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Sample records for dorsal premotor cortex

  1. Multimodal Connectivity of Motor Learning-Related Dorsal Premotor Cortex

    PubMed Central

    Hardwick, Robert M.; Lesage, Elise; Eickhoff, Claudia R; Clos, Mareike; Fox, Peter; Eickhoff, Simon B.

    2015-01-01

    The dorsal premotor cortex (dPMC) is a key region for motor learning and sensorimotor integration, yet we have limited understanding of its functional interactions with other regions. Previous work has started to examine functional connectivity in several brain areas using resting state functional connectivity (RSFC) and meta-analytical connectivity modelling (MACM). More recently, structural covariance (SC) has also been proposed as a technique that may also allow delineation of functional connectivity. Here we applied these three approaches to provide a comprehensive characterization of functional connectivity with a seed in the left dPMC that a previous meta-analysis of functional neuroimaging studies has identified as playing a key role in motor learning. Using data from two sources (the Rockland sample, containing resting state data and anatomical scans from 132 participants, and the BrainMap database, which contains peak activation foci from over 10,000 experiments), we conducted independent whole-brain functional connectivity mapping analyses of a dPMC seed. RSFC and MACM revealed similar connectivity maps spanning prefrontal, premotor and parietal regions, while the SC map identified more widespread frontal regions. Analyses indicated a relatively consistent pattern of functional connectivity between RSFC and MACM that was distinct from that identified by SC. Notably, results indicate the seed is functionally connected to areas involved in visuomotor control and executive functions, suggesting the dPMC acts as an interface between motor control and cognition. PMID:26282855

  2. Dorsal premotor cortex and conditional movement selection: A PET functional mapping study.

    PubMed

    Grafton, S T; Fagg, A H; Arbib, M A

    1998-02-01

    Positron emission tomography (PET) brain mapping was used to investigate whether or not human dorsal premotor cortex is involved in selecting motor acts based on arbitrary visual stimuli. Normal subjects performed four movement selection tasks. A manipulandum with three graspable stations was used. An imperative visual cue (LEDs illuminated in random order) indicated which station to grasp next with no instructional delay period. In a power task, a large aperture power grip was used for all trials, irrespective of the LED color. In a precision task, a pincer grasp of thumb and index finger was used. In a conditional task, the type of grasp (power or precision) was randomly determined by LED color. Comparison of the conditional selection task versus the average of the power and precision tasks revealed increased blood flow in left dorsal premotor cortex and superior parietal lobule. The average rate of producing the different grasp types and transport to the manipulandum stations was equivalent across this comparison, minimizing the contribution of movement attributes such as planning the individual movements (as distinct from planning associated with use of instructional stimuli), kinematics, or direction of target or limb movement. A comparison of all three movement tasks versus a rest task identified movement related activity involving a large area of central, precentral and postcentral cortex. In the region of the precentral sulcus movement related activity was located immediately caudal to the area activated during selection. The results establish a role for human dorsal premotor cortex and superior parietal cortex in selecting stimulus guided movements and suggest functional segregation within dorsal premotor cortex.

  3. Multisynaptic projections from the ventrolateral prefrontal cortex to the dorsal premotor cortex in macaques - anatomical substrate for conditional visuomotor behavior.

    PubMed

    Takahara, Daisuke; Inoue, Ken-Ichi; Hirata, Yoshihiro; Miyachi, Shigehiro; Nambu, Atsushi; Takada, Masahiko; Hoshi, Eiji

    2012-11-01

    Lines of evidence indicate that both the ventrolateral prefrontal cortex (vlPFC) (areas 45/12) and dorsal premotor cortex (PMd) (rostral F2 in area 6) are crucially involved in conditional visuomotor behavior, in which it is required to determine an action based on an associated visual object. However, virtually no direct projections appear to exist between the vlPFC and PMd. In the present study, to elucidate possible multisynaptic networks linking the vlPFC to the PMd, we performed a series of neuroanatomical tract-tracing experiments in macaque monkeys. First, we identified cortical areas that send projection fibers directly to the PMd by injecting Fast Blue into the PMd. Considerable retrograde labeling occurred in the dorsal prefrontal cortex (dPFC) (areas 46d/9/8B/8Ad), dorsomedial motor cortex (dmMC) (F7 and presupplementary motor area), rostral cingulate motor area, and ventral premotor cortex (F5 and area 44), whereas the vlPFC was virtually devoid of neuronal labeling. Second, we injected the rabies virus, a retrograde transneuronal tracer, into the PMd. At 3 days after the rabies injections, second-order neurons were labeled in the vlPFC (mainly area 45), indicating that the vlPFC disynaptically projects to the PMd. Finally, to determine areas that connect the vlPFC to the PMd indirectly, we carried out an anterograde/retrograde dual-labeling experiment in single monkeys. By examining the distribution of axon terminals labeled from the vlPFC and cell bodies labeled from the PMd, we found overlapping labels in the dPFC and dmMC. These results indicate that the vlPFC outflow is directed toward the PMd in a multisynaptic fashion through the dPFC and/or dmMC.

  4. Inhibition of the dorsal premotor cortex does not repair surround inhibition in writer's cramp patients.

    PubMed

    Veugen, Lidwien C; Hoffland, Britt S; Stegeman, Dick F; van de Warrenburg, Bart P

    2013-03-01

    Writer's cramp is a task-specific form of focal dystonia, characterized by abnormal movements and postures of the hand and arm during writing. Two consistent abnormalities in its pathophysiology are a loss of surround inhibition and overactivity of the dorsal premotor cortex (PMd). This study aimed to assess a possible link between these two phenomena by investigating whether PMd inhibition leads to an improvement of surround inhibition, in parallel with previously demonstrated writing improvement. Fifteen writer's cramp patients and ten controls performed a simple motor hand task during which surround inhibition was measured using transcranial magnetic stimulation. Motor cortical excitability was measured of the active and surround muscles at three phases of the task. Surround inhibition and writing performance were assessed before and after PMd inhibitory continuous theta burst stimulation. In contrast to healthy controls, patients did not show inhibition of the abductor digiti minimi muscle during movement initiation of the first dorsal interosseus muscle, confirming the loss of surround inhibition. PMd inhibition led to an improvement of writing speed in writer's cramp patients. However, in both groups, no changes in surround inhibition were observed. The results confirm a role for the PMd in the pathophysiology of writer's cramp. We show that PMd inhibition does not lead to restoration of the surround inhibition defect in writer's cramp, despite the improvement in writing. This questions the involvement of the PMd in the loss of surround inhibition, and perhaps also the direct link between surround inhibition and dystonia.

  5. Uncertainty leads to persistent effects on reach representations in dorsal premotor cortex

    PubMed Central

    Dekleva, Brian M; Ramkumar, Pavan; Wanda, Paul A; Kording, Konrad P; Miller, Lee E

    2016-01-01

    Every movement we make represents one of many possible actions. In reaching tasks with multiple targets, dorsal premotor cortex (PMd) appears to represent all possible actions simultaneously. However, in many situations we are not presented with explicit choices. Instead, we must estimate the best action based on noisy information and execute it while still uncertain of our choice. Here we asked how both primary motor cortex (M1) and PMd represented reach direction during a task in which a monkey made reaches based on noisy, uncertain target information. We found that with increased uncertainty, neurons in PMd actually enhanced their representation of unlikely movements throughout both planning and execution. The magnitude of this effect was highly variable across sessions, and was correlated with a measure of the monkeys’ behavioral uncertainty. These effects were not present in M1. Our findings suggest that PMd represents and maintains a full distribution of potentially correct actions. DOI: http://dx.doi.org/10.7554/eLife.14316.001 PMID:27420609

  6. Inhibition of the contralesional dorsal premotor cortex improves motor function of the affected hand following stroke.

    PubMed

    Lüdemann-Podubecká, J; Bösl, K; Nowak, D A

    2016-04-01

    Numerous studies have shown that repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) may improve motor function of the affected hand after stroke. The effects of 1 Hz rTMS applied over the contralesional dorsal premotor cortex (PMd) on hand function and cortical neurophysiology in subacute stroke were examined. Ten subacute stroke patients with mild hand motor impairment were enrolled in a prospective, double-blind, randomized, placebo-controlled, crossover study with two intervention sessions. 1 Hz rTMS was applied over the contralesional PMd (real rTMS, 900 pulses at 110% of the motor threshold; sham rTMS, 900 pulses at 0% of the motor threshold). Tests of hand function (Jebsen-Taylor hand function test, box and block test) and neurophysiological evaluations (resting motor threshold, motor evoked potentials, cortical silent period, ipsilateral silent period) were obtained from both hands and hemispheres prior to (baseline) and after each treatment. Hand function tests revealed significant improvement of motor function of the affected but not of the unaffected hand after real rTMS only. Neither intervention changed the neurophysiological measures in comparison to baseline. One hertz rTMS over the contralesional PMd improves motor function of the affected hand in subacute stroke. The PMd may be a novel rTMS target to treat motor impairment after stroke. © 2016 EAN.

  7. Distinct neural patterns enable grasp types decoding in monkey dorsal premotor cortex.

    PubMed

    Hao, Yaoyao; Zhang, Qiaosheng; Controzzi, Marco; Cipriani, Christian; Li, Yue; Li, Juncheng; Zhang, Shaomin; Wang, Yiwen; Chen, Weidong; Chiara Carrozza, Maria; Zheng, Xiaoxiang

    2014-12-01

    Recent studies have shown that dorsal premotor cortex (PMd), a cortical area in the dorsomedial grasp pathway, is involved in grasp movements. However, the neural ensemble firing property of PMd during grasp movements and the extent to which it can be used for grasp decoding are still unclear. To address these issues, we used multielectrode arrays to record both spike and local field potential (LFP) signals in PMd in macaque monkeys performing reaching and grasping of one of four differently shaped objects. Single and population neuronal activity showed distinct patterns during execution of different grip types. Cluster analysis of neural ensemble signals indicated that the grasp related patterns emerged soon (200-300 ms) after the go cue signal, and faded away during the hold period. The timing and duration of the patterns varied depending on the behaviors of individual monkey. Application of support vector machine model to stable activity patterns revealed classification accuracies of 94% and 89% for each of the two monkeys, indicating a robust, decodable grasp pattern encoded in the PMd. Grasp decoding using LFPs, especially the high-frequency bands, also produced high decoding accuracies. This study is the first to specify the neuronal population encoding of grasp during the time course of grasp. We demonstrate high grasp decoding performance in PMd. These findings, combined with previous evidence for reach related modulation studies, suggest that PMd may play an important role in generation and maintenance of grasp action and may be a suitable locus for brain-machine interface applications.

  8. Synchronization patterns suggest different functional organization in parietal reach region and dorsal premotor cortex.

    PubMed

    Chakrabarti, Shubhodeep; Martinez-Vazquez, Pablo; Gail, Alexander

    2014-12-15

    The parietal reach region (PRR) and dorsal premotor cortex (PMd) form part of the fronto-parietal reach network. While neural selectivity profiles of single-cell activity in these areas can be remarkably similar, other data suggest that both areas serve different computational functions in visually guided reaching. Here we test the hypothesis that different neural functional organizations characterized by different neural synchronization patterns might be underlying the putatively different functional roles. We use cross-correlation analysis on single-unit activity (SUA) and multiunit activity (MUA) to determine the prevalence of synchronized neural ensembles within each area. First, we reliably find synchronization in PRR but not in PMd. Second, we demonstrate that synchronization in PRR is present in different cognitive states, including "idle" states prior to task-relevant instructions and without neural tuning. Third, we show that local field potentials (LFPs) in PRR but not PMd are characterized by an increased power and spike field coherence in the beta frequency range (12-30 Hz), further indicating stronger synchrony in PRR compared with PMd. Finally, we show that neurons with similar tuning properties tend to be correlated in their random spike rate fluctuations in PRR but not in PMd. Our data support the idea that PRR and PMd, despite striking similarity in single-cell tuning properties, are characterized by unequal local functional organization, which likely reflects different network architectures to support different functional roles within the fronto-parietal reach network.

  9. Information Analysis on Neural Tuning in Dorsal Premotor Cortex for Reaching and Grasping

    PubMed Central

    Cao, Yan; Hao, Yaoyao; Liao, Yuxi; Xu, Kai; Wang, Yiwen; Zhang, Shaomin; Zhang, Qiaosheng; Chen, Weidong; Zheng, Xiaoxiang

    2013-01-01

    Previous studies have shown that the dorsal premotor cortex (PMd) neurons are relevant to reaching as well as grasping. In order to investigate their specific contribution to reaching and grasping, respectively, we design two experimental paradigms to separate these two factors. Two monkeys are instructed to reach in four directions but grasp the same object and grasp four different objects but reach in the same direction. Activities of the neuron ensemble in PMd of the two monkeys are collected while performing the tasks. Mutual information (MI) is carried out to quantitatively evaluate the neurons' tuning property in both tasks. We find that there exist neurons in PMd that are tuned only to reaching, tuned only to grasping, and tuned to both tasks. When applied with a support vector machine (SVM), the movement decoding accuracy by the tuned neuron subset in either task is quite close to the performance by full ensemble. Furthermore, the decoding performance improves significantly by adding the neurons tuned to both tasks into the neurons tuned to one property only. These results quantitatively distinguish the diversity of the neurons tuned to reaching and grasping in the PMd area and verify their corresponding contributions to BMI decoding. PMID:23781275

  10. The role of dorsal premotor cortex in mental rotation: A transcranial magnetic stimulation study.

    PubMed

    Cona, Giorgia; Panozzo, Giulia; Semenza, Carlo

    2017-08-01

    Although activation of dorsal premotor cortex (PMd) has been consistently observed in the neuroimaging studies of mental rotation, the functional meaning of PMd activation is still unclear and multiple alternative explanations have been suggested. The present study used repetitive transcranial magnetic stimulation (rTMS) to investigate the role of PMd in mental rotation. Two tasks were used, involving mental rotation of hands and abstract objects, with either matching (same stimuli) or mirror stimuli. Compared to sham stimulation, TMS over right and left PMd regions significantly affected accuracy in the object task, specifically for the same stimuli. Furthermore, response times were longer following right PMd stimulation in both the object and the hand tasks, but again, selectively for the same stimuli. The effect of rotational angle on response times and accuracies was greater for the same stimuli. Moreover TMS over PMd impaired the performance accuracy selectively in these stimuli, mainly in a task that included abstract objects. For these reasons, the present findings indicate a contribution of PMd to mental rotation. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Modulation of physiological mirror activity with transcranial direct current stimulation over dorsal premotor cortex.

    PubMed

    Beaulé, Vincent; Tremblay, Sara; Lafleur, Louis-Philippe; Ferland, Marie C; Lepage, Jean-François; Théoret, Hugo

    2016-11-01

    Humans have a natural tendency towards symmetrical movements, which rely on a distributed cortical network that allows for complex unimanual movements. Studies on healthy humans using rTMS have shown that disruption of this network, and particularly the dorsal premotor cortex (dPMC), can result in increased physiological mirror movements. The aim of the present set of experiments was to further investigate the role of dPMC in restricting motor output to the contralateral hand and determine whether physiological mirror movements could be decreased in healthy individuals. Physiological mirror movements were assessed before and after transcranial direct current stimulation (tDCS) over right and left dPMC in three conditions: bilateral, unilateral left and unilateral right stimulation. Mirror EMG activity was assessed immediately before, 0, 10 and 20 min after tDCS. Results show that physiological mirroring increased significantly in the hand ipsilateral to cathodal stimulation during bilateral stimulation of the dPMC, 10 and 20 min after stimulation compared to baseline. There was no significant modulation of physiological mirroring in the hand ipsilateral to anodal stimulation in the bilateral condition or following unilateral anodal or unilateral cathodal stimulation. The present data further implicate the dPMC in the control of unimanual hand movements and show that physiological mirroring can be increased but not decreased with dPMC tDCS.

  12. Interhemispheric interaction between human dorsal premotor and contralateral primary motor cortex.

    PubMed

    Mochizuki, Hitoshi; Huang, Ying-Zu; Rothwell, John C

    2004-11-15

    We used transcranial magnetic stimulation (TMS) in a paired pulse protocol to investigate interhemispheric interactions between the right dorsal premotor (dPM) and left primary motor cortex (M1) using interstimulus intervals of 4, 6, 8, 10, 12, 16 and 20 ms in ten healthy subjects. A conditioning stimulus over right dPM at an intensity of either 90 or 110% resting motor threshold (RMT) suppressed motor-evoked potentials (MEPs) evoked in the first dorsal interosseous (FDI) muscle by stimulation of left M1. Maximum effects occurred for interstimulus intervals (ISIs) of 8-10 ms. There was no effect if the conditioning stimulus was applied 2.5 cm lateral, anterior or medial to dPM. The effect differed from previously described M1 interhemispheric inhibition in that the threshold for the latter was greater than 90% RMT, whereas stimulation of the dPM at the same intensity led to significant inhibition. In addition, voluntary contraction of the left FDI (i.e. contralateral to the conditioning TMS) enhanced interhemispheric inhibition from right M1 but had no effect on the inhibition from right dPM. Finally, conditioning to right dPM at 90% RMT reduced short-interval intracortical inhibition (SICI; at ISI = 2 ms) in left M1 whilst there was no effect if the conditioning stimulus was applied to right M1. We conclude that conditioning TMS over dPM has effects that differ from the previous pattern of interhemispheric inhibition described between bilateral M1s. This may reflect the existence of commissural fibres between dPM and contralateral M1 that may play a role in bimanual coordination.

  13. Weight-specific anticipatory coding of grip force in human dorsal premotor cortex.

    PubMed

    van Nuenen, Bart F L; Kuhtz-Buschbeck, Johann; Schulz, Christian; Bloem, Bastiaan R; Siebner, Hartwig R

    2012-04-11

    The dorsal premotor cortex (PMd) uses prior sensory information for motor preparation. Here, we used a conditioning-and-map approach in 11 healthy male humans (mean age 27 years) to further clarify the role of PMd in anticipatory motor control. We transiently disrupted neuronal processing in PMd, using either continuous theta burst stimulation (cTBS) at 80% (inhibitory cTBS) or 30% (sham cTBS) of active motor threshold. The conditioning effects of cTBS on preparatory brain activity were assessed with functional MRI, while participants lifted a light or heavy weight in response to a go-cue (S2). An additional pre-cue (S1) correctly predicted the weight in 75% of the trials. Participants were asked to use this prior information to prepare for the lift. In the sham condition, grip force showed a consistent undershoot, if the S1 incorrectly prompted the preparation of a light lift. Likewise, an S1 that falsely announced a heavy weight produced a consistent overshoot in grip force. In trials with incorrect S1, preparatory activity in left PMd during the S1-S2 delay period predicted grip force undershoot but not overshoot. Real cTBS selectively abolished this undershoot in grip force. Furthermore, preparatory S1-S2 activity in left PMd no longer predicted the individual undershoot after real cTBS. Our results provide converging evidence for a causal involvement of PMd in anticipatory downscaling but not upscaling of grip force, suggesting an inhibitory role of PMd in anticipatory grip force control during object lifting.

  14. Distinct neural patterns enable grasp types decoding in monkey dorsal premotor cortex

    NASA Astrophysics Data System (ADS)

    Hao, Yaoyao; Zhang, Qiaosheng; Controzzi, Marco; Cipriani, Christian; Li, Yue; Li, Juncheng; Zhang, Shaomin; Wang, Yiwen; Chen, Weidong; Chiara Carrozza, Maria; Zheng, Xiaoxiang

    2014-12-01

    Objective. Recent studies have shown that dorsal premotor cortex (PMd), a cortical area in the dorsomedial grasp pathway, is involved in grasp movements. However, the neural ensemble firing property of PMd during grasp movements and the extent to which it can be used for grasp decoding are still unclear. Approach. To address these issues, we used multielectrode arrays to record both spike and local field potential (LFP) signals in PMd in macaque monkeys performing reaching and grasping of one of four differently shaped objects. Main results. Single and population neuronal activity showed distinct patterns during execution of different grip types. Cluster analysis of neural ensemble signals indicated that the grasp related patterns emerged soon (200-300 ms) after the go cue signal, and faded away during the hold period. The timing and duration of the patterns varied depending on the behaviors of individual monkey. Application of support vector machine model to stable activity patterns revealed classification accuracies of 94% and 89% for each of the two monkeys, indicating a robust, decodable grasp pattern encoded in the PMd. Grasp decoding using LFPs, especially the high-frequency bands, also produced high decoding accuracies. Significance. This study is the first to specify the neuronal population encoding of grasp during the time course of grasp. We demonstrate high grasp decoding performance in PMd. These findings, combined with previous evidence for reach related modulation studies, suggest that PMd may play an important role in generation and maintenance of grasp action and may be a suitable locus for brain-machine interface applications.

  15. Melodic Priming of Motor Sequence Performance: The Role of the Dorsal Premotor Cortex.

    PubMed

    Stephan, Marianne A; Brown, Rachel; Lega, Carlotta; Penhune, Virginia

    2016-01-01

    The purpose of this study was to determine whether exposure to specific auditory sequences leads to the induction of new motor memories and to investigate the role of the dorsal premotor cortex (dPMC) in this crossmodal learning process. Fifty-two young healthy non-musicians were familiarized with the sound to key-press mapping on a computer keyboard and tested on their baseline motor performance. Each participant received subsequently either continuous theta burst stimulation (cTBS) or sham stimulation over the dPMC and was then asked to remember a 12-note melody without moving. For half of the participants, the contour of the melody memorized was congruent to a subsequently performed, but never practiced, finger movement sequence (Congruent group). For the other half, the melody memorized was incongruent to the subsequent finger movement sequence (Incongruent group). Hearing a congruent melody led to significantly faster performance of a motor sequence immediately thereafter compared to hearing an incongruent melody. In addition, cTBS speeded up motor performance in both groups, possibly by relieving motor consolidation from interference by the declarative melody memorization task. Our findings substantiate recent evidence that exposure to a movement-related tone sequence can induce specific, crossmodal encoding of a movement sequence representation. They further suggest that cTBS over the dPMC may enhance early offline procedural motor skill consolidation in cognitive states where motor consolidation would normally be disturbed by concurrent declarative memory processes. These findings may contribute to a better understanding of auditory-motor system interactions and have implications for the development of new motor rehabilitation approaches using sound and non-invasive brain stimulation as neuromodulatory tools.

  16. Melodic Priming of Motor Sequence Performance: The Role of the Dorsal Premotor Cortex

    PubMed Central

    Stephan, Marianne A.; Brown, Rachel; Lega, Carlotta; Penhune, Virginia

    2016-01-01

    The purpose of this study was to determine whether exposure to specific auditory sequences leads to the induction of new motor memories and to investigate the role of the dorsal premotor cortex (dPMC) in this crossmodal learning process. Fifty-two young healthy non-musicians were familiarized with the sound to key-press mapping on a computer keyboard and tested on their baseline motor performance. Each participant received subsequently either continuous theta burst stimulation (cTBS) or sham stimulation over the dPMC and was then asked to remember a 12-note melody without moving. For half of the participants, the contour of the melody memorized was congruent to a subsequently performed, but never practiced, finger movement sequence (Congruent group). For the other half, the melody memorized was incongruent to the subsequent finger movement sequence (Incongruent group). Hearing a congruent melody led to significantly faster performance of a motor sequence immediately thereafter compared to hearing an incongruent melody. In addition, cTBS speeded up motor performance in both groups, possibly by relieving motor consolidation from interference by the declarative melody memorization task. Our findings substantiate recent evidence that exposure to a movement-related tone sequence can induce specific, crossmodal encoding of a movement sequence representation. They further suggest that cTBS over the dPMC may enhance early offline procedural motor skill consolidation in cognitive states where motor consolidation would normally be disturbed by concurrent declarative memory processes. These findings may contribute to a better understanding of auditory-motor system interactions and have implications for the development of new motor rehabilitation approaches using sound and non-invasive brain stimulation as neuromodulatory tools. PMID:27242414

  17. Bilateral primary motor cortex circuitry is modulated due to theta burst stimulation to left dorsal premotor cortex and bimanual training.

    PubMed

    Neva, Jason L; Vesia, Michael; Singh, Amaya M; Staines, W Richard

    2015-08-27

    Motor preparatory and execution activity is enhanced after a single session of bimanual visuomotor training (BMT). Recently, we have shown that increased primary motor cortex (M1) excitability occurs when BMT involves simultaneous activation of homologous muscles and these effects are enhanced when BMT is preceded by intermittent theta burst stimulation (iTBS) to the left dorsal premotor cortex (lPMd). The neural mechanisms underlying these modulations are unclear, but may include interhemispheric interactions between homologous M1s and connectivity with premotor regions. The purpose of this study was to investigate the possible intracortical and interhemispheric modulations of the extensor carpi radials (ECR) representation in M1 bilaterally due to: (1) BMT, (2) iTBS to lPMd, and (3) iTBS to lPMd followed by BMT. This study tests three related hypotheses: (1) BMT will enhance excitability within and between M1 bilaterally, (2) iTBS to lPMd will primarily enhance left M1 (lM1) excitability, and (3) the combination of these interventions will cause a greater enhancement of bilateral M1 excitability. We used single and paired-pulse transcranial magnetic stimulation (TMS) to quantify M1 circuitry bilaterally. The results demonstrate the neural mechanisms underlying the early markers of rapid functional plasticity associated with BMT and iTBS to lPMd primarily relate to modulations of long-interval inhibitory (i.e. GABAB-mediated) circuitry within and between M1s. This work provides novel insight into the underlying neural mechanisms involved in M1 excitability changes associated with BMT and iTBS to lPMd. Critically, this work may inform rehabilitation training and stimulation techniques that modulate cortical plasticity after brain injury.

  18. The heterogeneity of the left dorsal premotor cortex evidenced by multimodal connectivity-based parcellation and functional characterization.

    PubMed

    Genon, Sarah; Reid, Andrew; Li, Hai; Fan, Lingzhong; Müller, Veronika I; Cieslik, Edna C; Hoffstaedter, Felix; Langner, Robert; Grefkes, Christian; Laird, Angela R; Fox, Peter T; Jiang, Tianzi; Amunts, Katrin; Eickhoff, Simon B

    2017-02-14

    Despite the common conception of the dorsal premotor cortex (PMd) as a single brain region, its diverse connectivity profiles and behavioral heterogeneity argue for a differentiated organization of the PMd. A previous study revealed that the right PMd is characterized by a rostro-caudal and a ventro-dorsal distinction dividing it into five subregions: rostral, central, caudal, ventral and dorsal. The present study assessed whether a similar organization is present in the left hemisphere, by capitalizing on a multimodal data-driven approach combining connectivity-based parcellation (CBP) based on meta-analytic modeling, resting-state functional connectivity, and probabilistic diffusion tractography. The resulting PMd modules were then characterized based on multimodal functional connectivity and a quantitative analysis of associated behavioral functions. Analyzing the clusters consistent across all modalities revealed an organization of the left PMd that mirrored its right counterpart to a large degree. Again, caudal, central and rostral modules reflected a cognitive-motor gradient and a premotor eye-field was found in the ventral part of the left PMd. In addition, a distinct module linked to abstract cognitive functions was observed in the rostro-ventral left PMd across all CBP modalities, implying greater differentiation of higher cognitive functions for the left than the right PMd.

  19. Involvement of the human dorsal premotor cortex in unimanual motor control: an interference approach using transcranial magnetic stimulation.

    PubMed

    Cincotta, Massimo; Borgheresi, Alessandra; Balestrieri, Fabrizio; Giovannelli, Fabio; Rossi, Simone; Ragazzoni, Aldo; Zaccara, Gaetano; Ziemann, Ulf

    2004-09-02

    Unilateral movements are enabled through a distributed network of motor cortical areas but the relative contribution from the parts of this network is largely unknown. Failure of this network potentially results in mirror activation of the primary motor cortex (M1) ipsilateral to the intended movement. Here we tested the role of the right dorsal premotor cortex (dPMC) in 11 healthy subjects by disrupting its activity with 20 Hz repetitive transcranial magnetic stimulation (rTMS) whilst the subjects exerted a unilateral contraction of the left first dorsal interosseous (FDI). We found that disruption of right dPMC enhanced mirror activation of the ipsilateral left M1, as probed by motor evoked potential (MEP) amplitude to the right FDI. This was not the case with sham rTMS, when rTMS was directed to the right M1, or with rTMS of the right dPMC but without contraction of the left FDI. Findings suggest that activity in the dPMC contributes to the suppression of mirror movements during intended unilateral movements.

  20. Testing the Role of Dorsal Premotor Cortex in Auditory-Motor Association Learning Using Transcranical Magnetic Stimulation (TMS)

    PubMed Central

    Lega, Carlotta; Stephan, Marianne A.; Zatorre, Robert J.; Penhune, Virginia

    2016-01-01

    Interactions between the auditory and the motor systems are critical in music as well as in other domains, such as speech. The premotor cortex, specifically the dorsal premotor cortex (dPMC), seems to play a key role in auditory-motor integration, and in mapping the association between a sound and the movement used to produce it. In the present studies we tested the causal role of the dPMC in learning and applying auditory-motor associations using 1 Hz repetitive Transcranical Magnetic Stimulation (rTMS). In this paradigm, non-musicians learn a set of auditory-motor associations through melody training in two contexts: first when the sound to key-press mapping was in a conventional sequential order (low to high tones mapped onto keys from left to right), and then when it was in a novel scrambled order. Participant’s ability to match the four pitches to four computer keys was tested before and after the training. In both experiments, the group that received 1 Hz rTMS over the dPMC showed no significant improvement on the pitch-matching task following training, whereas the control group (who received rTMS to visual cortex) did. Moreover, in Experiment 2 where the pitch-key mapping was novel, rTMS over the dPMC also interfered with learning. These findings suggest that rTMS over dPMC disturbs the formation of auditory-motor associations, especially when the association is novel and must be learned rather explicitly. The present results contribute to a better understanding of the role of dPMC in auditory-motor integration, suggesting a critical role of dPMC in learning the link between an action and its associated sound. PMID:27684369

  1. Continuous theta-burst stimulation over the dorsal premotor cortex interferes with associative learning during object lifting.

    PubMed

    Nowak, Dennis A; Berner, Julia; Herrnberger, Bärbel; Kammer, Thomas; Grön, Georg; Schönfeldt-Lecuona, Carlos

    2009-04-01

    When lifting objects of different mass, humans scale grip force according to the expected mass. In this context, humans are able to associate a sensory cue, such as a colour, to a particular mass of an object and link this association to the grip forces necessary for lifting. Here, we study the role of the dorsal premotor cortex (PMd) in setting-up an association between a colour cue and a particular mass to be lifted. Healthy right-handed subjects used a precision grip between the index finger and thumb to lift two different masses. Colour cues provided information about which of the two masses subjects would have to lift. Subjects first performed a series of lifts with the right hand to establish a stable association between a colour cue and a mass, followed by 20sec of continuous high frequency repetitive trancranial magnetic stimulation using a recently developed protocol (continuous theta-burst stimulation, cTBS) over (i) the left primary motor cortex, (ii) the left PMd and (iii) the left occipital cortex to be commenced by another series of lifts with either the right or left hand. cTBS over the PMd, but not over the primary motor cortex or O1, disrupted the predictive scaling of isometric finger forces based on colour cues, irrespective of whether the right or left hand performed the lifts after the stimulation. Our data highlight the role of the PMd to generalize and maintain associative memory processes relevant for predictive control of grip forces during object manipulation.

  2. Low-frequency transcranial magnetic stimulation over left dorsal premotor cortex improves the dynamic control of visuospatially cued actions

    PubMed Central

    Ward, Nick S.; Bestmann, Sven; Hartwigsen, Gesa; Weiss, Michael M.; Christensen, Lars O.D.; Frackowiak, Richard S.J.; Rothwell, John C.; Siebner, Hartwig R.

    2013-01-01

    Left rostral dorsal premotor cortex (rPMd) and supramarginal gyrus (SMG) have been implicated in the dynamic control of actions. In 12 right-handed healthy individuals we applied 30 minutes of low-frequency (1Hz) repetitive transcranial magnetic stimulation (rTMS) over left rPMd to investigate the involvement of left rPMd and SMG in the rapid adjustment of actions guided by visuospatial cues. After rTMS, subjects underwent functional magnetic resonance imaging while making spatially congruent button presses with right or left index finger in response to a left- or right-sided target. Subjects were asked to covertly prepare motor responses as indicated by a directional cue presented one second before the target. On 20% of trials the cue was invalid requiring subjects to re-adjust their motor plan according to the target location. Compared to sham rTMS, real rTMS increased the number of correct responses in invalidly cued trials. After real rTMS, task-related activity of the stimulated left rPMd showed increased task-related coupling with activity in ipsilateral SMG and adjacent anterior intraparietal area (AIP). Individuals who showed a stronger increase in left-hemispheric premotor-parietal connectivity also made fewer errors on invalidly cued trials after rTMS. The results suggest that rTMS over left rPMd improved the ability to dynamically adjust visuospatial response mapping by strengthening left-hemispheric connectivity between rPMd and the SMG-AIP region. These results support the notion that left rPMd and SMG-AIP contribute towards dynamic control of actions, and demonstrate that low-frequency rTMS can enhance functional coupling between task-relevant brain regions and improve some aspects of motor performance. PMID:20610756

  3. Contribution of writing to reading: Dissociation between cognitive and motor process in the left dorsal premotor cortex.

    PubMed

    Pattamadilok, Chotiga; Ponz, Aurélie; Planton, Samuel; Bonnard, Mireille

    2016-04-01

    Functional brain imaging studies reported activation of the left dorsal premotor cortex (PMd), that is, a main area in the writing network, in reading tasks. However, it remains unclear whether this area is causally relevant for written stimulus recognition or its activation simply results from a passive coactivation of reading and writing networks. Here, we used chronometric paired-pulse transcranial magnetic stimulation (TMS) to address this issue by disrupting the activity of the PMd, the so-called Exner's area, while participants performed a lexical decision task. Both words and pseudowords were presented in printed and handwritten characters. The latter was assumed to be closely associated with motor representations of handwriting gestures. We found that TMS over the PMd in relatively early time-windows, i.e., between 60 and 160 ms after the stimulus onset, increased reaction times to pseudoword without affecting word recognition. Interestingly, this result pattern was found for both printed and handwritten characters, that is, regardless of whether the characters evoked motor representations of writing actions. Our result showed that under some circumstances the activation of the PMd does not simply result from passive association between reading and writing networks but has a functional role in the reading process. At least, at an early stage of written stimuli recognition, this role seems to depend on a common sublexical and serial process underlying writing and pseudoword reading rather than on an implicit evocation of writing actions during reading as typically assumed.

  4. The activity in the contralateral primary motor cortex, dorsal premotor and supplementary motor area is modulated by performance gains

    PubMed Central

    Sosnik, Ronen; Flash, Tamar; Sterkin, Anna; Hauptmann, Bjoern; Karni, Avi

    2014-01-01

    There is growing experimental evidence that the engagement of different brain areas in a given motor task may change with practice, although the specific brain activity patterns underlying different stages of learning, as defined by kinematic or dynamic performance indices, are not well understood. Here we studied the change in activation in motor areas during practice on sequences of handwriting-like trajectories, connecting four target points on a digitizing table “as rapidly and as accurately as possible” while lying inside an fMRI scanner. Analysis of the subjects' pooled kinematic and imaging data, acquired at the beginning, middle, and end of the training period, revealed no correlation between the amount of activation in the contralateral M1, PM (dorsal and ventral), supplementary motor area (SMA), preSMA, and Posterior Parietal Cortex (PPC) and the amount of practice per-se. Single trial analysis has revealed that the correlation between the amount of activation in the contralateral M1 and trial mean velocity was partially modulated by performance gains related effects, such as increased hand motion smoothness. Furthermore, it was found that the amount of activation in the contralateral preSMA increased when subjects shifted from generating straight point-to-point trajectories to their spatiotemporal concatenation into a smooth, curved trajectory. Altogether, our results indicate that the amount of activation in the contralateral M1, PMd, and preSMA during the learning of movement sequences is correlated with performance gains and that high level motion features (e.g., motion smoothness) may modulate, or even mask correlations between activity changes and low-level motion attributes (e.g., trial mean velocity). PMID:24795591

  5. Movement related cortical potentials of cued versus self-initiated movements: double dissociated modulation by dorsal premotor cortex versus supplementary motor area rTMS.

    PubMed

    Lu, Ming-Kuei; Arai, Noritoshi; Tsai, Chon-Haw; Ziemann, Ulf

    2012-04-01

    The dorsal premotor cortex (PMd) is thought to play a significant role in movement preparation cued by sensory information rather than in self-initiated movements. The evidence in humans for this contention is still circumstantial. Here we explored the effects of modulation of PMd by excitability decreasing 1 Hz repetitive transcranial magnetic stimulation (rTMS) versus excitability increasing 5 Hz rTMS on two forms of movement related cortical potentials: contingent negative variation (CNV) versus Bereitschaftspotential (BP) reflecting externally cued versus self-triggered movement preparation. Ten healthy right-handed subjects performed visually cued or self-triggered simple sequential finger movements with their right hand. CNV and BP were recorded by 25 EEG electrodes covering the fronto-centro-parietal cortex and divided into an early (1500-500 ms before a go-signal or movement onset) and a late potential (500-0 ms). MRI-navigated 1 Hz rTMS of the left PMd resulted in significant increase of the late CNV over the left central region predominantly contralateral to the prepared right hand movement, while 5 Hz rTMS had no effect on CNV. In contrast, 1 and 5 Hz rTMS did not modify BP. Control experiments of 1 Hz rTMS of the supplementary motor area (SMA) and of low-intensity 1 Hz rTMS of the left primary motor cortex did not change CNV, but 1 Hz SMA-rTMS increased late BP. This double dissociation of effects of PMd-rTMS versus SMA-rTMS on CNV versus BP provides direct evidence that the left PMd in humans is more involved in preparatory processes of externally cued rather than self-initiated movements, contrasting with an opposite role of the SMA. Copyright © 2011 Wiley Periodicals, Inc.

  6. One hertz repetitive transcranial magnetic stimulation over dorsal premotor cortex enhances offline motor memory consolidation for sequence-specific implicit learning.

    PubMed

    Meehan, S K; Zabukovec, J R; Dao, E; Cheung, K L; Linsdell, M A; Boyd, L A

    2013-10-01

    Consolidation of motor memories associated with skilled practice can occur both online, concurrent with practice, and offline, after practice has ended. The current study investigated the role of dorsal premotor cortex (PMd) in early offline motor memory consolidation of implicit sequence-specific learning. Thirty-three participants were assigned to one of three groups of repetitive transcranial magnetic stimulation (rTMS) over left PMd (5 Hz, 1 Hz or control) immediately following practice of a novel continuous tracking task. There was no additional practice following rTMS. This procedure was repeated for 4 days. The continuous tracking task contained a repeated sequence that could be learned implicitly and random sequences that could not. On a separate fifth day, a retention test was performed to assess implicit sequence-specific motor learning of the task. Tracking error was decreased for the group who received 1 Hz rTMS over the PMd during the early consolidation period immediately following practice compared with control or 5 Hz rTMS. Enhanced sequence-specific learning with 1 Hz rTMS following practice was due to greater offline consolidation, not differences in online learning between the groups within practice days. A follow-up experiment revealed that stimulation of PMd following practice did not differentially change motor cortical excitability, suggesting that changes in offline consolidation can be largely attributed to stimulation-induced changes in PMd. These findings support a differential role for the PMd in support of online and offline sequence-specific learning of a visuomotor task and offer converging evidence for competing memory systems. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  7. Processing of visual signals for direct specification of motor targets and for conceptual representation of action targets in the dorsal and ventral premotor cortex.

