the development of unbiased assessments that facilitate the disease characterization, independently of the particular examiner. This paper proposes a new objective screening of patients with Parkinson, an approach that optimally combines ipsilateral global descriptors. These ipsilateral gait features are simple upper-lower limb relationships in frequency and relative phase spaces. These low level characteristics feed a simple SVM classifier with a polynomial kernel function. The strategy was assessed in a binary classification task, normal against Parkinson, under a leave-one-out scheme in a population of 16 Parkinson patients and 7 healthy control subjects. Results showed an accuracy of 94;6% using relative phase spaces and 82;1% with simple frequency relations.
Gu, Xiaosi; Hof, Patrick R.; Friston, Karl J.; Fan, Jin
This paper reviews the foundation for a role of the human anterior insular cortex (AIC) in emotional awareness, defined as the conscious experience of emotions. We first introduce the neuroanatomical features of AIC and existing findings on emotional awareness. Using empathy, the awareness and understanding of other people’s emotional states, as a test case, we then present evidence to demonstrate: 1) AIC and anterior cingulate cortex (ACC) are commonly coactivated as revealed by a meta-analysis, 2) AIC is functionally dissociable from ACC, 3) AIC integrates stimulus-driven and top-down information, and 4) AIC is necessary for emotional awareness. We propose a model in which AIC serves two major functions: integrating bottom-up interoceptive signals with top-down predictions to generate a current awareness state and providing descending predictions to visceral systems that provide a point of reference for autonomic reflexes. We argue that AIC is critical and necessary for emotional awareness. PMID:23749500
Song, Jae-Yoon; Park, Jae-Wan; Lee, Chan-Bok; Eun, Denny; Jang, Jung-Hoon; Lee, Ho-Jin; Hyun, Gwang-Suk; Park, Jung-Min; Cha, Jun-Youl; Cho, Nam-Heung; Ko, Il-Gyu; Jin, Jun-Jang; Jin, Yong-Yun; Ham, Do-Woong; Jee, Yong-Seok
The number of injuries that force golfers to quit is also increasing. In particular, the upper body injuries are concerns for amateur golfers. This study was conducted not only to investigate muscular balance, such as ipsilateral and bilateral ratios of the upper body, but to also evaluate the possible problems of muscular joints in amateur golfers. Male golfers (n=10) and a healthy control group (n=10) were recruited for the assessment of muscular function in the upper body, which was measured by an isokinetic dynamometer at 60°/sec. The tested parts were trunk, wrist, forearm, elbow, and shoulder joints. Mann-Whitney U-test was used to evaluate the significance of the differences between groups. The ipsilateral ratios of peak torque or work per repetition (WR) of trunk flexor and extensor in the golfers were not significantly different compared to those of the control group. These results were similar to the shoulder horizontal abductor and adductor. However, there were significant differences in the ipsilateral and bilateral ratios of the wrist, forearm, and elbow joints. Especially, the WR of the wrist flexor, forearm pronator, and elbow flexor on the left side of amateur golfers showed imbalances in bilateral ratios. Moreover, the WR of the wrist and elbow flexors on the left side of amateur golfers were lower than those of the wrist and elbow extensors. Therefore, amateur golfers should strive to prevent injuries of the wrist, forearm, and elbow joints and to reinforce the endurance on those parts of the left side.
Song, Jae-Yoon; Park, Jae-Wan; Lee, Chan-Bok; Eun, Denny; Jang, Jung-Hoon; Lee, Ho-Jin; Hyun, Gwang-Suk; Park, Jung-Min; Cha, Jun-Youl; Cho, Nam-Heung; Ko, Il-Gyu; Jin, Jun-Jang; Jin, Yong-Yun; Ham, Do-Woong; Jee, Yong-Seok
The number of injuries that force golfers to quit is also increasing. In particular, the upper body injuries are concerns for amateur golfers. This study was conducted not only to investigate muscular balance, such as ipsilateral and bilateral ratios of the upper body, but to also evaluate the possible problems of muscular joints in amateur golfers. Male golfers (n=10) and a healthy control group (n=10) were recruited for the assessment of muscular function in the upper body, which was measured by an isokinetic dynamometer at 60°/sec. The tested parts were trunk, wrist, forearm, elbow, and shoulder joints. Mann–Whitney U-test was used to evaluate the significance of the differences between groups. The ipsilateral ratios of peak torque or work per repetition (WR) of trunk flexor and extensor in the golfers were not significantly different compared to those of the control group. These results were similar to the shoulder horizontal abductor and adductor. However, there were significant differences in the ipsilateral and bilateral ratios of the wrist, forearm, and elbow joints. Especially, the WR of the wrist flexor, forearm pronator, and elbow flexor on the left side of amateur golfers showed imbalances in bilateral ratios. Moreover, the WR of the wrist and elbow flexors on the left side of amateur golfers were lower than those of the wrist and elbow extensors. Therefore, amateur golfers should strive to prevent injuries of the wrist, forearm, and elbow joints and to reinforce the endurance on those parts of the left side. PMID:27162771
Lee, D H
Ectopic pregnancy is associated with maternal morbidity and mortality during early pregnancy. Ectopic pregnancy occurs in approximately 2% of all pregnancies, and the risk of ectopic pregnancy is increased by eight-fold in women with a history of eopic pregnancy. However, recurrent ectopic pregnancy after ipsilateral partial salpingectomy is quite rare. The authors experienced a case of recurrent ectopic pregnancy in the distal remnant after right partial salpingectomy. In this case report, they discuss this unusual case and provide a brief review of the literature.
Welch, Babu G
The case is a 55-year-old female who presented with dizziness as the chief complaint. She has a family history of two relatives with subarachnoid hemorrhage. Digital subtraction angiography revealed the presence of a left-sided posterior communicating artery aneurysm and an ipsilateral superior cerebellar artery (SCA) aneurysm. Due to the smaller nature of the SCA, a decision was made to proceed with surgical clipping of both lesions through a pterional approach. A narrated video with illustrations depicts the intraoperative management of these lesions with postoperative angiography results. The video can be found here: http://youtu.be/HCHToSsXv-4 .
Rousseaux, M; Godefroy, O; Cabaret, M; Bernati, T
Disorders of executive function and motor control are considered to be classical consequences of prefrontal lesions. The aim of this study was to investigate these disorders and their evolution in a series of patients presenting with prefrontal and cingulate lesion following rupture of an anterior communicating artery aneurysm. Twenty one subjects were included, and assessed in the secondary and late post stroke phases. We have used the following tests to assess planning and/or execution time and performance: Trail Making test, Wisconsin Card Sorting Test, London Tower Test, Shopping Test of Martin, sequential gestual test and contradictory responses test from Luria. Correlations between these parameters were used to evaluate subjects strategy. In evaluation of execution time, patients were slower than controls, and the difference was more marked using the Trail Making Test (p < 0.01) and the London Tower Test (p < 0.01). Furthermore, the initiation time was increased in the London Tower Test (p < 0.01), this suggesting that they were slower than impulsive. Groups analysis showed that their performance level was most often similar to that of of controls, even in the secondary phase, with the exception of the number of problems solved whatever number of moves in the London Tower test (p < 0.01) and of the percentage of errors in the sequential motor task (p < 0.03). Similar results were observed in the evaluation of single cases. Correlations between execution time and performance were most often significant and negative, in patients and controls. These results suggest that the management of the speed-accuracy compromise was relatively similar, and that impulsivity, which associates reduction of time to poor performance, was absent or mild. Cingulate, and caudate lesions were identified as the source of most cognitive disorders.
BANERJEE, B.; MEDDA, B. K.; POCHIRAJU, S.; KANNAMPALLI, P.; LANG, I. M.; SENGUPTA, J. N.; SHAKER, R.
Background We recently reported an increase in N-methyl-d-aspartate (NMDA) receptor subunit expression and CaMKII-dependent phosphorylation of NR2B in the rostral cingulate cortical (rCC) neurons following esophageal acid exposure in rats. As α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors mediate the fast excitatory transmission and play a critical role in synaptic plasticity, in this study, we investigated the effect of esophageal acid exposure in rats on the expression of AMPA receptor subunits and the involvement of these molecular alterations in acid-induced sensitization of neurons in the anterior cingulate (ACC) and midcingulate (MCC) cortices. Methods In molecular study, we examined GluA1 and GluA2 expression and phosphorylation in membrane preparations and in the isolated postsynaptic densities (PSDs) from rats receiving acute esophageal exposure of either saline (control group) or 0.1 NHCl (experimental group). In electrophysiological study, the effect of selective AMPA receptor (Ca2+ permeable) antagonist IEM-1460 and CaMKII inhibitor KN-93 was tested on responses of cortical neurons during acid infusion to address the underlying molecular mechanism of acid-induced sensitization. Key Results The acid exposure significantly increased expression of GluA1, pGluA1Ser831, and phosphorylated CaMKIIThr286, in the cortical membrane preparations. In isolated PSDs, a significant increase in pGluA1Ser831 was observed in acid-treated rats compared with controls. Microinjection of IEM-1460 or KN-93 near the recording site significantly attenuated acid-induced sensitization of cortical neurons. Conclusions & Inferences The underlying mechanism of acid-induced cortical sensitization involves upregulation and CaMKII-mediated phosphorylation of GluA1. These molecular changes of AMPA receptors subunit GluA1 in the cortical neurons might play an important role in acid-induced esophageal hypersensitivity. PMID:24118589
Background Cortical neurons display network-level dynamics with unique spatiotemporal patterns that construct the backbone of processing information signals and contribute to higher functions. Recent years have seen a wealth of research on the characteristics of neuronal networks that are sufficient conditions to activate or cease network functions. Local field potentials (LFPs) exhibit a scale-free and unique event size distribution (i.e., a neuronal avalanche) that has been proven in the cortex across species, including mice, rats, and humans, and may be used as an index of cortical excitability. In the present study, we induced seizure activity in the anterior cingulate cortex (ACC) with medial thalamic inputs and evaluated the impact of cortical excitability and thalamic inputs on network-level dynamics. We measured LFPs from multi-electrode recordings in mouse cortical slices and isoflurane-anesthetized rats. Results The ACC activity exhibited a neuronal avalanche with regard to avalanche size distribution, and the slope of the power-law distribution of the neuronal avalanche reflected network excitability in vitro and in vivo. We found that the slope of the neuronal avalanche in seizure-like activity significantly correlated with cortical excitability induced by γ-aminobutyric acid system manipulation. The thalamic inputs desynchronized cingulate seizures and affected the level of cortical excitability, the modulation of which could be determined by the slope of the avalanche size. Conclusions We propose that the neuronal avalanche may be a tool for analyzing cortical activity through LFPs to determine alterations in network dynamics. PMID:24387299
Thömke, Frank; Marx, Jürgen J; Cruccu, Giorgio; Stoeter, Peter; Hopf, Hanns C
There is a suprasegmental influence on the masseter reflex (MassR) in animals, which is mediated via the fifth nerve spinal nucleus (5SpN). Corresponding data in humans are lacking. Out of 268 prospectively recruited patients with clinical signs of acute brainstem infarctions, we identified 38 with magnetic resonance imaging (MRI)-documented unilateral infarcts caudal to the levels of the fifth nerve motor and main sensory nuclei. All had biplanar T2- and echo planar diffusion-weighted MRI and MassR testing. Five patients (13%) had ipsilateral MassR abnormalities. In all, the infarcts involved the region of the 5SpN. Patients with medullary infarcts involving the region of the 5SpN may thus have ipsilateral MassR abnormalities. This possibly represents an interruption of an excitatory projection mediated via the 5SpN to masseter motoneurons in the fifth nerve motor nucleus. MassR abnormalities with medullary lesions restrict the topodiagnostic value of the MassR.
Kennerley, Steven W.; Friston, Karl; Bestmann, Sven
Integrating costs and benefits is crucial for optimal decision-making. Although much is known about decisions that involve outcome-related costs (e.g., delay, risk), many of our choices are attached to actions and require an evaluation of the associated motor costs. Yet how the brain incorporates motor costs into choices remains largely unclear. We used human fMRI during choices involving monetary reward and physical effort to identify brain regions that serve as a choice comparator for effort-reward trade-offs. By independently varying both options' effort and reward levels, we were able to identify the neural signature of a comparator mechanism. A network involving supplementary motor area and the caudal portion of dorsal anterior cingulate cortex encoded the difference in reward (positively) and effort levels (negatively) between chosen and unchosen choice options. We next modeled effort-discounted subjective values using a novel behavioral model. This revealed that the same network of regions involving dorsal anterior cingulate cortex and supplementary motor area encoded the difference between the chosen and unchosen options' subjective values, and that activity was best described using a concave model of effort-discounting. In addition, this signal reflected how precisely value determined participants' choices. By contrast, separate signals in supplementary motor area and ventromedial prefrontal cortex correlated with participants' tendency to avoid effort and seek reward, respectively. This suggests that the critical neural signature of decision-making for choices involving motor costs is found in human cingulate cortex and not ventromedial prefrontal cortex as typically reported for outcome-based choice. Furthermore, distinct frontal circuits seem to drive behavior toward reward maximization and effort minimization. SIGNIFICANCE STATEMENT The neural processes that govern the trade-off between expected benefits and motor costs remain largely unknown. This is
Cosmelli, Diego; López, Vladimir; Lachaux, Jean-Philippe; López-Calderón, Javier; Renault, Bernard; Martinerie, Jacques; Aboitiz, Francisco
We studied brain activity during the displacement of attention in a modified visuo-spatial orienting paradigm. Using a behaviorally relevant no-shift condition as a control, we asked whether ipsi- or contralateral parietal alpha band activity is specifically related to covert shifts of attention. Cue-related event-related potentials revealed an attention directing anterior negativity (ADAN) contralateral to the shift of attention and P3 and contingent negative variation waveforms that were enhanced in both shift conditions as compared to the no-shift task. When attention was shifted away from fixation, alpha band activity over parietal regions ipsilateral to the attended hemifield was enhanced relative to the control condition, albeit with different dynamics in the upper and lower alpha subbands. Contralateral-to-attended parietal alpha band activity was indistinguishable from the no-shift task.
Pestana, Elia M; Gupta, Ajay
We report an infant with left eye blinking seizures accompanying a left (ipsilateral) fronto-temporal scalp EEG ictal pattern. The epileptogenic lesion was a left frontal encephalomalacia along the ventriculo-peritoneal shunt tract. The shunt was inserted for treatment of communicating hydrocephalus. This case illustrates the lateralizing value of the ictal blinking. Review of the literature suggests that seizures with unilateral blinking are likely to be produced by activation of ipsilateral trigeminal fibers innervating subdural intracranial structures and pial vessels in temporal and frontal lobes. Ipsilateral blinking could also be produced by activation of the ipsilateral cerebellar hemisphere.
Schrafl-Altermatt, Miriam; Dietz, Volker
Task-specific neural coupling during cooperative hand movements has been described in healthy volunteers, manifested by bilateral reflex electromyographic responses in forearm muscles following unilateral ulnar nerve stimulation and by task-specific activation of secondary somatosensory cortical areas (S2) in functional MRI. The aim of this study was to investigate the role of sensory input to the ipsilateral and contralateral cortex during a cooperative task. Somatosensory evoked potentials from the ulnar nerve were recorded over the ipsilateral and contralateral cortex during resting and during cooperative and noncooperative hand movements. Ipsilateral potentials with smaller amplitude were present under all conditions in almost all participants. In relation to the resting condition, the amplitudes of both the ipsilateral and the contralateral potential were reduced during the cooperative and the noncooperative tasks. Nevertheless, the reduction in amplitude was similar for the ipsilateral and the contralateral potentials in the noncooperative task, but less on the ipsilateral compared with the contralateral side during the cooperative task. The ratio of ipsilateral/contralateral somatosensory evoked potential amplitude was thus significantly larger during the cooperative task compared with the control task and the resting condition. This indicates a functional role of ipsilateral pathways connecting the cervical spinal cord with the cortex during the cooperative task. These observations favor the idea of a task-specific mediation of sensory input from both hands to the ipsilateral and contralateral hemispheres as the basis of neuronal coupling.