    PubMed

    Yamagata, Tomoko; Nakayama, Yoshihisa; Tanji, Jun; Hoshi, Eiji

    2009-12-01

    Previous reports have indicated that the premotor cortex (PM) uses visual information for either direct guidance of limb movements or indirect specification of action targets at a conceptual level. We explored how visual inputs signaling these two different categories of information are processed by PM neurons. Monkeys performed a delayed reaching task after receiving two different sets of visual instructions, one directly specifying the spatial location of a motor target (a direct spatial-target cue) and the other providing abstract information about the spatial location of a motor target by indicating whether to select the right or left target at a conceptual level (a symbolic action-selection cue). By comparing visual responses of PM neurons to the two sets of visual cues, we found that the conceptual action plan indicated by the symbolic action-selection cue was represented predominantly in dorsal PM (PMd) neurons with a longer latency (150 ms), whereas both PMd and ventral PM (PMv) neurons responded with a shorter latency (90 ms) when the motor target was directly specified with the direct spatial-target cue. We also found that excited, but not inhibited, responses of PM neurons to the direct spatial-target cue were biased toward contralateral preference. In contrast, responses to the symbolic action-selection cue were either excited or inhibited without laterality preference. Taken together, these results suggest that the PM constitutes a pair of distinct circuits for visually guided motor act; one circuit, linked more strongly with PMd, carries information for retrieving action instruction associated with a symbolic cue, and the other circuit, linked with PMd and PMv, carries information for directly specifying a visuospatial position of a reach target.

  8. Dorsal premotor cortex: neural correlates of reach target decisions based on a color-location matching rule and conflicting sensory evidence.

    PubMed

    Coallier, Émilie; Michelet, Thomas; Kalaska, John F

    2015-06-01

    We recorded single-neuron activity in dorsal premotor (PMd) and primary motor cortex (M1) of two monkeys in a reach-target selection task. The monkeys chose between two color-coded potential targets by determining which target's color matched the predominant color of a multicolored checkerboard-like Decision Cue (DC). Different DCs contained differing numbers of colored squares matching each target. The DCs provided evidence about the correct target ranging from unambiguous (one color only) to very ambiguous and conflicting (nearly equal number of squares of each color). Differences in choice behavior (reach response times and success rates as a function of DC ambiguity) of the monkeys suggested that each applied a different strategy for using the target-choice evidence in the DCs. Nevertheless, the appearance of the DCs evoked a transient coactivation of PMd neurons preferring both potential targets in both monkeys. Reach response time depended both on how long it took activity to increase in neurons that preferred the chosen target and on how long it took to suppress the activity of neurons that preferred the rejected target, in both correct-choice and error-choice trials. These results indicate that PMd neurons in this task are not activated exclusively by a signal proportional to the net color bias of the DCs. They are instead initially modulated by the conflicting evidence supporting both response choices; final target selection may result from a competition between representations of the alternative choices. The results also indicate a temporal overlap between action selection and action initiation processes in PMd and M1.

  9. Dorsal premotor cortex: neural correlates of reach target decisions based on a color-location matching rule and conflicting sensory evidence

    PubMed Central

    Coallier, Émilie; Michelet, Thomas

    2015-01-01

    We recorded single-neuron activity in dorsal premotor (PMd) and primary motor cortex (M1) of two monkeys in a reach-target selection task. The monkeys chose between two color-coded potential targets by determining which target's color matched the predominant color of a multicolored checkerboard-like Decision Cue (DC). Different DCs contained differing numbers of colored squares matching each target. The DCs provided evidence about the correct target ranging from unambiguous (one color only) to very ambiguous and conflicting (nearly equal number of squares of each color). Differences in choice behavior (reach response times and success rates as a function of DC ambiguity) of the monkeys suggested that each applied a different strategy for using the target-choice evidence in the DCs. Nevertheless, the appearance of the DCs evoked a transient coactivation of PMd neurons preferring both potential targets in both monkeys. Reach response time depended both on how long it took activity to increase in neurons that preferred the chosen target and on how long it took to suppress the activity of neurons that preferred the rejected target, in both correct-choice and error-choice trials. These results indicate that PMd neurons in this task are not activated exclusively by a signal proportional to the net color bias of the DCs. They are instead initially modulated by the conflicting evidence supporting both response choices; final target selection may result from a competition between representations of the alternative choices. The results also indicate a temporal overlap between action selection and action initiation processes in PMd and M1. PMID:25787952

  10. 1 Hz repetitive transcranial magnetic stimulation over dorsal premotor cortex enhances offline motor memory consolidation for sequence-specific implicit learning

    PubMed Central

    Meehan, S.K.; Zabukovec, J.R.; Dao, E.; Cheung, K.L.; Linsdell, M.A.; Boyd, L.A.

    2016-01-01

    Consolidation of motor memories associated with skilled practice can occur both online, concurrent with practice, and offline, after practice has ended. The current study investigated the role of dorsal premotor cortex (PMd) in early offline motor memory consolidation of implicit sequence specific learning. Thirty-three participants were assigned to one of three groups of repetitive TMS over left PMd (5 Hz, 1 Hz or control) immediately following practice of a novel continuous tracking task. There was no additional practice following repetitive TMS. This procedure was repeated for 4 days. The continuous tracking task contained a repeated sequence that could be learned implicitly and random sequences that could not. On a separate fifth day, a retention test was performed to assess implicit sequence-specific motor learning of the task. Tracking error was decreased for the group who received 1 Hz repetitive TMS over the PMd during the early consolidation period immediately following practice compared to control or 5 Hz repetitive TMS. Enhanced sequence specific learning with 1 Hz repetitive TMS following practice was due to greater offline consolidation, not differences in online learning between the groups within practice days. A follow-up experiment revealed that stimulation of PMd following practice did not differentially change motor cortical excitability, suggesting that changes in offline consolidation can be largely attributed to stimulation induced changes in PMd. These findings support a differential role for the PMd in support of online and offline sequence specific learning of a visuomotor task and offer converging evidence for competing memory systems. PMID:23834742

  11. Premotor cortex mediates perceptual performance.

    PubMed

    Callan, Daniel; Callan, Akiko; Gamez, Mario; Sato, Masa-aki; Kawato, Mitsuo

    2010-06-01

    Articulatory goals have long been proposed to mediate perception. Examples include direct realist and constructivist (analysis by synthesis) theories of speech perception. Although the activity in brain regions involved with action production has been shown to be present during action observation (Mirror Neuron System), the relationship of this activity to perceptual performance has not been clearly demonstrated at the event level. To this end we used functional magnetic resonance imaging fMRI and magnetoencephalography MEG to measure brain activity for correct and incorrect trials of an auditory phonetic identification in noise task. FMRI analysis revealed activity in the premotor cortex including the neighboring frontal opercular part of Broca's area (PMC/Broca's) for both perception and production tasks involving the same phonetic stimuli (potential mirror system site) that was significantly greater for correct over incorrect perceptual identification trials. Time-frequency analysis of single trials conducted over MEG current localized to PMC/Broca's using a hierarchical variational Bayesian source analysis technique revealed significantly greater event-related synchronization ERS and desynchronization ERD for correct over incorrect trials in the alpha, beta, and gamma frequency range prior to and after stimulus presentation. Together, these fMRI and MEG results are consistent with the hypothesis that articulatory processes serve to facilitate perceptual performance, while further dispelling concerns that activity found in ventral PMC/Broca's (mirror system) is merely a product of covert production of the perceived action. The finding of performance predictive activity prior to stimulus onset as well as activity related to task difficulty instead of information available in stimulation are consistent with constructivist and contrary to direct realist theories of perception.

  12. Writer's cramp: increased dorsal premotor activity during intended writing.

    PubMed

    Delnooz, Cathérine C S; Helmich, Rick C; Medendorp, W P; Van de Warrenburg, Bart P C; Toni, Ivan

    2013-03-01

    Simple writer's cramp (WC) is a task-specific form of dystonia, characterized by abnormal movements and postures of the hand during writing. It is extremely task-specific, since dystonic symptoms can occur when a patient uses a pencil for writing, but not when it is used for sharpening. Maladaptive plasticity, loss of inhibition, and abnormal sensory processing are important pathophysiological elements of WC. However, it remains unclear how those elements can account for its task-specificity. We used fMRI to isolate cerebral alterations associated with the task-specificity of simple WC. Subjects (13 simple WC patients, 20 matched controls) imagined grasping a pencil to either write with it or sharpen it. On each trial, we manipulated the pencil's position and the number of imagined movements, while monitoring variations in motor output with electromyography. We show that simple WC is characterized by abnormally increased activity in the dorsal premotor cortex (PMd) when imagined actions are specifically related to writing. This cerebral effect was independent from the known deficits in dystonia in generating focal motor output and in processing somatosensory feedback. This abnormal activity of the PMd suggests that the task-specific element of simple WC is primarily due to alterations at the planning level, in the computations that transform a desired action outcome into the motor commands leading to that action. These findings open the way for testing the therapeutic value of interventions that take into account the computational substrate of task-specificity in simple WC, e.g. modulations of PMd activity during the planning phase of writing.

  13. Relationship between the corticostriatal terminals from areas 9 and 46, and those from area 8A, dorsal and rostral premotor cortex and area 24c: an anatomical substrate for cognition to action

    PubMed Central

    Calzavara, Roberta; Mailly, Philippe; Haber, Suzanne N

    2007-01-01

    Our previous data indicate that there are specific features of the corticostriatal pathways from the prefrontal cortex. First, corticostriatal pathways are composed of focal, circumscribed projections and of diffuse, widespread projections. Second, there is some convergence between terminal fields from different functional regions of the prefrontal cortex. Third, anterior cingulate projections from area 24b occupy a large region of the rostral striatum. The goal of this study was to determine whether these features are also common to the corticostriatal projections from area 8A (including the frontal eye field; FEF), the supplementary eye field (SEF), dorsal and rostral premotor cortex (PMdr) and area 24c. Using a new approach of three-dimensional reconstruction of the corticostriatal pathways, along with dual cortical tracer injections, we mapped the corticostriatal terminal fields from areas 9 and 46, 8A-FEF, SEF, PMdr and 24b and c. In addition, we placed injections of retrogradely transported tracers into key striatal regions. The results demonstrated that: (i) a diffuse projection system is a common feature of the corticostriatal projections from different frontal regions; (ii) key striatal regions receive convergent projections from areas 9 and 46 and from areas 8A-FEF, SEF, PMdr and 24c, suggesting a potential pivotal role of these striatal regions in integrating cortical information; (iii) projections from area 24c, like those from area 24b, terminate widely throughout the striatum, interfacing with terminals from several frontal areas. These features of the corticostriatal frontal pathways suggest a potential integrative striatal network for learning. PMID:17892479

  14. Ipsilateral cortical connections of dorsal and ventral premotor areas in New World owl monkeys.

    PubMed

    Stepniewska, Iwona; Preuss, Todd M; Kaas, Jon H

    2006-04-20

    In order to compare connections of premotor cortical areas of New World monkeys with those of Old World macaque monkeys and prosimian galagos, we placed injections of fluorescent tracers and wheat germ agglutinin-horseradish peroxidase (WGA-HRP) in dorsal (PMD) and ventral (PMV) premotor areas of owl monkeys. Motor areas and injection sites were defined by patterns of movements electrically evoked from the cortex with microelectrodes. Labeled neurons and axon terminals were located in brain sections cut either in the coronal plane or parallel to the surface of flattened cortex, and they related to architectonically and electrophysiologically defined cortical areas. Both the PMV and PMD had connections with the primary motor cortex (M1), the supplementary motor area (SMA), cingulate motor areas, somatosensory areas S2 and PV, and the posterior parietal cortex. Only the PMV had connections with somatosensory areas 3a, 1, 2, PR, and PV. The PMD received inputs from more caudal portions of the cortex of the lateral sulcus and more medial portions of the posterior parietal cortex than the PMV. The PMD and PMV were only weakly interconnected. New World owl monkeys, Old World macaque monkeys, and galagos share a number of PMV and PMD connections, suggesting preservation of a common sensorimotor network from early primates. Comparisons of PMD and PMV connectivity with the cortex of the lateral sulcus and posterior parietal cortex of owl monkeys, galagos, and macaques help identify areas that could be homologous.

  15. Robust neuronal dynamics in premotor cortex during motor planning

    PubMed Central

    Li, Nuo; Daie, Kayvon; Svoboda, Karel; Druckmann, Shaul

    2016-01-01

    Neural activity maintains representations that bridge past and future events, often over many seconds. Network models can produce persistent and ramping activity, but the positive feedback that is critical for these slow dynamics can cause sensitivity to perturbations. Here we use electrophysiology and optogenetic perturbations in mouse premotor cortex to probe robustness of persistent neural representations during motor planning. Preparatory activity is remarkably robust to large-scale unilateral silencing: detailed neural dynamics that drive specific future movements were quickly and selectively restored by the network. Selectivity did not recover after bilateral silencing of premotor cortex. Perturbations to one hemisphere are thus corrected by information from the other hemisphere. Corpus callosum bisections demonstrated that premotor cortex hemispheres can maintain preparatory activity independently. Redundancy across selectively coupled modules, as we observed in premotor cortex, is a hallmark of robust control systems. Network models incorporating these principles show robustness that is consistent with data. PMID:27074502

  16. The primary motor and premotor areas of the human cerebral cortex.

    PubMed

    Chouinard, Philippe A; Paus, Tomás

    2006-04-01

    Brodmann's cytoarchitectonic map of the human cortex designates area 4 as cortex in the anterior bank of the precentral sulcus and area 6 as cortex encompassing the precentral gyrus and the posterior portion of the superior frontal gyrus on both the lateral and medial surfaces of the brain. More than 70 years ago, Fulton proposed a functional distinction between these two areas, coining the terms primary motor area for cortex in Brodmann area 4 and premotor area for cortex in Brodmann area 6. The parcellation of the cortical motor system has subsequently become more complex. Several nonprimary motor areas have been identified in the brain of the macaque monkey, and associations between anatomy and function in the human brain are being tested continuously using brain mapping techniques. In the present review, the authors discuss the unique properties of the primary motor area (M1), the dorsal portion of the premotor cortex (PMd), and the ventral portion of the premotor cortex (PMv). They end this review by discussing how the premotor areas influence M1.

  17. Role of the primary motor and dorsal premotor cortices in the anticipation of forces during object lifting.

    PubMed

    Chouinard, Philippe A; Leonard, Gabriel; Paus, Tomás

    2005-03-02

    When lifting small objects, people apply forces that match the expected weight of the object. This expectation relies in part on information acquired during a previous lift and on associating a certain weight with a particular object. Our study examined the role of the primary motor and dorsal premotor cortices in predicting weight based either on information acquired during a previous lift (no-cue experiment) or on arbitrary color cues associated with a particular weight (cue experiment). In the two experiments, subjects used precision grip to lift two different weights in a series of trials both before and after we applied low-frequency repetitive transcranial magnetic stimulation over the primary motor and dorsal premotor cortices. In the no-cue experiment, subjects did not receive any previous information about which of two weights they would have to lift. In the cue experiment, a color cue provided information about which of the two weights subjects would have to lift. Our results demonstrate a double dissociation in the effects induced by repetitive stimulation. When applied over the primary motor cortex, repetitive stimulation disrupted the scaling of forces based on information acquired during a previous lift. In contrast, when applied over the dorsal premotor cortex, repetitive stimulation disrupted the scaling of forces based on arbitrary color cues. We conclude that the primary motor and dorsal premotor cortices have unique roles during the anticipatory scaling of forces associated with the lifting of different weights.

  18. Heterogeneous Attractor Cell Assemblies for Motor Planning in Premotor Cortex

    PubMed Central

    Pani, Pierpaolo; Mirabella, Giovanni; Costa, Stefania; Del Giudice, Paolo

    2013-01-01

    Cognitive functions like motor planning rely on the concerted activity of multiple neuronal assemblies underlying still elusive computational strategies. During reaching tasks, we observed stereotyped sudden transitions (STs) between low and high multiunit activity of monkey dorsal premotor cortex (PMd) predicting forthcoming actions on a single-trial basis. Occurrence of STs was observed even when movement was delayed or successfully canceled after a stop signal, excluding a mere substrate of the motor execution. An attractor model accounts for upward STs and high-frequency modulations of field potentials, indicative of local synaptic reverberation. We found in vivo compelling evidence that motor plans in PMd emerge from the coactivation of such attractor modules, heterogeneous in the strength of local synaptic self-excitation. Modules with strong coupling early reacted with variable times to weak inputs, priming a chain reaction of both upward and downward STs in other modules. Such web of “flip-flops” rapidly converged to a stereotyped distributed representation of the motor program, as prescribed by the long-standing theory of associative networks. PMID:23825419

  19. Encoding of Both Reaching and Grasping Kinematics in Dorsal and Ventral Premotor Cortices.

    PubMed

    Takahashi, Kazutaka; Best, Matthew D; Huh, Noah; Brown, Kevin A; Tobaa, Adil A; Hatsopoulos, Nicholas G

    2017-02-15

    Classically, it has been hypothesized that reach-to-grasp movements arise from two discrete parietofrontal cortical networks. As part of these networks, the dorsal premotor cortex (PMd) has been implicated in the control of reaching movements of the arm, whereas the ventral premotor cortex (PMv) has been associated with the control of grasping movements of the hand. Recent studies have shown that such a strict delineation of function along anatomical boundaries is unlikely, partly because reaching to different locations can alter distal hand kinematics and grasping different objects can affect kinematics of the proximal arm. Here, we used chronically implanted multielectrode arrays to record unit-spiking activity in both PMd and PMv simultaneously while rhesus macaques engaged in a reach-to-grasp task. Generalized linear models were used to predict the spiking activity of cells in both areas as a function of different kinematic parameters, as well as spike history. To account for the influence of reaching on hand kinematics and vice versa, we applied demixed principal components analysis to define kinematics synergies that maximized variance across either different object locations or grip types. We found that single cells in both PMd and PMv encode the kinematics of both reaching and grasping synergies, suggesting that this classical division of reach and grasp in PMd and PMv, respectively, does not accurately reflect the encoding preferences of cells in those areas.SIGNIFICANCE STATEMENT For reach-to-grasp movements, the dorsal premotor cortex (PMd) has been implicated in the control of reaching movements of the arm, whereas the ventral premotor cortex (PMv) has been associated with the control of grasping movements of the hand. We recorded unit-spiking activity in PMd and PMv simultaneously while macaques performed a reach-to-grasp task. We modeled the spiking activity of neurons as a function of kinematic parameters and spike history. We applied demixed

  20. A Mediating Role of the Premotor Cortex in Phoneme Segmentation

    ERIC Educational Resources Information Center

    Sato, Marc; Tremblay, Pascale; Gracco, Vincent L.

    2009-01-01

    Consistent with a functional role of the motor system in speech perception, disturbing the activity of the left ventral premotor cortex by means of repetitive transcranial magnetic stimulation (rTMS) has been shown to impair auditory identification of syllables that were masked with white noise. However, whether this region is crucial for speech…

  1. A Mediating Role of the Premotor Cortex in Phoneme Segmentation

    ERIC Educational Resources Information Center

    Sato, Marc; Tremblay, Pascale; Gracco, Vincent L.

    2009-01-01

    Consistent with a functional role of the motor system in speech perception, disturbing the activity of the left ventral premotor cortex by means of repetitive transcranial magnetic stimulation (rTMS) has been shown to impair auditory identification of syllables that were masked with white noise. However, whether this region is crucial for speech…

  2. Shaping the excitability of human motor cortex with premotor rTMS

    PubMed Central

    Rizzo, Vincenzo; Siebner, Hartwig R; Modugno, Nicola; Pesenti, Alessandra; Münchau, Alexander; Gerschlager, Willibald; Webb, Ruth M; Rothwell, John C

    2004-01-01

    Recent studies have shown that low-frequency repetitive transcranial magnetic stimulation (rTMS) to the left dorsal premotor cortex has a lasting influence on the excitability of specific neuronal subpopulations in the ipsilateral primary motor hand area (M1HAND). Here we asked how these premotor to motor interactions are shaped by the intensity and frequency of rTMS and the orientation of the stimulating coil. We confirmed that premotor rTMS at 1 Hz and an intensity of 90% active motor threshold (AMT) produced a lasting decrease in corticospinal excitability probed with single-pulse TMS over the left M1HAND. Reducing the intensity to 80% AMT increased paired-pulse excitability at an interstimulus interval (ISI) of 7 ms. Opposite effects occurred if rTMS was given at 5 Hz: at 90% AMT, corticospinal excitability increased; at 80% AMT, paired-pulse excitability at ISI = 7 ms decreased. No effects were seen if rTMS was applied at the same intensities to prefrontal or primary motor cortices. These findings indicate that the intensity of premotor rTMS determines the net effect of conditioning on distinct populations of neurones in the ipsilateral M1HAND, but it is the frequency of rTMS that determines the direction of the induced change. By selecting the appropriate intensity and frequency, premotor rTMS allows to induce a predictable up- or down-regulation of the excitability in distinct neuronal circuits of human M1HAND. PMID:14555728

  3. Multisensory and modality specific processing of visual speech in different regions of the premotor cortex

    PubMed Central

    Callan, Daniel E.; Jones, Jeffery A.; Callan, Akiko

    2014-01-01

    Behavioral and neuroimaging studies have demonstrated that brain regions involved with speech production also support speech perception, especially under degraded conditions. The premotor cortex (PMC) has been shown to be active during both observation and execution of action (“Mirror System” properties), and may facilitate speech perception by mapping unimodal and multimodal sensory features onto articulatory speech gestures. For this functional magnetic resonance imaging (fMRI) study, participants identified vowels produced by a speaker in audio-visual (saw the speaker's articulating face and heard her voice), visual only (only saw the speaker's articulating face), and audio only (only heard the speaker's voice) conditions with varying audio signal-to-noise ratios in order to determine the regions of the PMC involved with multisensory and modality specific processing of visual speech gestures. The task was designed so that identification could be made with a high level of accuracy from visual only stimuli to control for task difficulty and differences in intelligibility. The results of the functional magnetic resonance imaging (fMRI) analysis for visual only and audio-visual conditions showed overlapping activity in inferior frontal gyrus and PMC. The left ventral inferior premotor cortex (PMvi) showed properties of multimodal (audio-visual) enhancement with a degraded auditory signal. The left inferior parietal lobule and right cerebellum also showed these properties. The left ventral superior and dorsal premotor cortex (PMvs/PMd) did not show this multisensory enhancement effect, but there was greater activity for the visual only over audio-visual conditions in these areas. The results suggest that the inferior regions of the ventral premotor cortex are involved with integrating multisensory information, whereas, more superior and dorsal regions of the PMC are involved with mapping unimodal (in this case visual) sensory features of the speech signal with

  4. Exploring the contributions of premotor and parietal cortex to spatial compatibility using image-guided TMS.

    PubMed

    Koski, Lisa; Molnar-Szakacs, Istvan; Iacoboni, Marco

    2005-01-15

    Functional brain imaging studies have demonstrated increased activity in dorsal premotor and posterior parietal cortex when performing spatial stimulus-response compatibility tasks (SRC). We tested the specific role of these regions in stimulus-response mapping using single-pulse transcranial magnetic stimulation (TMS). Subjects were scanned using functional magnetic resonance imaging (fMRI) prior to the TMS session during performance of a task in which spatial compatibility was manipulated. For each subject, the area of increased signal within the regions of interest was registered onto their own high-resolution T1-weighted anatomic scan. TMS was applied to these areas for each subject using a frameless stereotaxic system. Task accuracy and reaction time (RT) were measured during blocks of compatible or incompatible trials and during blocks of real TMS or sham stimulation. On each trial, a single TMS pulse was delivered at 50, 100, 150, or 200 ms after the onset of the stimulus in the left or right visual field. TMS over the left premotor cortex produced various facilitatory effects, depending on the timing of the stimulation. At short intervals, TMS appeared to prime the left dorsal premotor cortex to select a right-hand response more quickly, regardless of stimulus-response compatibility. The strongest effect of stimulation, however, occurred at the 200-ms interval, when TMS facilitated left-hand responses during the incompatible condition. Facilitation of attention to the contralateral visual hemifield was observed during stimulation over the parietal locations. We conclude that the left premotor cortex is one of the cortical regions responsible for overriding automatic stimulus-response associations.

  5. Prediction processes during multiple object tracking (MOT): involvement of dorsal and ventral premotor cortices

    PubMed Central

    Atmaca, Silke; Stadler, Waltraud; Keitel, Anne; Ott, Derek V M; Lepsien, Jöran; Prinz, Wolfgang

    2013-01-01

    Background The multiple object tracking (MOT) paradigm is a cognitive task that requires parallel tracking of several identical, moving objects following nongoal-directed, arbitrary motion trajectories. Aims The current study aimed to investigate the employment of prediction processes during MOT. As an indicator for the involvement of prediction processes, we targeted the human premotor cortex (PM). The PM has been repeatedly implicated to serve the internal modeling of future actions and action effects, as well as purely perceptual events, by means of predictive feedforward functions. Materials and methods Using functional magnetic resonance imaging (fMRI), BOLD activations recorded during MOT were contrasted with those recorded during the execution of a cognitive control task that used an identical stimulus display and demanded similar attentional load. A particular effort was made to identify and exclude previously found activation in the PM-adjacent frontal eye fields (FEF). Results We replicated prior results, revealing occipitotemporal, parietal, and frontal areas to be engaged in MOT. Discussion The activation in frontal areas is interpreted to originate from dorsal and ventral premotor cortices. The results are discussed in light of our assumption that MOT engages prediction processes. Conclusion We propose that our results provide first clues that MOT does not only involve visuospatial perception and attention processes, but prediction processes as well. PMID:24363971

  6. Long-range neural activity evoked by premotor cortex stimulation: a TMS/EEG co-registration study

    PubMed Central

    Zanon, Marco; Battaglini, Piero P.; Jarmolowska, Joanna; Pizzolato, Gilberto; Busan, Pierpaolo

    2013-01-01

    The premotor cortex is one of the fundamental structures composing the neural networks of the human brain. It is implicated in many behaviors and cognitive tasks, ranging from movement to attention and eye-related activity. Therefore, neural circuits that are related to premotor cortex have been studied to clarify their connectivity and/or role in different tasks. In the present work, we aimed to investigate the propagation of the neural activity evoked in the dorsal premotor cortex using transcranial magnetic stimulation/electroencephalography (TMS/EEG). Toward this end, interest was focused on the neural dynamics elicited in long-ranging temporal and spatial networks. Twelve healthy volunteers underwent a single-pulse TMS protocol in a resting condition with eyes closed, and the evoked activity, measured by EEG, was compared to a sham condition in a time window ranging from 45 ms to about 200 ms after TMS. Spatial and temporal investigations were carried out with sLORETA. TMS was found to induce propagation of neural activity mainly in the contralateral sensorimotor and frontal cortices, at about 130 ms after delivery of the stimulus. Different types of analyses showed propagated activity also in posterior, mainly visual, regions, in a time window between 70 and 130 ms. Finally, a likely “rebounding” activation of the sensorimotor and frontal regions, was observed in various time ranges. Taken together, the present findings further characterize the neural circuits that are driven by dorsal premotor cortex activation in healthy humans. PMID:24324426

  7. Neural encoding of auditory discrimination in ventral premotor cortex

    PubMed Central

    Lemus, Luis; Hernández, Adrián; Romo, Ranulfo

    2009-01-01

    Monkeys have the capacity to accurately discriminate the difference between two acoustic flutter stimuli. In this task, monkeys must compare information about the second stimulus to the memory trace of the first stimulus, and must postpone the decision report until a sensory cue triggers the beginning of the decision motor report. The neuronal processes associated with the different components of this task have been investigated in the primary auditory cortex (A1); but, A1 seems exclusively associated with the sensory and not with the working memory and decision components of this task. Here, we show that ventral premotor cortex (VPC) neurons reflect in their activities the current and remembered acoustic stimulus, their comparison, and the result of the animal's decision report. These results provide evidence that the neural dynamics of VPC is involved in the processing steps that link sensation and decision-making during auditory discrimination. PMID:19667191

  8. Increased premotor cortex activation in high functioning autism during action observation.

    PubMed

    Perkins, Tom J; Bittar, Richard G; McGillivray, Jane A; Cox, Ivanna I; Stokes, Mark A

    2015-04-01

    The mirror neuron (MN) hypothesis of autism has received considerable attention, but to date has produced inconsistent findings. Using functional MRI, participants with high functioning autism or Asperger's syndrome were compared to typically developing individuals (n=12 in each group). Participants passively observed hand gestures that included waving, pointing, and grasping. Concerning the MN network, both groups activated similar regions including prefrontal, inferior parietal and superior temporal regions, with the autism group demonstrating significantly greater activation in the dorsal premotor cortex. Concerning other regions, participants with autism demonstrated increased activity in the anterior cingulate and medial frontal gyrus, and reduced activation in calcarine, cuneus, and middle temporal gyrus. These results suggest that during observation of hand gestures, frontal cortex activation is affected in autism, which we suggest may be linked to abnormal functioning of the MN system.

  9. The role of the premotor cortex and the primary motor cortex in action verb comprehension: evidence from Granger causality analysis.

    PubMed

    Yang, Jie; Shu, Hua

    2012-08-01

    Although numerous studies find the premotor cortex and the primary motor cortex are involved in action language comprehension, so far the nature of these motor effects is still in controversy. Some researchers suggest that the motor effects reflect that the premotor cortex and the primary motor cortex make functional contributions to the semantic access of action verbs, while other authors argue that the motor effects are caused by comprehension. In the current study, we used Granger causality analysis to investigate the roles of the premotor cortex and the primary motor cortex in processing of manual-action verbs. Regions of interest were selected in the primary motor cortex (M1) and the premotor cortex based on a hand motion task, and in the left posterior middle temporal gyrus (lexical semantic area) based on the reading task effect. We found that (1) the left posterior middle temporal gyrus had a causal influence on the left M1; and (2) the left posterior middle temporal gyrus and the left premotor cortex had bidirectional causal relations. These results suggest that the premotor cortex and the primary motor cortex play different roles in manual verb comprehension. The premotor cortex may be involved in motor simulation that contributes to action language processing, while the primary motor cortex may be engaged in a processing stage influenced by the meaning access of manual-action verbs. Further investigation combining effective connectivity analysis and technique with high temporal resolution is necessary for better clarification of the roles of the premotor cortex and the primary motor cortex in action language comprehension.

  10. An oculomotor representation area within the ventral premotor cortex

    PubMed Central

    Fujii, Naotaka; Mushiake, Hajime; Tanji, Jun

    1998-01-01

    We explored the ventral part of the premotor cortex (PMV) with intracortical microstimulation (ICMS) while monkeys performed a visual fixation task, to see whether the PMV is involved in oculomotor control. ICMS evoked saccades from a small-restricted region in the PMV, without evoking movements in the limbs, neck, or body. We found the saccade-evoking site in the PMV in a total of three hemispheres in two monkeys. Quantitative analysis of the effects of eye position on saccades evoked by microstimulation of the PMV characterized the evoked saccades as goal directed. The nature of the saccades evoked in the PMV contrasted with the fixed vector nature of saccades evoked by ICMS of the frontal eye field. We also found that neurons in this restricted area of the PMV were active while the animals were performing a saccade task that required them to make saccades toward targets without arm movements. These data provide evidence for the presence of an oculomotor-specific subregion within the PMV. This subregion and the surrounding skeletomotor-representing regions of the PMV seem to coordinate oculomotor and skeletomotor control in performing goal-directed motor tasks. PMID:9751785

  11. Differential activity in the premotor cortex subdivisions in humans during mental calculation and verbal rehearsal tasks: a functional magnetic resonance imaging study.

    PubMed

    Hanakawa, Takashi; Honda, Manabu; Okada, Tomohisa; Fukuyama, Hidenao; Shibasaki, Hiroshi

    2003-08-28

    To investigate a possible role of the lateral premotor cortex in human cognitive processes, we compared brain activity during mental-operation numeral (MO-numeral) and verbal rehearsal (VR) tasks, using block-design functional MRI. Sixteen healthy subjects serially added a series of single-digit numbers during the MO-numeral task and silently rehearsed a memorized seven-digit number during the VR task. Each task condition was contrasted with a visual fixation task. Both MO-numeral and VR tasks revealed activity within the lateral premotor cortex among others. The rostral and dorsal part of the lateral premotor cortex (PMdr) showed significantly greater activity during the MO-numeral task than the VR task whereas its caudal part (PMdc) was similarly active during the two tasks. The present study suggests that the PMdr and PMdc are involved in different non-motor cognitive processes.

  12. Activation and connectivity patterns of the presupplementary and dorsal premotor areas during free improvisation of melodies and rhythms.

    PubMed

    de Manzano, Örjan; Ullén, Fredrik

    2012-10-15

    Free, i.e. non-externally cued generation of movement sequences is fundamental to human behavior. We have earlier hypothesized that the dorsal premotor cortex (PMD), which has been consistently implicated in cognitive aspects of planning and selection of spatial motor sequences may be particularly important for the free generation of spatial movement sequences, whereas the pre-supplementary motor area (pre-SMA), which shows increased activation during perception, learning and reproduction of temporal sequences, may contribute more to the generation of temporal structures. Here we test this hypothesis using fMRI and musical improvisation in professional pianists as a model behavior. We employed a 2 × 2 factorial design with the factors Melody (Specified/Improvised) and Rhythm (Specified/Improvised). The main effect analyses partly confirmed our hypothesis: there was a main effect of Melody in the PMD; the pre-SMA was present in the main effect of Rhythm, as predicted, as well as in the main effect of Melody. A psychophysiological interaction analysis of functional connectivity demonstrated that the correlation in activity between the pre-SMA and cerebellum was higher during rhythmic improvisation than during the other conditions. In summary, there were only subtle differences in activity level between the pre-SMA and PMD during improvisation, regardless of condition. Consequently, the free generation of rhythmic and melodic structures, appears to be largely integrated processes but the functional connectivity between premotor areas and other regions may change during free generation in response to sequence-specific spatiotemporal demands.

  13. Transcranial direct current stimulation of the premotor cortex: effects on hand dexterity.

    PubMed

    Pavlova, Elena; Kuo, Min-Fang; Nitsche, Michael A; Borg, Jörgen

    2014-08-12

    Premotor cortex activity is associated with complex motor performance and motor learning and offers a potential target to improve dexterity by transcranial direct current stimulation (tDCS). We explored the effects of tDCS of premotor cortex on performance of a Strength-Dexterity test in healthy subjects. During the test a slender spring held between thumb and index finger should be compressed as much as possible without buckling. Finger forces assessed in the test provided a measure of dexterity. First, task performance was tested in 12 persons during anodal tDCS to the primary motor cortex (M1) contralateral to the performing hand, and sham stimulation. Another 12 persons participated in five sessions of anodal and cathodal tDCS over the left and the right premotor cortex and sham stimulation. tDCS over M1 as well as over the left, but not the right premotor cortex resulted in significant improvement of performance. Performance alterations correlated positively between left anodal and right cathodal tDCS and negatively between anodal tDCS of the two sides. Effective polarity for premotor stimulation to improve task performance differed between participants. Individuals who improved with anodal stimulation used lower finger force and experienced the test as more difficult compared to those who improved with cathodal stimulation. This study demonstrates that tDCS over the left premotor cortex can improve performance of a dexterity demanding task. The effective polarity of stimulation depends on the task performance strategies. The study moreover shows a functional relevance of interactions between the left and right premotor cortex. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Contribution of the premotor cortex to consolidation of motor sequence learning in humans during sleep.

    PubMed

    Nitsche, Michael A; Jakoubkova, Michaela; Thirugnanasambandam, Nivethida; Schmalfuss, Leonie; Hullemann, Sandra; Sonka, Karel; Paulus, Walter; Trenkwalder, Claudia; Happe, Svenja

    2010-11-01

    Motor learning and memory consolidation require the contribution of different cortices. For motor sequence learning, the primary motor cortex is involved primarily in its acquisition. Premotor areas might be important for consolidation. In accordance, modulation of cortical excitability via transcranial DC stimulation (tDCS) during learning affects performance when applied to the primary motor cortex, but not premotor cortex. We aimed to explore whether premotor tDCS influences task performance during motor memory consolidation. The impact of excitability-enhancing, -diminishing, or placebo premotor tDCS during rapid eye movement (REM) sleep on recall in the serial reaction time task (SRTT) was explored in healthy humans. The motor task was learned in the evening. Recall was performed immediately after tDCS or the following morning. In two separate control experiments, excitability-enhancing premotor tDCS was performed 4 h after task learning during daytime or immediately before conduction of a simple reaction time task. Excitability-enhancing tDCS performed during REM sleep increased recall of the learned movement sequences, when tested immediately after stimulation. REM density was enhanced by excitability-increasing tDCS and reduced by inhibitory tDCS, but did not correlate with task performance. In the control experiments, tDCS did not improve performance. We conclude that the premotor cortex is involved in motor memory consolidation during REM sleep.

  15. Reputation in an economic game modulates premotor cortex activity during action observation.

    PubMed

    Farmer, Harry; Apps, Matthew; Tsakiris, Manos

    2016-09-01

    Our interactions with other people - and our processing of their actions - are shaped by their reputation. Research has identified an Action Observation Network (AON) which is engaged when observing other people's actions. Yet, little is known about how the processing of others' actions is influenced by another's reputation. Is the response of the AON modulated by the reputation of the actor? We developed a variant of the ultimatum game in which participants watched either the visible or occluded actions of two 'proposers'. These actions were tied to decisions of how to split a pot of money although the proposers' decisions on each trial were not known to participants when observing the actions. One proposer made fair offers on the majority of trials, establishing a positive reputation, whereas the other made predominantly, unfair offers resulting in a negative reputation. We found significant activations in two regions of the left dorsal premotor cortex (dPMC). The first of these showed a main effect of reputation with greater activation for the negative reputation proposer than the positive reputation proposer. Furthermore individual differences in trust ratings of the two proposers covaried with activation in the right primary motor cortex (M1). The second showed an interaction between visibility and reputation driven by a greater effect of reputation when participants were observing an occluded action. Our findings show that the processing of others' actions in the AON is modulated by an actor's reputation, and suggest a predictive role for the PMC during action observation.

  16. The importance of premotor cortex for supporting speech production after left capsular-putaminal damage.

    PubMed

    Seghier, Mohamed L; Bagdasaryan, Juliana; Jung, Dorit E; Price, Cathy J

    2014-10-22

    The left putamen is known to be important for speech production, but some patients with left putamen damage can produce speech remarkably well. We investigated the neural mechanisms that support this recovery by using a combination of techniques to identify the neural regions and pathways that compensate for loss of the left putamen during speech production. First, we used fMRI to identify the brain regions that were activated during reading aloud and picture naming in a patient with left putamen damage. This revealed that the patient had abnormally high activity in the left premotor cortex. Second, we used dynamic causal modeling of the patient's fMRI data to understand how this premotor activity influenced other speech production regions and whether the same neural pathway was used by our 24 neurologically normal control subjects. Third, we validated the compensatory relationship between putamen and premotor cortex by showing, in the control subjects, that lower connectivity through the putamen increased connectivity through premotor cortex. Finally, in a lesion-deficit analysis, we demonstrate the explanatory power of our fMRI results in new patients who had damage to the left putamen, left premotor cortex, or both. Those with damage to both had worse reading and naming scores. The results of our four-pronged approach therefore have clinical implications for predicting which patients are more or less likely to recover their speech after left putaminal damage. Copyright © 2014 Seghier et al.

  17. Prefrontal and agranular cingulate projections to the dorsal premotor areas F2 and F7 in the macaque monkey.

    PubMed

    Luppino, Giuseppe; Rozzi, Stefano; Calzavara, Roberta; Matelli, Massimo

    2003-02-01

    The superior sector of Brodmann area 6 (dorsal premotor cortex, PMd) of the macaque monkey consists of a rostral and a caudal architectonic area referred to as F7 and F2, respectively. The aim of this study was to define the origin of prefrontal and agranular cingulate afferents to F7 and F2, in the light of functional and hodological evidence showing that these areas do not appear to be functionally homogeneous. Different sectors of F7 and F2 were injected with neural tracers in seven monkeys and the retrograde labelling was qualitatively and quantitatively analysed. The dorsorostral part of F7 (supplementary eye field, F7-SEF) was found to be a target of strong afferents from the frontal eye field (FEF), from the dorsolateral prefrontal regions located dorsally (DLPFd) and ventrally (DLPFv) to the principal sulcus and from cingulate areas 24a, 24b and 24c. In contrast, the remaining part of F7 (F7-non SEF) is only a target of the strong afferents from DLPFd. Finally, the ventrorostral part of F2 (F2vr), but not the F2 sector located around the superior precentral dimple (F2d), receives a minor, but significant, input from DLPFd and a relatively strong input from the cingulate gyrus (areas 24a and 24b) and area 24d. Present data provide strong hodological support in favour of the idea that areas F7 and F2 are formed by two functionally distinct sectors.

  18. Dorsal Premotor Neurons Encode the Relative Position of the Hand, Eye, and Goal during Reach Planning

    PubMed Central

    Pesaran, Bijan; Nelson, Matthew J.; Andersen, Richard A.

    2011-01-01

    Summary When reaching to grasp an object, we often move our arm and orient our gaze together. How are these movements coordinated? To investigate this question, we studied neuronal activity in the dorsal premotor area (PMd) and the medial intraparietal area (area MIP) of two monkeys while systematically varying the starting position of the hand and eye during reaching. PMd neurons encoded the relative position of the target, hand, and eye. MIP neurons encoded target location with respect to the eye only. These results indicate that whereas MIP encodes target locations in an eye-centered reference frame, PMd uses a relative position code that specifies the differences in locations between all three variables. Such a relative position code may play an important role in coordinating hand and eye movements by computing their relative position. PMID:16815337

  19. TMS-Induced Modulation of Action Sentence Priming in the Ventral Premotor Cortex

    ERIC Educational Resources Information Center

    Tremblay, Pascale; Sato, Marc; Small, Steven L.

    2012-01-01

    Despite accumulating evidence that cortical motor areas, particularly the lateral premotor cortex, are activated during language comprehension, the question of whether motor processes help mediate the semantic encoding of language remains controversial. To address this issue, we examined whether low frequency (1 Hz) repetitive transcranial…

  20. [Neural correlates of perceptual decisions: the role of the ventral premotor cortex].

    PubMed

    Pardo-Vázquez, José L; Acuña, Carlos

    2014-05-01

    Although the premotor cortex was initially viewed as the substrate of pure motor functions, it was soon realized that this cortical region is also involved in higher order cognitive processes. By using behavioral tasks together with electrophysiological recordings it has been possible to advance in our understanding on the functional role of this area. Given its pattern of connections, the premotor ventral cortex is well suited to participate in perceptual decisions, in which sensory information is combined with knowledge on previous outcomes and expectancies to reach a behavioral choice. The neuronal correlates of the decision process have been described in several cortical areas of primates. In this work we describe our experimental results showing that different stages or elements of perceptual decisions are encoded in the firing rate of premotor ventral cortex neurons. This provides compelling evidence suggesting that this area is involved in the use of sensory evidence -maintained in working memory or retrieved from long-term memory- to reach a decision. Furthermore, after the behavioral response the same neurons convey all the information needed to evaluate the outcome of the choice. This suggests that the premotor ventral cortex could participate in shaping future behavior as a result of this evaluation.

  1. TMS-Induced Modulation of Action Sentence Priming in the Ventral Premotor Cortex

    ERIC Educational Resources Information Center

    Tremblay, Pascale; Sato, Marc; Small, Steven L.

    2012-01-01

    Despite accumulating evidence that cortical motor areas, particularly the lateral premotor cortex, are activated during language comprehension, the question of whether motor processes help mediate the semantic encoding of language remains controversial. To address this issue, we examined whether low frequency (1 Hz) repetitive transcranial…

  2. Rewiring the Brain: Potential Role of the Premotor Cortex in Motor Control, Learning, and Recovery of Function Following Brain Injury

    PubMed Central

    Kantak, Shailesh S.; Stinear, James W.; Buch, Ethan R.; Cohen, Leonardo G.

    2016-01-01

    The brain is a plastic organ with a capability to reorganize in response to behavior and/or injury. Following injury to the motor cortex or emergent corticospinal pathways, recovery of function depends on the capacity of surviving anatomical resources to recover and repair in response to task-specific training. One such area implicated in poststroke reorganization to promote recovery of upper extremity recovery is the premotor cortex (PMC). This study reviews the role of distinct subdivisions of PMC: dorsal (PMd) and ventral (PMv) premotor cortices as critical anatomical and physiological nodes within the neural networks for the control and learning of goal-oriented reach and grasp actions in healthy individuals and individuals with stroke. Based on evidence emerging from studies of intrinsic and extrinsic connectivity, transcranial magnetic stimulation, functional neuroimaging, and experimental studies in animals and humans, the authors propose 2 distinct patterns of reorganization that differentially engage ipsilesional and contralesional PMC. Research directions that may offer further insights into the role of PMC in motor control, learning, and poststroke recovery are also proposed. This research may facilitate neuroplasticity for maximal recovery of function following brain injury. PMID:21926382

  3. Different distal-proximal movement balances in right- and left-hand writing may hint at differential premotor cortex involvement.

    PubMed

    Potgieser, A R E; de Jong, B M

    2011-12-01

    Right-handed people generally write with their right hand. Language expressed in script is thus performed with the hand also preferred for skilled motor tasks. This may suggest an efficient functional interaction between the language area of Broca and the adjacent ventral premotor cortex (PMv) in the left (dominant) hemisphere. Pilot observations suggested that distal movements are particularly implicated in cursive writing with the right hand and proximal movements in left-hand writing, which generated ideas concerning hemisphere-specific roles of PMv and dorsal premotor cortex (PMd). Now we examined upper-limb movements in 30 right-handed participants during right- and left-hand writing, respectively. Quantitative description of distal and proximal movements demonstrated a significant difference between movements in right- and left-hand writing (p<.001, Wilcoxon signed-rank test). A Distal Movement Excess (DME) characterized writing with the right hand, while proximal and distal movements similarly contributed to left-hand writing. Although differences between non-language drawings were not tested, we propose that the DME in right-hand writing may reflect functional dominance of PMv in the left hemisphere. More proximal movements in left-hand writing might be related to PMd dominance in right-hemisphere motor control, logically implicated in spatial visuomotor transformations as seen in reaching.

  4. Decreased Premotor Cortex Volume in Victims of Urban Violence with Posttraumatic Stress Disorder

    PubMed Central

    Rocha-Rego, Vanessa; Pereira, Mirtes G.; Oliveira, Leticia; Mendlowicz, Mauro V.; Fiszman, Adriana; Marques-Portella, Carla; Berger, William; Chu, Carlton; Joffily, Mateus; Moll, Jorge; Mari, Jair J.; Figueira, Ivan; Volchan, Eliane

    2012-01-01

    Background Studies addressing posttraumatic stress disorder (PTSD) have demonstrated that PTSD patients exhibit structural abnormalities in brain regions that relate to stress regulation and fear responses, such as the hippocampus, amygdala, anterior cingulate cortex, and ventromedial prefrontal cortex. Premotor cortical areas are involved in preparing to respond to a threatening situation and in representing the peripersonal space. Urban violence is an important and pervasive cause of human suffering, especially in large urban centers in the developing world. Violent events, such as armed robbery, are very frequent in certain cities, and these episodes increase the risk of PTSD. Assaultive trauma is characterized by forceful invasion of the peripersonal space; therefore, could this traumatic event be associated with structural alteration of premotor areas in PTSD? Methodology/Principal Findings Structural magnetic resonance imaging scans were acquired from a sample of individuals that had been exposed to urban violence. This sample consisted of 16 PTSD patients and 16 age- and gender-matched controls. Psychometric questionnaires differentiated PTSD patients from trauma-exposed controls with regard to PTSD symptoms, affective, and resilience predispositions. Voxel-based morphometric analysis revealed that, compared with controls, the PTSD patients presented significant reductions in gray matter volume in the ventral premotor cortex and in the pregenual anterior cingulate cortex. Conclusions Volume reduction in the premotor cortex that is observed in victims of urban violence with PTSD may be associated with a disruption in the dynamical modulation of the safe space around the body. The finding that PTSD patients presented a smaller volume of pregenual anterior cingulate cortex is consistent with the results of other PTSD neuroimaging studies that investigated different types of traumatic events. PMID:22952599

  5. Increased resting state connectivity between ipsilesional motor cortex and contralesional premotor cortex after transcranial direct current stimulation with physical therapy.

    PubMed

    Chen, Joyce L; Schlaug, Gottfried

    2016-03-16

    Non-invasive stimulation of the brain using transcranial direct current stimulation (tDCS) during motor rehabilitation can improve the recovery of movements in individuals with stroke. However, the neural substrates that underlie the clinical improvements are not well understood. In this proof-of-principle open-label pilot study, five individuals with stroke received 10 sessions of tDCS while undergoing usual care physical/occupational therapy for the arm and hand. Motor impairment as indexed by the Upper Extremity Fugl Meyer assessment was significantly reduced after the intervention. Resting state fMRI connectivity increased between ipsilesional motor cortex and contralesional premotor cortex after the intervention. These findings provide preliminary evidence that the neural underpinnings of tDCS coupled with rehabilitation exercises, may be mediated by interactions between motor and premotor cortex. The latter, of which has been shown to play an important role in the recovery of movements post-stroke. Our data suggest premotor cortex could be tested as a target region for non-invasive brain-stimulation to enhance connectivity between regions that might be beneficial for stroke motor recovery.

  6. Increased resting state connectivity between ipsilesional motor cortex and contralesional premotor cortex after transcranial direct current stimulation with physical therapy

    PubMed Central

    Chen, Joyce L; Schlaug, Gottfried

    2016-01-01

    Non-invasive stimulation of the brain using transcranial direct current stimulation (tDCS) during motor rehabilitation can improve the recovery of movements in individuals with stroke. However, the neural substrates that underlie the clinical improvements are not well understood. In this proof-of-principle open-label pilot study, five individuals with stroke received 10 sessions of tDCS while undergoing usual care physical/occupational therapy for the arm and hand. Motor impairment as indexed by the Upper Extremity Fugl Meyer assessment was significantly reduced after the intervention. Resting state fMRI connectivity increased between ipsilesional motor cortex and contralesional premotor cortex after the intervention. These findings provide preliminary evidence that the neural underpinnings of tDCS coupled with rehabilitation exercises, may be mediated by interactions between motor and premotor cortex. The latter, of which has been shown to play an important role in the recovery of movements post-stroke. Our data suggest premotor cortex could be tested as a target region for non-invasive brain-stimulation to enhance connectivity between regions that might be beneficial for stroke motor recovery. PMID:26980052

  7. Role of human premotor dorsal region in learning a conditional visuomotor task.

    PubMed

    Parikh, Pranav J; Santello, Marco

    2017-01-01

    Conditional learning is an important component of our everyday activities (e.g., handling a phone or sorting work files) and requires identification of the arbitrary stimulus, accurate selection of the motor response, monitoring of the response, and storing in memory of the stimulus-response association for future recall. Learning this type of conditional visuomotor task appears to engage the premotor dorsal region (PMd). However, the extent to which PMd might be involved in specific or all processes of conditional learning is not well understood. Using transcranial magnetic stimulation (TMS), we demonstrate the role of human PMd in specific stages of learning of a novel conditional visuomotor task that required subjects to identify object center of mass using a color cue and to apply appropriate torque on the object at lift onset to minimize tilt. TMS over PMd, but not vertex, increased error in torque exerted on the object during the learning trials. Analyses of digit position and forces further revealed that the slowing in conditional visuomotor learning resulted from impaired monitoring of the object orientation during lift, rather than stimulus identification, thus compromising the ability to accurately reduce performance error across trials. Importantly, TMS over PMd did not alter production of torque based on the recall of learned color-torque associations. We conclude that the role of PMd for conditional learning is highly sensitive to the stage of learning visuomotor associations.

  8. μ-suppression during action observation and execution correlates with BOLD in dorsal premotor, inferior parietal, and SI cortices.

    PubMed

    Arnstein, Dan; Cui, Fang; Keysers, Christian; Maurits, Natasha M; Gazzola, Valeria

    2011-10-05

    The discovery of mirror neurons in the monkey, that fire during both the execution and the observation of the same action, sparked great interest in studying the human equivalent. For over a decade, both functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) have been used to quantify activity in the human mirror neuron system (MNS)-yet, little is still known about how fMRI and EEG measures of the MNS relate to each other. To test the frequent assumption that regions of the MNS as evidenced by fMRI are the origin of the suppression of the EEG μ-rhythm during both action execution and observation, we recorded EEG and BOLD-fMRI signals simultaneously while participants observed and executed actions. We found that the suppression of the μ-rhythm in EEG covaried with BOLD activity in typical MNS regions, inferior parietal lobe (IPL), dorsal premotor (dPM) and primary somatosensory cortex (BA2), during both action observation and execution. In contrast, in BA44, only nonoverlapping voxels correlated with μ-suppression during observation and execution. These findings provide direct support for the notion that μ-suppression is a valid indicator of MNS activity in BA2, IPL, and dPM, but argues against the idea that mirror neurons in BA44 are the prime source of μ-suppression. These results shed light on the neural basis of μ-suppression and provide a basis for integrating more closely the flourishing but often separate literatures on the MNS using fMRI and EEG.

  9. Premotor cortex is sensitive to auditory-visual congruence for biological motion.

    PubMed

    Wuerger, Sophie M; Parkes, Laura; Lewis, Penelope A; Crocker-Buque, Alex; Rutschmann, Roland; Meyer, Georg F

    2012-03-01

    The auditory and visual perception systems have developed special processing strategies for ecologically valid motion stimuli, utilizing some of the statistical properties of the real world. A well-known example is the perception of biological motion, for example, the perception of a human walker. The aim of the current study was to identify the cortical network involved in the integration of auditory and visual biological motion signals. We first determined the cortical regions of auditory and visual coactivation (Experiment 1); a conjunction analysis based on unimodal brain activations identified four regions: middle temporal area, inferior parietal lobule, ventral premotor cortex, and cerebellum. The brain activations arising from bimodal motion stimuli (Experiment 2) were then analyzed within these regions of coactivation. Auditory footsteps were presented concurrently with either an intact visual point-light walker (biological motion) or a scrambled point-light walker; auditory and visual motion in depth (walking direction) could either be congruent or incongruent. Our main finding is that motion incongruency (across modalities) increases the activity in the ventral premotor cortex, but only if the visual point-light walker is intact. Our results extend our current knowledge by providing new evidence consistent with the idea that the premotor area assimilates information across the auditory and visual modalities by comparing the incoming sensory input with an internal representation.

  10. Viewing the motion of human body parts activates different regions of premotor, temporal, and parietal cortex.

    PubMed

    Wheaton, Kylie J; Thompson, James C; Syngeniotis, Ari; Abbott, David F; Puce, Aina

    2004-05-01

    Activation of premotor and temporoparietal cortex occurs when we observe others movements, particularly relating to objects. Viewing the motion of different body parts without the context of an object has not been systematically evaluated. During a 3T fMRI study, 12 healthy subjects viewed human face, hand, and leg motion, which was not directed at or did not involve an object. Activation was identified relative to static images of the same human face, hand, and leg in both individual subject and group average data. Four clear activation foci emerged: (1) right MT/V5 activated to all forms of viewed motion; (2) right STS activated to face and leg motion; (3) ventral premotor cortex activated to face, hand, and leg motion in the right hemisphere and to leg motion in the left hemisphere; and (4) anterior intraparietal cortex (aIP) was active bilaterally to viewing hand motion and in the right hemisphere leg motion. In addition, in the group data, a somatotopic activation pattern for viewing face, hand, and leg motion occurred in right ventral premotor cortex. Activation patterns in STS and aIP were more complex--typically activation foci to viewing two types of human motion showed some overlap. Activation in individual subjects was similar; however, activation to hand motion also occurred in the STS with a variable location across subjects--explaining the lack of a clear activation focus in the group data. The data indicate that there are selective responses to viewing motion of different body parts in the human brain that are independent of object or tool use.

  11. Mirror Neurons of Ventral Premotor Cortex Are Modulated by Social Cues Provided by Others' Gaze

    PubMed Central

    Festante, Fabrizia; Cilia, Adriana; Loiacono, Veronica; Bimbi, Marco; Fogassi, Leonardo; Ferrari, Pier Francesco

    2016-01-01

    Mirror neurons (MNs) in the inferior parietal lobule and ventral premotor cortex (PMv) can code the intentions of other individuals using contextual cues. Gaze direction is an important social cue that can be used for understanding the meaning of actions made by other individuals. Here we addressed the issue of whether PMv MNs are influenced by the gaze direction of another individual. We recorded single-unit activity in macaque PMv while the monkey was observing an experimenter performing a grasping action and orienting his gaze either toward (congruent gaze condition) or away (incongruent gaze condition) from a target object. The results showed that one-half of the recorded MNs were modulated by the gaze direction of the human agent. These gaze-modulated neurons were evenly distributed between those preferring a gaze direction congruent with the direction where the grasping action was performed and the others that preferred an incongruent gaze. Whereas the presence of congruent responses is in line with the usual coupling of hand and gaze in both executed and observed actions, the incongruent responses can be explained by the long exposure of the monkeys to this condition. Our results reveal that the representation of observed actions in PMv is influenced by contextual information not only extracted from physical cues, but also from cues endowed with biological or social value. SIGNIFICANCE STATEMENT In this study, we present the first evidence showing that social cues modulate MNs in the monkey ventral premotor cortex. These data suggest that there is an integrated representation of other's hand actions and gaze direction at the single neuron level in the ventral premotor cortex, and support the hypothesis of a functional role of MNs in decoding actions and understanding motor intentions. PMID:26985026

  12. Integration of Visual and Proprioceptive Limb Position Information in Human Posterior Parietal, Premotor, and Extrastriate Cortex.

    PubMed

    Limanowski, Jakub; Blankenburg, Felix

    2016-03-02

    The brain constructs a flexible representation of the body from multisensory information. Previous work on monkeys suggests that the posterior parietal cortex (PPC) and ventral premotor cortex (PMv) represent the position of the upper limbs based on visual and proprioceptive information. Human experiments on the rubber hand illusion implicate similar regions, but since such experiments rely on additional visuo-tactile interactions, they cannot isolate visuo-proprioceptive integration. Here, we independently manipulated the position (palm or back facing) of passive human participants' unseen arm and of a photorealistic virtual 3D arm. Functional magnetic resonance imaging (fMRI) revealed that matching visual and proprioceptive information about arm position engaged the PPC, PMv, and the body-selective extrastriate body area (EBA); activity in the PMv moreover reflected interindividual differences in congruent arm ownership. Further, the PPC, PMv, and EBA increased their coupling with the primary visual cortex during congruent visuo-proprioceptive position information. These results suggest that human PPC, PMv, and EBA evaluate visual and proprioceptive position information and, under sufficient cross-modal congruence, integrate it into a multisensory representation of the upper limb in space. The position of our limbs in space constantly changes, yet the brain manages to represent limb position accurately by combining information from vision and proprioception. Electrophysiological recordings in monkeys have revealed neurons in the posterior parietal and premotor cortices that seem to implement and update such a multisensory limb representation, but this has been difficult to demonstrate in humans. Our fMRI experiment shows that human posterior parietal, premotor, and body-selective visual brain areas respond preferentially to a virtual arm seen in a position corresponding to one's unseen hidden arm, while increasing their communication with regions conveying visual

  13. Mirror Neurons of Ventral Premotor Cortex Are Modulated by Social Cues Provided by Others' Gaze.

    PubMed

    Coudé, Gino; Festante, Fabrizia; Cilia, Adriana; Loiacono, Veronica; Bimbi, Marco; Fogassi, Leonardo; Ferrari, Pier Francesco

    2016-03-16

    Mirror neurons (MNs) in the inferior parietal lobule and ventral premotor cortex (PMv) can code the intentions of other individuals using contextual cues. Gaze direction is an important social cue that can be used for understanding the meaning of actions made by other individuals. Here we addressed the issue of whether PMv MNs are influenced by the gaze direction of another individual. We recorded single-unit activity in macaque PMv while the monkey was observing an experimenter performing a grasping action and orienting his gaze either toward (congruent gaze condition) or away (incongruent gaze condition) from a target object. The results showed that one-half of the recorded MNs were modulated by the gaze direction of the human agent. These gaze-modulated neurons were evenly distributed between those preferring a gaze direction congruent with the direction where the grasping action was performed and the others that preferred an incongruent gaze. Whereas the presence of congruent responses is in line with the usual coupling of hand and gaze in both executed and observed actions, the incongruent responses can be explained by the long exposure of the monkeys to this condition. Our results reveal that the representation of observed actions in PMv is influenced by contextual information not only extracted from physical cues, but also from cues endowed with biological or social value. In this study, we present the first evidence showing that social cues modulate MNs in the monkey ventral premotor cortex. These data suggest that there is an integrated representation of other's hand actions and gaze direction at the single neuron level in the ventral premotor cortex, and support the hypothesis of a functional role of MNs in decoding actions and understanding motor intentions. Copyright © 2016 the authors 0270-6474/16/363145-12$15.00/0.

  14. Decision-Making in the Ventral Premotor Cortex Harbinger of Action

    PubMed Central

    Pardo-Vazquez, Jose L.; Padron, Isabel; Fernandez-Rey, Jose; Acuña, Carlos

    2011-01-01

    Although the premotor (PM) cortex was once viewed as the substrate of pure motor functions, soon it was realized that it was involved in higher brain functions. By this it is meant that the PM cortex functions would better be explained as motor set, preparation for limb movement, or sensory guidance of movement rather than solely by a fixed link to motor performance. These findings, together with a better knowledge of the PM cortex histology and hodology in human and non-human primates prompted quantitative studies of this area combining behavioral tasks with electrophysiological recordings. In addition, the exploration of the PM cortex neurons with qualitative methods also suggested its participation in higher functions. Behavioral choices frequently depend on temporal cues, which together with knowledge of previous outcomes and expectancies are combined to decide and choose a behavioral action. In decision-making the knowledge about the consequences of decisions, either correct or incorrect, is fundamental because they can be used to adapt future behavior. The neuronal correlates of a decision process have been described in several cortical areas of primates. Among them, there is evidence that the monkey ventral premotor (PMv) cortex, an anatomical and physiological well-differentiated area of the PM cortex, supports both perceptual decisions and performance monitoring. Here we review the evidence that the steps in a decision-making process are encoded in the firing rate of the PMv neurons. This provides compelling evidence suggesting that the PMv is involved in the use of recent and long-term sensory memory to decide, execute, and evaluate the outcomes of the subjects’ choices. PMID:21991249

  15. Intrinsic functional architecture of the macaque dorsal and ventral lateral frontal cortex.

    PubMed

    Goulas, Alexandros; Stiers, Peter; Hutchison, R Matthew; Everling, Stefan; Petrides, Michael; Margulies, Daniel S

    2017-03-01

    Investigations of the cellular and connectional organization of the lateral frontal cortex (LFC) of the macaque monkey provide indispensable knowledge for generating hypotheses about the human LFC. However, despite numerous investigations, there are still debates on the organization of this brain region. In vivo neuroimaging techniques such as resting-state functional magnetic resonance imaging (fMRI) can be used to define the functional circuitry of brain areas, producing results largely consistent with gold-standard invasive tract-tracing techniques and offering the opportunity for cross-species comparisons within the same modality. Our results using resting-state fMRI from macaque monkeys to uncover the intrinsic functional architecture of the LFC corroborate previous findings and inform current debates. Specifically, within the dorsal LFC, we show that 1) the region along the midline and anterior to the superior arcuate sulcus is divided in two areas separated by the posterior supraprincipal dimple, 2) the cytoarchitectonically defined area 6DC/F2 contains two connectional divisions, and 3) a distinct area occupies the cortex around the spur of the arcuate sulcus, updating what was previously proposed to be the border between dorsal and ventral motor/premotor areas. Within the ventral LFC, the derived parcellation clearly suggests the presence of distinct areas: 1) an area with a somatomotor/orofacial connectional signature (putative area 44), 2) an area with an oculomotor connectional signature (putative frontal eye fields), and 3) premotor areas possibly hosting laryngeal and arm representations. Our results illustrate in detail the intrinsic functional architecture of the macaque LFC, thus providing valuable evidence for debates on its organization.NEW & NOTEWORTHY Resting-state functional MRI is used as a complementary method to invasive techniques to inform current debates on the organization of the macaque lateral frontal cortex. Given that the macaque

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

    PubMed Central

    Roy, Sabyasachi; Zhao, Lingyun

    2016-01-01

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

  17. Premotor Cortex Activation Elicited during Word Comprehension Relies on Access of Specific Action Concepts.

    PubMed

    Lin, Nan; Wang, Xiaoying; Zhao, Ying; Liu, Yanping; Li, Xingshan; Bi, Yanchao

    2015-10-01

    The relationship between the lexical-semantic and sensory-motor systems is an important topic in cognitive neuroscience. An important finding indicating that these two systems interact is that reading action verbs activates the motor system of the human brain. Two constraints have been proposed to modulate this activation: the effector information associated with the action concepts and statistical regularities between sublexical features and grammatical classes. Using fMRI, we examined whether these two types of information can activate the motor system in the absence of specific motor-semantic content by manipulating the existence of a sublexical cue, called the hand radical, which strongly indicates the semantic feature "hand-related" and grammatical class "verb." Although hand radical characters referring to specific manual actions evoked stronger activation in the premotor cortex than the control characters, hand radical pseudocharacters did not evoke specific activation within the motor system. These results indicated that activation of the premotor cortex during word reading relies on the access of specific action concepts.

  18. Beta activity in the premotor cortex is increased during stabilized as compared to normal walking

    PubMed Central

    Bruijn, Sjoerd M.; Van Dieën, Jaap H.; Daffertshofer, Andreas

    2015-01-01

    Walking on two legs is inherently unstable. Still, we humans perform remarkable well at it, mostly without falling. To gain more understanding of the role of the brain in controlling gait stability we measured brain activity using electro-encephalography (EEG) during stabilized and normal walking. Subjects walked on a treadmill in two conditions, each lasting 10 min; normal, and while being laterally stabilized by elastic cords. Kinematics of trunk and feet, electro-myography (EMG) of neck muscles, as well as 64-channel EEG were recorded. To assess gait stability the local divergence exponent, step width, and trunk range of motion were calculated from the kinematic data. We used independent component (IC) analysis to remove movement, EMG, and eyeblink artifacts from the EEG, after which dynamic imaging of coherent sources beamformers were determined to identify cortical sources that showed a significant difference between conditions. Stabilized walking led to a significant increase in gait stability, i.e., lower local divergence exponents. Beamforming analysis of the beta band activity revealed significant sources in bilateral pre-motor cortices. Projection of sensor data on these sources showed a significant difference only in the left premotor area, with higher beta power during stabilized walking, specifically around push-off, although only significant around contralateral push-off. It appears that even during steady gait the cortex is involved in the control of stability. PMID:26578937

  19. The Encoding of Decision Difficulty and Movement Time in the Primate Premotor Cortex

    PubMed Central

    Pardo-Vazquez, Jose L.; Acuña, Carlos; Deco, Gustavo

    2015-01-01

    Estimating the difficulty of a decision is a fundamental process to elaborate complex and adaptive behaviour. In this paper, we show that the movement time of behaving monkeys performing a decision-making task is correlated with decision difficulty and that the activity of a population of neurons in ventral Premotor cortex correlates with the movement time. Moreover, we found another population of neurons that encodes the discriminability of the stimulus, thereby supplying another source of information about the difficulty of the decision. The activity of neurons encoding the difficulty can be produced by very different computations. Therefore, we show that decision difficulty can be encoded through three different mechanisms: 1. Switch time coding, 2. rate coding and 3. binary coding. This rich representation reflects the basis of different functional aspects of difficulty in the making of a decision and the possible role of difficulty estimation in complex decision scenarios. PMID:26556807

  20. Dynamic Control of Response Criterion in Premotor Cortex during Perceptual Detection under Temporal Uncertainty.

    PubMed

    Carnevale, Federico; de Lafuente, Victor; Romo, Ranulfo; Barak, Omri; Parga, Néstor

    2015-05-20

    Under uncertainty, the brain uses previous knowledge to transform sensory inputs into the percepts on which decisions are based. When the uncertainty lies in the timing of sensory evidence, however, the mechanism underlying the use of previously acquired temporal information remains unknown. We study this issue in monkeys performing a detection task with variable stimulation times. We use the neural correlates of false alarms to infer the subject's response criterion and find that it modulates over the course of a trial. Analysis of premotor cortex activity shows that this modulation is represented by the dynamics of population responses. A trained recurrent network model reproduces the experimental findings and demonstrates a neural mechanism to benefit from temporal expectations in perceptual detection. Previous knowledge about the probability of stimulation over time can be intrinsically encoded in the neural population dynamics, allowing a flexible control of the response criterion over time.

  1. The Computational and Neural Basis of Rhythmic Timing in Medial Premotor Cortex.

    PubMed

    Merchant, Hugo; Averbeck, Bruno B

    2017-04-26

    The neural underpinnings of rhythmic behavior, including music and dance, have been studied using the synchronization-continuation task (SCT), where subjects initially tap in synchrony with an isochronous metronome and then keep tapping at a similar rate via an internal beat mechanism. Here, we provide behavioral and neural evidence that supports a resetting drift-diffusion model (DDM) during SCT. Behaviorally, we show the model replicates the linear relation between the mean and standard-deviation of the intervals produced by monkeys in SCT. We then show that neural populations in the medial premotor cortex (MPC) contain an accurate trial-by-trial representation of elapsed-time between taps. Interestingly, the autocorrelation structure of the elapsed-time representation is consistent with a DDM. These results indicate that MPC has an orderly representation of time with features characteristic of concatenated DDMs and that this population signal can be used to orchestrate the rhythmic structure of the internally timed elements of SCT.SIGNIFICANCE STATEMENT The present study used behavioral data, ensemble recordings from medial premotor cortex (MPC) in macaque monkeys, and computational modeling, to establish evidence in favor of a class of drift-diffusion models of rhythmic timing during a synchronization-continuation tapping task (SCT). The linear relation between the mean and standard-deviation of the intervals produced by monkeys in SCT is replicated by the model. Populations of MPC cells faithfully represent the elapsed time between taps, and there is significant trial-by-trial relation between decoded times and the timing behavior of the monkeys. Notably, the neural decoding properties, including its autocorrelation structure are consistent with a set of drift-diffusion models that are arranged sequentially and that are resetting in each SCT tap. Copyright © 2017 the authors 0270-6474/17/374552-13$15.00/0.

  2. Linking Objects to Actions: Encoding of Target Object and Grasping Strategy in Primate Ventral Premotor Cortex

    PubMed Central

    Franquemont, Lachlan; Black, Michael J.; Donoghue, John P.

    2015-01-01

    Neural activity in ventral premotor cortex (PMv) has been associated with the process of matching perceived objects with the motor commands needed to grasp them. It remains unclear how PMv networks can flexibly link percepts of objects affording multiple grasp options into a final desired hand action. Here, we use a relational encoding approach to track the functional state of PMv neuronal ensembles in macaque monkeys through the process of passive viewing, grip planning, and grasping movement execution. We used objects affording multiple possible grip strategies. The task included separate instructed delay periods for object presentation and grip instruction. This approach allowed us to distinguish responses elicited by the visual presentation of the objects from those associated with selecting a given motor plan for grasping. We show that PMv continuously incorporates information related to object shape and grip strategy as it becomes available, revealing a transition from a set of ensemble states initially most closely related to objects, to a new set of ensemble patterns reflecting unique object-grip combinations. These results suggest that PMv dynamically combines percepts, gradually navigating toward activity patterns associated with specific volitional actions, rather than directly mapping perceptual object properties onto categorical grip representations. Our results support the idea that PMv is part of a network that dynamically computes motor plans from perceptual information. SIGNIFICANCE STATEMENT The present work demonstrates that the activity of groups of neurons in primate ventral premotor cortex reflects information related to visually presented objects, as well as the motor strategy used to grasp them, linking individual objects to multiple possible grips. PMv could provide useful control signals for neuroprosthetic assistive devices designed to interact with objects in a flexible way. PMID:26224870

  3. Trial-to-trial adjustments of speed-accuracy trade-offs in premotor and primary motor cortex.

    PubMed

    Thura, David; Guberman, Guido; Cisek, Paul

    2017-02-01

    Recent studies have shown that activity in sensorimotor structures varies depending on the speed-accuracy trade-off (SAT) context in which a decision is made. Here we tested the hypothesis that the same areas also reflect a more local adjustment of SAT established between individual trials, based on the outcome of the previous decision. Two monkeys performed a reaching decision task in which sensory evidence continuously evolves during the time course of a trial. In two SAT contexts, we compared neural activity in trials following a correct choice vs. those following an error. In dorsal premotor cortex (PMd), we found that 23% of cells exhibited significantly weaker baseline activity after error trials, and for ∼30% of these this effect persisted into the deliberation epoch. These cells also contributed to the process of combining sensory evidence with the growing urgency to commit to a choice. We also found that the activity of 22% of PMd cells was increased after error trials. These neurons appeared to carry less information about sensory evidence and time-dependent urgency. For most of these modulated cells, the effect was independent of whether the previous error was expected or unexpected. We found similar phenomena in primary motor cortex (M1), with 25% of cells decreasing and 34% increasing activity after error trials, but unlike PMd, these neurons showed less clear differences in their response properties. These findings suggest that PMd and M1 belong to a network of brain areas involved in SAT adjustments established using the recent history of reinforcement.

  4. A network centered on ventral premotor cortex exerts both facilitatory and inhibitory control over primary motor cortex during action reprogramming

    PubMed Central

    Buch, ER; Mars, RB; Boorman, ED; Rushworth, MFS

    2010-01-01

    Ventral premotor cortex (PMv) is widely accepted to exert an important influence over primary motor cortex (M1) when hand movements are made. Although study of these interactions has typically focused on their excitatory nature, given its strong connections with both ventral and opercular frontal regions, one feature of PMv's influence over M1 may be inhibitory. Paired-pulse transcranial magnetic stimulation (ppTMS) was used to examine functional interactions between human PMv and M1 during the selection and reprogramming of a naturalistic goal-directed action. One of two cylinders was illuminated on each trial. It was then grasped and picked up. On some trials, however, subjects had to re-program the action as the illuminated cylinder was switched off and the other illuminated simultaneously with reach initiation. At a neurophysiological level, the PMv paired-pulse effect (PPE) on M1 corticospinal activity was facilitatory after the initial target presentation and during movement initiation. When reprogramming was required however, the PPE became strongly inhibitory. This context-dependent change from facilitation to inhibition occurred within 75ms of the change of target. Behaviorally, PMv-M1 ppTMS disrupted reprogramming. Diffusion-weighted magnetic resonance image (DW-MRI) scans were taken of each subject. Intersubject differences in the facilitation–inhibition contrast of PMv–M1 interactions were correlated with fractional anisotropy of white-matter in ventral prefrontal, premotor, and intraparietal brain areas. These results suggest that a network of brain areas centered on PMv inhibits M1 corticospinal activity associated with undesired movements when action plans change. PMID:20107065

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

    PubMed

    Roy, Sabyasachi; Zhao, Lingyun; Wang, Xiaoqin

    2016-11-30

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

  6. Functional significance of the electrocorticographic auditory responses in the premotor cortex

    PubMed Central

    Tanji, Kazuyo; Sakurada, Kaori; Funiu, Hayato; Matsuda, Kenichiro; Kayama, Takamasa; Ito, Sayuri; Suzuki, Kyoko

    2015-01-01

    Other than well-known motor activities in the precentral gyrus, functional magnetic resonance imaging (fMRI) studies have found that the ventral part of the precentral gyrus is activated in response to linguistic auditory stimuli. It has been proposed that the premotor cortex in the precentral gyrus is responsible for the comprehension of speech, but the precise function of this area is still debated because patients with frontal lesions that include the precentral gyrus do not exhibit disturbances in speech comprehension. We report on a patient who underwent resection of the tumor in the precentral gyrus with electrocorticographic recordings while she performed the verb generation task during awake brain craniotomy. Consistent with previous fMRI studies, high-gamma band auditory activity was observed in the precentral gyrus. Due to the location of the tumor, the patient underwent resection of the auditory responsive precentral area which resulted in the post-operative expression of a characteristic articulatory disturbance known as apraxia of speech (AOS). The language function of the patient was otherwise preserved and she exhibited intact comprehension of both spoken and written language. The present findings demonstrated that a lesion restricted to the ventral precentral gyrus is sufficient for the expression of AOS and suggest that the auditory-responsive area plays an important role in the execution of fluent speech rather than the comprehension of speech. These findings also confirm that the function of the premotor area is predominantly motor in nature and its sensory responses is more consistent with the “sensory theory of speech production,” in which it was proposed that sensory representations are used to guide motor-articulatory processes. PMID:25852457

  7. Single Neurons in M1 and Premotor Cortex Directly Reflect Behavioral Interference

    PubMed Central

    Zach, Neta; Inbar, Dorrit; Grinvald, Yael; Vaadia, Eilon

    2012-01-01

    Some motor tasks, if learned together, interfere with each other's consolidation and subsequent retention, whereas other tasks do not. Interfering tasks are said to employ the same internal model whereas noninterfering tasks use different models. The division of function among internal models, as well as their possible neural substrates, are not well understood. To investigate these questions, we compared responses of single cells in the primary motor cortex and premotor cortex of primates to interfering and noninterfering tasks. The interfering tasks were visuomotor rotation followed by opposing visuomotor rotation. The noninterfering tasks were visuomotor rotation followed by an arbitrary association task. Learning two noninterfering tasks led to the simultaneous formation of neural activity typical of both tasks, at the level of single neurons. In contrast, and in accordance with behavioral results, after learning two interfering tasks, only the second task was successfully reflected in motor cortical single cell activity. These results support the hypothesis that the representational capacity of motor cortical cells is the basis of behavioral interference and division between internal models. PMID:22427923

  8. Species-specific response to human infant faces in the premotor cortex.

    PubMed

    Caria, Andrea; Falco, Simona de; Venuti, Paola; Lee, Sangkyun; Esposito, Gianluca; Rigo, Paola; Birbaumer, Niels; Bornstein, Marc H

    2012-04-02

    The human infant face represents an essential source of communicative signals on the basis of which adults modulate their interactions with infants. Behavioral studies demonstrate that infants' faces activate sensitive and attuned responses in adults through their gaze, face expression, voice, and gesture. In this study we aimed to identify brain responses that underlie adults' general propensity to respond to infant faces. We recorded fMRI during adults' (non-parents) processing of unfamiliar infant faces compared to carefully matched adult faces and infrahuman mammal infant and adult faces. Human infant faces activated several brain systems including the lateral premotor cortex, supplementary motor area, cingulate cortex, anterior insula and the thalamus. Activation of these brain circuits suggests adults' preparation for communicative behavior with infants as well as attachment and caregiving. The same brain regions preferentially responded to human infant faces when compared to animal infant faces, indicating species-specific adult brain responses. Moreover, results of support vector machine based classification analysis indicated that these regions allowed above chance-level prediction of brain state during perception of human infant faces. The complex of brain responses to human infant faces appears to include biological mechanisms that underlie responsiveness and a caring inclination toward young children which appear to transcend adult's biological relationship to the baby. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Species-specific response to human infant faces in the premotor cortex

    PubMed Central

    Caria, Andrea; de Falco, Simona; Venuti, Paola; Lee, Sangkyun; Esposito, Gianluca; Rigo, Paola; Birbaumer, Niels; Bornstein, Marc H.