Bodin, Frédéric; Dissaux, Caroline; Steib, Jean-Paul; Massard, Gilbert
Radical resection of an extended malignant sarcoma of the chest wall requires full-thickness thoracic chest wall reconstruction. Reconstruction is tedious in the case of posteriorly located tumours, because the ipsilateral pedicled myocutaneous latissimus dorsi flap is involved and hence not usable for soft tissue coverage. We report an original case of a left giant dorsal chondrosarcoma originating from the 11th costovertebral joint. After extended resection and skeletal reconstruction, soft tissue coverage was achieved with an original contralateral free flap encompassing both latissimus dorsi and serratus anterior muscles. The flap pedicle was anastomosed to the ipsilateral thoracodorsal vessels.
Balsters, Joshua H.; Mantini, Dante; Apps, Matthew A.J.; Eickhoff, Simon B.; Wenderoth, Nicole
Although resting state fMRI (RS-fMRI) is increasingly used to generate biomarkers of psychiatric illnesses, analytical choices such as seed size and placement can lead to variable findings. Seed placement especially impacts on RS-fMRI studies of Autism Spectrum Disorder (ASD), because individuals with ASD are known to possess more variable network topographies. Here, we present a novel pipeline for analysing RS-fMRI in ASD using the cingulate cortex as an exemplar anatomical region of interest. Rather than using seeds based on previous literature, or gross morphology, we used a combination of structural information, task-independent (RS-fMRI) and task-dependent functional connectivity (Meta-Analytic Connectivity Modeling) to partition the cingulate cortex into six subregions with unique connectivity fingerprints and diverse behavioural profiles. This parcellation was consistent between groups and highly replicable across individuals (up to 93% detection) suggesting that the organisation of cortico-cingulo connections is highly similar between groups. However, our results showed an age-related increase in connectivity between the anterior middle cingulate cortex and right lateral prefrontal cortex in ASD, whilst this connectivity decreased in controls. There was also a Group × Grey Matter (GM) interaction, showing increased connectivity between the anterior cingulate cortex and the rectal gyrus in concert with increasing rectal gyrus GM in controls. By comparing our approach to previously established methods we revealed that our approach improves network detection in both groups, and that the ability to detect group differences using 4 mm radius spheres varies greatly with seed placement. Using our multi-modal approach we find disrupted cortico-cingulo circuits that, based on task-dependent information, may contribute to ASD deficits in attention and social interaction. Moreover, we highlight how more sensitive approaches to RS-fMRI are crucial for establishing
Towards clinically useful neuroimaging in depression treatment: Is subgenual cingulate activity robustly prognostic for depression outcome in Cognitive Therapy across studies, scanners, and patient characteristics?
Siegle, Greg J.; Thompson, Wesley K.; Collier, Amanda; Berman, Susan R.; Feldmiller, Joshua; Thase, Michael E.; Friedman, Edward S.
Context 40–60% of unmedicated depressed individuals respond to Cognitive Therapy (CT) in controlled trials. Multiple previous studies suggest that activity in the subgenual anterior cingulate predicts outcome in CT for depression, but there have been no prospective replications. Objective This study prospectively examined whether subgenual cingulate activity is a reliable and robust prognostic outcome marker for CT for depression and whether its activity changes in treatment. Design Two inception cohorts were assessed with fMRI on different scanners on a task sensitive to sustained emotional information processing before and after 16–20 sessions of CT, along with a sample of control participants tested at comparable intervals. Setting Therapy took place in a hospital outpatient clinic. Patients Participants included 49 unmedicated depressed adults and 35 healthy control participants. Main Outcome Measures Pre-treatment subgenual anterior cingulate activity in an a priori region in response to negative words was correlated with residual severity and used to classify response and remission. Results As expected, in both samples, participants with the lowest pre-treatment sustained subgenual cingulate (sgACC; BA25) reactivity in response to negative words displayed the most improvement in CT (R2=.29, >75% correct classification of response, >70% correct classification of remission). Other a priori regions explained additional variance. Response/Remission in Cohort 2 was predicted based on thresholds from Cohort 1. sgACC activity remained low for remitters following treatment. Conclusions Neuroimaging provides a quick, valid, and clinically applicable way of assessing neural systems associated with treatment response/remission. sgACC activity, in particular, may reflect processes which interfere with treatment, e.g,. emotion generation in addition to its putative regulatory role; alternately, its absence may facilitate treatment response. PMID:22945620
Anani, Abalo; Yannick, Dellanh; Gamal, Ayouba; Assang, Dossim
Anterior traumatic dislocations of the hip are much less common than posterior dislocations. To date, 14 cases of open anterior dislocation of the hip associated with such injuries, acetabular and femoral head fractures and femoral vascular and nerve damage have been reported. We present a case of a 23-year-old male who sustained open anterior dislocation of the hip with ipsilateral fracture of the greater trochanter after an accident on the public highway. Additional lesions included an iliac wing fracture and a perineal wound. We report this case because of the rarity and seriousness of this injury due to its progressive complications and difficulties related to its management, which are typical to a developing country like ours. PMID:27247749
Pektas, Suzan Demir; Akoglu, Gulsen; Metin, Ahmet; Adiyaman, Nuran Sungu; Demirseren, Mustafa Erol
Becker nevus syndrome (BNS) is a rare epidermal nevus syndrome characterized with Becker nevus and ipsilateral breast gland hypoplasia or other skin, skeletal and/or muscle tissue disorders. A 24-year-old woman presented with brown, irregular bordered patch with a diameter of approximately 10 cm which consisted of several small macules on the left breast skin. The ultrasonography and magnetic resonance imaging revealed left breast hypoplasia. Histopathological examination demonstrated minimal acanthosis, papillomatosis, increase in basal layer melanin and hypertrophy of the erector pili muscle. Immunohistochemical staining was positive for androgen in the epidermis, dermal stromal cells and skin appendages. Depending on the clinical and histopathological findings, the patient was diagnosed as BNS. Diagnosis of BNS needs careful examination of pigmented macules and patches since non-hairy BN may be easily overlooked. Patients with BN should be evaluated for associated abnormalities of BNS, in which the severity and extend of ectodermal involvement may differ from patient to other. PMID:25484431
Kovács, B; Kéri, S
Intranasally administered oxytocin gained popularity as a hormone facilitating trust, cooperation, and affiliation. However, the long-term consequences of oxytocin use are not known. Given that intensive media attention and advertisements of the "love hormone" might lead to a new form of misuse, we conducted an online survey and identified 41 individuals with oxytocin misuse. Misuse will be proposed throughout the manuscript instead of the more accurate "off-label use" for reasons of simplicity. We compared the social functions of oxytocin users with that of 41 matched control volunteers. We administered the "Reading the Mind in the Eyes Test" (RMET) and the National Institute of Health (NIH) Toolbox Adult Social Relationship Scales (NIH-ASRS) to delineate affective "theory of mind" and real-life social functions, respectively. Resting-state functional brain connectivity analyses were also carried out. Results revealed no significant differences between individuals with oxytocin misuse and control participants on the RMET and NIH-ASRS. However, individuals with oxytocin misuse showed an increased connectivity between the right amygdala and dorsal anterior cingulate cortex relative to the control group. Higher estimated cumulative doses of oxytocin were associated with enhanced amygdala-cingulate connectivity. These results show that individuals who have self-selected for and pursued oxytocin use have increased amygdala-cingulate resting connectivity, compared to individuals who have not used oxytocin, despite the lack of differences in RMET and NIH-ASRS scores. Further longitudinal studies are warranted to investigate the cause-effect relationship between oxytocin use and brain connectivity.
Hsu, Chun-Ting; Conrad, Markus; Jacobs, Arthur M
Immersion in reading, described as a feeling of 'getting lost in a book', is a ubiquitous phenomenon widely appreciated by readers. However, it has been largely ignored in cognitive neuroscience. According to the fiction feeling hypothesis, narratives with emotional contents invite readers more to be empathic with the protagonists and thus engage the affective empathy network of the brain, the anterior insula and mid-cingulate cortex, than do stories with neutral contents. To test the hypothesis, we presented participants with text passages from the Harry Potter series in a functional MRI experiment and collected post-hoc immersion ratings, comparing the neural correlates of passage mean immersion ratings when reading fear-inducing versus neutral contents. Results for the conjunction contrast of baseline brain activity of reading irrespective of emotional content against baseline were in line with previous studies on text comprehension. In line with the fiction feeling hypothesis, immersion ratings were significantly higher for fear-inducing than for neutral passages, and activity in the mid-cingulate cortex correlated more strongly with immersion ratings of fear-inducing than of neutral passages. Descriptions of protagonists' pain or personal distress featured in the fear-inducing passages apparently caused increasing involvement of the core structure of pain and affective empathy the more readers immersed in the text. The predominant locus of effects in the mid-cingulate cortex seems to reflect that the immersive experience was particularly facilitated by the motor component of affective empathy for our stimuli from the Harry Potter series featuring particularly vivid descriptions of the behavioural aspects of emotion.
Cetin, Ibrahim Ilker; Aktaş, Dilek; Tunçbilek, Ergül
This report describes a patient who had bilateral facial nerve paralysis, external ophthalmoplegia, absence of pectoralis major muscle at right side, ipsilateral hand and foot, and contralateral hand anomalies. To our knowledge, this is the first patient with Poland syndrome reported in combination with Moebius syndrome, presenting with contralateral hand and ipsilateral foot anomalies.
Fujiwara, Yusuke; Matsumoto, Riki; Nakae, Takuro; Usami, Kiyohide; Matsuhashi, Masao; Kikuchi, Takayuki; Yoshida, Kazumichi; Kunieda, Takeharu; Miyamoto, Susumu; Mima, Tatsuya; Ikeda, Akio; Osu, Rieko
The cortical motor areas are activated not only during contralateral limb movements but also during ipsilateral limb movements. Although these ipsilateral activities have been observed in several brain imaging studies, their functional role is poorly understood. Due to its high temporal resolution and low susceptibility to artifacts from body movements, the electrocorticogram (ECoG) is an advantageous measurement method for assessing the human brain function of motor behaviors. Here, we demonstrate that contra- and ipsilateral movements share a similarity in the high-frequency band of human ECoG signals. The ECoG signals were measured from the unilateral sensorimotor cortex while patients conducted self-paced movements of different body parts, contra- or ipsilateral to the measurement side. The movement categories (wrist, shoulder, or ankle) of ipsilateral movements were decoded as accurately as those of contralateral movements from spatial patterns of the high-frequency band of the precentral motor area (the primary motor and premotor areas). The decoder, trained in the high-frequency band of ipsilateral movements generalized to contralateral movements, and vice versa, confirmed that the activity patterns related to ipsilateral limb movements were similar to contralateral ones in the precentral motor area. Our results suggest that the high-frequency band activity patterns of ipsilateral and contralateral movements might be functionally coupled to control limbs, even during unilateral movements.
Khamassi, Mehdi; Quilodran, René; Enel, Pierre; Dominey, Peter F; Procyk, Emmanuel
To explain the high level of flexibility in primate decision-making, theoretical models often invoke reinforcement-based mechanisms, performance monitoring functions, and core neural features within frontal cortical regions. However, the underlying biological mechanisms remain unknown. In recent models, part of the regulation of behavioral control is based on meta-learning principles, for example, driving exploratory actions by varying a meta-parameter, the inverse temperature, which regulates the contrast between competing action probabilities. Here we investigate how complementary processes between lateral prefrontal cortex (LPFC) and dorsal anterior cingulate cortex (dACC) implement decision regulation during exploratory and exploitative behaviors. Model-based analyses of unit activity recorded in these 2 areas in monkeys first revealed that adaptation of the decision function is reflected in a covariation between LPFC neural activity and the control level estimated from the animal's behavior. Second, dACC more prominently encoded a reflection of outcome uncertainty useful for control regulation based on task monitoring. Model-based analyses also revealed higher information integration before feedback in LPFC, and after feedback in dACC. Overall the data support a role of dACC in integrating reinforcement-based information to regulate decision functions in LPFC. Our results thus provide biological evidence on how prefrontal cortical subregions may cooperate to regulate decision-making.
Simões-Franklin, Cristina; Hester, Robert; Shpaner, Marina; Foxe, John J; Garavan, Hugh
Reacting appropriately to errors during task performance is fundamental to successful negotiation of our environment. This is especially true when errors will result in a significant penalty for the person performing a given task, be they financial or otherwise. Error responses and monitoring states were manipulated in a GO/NOGO task by introducing a financial punishment for errors. This study employed a mixed block design alternating between punishment and no punishment (neutral) conditions, enabling an assessment of tonic changes associated with cognitive control as well as trial-specific effects. Behavioural results revealed slower responses and fewer commission errors in the punishment condition. The dorsal anterior cingulate cortex (ACC) had equal trial-specific activity for errors in the neutral and punishment conditions but had greater tonic activity throughout the punishment condition. A region of interest analysis revealed different activation patterns between the dorsal and the rostral parts of the ACC with the rostral ACC having only trial-specific activity for errors in the punishment condition, an activity profile similar to one observed in the nucleus accumbens. This study suggests that there is a motivational influence on cognitive processes in the ACC and nucleus accumbens and hints at a dissociation between tonic proactive activity and phasic reactive error-related activity.
Goldstein, R.Z.; Goldstein, R.Z.; Woicik, P.A.; Maloney, T.; Tomasi, D.; Alia-Klein, N.; Shan, J.; Honorario, J.; Samaras, d.; Wang, R.; Telang, F.; Wang, G.-J.; Volkow, N.D.
Anterior cingulate cortex (ACC) hypoactivations during cognitive demand are a hallmark deficit in drug addiction. Methylphenidate (MPH) normalizes cortical function, enhancing task salience and improving associated cognitive abilities, in other frontal lobe pathologies; however, in clinical trials, MPH did not improve treatment outcome in cocaine addiction. We hypothesized that oral MPH will attenuate ACC hypoactivations and improve associated performance during a salient cognitive task in individuals with cocaine-use disorders (CUD). In the current functional MRI study, we used a rewarded drug cue-reactivity task previously shown to be associated with hypoactivations in both major ACC subdivisions (implicated in default brain function) in CUD compared with healthy controls. The task was performed by 13 CUD and 14 matched healthy controls on 2 d: after ingesting a single dose of oral MPH (20 mg) or placebo (lactose) in a counterbalanced fashion. Results show that oral MPH increased responses to this salient cognitive task in both major ACC subdivisions (including the caudal-dorsal ACC and rostroventromedial ACC extending to the medial orbitofrontal cortex) in the CUD. These functional MRI results were associated with reduced errors of commission (a common impulsivity measure) and improved task accuracy, especially during the drug (vs. neutral) cue-reactivity condition in all subjects. The clinical application of such MPH-induced brain-behavior enhancements remains to be tested.