    2012-01-01

    The human infant face represents an essential source of communicative signals on the basis of which adults modulate their interactions with infants. Behavioral studies demonstrate that infants faces activate sensitive and attuned responses in adults through their gaze, face expression, voice, and gesture. In this study we aimed to identify brain responses that underlie adults’ general propensity to respond to infant faces. We recorded fMRI during adults’ (non-parents) processing of unfamiliar infant faces compared to carefully matched adult faces and infrahuman mammal infant and adult faces. Human infant faces activated several brain systems including the lateral premotor cortex, supplementary motor area, cingulate cortex, anterior insula and the thalamus. Activation of these brain circuits suggests adults’ preparation for communicative behavior with infants as well as attachment and caregiving. The same brain regions preferentially responded to human infant faces when compared to animal infant faces, indicating species-specific adult brain responses. Moreover, results of support vector machine based classification analysis indicated that these regions allowed above chance-level prediction of brain state during perception of human infant faces. The complex of brain responses to human infant faces appear to include biological mechanisms that underlie responsiveness and a caring inclination toward young children which appear to transcend adult’s biological relationship to the baby. PMID:22230948

  10. Do premotor interneurons act in parallel on spinal motoneurons and on dorsal horn spinocerebellar and spinocervical tract neurons in the cat?

    PubMed

    Krutki, Piotr; Jelen, Sabina; Jankowska, Elzbieta

    2011-04-01

    It has previously been established that ventral spinocerebellar tract (VSCT) neurons and dorsal spinocerebellar tract neurons located in Clarke's column (CC DSCT neurons) forward information on actions of premotor interneurons in reflex pathways from muscle afferents on α-motoneurons. Whether DSCT neurons located in the dorsal horn (dh DSCT neurons) and spinocervical tract (SCT) neurons are involved in forwarding similar feedback information has not yet been investigated. The aim of the present study was therefore to examine the input from premotor interneurons to these neurons. Electrical stimuli were applied within major hindlimb motor nuclei to activate axon-collaterals of interneurons projecting to these nuclei, and intracellular records were obtained from dh DSCT and SCT neurons. Direct actions of the stimulated interneurons were differentiated from indirect actions by latencies of postsynaptic potentials evoked by intraspinal stimuli and by the absence or presence of temporal facilitation. Direct actions of premotor interneurons were found in a smaller proportion of dh DSCT than of CC DSCT neurons. However, they were evoked by both excitatory and inhibitory interneurons, whereas only inhibitory premotor interneurons were previously found to affect CC DSCT neurons [as indicated by monosynaptic excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) in dh DSCT and only IPSPs in CC DSCT neurons]. No effects of premotor interneurons were found in SCT neurons, since monosynaptic EPSPs or IPSPs were only evoked in them by stimuli applied outside motor nuclei. The study thus reveals a considerable differentiation of feedback information provided by different populations of ascending tract neurons.

  11. Gateways of ventral and dorsal streams in mouse visual cortex

    PubMed Central

    Wang, Quanxin; Gao, Enquan; Burkhalter, Andreas

    2011-01-01

    It is widely held that the spatial processing functions underlying rodent navigation are similar to those encoding human episodic memory (Doeller et al, 2010). Spatial and nonspatial information are provided by all senses including vision. It has been suggested that visual inputs are fed to the navigational network in cortex and hippocampus through dorsal and ventral intracortical streams (Whitlock et al, 2008), but this has not been shown directly in rodents. We have used cyto- and chemoarchitectonic markers, topographic mapping of receptive fields and pathway tracing to determine in mouse visual cortex whether the lateromedial (LM) and the anterolateral fields (AL), which are the principal targets of primary visual cortex (V1) (Wang and Burkhalter, 2007) specialized for processing nonspatial and spatial visual information (Gao et al, 2006), are distinct areas with diverse connections. We have found that the LM/AL border coincides with a change in type 2 muscarinic acetylcholine receptor (m2AChR) expression in layer 4 and with the representation of the lower visual field periphery. Our quantitative analyses further show that LM strongly projects to temporal cortex as well as the lateral entorhinal cortex, which has weak spatial selectivity (Hargreaves et al, 2005). In contrast, AL has stronger connections with posterior parietal cortex, motor cortex and the spatially selective medial entorhinal cortex (Haftig et al, 2005). These results support the notion that LM and AL are architecturally, topographically and connectionally distinct areas of extrastriate visual cortex and that they are gateways for ventral and dorsal streams. PMID:21289200

  12. A cluster analysis of neuronal activity in the dorsal premotor cortical area for neuroprosthetic control.

    PubMed

    Ye, N; Roontiva, A; He, J

    2008-01-01

    With the use of the neuronal data acquisition technology, millisecond-level multi-electrode data from several regions of the premotor area were obtained from two rhesus monkeys trained to perform arm-reach tasks with visual cues in virtual reality. In each trial, animals were required to select and perform one of the four possible arm reaching movements to the target on the top-left or top-right of the virtual reality space. They were also required to decide whether they would move their arms straight to the target or curve them in order to avoid the obstacle that was presented. After the acquired neuronal signals were processed, unsupervised Hierarchical clustering and K-means clustering were performed to uncover the similarity and difference in the average firing rate of spike train data between neurons and phases for each experiment condition. The clustering results indicate the similarity of neuronal data in the movement planning and actual movement phases, and the difference of such data from the data in information processing phases. Furthermore, the clustering results show that when the target location is on the right, the move planning started earlier. The analysis of variance (ANOVA) on the neuronal data confirms the results from the hierarchical clustering.

  13. Corticospinal Neurons in Macaque Ventral Premotor Cortex with Mirror Properties: A Potential Mechanism for Action Suppression?

    PubMed Central

    Kraskov, Alexander; Dancause, Numa; Quallo, Marsha M.; Shepherd, Samantha; Lemon, Roger N.

    2009-01-01

    Summary The discovery of “mirror neurons” in area F5 of the ventral premotor cortex has prompted many theories as to their possible function. However, the identity of mirror neurons remains unknown. Here, we investigated whether identified pyramidal tract neurons (PTNs) in area F5 of two adult macaques exhibited “mirror-like” activity. About half of the 64 PTNs tested showed significant modulation of their activity while monkeys observed precision grip of an object carried out by an experimenter, with somewhat fewer showing modulation during precision grip without an object or grasping concealed from the monkey. Therefore, mirror-like activity can be transmitted directly to the spinal cord via PTNs. A novel finding is that many PTNs (17/64) showed complete suppression of discharge during action observation, while firing actively when the monkey grasped food rewards. We speculate that this suppression of PTN discharge might be involved in the inhibition of self-movement during action observation. PMID:20064397

  14. Corticospinal neurons in macaque ventral premotor cortex with mirror properties: a potential mechanism for action suppression?

    PubMed

    Kraskov, Alexander; Dancause, Numa; Quallo, Marsha M; Shepherd, Samantha; Lemon, Roger N

    2009-12-24

    The discovery of "mirror neurons" in area F5 of the ventral premotor cortex has prompted many theories as to their possible function. However, the identity of mirror neurons remains unknown. Here, we investigated whether identified pyramidal tract neurons (PTNs) in area F5 of two adult macaques exhibited "mirror-like" activity. About half of the 64 PTNs tested showed significant modulation of their activity while monkeys observed precision grip of an object carried out by an experimenter, with somewhat fewer showing modulation during precision grip without an object or grasping concealed from the monkey. Therefore, mirror-like activity can be transmitted directly to the spinal cord via PTNs. A novel finding is that many PTNs (17/64) showed complete suppression of discharge during action observation, while firing actively when the monkey grasped food rewards. We speculate that this suppression of PTN discharge might be involved in the inhibition of self-movement during action observation. 2009 Elsevier Inc. All rights reserved.

  15. Stimulus expectancy modulates inferior frontal gyrus and premotor cortex activity in auditory perception.

    PubMed

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

    2012-04-01

    In studies on auditory speech perception, participants are often asked to perform active tasks, e.g. decide whether the perceived sound is a speech sound or not. However, information about the stimulus, inherent in such tasks, may induce expectations that cause altered activations not only in the auditory cortex, but also in frontal areas such as inferior frontal gyrus (IFG) and motor cortices, even in the absence of an explicit task. To investigate this, we applied spectral mixes of a flute sound and either vowels or specific music instrument sounds (e.g. trumpet) in an fMRI study, in combination with three different instructions. The instructions either revealed no information about stimulus features, or explicit information about either the music instrument or the vowel features. The results demonstrated that, besides an involvement of posterior temporal areas, stimulus expectancy modulated in particular a network comprising IFG and premotor cortices during this passive listening task. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Multimodal architectonic subdivision of the rostral part (area F5) of the macaque ventral premotor cortex.

    PubMed

    Belmalih, Abdelouahed; Borra, Elena; Contini, Massimo; Gerbella, Marzio; Rozzi, Stefano; Luppino, Giuseppe

    2009-01-10

    We used a cyto-, myelo-, and chemoarchitectonic (distribution of SMI-32 and calbindin immunoreactivity) approach to assess whether the rostral histochemical area F5 of the ventral premotor cortex (PMv) comprises architectonically distinct areas, possibly corresponding to functionally different fields. Three areas were identified, occupying different parts of F5. One area, designated as "convexity" F5 (F5c), extends on the postarcuate convexity cortex adjacent to the inferior arcuate sulcus and is characterized, cytoarchitectonically, by a poorly laminated appearance, resulting from an overall cell population rather homogeneous in size and density. The other two areas, designated as "posterior" and "anterior" F5 (F5p and F5a, respectively), lie within the postarcuate bank at different anteroposterior levels. Major cytoarchitectonic features of F5p are a layer III relatively homogeneous in cell size and density, a cell-dense layer Va, and the presence of relatively large pyramids in layer Vb. Major cytoarchitectonic features of F5a are the presence of relatively large pyramids in lowest layer III and a prominent, homogenous layer V. Furthermore, our results showed that F5c and F5p border caudally with a caudal PMv area corresponding to histochemical area F4, providing additional evidence for a general subdivision of the macaque PMv into a caudal and a rostral part, corresponding to F4 and to the F5 complex, respectively. The present data, together with other functional and connectional data, suggest that the three rostral PMv areas F5p, F5a, and F5c correspond to distinct cortical entities, possibly involved in different aspects of motor control and cognitive motor functions.

  17. Probing the interaction of the ipsilateral posterior parietal cortex with the premotor cortex using a novel transcranial magnetic stimulation technique

    PubMed Central

    Shields, Jessica; Park, Jung E.; Srivanitchapoom, Prachaya; Paine, Rainer; Thirugnanasambandam, Nivethida; Kukke, Sahana N.; Hallett, Mark

    2015-01-01

    Objective Functional imaging studies have shown that control of planned movement involves a distributed network that involves the premotor (PMv) and posterior parietal cortices (PPC). Similarly, anatomical studies show that these regions are densely interconnected via white matter tracts. We therefore hypothesized that the PPC influence over the motor cortex is partly via a connection with the PMv. Methods Using a novel three-pulse ipsilateral transcranial magnetic stimulation technique, we preconditioned the PPC (80%RMT) at ISIs from 4–15ms prior to stimulating the PMv and M1 at ISIs of 4 and 6ms. Results As previously shown, PMv-M1 paired-pulse stimulation resulted in inhibition of the MEP (90% RMT, 4–6ms) and PPC-M1 paired-pulse stimulation resulted in facilitation of the MEP (90% RMT, 4–8ms). PPC-M1 paired-pulse stimulation at 80%RMT preconditioning had no effect on M1. PPC-PMv-M1 stimulation resulted in reversal of inhibition observed with PMv-M1 stimulation at ISIs ranging from 6–15ms. Conclusions The reversal of inhibition observed with PPC-PMv-M1 stimulation suggests that the parietal connection to the PMv plays a role in the modulation of M1. Significance This is the first study to stimulate three intrahemispheric regions in order to test a disynaptic connection with M1. The described network may be important in a variety of movement disorders. PMID:26253032

  18. The Organization of Dorsal Frontal Cortex in Humans and Macaques

    PubMed Central

    Mars, Rogier B.; Noonan, MaryAnn P.; Neubert, Franz-Xaver; Jbabdi, Saad; O'Reilly, Jill X.; Filippini, Nicola; Thomas, Adam G.; Rushworth, Matthew F.

    2013-01-01

    The human dorsal frontal cortex has been associated with the most sophisticated aspects of cognition, including those that are thought to be especially refined in humans. Here we used diffusion-weighted magnetic resonance imaging (DW-MRI) and functional MRI (fMRI) in humans and macaques to infer and compare the organization of dorsal frontal cortex in the two species. Using DW-MRI tractography-based parcellation, we identified 10 dorsal frontal regions lying between the human inferior frontal sulcus and cingulate cortex. Patterns of functional coupling between each area and the rest of the brain were then estimated with fMRI and compared with functional coupling patterns in macaques. Areas in human medial frontal cortex, including areas associated with high-level social cognitive processes such as theory of mind, showed a surprising degree of similarity in their functional coupling patterns with the frontal pole, medial prefrontal, and dorsal prefrontal convexity in the macaque. We failed to find evidence for “new” regions in human medial frontal cortex. On the lateral surface, comparison of functional coupling patterns suggested correspondences in anatomical organization distinct from those that are widely assumed. A human region sometimes referred to as lateral frontal pole more closely resembled area 46, rather than the frontal pole, of the macaque. Overall the pattern of results suggest important similarities in frontal cortex organization in humans and other primates, even in the case of regions thought to carry out uniquely human functions. The patterns of interspecies correspondences are not, however, always those that are widely assumed. PMID:23884933

  19. Sensorimotor neural dynamics during isochronous tapping in the medial premotor cortex of the macaque.

    PubMed

    Merchant, Hugo; Pérez, Oswaldo; Bartolo, Ramón; Méndez, Juan Carlos; Mendoza, Germán; Gámez, Jorge; Yc, Karyna; Prado, Luis

    2015-03-01

    We determined the response properties of neurons in the primate medial premotor cortex that were classified as sensory or motor during isochronous tapping to a visual or auditory metronome, using different target intervals and three sequential elements in the task. The cell classification was based on a warping transformation, which determined whether the cell activity was statistically aligned to sensory or motor events, finding a large proportion of cells classified as sensory or motor. Two distinctive clusters of sensory cells were observed, i.e. one cell population with short response-onset latencies to the previous stimulus, and another that was probably predicting the occurrence of the next stimuli. These cells were called sensory-driven and stimulus-predicting neurons, respectively. Sensory-driven neurons showed a clear bias towards the visual modality and were more responsive to the first stimulus, with a decrease in activity for the following sequential elements of the metronome. In contrast, stimulus-predicting neurons were bimodal and showed similar response profiles across serial-order elements. Motor cells showed a consecutive activity onset across discrete neural ensembles, generating a rapid succession of activation patterns between the two taps defining a produced interval. The cyclical configuration in activation profiles engaged more motor cells as the serial-order elements progressed across the task, and the rate of cell recruitment over time decreased as a function of the target interval. Our findings support the idea that motor cells were responsible for the rhythmic progression of taps in the task, gaining more importance as the trial advanced, while, simultaneously, the sensory-driven cells lost their functional impact.

  20. Inhibitory stimulation of the ventral premotor cortex temporarily interferes with musical beat rate preference.

    PubMed

    Kornysheva, Katja; von Anshelm-Schiffer, Anne-Marike; Schubotz, Ricarda I

    2011-08-01

    Behavioral studies suggest that preference for a beat rate (tempo) in auditory sequences is tightly linked to the motor system. However, from a neuroscientific perspective the contribution of motor-related brain regions to tempo preference in the auditory domain remains unclear. A recent fMRI study (Kornysheva et al. [2010]: Hum Brain Mapp 31:48-64) revealed that the activity increase in the left ventral premotor cortex (PMv) is associated with the preference for a tempo of a musical rhythm. The activity increase correlated with how strongly the subjects preferred a tempo. Despite this evidence, it remains uncertain whether an interference with activity in the left PMv affects tempo preference strength. Consequently, we conducted an offline repetitive transcranial magnetic stimulation (rTMS) study, in which the cortical excitability in the left PMv was temporarily reduced. As hypothesized, 0.9 Hz rTMS over the left PMv temporarily affected individual tempo preference strength depending on the individual strength of tempo preference in the control session. Moreover, PMv stimulation temporarily interfered with the stability of individual tempo preference strength within and across sessions. These effects were specific to the preference for tempo in contrast to the preference for timbre, bound to the first half of the experiment following PMv stimulation and could not be explained by an impairment of tempo recognition. Our results corroborate preceding fMRI findings and suggest that activity in the left PMv is part of a network that affects the strength of beat rate preference. Copyright © 2010 Wiley-Liss, Inc.

  1. Patterns of neural activity in the human ventral premotor cortex reflect a whole-body multisensory percept.

    PubMed

    Gentile, Giovanni; Björnsdotter, Malin; Petkova, Valeria I; Abdulkarim, Zakaryah; Ehrsson, H Henrik

    2015-04-01

    Previous research has shown that the integration of multisensory signals from the body in fronto-parietal association areas underlies the perception of a body part as belonging to one's physical self. What are the neural mechanisms that enable the perception of one's entire body as a unified entity? In one behavioral and one fMRI multivoxel pattern analysis experiment, we used a full-body illusion to investigate how congruent visuo-tactile signals from a single body part facilitate the emergence of the sense of ownership of the entire body. To elicit this illusion, participants viewed the body of a mannequin from the first-person perspective via head-mounted displays while synchronous touches were applied to the hand, abdomen, or leg of the bodies of the participant and the mannequin; asynchronous visuo-tactile stimuli served as controls. The psychometric data indicated that the participants perceived ownership of the entire artificial body regardless of the body segment that received the synchronous visuo-tactile stimuli. Based on multivoxel pattern analysis, we found that the neural responses in the left ventral premotor cortex displayed illusion-specific activity patterns that generalized across all tested pairs of body parts. Crucially, a tripartite generalization analysis revealed the whole-body specificity of these premotor activity patterns. Finally, we also identified multivoxel patterns in the premotor, intraparietal, and lateral occipital cortices and in the putamen that reflected multisensory responses specific to individual body parts. Based on these results, we propose that the dynamic formation of a whole-body percept may be mediated by neuronal populations in the ventral premotor cortex that contain visuo-tactile receptive fields encompassing multiple body segments.

  2. Patterns of neural activity in the human ventral premotor cortex reflect a whole-body multisensory percept

    PubMed Central

    Gentile, Giovanni; Björnsdotter, Malin; Petkova, Valeria I.; Abdulkarim, Zakaryah; Ehrsson, H. Henrik

    2015-01-01

    Previous research has shown that the integration of multisensory signals from the body in fronto-parietal association areas underlies the perception of a body part as belonging to one's physical self. What are the neural mechanisms that enable the perception of one's entire body as a unified entity? In one behavioral and one fMRI multivoxel pattern analysis experiment, we used a full-body illusion to investigate how congruent visuo-tactile signals from a single body part facilitate the emergence of the sense of ownership of the entire body. To elicit this illusion, participants viewed the body of a mannequin from the first-person perspective via head-mounted displays while synchronous touches were applied to the hand, abdomen, or leg of the bodies of the participant and the mannequin; asynchronous visuo-tactile stimuli served as controls. The psychometric data indicated that the participants perceived ownership of the entire artificial body regardless of the body segment that received the synchronous visuo-tactile stimuli. Based on multivoxel pattern analysis, we found that the neural responses in the left ventral premotor cortex displayed illusion-specific activity patterns that generalized across all tested pairs of body parts. Crucially, a tripartite generalization analysis revealed the whole-body specificity of these premotor activity patterns. Finally, we also identified multivoxel patterns in the premotor, intraparietal, and lateral occipital cortices and in the putamen that reflected multisensory responses specific to individual body parts. Based on these results, we propose that the dynamic formation of a whole-body percept may be mediated by neuronal populations in the ventral premotor cortex that contain visuo-tactile receptive fields encompassing multiple body segments. PMID:25583608

  3. Selectivity for three-dimensional shape and grasping-related activity in the macaque ventral premotor cortex.

    PubMed

    Theys, Tom; Pani, Pierpaolo; van Loon, Johannes; Goffin, Jan; Janssen, Peter

    2012-08-29

    Anatomical studies indicate that area F5 in the macaque ventral premotor cortex consists of three different sectors. One of these is F5a in the posterior bank of the inferior arcuate sulcus, but no functional characterization of F5a at the single-cell level exists. We investigated the neuronal selectivity for three-dimensional (3D) shape and grasping activity in F5a. In contrast to neighboring regions F5p and 45B, the great majority of F5a neurons showed selectivity for disparity-defined curved surfaces, and most neurons preserved this selectivity across positions in depth, indicating higher-order disparity selectivity. Thus, as predicted by monkey fMRI data, F5a neurons showed robust 3D-shape selectivity in the absence of a motor response. To investigate the relationship between disparity selectivity and grasping activity, we recorded from 3D-shape-selective F5a neurons during a visually guided grasping task and during grasping in the dark. F5a neurons encoding the depth profile of curved surfaces frequently responded during grasping of real-world objects in the light, but not in the dark, whereas nearby neurons were also active in the dark. The presence of 3D-shape-selective and "visual-dominant" neurons demonstrates that the F5a sector is distinct from neighboring regions of ventral premotor cortex, in line with recent anatomical connectivity studies.

  4. Constraint-Induced Movement Therapy Combined with Transcranial Direct Current Stimulation over Premotor Cortex Improves Motor Function in Severe Stroke: A Pilot Randomized Controlled Trial.

    PubMed

    Andrade, Suellen M; Batista, Larissa M; Nogueira, Lídia L R F; de Oliveira, Eliane A; de Carvalho, Antonio G C; Lima, Soriano S; Santana, Jordânia R M; de Lima, Emerson C C; Fernández-Calvo, Bernardino

    2017-01-01

    Objective. We compared the effects of transcranial direct current stimulation at different cortical sites (premotor and motor primary cortex) combined with constraint-induced movement therapy for treatment of stroke patients. Design. Sixty patients were randomly distributed into 3 groups: Group A, anodal stimulation on premotor cortex and constraint-induced movement therapy; Group B, anodal stimulation on primary motor cortex and constraint-induced movement therapy; Group C, sham stimulation and constraint-induced movement therapy. Evaluations involved analysis of functional independence, motor recovery, spasticity, gross motor function, and muscle strength. Results. A significant improvement in primary outcome (functional independence) after treatment in the premotor group followed by primary motor group and sham group was observed. The same pattern of improvement was highlighted among all secondary outcome measures regarding the superior performance of the premotor group over primary motor and sham groups. Conclusions. Premotor cortex can contribute to motor function in patients with severe functional disabilities in early stages of stroke. This study was registered in ClinicalTrials.gov database (NCT 02628561).

  5. Constraint-Induced Movement Therapy Combined with Transcranial Direct Current Stimulation over Premotor Cortex Improves Motor Function in Severe Stroke: A Pilot Randomized Controlled Trial

    PubMed Central

    Batista, Larissa M.; Nogueira, Lídia L. R. F.; de Oliveira, Eliane A.; de Carvalho, Antonio G. C.; Lima, Soriano S.; Santana, Jordânia R. M.; de Lima, Emerson C. C.; Fernández-Calvo, Bernardino

    2017-01-01

    Objective. We compared the effects of transcranial direct current stimulation at different cortical sites (premotor and motor primary cortex) combined with constraint-induced movement therapy for treatment of stroke patients. Design. Sixty patients were randomly distributed into 3 groups: Group A, anodal stimulation on premotor cortex and constraint-induced movement therapy; Group B, anodal stimulation on primary motor cortex and constraint-induced movement therapy; Group C, sham stimulation and constraint-induced movement therapy. Evaluations involved analysis of functional independence, motor recovery, spasticity, gross motor function, and muscle strength. Results. A significant improvement in primary outcome (functional independence) after treatment in the premotor group followed by primary motor group and sham group was observed. The same pattern of improvement was highlighted among all secondary outcome measures regarding the superior performance of the premotor group over primary motor and sham groups. Conclusions. Premotor cortex can contribute to motor function in patients with severe functional disabilities in early stages of stroke. This study was registered in ClinicalTrials.gov database (NCT 02628561). PMID:28250992

  6. Ventral Premotor Cortex May Be Required for Dynamic Changes in the Feeling of Limb Ownership: A Lesion Study

    PubMed Central

    Zeller, Daniel; Gross, Catharina; Bartsch, Andreas; Johansen-Berg, Heidi; Classen, Joseph

    2011-01-01

    The feeling of “body ownership” may be experimentally investigated by perceptual illusions. The “rubber hand illusion” (RHI) leads human subjects to experience an artificial hand as their own. According to functional imaging, the ventral premotor cortex (PMv) plays a key role in the integration of multisensory inputs allowing the “incorporation” of the rubber hand into body representation. However, causal structure–function relationships can only be obtained by lesion studies. Here, we tested the RHI in 70 stroke patients and in 40 age-matched healthy controls. Additionally, asomatognosia, the unawareness of one’s own body parts, was assessed in a subgroup of 64 stroke patients. Ischemic lesions were delineated on diffusion-weighted magnetic resonance images and normalized. Right-hemispheric lesions were mirrored across the midline. Voxels that might be essential for RHI and/or somatognosia were defined by voxel-based lesion-symptom mapping. Probabilistic diffusion tractography was used to identify tracts passing through these voxels. Contralesional rubber hand illusion failure (RHIF) was observed in 18 (26%) of 70 stroke patients, an additional ipsilesional RHIF in seven of these patients. RHIF-associated lesion voxels were located subcortically adjacent to the insula, basal ganglia, and within the periventricular white matter. Tractography revealed fiber tract connections of these voxels with premotor, parietal, and prefrontal cortex. Contralesional asomatognosia was found in 18 (28%) of 64 stroke patients. In contrast to RHIF, asomatognosia-associated lesion voxels showed no connection with PMv. The results point to a role of PMv and its connections in mediating changes in the sense of limb ownership driven by multisensory stimulation. PMID:21451023

  7. Primary motor and premotor cortex in implicit sequence learning--evidence for competition between implicit and explicit human motor memory systems.

    PubMed

    Kantak, Shailesh S; Mummidisetty, Chaithanya K; Stinear, James W

    2012-09-01

    Implicit and explicit memory systems for motor skills compete with each other during and after motor practice. Primary motor cortex (M1) is known to be engaged during implicit motor learning, while dorsal premotor cortex (PMd) is critical for explicit learning. To elucidate the neural substrates underlying the interaction between implicit and explicit memory systems, adults underwent a randomized crossover experiment of anodal transcranial direct current stimulation (AtDCS) applied over M1, PMd or sham stimulation during implicit motor sequence (serial reaction time task, SRTT) practice. We hypothesized that M1-AtDCS during practice will enhance online performance and offline learning of the implicit motor sequence. In contrast, we also hypothesized that PMd-AtDCS will attenuate performance and retention of the implicit motor sequence. Implicit sequence performance was assessed at baseline, at the end of acquisition (EoA), and 24 h after practice (retention test, RET). M1-AtDCS during practice significantly improved practice performance and supported offline stabilization compared with Sham tDCS. Performance change from EoA to RET revealed that PMd-AtDCS during practice attenuated offline stabilization compared with M1-AtDCS and sham stimulation. The results support the role of M1 in implementing online performance gains and offline stabilization for implicit motor sequence learning. In contrast, enhancing the activity within explicit motor memory network nodes such as the PMd during practice may be detrimental to offline stabilization of the learned implicit motor sequence. These results support the notion of competition between implicit and explicit motor memory systems and identify underlying neural substrates that are engaged in this competition. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  8. A shared representation of the space near oneself and others in the human premotor cortex.

    PubMed

    Brozzoli, Claudio; Gentile, Giovanni; Bergouignan, Loretxu; Ehrsson, H Henrik

    2013-09-23

    Interactions between people require shared high-level cognitive representations of action goals, intentions, and mental states, but do people also share their representation of space? The human ventral premotor (PMv) and parietal cortices contain neuronal populations coding for the execution and observation of actions, analogous to the mirror neurons identified in monkeys. This neuronal system is tuned to the location of the acting person relative to the observer and the target of the action. Therefore, it can be theorized that the observer's brain constructs a low-level, body-centered representation of the space around others similar to one's own peripersonal space representation. Single-cell recordings have reported that parietal visuotactile neurons discharge for objects near specific parts of a monkey's own body and near the corresponding body parts of another individual. In humans, no neuroimaging study has investigated this issue. Here, we identified neuronal populations in the human PMv that encode the space near both one's own hand and another person's hand. The shared peripersonal space representation could support social interactions by coding sensory events, actions, and cognitive processes in a common spatial reference frame.

  9. Post-Stroke Longitudinal Alterations of Inter-Hemispheric Correlation and Hemispheric Dominance in Mouse Pre-Motor Cortex

    PubMed Central

    Panarese, Alessandro; Alia, Claudia; Micera, Silvestro; Caleo, Matteo; Di Garbo, Angelo

    2016-01-01

    Purpose Limited restoration of function is known to occur spontaneously after an ischemic injury to the primary motor cortex. Evidence suggests that Pre-Motor Areas (PMAs) may “take over” control of the disrupted functions. However, little is known about functional reorganizations in PMAs. Forelimb movements in mice can be driven by two cortical regions, Caudal and Rostral Forelimb Areas (CFA and RFA), generally accepted as primary motor and pre-motor cortex, respectively. Here, we examined longitudinal changes in functional coupling between the two RFAs following unilateral photothrombotic stroke in CFA (mm from Bregma: +0.5 anterior, +1.25 lateral). Methods Local field potentials (LFPs) were recorded from the RFAs of both hemispheres in freely moving injured and naïve mice. Neural signals were acquired at 9, 16 and 23 days after surgery (sub-acute period in stroke animals) through one bipolar electrode per hemisphere placed in the center of RFA, with a ground screw over the occipital bone. LFPs were pre-processed through an efficient method of artifact removal and analysed through: spectral,cross-correlation, mutual information and Granger causality analysis. Results Spectral analysis demonstrated an early decrease (day 9) in the alpha band power in both the RFAs. In the late sub-acute period (days 16 and 23), inter-hemispheric functional coupling was reduced in ischemic animals, as shown by a decrease in the cross-correlation and mutual information measures. Within the gamma and delta bands, correlation measures were already reduced at day 9. Granger analysis, used as a measure of the symmetry of the inter-hemispheric causal connectivity, showed a less balanced activity in the two RFAs after stroke, with more frequent oscillations of hemispheric dominance. Conclusions These results indicate robust electrophysiological changes in PMAs after stroke. Specifically, we found alterations in transcallosal connectivity, with reduced inter-hemispheric functional

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

    ERIC Educational Resources Information Center

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

    2012-01-01

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

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

    ERIC Educational Resources Information Center

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

    2012-01-01

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

  12. Dorsal anterior cingulate cortex and the value of control.

    PubMed

    Shenhav, Amitai; Cohen, Jonathan D; Botvinick, Matthew M

    2016-09-27

    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.

  13. The Dorsal Anterior Cingulate Cortex Modulates Dialectical Self-Thinking

    PubMed Central

    Wang, Fei; Peng, Kaiping; Bai, Yang; Li, Rui; Zhu, Ying; Sun, Pei; Guo, Hua; Yuan, Chun; Rotshtein, Pia; Sui, Jie

    2016-01-01

    Dialectical self-thinking involves holding the view that one can possess contradictory traits such as extraverted and introverted. Prior work has demonstrated that the dorsal part of anterior cingulate cortex (dACC) plays a crucial role in conflict monitoring as well as self-related processing. Here, we tested the function of dACC in dialectical self-thinking using a modified classical self-referential paradigm (self- vs. other-referential thinking), in which participants had to make a judgment whether a simultaneously presented pair of contradictory or non-contradictory traits properly described them while brain activity was recording using functional magnetic resonance imaging (fMRI). The data showed that activity in the dACC during the processing of self-relevant conflicting information was positively correlated with participants’ dispositional level of naïve dialecticism (measured with the Dialectical Self Scale). Psychophysiological interaction (PPI) analyses further revealed increased functional connectivity between the dACC and the caudate, middle temporal gyrus and hippocampus during the processing of self-relevant conflicting information for dialectical thinkers. These results support the hypothesis that the dACC has a key role in dialectical self-thinking. PMID:26903940

  14. Sequencing biological and physical events affects specific frequency bands within the human premotor cortex: an intracerebral EEG study.

    PubMed

    Caruana, Fausto; Sartori, Ivana; Lo Russo, Giorgio; Avanzini, Pietro

    2014-01-01

    Evidence that the human premotor cortex (PMC) is activated by cognitive functions involving the motor domain is classically explained as the reactivation of a motor program decoupled from its executive functions, and exploited for different purposes by means of a motor simulation. In contrast, the evidence that PMC contributes to the sequencing of non-biological events cannot be explained by the simulationist theory. Here we investigated how motor simulation and event sequencing coexist within the PMC and how these mechanisms interact when both functions are executed. We asked patients with depth electrodes implanted in the PMC to passively observe a randomized arrangement of images depicting biological actions and physical events and, in a second block, to sequence them in the correct order. This task allowed us to disambiguate between the simple observation of actions, their sequencing (recruiting different motor simulation processes), as well as the sequencing of non-biological events (recruiting a sequencer mechanism non dependant on motor simulation). We analysed the response of the gamma, alpha and beta frequency bands to evaluate the contribution of each brain rhythm to the observation and sequencing of both biological and non-biological stimuli. We found that motor simulation (biological>physical) and event sequencing (sequencing>observation) differently affect the three investigated frequency bands: motor simulation was reflected on the gamma and, partially, in the beta, but not in the alpha band. In contrast, event sequencing was also reflected on the alpha band.

  15. Modulatory Effects of the Ipsi and Contralateral Ventral Premotor Cortex (PMv) on the Primary Motor Cortex (M1) Outputs to Intrinsic Hand and Forearm Muscles in Cebus apella

    PubMed Central

    Quessy, Stephan; Côté, Sandrine L.; Hamadjida, Adjia; Deffeyes, Joan; Dancause, Numa

    2016-01-01

    The ventral premotor cortex (PMv) is a key node in the neural network involved in grasping. One way PMv can carry out this function is by modulating the outputs of the primary motor cortex (M1) to intrinsic hand and forearm muscles. As many PMv neurons discharge when grasping with either arm, both PMv within the same hemisphere (ipsilateral; iPMv) and in the opposite hemisphere (contralateral; cPMv) could modulate M1 outputs. Our objective was to compare modulatory effects of iPMv and cPMv on M1 outputs to intrinsic hand and forearm muscles. We used paired-pulse protocols with intracortical microstimulations in capuchin monkeys. A conditioning stimulus was applied in either iPMv or cPMv simultaneously or prior to a test stimulus in M1 and the effects quantified in electromyographic signals. Modulatory effects from iPMv were predominantly facilitatory, and facilitation was much more common and powerful on intrinsic hand than forearm muscles. In contrast, while the conditioning of cPMv could elicit facilitatory effects, in particular to intrinsic hand muscles, it was much more likely to inhibit M1 outputs. These data show that iPMv and cPMv have very different modulatory effects on the outputs of M1 to intrinsic hand and forearm muscles. PMID:27473318

  16. Modulatory Effects of the Ipsi and Contralateral Ventral Premotor Cortex (PMv) on the Primary Motor Cortex (M1) Outputs to Intrinsic Hand and Forearm Muscles in Cebus apella.

    PubMed

    Quessy, Stephan; Côté, Sandrine L; Hamadjida, Adjia; Deffeyes, Joan; Dancause, Numa

    2016-10-01

    The ventral premotor cortex (PMv) is a key node in the neural network involved in grasping. One way PMv can carry out this function is by modulating the outputs of the primary motor cortex (M1) to intrinsic hand and forearm muscles. As many PMv neurons discharge when grasping with either arm, both PMv within the same hemisphere (ipsilateral; iPMv) and in the opposite hemisphere (contralateral; cPMv) could modulate M1 outputs. Our objective was to compare modulatory effects of iPMv and cPMv on M1 outputs to intrinsic hand and forearm muscles. We used paired-pulse protocols with intracortical microstimulations in capuchin monkeys. A conditioning stimulus was applied in either iPMv or cPMv simultaneously or prior to a test stimulus in M1 and the effects quantified in electromyographic signals. Modulatory effects from iPMv were predominantly facilitatory, and facilitation was much more common and powerful on intrinsic hand than forearm muscles. In contrast, while the conditioning of cPMv could elicit facilitatory effects, in particular to intrinsic hand muscles, it was much more likely to inhibit M1 outputs. These data show that iPMv and cPMv have very different modulatory effects on the outputs of M1 to intrinsic hand and forearm muscles. © The Author 2016. Published by Oxford University Press.

  17. Response Properties of Motor Equivalence Neurons of the Primate Premotor Cortex

    PubMed Central

    Neromyliotis, Eleftherios; Moschovakis, A. K.

    2017-01-01

    To study the response properties of cells that could participate in eye-hand coordination we trained two macaque monkeys to perform center-out saccades and pointing movements with their right or left forelimb toward visual targets presented on a video display. We analyzed the phasic movement related discharges of neurons of the periarcuate cortex that fire before and during saccades and movements of the hand whether accompanied by movements of the other effector or not. Because such cells could encode an abstract form of the desired displacement vector without regard to the effector that would execute the movement we refer to such cells as motor equivalence neurons (Meq). Most of them (75%) were found in or near the smooth pursuit region and the grasp related region in the caudal bank of the arcuate sulcus. The onset of their phasic discharges preceded saccades by about 70 ms and hand movements by about 150 ms and was often correlated to both the onset of saccades and the onset of hand movements. The on-direction of Meq cells was uniformly distributed without preference for ipsiversive or contraversive movements. In about half of the Meq cells the preferred direction for saccades was the preferred direction for hand movements as well. In the remaining cells the difference was considerable (>90 deg), and the on-direction for eye-hand movements resembled that for isolated saccades in some cells and for isolated hand movements in others. A three layer neural network model that used Meq cells as its input layer showed that the combination of effector invariant discharges with non-invariant discharges could help reduce the number of decoding errors when the network attempts to compute the correct movement metrics of the right effector. PMID:28446867

  18. Limited plastic potential of the left ventral premotor cortex in speech articulation: evidence from intraoperative awake mapping in glioma patients.

    PubMed

    van Geemen, Kim; Herbet, Guillaume; Moritz-Gasser, Sylvie; Duffau, Hugues

    2014-04-01

    Despite previous lesional and functional neuroimaging studies, the actual role of the left ventral premotor cortex (vPMC), i.e., the lateral part of the precentral gyrus, is still poorly known. We report a series of eight patients with a glioma involving the left vPMC, who underwent awake surgery with intraoperative cortical and subcortical language mapping. The function of the vPMC, its subcortical connections, and its reorganization potential are investigated in the light of surgical findings and language outcome after resection. Electrostimulation of both the vPMC and subcortical white matter tract underneath the vPMC, that is, the anterior segment of the lateral part of the superior longitudinal fascicle (SLF), induced speech production disturbances with anarthria in all cases. Moreover, although some degrees of redistribution of the vPMC have been found in four patients, allowing its partial resection with no permanent speech disorders, this area was nonetheless still detected more medially in the precentral gyrus in the eight patients, despite its invasion by the glioma. Moreover, a direct connection of the vPMC with the SLF was preserved in all cases. Our original data suggest that the vPMC plays a crucial role in the speech production network and that its plastic potential is limited. We propose that this limitation is due to an anatomical constraint, namely the necessity for the left vPMC to remain connected to the lateral SLF. Beyond fundamental implications, such knowledge may have clinical applications, especially in surgery for tumors involving this cortico-subcortical circuit. Copyright © 2013 Wiley Periodicals, Inc.

  19. On the context-dependent nature of the contribution of the ventral premotor cortex to speech perception

    PubMed Central

    Tremblay, Pascale; Small, Steven L.

    2011-01-01

    What is the nature of the interface between speech perception and production, where auditory and motor representations converge? One set of explanations suggests that during perception, the motor circuits involved in producing a perceived action are in some way enacting the action without actually causing movement (covert simulation) or sending along the motor information to be used to predict its sensory consequences (i.e., efference copy). Other accounts either reject entirely the involvement of motor representations in perception, or explain their role as being more supportive than integral, and not employing the identical circuits used in production. Using fMRI, we investigated whether there are brain regions that are conjointly active for both speech perception and production, and whether these regions are sensitive to articulatory (syllabic) complexity during both processes, which is predicted by a covert simulation account. A group of healthy young adults (1) observed a female speaker produce a set of familiar words (perception), and (2) observed and then repeated the words (production). There were two types of words, varying in articulatory complexity, as measured by the presence or absence of consonant clusters. The simple words contained no consonant cluster (e.g. “palace”), while the complex words contained one to three consonant clusters (e.g. “planet”). Results indicate that the left ventral premotor cortex (PMv) was significantly active during speech perception and speech production but that activation in this region was scaled to articulatory complexity only during speech production, revealing an incompletely specified efferent motor signal during speech perception. The right planum temporal (PT) was also active during speech perception and speech production, and activation in this region was scaled to articulatory complexity during both production and perception. These findings are discussed in the context of current theories theory of

  20. Continuous theta burst stimulation over the left pre-motor cortex affects sensorimotor timing accuracy and supraliminal error correction.

    PubMed

    Bijsterbosch, Janine D; Lee, Kwang-Hyuk; Dyson-Sutton, William; Barker, Anthony T; Woodruff, Peter W R

    2011-09-02

    Adjustments to movement in response to changes in our surroundings are common in everyday behavior. Previous research has suggested that the left pre-motor cortex (PMC) is specialized for the temporal control of movement and may play a role in temporal error correction. The aim of this study was to determine the role of the left PMC in sensorimotor timing and error correction using theta burst transcranial magnetic stimulation (TBS). In Experiment 1, subjects performed a sensorimotor synchronization task (SMS) with the left and the right hand before and after either continuous or intermittent TBS (cTBS or iTBS). Timing accuracy was assessed during synchronized finger tapping with a regular auditory pacing stimulus. Responses following perceivable local timing shifts in the pacing stimulus (phase shifts) were used to measure error correction. Suppression of the left PMC using cTBS decreased timing accuracy because subjects tapped further away from the pacing tones and tapping variability increased. In addition, error correction responses returned to baseline tap-tone asynchrony levels faster following negative shifts and no overcorrection occurred following positive shifts after cTBS. However, facilitation of the left PMC using iTBS did not affect timing accuracy or error correction performance. Experiment 2 revealed that error correction performance may change with practice, independent of TBS. These findings provide evidence for a role of the left PMC in both sensorimotor timing and error correction in both hands. We propose that the left PMC may be involved in voluntarily controlled phase correction responses to perceivable timing shifts.

  1. Large identified pyramidal cells in macaque motor and premotor cortex exhibit "thin spikes": implications for cell type classification.

    PubMed

    Vigneswaran, Ganesh; Kraskov, Alexander; Lemon, Roger N

    2011-10-05

    Recent studies have suggested that extracellular recordings of putative cortical interneurons have briefer spikes than those of pyramidal neurons, providing a means of identifying cortical cell types in recordings from awake monkeys. To test this, we investigated the spike duration of antidromically identified pyramidal tract neurons (PTNs) recorded from primary motor (M1) or ventral premotor cortex (area F5) in 4 awake macaque monkeys. M1 antidromic latencies (ADLs) were skewed toward short ADLs (151 PTNs; 0.5-5.5 ms, median 1.1 ms) and significantly different from that of F5 ADLs (54 PTNs; 1.0-6.9 ms, median 2.6 ms). The duration of PTN spikes, recorded with a high-pass filter of 300 Hz and measured from the negative trough to the positive peak of the spike waveform, ranged from 0.15 to 0.71 ms. Importantly, we found a positive linear correlation between ADL and spike duration in both M1 (R(2) = 0.40, p < 0.001) and F5 (R(2) = 0.57, p < 0.001). Thus PTNs with the shortest ADL (fastest axons) had the briefest spikes, and since PTN soma size is correlated with axon size and conduction velocity, it is likely that the largest pyramidal neurons (Betz cells in M1) have spikes with short durations (0.15-0.45 ms), which overlap heavily with those reported for putative interneurons in previous studies in non-primates. In summary, one class of physiologically identified cortical pyramidal neuron exhibits a wide variety of spike durations and the results suggest that spike duration alone may not be a reliable indicator of cell type.

  2. Progressive loss of speech: a neuropsychological profile of premotor dysfunction.

    PubMed

    Didic, M; Ceccaldi, M; Poncet, M

    1998-01-01

    Several patients with 'progressive loss of speech output' or 'progressive anarthria' of degenerative origin have been reported in the literature. We report 5 clinical cases with slowly progressive loss of speech output and initially no deficit in other cognitive domains. The early clinical features were analysed in an attempt to identify the anatomo-functional systems implied in the degenerative process. The first phase of the disorder was characterised by impaired articulation consistent with speech apraxia, telegraphic style and a difficulty to elaborate a series of orofacial or hand movements. It is argued that these symptoms result from an impairment of complex motor processing due to dysfunction of the ventral premotor system. In the second phase, a decrease in spontaneous speech and self-initiated action was combined with exaggerated dependency on external stimuli, interpreted as dysfunction of the dorsal premotor system. We suggest that the neuropsychological profile of the disorder may result from progressive degeneration of the premotor cortex.

  3. A Major Human White Matter Pathway Between Dorsal and Ventral Visual Cortex.

    PubMed

    Takemura, Hiromasa; Rokem, Ariel; Winawer, Jonathan; Yeatman, Jason D; Wandell, Brian A; Pestilli, Franco

    2016-05-01

    Human visual cortex comprises many visual field maps organized into clusters. A standard organization separates visual maps into 2 distinct clusters within ventral and dorsal cortex. We combined fMRI, diffusion MRI, and fiber tractography to identify a major white matter pathway, the vertical occipital fasciculus (VOF), connecting maps within the dorsal and ventral visual cortex. We use a model-based method to assess the statistical evidence supporting several aspects of the VOF wiring pattern. There is strong evidence supporting the hypothesis that dorsal and ventral visual maps communicate through the VOF. The cortical projection zones of the VOF suggest that human ventral (hV4/VO-1) and dorsal (V3A/B) maps exchange substantial information. The VOF appears to be crucial for transmitting signals between regions that encode object properties including form, identity, and color and regions that map spatial information.

  4. Effectiveness and neural mechanisms associated with tDCS delivered to premotor cortex in stroke rehabilitation: study protocol for a randomized controlled trial.

    PubMed

    Plow, Ela B; Cunningham, David A; Beall, Erik; Jones, Stephen; Wyant, Alexandria; Bonnett, Corin; Yue, Guang H; Lowe, Mark; Wang, Xiao-Feng; Sakaie, Ken; Machado, Andre

    2013-10-12

    More than 60% of stroke survivors experience residual deficits of the paretic upper limb/hand. Standard rehabilitation generates modest gains. Stimulation delivered to the surviving Primary Motor Cortex in the stroke-affected hemisphere has been considered a promising adjunct. However, recent trials challenge its advantage. We discuss our pilot clinical trial that aims to address factors implicated in divergent success of the approach. We assess safety, feasibility and efficacy of targeting an alternate locus during rehabilitation- the premotor cortex. In anticipating variance across patients, we measure neural markers differentiating response from non-response. In a randomized, sham-controlled, double-blinded pilot clinical study, patients with chronic stroke (n = 20) are assigned to receive transcranial direct current stimulation delivered to the premotor cortex or sham during rehabilitation of the paretic arm/hand. Patients receive the designated intervention for 30 min, twice a day for 3 days a week for 5 weeks. We assess hand function and patients' reports of use of paretic hand. A general linear mixed methods model will analyze changes from pre- to post-intervention. Responders and non-responders will be compared upon baseline level of function, and neural substrates, including function and integrity of output tracts, bi-hemispheric balance, and lesion profile. Incidence of adverse events will be compared using Fisher's Exact test, while rigor of blinding will be assessed with Chi-square analysis to ascertain feasibility. Variable success of cortical stimulation in rehabilitation can be related to gaps in theoretical basis and clinical investigation. Given that most patients with severe deficits have damage to the primary motor cortex or its output pathways, it would be futile to target stimulation to this site. We suggest targeting premotor cortex because it contributes substantially to descending output, a role that is amplified with greater damage to the

  5. Effectiveness and neural mechanisms associated with tDCS delivered to premotor cortex in stroke rehabilitation: study protocol for a randomized controlled trial

    PubMed Central

    2013-01-01

    Background More than 60% of stroke survivors experience residual deficits of the paretic upper limb/hand. Standard rehabilitation generates modest gains. Stimulation delivered to the surviving Primary Motor Cortex in the stroke-affected hemisphere has been considered a promising adjunct. However, recent trials challenge its advantage. We discuss our pilot clinical trial that aims to address factors implicated in divergent success of the approach. We assess safety, feasibility and efficacy of targeting an alternate locus during rehabilitation- the premotor cortex. In anticipating variance across patients, we measure neural markers differentiating response from non-response. Methods/Design In a randomized, sham-controlled, double-blinded pilot clinical study, patients with chronic stroke (n = 20) are assigned to receive transcranial direct current stimulation delivered to the premotor cortex or sham during rehabilitation of the paretic arm/hand. Patients receive the designated intervention for 30 min, twice a day for 3 days a week for 5 weeks. We assess hand function and patients’ reports of use of paretic hand. A general linear mixed methods model will analyze changes from pre- to post-intervention. Responders and non-responders will be compared upon baseline level of function, and neural substrates, including function and integrity of output tracts, bi-hemispheric balance, and lesion profile. Incidence of adverse events will be compared using Fisher’s Exact test, while rigor of blinding will be assessed with Chi-square analysis to ascertain feasibility. Discussion Variable success of cortical stimulation in rehabilitation can be related to gaps in theoretical basis and clinical investigation. Given that most patients with severe deficits have damage to the primary motor cortex or its output pathways, it would be futile to target stimulation to this site. We suggest targeting premotor cortex because it contributes substantially to descending output, a

  6. Differential effects of continuous theta burst stimulation over left premotor cortex and right prefrontal cortex on modulating upper limb somatosensory input.

    PubMed

    Brown, Matt J N; Staines, W Richard

    2016-02-15

    Somatosensory evoked potentials (SEPs) represent somatosensory processing in non-primary motor areas (i.e. frontal N30 and N60) and somatosensory cortices (i.e. parietal P50). It is well-known that the premotor cortex (PMC) and prefrontal cortex (PFC) are involved in the preparation and planning of upper limb movements but it is currently unclear how they modulate somatosensory processing for upper limb motor control. In the current study, two experiments examined SEP modulations after continuous theta burst stimulation (cTBS) was used to transiently disrupt the left PMC (Experiment 1) and right PFC (Experiment 2). Both Experiment 1 (n=15) and Experiment 2 (n=16) used pre-post experimental designs. In both experiments participants performed a task requiring detection of varying amplitudes of attended vibrotactile (VibT) stimuli to the left index finger (D2) and execution of a pre-matched finger sequence with the right (contralateral) hand to specific VibT targets. During the task, SEPs were measured to median nerve (MN) stimulations time-locked during pre-stimulus (250 ms before VibT), early response selection (250 ms after VibT), late preparatory (750 ms after VibT) and execution (1250 ms VibT) phases. The key findings of Experiment 1 revealed significant decreases in N30 and N60 peak amplitudes after cTBS to PMC. In contrast, the results of Experiment 2, also found significant decreased N60 peak amplitudes as well as trends for increased N30 and P50 peak amplitudes. A direct comparison of Experiment 1 and Experiment 2 confirmed differential modulation of N30 peak amplitudes after PMC (gated) compared to PFC (enhanced) cTBS. Collectively, these results support that both the left PMC and right PFC have modulatory roles on early somatosensory input into non-primary motor areas, such as PMC and supplementary motor area (SMA), represented by frontal N30 and N60 SEPs. These results confirm that PMC and PFC are both part of a network that regulates somatosensory input

  7. Perception and Action Selection Dissociate Human Ventral and Dorsal Cortex

    ERIC Educational Resources Information Center

    Ikkai, Akiko; Jerde, Trenton A.; Curtis, Clayton E.

    2011-01-01

    We test theories about the functional organization of the human cortex by correlating brain activity with demands on perception versus action selection. Subjects covertly searched for a target among an array of 4, 8, or 12 items (perceptual manipulation) and then, depending on the color of the array, made a saccade toward, away from, or at a right…

  8. Network Profiles of the Dorsal Anterior Cingulate and Dorsal Prefrontal Cortex in Schizophrenia During Hippocampal-Based Associative Memory

    PubMed Central

    Woodcock, Eric A.; Wadehra, Sunali; Diwadkar, Vaibhav A.

    2016-01-01

    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

  9. Network Profiles of the Dorsal Anterior Cingulate and Dorsal Prefrontal Cortex in Schizophrenia During Hippocampal-Based Associative Memory.

    PubMed

    Woodcock, Eric A; Wadehra, Sunali; Diwadkar, Vaibhav A

    2016-01-01

    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.

  10. A Disynaptic Relay from Superior Colliculus to Dorsal Stream Visual Cortex in Macaque Monkey

    PubMed Central

    Lyon, David C.; Nassi, Jonathan J.; Callaway, Edward M.

    2010-01-01

    The superior colliculus (SC) is the first station in a subcortical relay of retinal information to extrastriate visual cortex. Ascending SC projections pass through pulvinar and LGN on their way to cortex, but it is not clear how many synapses are required to complete these circuits or which cortical areas are involved. To examine this relay directly, we injected transynaptic rabies virus into several extrastriate visual areas. We observed disynaptically labeled cells in superficial, retino-recipient SC layers from injections in dorsal stream areas MT and V3, but not the earliest extrastriate area, V2, nor ventral stream area V4. This robust SC-dorsal stream pathway is most likely relayed through the inferior pulvinar and can provide magnocellular-like sensory inputs necessary for motion perception and the computation of orienting movements. Furthermore, by circumventing primary visual cortex, this pathway may also underlie the remaining visual capacities associated with blindsight. PMID:20152132

  11. Dorsal medial prefrontal cortex contributes to conditioned taste aversion memory consolidation and retrieval.

    PubMed

    Gonzalez, Maria Carolina; Villar, Maria Eugenia; Igaz, Lionel M; Viola, Haydée; Medina, Jorge H

    2015-12-01

    The medial prefrontal cortex (mPFC) is known for its role in decision making and memory processing, including the participation in the formation of extinction memories. However, little is known regarding its contribution to aversive memory consolidation. Here we demonstrate that neural activity and protein synthesis are required in the dorsal mPFC for memory formation of a conditioned taste aversion (CTA) task and that this region is involved in the retrieval of recent and remote long-term CTA memory. In addition, both NMDA receptor and CaMKII activity in dorsal mPFC are needed for CTA memory consolidation, highlighting the complexity of mPFC functions.

  12. Sustained Attentional States Require Distinct Temporal Involvement of the Dorsal and Ventral Medial Prefrontal Cortex

    PubMed Central

    Luchicchi, Antonio; Mnie-Filali, Ouissame; Terra, Huub; Bruinsma, Bastiaan; de Kloet, Sybren F.; Obermayer, Joshua; Heistek, Tim S.; de Haan, Roel; de Kock, Christiaan P. J.; Deisseroth, Karl; Pattij, Tommy; Mansvelder, Huibert D.

    2016-01-01

    Attending the sensory environment for cue detection is a cognitive operation that occurs on a time scale of seconds. The dorsal and ventral medial prefrontal cortex (mPFC) contribute to separate aspects of attentional processing. Pyramidal neurons in different parts of the mPFC are active during cognitive behavior, yet whether this activity is causally underlying attentional processing is not known. We aimed to determine the precise temporal requirements for activation of the mPFC subregions during the seconds prior to cue detection. To test this, we used optogenetic silencing of dorsal or ventral mPFC pyramidal neurons at defined time windows during a sustained attentional state. We find that the requirement of ventral mPFC pyramidal neuron activity is strictly time-locked to stimulus detection. Inhibiting the ventral mPFC 2 s before or during cue presentation reduces response accuracy and hampers behavioral inhibition. The requirement for dorsal mPFC activity on the other hand is temporally more loosely related to a preparatory attentional state, and short lapses in pyramidal neuron activity in dorsal mPFC do not affect performance. This only occurs when the dorsal mPFC is inhibited during the entire preparatory period. Together, our results reveal that a dissociable temporal recruitment of ventral and dorsal mPFC is required during attentional processing. PMID:27630545

  13. Dynamic premotor-to-parietal interactions during spatial imagery.

    PubMed

    Sack, Alexander T; Jacobs, Christianne; De Martino, Federico; Staeren, Noel; Goebel, Rainer; Formisano, Elia

    2008-08-20

    The neurobiological processes underlying mental imagery are a matter of debate and controversy among neuroscientists, cognitive psychologists, philosophers, and biologists. Recent neuroimaging studies demonstrated that the execution of mental imagery activates large frontoparietal and occipitotemporal networks in the human brain. These previous imaging studies, however, neglected the crucial interplay within and across the widely distributed cortical networks of activated brain regions. Here, we combined time-resolved event-related functional magnetic resonance imaging with analyses of interactions between brain regions (functional and effective brain connectivity) to unravel the premotor-parietal dynamics underlying spatial imagery. Participants had to sequentially construct and spatially transform a mental visual object based on either verbal or visual instructions. By concurrently accounting for the full spatiotemporal pattern of brain activity and network connectivity, we functionally segregated an early from a late premotor-parietal imagery network. Moreover, we revealed that the modality-specific information upcoming from sensory brain regions is first sent to the premotor cortex and then to the medial-dorsal parietal cortex, i.e., top-down from the motor to the perceptual pole during spatial imagery. Importantly, we demonstrate that the premotor cortex serves as the central relay station, projecting to parietal cortex at two functionally distinct stages during spatial imagery. Our approach enabled us to disentangle the multicomponential cognitive construct of mental imagery into its different cognitive subelements. We discuss and explicitly assign these mental subprocesses to each of the revealed effective brain connectivity networks and present an integrative neurobiological model of spatial imagery.

  14. Network analysis of corticocortical connections reveals ventral and dorsal processing streams in mouse visual cortex

    PubMed Central

    Wang, Quanxin; Sporns, Olaf; Burkhalter, Andreas

    2012-01-01

    Much of the information used for visual perception and visually guided actions is processed in complex networks of connections within the cortex. To understand how this works in the normal brain and to determine the impact of disease, mice are promising models. In primate visual cortex, information is processed in a dorsal stream specialized for visuospatial processing and guided action and a ventral stream for object recognition. Here, we traced the outputs of 10 visual areas and used quantitative graph analytic tools of modern network science to determine, from the projection strengths in 39 cortical targets, the community structure of the network. We found a high density of the cortical graph that exceeded that previously shown in monkey. Each source area showed a unique distribution of projection weights across its targets (i.e. connectivity profile) that was well-fit by a lognormal function. Importantly, the community structure was strongly dependent on the location of the source area: outputs from medial/anterior extrastriate areas were more strongly linked to parietal, motor and limbic cortex, whereas lateral extrastriate areas were preferentially connected to temporal and parahippocampal cortex. These two subnetworks resemble dorsal and ventral cortical streams in primates, demonstrating that the basic layout of cortical networks is conserved across species. PMID:22457489

  15. Neuroanatomical study on the tecto-suprageniculate-dorsal auditory cortex pathway in the rat.

    PubMed

    Horie, M; Meguro, R; Hoshino, K; Ishida, N; Norita, M

    2013-01-03

    Previous anatomical and physiological studies suggest that the superior colliculus sends integrated sensory information to the multimodal cortical areas via the thalamic suprageniculate nucleus (SG). However, the detailed distribution of rat tecto-SG axon terminals and SG neurons projecting to the multimodal cortex, as well as synaptic connections between these tectal axons and SG neurons, remains unclear. In this study, the organization of the tecto-thalamo-cortical pathway was investigated via combined injections of anterograde and retrograde tracers followed by light and electron microscopic observations. Injections of a retrograde tracer, cholera toxin B subunit (CTB), into the temporal cortex, area 2, dorsal part (Te2D), and injections of an anterograde tracer, biotinylated dextran amine (BDA), into the deep layers of the superior colliculus produced the following results: (1) Retrogradely CTB-labeled neurons were found throughout SG, predominantly in its rostral part. CTB-labeled neurons were also found in other cortical areas such as the visual cortex, the auditory cortex, the parietal association cortex, and the perirhinal cortex. (2) Anterogradely BDA-labeled axons and their terminals were also observed throughout SG. Dual visualization of BDA and CTB showed that retrogradely labeled SG neurons and anterogradely labeled tectal axon terminal boutons overlapped considerably in the rostral part of SG, and their direct synaptic contacts were also confirmed via electron microscopy. These findings suggest that multimodal information from the superior colliculus can be processed directly in SG neurons projecting to Te2D.

  16. View-based encoding of actions in mirror neurons of area f5 in macaque premotor cortex.

    PubMed

    Caggiano, Vittorio; Fogassi, Leonardo; Rizzolatti, Giacomo; Pomper, Joern K; Thier, Peter; Giese, Martin A; Casile, Antonino

    2011-01-25

    Converging experimental evidence indicates that mirror neurons in the monkey premotor area F5 encode the goals of observed motor acts [1-3]. However, it is unknown whether they also contribute to encoding the perspective from which the motor acts of others are seen. In order to address this issue, we recorded the visual responses of mirror neurons of monkey area F5 by using a novel experimental paradigm based on the presentation of movies showing grasping motor acts from different visual perspectives. We found that the majority of the tested mirror neurons (74%) exhibited view-dependent activity with responses tuned to specific points of view. A minority of the tested mirror neurons (26%) exhibited view-independent responses. We conclude that view-independent mirror neurons encode action goals irrespective of the details of the observed motor acts, whereas the view-dependent ones might either form an intermediate step in the formation of view independence or contribute to a modulation of view-dependent representations in higher-level visual areas, potentially linking the goals of observed motor acts with their pictorial aspects. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Intracellular responses to frequency modulated tones in the dorsal cortex of the mouse inferior colliculus

    PubMed Central

    Geis, H.-Rüdiger A. P.; Borst, J. Gerard G.

    2013-01-01

    Frequency modulations occur in many natural sounds, including vocalizations. The neuronal response to frequency modulated (FM) stimuli has been studied extensively in different brain areas, with an emphasis on the auditory cortex and the central nucleus of the inferior colliculus. Here, we measured the responses to FM sweeps in whole-cell recordings from neurons in the dorsal cortex of the mouse inferior colliculus. Both up- and downward logarithmic FM sweeps were presented at two different speeds to both the ipsi- and the contralateral ear. Based on the number of action potentials that were fired, between 10 and 24% of cells were selective for rate or direction of the FM sweeps. A somewhat lower percentage of cells, 6–21%, showed selectivity based on EPSP size. To study the mechanisms underlying the generation of FM selectivity, we compared FM responses with responses to simple tones in the same cells. We found that if pairs of neurons responded in a similar way to simple tones, they generally also responded in a similar way to FM sweeps. Further evidence that FM selectivity can be generated within the dorsal cortex was obtained by reconstructing FM sweeps from the response to simple tones using three different models. In about half of the direction selective neurons the selectivity was generated by spectrally asymmetric synaptic inhibition. In addition, evidence for direction selectivity based on the timing of excitatory responses was also obtained in some cells. No clear evidence for the local generation of rate selectivity was obtained. We conclude that FM direction selectivity can be generated within the dorsal cortex of the mouse inferior colliculus by multiple mechanisms. PMID:23386812

  18. Effects of muscimol inactivations of functional domains in motor, premotor, and posterior parietal cortex on complex movements evoked by electrical stimulation

    PubMed Central

    Gharbawie, Omar A.; Burish, Mark J.; Kaas, Jon H.

    2013-01-01

    Parietal and frontal cortex are central to controlling forelimb movements. We previously showed that movements such as reach, grasp, and defense can be evoked from primary motor (M1), premotor (PMC), and posterior parietal (PPC) cortex when 500-ms trains of electrical pulses are delivered via microelectrodes. Stimulation sites that evoked a specific movement clustered into domains, which shared a topographic pattern in New World monkeys and prosimian galagos. Matched functional domains in parietal and frontal cortex were preferentially interconnected. We reasoned that matched functional domains form parallel networks involved in specific movements. To test the roles of domains in M1, PMC, and PPC, we systematically inactivated with muscimol domains in one region and determined if functional changes occurred in matching domains in other regions. The most common changes were higher current thresholds for stimulation-evoked movements and shorter, not fully developed, trajectories of movements. Inactivations of an M1 functional domain greatly reduced or abolished movements evoked from the matching domains in PMC or PPC, whereas movements evoked from nonmatching domains remained mostly unaffected. In contrast, inactivating PMC or PPC domains did not consistently abolish the ability to evoke movements from matching M1 domains. However, inactivation of PMC domains suppressed or altered the movements evoked from PPC domains. Thus movement sequences evoked from PMC depend on M1 and movement sequences evoked from PPC depend on both M1 and PMC. Overall, the results support the conclusion that PPC, PMC, and M1 are subdivided into functional domains that are hierarchically related within parallel networks. PMID:24353298

  19. Impairment in Delayed Non-Matching to Sample Following Lesions of Dorsal Prefrontal Cortex

    PubMed Central

    Moore, Tara L; Schettler, Stephen P.; Killiany, Ronald J.; Rosene, Douglas L.; Moss, Mark B.

    2012-01-01

    The prefrontal cortex has been identified as essential for executive function, as well as for aspects of rule learning and recognition memory. As part of our studies to assess prefrontal cortical function in the monkey, we evaluated the effects of damage to the dorsal prefrontal cortex (DPFC) on the Category Set Shifting Task (CSST), a test of abstraction and set-shifting, and on the Delayed Non Matching-to-Sample (DNMS) task, a benchmark test of rule learning and recognition memory. The DPFC lesions in this study included dorsolateral and dorsomedial aspects of the PFC. In a previous report, we published evidence of an impairment on the CSST as a consequence of DPFC lesions (Moore et al, 2009). Here we report that monkeys with lesions of the DPFC were also markedly impaired relative to controls on both the acquisition (rule learning) and performance (recognition memory) conditions of trial-unique DNMS. The presence and extent of the deficits that we observed were of some surprise and support the possibility that the dorsal prefrontal cortex plays a more direct role in learning and recognition memory than had been previously thought. PMID:23088539

  20. Impairment in delayed nonmatching to sample following lesions of dorsal prefrontal cortex.

    PubMed

    Moore, Tara L; Schettler, Stephen P; Killiany, Ronald J; Rosene, Douglas L; Moss, Mark B

    2012-12-01

    The prefrontal cortex has been identified as essential for executive function, as well as for aspects of rule learning and recognition memory. As part of our studies to assess prefrontal cortical function in the monkey, we evaluated the effects of damage to the dorsal prefrontal cortex (DPFC) on the Category Set Shifting Task (CSST), a test of abstraction and set-shifting, and on the Delayed Nonmatching to Sample (DNMS) task, a benchmark test of rule learning and recognition memory. The DPFC lesions in this study included dorsolateral and dorsomedial aspects of the PFC. In a previous report, we published evidence of an impairment on the CSST as a consequence of DPFC lesions (Moore, Schettler, Killiany, Rosene, & Moss, 2009). Here we report that monkeys with lesions of the DPFC were also markedly impaired relative to controls on both the acquisition (rule learning) and performance (recognition memory) conditions of trial-unique DNMS. The presence and extent of the deficits that we observed were of some surprise and support the possibility that the dorsal prefrontal cortex plays a more direct role in learning and recognition memory than had been previously thought.

  1. Practice explains abolished behavioural adaptation after human dorsal anterior cingulate cortex lesions.

    PubMed

    van Steenbergen, H; Haasnoot, E; Bocanegra, B R; Berretty, E W; Hommel, B

    2015-04-08

    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.

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

    PubMed

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

    2016-11-01

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

  3. 7 Tesla fMRI Reveals Systematic Functional Organization for Binocular Disparity in Dorsal Visual Cortex

    PubMed Central

    Goncalves, Nuno R.; Ban, Hiroshi; Sánchez-Panchuelo, Rosa M.; Francis, Susan T.; Schluppeck, Denis

    2015-01-01

    The binocular disparity between the views of the world registered by the left and right eyes provides a powerful signal about the depth structure of the environment. Despite increasing knowledge of the cortical areas that process disparity from animal models, comparatively little is known about the local architecture of stereoscopic processing in the human brain. Here, we take advantage of the high spatial specificity and image contrast offered by 7 tesla fMRI to test for systematic organization of disparity representations in the human brain. Participants viewed random dot stereogram stimuli depicting different depth positions while we recorded fMRI responses from dorsomedial visual cortex. We repeated measurements across three separate imaging sessions. Using a series of computational modeling approaches, we report three main advances in understanding disparity organization in the human brain. First, we show that disparity preferences are clustered and that this organization persists across imaging sessions, particularly in area V3A. Second, we observe differences between the local distribution of voxel responses in early and dorsomedial visual areas, suggesting different cortical organization. Third, using modeling of voxel responses, we show that higher dorsal areas (V3A, V3B/KO) have properties that are characteristic of human depth judgments: a simple model that uses tuning parameters estimated from fMRI data captures known variations in human psychophysical performance. Together, these findings indicate that human dorsal visual cortex contains selective cortical structures for disparity that may support the neural computations that underlie depth perception. PMID:25698743

  4. 7 tesla FMRI reveals systematic functional organization for binocular disparity in dorsal visual cortex.

    PubMed

    Goncalves, Nuno R; Ban, Hiroshi; Sánchez-Panchuelo, Rosa M; Francis, Susan T; Schluppeck, Denis; Welchman, Andrew E

    2015-02-18

    The binocular disparity between the views of the world registered by the left and right eyes provides a powerful signal about the depth structure of the environment. Despite increasing knowledge of the cortical areas that process disparity from animal models, comparatively little is known about the local architecture of stereoscopic processing in the human brain. Here, we take advantage of the high spatial specificity and image contrast offered by 7 tesla fMRI to test for systematic organization of disparity representations in the human brain. Participants viewed random dot stereogram stimuli depicting different depth positions while we recorded fMRI responses from dorsomedial visual cortex. We repeated measurements across three separate imaging sessions. Using a series of computational modeling approaches, we report three main advances in understanding disparity organization in the human brain. First, we show that disparity preferences are clustered and that this organization persists across imaging sessions, particularly in area V3A. Second, we observe differences between the local distribution of voxel responses in early and dorsomedial visual areas, suggesting different cortical organization. Third, using modeling of voxel responses, we show that higher dorsal areas (V3A, V3B/KO) have properties that are characteristic of human depth judgments: a simple model that uses tuning parameters estimated from fMRI data captures known variations in human psychophysical performance. Together, these findings indicate that human dorsal visual cortex contains selective cortical structures for disparity that may support the neural computations that underlie depth perception.

  5. Interareal Spike-Train Correlations of Anterior Cingulate and Dorsal Prefrontal Cortex during Attention Shifts.

    PubMed

    Oemisch, Mariann; Westendorff, Stephanie; Everling, Stefan; Womelsdorf, Thilo

    2015-09-23

    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

  6. Retinotopic organization of extrastriate cortex in the owl monkey--dorsal and lateral areas.

    PubMed

    Sereno, Martin I; McDonald, Colin T; Allman, John M

    2015-01-01

    Dense retinotopy data sets were obtained by microelectrode visual receptive field mapping in dorsal and lateral visual cortex of anesthetized owl monkeys. The cortex was then physically flatmounted and stained for myelin or cytochrome oxidase. Retinotopic mapping data were digitized, interpolated to a uniform grid, analyzed using the visual field sign technique-which locally distinguishes mirror image from nonmirror image visual field representations-and correlated with the myelin or cytochrome oxidase patterns. The region between V2 (nonmirror) and MT (nonmirror) contains three areas-DLp (mirror), DLi (nonmirror), and DLa/MTc (mirror). DM (mirror) was thin anteroposteriorly, and its reduced upper field bent somewhat anteriorly away from V2. DI (nonmirror) directly adjoined V2 (nonmirror) and contained only an upper field representation that also adjoined upper field DM (mirror). Retinotopy was used to define area VPP (nonmirror), which adjoins DM anteriorly, area FSTd (mirror), which adjoins MT ventrolaterally, and TP (mirror), which adjoins MT and DLa/MTc dorsoanteriorly. There was additional retinotopic and architectonic evidence for five more subdivisions of dorsal and lateral extrastriate cortex-TA (nonmirror), MSTd (mirror), MSTv (nonmirror), FSTv (nonmirror), and PP (mirror). Our data appear quite similar to data from marmosets, though our field sign-based areal subdivisions are slightly different. The region immediately anterior to the superiorly located central lower visual field V2 varied substantially between individuals, but always contained upper fields immediately touching lower visual field V2. This region appears to vary even more between species. Though we provide a summary diagram, given within- and between-species variation, it should be regarded as a guide to parsing complex retinotopy rather than a literal representation of any individual, or as the only way to agglomerate the complex mosaic of partial upper and lower field, mirror- and

  7. Electrophysiological properties of ependymal cells (radial glia) in dorsal cortex of the turtle, Pseudemys scripta.

    PubMed Central

    Connors, B W; Ransom, B R

    1987-01-01

    1. We have investigated the electrophysiological properties of ependymal cells in the isolated dorsal cortex of the turtle, Pseudemys scripta. The cell bodies of these radial glia form an epithelium at the ventricular surface, and each cell sends one or more branching processes through the cortex to the pial surface. Very few non-ependymal glia exist in the dorsal cortex. 2. Ependymal cells had high resting membrane potentials (-90 mV), very fast time constants and a lack of intrinsic excitability or synaptic potentials. 3. Changes in the K+ concentration ([K+]) of the bathing solution caused near-Nernstian changes of ependymal membrane potentials. When local neuronal pathways were activated, ependymal cells slowly depolarized while extracellular voltage shifted negatively. Simultaneous measurements of extracellular [K+] ([K+]o) near the impaled ependymal cell body showed that these slow depolarizations were fully accounted for by activity-dependent increases in [K+]o. Similar measurements during focal pressure applications of solutions with high [K+] suggested that intrasomatic recordings reflect predominantly the [K+]o adjacent to the cell body, and not the intracortical process. 4. Intracellular injections of the fluorescent dye Lucifer Yellow CH, and simultaneous recordings from neighbouring cells, indicated that ependymal cells are chemically and electrically coupled to one another. Increasing the ambient CO2 level from 5 to 40% depolarized cells, increased their input resistance, and abolished interglial dye coupling. 5. The physiological properties of ependymal cells are very similar to those of a variety of glial cell types in a range of vertebrate and invertebrate species. In the absence of other types of glia, radial glia may function as the sole cellular mediators of K+ redistribution (i.e. K+ spatial buffering) following neural activity, as well as the generators of slow extracellular potentials. Images Plate 1 Plate 2 PMID:3116210

  8. Temporal evolution of both premotor and motor cortical tuning properties reflect changes in limb biomechanics.

    PubMed

    Suminski, Aaron J; Mardoum, Philip; Lillicrap, Timothy P; Hatsopoulos, Nicholas G

    2015-04-01

    A prevailing theory in the cortical control of limb movement posits that premotor cortex initiates a high-level motor plan that is transformed by the primary motor cortex (MI) into a low-level motor command to be executed. This theory implies that the premotor cortex is shielded from the motor periphery, and therefore, its activity should not represent the low-level features of movement. Contrary to this theory, we show that both dorsal (PMd) and ventral premotor (PMv) cortexes exhibit population-level tuning properties that reflect the biomechanical properties of the periphery similar to those observed in M1. We recorded single-unit activity from M1, PMd, and PMv and characterized their tuning properties while six rhesus macaques performed a reaching task in the horizontal plane. Each area exhibited a bimodal distribution of preferred directions during execution consistent with the known biomechanical anisotropies of the muscles and limb segments. Moreover, these distributions varied in orientation or shape from planning to execution. A network model shows that such population dynamics are linked to a change in biomechanics of the limb as the monkey begins to move, specifically to the state-dependent properties of muscles. We suggest that, like M1, neural populations in PMd and PMv are more directly linked with the motor periphery than previously thought.