Teuchies, Martyn; Demanet, Jelle; Sidarus, Nura; Haggard, Patrick; Stevens, Michaël A; Brass, Marcel
The ability to make voluntary, free choices is fundamental to what it means to be human. A key brain region that is involved in free choices is the rostral cingulate zone (RCZ), which is part of the medial frontal cortex. Previous research has shown that activity in this brain region can be modulated by bottom-up information while making free choices. The current study extends those findings, and shows, for the first time, that activation in the RCZ can also be modulated by subliminal information. We used a subliminal response priming paradigm to bias free and cued choices. We observed more activation in the RCZ when participants made a choice that went against the prime's suggestion, compared to when they chose according to the prime. This shows that the RCZ plays an important role in overcoming externally-triggered conflict between different response options, even when the stimuli triggering this conflict are not consciously perceived. Our results suggest that an important mechanism of endogenous action in the RCZ may therefore involve exerting an internally-generated action choice against conflicting influences, such as external sensory evidence. We further found that subliminal information also modulated activity in the anterior insula and the supramarginal gyrus.
Meier, Michael L.; Stämpfli, Phillipp; Vrana, Andrea; Humphreys, Barry K.; Seifritz, Erich; Hotz-Boendermaker, Sabina
In most individuals suffering from chronic low back pain, psychosocial factors, specifically fear avoidance beliefs (FABs), play central roles in the absence of identifiable organic pathology. On a neurobiological level, encouraging research has shown brain system correlates of somatic and psychological factors during the transition from (sub) acute to chronic low back pain. The characterization of brain imaging signatures in pain-free individuals before any injury will be of high importance regarding the identification of relevant networks for low back pain (LBP) vulnerability. Fear-avoidance beliefs serve as strong predictors of disability and chronification in LBP and current research indicates that back pain related FABs already exist in the general and pain-free population. Therefore, we aimed at investigating possible differential neural functioning between high- and low fear-avoidant individuals in the general population using functional magnetic resonance imaging. Results revealed that pain-free individuals without a history of chronic pain episodes could be differentiated in amygdala activity and connectivity to the pregenual anterior cingulate cortex by their level of back pain related FABs. These results shed new light on brain networks underlying psychological factors that may become relevant for enhanced disability in a future LBP episode. PMID:26257635
Narushima, Kenji; McCormick, Laurie; Yamada, Throu; Thatcher, Robert; Robinson, Robert G.
Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for depression. Increased metabolism in the anterior cingulate cortex (ACC) is a known predictor for antidepressant response. The authors assessed whether increased theta power within the ACC predicts rTMS response in participants with vascular depression. Sixty-five participants were randomized to active or sham rTMS. Outcome was assessed using the Hamilton Depression Rating Scale. Electroencephalography was obtained, and comparisons were made among each group with a normative database using low-resolution electromagnetic tomography. Results suggest that vascular depression participants respond well to rTMS and that increased low-theta power in the subgenual ACC predicts response to rTMS. PMID:20160213
Dharmaratne, Nuwan; Glendining, Kelly A.; Young, Timothy R.; Tran, Heidi; Sawatari, Atomu; Leamey, Catherine A.
Background The alignment of ipsilaterally and contralaterally projecting retinal axons that view the same part of visual space is fundamental to binocular vision. While much progress has been made regarding the mechanisms which regulate contralateral topography, very little is known of the mechanisms which regulate the mapping of ipsilateral axons such that they align with their contralateral counterparts. Results Using the advantageous model provided by the mouse retinocollicular pathway, we have performed anterograde tracing experiments which demonstrate that ipsilateral retinal axons begin to form terminal zones (TZs) in the superior colliculus (SC), within the first few postnatal days. These appear mature by postnatal day 11. Importantly, TZs formed by ipsilaterally-projecting retinal axons are spatially offset from those of contralaterally-projecting axons arising from the same retinotopic location from the outset. This pattern is consistent with that required for adult visuotopy. We further demonstrate that a member of the Ten-m/Odz/Teneurin family of homophilic transmembrane glycoproteins, Ten-m3, is an essential regulator of ipsilateral retinocollicular topography. Ten-m3 mRNA is expressed in a high-medial to low-lateral gradient in the developing SC. This corresponds topographically with its high-ventral to low-dorsal retinal gradient. In Ten-m3 knockout mice, contralateral ventrotemporal axons appropriately target rostromedial SC, whereas ipsilateral axons exhibit dramatic targeting errors along both the mediolateral and rostrocaudal axes of the SC, with a caudal shift of the primary TZ, as well as the formation of secondary, caudolaterally displaced TZs. In addition to these dramatic ipsilateral-specific mapping errors, both contralateral and ipsilateral retinocollicular TZs exhibit more subtle changes in morphology. Conclusions We conclude that important aspects of adult visuotopy are established via the differential sensitivity of ipsilateral and
Remondes, Miguel; Wilson, Matthew A
Interactions between cortex and hippocampus are believed to play a role in the acquisition and maintenance of memories. Distinct types of coordinated oscillatory activity, namely at theta frequency, are hypothesized to regulate information processing in these structures. We investigated how information processing in cingulate cortex and hippocampus relates to cingulate-hippocampus coordination in a behavioral task where rats choose from four possible trajectories according to a sequence. We found that the accuracy with which cingulate and hippocampal populations encode individual trajectories changes with the pattern of cingulate-hippocampal theta coherence, over the course of a trial. Initial theta coherence at ∼8Hz during trial onsets lowers by ∼1Hz as animals enter decision stages. At these stages, hippocampus precedes cingulate in processing increased amounts of task-relevant information. We hypothesize that lower theta frequency coordinates the integration of hippocampal contextual information by cingulate neuronal populations, to inform choices in a task-phase dependent manner. PMID:24239123
Baldissera, Fausto; Borroni, Paola; Cavallari, Paolo; Cerri, Gabriella
Excitability of the H-reflex in the relaxed flexor carpi radialis (FCR) muscle was tested during voluntary oscillations of the ipsilateral foot at five evenly spaced delays during a 600 ms cycle. In some experiments the H-reflex was conditioned by transcranial magnetic stimulation (TMS). With the hand prone, the amplitude of the FCR H-reflex was modulated sinusoidally with the same period as the foot oscillation, the modulation peak occurring in coincidence with contraction of the foot plantar-flexor soleus and the trough during contraction of the extensor tibialis anterior. When the H-reflex was facilitated by TMS at short latency (conditioning-test interval: -2 to -3.5 ms), the modulation was larger than that occurring with an unconditioned reflex of comparable size. This suggests that both the peripheral and the corticospinal components of the facilitated response were modulated in parallel. When the H-reflex was tested 40-60 ms after conditioning, i.e. during the cortical "silent period" induced by TMS, no direct effect was produced on the reflex size but the foot-associated modulation was deeply depressed. These results suggest that the reflex modulation may depend on activity fluctuations in the cortical motor area innervating the forearm motoneurones. It is proposed that when the foot is rhythmically oscillated, along with the full activation of the foot cortical area a simultaneous lesser co-activation of the forearm area produces a subliminal cyclic modulation of cervical motoneurones excitability. Should the two limbs be moved together, the time course of this modulation would favour isodirectional movements of the prone hand and foot, indeed the preferential coupling observed when hand and foot are voluntarily oscillated.
Shinoura, Nobusada; Suzuki, Yuichi; Watanabe, Yasuko; Yamada, Ryozi; Tabei, Yusuke; Saito, Kuniaki; Yagi, Kazuo
Mirror therapy is effective in the rehabilitation of patients with hemiparesis, but its mechanism is not clear. In this study, a patient with brain tumor (patient 1) who underwent mirror therapy after surgery and showed drastic recovery of hand paresis, a patient with visual memory disturbance (patient 2), and five normal volunteers performed tasks related to mirror therapy in fMRI study. In patient 1 and all normal volunteers, right and left hand clenching with looking at a mirror (eye open) activated outside of cerebellum, while right and left hands clenching with eye closed activated inside of cerebellum. In patient 2, mirror therapy did not activate outside of cerebellum. In patient 1, and 3 out of 5 normal volunteers, the area of right (affected) M1 activated by right and left hands clenching with eye open was more than that by right and left hands clenching with eye closed, and that right M1 was activated by right hand clenching with eye open. In conclusion, mirror therapy facilitate the paresis of patients by activating ipsilateral M1 and outside of cerebellum, which is possibly related to visual memory function.
Otçu, Selçuk; Durakoğugil, Murat; Orer, Hakan S; Tanyel, Feridun C
The decrease in blood flow due to the activation of sympathetic system has been suggested to play a role in contralateral testicular deterioration associated with unilateral testicular torsion. Sympathetic nerve discharges (SND) from the genitofemoral nerve were evaluated before and during unilateral testicular torsion. Under urethane anesthesia, arterial blood pressure and SND from splanchnic and right genitofemoral nerves were recorded in 12 male Sprague-Dawley rats, 8 of which were included in subsequent analyses. After control recordings of basal discharges for 2 min the left testis was twisted 720 degrees counterclockwise, and recording was resumed for an additional 30 min. Changes in nerve activity were calculated by measuring the area under the autospectrum curve, and alterations were compared. Following testicular torsion no significant changes were obtained for splanchnic SND, but the amplitude of SND from contralateral genitofemoral nerve showed an overall increase of 21.20+/-7.03% in six rats. This increase lasted about 10-15 min and activities returned to pretorsion levels. In two other rats no significant change was observed in either splanchnic or genitofemoral SND. Ipsilateral testicular torsion results in a transient increase in genitofemoral SND. A possible autonomic reflex mechanism may exist, and it may be activated by noxious stimuli from contralateral side. This reflex mechanism may initiate a series of events that lead to the injury of contralateral testis.
Curran, A R; Kuo, K N; Lubicky, J P
Eight pediatric patients who underwent nine simultaneous ipsilateral femoral and tibial lengthenings with the Ilizarov external fixator were reviewed. The patient's demographics, diagnoses, corticotomy levels, mechanical axes, healing indices, amounts of lengthening, and complications were recorded. The patients' average age was 8 years 10 months (5 years 4 months-15 years 10 months) with an average follow-up of 49 months (30-88 months). The percentage of femoral lengthening averaged 16.7% (8-23%) with an average healing index of 28 days/cm (20-38 days/cm). The percentage of tibial lengthening averaged 18% (9.6-23.6%) with an average healing index of 29 days/cm (1940 days/cm). Four complications in three patients occurred as a direct result of the lengthening process. Three of the complications involved soft-tissue contractures, which were each successfully treated with one additional surgical procedure, whereas the fourth complication involved poor bone regeneration and required bone grafting and additional immobilization.
Romness, D W; Morrey, B F
Sixteen total knee arthroplasties performed between 1977 and 1985 in 13 patients with prior ipsilateral hip arthrodesis or ankylosis were studied to determine the preferred sequence and long-term follow-up of procedures in this clinical setting. Twelve of 16 underwent fusion takedown and total hip arthroplasty prior to knee replacement. The average age at total knee arthroplasty was 52.7 years and the average time from hip fusion to total knee arthroplasty was 36.3 years. Mean follow-up after total knee arthroplasty was 5.5 years (range, 2.3 to 10 years). The Hospital for Special Surgery knee score increased from a mean of 31.8 preoperatively to 72.2 after surgery. In patients who had conversion of the hip fusion prior to knee replacement, knee scores were 28 before and 72.5 after both procedures. Patients who retained their hip fusion had mean scores of 43.5 and 72.1, respectively. None of the knees has been removed and 14 of 16 had no pain at last follow-up. One had mild pain and one had moderate pain attributed to pes anserine bursitis. Although the numbers are small, this experience reveals that takedown of the fusion with total hip arthroplasty is an effective technique before performing the knee replacement. Though successful in some instances, the experience is too small to show that if hip fusion is in good position, knee replacement without fusion takedown is acceptable.
Botticelli, A R; Villani, M; Angiari, P; Peserico, L
A case of meningeal melanocytoma of the left Meckel's cave associated with ipsilateral Ota's nevus in a 43-year-old woman, was studied by light and electron microscopy. The cells of the tumor were characterized by the presence of dendritic cytoplasmic processes, melanosomes and premelanosomes; hence, they were deemed as neoplastic melanocytes. Moreover, the tumor was lacking in histologic and ultrastructural features of pigmented meningioma, melanotic Schwannoma and primary meningeal melanoma. The prolonged clinical course was different from primary and metastatic malignant melanomas of the meninges. The best treatment appears to be radical excision, when possible; otherwise, the local or partial enucleation followed by radiation therapy has been found to be the best curative to date. On the whole, meningeal melanocytoma cannot be considered as entirely benign, given its morphologic patterns that resemble those of uveal melanoma, and its potential for recurrence. The association of this tumor with Ota's nevus is referred to as having a common origin from an arrested migration of melanoblasts at different stages.
Marcucci, Florencia; Cerullo, Isadora
The increasing availability of transcriptomic technologies within the last decade has facilitated high-throughput identification of gene expression differences that define distinct cell types as well as the molecular pathways that drive their specification. The retinal projection neurons, retinal ganglion cells (RGCs), can be categorized into distinct morphological and functional subtypes and by the laterality of their projections. Here, we present a method for purifying the sparse population of ipsilaterally projecting RGCs in mouse retina from their contralaterally projecting counterparts during embryonic development through rapid retrograde labeling followed by fluorescence-activated cell sorting. Through microarray analysis, we uncovered the distinct molecular signatures that define and distinguish ipsilateral and contralateral RGCs during the critical period of axonal outgrowth and decussation, with more than 300 genes differentially expressed within these two cell populations. Among the differentially expressed genes confirmed through in vivo expression validation, several genes that mark “immaturity” are expressed within postmitotic ipsilateral RGCs. Moreover, at least one complementary pair, Igf1 and Igfbp5, is upregulated in contralateral or ipsilateral RGCs, respectively, and may represent signaling pathways that determine ipsilateral versus contralateral RGC identity. Importantly, the cell cycle regulator cyclin D2 is highly expressed in peripheral ventral retina with a dynamic expression pattern that peaks during the period of ipsilateral RGC production. Thus, the molecular signatures of ipsilateral and contralateral RGCs and the mechanisms that regulate their differentiation are more diverse than previously expected. PMID:27957530
Herbet, Guillaume; Lafargue, Gilles; de Champfleur, Nicolas Menjot; Moritz-Gasser, Sylvie; le Bars, Emmanuelle; Bonnetblanc, François; Duffau, Hugues
Neurophysiological and neuroimaging studies including both patients with disorders of consciousness and healthy subjects with modified states of consciousness suggest a crucial role of the medial posteroparietal cortex in conscious information processing. However no direct neuropsychological evidence supports this hypothesis and studies including patients with restricted lesions of this brain region are almost non-existent. Using direct intraoperative electrostimulations, we showed in a rare patient that disrupting the subcortical connectivity of the left posterior cingulate cortex (PCC) reliably induced a breakdown in conscious experience. This acute phenomenon was mainly characterized by a transient behavioral unresponsiveness with loss of external connectedness. In all cases, when he regained consciousness, the patient described himself as in dream, outside the operating room. This finding suggests that functional integrity of the PPC connectivity is necessary for maintaining consciousness of external environment.
Ridout, Nathan; O'Carroll, Ronan E; Dritschel, Barbara; Christmas, David; Eljamel, Muftah; Matthews, Keith
Four patients that had received an anterior cingulotomy (ACING) and five patients that had received both an ACING and an anterior capsulotomy (ACAPS) as an intervention for chronic, treatment refractory depression were presented with a series of dynamic emotional stimuli and invited to identify the emotion portrayed. Their performance was compared with that of a group of non-surgically treated patients with major depression (n=17) and with a group of matched, never-depressed controls (n=22). At the time of testing, four of the nine neurosurgery patients had recovered from their depressive episode, whereas five remained depressed. Analysis of emotion recognition accuracy revealed no significant differences between depressed and non-depressed neurosurgically treated patients. Similarly, no significant differences were observed between the patients treated with ACING alone and those treated with both ACING and ACAPS. Comparison of the emotion recognition accuracy of the neurosurgically treated patients and the depressed and healthy control groups revealed that the surgically treated patients exhibited a general impairment in their recognition accuracy compared to healthy controls. Regression analysis revealed that participants' emotion recognition accuracy was predicted by the number of errors they made on the Stroop colour-naming task. It is plausible that the observed deficit in emotion recognition accuracy was a consequence of impaired attentional control, which may have been a result of the surgical lesions to the anterior cingulate cortex.