  9. Spatiotemporal Spike Coding of Behavioral Adaptation in the Dorsal Anterior Cingulate Cortex

    PubMed Central

    Logiaco, Laureline; Quilodran, René; Procyk, Emmanuel; Arleo, Angelo

    2015-01-01

    The frontal cortex controls behavioral adaptation in environments governed by complex rules. Many studies have established the relevance of firing rate modulation after informative events signaling whether and how to update the behavioral policy. However, whether the spatiotemporal features of these neuronal activities contribute to encoding imminent behavioral updates remains unclear. We investigated this issue in the dorsal anterior cingulate cortex (dACC) of monkeys while they adapted their behavior based on their memory of feedback from past choices. We analyzed spike trains of both single units and pairs of simultaneously recorded neurons using an algorithm that emulates different biologically plausible decoding circuits. This method permits the assessment of the performance of both spike-count and spike-timing sensitive decoders. In response to the feedback, single neurons emitted stereotypical spike trains whose temporal structure identified informative events with higher accuracy than mere spike count. The optimal decoding time scale was in the range of 70–200 ms, which is significantly shorter than the memory time scale required by the behavioral task. Importantly, the temporal spiking patterns of single units were predictive of the monkeys’ behavioral response time. Furthermore, some features of these spiking patterns often varied between jointly recorded neurons. All together, our results suggest that dACC drives behavioral adaptation through complex spatiotemporal spike coding. They also indicate that downstream networks, which decode dACC feedback signals, are unlikely to act as mere neural integrators. PMID:26266537

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

    PubMed Central

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

    2016-01-01

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

  11. Mental rotation and object categorization share a common network of prefrontal and dorsal and ventral regions of posterior cortex.

    PubMed

    Schendan, Haline E; Stern, Chantal E

    2007-04-15

    The multiple-views-plus-transformation variant of object model verification theories predicts that parietal regions that are critical for mental rotation contribute to visual object cognition. Some neuroimaging studies have shown that the intraparietal sulcus region is critically involved in mental rotation. Other studies indicate that both ventral and dorsal posterior regions are object-sensitive and involved in object perception and categorization tasks. However, it is unknown whether dorsal object-sensitive areas overlap with regions recruited for object mental rotation. Functional magnetic resonance imaging was used to test this directly. Participants performed standard tasks of object categorization, mental rotation, and eye movements. Results provided clear support for the prediction, demonstrating overlap between dorsal object-sensitive regions in ventral-caudal intraparietal sulcus (vcIPS) and an adjacent dorsal occipital area and the regions that are activated during mental rotation but not during saccades. In addition, object mental rotation (but not saccades) activated object-sensitive areas in lateral dorsal occipitotemporal cortex (DOT), and both mental rotation and object categorization recruited ventrolateral prefrontal cortex areas implicated in attention, working memory, and cognitive control. These findings provide clear evidence that a prefrontal-posterior cortical system implicated in mental rotation, including the occipitoparietal regions critical for this spatial task, is recruited during visual object categorization. Altogether, the findings provide a key link in understanding the role of dorsal and ventral visual areas in spatial and object perception and cognition: Regions in occipitoparietal cortex, as well as DOT cortex, have a general role in visual object cognition, supporting not only mental rotation but also categorization.

  12. Functional connectivity alteration after real-time fMRI motor imagery training through self-regulation of activities of the right premotor cortex.

    PubMed

    Xie, Fufang; Xu, Lele; Long, Zhiying; Yao, Li; Wu, Xia

    2015-05-01

    Real-time functional magnetic resonance imaging technology (real-time fMRI) is a novel method that can be used to investigate motor imagery training, it has attracted increasing attention in recent years, due to its ability to facilitate subjects in regulating the activities of specific brain regions to influence their behaviors. Lots of researchers have demonstrated that the right premotor area play critical roles during real-time fMRI motor imagery training. Thus, it has been hypothesized that modulating the activity of right premotor area may result in an alteration of the functional connectivity between the premotor area and other motor-related regions. The results indicated that the functional connectivity between the bilateral premotor area and right posterior parietal lobe significantly decreased during the imagination task. This finding is new evidence that real-time fMRI is effective and can provide a theoretical guidance for the alteration of the motor function of brain regions associated with motor imagery training.

  13. Inflexible Functional Connectivity of the Dorsal Anterior Cingulate Cortex in Adolescent Major Depressive Disorder.

    PubMed

    Ho, Tiffany C; Sacchet, Matthew D; Connolly, Colm G; Margulies, Daniel S; Tymofiyeva, Olga; Paulus, Martin P; Simmons, Alan N; Gotlib, Ian H; Yang, Tony T

    2017-05-29

    Recent evidence suggests that anterior cingulate cortex (ACC) maturation during adolescence contributes to or underlies the development of major depressive disorder (MDD) during this sensitive period. The ACC is a structure that sits at the intersection of several task-positive networks (eg, central executive network, CEN), which are still developing during adolescence. While recent work using seed-based approaches indicate that depressed adolescents show limited task-evoked vs resting-state connectivity (termed 'inflexibility') between the ACC and task-negative networks, no study has used network-based approaches to investigate inflexibility of the ACC in task-positive networks to understand adolescent MDD. Here, we used graph theory to compare flexibility of network-level topology in eight subregions of the ACC (spanning three task-positive networks) in 42 unmedicated adolescents with MDD and 53 well-matched healthy controls. All participants underwent fMRI scanning during resting state and a response inhibition task that robustly engages task-positive networks. Relative to controls, depressed adolescents were characterized by inflexibility in local efficiency of a key ACC node in the CEN: right dorsal anterior cingulate cortex/medial frontal gyrus (R dACC/MFG). Furthermore, individual differences in flexibility of local efficiency of R dACC/MFG significantly predicted inhibition performance, consistent with current literature demonstrating that flexible network organization affords successful cognitive control. Finally, reduced local efficiency of dACC/MFG during the task was significantly associated with an earlier age of depression onset, consistent with prior work suggesting that MDD may alter functional network development. Our results support a neurodevelopmental hypothesis of MDD wherein dysfunctional self-regulation is potentially reflected by altered ACC maturation.Neuropsychopharmacology advance online publication, 19 July 2017; doi:10.1038/npp.2017.103.

  14. Dorsal anterior cingulate cortex modulates supplementary motor area in coordinated unimanual motor behavior.

    PubMed

    Asemi, Avisa; Ramaseshan, Karthik; Burgess, Ashley; Diwadkar, Vaibhav A; Bressler, Steven L

    2015-01-01

    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.

  15. Dorsal anterior cingulate cortex modulates supplementary motor area in coordinated unimanual motor behavior

    PubMed Central

    Asemi, Avisa; Ramaseshan, Karthik; Burgess, Ashley; Diwadkar, Vaibhav A.; Bressler, Steven L.

    2015-01-01

    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

  16. Dorsal medial prefrontal cortex plays a necessary role in rapid error prediction in humans

    PubMed Central

    Modirrousta, Mandana; Fellows, Lesley K

    2009-01-01

    Activity in human dorsal anterior cingulate cortex (dACC) is correlated with errors, near-misses, and response conflict. Based on these observations, this region has been cast as playing a central role in models of error processing, conflict monitoring, and cognitive control. However, clear evidence that this region of the brain is necessary for these processes has been elusive. We studied the effects of damage to this region on four different error-related measures in 5 patients, and 19 healthy participants. Most error-related indices were not affected by such damage: patients had intact post-error slowing, and were able to report and to correct errors after they were made with accuracies comparable to the control group. However, all 5 patients were notably slow to correct errors, suggesting a deficit in on-line error prediction. This slowing was associated with impairment in the conscious prediction of error likelihood prior to a response. This finding constitutes important converging evidence for a critical role for human dACC in error monitoring, and sheds light on the selectivity and timing of the error-related process affected by dACC damage. PMID:19091989

  17. Dissociation of retinal and headcentric disparity signals in dorsal human cortex

    PubMed Central

    Arnoldussen, David M.; Goossens, Jeroen; van Den Berg, Albert V.

    2015-01-01

    Recent fMRI studies have shown fusion of visual motion and disparity signals for shape perception (Ban et al., 2012), and unmasking camouflaged surfaces (Rokers et al., 2009), but no such interaction is known for typical dorsal motion pathway tasks, like grasping and navigation. Here, we investigate human speed perception of forward motion and its representation in the human motion network. We observe strong interaction in medial (V3ab, V6) and lateral motion areas (MT+), which differ significantly. Whereas the retinal disparity dominates the binocular contribution to the BOLD activity in the anterior part of area MT+, headcentric disparity modulation of the BOLD response dominates in area V3ab and V6. This suggests that medial motion areas not only represent rotational speed of the head (Arnoldussen et al., 2011), but also translational speed of the head relative to the scene. Interestingly, a strong response to vergence eye movements was found in area V1, which showed a dependency on visual direction, just like vertical-size disparity. This is the first report of a vertical-size disparity correlate in human striate cortex. PMID:25759642

  18. Chemogenetic Inactivation of Dorsal Anterior Cingulate Cortex Neurons Disrupts Attentional Behavior in Mouse

    PubMed Central

    Koike, Hiroyuki; Demars, Michael P; Short, Jennifer A; Nabel, Elisa M; Akbarian, Schahram; Baxter, Mark G; Morishita, Hirofumi

    2016-01-01

    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

  19. Lesions to the ventral, but not the dorsal, medial prefrontal cortex enhance latent inhibition.

    PubMed

    George, David N; Duffaud, Anaïs M; Pothuizen, Helen H J; Haddon, Josephine E; Killcross, Simon

    2010-04-01

    The acquisition of a conditioned response to a stimulus when it is paired with a reinforcer is retarded if the stimulus has previously been repeatedly pre-exposed in the absence of the reinforcer. This effect, called latent inhibition, has previously been found to be insensitive to lesions of the medial prefrontal cortex (mPFC) in rats. Using an on-baseline conditioned emotional response procedure, which is especially sensitive to small variations in the absolute magnitude of latent inhibition, we found increased latent inhibition following excitotoxic lesions of the mPFC (Experiment 1) or the ventral mPFC alone (Experiment 2) as compared with sham-operated control rats. Lesions restricted to the dorsal mPFC, however, were without effect (Experiment 2). These results are consistent with those of experiments employing another type of interference procedure, extinction. Together, these findings suggest that when different contingencies between a stimulus and a reinforcer are established in separate learning phases, lesions to the ventral mPFC result in increased interference between first-learned and second-learned contingencies. As a consequence, retrieval of the second-learned contingency is impaired, and performance is dominated by the first-learned contingency. These findings are discussed in light of the use of latent inhibition to model cognitive deficits in schizophrenia.

  20. Deep brain stimulation of the dorsal anterior cingulate cortex for the treatment of chronic neuropathic pain.

    PubMed

    Russo, Jennifer F; Sheth, Sameer A

    2015-06-01

    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.

  1. Decreased expression of nociceptin/orphanin FQ in the dorsal anterior cingulate cortex of suicides.

    PubMed

    Lutz, Pierre-Eric; Zhou, Yi; Labbe, Aurélie; Mechawar, Naguib; Turecki, Gustavo

    2015-11-01

    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.

  2. Decreased Expression of Nociceptin/Orphanin FQ in the dorsal Anterior Cingulate Cortex of Suicides

    PubMed Central

    Lutz, Pierre-Eric; Zhou, Yi; Labbe, Aurélie; Mechawar, Naguib; Turecki, Gustavo

    2015-01-01

    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

  3. Asymmetry of the dorsal anterior cingulate cortex: evidences from multiple modalities of MRI.

    PubMed

    Wang, Jue; Liu, Dong-Qiang; Zhang, Han; Zhu, Wei-Xuan; Dong, Zhang-Ye; Zang, Yu-Feng

    2013-04-01

    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.

  4. High-Resolution Mapping of Anatomical Connections in Marmoset Extrastriate Cortex Reveals a Complete Representation of the Visual Field Bordering Dorsal V2

    PubMed Central

    Jeffs, Janelle; Federer, Frederick; Ichida, Jennifer M.

    2013-01-01

    The primate visual cortex consists of many areas. The posterior areas (V1, V2, V3, and middle temporal) are thought to be common to all primate species. However, the organization of cortex immediately anterior to area V2 (the “third tier” cortex) remains controversial, particularly in New World primates. The main point of contention has been whether the third tier cortex consists of a single area V3, representing lower and upper visual quadrants in dorsal and ventral cortex, respectively, or of 2 distinct areas (the dorsomedial [DM] area and a V3-like area). Resolving this controversy is crucial to understand the function and evolution of the third tier cortex. We have addressed this issue in marmosets, by performing high-precision mapping of corticocortical connections in cortex bordering dorsal V2. Multiple closely spaced neuroanatomical tracer injections were placed across the full width of dorsal V2 or adjacent anterior cortex, and the location of resulting labeled cells mapped throughout whole flattened visual cortex. The resulting topographic patterns of labeled connections allowed us to define areas and their boundaries. We found that a complete representation of the visual field borders dorsal V2 and that the third tier cortex consists of 2 distinct areas. These results unequivocally support the DM model. PMID:22523183

  5. Visual response properties of cells in the ventral and dorsal parts of the macaque inferotemporal cortex.

    PubMed

    Tamura, H; Tanaka, K

    2001-05-01

    We recorded from cells in the anterio-ventral (TEav) and anterio- dorsal (TEad) parts of area TE of the inferotemporal cortex and examined their responses to a set of 100 visual stimuli in awake, fixating monkeys. In both TEav and TEad we found that, depending on the stimulus, the time course of responses varied considerably within individual cells and that there were three main factors in the variation. One factor is variance in the balance between the initial transient part of responses around 130 ms after stimulus onset and the later part after 240 ms from stimulus onset. The later parts of responses were more stimulus selective. The second factor is variance in the latency of response onset and peak and the third is variance in the speed of decay from the peak within the initial part of the responses. Stronger responses had shorter onset and peak latencies and longer decay times. The results suggest that stimulus images can be discriminated very rapidly in TEav and TEad by detecting differences in response onset. TEav cells differed from TEad cells in that they were more difficult to activate than TEad cells: the proportion of responsive TEav cells was smaller, the maximal responses of individual cells were smaller than in TEad and the number of stimuli that evoked significant responses in individual responsive cells was also smaller than in TEad. Moreover, TEav cells, overall, responded more strongly to more colorful object images than less colorful ones, while TEad cells did not show such a tendency. However, the minimum onset latency of individual cells and the sharpness of stimulus selectivity did not differ significantly between TEav and TEad. Responses of TEav cells are as selective as those of TEad cells, although there remains a possibility that the domain of selectivity differs between the two areas. These results support an earlier anatomical finding that TEav and TEad are located at the same hierarchical level of separate serial pathways rather than

  6. Impaired learning from errors in cannabis users: Dorsal anterior cingulate cortex and hippocampus hypoactivity.

    PubMed

    Carey, Susan E; Nestor, Liam; Jones, Jennifer; Garavan, Hugh; Hester, Robert

    2015-10-01

    The chronic use of cannabis has been associated with error processing dysfunction, in particular, hypoactivity in the dorsal anterior cingulate cortex (dACC) during the processing of cognitive errors. Given the role of such activity in influencing post-error adaptive behaviour, we hypothesised that chronic cannabis users would have significantly poorer learning from errors. Fifteen chronic cannabis users (four females, mean age=22.40 years, SD=4.29) and 15 control participants (two females, mean age=23.27 years, SD=3.67) were administered a paired associate learning task that enabled participants to learn from their errors, during fMRI data collection. Compared with controls, chronic cannabis users showed (i) a lower recall error-correction rate and (ii) hypoactivity in the dACC and left hippocampus during the processing of error-related feedback and re-encoding of the correct response. The difference in error-related dACC activation between cannabis users and healthy controls varied as a function of error type, with the control group showing a significantly greater difference between corrected and repeated errors than the cannabis group. The present results suggest that chronic cannabis users have poorer learning from errors, with the failure to adapt performance associated with hypoactivity in error-related dACC and hippocampal regions. The findings highlight a consequence of performance monitoring dysfunction in drug abuse and the potential consequence this cognitive impairment has for the symptom of failing to learn from negative feedback seen in cannabis and other forms of dependence. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. The entorhinal cortex, but not the dorsal hippocampus, is necessary for single-cue latent learning.

    PubMed

    Stouffer, Eric M

    2010-09-01

    Two experiments were conducted to examine the roles of the entorhinal cortex (EC), dorsal hippocampus (DH), and ventral hippocampus (VH) in a modified Latent Cue Preference (LCP) task. The modified LCP task utilized one visual cue in each compartment, compared to several multimodal cues used in a previous version. In the single-cue LCP task, water-replete rats drink water in one compartment of the LCP box on 1 day, and then have no water in a second compartment of the LCP box the following day (one training trial), for a total of three training trials. Rats are then water-deprived prior to a preference test, in which they are allowed to move freely between the two compartments with the water removed. Latent learning is demonstrated when water-deprived rats spend more time in the compartment that previously contained the water. Experiment 1 demonstrated that the single-cue LCP task results in the same irrelevant-incentive latent learning as the multicue LCP task. In addition, Experiment 1 replicated the finding that a compartment preference based on this latent learning requires a deprivation state during the preference test, while a compartment preference based on conditioning does not. Experiment 2 examined the effects of pretraining neurotoxin lesions of the EC, DH, and VH on this single-cue LCP task. Results showed that lesions of the EC and VH disrupted the irrelevant-incentive latent learning, while lesions of the DH did not. These results indicate that a latent learning task that involves one discrete compartment cue, rather than several compartmental cues, does not require the DH. Therefore, the EC appears to play a central role in single-cue latent learning in the LCP task.

  8. Neurons in dorsal anterior cingulate cortex signal postdecisional variables in a foraging task.

    PubMed

    Blanchard, Tommy C; Hayden, Benjamin Y

    2014-01-08

    The dorsal anterior cingulate cortex (dACC) is a key hub of the brain's executive control system. Although a great deal is known about its role in outcome monitoring and behavioral adjustment, whether and how it contributes to the decision process remain unclear. Some theories suggest that dACC neurons track decision variables (e.g., option values) that feed into choice processes and is thus "predecisional." Other theories suggest that dACC activity patterns differ qualitatively depending on the choice that is made and is thus "postdecisional." To compare these hypotheses, we examined responses of 124 dACC neurons in a simple foraging task in which monkeys accepted or rejected offers of delayed rewards. In this task, options that vary in benefit (reward size) and cost (delay) appear for 1 s; accepting the option provides the cued reward after the cued delay. To get at dACC neurons' contributions to decisions, we focused on responses around the time of choice, several seconds before the reward and the end of the trial. We found that dACC neurons signal the foregone value of the rejected option, a postdecisional variable. Neurons also signal the profitability (that is, the relative value) of the offer, but even these signals are qualitatively different on accept and reject decisions, meaning that they are also postdecisional. These results suggest that dACC can be placed late in the decision process and also support models that give it a regulatory role in decision, rather than serving as a site of comparison.

  9. Dorsal Raphe Nucleus Down-Regulates Medial Prefrontal Cortex during Experience of Flow

    PubMed Central

    Ulrich, Martin; Keller, Johannes; Grön, Georg

    2016-01-01

    Previous neuroimaging studies have suggested that the experience of flow aligns with a relative increase in activation of the dorsal raphe nucleus (DRN), and relative activation decreases of the medial prefrontal cortex (MPFC) and of the amygdala (AMY). In the present study, Dynamic Causal Modeling (DCM) was used to explore effective connectivity between those brain regions. To test our hypothesis that the DRN causally down-regulates activity of the MPFC and/or of the AMY, 23 healthy male students solved mental arithmetic tasks of varying difficulty during functional magnetic resonance imaging. A “flow” condition, with task demands automatically balanced with participants’ skill level, was compared with conditions of “boredom” and “overload”. DCM models were constructed modeling full reciprocal endogenous connections between the DRN, the MPFC, the AMY, and the calcarine. The calcarine was included to allow sensory input to enter the system. Experimental conditions were modeled as exerting modulatory effects on various possible connections between the DRN, the MPFC, and the AMY, but not on self-inhibitory connections, yielding a total of 64 alternative DCM models. Model space was partitioned into eight families based on commonalities in the arrangement of the modulatory effects. Random effects Bayesian Model Selection (BMS) was applied to identify a possible winning family (and model). Although BMS revealed a clear winning family, an outstanding winning model could not be identified. Therefore, Bayesian Model Averaging was performed over models within the winning family to obtain representative DCM parameters for subsequent analyses to test our hypothesis. In line with our expectations, Bayesian averaged parameters revealed stronger down-regulatory influence of the DRN on the MPFC when participants experienced flow relative to control conditions. In addition, these condition-dependent modulatory effects significantly predicted participants

  10. Dorsal anterior cingulate and ventromedial prefrontal cortex have inverse roles in both foraging and economic choice.

    PubMed

    Shenhav, Amitai; Straccia, Mark A; Botvinick, Matthew M; Cohen, Jonathan D

    2016-12-01

    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.

  11. Dorsal Raphe Nucleus Down-Regulates Medial Prefrontal Cortex during Experience of Flow.

    PubMed

    Ulrich, Martin; Keller, Johannes; Grön, Georg

    2016-01-01

    Previous neuroimaging studies have suggested that the experience of flow aligns with a relative increase in activation of the dorsal raphe nucleus (DRN), and relative activation decreases of the medial prefrontal cortex (MPFC) and of the amygdala (AMY). In the present study, Dynamic Causal Modeling (DCM) was used to explore effective connectivity between those brain regions. To test our hypothesis that the DRN causally down-regulates activity of the MPFC and/or of the AMY, 23 healthy male students solved mental arithmetic tasks of varying difficulty during functional magnetic resonance imaging. A "flow" condition, with task demands automatically balanced with participants' skill level, was compared with conditions of "boredom" and "overload". DCM models were constructed modeling full reciprocal endogenous connections between the DRN, the MPFC, the AMY, and the calcarine. The calcarine was included to allow sensory input to enter the system. Experimental conditions were modeled as exerting modulatory effects on various possible connections between the DRN, the MPFC, and the AMY, but not on self-inhibitory connections, yielding a total of 64 alternative DCM models. Model space was partitioned into eight families based on commonalities in the arrangement of the modulatory effects. Random effects Bayesian Model Selection (BMS) was applied to identify a possible winning family (and model). Although BMS revealed a clear winning family, an outstanding winning model could not be identified. Therefore, Bayesian Model Averaging was performed over models within the winning family to obtain representative DCM parameters for subsequent analyses to test our hypothesis. In line with our expectations, Bayesian averaged parameters revealed stronger down-regulatory influence of the DRN on the MPFC when participants experienced flow relative to control conditions. In addition, these condition-dependent modulatory effects significantly predicted participants' experienced degree of

  12. Dorsal anterior cingulate cortex integrates reinforcement history to guide voluntary behavior.

    PubMed

    Holroyd, Clay B; Coles, Michael G H

    2008-05-01

    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.

  13. Optogenetic Inhibition of Dorsal Medial Prefrontal Cortex Attenuates Stress-Induced Reinstatement of Palatable Food Seeking in Female Rats

    PubMed Central

    Calu, Donna J.; Kawa, Alex B.; Marchant, Nathan J.; Navarre, Brittany M.; Henderson, Mark J.; Chen, Billy; Yau, Hau-Jie; Bossert, Jennifer M.; Schoenbaum, Geoffrey; Deisseroth, Karl; Harvey, Brandon K.; Hope, Bruce T.; Shaham, Yavin

    2013-01-01

    Relapse to maladaptive eating habits during dieting is often provoked by stress. Recently, we identified a role of dorsal medial prefrontal cortex (mPFC) neurons in stress-induced reinstatement of palatable food seeking in male rats. It is unknown whether endogenous neural activity in dorsal mPFC drives stress-induced reinstatement in female rats. Here, we used an optogenetic approach, in which female rats received bilateral dorsal mPFC microinjections of viral constructs coding light-sensitive eNpHR3.0 – eYFP or control eYFP protein and intracranial fiber optic implants. Rats were food restricted and trained to lever press for palatable food pellets. Subsequently, pellets were removed, and lever pressing was extinguished; then the effect of bilateral dorsal mPFC light delivery on reinstatement of food seeking was assessed after injections of the pharmacological stressor yohimbine (an α-2 andrenoceptor antagonist) or pellet priming, a manipulation known to provoke food seeking in hungry rats. Dorsal mPFC light delivery attenuated yohimbine-induced reinstatement of food seeking in eNpHR3.0-injected but not eYFP-injected rats. This optical manipulation had no effect on pellet-priming-induced reinstatement or ongoing food-reinforced responding. Dorsal mPFC light delivery attenuated yohimbine-induced Fos immuno-reactivity and disrupted neural activity during in vivo electrophysiological recording in awake rats. Optical stimulation caused significant outward currents and blocked electrically evoked action potentials in eNpHR3.0-injected but not eYFP-injected mPFC hemispheres. Light delivery alone caused no significant inflammatory response in mPFC. These findings indicate that intracranial light delivery in eNpHR3.0 rats disrupts endogenous dorsal mPFC neural activity that plays a role in stress-induced relapse to food seeking in female rats. PMID:23283335

  14. Childhood Emotional Maltreatment Severity Is Associated with Dorsal Medial Prefrontal Cortex Responsivity to Social Exclusion in Young Adults

    PubMed Central

    van Harmelen, Anne-Laura; Hauber, Kirsten; Gunther Moor, Bregtje; Spinhoven, Philip; Boon, Albert E.; Crone, Eveline A.; Elzinga, Bernet M.

    2014-01-01

    Children who have experienced chronic parental rejection and exclusion during childhood, as is the case in childhood emotional maltreatment, may become especially sensitive to social exclusion. This study investigated the neural and emotional responses to social exclusion (with the Cyberball task) in young adults reporting childhood emotional maltreatment. Using functional magnetic resonance imaging, we investigated brain responses and self-reported distress to social exclusion in 46 young adult patients and healthy controls (mean age = 19.2±2.16) reporting low to extreme childhood emotional maltreatment. Consistent with prior studies, social exclusion was associated with activity in the ventral medial prefrontal cortex and posterior cingulate cortex. In addition, severity of childhood emotional maltreatment was positively associated with increased dorsal medial prefrontal cortex responsivity to social exclusion. The dorsal medial prefrontal cortex plays a crucial role in self-and other-referential processing, suggesting that the more individuals have been rejected and maltreated in childhood, the more self- and other- processing is elicited by social exclusion in adulthood. Negative self-referential thinking, in itself, enhances cognitive vulnerability for the development of psychiatric disorders. Therefore, our findings may underlie the emotional and behavioural difficulties that have been reported in adults reporting childhood emotional maltreatment. PMID:24416347

  15. Childhood emotional maltreatment severity is associated with dorsal medial prefrontal cortex responsivity to social exclusion in young adults.

    PubMed

    van Harmelen, Anne-Laura; Hauber, Kirsten; Gunther Moor, Bregtje; Spinhoven, Philip; Boon, Albert E; Crone, Eveline A; Elzinga, Bernet M

    2014-01-01

    Children who have experienced chronic parental rejection and exclusion during childhood, as is the case in childhood emotional maltreatment, may become especially sensitive to social exclusion. This study investigated the neural and emotional responses to social exclusion (with the Cyberball task) in young adults reporting childhood emotional maltreatment. Using functional magnetic resonance imaging, we investigated brain responses and self-reported distress to social exclusion in 46 young adult patients and healthy controls (mean age = 19.2±2.16) reporting low to extreme childhood emotional maltreatment. Consistent with prior studies, social exclusion was associated with activity in the ventral medial prefrontal cortex and posterior cingulate cortex. In addition, severity of childhood emotional maltreatment was positively associated with increased dorsal medial prefrontal cortex responsivity to social exclusion. The dorsal medial prefrontal cortex plays a crucial role in self-and other-referential processing, suggesting that the more individuals have been rejected and maltreated in childhood, the more self- and other- processing is elicited by social exclusion in adulthood. Negative self-referential thinking, in itself, enhances cognitive vulnerability for the development of psychiatric disorders. Therefore, our findings may underlie the emotional and behavioural difficulties that have been reported in adults reporting childhood emotional maltreatment.

  16. Parieto-premotor areas mediate directional interference during bimanual movements.

    PubMed

    Wenderoth, Nicole; Debaere, Filiep; Sunaert, Stefan; van Hecke, Paul; Swinnen, Stephan P

    2004-10-01

    In bimanual movements, interference emerges when limbs are moved simultaneously along incompatible directions. The neural substrate and mechanisms underlying this phenomenon are largely unknown. We used functional magnetic resonance imaging to compare brain activation during directional incompatible versus compatible bimanual movements. Our main results were that directional interference emerges primarily within superior parietal, intraparietal and dorsal premotor areas of the right hemisphere. The same areas were also activated when the unimanual subtasks were executed in isolation. In light of previous findings in monkeys and humans, we conclude that directional interference activates a parieto-premotor circuit that is involved in the control of goal-directed movements under somatosensory guidance. Moreover, our data suggest that the parietal cortex might represent an important locus for integrating spatial aspects of the limbs' movements into a common action. It is hypothesized to be the candidate structure from where interference arises when directionally incompatible movements are performed. We discuss the possibility that interference emerges when computational resources in these parietal areas are insufficient to code two incompatible movement directions independently from each other.

  17. Temporal filtering of reward signals in the dorsal anterior cingulate cortex during a mixed-strategy game

    PubMed Central

    Seo, Hyojung; Lee, Daeyeol

    2008-01-01

    The process of decision making in humans and other animals is adaptive and can be tuned through experience so as to optimize the outcomes of their choices in a dynamic environment. Previous studies have demonstrated that the anterior cingulate cortex plays an important role in updating the animal’s behavioral strategies when the action-outcome contingencies change. Moreover, neurons in the anterior cingulate cortex often encode the signals related to expected or actual reward. We investigated whether reward-related activity in the anterior cingulate cortex is affected by the animal’s previous reward history. This was tested in rhesus monkeys trained to make binary choices in a computer-simulated competitive zero-sum game. The animal’s choice behavior was relatively close to the optimal strategy, but also revealed small but systematic biases that are consistent with the use of a reinforcement learning algorithm. In addition, the activity of neurons in the dorsal anterior cingulate cortex that was related to the reward received by the animal in a given trial was often modulated by the rewards in the previous trials. Some of these neurons encoded the rate of rewards in previous trials, whereas others displayed activity modulations more closely related to the reward prediction errors. By contrast, signals related to the animal’s choices were only weakly represented in this cortical area. These results suggest that neurons in the dorsal anterior cingulate cortex might be involved in the subjective evaluation of choice outcomes based on the animal’s reward history. PMID:17670983

  18. Cerebral pathological and compensatory mechanisms in the premotor phase of leucine-rich repeat kinase 2 parkinsonism.

    PubMed

    van Nuenen, Bart F L; Helmich, Rick C; Ferraye, Murielle; Thaler, Avner; Hendler, Talma; Orr-Urtreger, Avi; Mirelman, Anat; Bressman, Susan; Marder, Karen S; Giladi, Nir; van de Warrenburg, Bart P C; Bloem, Bastiaan R; Toni, Ivan

    2012-12-01

    Compensatory cerebral mechanisms can delay motor symptom onset in Parkinson's disease. We aim to characterize these compensatory mechanisms and early disease-related changes by quantifying movement-related cerebral function in subjects at significantly increased risk of developing Parkinson's disease, namely carriers of a leucine-rich repeat kinase 2-G2019S mutation associated with dominantly inherited parkinsonism. Functional magnetic resonance imaging was used to examine cerebral activity evoked during internal selection of motor representations, a core motor deficit in clinically overt Parkinson's disease. Thirty-nine healthy first-degree relatives of Ashkenazi Jewish patients with Parkinson's disease, who carry the leucine-rich repeat kinase 2-G2019S mutation, participated in this study. Twenty-one carriers of the leucine-rich repeat kinase 2-G2019S mutation and 18 non-carriers of this mutation were engaged in a motor imagery task (laterality judgements of left or right hands) known to be sensitive to motor control parameters. Behavioural performance of both groups was matched. Mutation carriers and non-carriers were equally sensitive to the extent and biomechanical constraints of the imagined movements in relation to the current posture of the participants' hands. Cerebral activity differed between groups, such that leucine-rich repeat kinase 2-G2019S carriers had reduced imagery-related activity in the right caudate nucleus and increased activity in the right dorsal premotor cortex. More severe striatal impairment was associated with stronger effective connectivity between the right dorsal premotor cortex and the right extrastriate body area. These findings suggest that altered movement-related activity in the caudate nuclei of leucine-rich repeat kinase 2-G2019S carriers might remain behaviourally latent by virtue of cortical compensatory mechanisms involving long-range connectivity between the dorsal premotor cortex and posterior sensory regions. These

  19. Memory consolidation of fear conditioning: Bi-stable amygdala connectivity with dorsal anterior cingulate and medial prefrontal cortex

    PubMed Central

    Feng, Pan; Chen, Zhencai; Lei, Xu

    2014-01-01

    Investigations of fear conditioning in rodents and humans have illuminated the neural mechanisms of fear acquisition and extinction. However, the neural mechanism of memory consolidation of fear conditioning is not well understood. To address this question, we measured brain activity and the changes in functional connectivity following fear acquisition using resting-state functional magnetic resonance imaging. The amygdala–dorsal anterior cingulate cortex (dACC) and hippocampus–insula functional connectivity were enhanced, whereas the amygdala–medial prefrontal cortex (mPFC) functional coupling was decreased during fear memory consolidation. Furthermore, the amygdala–mPFC functional connectivity was negatively correlated with the subjective fear ratings. These findings suggest the amygdala functional connectivity with dACC and mPFC may play an important role in memory consolidation of fear conditioning. The change of amygdala-mPFC functional connectivity could predict the subjective fear. Accordingly, this study provides a new perspective for understanding fear memory consolidation. PMID:24194579

  20. Inactivation of the dorsal hippocampus or the medial prefrontal cortex impairs retrieval but has differential effect on spatial memory reconsolidation.

    PubMed

    Rossato, Janine I; Köhler, Cristiano A; Radiske, Andressa; Bevilaqua, Lia R M; Cammarota, Martín

    2015-11-01

    Active memories can incorporate new information through reconsolidation. However, the notion that memory retrieval is necessary for reconsolidation has been recently challenged. Non-reinforced retrieval induces hippocampus and medial prefrontal cortex (mPFC)-dependent reconsolidation of spatial memory in the Morris water maze (MWM). We found that the effect of protein synthesis inhibition on this process is abolished when retrieval of the learned spatial preference is hindered through mPFC inactivation but not when it is blocked by deactivation of dorsal CA1. Our results do not fully agree with the hypothesis that retrieval is unneeded for reconsolidation. Instead, they support the idea that a hierarchic interaction between the hippocampus and the mPFC controls spatial memory in the MWM, and indicate that this cortex is sufficient to retrieve the information essential to reconsolidate the spatial memory trace, even when the hippocampus is inactivated.

  1. Disrupted MEK/ERK signaling in the medial orbital cortex and dorsal endopiriform nuclei of the prefrontal cortex in a chronic restraint stress mouse model of depression.

    PubMed

    Leem, Yea-Hyun; Yoon, Sang-Sun; Kim, Yu-Han; Jo, Sangmee Ahn

    2014-09-19

    Depression is one of the most prevalent mental illnesses, and causes a constant feeling of sadness and lose of interest, which often leads to suicide. Evidence suggests that depression is associated with aberrant MEK/ERK signaling. However, studies on MEK/ERK signaling in depression have only been done in a few brain regions, such as the hippocampus and mesolimbic reward pathways. Recent studies also implicate the involvement of the prefrontal cortex in depression. Thus, we examined the changes in MEK/ERK signaling in subregions of the prefrontal cortex of C57BL/6 mice by immunohistochemistry using phospho-MEK1/2 (Ser 217/221) and ERK1/2 (Thr202/Tyr204) antibodies. Mice were subjected to 21 consecutive days of restraint stress (for 2h daily), and depression-like behavior was evaluated using a sociability test and tail suspension test. The antidepressant, imipramine (20mg/kg) was injected intraperitoneally 30min before restraint stress exposure. Chronic/repeated restraint stress produced depressive-like behavior, such as increased social avoidance in the social interaction test, and enhanced immobility time in the tail suspension test. This depressive behavior was ameliorated by imipramine. The behavioral changes well corresponded to a decrease in MEK/ERK immunoreactivity in the medial orbital (MO) cortex and dorsal endopiriform nuclei (DEn), which was averted by imipramine, but not in cingulate, prelimbic, infralimbic, and motor cortex. These results suggest that MEK/ERK signaling is disrupted in the DEn and MO subregions of the prefrontal cortex in the depressive phenotype, and that blocking a decrease in activated MEK/ERK is inherent to the antidepressant imipramine response.

  2. The effect of regulatory mode on procrastination: Bi-stable parahippocampus connectivity with dorsal anterior cingulate and anterior prefrontal cortex.

    PubMed

    Zhang, Chenyan; Ni, Yan; Feng, Tingyong

    2017-06-30

    Previous research has elucidated that procrastination can be influenced by regulatory mode orientations. However, the neural mechanism of regulatory modes affecting procrastination is not well understood. To address this question, we employed resting-state functional magnetic resonance imaging (RS-fMRI) to test the influence of two regulatory modes (assessment and locomotion) on procrastination. The behavioral results showed that procrastination was positively correlated with assessment orientation but negatively correlated with locomotion orientation. Neuroimaging results indicated that the functional connectivity between parahippocampal cortex (PHC) and dorsal anterior cingulate (dACC) was negatively correlated with assessment scores, while the functional connectivity between anterior prefrontal cortex (aPFC) and parahippocampal cortex (PHC) was negatively correlated with locomotion scores. Critically, mediation analysis showed that the different effects of two distinct regulatory modes on procrastination were mediated by PHC-dACC and aPFC-PHC functional connectivity respectively. These results suggested that people's procrastination could be predicted by regulatory mode orientations, which is mediated by PHC connectivity with dACC and aPFC respectively. The present study extends our knowledge on procrastination and provides neural mechanism for understanding the link between regulatory mode orientations and procrastination. Copyright © 2017. Published by Elsevier B.V.

  3. Preliminary study of the regenerative processes of the dorsal cortex of the telencephalon of Lacerta viridis.

    PubMed

    Minelli, G; del Grande, P; Mambelli, M C

    1977-01-01

    The authors removed from Lacerta viridis specimens part of the dorsal hippocampus of one telencephalic hemisphere. The animals were sacrificed 110 and 260 days after the operation; 24 hours before the operation on the encephalon, each was dosed with 6--3H thymidine. An examination of the historadiographic slides showed a clear remedial process in the operated area which, 260 days after has renewed in thickness but was still minus its characteristic cellular layer. The area of the telencephalon affected by the remedial process was examined by the authors and they have put forward the hypothesis that in relation to the type of operation performed, said area is localized prevalently in the dorsal hippocampus of the caudal half of the telencephalic hemispherg. The authors have also shown that the remedial procress, though attenuated is still in progress. 260 days after the operation.

  4. The integration of motion and disparity cues to depth in dorsal visual cortex.

    PubMed

    Ban, Hiroshi; Preston, Tim J; Meeson, Alan; Welchman, Andrew E

    2012-02-12

    Humans exploit a range of visual depth cues to estimate three-dimensional structure. For example, the slant of a nearby tabletop can be judged by combining information from binocular disparity, texture and perspective. Behavioral tests show humans combine cues near-optimally, a feat that could depend on discriminating the outputs from cue-specific mechanisms or on fusing signals into a common representation. Although fusion is computationally attractive, it poses a substantial challenge, requiring the integration of quantitatively different signals. We used functional magnetic resonance imaging (fMRI) to provide evidence that dorsal visual area V3B/KO meets this challenge. Specifically, we found that fMRI responses are more discriminable when two cues (binocular disparity and relative motion) concurrently signal depth, and that information provided by one cue is diagnostic of depth indicated by the other. This suggests a cortical node important when perceiving depth, and highlights computations based on fusion in the dorsal stream.