Gulick, Danielle; Gould, Thomas J
The current study examined the effects of nicotine infusion into the dorsal hippocampus or anterior cingulate on fear conditioning and on ethanol-induced deficits in fear conditioning, and whether these effects involved receptor activation or inactivation. Conditioning consisted of two white noise (30 s, 85 dB)-foot-shock (2 s, 0.57 mA) pairings. Saline or ethanol was administered to C57BL/6 mice 15 min before training and saline or nicotine was administered 5 min before training or before training and testing. The ability of the high-affinity nicotinic acetylcholinergic receptor (nAChR) antagonist dihydro-beta-erythroidine (DHbetaE) to modulate the effects of ethanol and nicotine was also tested; saline or DHbetaE was administered 25 (injection) or 15 (infusion) minutes before training or before training and testing. Infusion of nicotine into the hippocampus enhanced contextual fear conditioning but had no effect on ethanol-induced learning deficits. Infusion of nicotine into the anterior cingulate ameliorated ethanol-induced deficits in contextual and cued fear conditioning but had no effect on learning in ethanol-naive mice. DHbetaE blocked the effects of nicotine on ethanol-induced deficits; interestingly, DHbetaE alone and co-administration of subthreshold doses of DHbetaE and nicotine also ameliorated ethanol-induced deficits but failed to enhance learning. Finally, DHbetaE failed to ameliorate ethanol-induced deficits in beta2 nAChR subunit knockout mice. These results suggest that nicotine acts in the hippocampus to enhance contextual learning, but acts in the cingulate to ameliorate ethanol-induced learning deficits through inactivation of high-affinity beta2 subunit-containing nAChRs.
Weis, S; Llenos, I C; Sabunciyan, S; Dulay, J R; Isler, L; Yolken, R; Perron, H
The human endogenous retrovirus (HERV)-W multicopy family was identified in human DNA from the previously characterized multiple sclerosis associated retroviral element (MSRV). Upregulation of the HERV-W POL has been reported in cerebrospinal fluid of patients with schizophrenia. The expression of capsid (GAG) protein of HERV-W was studied by immunohistochemistry and western blotting in postmortem brain tissue of the anterior cingulate cortex and hippocampal formation of normal controls and of patients with schizophrenia, bipolar disorder and major depression. A physiological expression of GAG protein was detected in neurons as well as astroglial cells in normal brain both in the anterior cingulate cortex and in the hippocampal formation. There was a statistically significant reduction of this expression in neurons and astroglial cells in brains from individuals with schizophrenia, major depression, and bipolar disorder. The results from the present study confirm that GAG protein encoded by the HERV-W multicopy gene family is expressed in cells of the central nervous system under normal conditions. Our findings of a cell type-, brain region- and disease-specific reduced expression in schizophrenia, major depression, and bipolar disorder are compatible with a pathophysiological role of HERVs in human brain disorders. The causes and biological consequences of this differential regulation will be the subject of further investigations.
Subcortical projections to the anterior thalamic nuclei were studied in the rat, with special reference to projections from the mammillary nuclei, by retrograde and anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase. The medial mammillary nucleus (MM) projects predominantly ipsilaterally to the entire anterior thalamic nuclei, whereas the lateral mammillary nucleus projects bilaterally to the anterodorsal nucleus (AD) of the anterior thalamic nuclei. A topographic relationship was recognized between the MM and the anterior thalamic nuclei. The dorsal region of the pars mediana of the MM projects to the interanteromedial nucleus (IAM), whereas the ventral region projects to the rostral part of the anteromedial nucleus (AM). The dorsal and the ventral regions of the pars medialis project to the dorsomedial part of the AM at its caudal and rostral levels, respectively. The dorsomedial region of the pars lateralis projects to the ventral AM. The ventrolateral region of the pars lateralis projects to the ventral part of the anteroventral nucleus (AV) in such a manner that rostral cells project rostrally and caudal cells project caudally. The pars basalis projects predominantly ipsilaterally to the dorsolateral AV and bilaterally to the AD. The rostrolateral region of the pars posterior projects to the lateral AV, whereas the medial and the caudal regions of the pars posterior project to the dorsomedial AV. The rostrodorsal part of the nucleus reticularis thalami was found to project to the anterior thalamic nuclei; cells located rostrally in this part project to the IAM and AM, whereas cells located caudodorsally project to the AV and AD. The laterodorsal tegmental nucleus projects predominantly ipsilaterally to the AV, especially to its dorsolateral part. The present study demonstrates that subdivisions of the subcortical structures are connected to the subnuclei of the anterior thalamic nuclei, with a clear-cut topography arranged in
Forer, Boaz; Hui, Ng Yuk; Sethi, Dharmbir Singh
A 50-year-old Chinese man presented with rapidly progressive unilateral ophthalmoplegia and then an ipsilateral afferent pupil defect. CT and MRI revealed a mass centered in the anterior clinoid process causing bone destruction and showing high T1 and T2 signal intensity indicative of mucosal protein secretion. These imaging features suggested a mucocele, which may have resulted from sequestration of a clinoidal extension of the sphenoid sinus. The sphenoid sinus was opened via an image-guided endoscopic approach, and the lesion incised. There were no complications. The ophthalmoplegia and afferent pupil defect had completely resolved within 1 week of surgery. This is the eighth reported case of anterior clinoidal mucocele, a rare cause of ophthalmoplegia or optic neuropathy. Advances in endoscopic instrumentation, navigation systems, and intraoperative imaging have reduced the operative risk and made the endoscopic approach a feasible and safer alternative to open surgery for this condition.
Corradi-Dell'Acqua, Corrado; Tusche, Anita; Vuilleumier, Patrik; Singer, Tania
The anterior insula (AI) and mid-anterior cingulate cortex (mACC) have repeatedly been implicated in first-hand and vicarious experiences of pain, disgust and unfairness. However, it is debated whether these regions process different aversive events through a common modality-independent code, reflecting the shared unpleasantness of the experiences or through independent modality-specific representations. Using functional magnetic resonance imaging, we subjected 19 participants (and 19 confederates) to equally unpleasant painful and disgusting stimulations, as well as unfair monetary treatments. Multivoxel pattern analysis identified modality-independent activation maps in the left AI and mACC, pointing to common coding of affective unpleasantness, but also response patterns specific for the events' sensory properties and the person to whom it was addressed, particularly in the right AI. Our results provide evidence of both functional specialization and integration within AI and mACC, and support a comprehensive role of this network in processing aversive experiences for self and others. PMID:26988654
Soares, Célia A; Mason, Carol A
During development of the mammalian eye, the first retinal ganglion cells (RGCs) that extend to the brain are located in the dorsocentral (DC) retina. These RGCs extend to either ipsilateral or contralateral targets, but the ipsilateral projections do not survive into postnatal periods. The function and means of disappearance of the transient ipsilateral projection are not known. We have followed the course of this transient early ipsilateral cohort of RGCs, paying attention to how far they extend, whether they enter targets and if so, which ones, and the time course of their disappearance. The DC ipsilateral RGC axons were traced using DiI labeling at E13.5 and E15.5 to compare the proportion of ipsi- versus contralateral projections during the first period of growth. In utero electroporation of E12.5 retina with GFP constructs was used to label axons that could be visualized at succeeding time points into postnatal ages. Our results show that the earliest ipsilateral axons grow along the cellular border of the brain, and are segregated from the laterally positioned contralateral axons from the same retinal origin. In agreement with previous reports, although many early RGCs extend ipsilaterally, after E16 their number rapidly declines. Nonetheless, some ipsilateral axons from the DC retina enter the superior colliculus and arborize minimally, but very few enter the dorsal lateral geniculate nucleus and those that do extend only short branches. While the mechanism of selective axonal disappearance remains elusive, these data give further insight into establishment of the visual pathways.
Kose, O; Durakbasa, M O; Islam, N C
Elbow dislocation associated with both ipsilateral radial and ulnar shaft fractures is a rare pattern of injury, although it is common for elbow dislocation and forearm fractures to occur separately. We report a case of an 80-year-old woman who had a posterolateral elbow dislocation and ipsilateral radial and ulnar shaft fractures and underwent closed reduction and plate fixation. She had an excellent outcome after 22 months of follow-up.
Soares, Célia A.; Mason, Carol A.
During development of the mammalian eye, the first retinal ganglion cells (RGCs) that extend to the brain are located in the dorsocentral retina. These RGCs extend to either ipsilateral or contralateral targets, but the ipsilateral projections do not survive into postnatal periods. The function and means of disappearance of the transient ipsilateral projection are not known. We have followed the course of this transient early ipsilateral cohort of RGCs, paying attention to how far they extend, whether they enter targets and if so, which ones, and the time course of their disappearance. The dorsocentral ipsilateral RGC axons were traced using DiI labeling at E13.5 and 15.5 to compare the proportion of ipsi-versus contralateral projections during the first period of growth. In utero electroporation of E12.5 retina with GFP constructs was used to label axons that could be visualized at succeeding time points into postnatal ages. Our results show that the earliest ipsilateral axons grow along the cellular border of the brain, and are segregated from the laterally-postioned contralateral axons from the same retinal origin. In agreement with previous reports, although many early RGCs extend ipsilaterally, after E16 their number rapidly declines. Nonetheless, some ipsilateral axons from the dorsocentral retina enter the superior colliculus (SC) and arborize minimally, but very few enter the dorsal lateral geniculate nucleus (dLGN) and those that do extend only short branches. While the mechanism of selective axonal disappearance remains elusive, these data give further insight into establishment of the visual pathways. PMID:25788284
Jørgensen, Kjetil Nordbø; Psychol, Cand; Skjærvø, Ingeborg; Mørch-Johnsen, Lynn; Haukvik, Unn Kristin; Lange, Elisabeth Heffermehl; Melle, Ingrid; Andreassen, Ole Andreas; Agartz, Ingrid
Background Magnetic resonance imaging (MRI) studies show reduced cortical thickness in patients with schizophrenia and bipolar disorder. These subtle brain abnormalities may provide insight into illness mechanisms. However, environmental and lifestyle-related factors, such as cigarette smoking, may contribute to brain structure changes. Cigarette smoking is highly prevalent in patients with severe mental illness. In nonpsychiatric samples, smoking has been associated with reduced thickness in the anterior (ACC) and posterior cingulate cortices, the insular cortex (INS), the dorsolateral prefrontal cortex and the orbitofrontal cortex. Methods We examined MRI scans from patients with schizophrenia, other psychotic disorders or bipolar disorder and healthy controls using FreeSurfer. Results We included 506 patients (49% smokers) and 237 controls (20% smokers) in our study. We found reduced cortical thickness in the left rostral ACC and the left INS in smoking patients compared with nonsmoking patients, but this difference was not found among healthy controls. No dose–response relationship was found between amount of smoking and cortical thickness in these regions. Among patients, maps of thickness along the whole cortical surface revealed reduced insular thickness but no effects in other regions. Among healthy controls, similar analyses revealed increased age-related cortical thinning in the left occipital lobe among smokers compared with nonsmokers. Limitations The causal direction could not be determined owing to the cross-sectional design and lack of detailed data on smoking addiction and smoking history. Conclusion The effect of cigarette smoking should be considered in MRI studies of patients with severe mental illness. PMID:25672482
Liu, Xiaoyi; Wang, Xijin; Lai, Yunyao; Hao, Chuanxi; Chen, Lei; Zhou, Zhenyu; Yu, Xin; Hong, Nan
While several morphometric studies have postulated a critical contribution of the cingulate cortex (CC) to the pathophysiology of schizophrenia based on abnormalities in CC volume, other studies have been inconclusive. Most such studies have focused only on changes in cortical volume, whereas other morphometric parameters such as surface area and cortical thickness could be more relevant and possibly account for these discrepancies. Furthermore, factors such as antipsychotic drug use and treatment duration may also influence cortical morphology. To clarify the association between schizophrenia and CC deficits, we investigated morphometric abnormalities of the CC in antipsychotic drug (AD)-naïve chronic schizophrenia patients by comparing T1-weighted magnetic resonance images (T1WI-MRI) from patients (n=17) to healthy controls (n=17) using the surface-based morphometry program FreeSurfer. Partial correlations were examined between abnormal morphometric measures and both clinical variables and cognitive performance scores. Compared to healthy controls, drug-naïve schizophrenia patients exhibited significantly lower volumes in both left rostral anterior CC (rACC) and left posterior CC (PCC). These reductions in CC volume resulted from reduced surface area rather than reduced cortical thickness. There was also a significant relationship between left PCC volume and working memory in patients. No significant correlations were observed between CC volume and clinical variables. The results suggest that abnormalities in the CC as manifested by reduced surface area may contribute to cognitive dysfunction in schizophrenia. This article is part of a Special Issue entitled SI: PSC and the brain.
Vogt, B A; Derbyshire, S; Jones, A K
Neurosurgical and positron emission tomography (PET) human studies and animal electrophysiological studies show that part of the anterior cingulate cortex (ACC) is nociceptive. Since the contribution of the ACC to pain processing is poorly understood, this study employed PET and magnetic resonance (MR) image co-registration in grouped and individual cases to locate regions of altered relative regional cerebral blood flow (rCBF). Seven right-handed, neurologically intact males were subjects; each received neuropsychological and pain threshold testing. Subjects were scanned during infusion of H2[15O]: four randomized scans during innocuous heat stimulation to the back of the left hand and four scans during noxious but bearable heat to the same place. The averaged rCBF values during innocuous stimuli were subtracted from those during noxious stimuli and statistical parametric maps (SPMs) for the group were computed to identify regions of altered relative rCBF. Finally, single-subject PET images of elevated and reduced rCBF were co-registered with MR images and projected onto reconstructions of the medial surface of the hemisphere. The SPM analysis of the group showed one site with elevated rCBF in the midcingulate cortex and one in the perigenual cortex predominantly contralateral to the side of stimulation. There were bilateral sites of reduced rCBF in the cingulofrontal transitional cortex and in the posterior cingulate cortex (PCC). Co-registered PET and MR images for individuals showed that only one case had a single, large region of elevated rCBF, while the others had a number of smaller regions. Six cases had at least one significant elevation of rCBF in the right hemisphere that primarily involved area 24b'; five of these cases also had an elevation in area 32', while the seventh case had elevated rCBF in these areas in the left hemisphere. The rostral site of elevated rCBF in the group was at the border of areas 24/24' and areas 32/32' although most cases had
Keidel, James L.; Ing, Leslie P.; Horner, Aidan J.
It is well-established that active rehearsal increases the efficacy of memory consolidation. It is also known that complex events are interpreted with reference to prior knowledge. However, comparatively little attention has been given to the neural underpinnings of these effects. In healthy adults humans, we investigated the impact of effortful, active rehearsal on memory for events by showing people several short video clips and then asking them to recall these clips, either aloud (Experiment 1) or silently while in an MRI scanner (Experiment 2). In both experiments, actively rehearsed clips were remembered in far greater detail than unrehearsed clips when tested a week later. In Experiment 1, highly similar descriptions of events were produced across retrieval trials, suggesting a degree of semanticization of the memories had taken place. In Experiment 2, spatial patterns of BOLD signal in medial temporal and posterior midline regions were correlated when encoding and rehearsing the same video. Moreover, the strength of this correlation in the posterior cingulate predicted the amount of information subsequently recalled. This is likely to reflect a strengthening of the representation of the video's content. We argue that these representations combine both new episodic information and stored semantic knowledge (or “schemas”). We therefore suggest that posterior midline structures aid consolidation by reinstating and strengthening the associations between episodic details and more generic schematic information. This leads to the creation of coherent memory representations of lifelike, complex events that are resistant to forgetting, but somewhat inflexible and semantic-like in nature. SIGNIFICANCE STATEMENT Memories are strengthened via consolidation. We investigated memory for lifelike events using video clips and showed that rehearsing their content dramatically boosts memory consolidation. Using MRI scanning, we measured patterns of brain activity while
Hobbs, Nicola Z; Pedrick, Amy V; Say, Miranda J; Frost, Chris; Dar Santos, Rachelle; Coleman, Allison; Sturrock, Aaron; Craufurd, David; Stout, Julie C; Leavitt, Blair R; Barnes, Josephine; Tabrizi, Sarah J; Scahill, Rachael I
The impact of Huntington's disease neuropathology on the structure of the cingulate is uncertain, with evidence of both cortical enlargement and atrophy in this structure in early clinical disease. We sought to determine differences in cingulate volume between premanifest Huntington's disease and early Huntington's disease groups compared with controls using detailed manual measurements. Thirty controls, 30 subjects with premanifest Huntington's disease, and 30 subjects with early Huntington's disease were selected from the Vancouver site of the TRACK-HD study. Subjects underwent 3 Tesla magnetic resonance imaging and motor, cognitive, and neuropsychiatric assessment. The cingulate was manually delineated and subdivided into rostral, caudal, and posterior segments. Group differences in volume and associations with performance on 4 tasks thought to utilize cingulate function were examined, with adjustment for appropriate covariates. Cingulate volumes were, on average, 1.7 mL smaller in early Huntington's disease (P=.001) and 0.9 mL smaller in premanifest Huntington's disease (P=.1) compared with controls. Smaller volumes in subsections of the cingulate were associated with impaired recognition of negative emotions (P=.04), heightened depression (P=.009), and worse visual working memory performance (P=.01). There was no evidence of associations between volume and ability on a performance-monitoring task. This study disputes previous findings of enlargement of the cingulate cortex in Huntington's disease and instead suggests that the cingulate undergoes structural degeneration during early Huntington's disease with directionally consistent, nonsignificant differences seen in premanifest Huntington's disease. Cingulate atrophy may contribute to deficits in mood, emotional processing, and visual working memory in Huntington's disease.
... Week of Healthy Breakfasts Shyness Anterior Cruciate Ligament (ACL) Injuries KidsHealth > For Teens > Anterior Cruciate Ligament (ACL) ... and Recovery Coping With an ACL Injury About ACL Injuries A torn anterior cruciate ligament (ACL) is ...
Miliam, Palle B; Basse, Peter N
Anterior tarsal tunnel syndrome is a rare entrapment neuropathy of the deep peroneal nerve beneath the extensor retinaculum of the ankle. It may be rare because it is underrecognized clinically.We present a case regarding a 29-year-old man, drummer, who for one and a half year experienced clinical symptoms of anterior tarsal tunnel syndrome. A surgical decompression of the anterior tarsal tunnel was performed, and at the check three months later the symptoms where gone. One year after, there were still no symptoms.
Monteagudo, B; Cabanillas, M; de las Heras, C; Cacharrón, J M
Anterior cervical hypertrichosis was described by Trattner and coworkers in 1991. It consists of a
Yao, Ning; Qiao, Hui; Shu, Ning; Wang, Zide; Chen, Daxing; Wu, Liang; Deng, Xiaofeng; Xu, Yulun
A remarkable preservation of sensorimotor function is observed in patients with refractory epilepsy who were treated by hemispherectomy. Cortical regions in the remaining hemisphere or contralateral subcortical region contribute to the residual sensorimotor function. Somatosensory evoked field (SEF) is used to investigate the residual sensory function in hemispherectomized patients. The SEFs are usually recorded with magnetoencephalography (MEG). The objective is to investigate the ipsilateral cortical regions associated with residual sensory function in hemispherectomized patients using somatosensory evoked field techniques. Six patients with anatomical hemispherectomy were included. Ipsilateral and contralateral sensory functions were assessed by physical examination. Somatosensory evoked fields to electrical stimulation of the bilateral median nerves were recorded by MEG in the hemispherectomized patients and six control subjects. The stimulus intensity was adjusted to the minimum threshold that elicited a thumb twitch. The presumed neuronal source was identified as the equivalent current dipole. Six patients demonstrated different degrees of residual sensory function. Three patients had somatosensory evoked field activation in the ipsilateral cortex upon electrical stimulation of the hemiplegic hand. In these patients the locations of the ipsilateral sensorimotor cortex activation were in the primary somatosensory cortex (SI). The latency of the reliable somatosensory evoked field after stimulation of the median nerve was significantly longer for responses from the hemiplegic side compared with responses to stimulation of the median nerve from the normal side. In conclusion, ipsilateral sensory function has a time-locked relation to the cortical electromagnetic activation in the SI area of hemispherectomized patients.
Liu, Xiuping; Yan, Yuchu; Wang, Yalong; Yan, Jun
Background Cortical neurons implement a high frequency-specific modulation of subcortical nuclei that includes the cochlear nucleus. Anatomical studies show that corticofugal fibers terminating in the auditory thalamus and midbrain are mostly ipsilateral. Differently, corticofugal fibers terminating in the cochlear nucleus are bilateral, which fits to the needs of binaural hearing that improves hearing quality. This leads to our hypothesis that corticofugal modulation of initial neural processing of sound information from the contralateral and ipsilateral ears could be equivalent or coordinated at the first sound processing level. Methodology/Principal Findings With the focal electrical stimulation of the auditory cortex and single unit recording, this study examined corticofugal modulation of the ipsilateral cochlear nucleus. The same methods and procedures as described in our previous study of corticofugal modulation of contralateral cochlear nucleus were employed simply for comparison. We found that focal electrical stimulation of cortical neurons induced substantial changes in the response magnitude, response latency and receptive field of ipsilateral cochlear nucleus neurons. Cortical stimulation facilitated auditory response and shortened the response latency of physiologically matched neurons whereas it inhibited auditory response and lengthened the response latency of unmatched neurons. Finally, cortical stimulation shifted the best frequencies of cochlear neurons towards those of stimulated cortical neurons. Conclusion Our data suggest that cortical neurons enable a high frequency-specific remodelling of sound information processing in the ipsilateral cochlear nucleus in the same manner as that in the contralateral cochlear nucleus. PMID:21124980
Liu, Fubing; Jiang, Chun
The aim of this study was to evaluate the risk factors between ipsilateral and contralateral reherniation and to compare the effectiveness of miniopen transforaminal lumbar interbody fusion (TLIF) with unilateral fixation for each group. From November 2007 to December 2014, clinical and radiographic data of each group (ipsilateral or contralateral reherniation) were collected and compared. Functional assessment (Visual Analog Scale (VAS) score and Japanese Orthopaedic Association (JOA)) and radiographic evaluation (fusion status, disc height, lumbar lordosis (LL), and functional spine unit (FSU) angle) were applied to compare surgical effect for each group preoperatively and at final followup. MacNab questionnaire was applied to further evaluate the satisfactory rate after the discectomy and fusion. No difference except pain-free interval was found between ipsilateral and contralateral groups. There was a significant difference in operative time between two groups. No differences were found in clinical and radiographic data for assessment of surgical effect between two groups. The satisfactory rate was decreasing in both groups with time passing after discectomy. Difference in pain-free interval may be a distinction for ipsilateral and contralateral reherniation. Miniopen TLIF with unilateral pedicle screw fixation can be a recommendable way for single level reherniation regardless of ipsilateral or contralateral reherniation. PMID:27885358
Chen, Ying-Yi; Huang, Hsu-Kai; Chang, Hung; Lee, Shih-Chun
Background Preventive surgery for contralateral recurrence of primary spontaneous pneumothorax (PSP) remains controversial and few studies discussed both ipsilateral and contralateral recurrences simultaneously. Thus, we aimed to identify the predictors of ipsilateral and contralateral PSP recurrence and to review literatures on the association of blebs/bullae on HRCT with PSP recurrence. Methods We retrospectively reviewed consecutive patients who were treated at our hospital for first recurrence of PSP between January 2001 and December 2005. Results This study included 553 patients who were followed-up for a mean period of 124 months. Ipsilateral and contralateral recurrence of PSP developed in 19.35% and 15.19% of patients, respectively. In the Cox regression analysis, the only significant predictors were no video-assisted thoracoscopic surgery (VATS) bullectomy (OR: 16.629, P<0.001) for ipsilateral recurrence, and the presence of blebs/bullae on HRCT (OR: 3.215, P=0.024) and low BMI (<18.5 kg/m2) (OR: 1.560, P=0.045) for contralateral recurrence. Conclusions VATS bullectomy was a strong independent predictor for prevention of ipsilateral PSP recurrence. Patients with contralateral blebs or bullae on chest HRCT or those with low BMI may be candidates for preventive VATS bullectomy to avoid recurrences and possible complications. PMID:28066601
recorded electroencephalography from 32 combat veterans with mTBI—17 of whom were also comorbid for PTSD (mTBIþPTSD) and 15 without PTSD (mTBI-only...C.F., Falkenstein, M., Herrmann, C.S., 2013. Electroencephalography of response inhibition tasks: functional net- works and cognitive contributions...particularly affected by PTSD. To further test this hypothesis, we recorded electroencephalography from 32 combat veterans with mTBI—17 of whom were
Thompson, Peter M.; Cruz, Dianne A.; Fucich, Elizabeth A.; Olukotun, Dianna Y.; Takahashi, Masami; Itakura, Makoto
SNAP-25 is a neurotransmitter vesicular docking protein which has been associated with brain disorders such as attention deficit hyperactivity disorder, bipolar disorder and schizophrenia. In this project, we were interested if clinical factors are associated with differential SNAP-25 expression. We examined the SNAP-25 isoform mRNA and protein levels in postmortem cortex Brodmann's area 9 (BA9) and BA24 (n = 29). Subjects were divided by psychiatric diagnosis, clinical variables including mood state in the last week of life and lifetime impulsiveness. We found affected subjects with a diagnosis of alcohol use disorder (AUD) had a lower level of SNAP-25b BA24 protein compared to those without AUD. Hispanic subjects had lower levels of SNAP-25a, b and BA9 mRNA than Anglo-American subjects. Subjects who smoked had a total pan (total) SNAP-25 BA9/BA24 ratio. Subjects in the group with a low level of anxious-psychotic symptoms had higher SNAP-25a BA24 mRNA compared to normal controls, and both the high and low symptoms groups had higher pan (total) SNAP-25 BA9/BA24 ratios than normal controls. These data expand our understanding of clinical factors associated with SNAP-25. They suggest that SNAP-25 total and isoform levels may be useful biomarkers beyond limited neurological and psychiatric diagnostic categories. PMID:27606314
Mirzadeh, Zaman; Sanai, Nader; Lawton, Michael T
The authors introduce the azygos anterior cerebral artery (ACA) bypass as an option for revascularizing distal ACA territories, as part of a strategy to trap giant anterior communicating artery (ACoA) aneurysms. In this procedure, the aneurysm is exposed with an orbitozygomatic-pterional craniotomy and distal ACA vessels are exposed with a bifrontal craniotomy. The uninvolved contralateral A(2) segment of the ACA serves as a donor vessel for a short radial artery graft. The contralateral pericallosal artery (PcaA) and the callosomarginal artery (CmaA) are connected to the graft in the interhemispheric fissure using the double reimplantation technique. Three anastomoses create an azygos system supplying the entire ACA territory, enabling the surgeon to trap the aneurysm incompletely. Retrograde flow from the CmaA supplies the ipsilateral recurrent artery of Heubner, and the aneurysm lumen thromboses. The azygos bypass was successfully performed to treat a 47-year-old woman with a giant, thrombotic ACoA aneurysm supplied by the A(1) segment of the left ACA, with left PcaA and CmaA originating from the aneurysm base. The authors conclude that the azygos ACA bypass is a novel option for revascularizing PcaA and CmaA, as part of the overall treatment of giant ACoA aneurysms.
Gainotti, G; Giustolisi, L; Nocentini, U
To explain the prevalence of unilateral spatial neglect in patients with right brain damage, Heilman et al have suggested that the attentional neurons of the right parietal lobe might have bilateral receptive fields, whereas the homologous cells of the left hemisphere would have strictly contralateral receptive fields. One implication of this theory is that patients with right brain damage should show a prevalence of disorders of visual attention not only in the half space contralateral to the damaged hemisphere, but also in the ipsilateral one. To check this theory, 50 control subjects, 102 right and 125 left brain-damaged patients were given a drawing completion task in which patients were requested to complete the missing parts of a star, a cube and a house. Omissions of lines lying on the sides of the models contralateral and ipsilateral to the damaged hemisphere were taken separately into account. Results did not confirm the hypothesis, since right brain-damaged patients failed to complete the contralateral sides of the models much more frequently than patients with left brain injury, but no difference was found between the two hemispheric groups when ipsilateral disorders of visual attention were taken into account. Furthermore, no correlation was found between omissions of lines lying on the sides of the models contralateral and ipsilateral to the damaged hemisphere. This finding suggests that contralateral and ipsilateral disorders of visual attention are not due to the same mechanism in right brain-damaged patients. The alternative hypothesis viewing ipsilateral disorders as resulting from a widespread lowering of general attention (and only contralateral neglect reflecting a specific disorder of visual attention) was supported by results obtained on a verbal memory test, used to evaluate the general cognitive and attention level of the patients. Patients with clear-cut ipislateral inattention obtained very low scores on this test, whereas patients with
Gainotti, G; Giustolisi, L; Nocentini, U
To explain the prevalence of unilateral spatial neglect in patients with right brain damage, Heilman et al have suggested that the attentional neurons of the right parietal lobe might have bilateral receptive fields, whereas the homologous cells of the left hemisphere would have strictly contralateral receptive fields. One implication of this theory is that patients with right brain damage should show a prevalence of disorders of visual attention not only in the half space contralateral to the damaged hemisphere, but also in the ipsilateral one. To check this theory, 50 control subjects, 102 right and 125 left brain-damaged patients were given a drawing completion task in which patients were requested to complete the missing parts of a star, a cube and a house. Omissions of lines lying on the sides of the models contralateral and ipsilateral to the damaged hemisphere were taken separately into account. Results did not confirm the hypothesis, since right brain-damaged patients failed to complete the contralateral sides of the models much more frequently than patients with left brain injury, but no difference was found between the two hemispheric groups when ipsilateral disorders of visual attention were taken into account. Furthermore, no correlation was found between omissions of lines lying on the sides of the models contralateral and ipsilateral to the damaged hemisphere. This finding suggests that contralateral and ipsilateral disorders of visual attention are not due to the same mechanism in right brain-damaged patients. The alternative hypothesis viewing ipsilateral disorders as resulting from a widespread lowering of general attention (and only contralateral neglect reflecting a specific disorder of visual attention) was supported by results obtained on a verbal memory test, used to evaluate the general cognitive and attention level of the patients. Patients with clear-cut ipislateral inattention obtained very low scores on this test, whereas patients with
Wong, Yuen Shan; Tam, Yuk Him; Pang, Kristine Kit Yi
We report on two children aged 2 and 6 years, who underwent laparoscopic ipsilateral ureteroureterostomy for their renal duplex anomalies. Both patients had complete duplex and were investigated by ultrasound, micturating cystourethrogram, magnetic resonance urography, and radioisotope scan. One patient had high-grade vesicoureteral reflux to lower moiety complicated with recurrent urinary tract infections, while the other had obstruction to upper moiety due to ectopic ureter. The pathological moieties of both patients were functional. Both patients underwent laparoscopic ipsilateral ureteroureterostomy uneventfully without any intraoperative complications. Postoperative imagings confirmed successful outcomes after surgery. PMID:27014651
Coulier, Julie; Rommel, Denis; Boschi, Antonella
Background Horner syndrome (HS), also known as Claude-Bernard-Horner syndrome or oculosympathetic palsy, comprises ipsilateral ptosis, miosis, and facial anhidrosis. Case Report We report herein the case of a 67-year-old man who presented with congenital HS associated with ipsilateral hypoplasia of the internal carotid artery (ICA), as revealed by heterochromia iridis and confirmed by computed tomography (CT). Conclusions CT evaluation of the skull base is essential to establish this diagnosis and distinguish aplasia from agenesis/hypoplasia (by the absence or hypoplasia of the carotid canal) or from acquired ICA obstruction as demonstrated by angiographic CT. PMID:25749818
Weintraub, S; Mesulam, M M
Tasks based on visuomotor scanning and tactile exploration were used to quantitate neglect behavior in patients with unilateral brain damage and in normal control subjects. The results confirm previous observations that contralateral neglect is markedly more severe following right-hemisphere injury and that it is independent of the modality of sensory input or motor output. In addition, patients with right-hemisphere injury also showed multimodal neglect for targets in the hemisphere ipsilateral to the brain lesion. The emergence of both contralateral and ipsilateral neglect in these patients strongly supports a model of right-hemispheric dominance for the distribution of attention within the extrapersonal space.