  5. Neuronal activity in primate dorsal anterior cingulate cortex signals task conflict and predicts adjustments in pupil-linked arousal.

    PubMed

    Ebitz, R Becket; Platt, Michael L

    2015-02-04

    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. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Neuronal activity in primate dorsal anterior cingulate cortex signals task conflict and predicts adjustments in pupil-linked arousal

    PubMed Central

    Ebitz, R. Becket; Platt, Michael L.

    2014-01-01

    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

  7. Understanding the Dorsal and Ventral Systems of the Human Cerebral Cortex: Beyond Dichotomies

    ERIC Educational Resources Information Center

    Borst, Gregoire; Thompson, William L.; Kosslyn, Stephen M.

    2011-01-01

    Traditionally, characterizations of the macrolevel functional organization of the human cerebral cortex have focused on the left and right cerebral hemispheres. However, the idea of left brain versus right brain functions has been shown to be an oversimplification. We argue here that a top-bottom divide, rather than a left-right divide, is a more…

  8. Understanding the Dorsal and Ventral Systems of the Human Cerebral Cortex: Beyond Dichotomies

    ERIC Educational Resources Information Center

    Borst, Gregoire; Thompson, William L.; Kosslyn, Stephen M.

    2011-01-01

    Traditionally, characterizations of the macrolevel functional organization of the human cerebral cortex have focused on the left and right cerebral hemispheres. However, the idea of left brain versus right brain functions has been shown to be an oversimplification. We argue here that a top-bottom divide, rather than a left-right divide, is a more…

  9. Task-related modulation of effective connectivity during perceptual decision making: dissociation between dorsal and ventral prefrontal cortex.

    PubMed

    Akaishi, Rei; Ueda, Naoko; Sakai, Katsuyuki

    2013-01-01

    The dorsal and ventral parts of the lateral prefrontal cortex have been thought to play distinct roles in decision making. Although its dorsal part such as the frontal eye field (FEF) is shown to play roles in accumulation of sensory information during perceptual decision making, the role of the ventral prefrontal cortex (PFv) is not well-documented. Previous studies have suggested that the PFv is involved in selective attention to the task-relevant information and is associated with accuracy of the behavioral performance. It is unknown, however, whether the accumulation and selection processes are anatomically dissociated between the FEF and PFv. Here we show that, by using concurrent TMS and EEG recording, the short-latency (20-40 ms) TMS-evoked potentials after stimulation of the FEF change as a function of the time to behavioral response, whereas those after stimulation of the PFv change depending on whether the response is correct or not. The potentials after stimulation of either region did not show significant interaction between time to response and performance accuracy, suggesting dissociation between the processes subserved by the FEF and PFv networks. The results are consistent with the idea that the network involving the FEF plays a role in information accumulation, whereas the network involving the PFv plays a role in selecting task relevant information. In addition, stimulation of the FEF and PFv induced activation in common regions in the dorsolateral and medial frontal cortices, suggesting convergence of information processed in the two regions. Taken together, the results suggest dissociation between the FEF and PFv networks for their computational roles in perceptual decision making. The study also highlights the advantage of TMS-EEG technique in investigating the computational processes subserved by the neural network in the human brain with a high temporal resolution.

  10. Dorsal medial prefrontal cortex (MPFC) circuitry in rodent models of cocaine use: implications for drug addiction therapies.

    PubMed

    Jasinska, Agnes J; Chen, Billy T; Bonci, Antonello; Stein, Elliot A

    2015-03-01

    Although the importance of the medial prefrontal cortex (MPFC) in cocaine addiction is well established, its precise contribution to cocaine seeking, taking and relapse remains incompletely understood. In particular, across two different models of cocaine self-administration, pharmacological or optogenetic activation of the dorsal MPFC has been reported to sometimes promote and sometimes inhibit cocaine seeking. We highlight important methodological differences between the two experimental paradigms and propose a framework to potentially reconcile the apparent discrepancy. We also draw parallels between these pre-clinical models of cocaine self-administration and human neuro-imaging studies in cocaine users, and argue that both lines of evidence point to dynamic interactions between cue-reactivity processes and control processes within the dorsal MPFC circuitry. From a translational perspective, these findings underscore the importance of interventions and therapeutics targeting not just a brain region, but a specific computational process within that brain region, and may have implications for the design and implementation of more effective treatments for human cocaine addiction. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  11. Synaptic organization of striate cortex projections in the tree shrew: A comparison of the claustrum and dorsal thalamus.

    PubMed

    Day-Brown, Jonathan D; Slusarczyk, Arkadiusz S; Zhou, Na; Quiggins, Ranida; Petry, Heywood M; Bickford, Martha E

    2017-04-15

    The tree shrew (Tupaia belangeri) striate cortex is reciprocally connected with the dorsal lateral geniculate nucleus (dLGN), the ventral pulvinar nucleus (Pv), and the claustrum. In the Pv or the dLGN, striate cortex projections are thought to either strongly "drive", or more subtly "modulate" activity patterns respectively. To provide clues to the function of the claustrum, we compare the synaptic arrangements of striate cortex projections to the dLGN, Pv, and claustrum, using anterograde tracing and electron microscopy. Tissue was additionally stained with antibodies against γ-aminobutyric acid (GABA) to identify GABAergic interneurons and non-GABAergic projection cells. The striate cortex terminals were largest in the Pv (0.94 ± 0.08 μm(2) ), intermediate in the claustrum (0.34 ± 0.02 μm(2) ), and smallest in the dLGN (0.24 ± 0.01 μm(2) ). Contacts on interneurons were most common in the Pv (39%), intermediate in the claustrum (15%), and least common in the dLGN (12%). In the claustrum, non-GABAergic terminals (0.34 ± 0.01 μm(2) ) and striate cortex terminals were not significantly different in size. The largest terminals in the claustrum were GABAergic (0.51 ± 0.02 μm(2) ), and these terminals contacted dendrites and somata that were significantly larger (1.90 ± 0.30 μm(2) ) than those contacted by cortex or non-GABAergic terminals (0.28 ± 0.02 μm(2) and 0.25 ± 0.02 μm(2) , respectively). Our results indicate that the synaptic organization of the claustrum does not correspond to a driver/modulator framework. Instead, the circuitry of the claustrum suggests an integration of convergent cortical inputs, gated by GABAergic circuits. J. Comp. Neurol. 525:1403-1420, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  12. The integration of motion and disparity cues to depth in dorsal visual cortex

    PubMed Central

    Ban, Hiroshi; Preston, Tim J; Meeson, Alan; Welchman, Andrew E

    2012-01-01

    Humans exploit a range of visual depth cues to estimate three-dimensional (3D) structure. For example, the slant of a nearby tabletop can be judged by combining information from binocular disparity, texture and perspective. Behavioral tests show humans combine cues near-optimally, a feat that could depend on: (i) discriminating the outputs from cue-specific mechanisms, or (ii) fusing signals into a common representation. While fusion is computationally attractive, it poses a significant challenge, requiring the integration of quantitatively different signals. We used functional magnetic resonance imaging (fMRI) to provide evidence that dorsal visual area V3B/KO meets this challenge. Specifically, we found that fMRI responses are more discriminable when two cues (binocular disparity and relative motion) concurrently signal depth, and that information provided by one cue is diagnostic of depth indicated by the other. This suggests a cortical node important when perceiving depth, and highlights computations based on fusion in the dorsal stream. PMID:22327475

  13. STRESS-INDUCED CHANGES IN EXTRACELLULAR DOPAMINE AND SEROTONIN IN THE MEDIAL PREFRONTAL CORTEX AND DORSAL HIPPOCAMPUS OF PRENATALLY MALNOURISHED RATS

    PubMed Central

    Mokler, David J.; Torres, Olga I.; Galler, Janina R.; Morgane, Peter J.

    2009-01-01

    Prenatal protein malnutrition continues to be a significant problem in the world today. Exposure to prenatal protein malnutrition increases the risk of a number of neuropsychiatric disorders in adulthood including depression, schizophrenia and attentional deficit disorder. In the present experiment we have examined the effects of stress on extracellular serotonin (5-HT) and dopamine in the medial prefrontal cortex and dorsal hippocampus of rats exposed in utero to protein malnutrition. The medial prefrontal cortex and dorsal hippocampus were chosen as two limbic forebrain regions involved in learning and memory, attention and the stress response. Extracellular 5-HT and dopamine were determined in the medial prefrontal cortex and dorsal hippocampus of adult male Sprague-Dawley rats using dual probe in vivo microdialysis. Basal extracellular 5-HT did not differ between malnourished and well-nourished controls in either the medial prefrontal cortex or the dorsal hippocampus. Basal extracellular dopamine was significantly decreased in the medial prefrontal cortex of malnourished animals. Restraint stress (20 m) produced a significant rise in extracellular dopamine in the medial prefrontal cortex of well-nourished rats but did not alter release in malnourished rats. In malnourished rats, stress produced an increase in 5-HT in the hippocampus, whereas stress produced a decrease in 5-HT in the hippocampus of well-nourished rats. These data demonstrate that prenatal protein malnutrition alters dopaminergic neurotransmission in the medial prefrontal cortex as well as altering the dopaminergic and serotonergic response to stress. These changes may provide part of the bases for alterations in malnourished animals’ response to stress. PMID:17368432

  14. Stress-induced changes in extracellular dopamine and serotonin in the medial prefrontal cortex and dorsal hippocampus of prenatally malnourished rats.

    PubMed

    Mokler, David J; Torres, Olga I; Galler, Janina R; Morgane, Peter J

    2007-05-07

    Prenatal protein malnutrition continues to be a significant problem in the world today. Exposure to prenatal protein malnutrition increases the risk of a number of neuropsychiatric disorders in adulthood including depression, schizophrenia and attentional deficit disorder. In the present experiment, we have examined the effects of stress on extracellular serotonin (5-HT) and dopamine in the medial prefrontal cortex and dorsal hippocampus of rats exposed in utero to protein malnutrition. The medial prefrontal cortex and dorsal hippocampus were chosen as two limbic forebrain regions involved in learning and memory, attention and the stress response. Extracellular 5-HT and dopamine were determined in the medial prefrontal cortex and dorsal hippocampus of adult male Sprague-Dawley rats using dual probe in vivo microdialysis. Basal extracellular 5-HT did not differ between malnourished and well-nourished controls in either the medial prefrontal cortex or the dorsal hippocampus. Basal extracellular dopamine was significantly decreased in the medial prefrontal cortex of malnourished animals. Restraint stress (20 m) produced a significant rise in extracellular dopamine in the medial prefrontal cortex of well-nourished rats but did not alter release in malnourished rats. In malnourished rats, stress produced an increase in 5-HT in the hippocampus, whereas stress produced a decrease in 5-HT in the hippocampus of well-nourished rats. These data demonstrate that prenatal protein malnutrition alters dopaminergic neurotransmission in the medial prefrontal cortex as well as alters the dopaminergic and serotonergic response to stress. These changes may provide part of the bases for alterations in malnourished animals' response to stress.

  15. The Brain’s Dorsal Route for Speech Represents Word Meaning: Evidence from Gesture

    PubMed Central

    Josse, Goulven; Joseph, Sabine; Bertasi, Eric; Giraud, Anne-Lise

    2012-01-01

    The dual-route model of speech processing includes a dorsal stream that maps auditory to motor features at the sublexical level rather than at the lexico-semantic level. However, the literature on gesture is an invitation to revise this model because it suggests that the premotor cortex of the dorsal route is a major site of lexico-semantic interaction. Here we investigated lexico-semantic mapping using word-gesture pairs that were either congruent or incongruent. Using fMRI-adaptation in 28 subjects, we found that temporo-parietal and premotor activity during auditory processing of single action words was modulated by the prior audiovisual context in which the words had been repeated. The BOLD signal was suppressed following repetition of the auditory word alone, and further suppressed following repetition of the word accompanied by a congruent gesture (e.g. [“grasp” + grasping gesture]). Conversely, repetition suppression was not observed when the same action word was accompanied by an incongruent gesture (e.g. [“grasp” + sprinkle]). We propose a simple model to explain these results: auditory and visual information converge onto premotor cortex where it is represented in a comparable format to determine (in)congruence between speech and gesture. This ability of the dorsal route to detect audiovisual semantic (in)congruence suggests that its function is not restricted to the sublexical level. PMID:23049951

  16. The brain's dorsal route for speech represents word meaning: evidence from gesture.

    PubMed

    Josse, Goulven; Joseph, Sabine; Bertasi, Eric; Giraud, Anne-Lise

    2012-01-01

    The dual-route model of speech processing includes a dorsal stream that maps auditory to motor features at the sublexical level rather than at the lexico-semantic level. However, the literature on gesture is an invitation to revise this model because it suggests that the premotor cortex of the dorsal route is a major site of lexico-semantic interaction. Here we investigated lexico-semantic mapping using word-gesture pairs that were either congruent or incongruent. Using fMRI-adaptation in 28 subjects, we found that temporo-parietal and premotor activity during auditory processing of single action words was modulated by the prior audiovisual context in which the words had been repeated. The BOLD signal was suppressed following repetition of the auditory word alone, and further suppressed following repetition of the word accompanied by a congruent gesture (e.g. ["grasp" + grasping gesture]). Conversely, repetition suppression was not observed when the same action word was accompanied by an incongruent gesture (e.g. ["grasp" + sprinkle]). We propose a simple model to explain these results: auditory and visual information converge onto premotor cortex where it is represented in a comparable format to determine (in)congruence between speech and gesture. This ability of the dorsal route to detect audiovisual semantic (in)congruence suggests that its function is not restricted to the sublexical level.

  17. Is dorsal anterior cingulate cortex activation in response to social exclusion due to expectancy violation? An fMRI study

    PubMed Central

    Kawamoto, Taishi; Onoda, Keiichi; Nakashima, Ken'ichiro; Nittono, Hiroshi; Yamaguchi, Shuhei; Ura, Mitsuhiro

    2012-01-01

    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

  18. Listening to rhythms activates motor and premotor cortices.

    PubMed

    Bengtsson, Sara L; Ullén, Fredrik; Ehrsson, H Henrik; Hashimoto, Toshihiro; Kito, Tomonori; Naito, Eiichi; Forssberg, Hans; Sadato, Norihiro

    2009-01-01

    We used functional magnetic resonance imaging (fMRI) to identify brain areas involved in auditory rhythm perception. Participants listened to three rhythm sequences that varied in temporal predictability. The most predictable sequence was an isochronous rhythm sequence of a single interval (ISO). The other two sequences had nine intervals with unequal durations. One of these had interval durations of integer ratios relative to the shortest interval (METRIC). The other had interval durations of non-integer ratios relative to the shortest interval (NON-METRIC), and was thus perceptually more complex than the other two. In addition, we presented unpredictable sequences with randomly distributed intervals (RAN). We tested two hypotheses. Firstly, that areas involved in motor timing control would also process the temporal predictability of sensory cues. Therefore, there was no active task included in the experiment that could influence the participant perception or induce motor preparation. We found that dorsal premotor cortex (PMD), SMA, preSMA, and lateral cerebellum were more active when participants listen to rhythm sequences compared to random sequences. The activity pattern in supplementary motor area (SMA) and preSMA suggested a modulation dependent on sequence predictability, strongly suggesting a role in temporal sensory prediction. Secondly, we hypothesized that the more complex the rhythm sequence, the more it would engage short-term memory processes of the prefrontal cortex. We found that the superior prefrontal cortex was more active when listening to METRIC and NON-METRIC compared to ISO. We argue that the complexity of rhythm sequences is an important factor in modulating activity in many of the rhythm areas. However, the difference in complexity of our stimuli should be regarded as continuous.

  19. Dorsal hippocampus and medial prefrontal cortex each contribute to the retrieval of a recent spatial memory in rats.

    PubMed

    Cholvin, Thibault; Loureiro, Michaël; Cassel, Raphaelle; Cosquer, Brigitte; Herbeaux, Karin; de Vasconcelos, Anne Pereira; Cassel, Jean-Christophe

    2016-01-01

    Systems-level consolidation models propose that recent memories are initially hippocampus-dependent. When remote, they are partially or completely dependent upon the medial prefrontal cortex (mPFC). An implication of the mPFC in recent memory, however, is still debated. Different amounts of muscimol (MSCI 0, 30, 50, 80 and 250 ng in 1 µL PBS) were used to assess the impact of inactivation of the dorsal hippocampus (dHip) or the mPFC (targeting the prelimbic cortex) on a 24-h delayed retrieval of a platform location that rats had learned drug-free in a water maze. The two smallest amounts of MSCI (30 and 50 ng) did not affect recall, whatever the region. 80 ng MSCI infused into the dHip disrupted spatial memory retrieval, as did the larger amount. Infusion of MSCI into the mPFC did not alter performance in the 0-80 ng range. At 250 ng, it induced an as dramatic memory impairment as after efficient dHip inactivation. Stereological quantifications showed that 80 ng MSCI in the dHip and 250 ng MSCI in the mPFC induced a more than 80% reduction of c-Fos expression, suggesting that, beyond the amounts infused, it is the magnitude of the neuronal activity decrease which is determinant as to the functional outcome of the inactivation. Because, based on the literature, even 250 ng MSCI is a small amount, our results point to a contribution of the mPFC to the recall of a recently acquired spatial memory and thereby extend our knowledge about the functions of this major actor of cognition.

  20. Early Postnatal Lesion of the Medial Dorsal Nucleus Leads to Loss of Dendrites and Spines in Adult Prefrontal Cortex

    PubMed Central

    Marmolejo, Naydu; Paez, Jesse; Levitt, Jonathan B.; Jones, Liesl B.

    2013-01-01

    Research suggests that the medial dorsal nucleus (MD) of the thalamus influences pyramidal cell development in the prefrontal cortex (PFC) in an activity-dependent manner. The MD is reciprocally connected to the PFC. Many psychiatric disorders, such as schizophrenia, affect the PFC, and one of the most consistent findings in schizophrenia is a decrease in volume and neuronal number in the MD. Therefore, understanding the role the MD plays in the development of the PFC is important and may help in understanding the progression of psychiatric disorders that have their root in development. Focusing on the interplay between the MD and the PFC, this study examined the hypothesis that the MD plays a role in the dendritic development of pyramidal cells in the PFC. Unilateral electrolytic lesions of the MD in Long-Evans rat pups were made on postnatal day 4 (P4), and the animals developed to P60. We then examined dendritic morphology by examining MAP2 immunostaining and by using Golgi techniques to determine basilar dendrite number and spine density. Additionally, we examined pyramidal cell density in cingulate area 1 (Cg1), prelimbic region, and dorsolateral anterior cortex, which receive afferents from the MD. Thalamic lesions caused a mean MD volume decrease of 12.4% which led to a significant decrease in MAP2 staining in both superficial and deep layers in all 3 cortical areas. The lesions also caused a significant decrease in spine density and in the number of primary and secondary basilar dendrites on superficial and deep layer pyramidal neurons in all 3 regions. No significant difference was observed in pyramidal cell density in any of the regions or layers, but a nonsignificant increase in cell density was observed in 2 regions. Our data are thus consistent with the hypothesis that the MD plays a role in the development of the PFC and, therefore, may be a good model to begin to examine neurodevelopmental disorders such as autism and schizophrenia. PMID:23406908

  1. The functional role of dorso-lateral premotor cortex during mental rotation: an event-related fMRI study separating cognitive processing steps using a novel task paradigm.

    PubMed

    Lamm, Claus; Windischberger, Christian; Moser, Ewald; Bauer, Herbert

    2007-07-15

    Subjects deciding whether two objects presented at angular disparity are identical or mirror versions of each other usually show response times that linearly increase with the angle between objects. This phenomenon has been termed mental rotation. While there is widespread agreement that parietal cortex plays a dominant role in mental rotation, reports concerning the involvement of motor areas are less consistent. From a theoretical point of view, activation in motor areas suggests that mental rotation relies upon visuo-motor rather than visuo-spatial processing alone. However, the type of information that is processed by motor areas during mental rotation remains unclear. In this study we used event-related fMRI to assess whether activation in parietal and dorsolateral premotor areas (dPM) during mental rotation is distinctively related to processing spatial orientation information. Using a newly developed task paradigm we explicitly separated the processing steps (encoding, mental rotation proper and object matching) required by mental rotation tasks and additionally modulated the amount of spatial orientation information that had to be processed. Our results show that activation in dPM during mental rotation is not strongly modulated by the processing of spatial orientation information, and that activation in dPM areas is strongest during mental rotation proper. The latter finding suggests that dPM is involved in more generalized processes such as visuo-spatial attention and movement anticipation. We propose that solving mental rotation tasks is heavily dependent upon visuo-motor processes and evokes neural processing that may be considered as an implicit simulation of actual object rotation.

  2. Effects of aripiprazole and terguride on dopamine synthesis in the dorsal striatum and medial prefrontal cortex of preweanling rats.

    PubMed

    Iñiguez, S D; Cortez, A M; Crawford, C A; McDougall, S A

    2008-01-01

    The purpose of this study was to determine whether aripiprazole, a D2-like partial agonist increasingly prescribed to children, alters DA synthesis via actions at autoreceptors in the dorsal striatum and medial prefrontal cortex (mPFC) of preweanling rats. The ability of dopaminergic agents to alter DOPA accumulation in the striatum and mPFC was measured after NSD-1015 on postnatal day (PD) 20. Dopaminergic tone was manipulated by administering reserpine, gamma-butyrolactone (GBL), or through amphetamine withdrawal. Results showed that the partial agonists aripiprazole and terguride increased striatal DOPA accumulation under normosensitive conditions, but decreased DOPA accumulation in states of low dopaminergic tone. A different pattern of results was observed in the mPFC, because terguride and haloperidol, but not aripiprazole, increased DOPA accumulation under normosensitive conditions. In conclusion, the present data show that aripiprazole affects striatal synthesis modulating autoreceptors in an adult-typical manner during the late preweanling period. Unlike in adult rats, however, the mPFC of preweanling rats appears to contain transitory synthesis modulating autoreceptors that are sensitive to drug manipulation.

  3. Selective activation of dorsal raphe nucleus-projecting neurons in the ventral medial prefrontal cortex by controllable stress

    PubMed Central

    Baratta, Michael V.; Zarza, Christina M.; Gomez, Devan M.; Campeau, Serge; Watkins, Linda R.; Maier, Steven F.

    2009-01-01

    Exposure to uncontrollable stressors produces a variety of behavioral consequences (e.g. exaggerated fear, reduced social exploration) that do not occur if the stressor is controllable. In addition, an initial experience with a controllable stressor can block the behavioral and neural responses to a later uncontrollable stressor. The serotonergic (5-HT) dorsal raphe nucleus (DRN) has come to be viewed as a critical structure in mediating the behavioral effects of uncontrollable stress. Recent work suggests that the buffering effects of behavioral control on the DRN-dependent behavioral outcomes of uncontrollable stress require ventral medial prefrontal cortex (mPFCv) activation at the time of behavioral control. The present studies were conducted to directly determine whether or not controllable stress selectively activates DRN-projecting neurons within the mPFCv. To examine this possibility in the rat, we combined retrograde tracing (fluorogold iontophoresed into the DRN) with Fos immunohistochemistry, a marker for neural activation. Exposure to controllable, relative to uncontrollable, stress increased Fos expression in fluorogold-labeled neurons in the prelimbic region (PL) of the mPFCv. Furthermore, in a separate experiment, a prior experience with controllable stress led to potentiation of Fos expression in retrogradely labeled PL neurons in response to an uncontrollable stressor one week later. These results suggest that the PL selectively responds to behavioral control and utilizes such information to regulate the brainstem response to ongoing and subsequent stressors. PMID:19686468

  4. Target-specific modulation of the descending prefrontal cortex inputs to the dorsal raphe nucleus by cannabinoids

    PubMed Central

    Geddes, Sean D.; Assadzada, Saleha; Lemelin, David; Sokolovski, Alexandra; Bergeron, Richard; Haj-Dahmane, Samir; Béïque, Jean-Claude

    2016-01-01

    Serotonin (5-HT) neurons located in the raphe nuclei modulate a wide range of behaviors by means of an expansive innervation pattern. In turn, the raphe receives a vast array of synaptic inputs, and a remaining challenge lies in understanding how these individual inputs are organized, processed, and modulated in this nucleus to contribute ultimately to the core coding features of 5-HT neurons. The details of the long-range, top-down control exerted by the medial prefrontal cortex (mPFC) in the dorsal raphe nucleus (DRN) are of particular interest, in part, because of its purported role in stress processing and mood regulation. Here, we found that the mPFC provides a direct monosynaptic, glutamatergic drive to both DRN 5-HT and GABA neurons and that this architecture was conducive to a robust feed-forward inhibition. Remarkably, activation of cannabinoid (CB) receptors differentially modulated the mPFC inputs onto these cell types in the DRN, in effect regulating the synaptic excitatory/inhibitory balance governing the excitability of 5-HT neurons. Thus, the CB system dynamically reconfigures the processing features of the DRN, a mood-related circuit believed to provide a concerted and distributed regulation of the excitability of large ensembles of brain networks. PMID:27114535

  5. Combat veterans with comorbid PTSD and mild TBI exhibit a greater inhibitory processing ERP from the dorsal anterior cingulate cortex.

    PubMed

    Shu, I-Wei; Onton, Julie A; O'Connell, Ryan M; Simmons, Alan N; Matthews, Scott C

    2014-10-30

    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.

  6. Sustained decrease in oxygenated hemoglobin during video games in the dorsal prefrontal cortex: a NIRS study of children.

    PubMed

    Matsuda, Goh; Hiraki, Kazuo

    2006-02-01

    Traditional neuroimaging studies have mainly focused on brain activity derived from a simple stimulus and task. Therefore, little is known about brain activity during daily operations. In this study, we investigated hemodynamic changes in the dorsal prefrontal cortex (DPFC) during video games as one of daily amusements, using near infrared spectroscopy technique. It was previously reported that oxygenated hemoglobin (oxyHb) in adults' DPFC decreased during prolonged game playing time. In the present study, we examined whether similar changes were observed in children. Twenty children (7-14 years old) participated in our study, but only 13 of them were eventually subject to analysis. They played one or two commercially available video games; namely a fighting and a puzzle game, for 5 min. We used changes in concentration of oxyHb as an indicator of brain activity and consequently, most of the children exhibited a sustained game-related oxyHb decrease in DPFC. Decrease patterns of oxyHb in children during video game playing time did not differ from those in adults. There was no significant correlation between ages or game performances and changes in oxyHb. These findings suggest that game-related oxyHb decrease in DPFC is a common phenomenon to adults and children at least older than 7 years old, and we suggest that this probably results from attention demand from the video games rather than from subject's age and performance.

  7. Intact renewal after extinction of conditioned suppression with lesions of either the retrosplenial cortex or dorsal hippocampus.

    PubMed

    Todd, Travis P; Jiang, Matthew Y; DeAngeli, Nicole E; Bucci, David J

    2017-03-01

    Extinction of fear to a Pavlovian conditioned stimulus (CS) is known to be context-specific. When the CS is tested outside the context of extinction, fear returns, or renews. Several studies have demonstrated that renewal depends upon the hippocampus, although there are also studies where renewal was not impacted by hippocampal damage, suggesting that under some conditions context encoding and/or retrieval of extinction depends upon other regions. One candidate region is the retrosplenial cortex (RSC), which is known to contribute to contextual and spatial learning and memory. Using a conditioned-suppression paradigm, Experiment 1 tested the impact of pre-training RSC lesions on renewal of extinguished fear. Consistent with previous studies, lesions of the RSC did not impact acquisition or extinction of conditioned fear to the CS. Further, there was no evidence that RSC lesions impaired renewal, indicating that contextual encoding and/or retrieval of extinction does not depend upon the RSC. In Experiment 2, post-extinction lesions of either the RSC or dorsal hippocampus (DH) also had no impact on renewal. However, in Experiment 3, both RSC and DH lesions did impair performance in an object-in-place procedure, an index of place memory. RSC and DH contributions to extinction and renewal are discussed.

  8. Threat-related learning relies on distinct dorsal prefrontal cortex network connectivity

    PubMed Central

    Wheelock, M. D.; Sreenivasan, K. R.; Wood, K. H.; Ver Hoef, L. W.; Deshpande, G.; Knight, D. C.

    2014-01-01

    Conditioned changes in the emotional response to threat (e.g. aversive unconditioned stimulus; UCS) are mediated in part by the prefrontal cortex (PFC). Unpredictable threats elicit large emotional responses, while the response is diminished when the threat is predictable. A better understanding of how PFC connectivity to other brain regions varies with threat predictability would provide important insights into the neural processes that mediate conditioned diminution of the emotional response to threat. The present study examined brain connectivity during predictable and unpredictable threat exposure using a fear conditioning paradigm (previously published in Wood et al., 2012) in which unconditioned functional magnetic resonance imaging data was reanalyzed to assess effective connectivity. Granger causality analysis was performed using the time series data from 15 activated regions of interest after hemodynamic deconvolution, to determine regional effective connectivity. In addition, connectivity path weights were correlated with trait anxiety measures to assess the relationship between negative affect and brain connectivity. Results indicate the dorsomedial PFC (dmPFC) serves as a neural hub that influences activity in other brain regions when threats are unpredictable. In contrast, the dorsolateral PFC (dlPFC) serves as a neural hub that influences the activity of other brain regions when threats are predictable. These findings are consistent with the view that the dmPFC coordinates brain activity to take action, perhaps in a reactive manner, when an unpredicted threat is encountered, while the dlPFC coordinates brain regions to take action, in what may be a more proactive manner, to respond to predictable threats. Further, dlPFC connectivity to other brain regions (e.g. ventromedial PFC, amygdala, and insula) varied with negative affect (i.e. trait anxiety) when the UCS was predictable, suggesting that stronger connectivity may be required for emotion

  9. The Dorsal Medial Prefrontal Cortex Is Recruited by High Construal of Non-social Stimuli

    PubMed Central

    Baetens, Kris L. M. R.; Ma, Ning; Van Overwalle, Frank

    2017-01-01

    The dorsomedial prefrontal cortex (dmPFC) is part of the mentalizing network, a set of brain regions consistently engaged in inferring mental states. However, its precise function in this network remains unclear. It has recently been proposed that the dmPFC is involved in high-level abstract (i.e., categorical) identification or construction of both social and non-social stimuli, referred to as “high construal.” This was based on the observation of greater activation in the dmPFC shared by a high construal social condition (trait inference based on visually presented behavior) and a high construal non-social condition (categorization of visually presented objects) vs. matched low construal conditions (visual description of the same pictures). However, dmPFC activation has been related to task contexts requiring responses based on self-guided generation of mental content or decisions as compared to responses more directly determined by the experimental context (e.g., free vs. rule-governed choice). The previously reported dmPFC activity may reflect differences in task constraint (i.e., the extent to which the task context guided the process) confounded with the construal manipulation. Therefore, in the present study, we manipulated construal level and constraint independently, while participants underwent functional magnetic resonance imaging (fMRI). As before, participants visually described (low level construal) or categorized (high level construal) pictures of objects. Orthogonal to this, the description or categorization task had to be performed on either one object (low constraint) or on two objects simultaneously (high constraint), limiting the number of possible responses. Statistical analysis revealed common greater activation in both high construal conditions (high and low constraint) than in their low construal counterparts, replicating the influence of construal level on dmPFC activation (greater involvement in high than low construal), but no

  10. The body and objects represented in the ventral stream of the parieto-premotor network.

    PubMed

    Murata, Akira; Wen, Wen; Asama, Hajime

    2016-03-01

    The network between the parietal cortex and premotor cortex has a pivotal role in sensory-motor control. Grasping-related neurons in the anterior intraparietal area (AIP) and the ventral premotor cortex (F5) showed complementary properties each other. The object information for grasping is sent from the parietal cortex to the premotor cortex for sensory-motor transformation, and the backward signal from the premotor cortex to parietal cortex can be considered an efference copy/corollary discharge that is used to predict sensory outcome during motor behavior. Mirror neurons that represent both own action and other's action are involved in this system. This system also very well fits with body schema that reflects online state of the body during motor execution. We speculate that the parieto-premotor network, which includes the mirror neuron system, is key for mapping one's own body and the bodies of others. This means that the neuronal substrates that control one's own action and the mirror neuron system are shared with the "who" system, which is related to the recognition of action contribution, i.e., sense of agency. Representation of own and other's body in the parieto-premotor network is key to link between sensory-motor control and higher-order cognitive functions.

  11. Premotor-motor interhemispheric inhibition is released during movement initiation in older but not young adults.

    PubMed

    Hinder, Mark R; Fujiyama, Hakuei; Summers, Jeffery J

    2012-01-01

    Neural interactions between contralateral motor regions are thought to be instrumental in the successful preparation, and execution, of volitional movements. Here we investigated whether healthy ageing is associated with a change in functional connectivity, as indicated by the ability to modulate interhemispheric interactions during movement preparation in a manner that assists rapid movement responses. Thirteen young (mean age 22.2 years) and thirteen older (68.5 years) adults rapidly abducted their left index finger as soon as possible in response to a visual imperative signal, presented 500 ms after a visual warning signal.Interactions between left dorsal premotor cortex (LPMd) and right primary motor cortex (RM1) and between left primary motor cortex (LM1) and RM1 were investigated at six time points between the warning signal and the volitional response using paired-pulse transcranial magnetic stimulation. Relative to the inhibitory interactions measured at rest, both young and older adults released LM1-RM1 inhibition beginning 250 ms after the warning signal, with no significant differences between groups. LPMd-RM1 interactions became facilitatory (from the onset of the imperative signal onwards) in the older, but not the young, group. Regression analyses revealed that for the older adults, modulation of LPMd-RM1 interactions early in the preparation period was associated with faster responses, suggesting that specifically timed modulation of these pathways may be a compensatory mechanism to offset, at least in part, slowing of motor responses. The results suggest a greater reliance on premotor regions during the preparation of simple motor actions with advancing age.

  12. Motor and premotor cortices in subcortical stroke: proton magnetic resonance spectroscopy measures and arm motor impairment.

    PubMed

    Craciunas, Sorin C; Brooks, William M; Nudo, Randolph J; Popescu, Elena A; Choi, In-Young; Lee, Phil; Yeh, Hung-Wen; Savage, Cary R; Cirstea, Carmen M

    2013-06-01

    Although functional imaging and neurophysiological approaches reveal alterations in motor and premotor areas after stroke, insights into neurobiological events underlying these alterations are limited in human studies. We tested whether cerebral metabolites related to neuronal and glial compartments are altered in the hand representation in bilateral motor and premotor areas and correlated with distal and proximal arm motor impairment in hemiparetic persons. In 20 participants at >6 months postonset of a subcortical ischemic stroke and 16 age- and sex-matched healthy controls, the concentrations of N-acetylaspartate and myo-inositol were quantified by proton magnetic resonance spectroscopy. Regions of interest identified by functional magnetic resonance imaging included primary (M1), dorsal premotor (PMd), and supplementary (SMA) motor areas. Relationships between metabolite concentrations and distal (hand) and proximal (shoulder/elbow) motor impairment using Fugl-Meyer Upper Extremity (FMUE) subscores were explored. N-Acetylaspartate was lower in M1 (P = .04) and SMA (P = .004) and myo-inositol was higher in M1 (P = .003) and PMd (P = .03) in the injured (ipsilesional) hemisphere after stroke compared with the left hemisphere in controls. N-Acetylaspartate in ipsilesional M1 was positively correlated with hand FMUE subscores (P = .04). Significant positive correlations were also found between N-acetylaspartate in ipsilesional M1, PMd, and SMA and in contralesional M1 and shoulder/elbow FMUE subscores (P = .02, .01, .02, and .02, respectively). Our preliminary results demonstrated that proton magnetic resonance spectroscopy is a sensitive method to quantify relevant neuronal changes in spared motor cortex after stroke and consequently increase our knowledge of the factors leading from these changes to arm motor impairment.

  13. Retroactive interference of object-in-context long-term memory: role of dorsal hippocampus and medial prefrontal cortex.

    PubMed

    Martínez, María Cecilia; Villar, María Eugenia; Ballarini, Fabricio; Viola, Haydée

    2014-12-01

    Retroactive interference (RI) is a type of amnesia in which a new learning experience can impair the expression of a previous one. It has been studied in several types of memories for over a century. Here, we aimed to study in the long-term memory (LTM) formation of an object-in-context task, defined as the recognition of a familiar object in a context different to that in which it was previously encountered. We trained rats with two sample trials, each taking place in a different context in association with different objects. Test sessions were performed 24 h later, to evaluate LTM for both object-context pairs using separate groups of trained rats. Furthermore, given the involvement of hippocampus (Hp) and medial prefrontal cortex (mPFC) in several recognition memories, we also analyzed the participation of these structures in the LTM formation of this task by the local infusion of muscimol. Our results show that object-in-context LTM formation is sensitive to RI by a different either familiar or novel object-context pair trial, experienced 1 h later. This interference occurs in a restricted temporal window and works on the LTM consolidation phase, leaving intact short-term memory expression. The second sample trial did not affect the object recognition part of the memory. Besides, muscimol treatment before the second sample trial blocks its object-in-context LTM and restores the first sample trial memory. We hypothesized that LTM-RI amnesia is probably caused by resources or cellular machinery competition in these brain regions when they are engaged in memory formation of the traces. In sum, when two different object-in-context memory traces are being processed, the second trace interferes with the consolidation of the first one requiring mPFC and CA1 dorsal Hp activation. © 2014 Wiley Periodicals, Inc.

  14. From attention to memory along the dorsal-ventral axis of the medial prefrontal cortex: some methodological considerations

    PubMed Central

    Cassaday, Helen J.; Nelson, Andrew J. D.; Pezze, Marie A.

    2014-01-01

    Distinctions along the dorsal-ventral axis of medial prefrontal cortex (mPFC), between anterior cingulate (AC), prelimbic (PL), and infralimbic (IL) sub-regions, have been proposed on a variety of neuroanatomical and neurophysiological grounds. Conventional lesion approaches (as well as some electrophysiological studies) have shown that these distinctions relate to function in that a number behavioral dissociations have been demonstrated, particularly using rodent models of attention, learning, and memory. For example, there is evidence to suggest that AC has a relatively greater role in attention, whereas IL is more involved in executive function. However, the well-established methods of behavioral neuroscience have the limitation that neuromodulation is not addressed. The neurotoxin 6-hydroxydopamine has been used to deplete dopamine (DA) in mPFC sub-regions, but these lesions are not selective anatomically and noradrenalin is typically also depleted. Microinfusion of drugs through indwelling cannulae provides an alternative approach, to address the role of neuromodulation and moreover that of specific receptor subtypes within mPFC sub-regions, but the effects of such treatments cannot be assumed to be anatomically restricted either. New methodological approaches to the functional delineation of the role of mPFC in attention, learning and memory will also be considered. Taken in isolation, the conventional lesion methods which have been a first line of approach may suggest that a particular mPFC sub-region is not necessary for a particular aspect of function. However, this does not exclude a neuromodulatory role and more neuropsychopharmacological approaches are needed to explain some of the apparent inconsistencies in the results. PMID:25249948

  15. Spatiotemporal trajectories of reactivation of somatosensory cortex by direct and secondary pathways after dorsal column lesions in squirrel monkeys.