Moore, M. R.; Garfin, S. R.; Hargens, A. R.
A 26-year-old man presented with ipsilateral femur and ankle fractures. The patient was treated with interlocking nail of his femur fracture, followed by open reduction and internal fixation of his ankle fracture under tourniquet control. Postoperatively, the patient developed compartment syndrome of his thigh with elevated pressures, requiring decompressive fasciotomies. This case illustrates the possible complication of treating a femur fracture with intramedullary nailing and then immediately applying a tourniquet to treat an ipsilateral extremity fracture. Because of the complication with this patient, we feel the procedure should be staged, or a tourniquet should be avoided if possible.
Sanfilippo, Christian J.
Background/Purpose: To report a case of congenital retinal macrovessel associated with cystoid macular edema and an ipsilateral intracranial venous malformation. Methods: Case report. Results: A 58-year-old woman with decreased vision was found to have a congenital retinal venous macrovessel associated with cystoid macular edema because of tributary venous occlusion. The patient underwent neuroimaging and an ipsilateral venous malformation of the frontal lobe was discovered. Conclusion: Congenital retinal macrovessel can occasionally be complicated by vascular occlusion and macular edema. The authors report a case of congenital retinal macrovessel associated with an intracranial venous malformation. Clinicians should be aware of this potential association, and further studies are warranted. PMID:26421894
The organization of the projections from the retrosplenial cortex (Brodmann's area 29) to the anterior thalamic nuclei was examined in the rat with retrograde transport of the cholera toxin B subunit and anterograde transport of biotinylated dextran amine. Areas 29a and 29b project mainly ipsilaterally to the rostral two-thirds of the anteroventral nucleus, with area 29a projecting more rostrodorsally than area 29b. Area 29c projects bilaterally to the ventromedial part of the anteroventral nucleus. The projections from area 29c are organized in a topographic pattern such that the rostral area 29c projects to the caudoventral part of the anteroventral nucleus, whereas the caudal area 29c projects to the more rostrodorsal parts. Caudal area 29d projects mainly ipsilaterally to the rostrodorsal part of the anteromedial nucleus, and the rostral and dorsal parts of the anteroventral nucleus, whereas rostral area 29d projects bilaterally to the caudodorsal part of the anteromedial nucleus and the caudolateral part of the anteroventral nucleus. All the areas of the retrosplenial cortex provide sparse projections, mainly ipsilateral, to the anterodorsal nucleus, with a crude topographic pattern such that the rostrocaudal axis of the retrosplenial cortex corresponds to the caudorostral axis of the anterodorsal nucleus. The results indicate that each area of the retrosplenial cortex has a distinct projection field within the anterior thalamic nuclei. This suggests that each of these projections transmits distinct information that is important for complex memory and learning functions, e.g. discriminative avoidance learning and spatial memory.
Leonard, Christiana M; Towler, Stephen; Welcome, Suzanne; Chiarello, Christine
Many structural brain asymmetries accompany left hemisphere language dominance. For example, the cingulate sulcus is larger in the medial cortex of the right hemisphere, while the more dorsal paracingulate sulcus is larger on the left. The functional significance of these asymmetries is unknown because fMRI studies rarely attempt to localize activation to specific sulci, possibly due to difficulties in consistent sulcal identification. In medial cortex, for example, there are many regions of partial sulcal overlap where MRI images do not provide sufficient information to unambiguously distinguish a paracingulate sulcus from a displaced anterior cingulate segment. As large samples of postmortem material are rarely available for cytoarchitectural studies of sulcal variation, we have investigated the effect of variation in boundary and sulcal definition on paracingulate asymmetry in the MRI scans of 200 healthy adults (100 men, 100 women). Although women displayed a reliable asymmetry in the size of the paracingulate sulcus, regardless of boundary definition or technique, asymmetry was greatest when (1) the measurement was limited to the midcingulate region between the genu and the anterior commissure; and (2) the more dorsal of two overlapping sulci was always classified as a paracingulate sulcus (rather than as a displaced cingulate segment). The fact that paracingulate asymmetry is maximal in the midcingulate region suggests that this region may play a particular role in hemispheric specialization for language. Future work should investigate the structural and functional correlates of sulcal variation in this region.
Kontogeorgakos, Vasileios; Koutalos, Antonios; Hantes, Michael; Manoudis, Gregory; Badras, Leonidas; Malizos, Konstantinos
A novel technique for managing ruptured tibialis anterior tendon complicated by infection and tendon substance loss in a young adult is described. A two-stage reconstruction technique with a silicon tube and tendon autograft was performed. At first, after local control of the infection, scar excision and placement of a silicone tube was performed. Ten weeks later, ipsilateral hamstrings tendons were harvested and bridged the 7 cm tendon gap. Eighteen months later, the patient has excellent clinical and functional outcome.
Alkawadri, Rafeed; Gonzalez-Martinez, Jorge; Gaspard, Nicolas; Alexopoulos, Andreas V
Little is known about the propagation of seizures arising from the cingulate gyrus, as cingulate coverage with interhemispheric subdural electrodes is usually challenging and incomplete due to inherent anatomical and vascular limitations. We present a case of lesional mid-cingulate epilepsy confirmed by stereotactically implanted intracranial depth electrodes and subsequent surgical resection. Hypermotor symptomatology was seen during the first seven seconds of seizure onset while the seizure was still confined to the mid-cingulate gyrus contacts. The patient had brief contralateral clonic movements as seizure propagated to the primary motor cortex. There was a high concordance between the primary propagation contacts, as delineated by intracranial EEG, and the contacts, with higher coherence values in the connectivity matrix. Interestingly, cingulate-extra-cingulate connectivity and spread to the primary motor, premotor, and prefrontal cortex was seen preceding spread to other cingulate contacts, of which one was less than 15 mm from the onset contact. This report is one of a few published, documenting propagation of seizures arising from the mid-cingulate cortex. As illustrated by these data, hypermotor semiology correlated with direct activation of the cingulate cortex. Subsequent seizure propagation activated an extensive extra-cingulate rather than an intra-cingulate epileptogenic network. Interestingly, had the region of onset not sampled, the seizure onset would have appeared as non-localizing widespread rhythms over the fronto-parietal convexities. Further studies to explore the propagation of seizures arising from the cingulate gyrus and the physiological and pathological connectivity patterns within the cingulate gyrus in humans are needed, preferably using stereotactic implantation. Specific targets to be investigated are also discussed.
Obregon, Mateo; Shillcock, Richard
Recognition of a single word is an elemental task in innumerable cognitive psychology experiments, but involves unexpected complexity. We test a controversial claim that the human fovea is vertically divided, with each half projecting to either the contralateral or ipsilateral hemisphere, thereby influencing foveal word recognition. We report a…
Brand, N.; Bossema, E. R.; van Ommen, M.; Moll, F. L.; Ackerstaff, R. G. A.
We evaluated hemispheric functions ipsilateral to the side of carotid endarterectomy (CEA) in patients with a severe stenosis in the left or right carotid artery. Assessments took place 1 day before and 3 months after CEA. Only right-handed males were included. Nineteen patients underwent surgery of the left carotid artery and 17 of the right.…
Suzuki, Tomotaka; Higashi, Toshio; Takagi, Mineko; Sugawara, Kenichi
In this study, we investigated how ipsilateral motor cortex (M1) activation during unimanual hand movements and hemispheric asymmetry changed after motor skill learning. Eleven right-handed participants preformed a two-ball-rotation motor task with the right and the left hand, separately, in all experimental sessions. Before and after exercise sessions, the degree of ipsilateral M1 activation during brief execution of the motor task was measured as changes in the size of motor-evoked potentials (MEPs) of the thenar and the first dorsal interosseous muscle of the nontask hand using transcranial magnetic stimulation. Before exercise, MEPs of the nontask hand were significantly facilitated on both sides during the motor task. After exercise, facilitation of MEPs of the nontask hand during the motor task was significantly reduced for the right hand (thenar: P=0.014, first dorsal interosseous: P=0.022) but not for the left hand. We conclude that ipsilateral M1 activation, associated with a complex motor task, is first symmetrical in both hemispheres. However, on exercise, ipsilateral activation is reduced only in left M1, indicating a stronger learning-dependent modification of motor networks within the left hemisphere.
Barfod, G; Steen Jensen, J; Hansen, D; Larsen, E; Menck, H; Olsen, B; Rosenklint, A
In a series of 74 ipsilateral fractures of the femoral shaft in relation to hemi-arthroplasties, treatment by a cemented long-stem total hip replacement was found to be superior to conservative treatment or internal fixation without removal of the prosthesis. Acceptable clinical results were obtained in 89 per cent of these cases.
Dong, Da-Wei; Zhang, Yu-Sheng; Yang, Wan-Yong; Wang-Qin, Run-Qi; Xu, An-Ding; Ruan, Yi-Wen
Hyperphosphorylation of tau has been considered as an important risk factor for neurodegenerative diseases. It has been found also in the cortex after focal cerebral ischemia. The present study is aimed at investigating changes of tau protein expression in the ipsilateral thalamus remote from the primary ischemic lesion site after distal middle cerebral artery occlusion (MCAO). The number of neurons in the ventroposterior thalamic nucleus (VPN) was evaluated using Nissl staining and neuronal nuclei (NeuN) immunostaining. Total tau and phosphorylated tau at threonine 231 (p-T231-tau) and serine 199 (p-S199-tau) levels, respectively, in the thalamus were measured using immunostaining and immunoblotting. Moreover, apoptosis was detected with terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP-biotin nick-end labeling (TUNEL) assay. It was found that the numbers of intact neurons and NeuN(+) cells within the ipsilateral VPN were reduced significantly compared with the sham-operated group, but the levels of p-T231-tau and p-S199-tau in the ipsilateral thalamus were increased significantly in rats subjected to ischemia for 3 days, 7 days and 28 days. Furthermore, the number of TUNEL-positive cells was increased in the ipsilateral VPN at 7 days and 28 days after MCAO. Thus, hyperphosphorylated tau protein is observed in ipsilateral thalamus after focal cerebral infarction in this study. Our findings suggest that the expression of hyperphosphorylated tau protein induced by ischemia may be associated with the secondary thalamic damage after focal cortical infarction via an apoptotic pathway.
Lee, Percy; Eppinga, Wietse; Lagerwaard, Frank; Cloughesy, Timothy; Slotman, Benjamin; Nghiemphu, Phioanh L.; Wang, Pin-Chieh; Kupelian, Patrick; Agazaryan, Nzhde; Demarco, John; Selch, Michael T.; Steinberg, Michael; Kang, Jung Julie
Purpose: Cancer stem cells (CSCs) may play a role in the recurrence of glioblastoma. They are believed to originate from neural stem cells in the subventricular zone (SVZ). Because of their radioresistance, we hypothesized that high doses of radiation (>59.4 Gy) to the SVZ are necessary to control CSCs and improve progression-free survival (PFS) or overall survival (OS) in glioblastoma. Methods and Materials: 173 patients with glioblastoma pooled from 2 academic centers were treated with resection followed by chemoradiation therapy. The SVZ was segmented on computed tomography to calculate radiation doses delivered to the presumptive CSC niches. The relationships between high SVZ doses and PFS and OS were examined using Cox proportional hazards models. Five covariates were included to estimate their impact on PFS or OS: ipsilateral and contralateral SVZ doses, clinical target volume dose, age, and extent of resection. Results: Median PFS and OS were 10.4 and 19.6 months for the cohort. The mean ipsilateral SVZ, contralateral SVZ, and clinical target volume doses were 49.2, 35.2, and 60.1 Gy, respectively. Twenty-one patients who received high ipsilateral SVZ dose (>59.4 Gy) had significantly longer median PFS (12.6 vs 9.9 months, P=.042) and longer OS (25.8 vs 19.2 months, P=.173). On multivariate analysis, high radiation therapy doses to ipsilateral SVZ remained a statistically significant independent predictor of improved PFS but not of OS. The extent of surgery affected both PFS and OS on multivariate analysis. Conclusion: High radiation therapy doses to ipsilateral CSC niches are associated with improved PFS in glioblastoma.
Lecce, Francesca; Rotondaro, Francesca; Bonnì, Sonia; Carlesimo, Augusto; Thiebaut de Schotten, Michel; Tomaiuolo, Francesco; Doricchi, Fabrizio
Motivational valence plays a key role in orienting spatial attention. Nonetheless, clinical documentation and understanding of motivationally based deficits of spatial orienting in the human is limited. Here in a series of one group-study and two single-case studies, we have examined right brain damaged patients (RBD) with and without left spatial neglect in a spatial reward-learning task, in which the motivational valence of the left contralesional and the right ipsilesional space was contrasted. In each trial two visual boxes were presented, one to the left and one to the right of central fixation. In one session monetary rewards were released more frequently in the box on the left side (75% of trials) whereas in another session they were released more frequently on the right side. In each trial patients were required to: 1) point to each one of the two boxes; 2) choose one of the boxes for obtaining monetary reward; 3) report explicitly the position of reward and whether this position matched or not the original choice. Despite defective spontaneous allocation of attention toward the contralesional space, RBD patients with left spatial neglect showed preserved contralesional reward learning, i.e., comparable to ipsilesional learning and to reward learning displayed by patients without neglect. A notable exception in the group of neglect patients was L.R., who showed no sign of contralesional reward learning in a series of 120 consecutive trials despite being able of reaching learning criterion in only 20 trials in the ipsilesional space. L.R. suffered a cortical-subcortical brain damage affecting the anterior components of the parietal-frontal attentional network and, compared with all other neglect and non-neglect patients, had additional lesion involvement of the medial anterior cingulate cortex (ACC) and of the adjacent sectors of the corpus callosum. In contrast to his lateralized motivational learning deficit, L.R. had no lateral bias in the early phases of
Field, David T; Inman, Laura A; Li, Li
Previous studies have shown that the human posterior cingulate contains a visual processing area selective for optic flow (CSv). However, other studies performed in both humans and monkeys have identified a somatotopic motor region at the same location (CMA). Taken together, these findings suggested the possibility that the posterior cingulate contains a single visuomotor integration region. To test this idea we used fMRI to identify both visual and motor areas of the posterior cingulate in the same brains and to test the activity of those regions during a visuomotor task. Results indicated that rather than a single visuomotor region the posterior cingulate contains adjacent but separate motor and visual regions. CSv lies in the fundus of the cingulate sulcus, while CMA lies in the dorsal bank of the sulcus, slightly superior in terms of stereotaxic coordinates. A surprising and novel finding was that activity in CSv was suppressed during the visuomotor task, despite the visual stimulus being identical to that used to localize the region. This may provide an important clue to the specific role played by this region in the utilization of optic flow to control self-motion.
Veldhuizen, Maria G; Douglas, Danielle; Aschenbrenner, Katja; Gitelman, Darren R; Small, Dana M
Despite the importance of breaches of taste identity expectation for survival, its neural correlate is unknown. We used fMRI in 16 women to examine brain response to expected and unexpected receipt of sweet taste and tasteless/odorless solutions. During expected trials (70%), subjects heard "sweet" or "tasteless" and received the liquid indicated by the cue. During unexpected trials (30%), subjects heard sweet but received tasteless or they heard tasteless but received sweet. After delivery, subjects indicated stimulus identity by pressing a button. Reaction time was faster and more accurate after valid cuing, indicating that the cues altered expectancy as intended. Tasting unexpected versus expected stimuli resulted in greater deactivation in fusiform gyri, possibly reflecting greater suppression of visual object regions when orienting to, and identifying, an unexpected taste. Significantly greater activation to unexpected versus expected stimuli occurred in areas related to taste (thalamus, anterior insula), reward [ventral striatum (VS), orbitofrontal cortex], and attention [anterior cingulate cortex, inferior frontal gyrus, intraparietal sulcus (IPS)]. We also observed an interaction between stimulus and expectation in the anterior insula (primary taste cortex). Here response was greater for unexpected versus expected sweet compared with unexpected versus expected tasteless, indicating that this region is preferentially sensitive to breaches of taste expectation. Connectivity analyses confirmed that expectation enhanced network interactions, with IPS and VS influencing insular responses. We conclude that unexpected oral stimulation results in suppression of visual cortex and upregulation of sensory, attention, and reward regions to support orientation, identification, and learning about salient stimuli.
DiDomenico, Lawrence A; Masternick, Eric B
Compression of the deep peroneal nerve is commonly referred to as anterior tarsal tunnel syndrome. Although rare, this syndrome remains poorly diagnosed. The syndrome is characterized by pain, weakness, and sensory changes of the foot and ankle. Non-operative measures should be attempted to reduce or remove the external compression along the anterior aspect of the foot and ankle. Other options include shoe modifications, cortisone injections,and physical therapy. If conservative management fails to relieve the symptoms, surgical decompression of the entrapped nerve can be performed. The deep peroneal nerve is released from compressive forces in the entrapment site. This can be performed at the more proximal level at the extensor retinaculum or more distally at the level of the tarsal metatarsal site.
Pitzer, G; Oursin, C; Wolfensberger, M
An anterior neopharyngeal pseudodiverticulum is a mucosal pouch located between the tongue and hypopharynx due to an epiglottis-like posterior tissue band that forms after total laryngectomy. This condition has rarely been mentioned in literature. Incidence, symptoms, treatment, and possible etiologic factors were examined. Twenty post-laryngectomy patients were questioned about swallowing disorders and were examined clinically and by barium swallow. Eleven patients were found to have a pseudodiverticulum, of which 9 patients suffered from dysphagia. We found no correlation between the formation of a pseudodiverticulum and radiotherapy or post-laryngectomy complications. All symptomatic patients were treated by dissecting the posterior tissue band endoscopically with a CO2-laser, bringing complete relief of symptoms in 8 of 9 patients. Our study showed that the anterior pseudodiverticulum can be a frequent cause of dysphagia after laryngectomy. It can easily be diagnosed clinically and radiologically. Endoscopic treatment with a CO2-laser is simple and effective.
The purpose of this study was to investigate metabolic changes associated with a right hypothalamic mass in a 26-year-old gelastic seizure patient. Positron emission tomography (PET) imaging of the brain was performed in the interictal state using 18F-fluorodeoxyglucose (18F-FDG) in this patient. Temporal lobe hypometabolism was noted ipsilateral to the hypothalamic lesion. The mass itself had little to no uptake of 18F-FDG. This is the first known PET imaging report of temporal lobe hypometabolism ipsilateral to a presumed hypothalamic hamartoma causing gelastic seizures. Further studies are needed in other patients to test whether interictal PET imaging may help plan the removal of epileptogenic hypothalamic lesions.
Sharma, S C; Tsai, C
In normal goldfish, optic axons innervate only the contralateral optic tectum. When one eye was enucleated and the optic nerve of the other eye crushed, the regenerating optic axons innervated both optic tecta. We studied the presence of bilaterally projecting retinal ganglion cells by double retrograde cell labeling methods using Nuclear Yellow and True Blue dyes. About 10% of the retinal ganglion cells were double labeled and these cells were found throughout the retina. In addition, HRP application to the ipsilateral tectum revealed retrogradely-labeled retinal ganglion cells of all morphological types. These results suggest that induced ipsilateral projections are formed by regenerating axon collaterals and that all cell types are involved in the generation of normal mirror image typography.
Madhar, M; Saidi, H; Fikry, T; Cermak, K; Moungondo, F; Schuind, F
Elbow dislocation associated with ipsilateral radial shaft fracture is an infrequent injury (nine cases reported in the literature). We present six new cases observed between 2006 and 2012, with an average age of 31 years and a mean follow-up of 18 months. The forearm fracture and ipsilateral dislocation of the elbow were probably caused by forearm hypersupination with extension of the elbow. The dislocation was reduced by manipulation before open reduction and osteosynthesis of the forearm fracture. Four elbows were stable after reduction; two markedly unstable elbows necessitated temporary humero-ulnar external fixation; one case needed a ligamentoplasty several months later. Despite the complexity of the traumatic lesion, the clinical and radiological outcomes were acceptable.
Johansson, H; Silfvenius, H
1. Evidence is presented for an input from ipsilateral hind limb group I muscle afferents and low threshold cutaneous afferents, to cells in the rostral division of the main cuneate nucleus (rMCN) and in the region of the descending vestibular nucleus and the nucleus X of Brodal & Pompeiano (1957a), the (DV-X). 2. Thirteen group I-rMCN cells were recorded from. The functional properties of these cells were similar to those of nueleus Z (Landgren & Silfvenius, 1971; Johansson & Silfvenius, 1977a, b). The cells were monosynaptically linked to spinal dorsolateral fascicle (DLF) fibres. Nine cells projected to the contralateral thalamus, i.e. a second group I hind limb bulbothalamic tract is described. Ten cells were synaptically activated from the ipsilateral cerebellum from the anterior projection zone of the dorsal spinocerebellar tract (DSCT). Axon-collateral activation by DSCT fibres was established for two of these cells. They were both bulbothalamic relay cells. For the remaining eight cells, activated from the cerebellum, this was not proven. These cells could, however, either be linked to DSCT fibres or to short axon-collaterals of a cell body of unknown location. A projection from the rMCN to the cerebellum is described and agrees with recent anatomical findings. Two cells were not excited from the cerebellum. 3. Four rMCN cells were activated by cutaneous afferents with their secondary axons in the DLF. Suggestive evidence for a bulbothalamic cutaneous hind limb path via the rMCN is presented. Two cells were activated from the cerebellum, presumably via axon-collaterals of nonsegmental cells. 4. Eight group I-DV-X cells were recorded from. They were monosynaptically linked to spinal DLF fibres and resembled functionally the nucleus Z and rMCN cells when stimulated from the periphery. Two cells projected to the contralateral thalamus, and two others were synaptically excited. Seven cells were activated from the ipsilateral cerebellum. Two of them projected to
Jones, R D; Donaldson, I M; Parkin, P J
After unilateral cerebral hemisphere stroke, resulting in contralateral arm symptoms but largely sparing higher cerebral function, ipsilateral arm function is generally considered to be unaffected. In this study, 8 subjects with acute unilateral cerebral infarction (confirmed by CT scan) and primarily motor deficits underwent 11 computerized and 6 clinical assessments between 11 days and 12 months poststroke, and were compared with 12 normal subjects. Computerized tests comprised 3 pursuit tracking tasks (preview-random, step and a combination of these), designed to measure different aspects of integrated sensory-motor (S-M) function, and 12 tasks aimed at breaking tracking into various sensory, perceptual and motor components (joint movement sense, visual resolution, object perception, static and dynamic visuospatial perception, range of movement, grip and arm strength, reaction time, speed, static and dynamic steadiness). The asymptomatic arm was impaired on all but one of the computerized tests throughout the 12-month period, although to a lesser degree than the symptomatic arm. Grip strength was marginally impaired initially. Incomplete neurological recovery was seen in the asymptomatic arm for all functions except strength, speed and steadiness, possibly indicating their resistance to improvement. Clinical assessment detected no asymptomatic arm impairment and only a mild transient deficit of higher mental function. Our data suggest that (1) all cerebral hemisphere areas involved in S-M functions can exert some degree of bilateral motor control; (2) ipsilateral influence is never greater than contralateral influence, and is usually considerably less; and (3) the proportion of ipsilateral to contralateral control is closely related to the degree of continuous sensory feedback required by the particular task. The mechanism and degree of ipsilateral dysfunction can be explained by a 3-tier cerebral model of S-M integration comprising a lower level of functions
Maeshima, Shinichiro; Tsunoda, Tetsuya; Okamoto, Sayaka; Ozeki, Yasunori; Sonoda, Shigeru
A 62-year-old right-handed man was diagnosed with a cerebral infarction in the ventromedial region of the left lower pons. He showed left abducens nerve palsy, left-sided supranuclear palsy of the lower part of the face and right hemiparesis. We hypothesized that the mechanism underlying the patient's ipsilateral supranuclear facial palsy involved the corticofacial fibers after they crossed the midline.
Vergeer, Marije R.; Doornaert, Patricia; Jonkman, Anja; Kaanders, Johannes H.A.M.; Ende, Piet L.A. van den; Jong, Martin A. de; Leemans, C. Rene; Langendijk, Johannes A.
Purpose: The purpose was to evaluate the contralateral nodal control (CLNC) in postoperative patients with oral and oropharyngeal cancer treated with ipsilateral irradiation of the neck and primary site. Late radiation-induced morbidity was also evaluated. Methods and Materials: The study included 123 patients with well-lateralized squamous cell carcinomas treated with surgery and unilateral postoperative irradiation. Most patients had tumors of the gingiva (41%) or buccal mucosa (21%). The majority of patients underwent surgery of the ipsilateral neck (n = 102 [83%]). The N classification was N0 in 73 cases (59%), N1 or N2a in 23 (19%), and N2b in 27 cases (22%). Results: Contralateral metastases developed in 7 patients (6%). The 5-year actuarial CLNC was 92%. The number of lymph node metastases was the only significant prognostic factor with regard to CLNC. The 5-year CLNC was 99% in N0 cases, 88% in N1 or N2a cases, and 73% in N2b cases (p = 0.008). Borderline significance (p = 0.06) was found for extranodal spread. Successful salvage could be performed in 71% of patients with contralateral metastases. The prevalence of Grade 2 or higher xerostomia was 2.6% at 5 years. Conclusions: Selected patients with oral or oropharyngeal carcinoma treated with primary surgery and postoperative ipsilateral radiotherapy have a very high CLNC with a high probability of successful salvage in case of contralateral metastases. However, bilateral irradiation should be applied in case of multiple lymph node metastases in the ipsilateral neck, particularly in the presence of extranodal spread. The incidence of radiation-induced morbidity is considerably lower as observed after bilateral irradiation.
Hotson, Guy; Fifer, Matthew S; Acharya, Soumyadipta; Benz, Heather L; Anderson, William S; Thakor, Nitish V; Crone, Nathan E
In patients with unilateral upper limb paralysis from strokes and other brain lesions, strategies for functional recovery may eventually include brain-machine interfaces (BMIs) using control signals from residual sensorimotor systems in the damaged hemisphere. When voluntary movements of the contralateral limb are not possible due to brain pathology, initial training of such a BMI may require use of the unaffected ipsilateral limb. We conducted an offline investigation of the feasibility of decoding ipsilateral upper limb movements from electrocorticographic (ECoG) recordings in three patients with different lesions of sensorimotor systems associated with upper limb control. We found that the first principal component (PC) of unconstrained, naturalistic reaching movements of the upper limb could be decoded from ipsilateral ECoG using a linear model. ECoG signal features yielding the best decoding accuracy were different across subjects. Performance saturated with very few input features. Decoding performances of 0.77, 0.73, and 0.66 (median Pearson's r between the predicted and actual first PC of movement using nine signal features) were achieved in the three subjects. The performance achieved here with small numbers of electrodes and computationally simple decoding algorithms suggests that it may be possible to control a BMI using ECoG recorded from damaged sensorimotor brain systems.
Ellis, Michael D; Drogos, Justin; Carmona, Carolina; Keller, Thierry; Dewald, Julius P A
The effect of reticular formation excitability on maximum voluntary torque (MVT) generation and associated muscle activation at the shoulder and elbow was investigated through natural elicitation (active head rotation) of the asymmetric tonic neck reflex (ATNR) in 26 individuals with stroke and 9 age-range-matched controls. Isometric MVT generation at the shoulder and elbow was quantified with the head rotated (face pointing) contralateral and ipsilateral to the paretic (stroke) and dominant (control) arm. Given the dominance of abnormal torque coupling of elbow flexion with shoulder abduction (flexion synergy) in stroke and well-developed animal models demonstrating a linkage between reticular formation and ipsilateral elbow flexors and shoulder abductors, we hypothesized that constituent torques of flexion synergy, specifically elbow flexion and shoulder abduction, would increase with contralateral head rotation. The findings of this investigation support this hypothesis. Increases in MVT for three of four flexion synergy constituents (elbow flexion, shoulder abduction, and shoulder external rotation) were observed during contralateral head rotation only in individuals with stroke. Electromyographic data of the associated muscle coactivations were nonsignificant but are presented for consideration in light of a likely underpowered statistical design for this specific variable. This study not only provides evidence for the reemergence of ATNR following stroke but also indicates a common neuroanatomical link, namely, an increased reliance on ipsilateral reticulospinal pathways, as the likely mechanism underlying the expression of both ATNR and flexion synergy that results in the loss of independent joint control.
Huang, Eugene H.; Strom, Eric A.; Valero, Vicente; Fornage, Bruno; Perkins, George H.; Oh, Julia L.; Yu, T.-K.; Tereffe, Welela; Woodward, Wendy A.; Hunt, Kelly K.; Meric-Bernstam, Funda; Sahin, Aysegul A.; Bedrosian, Isabelle; Hortobagyi, Gabriel N.; Buchholz, Thomas A. . E-mail: firstname.lastname@example.org
Purpose: To evaluate the locoregional efficacy of multimodality treatment for breast cancer patients who present with ipsilateral supraclavicular (SCV) disease without systemic metastases. Methods: We retrospectively reviewed the data from 71 patients with ipsilateral SCV involvement at presentation. SCV involvement in 16 patients (23%) was diagnosed by ultrasound examination only, without palpable disease. All patients were treated with curative intent using neoadjuvant chemotherapy, mastectomy or breast-conserving surgery (BCT), and radiotherapy. Results: The 5-year SCV control, locoregional control (LRC), disease-free survival, and overall survival rate was 90%, 77%, 30%, and 47%, respectively. Patients with persistent SCV disease after neoadjuvant chemotherapy by physical examination had a lower rate of LRC (64% vs. 86%, p = 0.026), as did those with persistent SCV disease by ultrasound examination (66% vs. 96%, p = 0.007). Of those with a complete response of SCV disease by physical examination after neoadjuvant chemotherapy, those with persistently abnormal ultrasound findings had significantly worse disease-free survival (0% vs. 55%, p = 0.03). BCT was not associated with lower rates of LRC (82% for BCT vs. 76% for mastectomy, p = 0.80). Conclusion: Radiotherapy achieved excellent LRC after surgery for patients with ipsilateral SCV metastases who achieved a complete response of the SCV disease after neoadjuvant chemotherapy. For patients who achieved a complete response of the SCV disease by physical examination, ultrasonography of the SCV fossa may help assess the risk of disease recurrence. SCV involvement should not be considered a contraindication for BCT.
Ramakantan, Ravi; Ketkar, Manoj; Maddali, Krishna; Deshmukh, Hemant
Purpose: We report an unusual pattern of referred pain to the ipsilateral forehead and orbit observed during bronchial artery embolization (BAE) for massive hemoptysis due to pulmonary tuberculosis (TB) and postulate possible neural mechanisms for its occurrence. Methods: Seven men, from a series of 194 patients (171 men, 23 women) undergoing BAE (right bronchial artery 4, left 3) with gelatin sponge for control of massive hemoptysis due to pulmonary TB form the subject of this report. Results: Embolization was successful in achieving control of hemoptysis in these patients and there were no complications following the embolization. Transient, moderately severe, ipsilateral supraorbital and/or retroorbital pain occurred only during the injection of the gelatin sponge contrast mixture into the bronchial artery. The pain did not occur during the injection of heparinized saline or ionic contrast medium. Conclusions: Referred pain during BAE is an unusual phenomenon. Acute vessel distension triggering visceral sensations is probably the causative mechanism. Sympathetic afferents from the bronchi coursing through the posterior pulmonary plexus eventually pass to the trigeminal ganglion via the carotid sympathetic chain. The ophthalmic and maxillary divisions of the trigeminal nerve then mediate pain sensation to the ipsilateral forehead and orbit. Similarly, parasympathetic afferents from the pulmonary plexus crossing the nucleus of the spinal tract of the trigeminal nerve may be responsible for interexchange of impulses to the neurons in this nucleus. Sensory fibers of the ophthalmic and maxillary nerves relaying in this nucleus are then involved in this pain being referred to the forehead and orbit.
Nezu, A; Kimura, S; Takeshita, S; Tanaka, M
The patterns of functional recovery after unilateral cerebral damage occurring in the prenatal to infantile periods were studied in nine patients with hemiplegic cerebral palsy. Motor evoked potentials (MEPs) recorded from the small hand muscles were investigated using focal transcranial magnetic stimulation (TMS). The MEPs findings could be separated into three subtypes based on the features of ipsilateral MEPs elicited by TMS over the unaffected motor cortex. Bilateral MEPs of similar latency were obtained in three patients. These patients each having a congenital lesion invariably exhibited mirror movements and severe hemiparesis. Meanwhile, ipsilateral MEPs with markedly prolonged latency were demonstrated in two other patients, who exhibited synergistic associated movements and severe hemiparesis caused by an acquired lesion. In the remaining four patients, who showed mild hemiparesis without such abnormal interlimb coordinations, there were no ipsilateral MEPs. Thus, we suggest that TMS is useful for confirming the electrophysiological findings relevant to functional recovery in hemiplegic cerebral palsy underlying such abnormal interlimb coordinations. Specifically, bilateral MEPs of similar latency were considered consistent with compensatory mirror movements originating from bilateral motor representation in the unaffected motor cortex.
Afrashtehfar, Cyrus Dean Mario; Piña-García, Adrián; Afrashtehfar, Kelvin Ian
Müllerian duct anomalies are a group of uncommon and underdiagnosed entities, which cause specific symptoms in adolescent females and may be associated with infertility as well as adverse pregnancy outcomes. These malformations occur as a result of an arrest or abnormal development of the Müllerian ducts in different stages of the female reproductive tract during gestation. Obstructed hemivagina and ipsilateral renal anomaly syndrome (OHVIRA), formerly known as the Herlyn-Werner-Wunderlich syndrome, is a rare entity characterized by the presence of a uterus didelphys with an obstructed hemivagina cause by a vaginal septum and the association of a renal anomaly (most commonly renal agenesis) ipsilateral to the obstruction. This syndrome may remain undiagnosed during childhood and usually becomes symptomatic after menarche, causing obstructive symptoms. Occasionally it may be identified after the evaluation of a patient with infertility or recurrent pregnancy loss. The clinical diagnosis is very challenging and requires imaging studies in which ultrasound and MRI play an essential role in the diagnosis, classification and treatment plan. Opportune diagnosis and treatment achieve complete improvement of symptoms, adequate reproductive prognosis and avoid major complications such as endometriosis, pelvic adhesions and infertility. The purpose of this review is to demonstrate the pathophysiology, clinical manifestations, diagnostic methods and treatment of the obstructed hemivagina and ipsilateral renal anomaly syndrome.
Son, Hee Eon; Park, Moon Sun; Kim, Seong Min; Jung, Sung Sam; Park, Ki Seok
Objective Paraclinoid segment internal carotid artery (ICA) aneurysms have historically been a technical challenge for neurovascular surgeons. The development of microsurgical approach, advances in surgical techniques, and endovascular procedures have improved the outcome for paraclinoid aneurysms. However, many authors have reported high complication rates from microsurgical treatments. Therefore, the present study reviews the microsurgical complications of the extradural anterior clinoidectomy for treating paraclinoid aneurysms and investigates the prevention and management of observed complications. Methods Between January 2004 and April 2008, 22 patients with 24 paraclinoid aneurysms underwent microsurgical direct clipping by a cerebrovascular team at a regional neurosurgical center. Microsurgery was performed via an ipsilateral pterional approach with extradural anterior clinoidectomy. We retrospectively reviewed patients' medical charts, office records, radiographic studies, and operative records. Results In our series, the clinical outcomes after an ipsilateral pterional approach with extradural anterior clinoidectomy for paraclinoid aneurysms were excellent or good (Glasgows Outcome Scale : GOS 5 or 4) in 87.5% of cases. The microsurgical complications related directly to the extradural anterior clinoidectomy included transient cranial nerve palsy (6), cerebrospinal fluid leak (1), worsened change in vision (1), unplanned ICA occlusion (1), and epidural hematoma (1). Only one of the complications resulted in permanent morbidity (4.2%), and none resulted in death. Conclusion Although surgical complications are still reported to occur more frequently for the treatment of paraclinoid aneurysms, the permanent morbidity and mortality resulting from a extradural anterior clinoidectomy in our series were lower than previously reported. Precise anatomical knowledge combined with several microsurgical tactics can help to achieve good outcomes with minimal
LLopis, Eva; Padrón, Mario
Anterior knee pain is a common complain in all ages athletes. It may be caused by a large variety of injuries. There is a continuum of diagnoses and most of the disorders are closely related. Repeated minor trauma and overuse play an important role for the development of lesions in Hoffa's pad, extensor mechanism, lateral and medial restrain structures or cartilage surface, however usually an increase or change of activity is referred. Although the direct relation of cartilage lesions, especially chondral, and pain is a subject of debate these lesions may be responsible of early osteoarthrosis and can determine athlete's prognosis. The anatomy and biomechanics of patellofemoral joint is complex and symptoms are often unspecific. Transient patellar dislocation has MR distinct features that provide evidence of prior dislocation and rules our complication. However, anterior knee pain more often is related to overuse and repeated minor trauma. Patella and quadriceps tendon have been also implicated in anterior knee pain, as well as lateral or medial restraint structures and Hoffa's pad. US and MR are excellent tools for the diagnosis of superficial tendons, the advantage of MR is that permits to rule out other sources of intraarticular derangements. Due to the complex anatomy and biomechanic of patellofemoral joint maltracking is not fully understood; plain films and CT allow the study of malalignment, new CT and MR kinematic studies have promising results but further studies are needed. Our purpose here is to describe how imaging techniques can be helpful in precisely defining the origin of the patient's complaint and thus improve understanding and management of these injuries.
Nardone, Raffaele; Höller, Yvonne; Höller, Peter; Thon, Natasha; Thomschewski, Aljoscha; Brigo, Francesco; Trinka, Eugen
Previous neuroimaging studies raised the hypothesis that enhanced activity in the ipsilateral motor cortex (M1) plays a contributing role in the compensation for the motor deficits resulting from a spinal cord injury (SCI). However, it is still unknown whether the activity in the ipsilateral M1 directly contributes to movement performance after SCI. To address this question, we evaluated in five subjects with chronic incomplete cervical SCI the effects of suprathreshold transcranial magnetic stimulation (TMS) to both hemispheres when a movement of the right and left hand was performed separately in the setting of a simple reaction time. We found that stimulation of each hemisphere resulted in delayed simple reaction times in the contralateral but not in the ipsilateral hand. These observations provide the first direct evidence in humans that the ipsilateral M1 did not contribute significantly to motor task performance after SCI.
Dottan, S; Levartovsky, S; Oliver, M
Pars plana anterior vitrectomy was performed in 9 patients with shallow anterior chamber after cataract extraction. Five patients had choroidal and/or ciliary body effusion (CCBE), and 4 had aphakic pupillary block (APB). Vitrectomy was performed only after medical treatment failed to restore a normal anterior chamber depth. In all patients the anterior chamber restored during surgery and remained so thereafter, although in patients with CCBE, the fundal pathology subsided days or even months later. The only surgical complication was a longstanding cystoid macular oedema in one patient. Pars plana vitrectomy would appear to have advantages over other surgical techniques, in similar circumstances.
Carbone, Antonio; Palleschi, Giovanni; Tomiselli, Giulio; Inghilleri, Maurizio; Rago, Rocco; Lenzi, Andrea; Pastore, Antonio Luigi
Few cases of unilateral renal agenesis associated with ipsilateral seminal vesicle ectasia or cyst have been reported. Two cases of unilateral renal aplastic dysplasia and ipsilateral ectopic ureter opening in the ejaculatory ducts associated with infertility secondary to bilateral obstruction of the seminal via are reported. Clinical and physical assessment including transrectal ultrasound and magnetic resonance imaging are proposed as a comprehensive algorithm for the diagnostic evaluation of the pelvic cystic masses.
Caston, J; Gribenski, A
In the frog, the influence of both the part of the efferent system which depends on ipsilateral vestibular inputs and the receptor-receptor fibre system on the afferent activity of semicircular canals is either null or facilitatory. The receptor-receptor fibre system being inhibitory, it seems that the part of the efferent vestibular activity which depends on ipsilateral vestibular inputs is facilitatory, which agrees with previous results.
Yokoyama, Osamu; Nakayama, Yoshihisa; Hoshi, Eiji
The caudal cingulate motor area (CMAc) and the supplementary motor area (SMA) play important roles in movement execution. The present study examined the neural mechanisms underlying these roles by investigating local field potentials (LFPs) from these areas while monkeys pressed buttons with either their left or right hand. During hand movement, power increases in the high-gamma (80-120 Hz) and theta (3-8 Hz) bands and a power decrease in the beta (12-30 Hz) band were observed in both the CMAc and SMA. High-gamma and beta activity in the SMA predominantly represented contralateral hand movements, whereas activity in the CMAc preferentially represented movement of either hand. Theta activity in both brain regions most frequently reflected movement of either hand, but a contralateral hand bias was more evident in the SMA than in the CMAc. An analysis of the relationships of the laterality representations between the high-gamma and theta bands at each recording site revealed that, irrespective of the hand preference for the theta band, the high-gamma band in the SMA preferentially represented contralateral hand movement, whereas the high-gamma band in the CMAc represented movement of either hand. These findings suggest that the input-output relationships for ipsilateral and contralateral hand movements in the CMAc and SMA differ in terms of their functionality. The CMAc may transform the input signals representing general aspects of movement into commands to perform movements with either hand, whereas the SMA may transform the input signals into commands to perform movement with the contralateral hand.
Nemeth, Gabor; Hassan, Ziad; Berta, Andras; Modis, Laszlo
We report an anterior megalophthalmos case with decreased corneal thickness and show the findings using Scheimpflug imaging. A 25-year-old male was diagnosed with anterior megalophthalmos. In both eyes, enlarged corneal length was measured. Beside a comparatively good visual acuity, a thin but clear cornea, a fairly deep anterior chamber, and central lens opacity were found. Scheimpflug images were taken using Pentacam HR. Scheimpflug-based imaging can provide us new data at the examination of this syndrome affecting the whole anterior segment. PMID:23275220
Altman, Gregory (Inventor); Kaplan, David (Inventor); Vunjak-Novakovic, Gordana (Inventor); Martin, Ivan (Inventor)
The present invention provides a method for producing an anterior cruciate ligament ex vivo. The method comprises seeding pluripotent stem cells in a three dimensional matrix, anchoring the seeded matrix by attachment to two anchors, and culturing the cells within the matrix under conditions appropriate for cell growth and regeneration, while subjecting the matrix to one or more mechanical forces via movement of one or both of the attached anchors. Bone marrow stromal cells are preferably used as the pluripotent cells in the method. Suitable matrix materials are materials to which cells can adhere, such as a gel made from collagen type I. Suitable anchor materials are materials to which the matrix can attach, such as Goinopra coral and also demineralized bone. Optimally, the mechanical forces to which the matrix is subjected mimic mechanical stimuli experienced by an anterior cruciate ligament in vivo. This is accomplished by delivering the appropriate combination of tension, compression, torsion, and shear, to the matrix. The bioengineered ligament which is produced by this method is characterized by a cellular orientation and/or matrix crimp pattern in the direction of the applied mechanical forces, and also by the production of collagen type I, collagen type III, and fibronectin proteins along the axis of mechanical load produced by the mechanical forces. Optimally, the ligament produced has fiber bundles which are arranged into a helical organization. The method for producing an anterior cruciate ligament can be adapted to produce a wide range of tissue types ex vivo by adapting the anchor size and attachment sites to reflect the size of the specific type of tissue to be produced, and also adapting the specific combination of forces applied, to mimic the mechanical stimuli experienced in vivo by the specific type of tissue to be produced. The methods of the present invention can be further modified to incorporate other stimuli experienced in vivo by the
Simmons, Alan; Stein, Murray B.; Strigo, Irina A; Arce, Estibaliz; Hitchcock, Carla; Paulus, Martin P.
Prior neuroimaging studies support the hypothesis that anticipation, an important component of anxiety, may be mediated by activation within the insular and medial prefrontal cortices including the anterior cingulate cortex. However, there is an insufficient understanding of how affective anticipation differs across anxiety groups in emotional brain loci and networks. We examined 14 anxiety positive (AP) and 14 anxiety normative (AN) individuals completing an affective picture anticipation task during functional magnetic resonance imaging (fMRI). Brain activation was examined across groups for cued anticipation (to aversive or pleasant stimuli). Both groups showed greater activation in the bilateral anterior insula during cued differential anticipation (i.e., aversive vs. pleasant) and activation on the right was significantly higher in AP compared to AN subjects. Functional connectivity showed that the left anterior insula was involved in a similar network during pleasant anticipation in both groups. The left anterior insula during aversive and the right anterior insula during all anticipation conditions co-activated with a cortical network consisting of frontal and parietal lobes in the AP group to a greater degree. These results are consistent with the hypothesis that anxiety is related to greater anticipatory reactivity in the brain and that there may be functional asymmetries in the brain that interact with psyc