    PubMed

    Qi, Hui-Xin; Wang, Feng; Liao, Chia-Chi; Friedman, Robert M; Tang, Chaohui; Kaas, Jon H; Avison, Malcolm J

    2016-11-15

    After lesions of the somatosensory dorsal column (DC) pathway, the cortical hand representation can become unresponsive to tactile stimuli, but considerable responsiveness returns over weeks of post-lesion recovery. The reactivation suggests that preserved subthreshold sensory inputs become potentiated and axon sprouting occurs over time to mediate recovery. Here, we studied the recovery process in 3 squirrel monkeys, using high-resolution cerebral blood volume-based functional magnetic resonance imaging (CBV-fMRI) mapping of contralateral somatosensory cortex responsiveness to stimulation of distal finger pads with low and high level electrocutaneous stimulation (ES) before and 2, 4, and 6weeks after a mid-cervical level contralateral DC lesion. Both low and high intensity ES of digits revealed the expected somatotopy of the area 3b hand representation in pre-lesion monkeys, while in areas 1 and 3a, high intensity stimulation was more effective in activating somatotopic patterns. Six weeks post-lesion, and irrespective of the severity of loss of direct DC inputs (98%, 79%, 40%), somatosensory cortical area 3b of all three animals showed near complete recovery in terms of somatotopy and responsiveness to low and high intensity ES. However there was significant variability in the patterns and amplitudes of reactivation of individual digit territories within and between animals, reflecting differences in the degree of permanent and/or transient silencing of primary DC and secondary inputs 2weeks post-lesion, and their spatio-temporal trajectories of recovery between 2 and 6weeks. Similar variations in the silencing and recovery of somatotopy and responsiveness to high intensity ES in areas 3a and 1 are consistent with individual differences in damage to and recovery of DC and spinocuneate pathways, and possibly the potentiation of spinothalamic pathways. Thus, cortical deactivation and subsequent reactivation depends not only on the degree of DC lesion, but also on

  16. Distinct behavioral consequences of short-term and prolonged GABAergic depletion in prefrontal cortex and dorsal hippocampus

    PubMed Central

    Reichel, Judith M.; Nissel, Sabine; Rogel-Salazar, Gabriela; Mederer, Anna; Käfer, Karola; Bedenk, Benedikt T.; Martens, Henrik; Anders, Rebecca; Grosche, Jens; Michalski, Dominik; Härtig, Wolfgang; Wotjak, Carsten T.

    2015-01-01

    GABAergic interneurons are essential for a functional equilibrium between excitatory and inhibitory impulses throughout the CNS. Disruption of this equilibrium can lead to various neurological or neuropsychiatric disorders such as epilepsy or schizophrenia. Schizophrenia itself is clinically defined by negative (e.g., depression) and positive (e.g., hallucinations) symptoms as well as cognitive dysfunction. GABAergic interneurons are proposed to play a central role in the etiology and progression of schizophrenia; however, the specific mechanisms and the time-line of symptom development as well as the distinct involvement of cortical and hippocampal GABAergic interneurons in the etiology of schizophrenia-related symptoms are still not conclusively resolved. Previous work demonstrated that GABAergic interneurons can be selectively depleted in adult mice by means of saporin-conjugated anti-vesicular GABA transporter antibodies (SAVAs) in vitro and in vivo. Given their involvement in schizophrenia-related disease etiology, we ablated GABAergic interneurons in the medial prefrontal cortex (mPFC) and dorsal hippocampus (dHPC) in adult male C57BL/6N mice. Subsequently we assessed alterations in anxiety, sensory processing, hyperactivity and cognition after long-term (>14 days) and short-term (<14 days) GABAergic depletion. Long-term GABAergic depletion in the mPFC resulted in a decrease in sensorimotor-gating and impairments in cognitive flexibility. Notably, the same treatment at the level of the dHPC completely abolished spatial learning capabilities. Short-term GABAergic depletion in the dHPC revealed a transient hyperactive phenotype as well as marked impairments regarding the acquisition of a spatial memory. In contrast, recall of a spatial memory was not affected by the same intervention. These findings emphasize the importance of functional local GABAergic networks for the encoding but not the recall of hippocampus-dependent spatial memories. PMID:25628548

  17. Distinct behavioral consequences of short-term and prolonged GABAergic depletion in prefrontal cortex and dorsal hippocampus.

    PubMed

    Reichel, Judith M; Nissel, Sabine; Rogel-Salazar, Gabriela; Mederer, Anna; Käfer, Karola; Bedenk, Benedikt T; Martens, Henrik; Anders, Rebecca; Grosche, Jens; Michalski, Dominik; Härtig, Wolfgang; Wotjak, Carsten T

    2014-01-01

    GABAergic interneurons are essential for a functional equilibrium between excitatory and inhibitory impulses throughout the CNS. Disruption of this equilibrium can lead to various neurological or neuropsychiatric disorders such as epilepsy or schizophrenia. Schizophrenia itself is clinically defined by negative (e.g., depression) and positive (e.g., hallucinations) symptoms as well as cognitive dysfunction. GABAergic interneurons are proposed to play a central role in the etiology and progression of schizophrenia; however, the specific mechanisms and the time-line of symptom development as well as the distinct involvement of cortical and hippocampal GABAergic interneurons in the etiology of schizophrenia-related symptoms are still not conclusively resolved. Previous work demonstrated that GABAergic interneurons can be selectively depleted in adult mice by means of saporin-conjugated anti-vesicular GABA transporter antibodies (SAVAs) in vitro and in vivo. Given their involvement in schizophrenia-related disease etiology, we ablated GABAergic interneurons in the medial prefrontal cortex (mPFC) and dorsal hippocampus (dHPC) in adult male C57BL/6N mice. Subsequently we assessed alterations in anxiety, sensory processing, hyperactivity and cognition after long-term (>14 days) and short-term (<14 days) GABAergic depletion. Long-term GABAergic depletion in the mPFC resulted in a decrease in sensorimotor-gating and impairments in cognitive flexibility. Notably, the same treatment at the level of the dHPC completely abolished spatial learning capabilities. Short-term GABAergic depletion in the dHPC revealed a transient hyperactive phenotype as well as marked impairments regarding the acquisition of a spatial memory. In contrast, recall of a spatial memory was not affected by the same intervention. These findings emphasize the importance of functional local GABAergic networks for the encoding but not the recall of hippocampus-dependent spatial memories.

  18. The Time Course of Activity within the Dorsal and Rostral-Ventral Anterior Cingulate Cortex in the Emotional Stroop Task.

    PubMed

    Feroz, Farah Shahnaz; Leicht, Gregor; Steinmann, Saskia; Andreou, Christina; Mulert, Christoph

    2017-01-01

    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.

  19. Dissociating the role of prefrontal and premotor cortices in controlling inhibitory mechanisms during motor preparation

    PubMed Central

    Duque, Julie; Labruna, Ludovica; Verset, Sophie; Olivier, Etienne; Ivry, Richard B.

    2012-01-01

    Top-down control processes are critical to select goal-directed actions in flexible environments. In humans, these processes include two inhibitory mechanisms that operate during response selection: one is involved in solving a competition between different response options, the other ensures that a selected response is initiated timely. Here, we evaluated the role of dorsal premotor cortex (PMd) and lateral prefrontal cortex (LPF) of healthy subjects in these two forms of inhibition by using an innovative transcranial magnetic stimulation (TMS) protocol combining repetitive TMS (rTMS) over PMd or LPF and a single pulse TMS (sTMS) over primary motor cortex (M1). sTMS over M1 allowed us to assess inhibitory changes in corticospinal excitability, while rTMS was used to produce transient disruption of PMd or LPF. We found that rTMS over LPF reduces inhibition associated with competition resolution whereas rTMS over PMd decreases inhibition associated with response impulse control. These results emphasize the dissociable contributions of these two frontal regions to inhibitory control during motor preparation. The association of LPF with competition resolution is consistent with the role of this area in relatively abstract aspects of control related to goal maintenance, ensuring that the appropriate response is selected in a variable context. In contrast, the association of PMd with impulse control is consistent with the role of this area in more specific processes related to motor preparation and initiation. PMID:22262879

  20. Role of the dorsal anterior cingulate cortex in obsessive-compulsive disorder: converging evidence from cognitive neuroscience and psychiatric neurosurgery.

    PubMed

    McGovern, Robert A; Sheth, Sameer A

    2017-01-01

    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

  1. Dorsal Anterior Cingulate Cortex Responses to Repeated Social Evaluative Feedback in Young Women with and without a History of Depression

    PubMed Central

    Dedovic, Katarina; Slavich, George M.; Muscatell, Keely A.; Irwin, Michael R.; Eisenberger, Naomi I.

    2016-01-01

    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

  2. Reduced gray matter volume of dorsal cingulate cortex in patients with obsessive-compulsive disorder: a voxel-based morphometric study.

    PubMed

    Matsumoto, Ryohei; Ito, Hiroshi; Takahashi, Hidehiko; Ando, Tomomichi; Fujimura, Yota; Nakayama, Kazuhiko; Okubo, Yoshiro; Obata, Takayuki; Fukui, Kenji; Suhara, Tetsuya

    2010-10-01

    Previous morphometric studies using magnetic resonance imaging (MRI) have revealed structural brain abnormalities in obsessive-compulsive disorder (OCD). The aim of the present study was to investigate the alterations in brain structure of patients with OCD using a voxel-based morphometry (VBM) method. Sixteen patients with OCD free of comorbid major depression, and 32 sex- and age-matched healthy subjects underwent MRI using a 1.5-T MR scanner. OCD severity was assessed with the Yale-Brown Obsessive-Compulsive Scale (mean ± SD: 22 ± 7.6; range: 7-32). MR images were spatially normalized and segmented using the VBM5 package (http://dbm.neuro.uni-jena.de/vbm/). Statistical analysis was performed using statistical parametric mapping software. Significant reductions in regional gray matter volume were detected in the left caudal anterior cingulate cortex and right dorsal posterior cingulate cortex in the patients with OCD as compared to healthy controls (uncorrected, P < 0.001). No significant differences in white matter volumes were observed in any brain regions of the patients. No significant correlation between Yale-Brown Obsessive-Compulsive Scale score and regional gray matter or white matter volume was observed. Regional gray matter alteration in the dorsal cingulate cortex, which is suggested to play a role in non-emotional cognitive processes, may be related to the pathophysiology in OCD. © 2010 The Authors. Psychiatry and Clinical Neurosciences © 2010 Japanese Society of Psychiatry and Neurology.

  3. Ventral and dorsal pathways for language

    PubMed Central

    Saur, Dorothee; Kreher, Björn W.; Schnell, Susanne; Kümmerer, Dorothee; Kellmeyer, Philipp; Vry, Magnus-Sebastian; Umarova, Roza; Musso, Mariacristina; Glauche, Volkmar; Abel, Stefanie; Huber, Walter; Rijntjes, Michel; Hennig, Jürgen; Weiller, Cornelius

    2008-01-01

    Built on an analogy between the visual and auditory systems, the following dual stream model for language processing was suggested recently: a dorsal stream is involved in mapping sound to articulation, and a ventral stream in mapping sound to meaning. The goal of the study presented here was to test the neuroanatomical basis of this model. Combining functional magnetic resonance imaging (fMRI) with a novel diffusion tensor imaging (DTI)-based tractography method we were able to identify the most probable anatomical pathways connecting brain regions activated during two prototypical language tasks. Sublexical repetition of speech is subserved by a dorsal pathway, connecting the superior temporal lobe and premotor cortices in the frontal lobe via the arcuate and superior longitudinal fascicle. In contrast, higher-level language comprehension is mediated by a ventral pathway connecting the middle temporal lobe and the ventrolateral prefrontal cortex via the extreme capsule. Thus, according to our findings, the function of the dorsal route, traditionally considered to be the major language pathway, is mainly restricted to sensory-motor mapping of sound to articulation, whereas linguistic processing of sound to meaning requires temporofrontal interaction transmitted via the ventral route. PMID:19004769

  4. Restoration of motor inhibition through an abnormal premotor-motor connection in dystonia

    PubMed Central

    Huang, Ying-Zu; Rothwell, John C; Lu, Chin-Song; Wang, JiunJie; Chen, Rou-Shayn

    2010-01-01

    To clarify the rationale for using rTMS of dorsal premotor cortex (PMd) to treat dystonia, we examined how the motor system reacts to an inhibitory form of rTMS applied to the PMd in healthy subjects and in a group of patients with focal hand dystonia and DYT1 gene carriers. Continuous theta burst transcranial magnetic stimulation (cTBS) with 300 and 600 pulses (cTBS300 and cTBS600) was applied to PMd and its after-effects were quantified by measuring the amplitude of MEPs evoked by single pulse transcranial magnetic stimulation (TMS) over the primary motor cortex (M1), short interval intracortical inhibition/facilitation (SICI/ICF) within M1, the third phase of spinal reciprocal inhibition (RI) and writing tests. In addition, in DYT1 gene carriers, the effects of cTBS300 over M1 and PMd on MEPs were studied in separate experiments. In healthy subjects cTBS300 and cTBS600 over PMd suppressed MEPs for 30min or more and cTBS600 decreased SICI and RI. In contrast, neither form of cTBS over PMd had any significant effect on MEPs, while cTBS600 increased effectiveness of SICI and RI and improved writing in patients with writer's cramp. NMDYT1 had a normal response to cTBS300 over left PMd. We suggest that the reduced PMd to M1 interaction in dystonic patients is likely to be due to reduced excitability of PMd-M1 connections. The possible therapeutic effects of premotor rTMS may therefore involve indirect effects of PMd on SICI and RI, which this study has shown can be normalised by cTBS. PMID:20309999

  5. Dorsal vs. ventral differences in fast Up-state-associated oscillations in the medial prefrontal cortex of the urethane-anesthetized rat

    PubMed Central

    Gretenkord, Sabine; Whittington, Miles A.; Gartside, Sarah E.

    2017-01-01

    Cortical slow oscillations (0.1–1 Hz), which may play a role in memory consolidation, are a hallmark of non-rapid eye movement (NREM) sleep and also occur under anesthesia. During slow oscillations the neuronal network generates faster oscillations on the active Up-states and these nested oscillations are particularly prominent in the PFC. In rodents the medial prefrontal cortex (mPFC) consists of several subregions: anterior cingulate cortex (ACC), prelimbic (PrL), infralimbic (IL), and dorsal peduncular cortices (DP). Although each region has a distinct anatomy and function, it is not known whether slow or fast network oscillations differ between subregions in vivo. We have simultaneously recorded slow and fast network oscillations in all four subregions of the rodent mPFC under urethane anesthesia. Slow oscillations were synchronous between the mPFC subregions, and across the hemispheres, with no consistent amplitude difference between subregions. Delta (2–4 Hz) activity showed only small differences between subregions. However, oscillations in the spindle (6–15 Hz)-, beta (20–30 Hz), gamma (30–80 Hz)-, and high-gamma (80–150 Hz)-frequency bands were consistently larger in the dorsal regions (ACC and PrL) compared with ventral regions (IL and DP). In dorsal regions the peak power of spindle, beta, and gamma activity occurred early after onset of the Up-state. In the ventral regions, especially the DP, the oscillatory power in the spindle-, beta-, and gamma-frequency ranges peaked later in the Up-state. These results suggest variations in fast network oscillations within the mPFC that may reflect the different functions and connectivity of these subregions. NEW & NOTEWORTHY We demonstrate, in the urethane-anesthetized rat, that within the medial prefrontal cortex (mPFC) there are clear subregional differences in the fast network oscillations associated with the slow oscillation Up-state. These differences, particularly between the dorsal and ventral

  6. Rule activity related to spatial and numerical magnitudes: comparison of prefrontal, premotor, and cingulate motor cortices.

    PubMed

    Eiselt, Anne-Kathrin; Nieder, Andreas

    2014-05-01

    In everyday situations, quantitative rules, such as "greater than/less than," need to be applied to a multitude of magnitude comparisons, be they sensory, spatial, temporal, or numerical. We have previously shown that rules applied to different magnitudes are encoded in the lateral PFC. To investigate if and how other frontal lobe areas also contribute to the encoding of quantitative rules applied to multiple magnitudes, we trained monkeys to switch between "greater than/less than" rules applied to either line lengths (spatial magnitudes) or dot numerosities (discrete numerical magnitudes). We recorded single-cell activity from the dorsal premotor cortex (dPMC) and cingulate motor cortex (CMA) and compared it with PFC activity. We found the largest proportion of quantitative rule-selective cells in PFC (24% of randomly selected cells), whereas neurons in dPMC and CMA rarely encoded the rule (6% of the cells). In addition, rule selectivity of individual cells was highest in PFC neurons compared with dPMC and CMA neurons. Rule-selective neurons that simultaneously represented the "greater than/less than" rules applied to line lengths and numerosities ("rule generalists") were exclusively present in PFC. In dPMC and CMA, however, neurons primarily encoded rules applied to only one of the two magnitude types ("rule specialists"). Our data suggest a special involvement of PFC in representing quantitative rules at an abstract level, both in terms of the proportion of neurons engaged and the coding capacities.

  7. The medullary dorsal reticular nucleus as a relay for descending pronociception induced by the mGluR5 in the rat infralimbic cortex.

    PubMed

    David-Pereira, Ana; Sagalajev, Boriss; Wei, Hong; Almeida, Armando; Pertovaara, Antti; Pinto-Ribeiro, Filipa

    2017-05-04

    Metabotropic glutamate receptor 5 (mGluR5) activation in the infralimbic cortex (IL) induces pronociceptive behavior in healthy and monoarthritic rats. Here we studied whether the medullary dorsal reticular nucleus (DRt) and the spinal TRPV1 are mediating the IL/mGluR5-induced spinal pronociception and whether the facilitation of pain behavior is correlated with changes in spinal dorsal horn neuron activity. For drug administrations, all animals had a cannula in the IL as well as a cannula in the DRt or an intrathecal catheter. Heat-evoked paw withdrawal was used to assess pain behavior in awake animals. Spontaneous and heat-evoked discharge rates of single DRt neurons or spinal dorsal horn wide-dynamic range (WDR) and nociceptive-specific (NS) neurons were evaluated in lightly anesthetized animals. Activation of the IL/mGluR5 facilitated nociceptive behavior in both healthy and monoarthritic animals, and this effect was blocked by lidocaine or GABA receptor agonists in the DRt. IL/mGluR5 activation increased spontaneous and heat-evoked DRt discharge rates in healthy but not monoarthritic rats. In the spinal dorsal horn, IL/mGluR5 activation increased spontaneous activity of WDR neurons in healthy animals only, whereas heat-evoked responses of WDR and NS neurons were increased in both experimental groups. Intrathecally administered TRPV1 antagonist prevented the IL/mGluR5-induced pronociception in both healthy and monoarthritic rats. The results suggest that the DRt is involved in relaying the IL/mGluR5-induced spinal pronociception in healthy control but not monoarthritic animals. Spinally, the IL/mGluR5-induced behavioral heat hyperalgesia is mediated by TRPV1 and associated with facilitated heat-evoked responses of WDR and NS neurons.

  8. Ventral Premotor to Primary Motor Cortical Interactions during Noxious and Naturalistic Action Observation

    ERIC Educational Resources Information Center

    Lago, Angel; Koch, Giacomo; Cheeran, Binith; Marquez, Gonzalo; Sanchez, Jose Andres; Ezquerro, Milagros; Giraldez, Manolo; Fernandez-del-Olmo, Miguel

    2010-01-01

    Within the motor system, cortical areas such as the primary motor cortex (M1) and the ventral premotor cortex (PMv), are thought to be activated during the observation of actions performed by others. However, it is not known how the connections between these areas become active during action observation or whether these connections are modulated…

  9. Ventral Premotor to Primary Motor Cortical Interactions during Noxious and Naturalistic Action Observation

    ERIC Educational Resources Information Center

    Lago, Angel; Koch, Giacomo; Cheeran, Binith; Marquez, Gonzalo; Sanchez, Jose Andres; Ezquerro, Milagros; Giraldez, Manolo; Fernandez-del-Olmo, Miguel

    2010-01-01

    Within the motor system, cortical areas such as the primary motor cortex (M1) and the ventral premotor cortex (PMv), are thought to be activated during the observation of actions performed by others. However, it is not known how the connections between these areas become active during action observation or whether these connections are modulated…

  10. Different Patterns of Cortical Inputs to Subregions of the Primary Motor Cortex Hand Representation in Cebus apella

    PubMed Central

    Dea, Melvin; Hamadjida, Adjia; Elgbeili, Guillaume; Quessy, Stephan; Dancause, Numa

    2016-01-01

    The primary motor cortex (M1) plays an essential role in the control of hand movements in primates and is part of a complex cortical sensorimotor network involving multiple premotor and parietal areas. In a previous study in squirrel monkeys, we found that the ventral premotor cortex (PMv) projected mainly to 3 regions within the M1 forearm representation [rostro-medial (RM), rostro-lateral (RL), and caudo-lateral (CL)] with very few caudo-medial (CM) projections. These results suggest that projections from premotor areas to M1 are not uniform, but rather segregated into subregions. The goal of the present work was to study how inputs from diverse areas of the ipsilateral cortical network are organized within the M1 hand representation. In Cebus apella, different retrograde neuroanatomical tracers were injected in 4 subregions of the hand area of M1 (RM, RL, CM, and CL). We found a different pattern of input to each subregion of M1. RM receives inputs predominantly from dorsal premotor cortex, RL from PMv, CM from area 5, and CL from area 2. These results support that the M1 hand representation is composed of several subregions, each part of a unique cortical network. PMID:26966266

  11. Different Patterns of Cortical Inputs to Subregions of the Primary Motor Cortex Hand Representation in Cebus apella.

    PubMed

    Dea, Melvin; Hamadjida, Adjia; Elgbeili, Guillaume; Quessy, Stephan; Dancause, Numa

    2016-04-01

    The primary motor cortex (M1) plays an essential role in the control of hand movements in primates and is part of a complex cortical sensorimotor network involving multiple premotor and parietal areas. In a previous study in squirrel monkeys, we found that the ventral premotor cortex (PMv) projected mainly to 3 regions within the M1 forearm representation [rostro-medial (RM), rostro-lateral (RL), and caudo-lateral (CL)] with very few caudo-medial (CM) projections. These results suggest that projections from premotor areas to M1 are not uniform, but rather segregated into subregions. The goal of the present work was to study how inputs from diverse areas of the ipsilateral cortical network are organized within the M1 hand representation. In Cebus apella, different retrograde neuroanatomical tracers were injected in 4 subregions of the hand area of M1 (RM, RL, CM, and CL). We found a different pattern of input to each subregion of M1. RM receives inputs predominantly from dorsal premotor cortex, RL from PMv, CM from area 5, and CL from area 2. These results support that the M1 hand representation is composed of several subregions, each part of a unique cortical network.

  12. The dorsal auditory pathway is involved in performance of both visual and auditory rhythms.

    PubMed

    Karabanov, Anke; Blom, Orjan; Forsman, Lea; Ullén, Fredrik

    2009-01-15

    We used functional magnetic resonance imaging to investigate the effect of two factors on the neural control of temporal sequence performance: the modality in which the rhythms had been trained, and the modality of the pacing stimuli preceding performance. The rhythms were trained 1-2 days before scanning. Each participant learned two rhythms: one was presented visually, the other auditorily. During fMRI, the rhythms were performed in blocks. In each block, four beats of a visual or auditory pacing metronome were followed by repetitive self-paced rhythm performance from memory. Data from the self-paced performance phase was analysed in a 2x2 factorial design, with the two factors Training Modality (auditory or visual) and Metronome Modality (auditory or visual), as well as with a conjunction analysis across all active conditions, to identify activations that were independent of both Training Modality and Metronome Modality. We found a significant main effect only for visual versus auditory Metronome Modality, in the left angular gyrus, due to a deactivation of this region after auditory pacing. The conjunction analysis revealed a set of brain areas that included dorsal auditory pathway areas (left temporo-parietal junction area and ventral premotor cortex), dorsal premotor cortex, the supplementary and presupplementary premotor areas, the cerebellum and the basal ganglia. We conclude that these regions are involved in controlling performance of well-learned rhythms, regardless of the modality in which the rhythms are trained and paced. This suggests that after extensive short-term training, all rhythms, even those that were both trained and paced in visual modality, had been transformed into auditory-motor representations. The deactivation of the angular cortex following auditory pacing may represent cross-modal auditory-visual inhibition.

  13. Interhemispheric visuo-motor integration in humans: the role of the superior parietal cortex.

    PubMed

    Iacoboni, Marco; Zaidel, Eran

    2004-01-01

    We used event-related functional magnetic resonance imaging (fMRI) to investigate the neural correlates of basic interhemispheric visuo-motor integration. In a simple reaction time task, subjects responded to lateralized left and right light flashes with unimanual left and right hand responses. Typically, reaction times are faster for uncrossed responses (that is, visual stimulus and response hand on the same side) than for crossed responses (that is, visual stimulus and response hand on opposite sides). The chronometric difference between crossed and uncrossed responses is called crossed-uncrossed difference (CUD) and it is typically taken to represent a behavioral estimate of interhemispheric transfer time. The fMRI results obtained in normal right-handers show that the crossed conditions yielded greater activity, compared to the uncrossed conditions, in bilateral prefrontal, bilateral dorsal premotor, and right superior parietal areas. These results suggest that multiple transfers between the hemispheres occur in parallel at the functional levels of sensory-motor integration (posterior parietal), decision-making (prefrontal) and preparation of motor response (premotor). To test the behavioral significance of these multiple transfers, we correlated the individual CUDs with the difference in signal intensity between crossed and uncrossed responses in the prefrontal, dorsal premotor, and right superior parietal activated areas. The analyses demonstrated a strong correlation between the CUD and signal intensity difference between crossed and uncrossed responses in the right superior parietal cortex. These data suggest a critical role of the superior parietal cortex in interhemispheric visuo-motor integration.

  14. Dissociating the roles of right ventral lateral and dorsal lateral prefrontal cortex in generation and maintenance of hypotheses in set-shift problems.

    PubMed

    Goel, Vinod; Vartanian, Oshin

    2005-08-01

    Although patient data have traditionally implicated the left prefrontal cortex (PFC) in hypothesis generation, recent lesion data implicate right PFC in hypothesis generation tasks that involve set shifts (lateral transformations). To test the involvement of the right prefrontal cortex in a hypothesis generation task involving set shifts, we scanned 13 normal subjects with fMRI as they completed Match Problems (a classic divergent thinking task) and a baseline task. In Match Problems subjects determined the number of possible solutions for each trial. Successful solutions are indicative of set shifts. In the baseline condition subjects evaluated the accuracy of hypothetical solutions to match problems. A comparison of Match Problems versus baseline trials revealed activation in right ventral lateral PFC (BA 47) and left dorsal lateral PFC (BA 46). A further comparison of successfully versus unsuccessfully completed Match Problems revealed activation in right ventral lateral PFC (BA 47), left middle frontal gyrus (BA 9) and left frontal pole (BA 10), thus identifying the former as a critical component of the neural mechanisms of set-shift transformation. By contrast, activation in right dorsal lateral PFC (BA 46) covaried as a function of the number of solutions generated in Match Problems, possibly due to increased working memory demands to maintain multiple solutions 'on-line', conflict resolution, or progress monitoring. These results go beyond the patient data by identifying the ventral lateral (BA 47) aspect of right PFC as being a critical component of the neural systems underlying lateral transformations, and demonstrate a dissociation between right VLPFC and DLPFC in hypotheses generation and maintenance.

  15. Brain mediators of cardiovascular responses to social threat, Part I: Reciprocal dorsal and ventral sub-regions of the medial prefrontal cortex and heart-rate reactivity

    PubMed Central

    Wager, Tor D.; Waugh, Christian E.; Lindquist, Martin; Noll, Doug C.; Fredrickson, Barbara L.; Taylor, Stephan F.

    2009-01-01

    Social threat is a key component of mental “stress” and a potent generator of negative emotions and physiological responses in the body. How the human brain processes social context and drives peripheral physiology, however, is relatively poorly understood. Human neuroimaging and animal studies implicate the dorsal medial prefrontal cortex (MPFC), though this heterogeneous region is likely to contain multiple sub-regions with diverse relationships with physiological reactivity and regulation. We used fMRI combined with a novel multi-level path analysis approach to identify brain mediators of the effects of a public speech preparation task (social evaluative threat, SET) on heart rate (HR). This model provides tests of functional pathways linking experimentally manipulated threat, regional fMRI activity, and physiological output, both across time (within person) and across individuals (between persons). It thus integrates time series connectivity and individual difference analyses in the same path model. The results provide evidence for two dissociable, inversely coupled sub-regions of MPFC that independently mediated HR responses. SET caused activity increases in a more dorsal pregenual cingulate region, whose activity was coupled with HR increases. Conversely, SET caused activity decreases in a right ventromedial/medial orbital region, which were coupled with HR increases. Individual differences in coupling strength in each pathway independently predicted individual differences in HR reactivity. These results underscore both the importance and heterogeneity of MPFC in generating physiological responses to threat. PMID:19465137

  16. Premotor Diagnosis of Parkinson's Disease.

    PubMed

    Reichmann, Heinz

    2017-08-03

    Typical Parkinsonian symptoms consist of bradykinesia plus rigidity and/or resting tremor. Some time later postural instability occurs. Pre-motor symptoms such as hyposmia, constipation, REM sleep behavior disorder and depression may antecede these motor symptoms for years. It would be ideal, if we had a biomarker which would allow to predict who with one or two of these pre-motor symptoms will develop the movement disorder Parkinson's disease (PD). Thus, it is interesting to learn that biopsies of the submandibular gland or colon biopsies may be a means to predict PD, if there is a high amout of abnormally folded alpha-synuclein and phosphorylated alpha-synuclein. This would be of relevance if we would have available means to stop the propagation of abnormal alpha-synuclein which is otherwise one of the reasons of this spreading disease PD.

  17. Preparatory band specific premotor cortical activity differentiates upper and lower extremity movement.

    PubMed

    Wheaton, Lewis A; Carpenter, Mackenzie; Mizelle, J C; Forrester, Larry

    2008-01-01

    Event related desynchronization (ERD) allows evaluation of brain signals in multiple frequency dimensions. The purpose of this study was to determine left hemispheric non-primary motor cortex differences at varying frequencies of premovement ERD for similar movements by end-effectors of the upper and lower extremities. We recorded 32-channel electroencephalography (EEG) while subjects performed self-paced right ankle dorsiflexion and wrist extension. Electromyography (EMG) was recorded over the tibialis anterior and extensor carpi ulnaris. EEG was analyzed for premovement ERD within the alpha (8-12 Hz), low beta (13-18 Hz) and high beta (18-22 Hz) frequencies over the premotor, motor, and sensory areas of the left and mesial cortex from -1.5 to 0 s before movement. Within the alpha and high beta bands, wrist movements showed limited topography, but greater ERD over posterior premotor cortex areas. Alpha ERD was also significantly greater over the lateral motor cortex for wrist movements. In the low beta band, wrist movements provided extensive ERD differences to include the left motor and mesial/lateral premotor areas, whereas ankle movements showed only limited ERD activity. Overall, alpha and high beta activity demonstrated distinctions that are consistent with mapping of wrist and ankle representations over the sensorimotor strip, whereas the low beta representation demonstrated the clearest distinctions between the limbs over widespread brain areas, particularly the lateral premotor cortex. This suggests limited leg premovement activity at the dorsolateral premotor cortex. Low beta ERD may be reflect joint or limb specific preparatory activity in the premotor area. Further work is required to better evaluate the extent of this low beta activity for multiple comparative joints.

  18. Prefrontal connections of the parabelt auditory cortex in macaque monkeys.

    PubMed

    Hackett, T A; Stepniewska, I; Kaas, J H

    1999-01-30

    regions of the frontal pole and more medial premotor and dorsal prefrontal cortex, but not with the extensive orbitofrontal region which has RPB and STGr connections. The results suggest that both RPB and CPB provide the major auditory connections with the region related to directing eye movements towards stimuli of interest, and the dorsal prefrontal cortex for working memory. Other auditory connections to these regions of the frontal lobe appear to be minor. RPB has connections with orbitofrontal cortex, important in psychosocial and emotional functions, while STGr primarily connects with orbital and polar prefrontal cortex. Copyright 1999 Elsevier Science B.V.

  19. Activation of premotor vocal areas during musical discrimination.

    PubMed

    Brown, Steven; Martinez, Michael J

    2007-02-01

    Two same/different discrimination tasks were performed by amateur-musician subjects in this functional magnetic resonance imaging study: Melody Discrimination and Harmony Discrimination. Both tasks led to activations not only in classic working memory areas--such as the cingulate gyrus and dorsolateral prefrontal cortex--but in a series of premotor areas involved in vocal-motor planning and production, namely the somatotopic mouth region of the primary and lateral premotor cortices, Broca's area, the supplementary motor area, and the anterior insula. A perceptual control task involving passive listening alone to monophonic melodies led to activations exclusively in temporal-lobe auditory areas. These results show that, compared to passive listening tasks, discrimination tasks elicit activation in vocal-motor planning areas.

  20. Fiber tracts of the dorsal language stream in the human brain.

    PubMed

    Yagmurlu, Kaan; Middlebrooks, Erik H; Tanriover, Necmettin; Rhoton, Albert L

    2016-05-01

    OBJECT The aim of this study was to examine the arcuate (AF) and superior longitudinal fasciculi (SLF), which together form the dorsal language stream, using fiber dissection and diffusion imaging techniques in the human brain. METHODS Twenty-five formalin-fixed brains (50 hemispheres) and 3 adult cadaveric heads, prepared according to the Klingler method, were examined by the fiber dissection technique. The authors' findings were supported with MR tractography provided by the Human Connectome Project, WU-Minn Consortium. The frequencies of gyral distributions were calculated in segments of the AF and SLF in the cadaveric specimens. RESULTS The AF has ventral and dorsal segments, and the SLF has 3 segments: SLF I (dorsal pathway), II (middle pathway), and III (ventral pathway). The AF ventral segment connects the middle (88%; all percentages represent the area of the named structure that is connected to the tract) and posterior (100%) parts of the superior temporal gyri and the middle part (92%) of the middle temporal gyrus to the posterior part of the inferior frontal gyrus (96% in pars opercularis, 40% in pars triangularis) and the ventral premotor cortex (84%) by passing deep to the lower part of the supramarginal gyrus (100%). The AF dorsal segment connects the posterior part of the middle (100%) and inferior temporal gyri (76%) to the posterior part of the inferior frontal gyrus (96% in pars opercularis), ventral premotor cortex (72%), and posterior part of the middle frontal gyrus (56%) by passing deep to the lower part of the angular gyrus (100%). CONCLUSIONS This study depicts the distinct subdivision of the AF and SLF, based on cadaveric fiber dissection and diffusion imaging techniques, to clarify the complicated language processing pathways.

  1. Roles of monkey premotor neuron classes in movement preparation and execution.

    PubMed

    Kaufman, Matthew T; Churchland, Mark M; Santhanam, Gopal; Yu, Byron M; Afshar, Afsheen; Ryu, Stephen I; Shenoy, Krishna V

    2010-08-01

    Dorsal premotor cortex (PMd) is known to be involved in the planning and execution of reaching movements. However, it is not understood how PMd plan activity-often present in the very same neurons that respond during movement-is prevented from itself producing movement. We investigated whether inhibitory interneurons might "gate" output from PMd, by maintaining high levels of inhibition during planning and reducing inhibition during execution. Recently developed methods permit distinguishing interneurons from pyramidal neurons using extracellular recordings. We extend these methods here for use with chronically implanted multi-electrode arrays. We then applied these methods to single- and multi-electrode recordings in PMd of two monkeys performing delayed-reach tasks. Responses of putative interneurons were not generally in agreement with the hypothesis that they act to gate output from the area: in particular it was not the case that interneurons tended to reduce their firing rates around the time of movement. In fact, interneurons increased their rates more than putative pyramidal neurons during both the planning and movement epochs. The two classes of neurons also differed in a number of other ways, including greater modulation across conditions for interneurons, and interneurons more frequently exhibiting increases in firing rate during movement planning and execution. These findings provide novel information about the greater responsiveness of putative PMd interneurons in motor planning and execution and suggest that we may need to consider new possibilities for how planning activity is structured such that it does not itself produce movement.

  2. Movement-related activity in the periarcuate cortex of monkeys during coordinated eye and hand movements.

    PubMed

    Kurata, Kiyoshi

    2017-09-20

    To determine the role of the periarcuate cortex during coordinated eye and hand movements in monkeys, the present study examined neuronal activity in this region during movement with the hand, eyes, or both as effectors toward a visuospatial target. Similar to the primary motor cortex (M1), the dorsal premotor cortex contained a higher proportion of neurons that were closely related to hand movements, whereas saccade-related neurons were frequently recorded from the frontal eye field (FEF). Interestingly, neurons that exhibited activity related to both eye and hand movements were recorded most frequently in the ventral premotor cortex (PMv), located between the FEF and M1. Neuronal activity in the periarcuate cortex was highly modulated during coordinated movements compared to either eye or hand movement only. Additionally, a small number of neurons were active specifically during one of the three task modes, which could be dissociated from the effector activity. In this case, neuron onset was either ahead of or behind the onset of eye and/or hand movement, and some neuronal activity lasted until reward delivery signaled successful completion of reaching. The present findings indicate that the periarcuate cortex, particularly the PMv, plays important roles in orchestrating coordinated movements from the initiation to the termination of reaching. Copyright © 2017, Journal of Neurophysiology.

  3. Virtual Reality and the Role of the Prefrontal Cortex in Adults and Children

    PubMed Central

    Jäncke, Lutz; Cheetham, Marcus; Baumgartner, Thomas

    2009-01-01

    In this review, the neural underpinnings of the experience of presence are outlined. Firstly, it is shown that presence is associated with activation of a distributed network, which includes the dorsal and ventral visual stream, the parietal cortex, the premotor cortex, mesial temporal areas, the brainstem and the thalamus. Secondly, the dorsolateral prefrontal cortex (DLPFC) is identified as a key node of the network as it modulates the activity of the network and the associated experience of presence. Thirdly, children lack the strong modulatory influence of the DLPFC on the network due to their unmatured frontal cortex. Fourthly, it is shown that presence-related measures are influenced by manipulating the activation in the DLPFC using transcranial direct current stimulation (tDCS) while participants are exposed to the virtual roller coaster ride. Finally, the findings are discussed in the context of current models explaining the experience of presence, the rubber hand illusion, and out-of-body experiences. PMID:19753097

  4. Virtual reality and the role of the prefrontal cortex in adults and children.

    PubMed

    Jäncke, Lutz; Cheetham, Marcus; Baumgartner, Thomas

    2009-05-01

    In this review, the neural underpinnings of the experience of presence are outlined. Firstly, it is shown that presence is associated with activation of a distributed network, which includes the dorsal and ventral visual stream, the parietal cortex, the premotor cortex, mesial temporal areas, the brainstem and the thalamus. Secondly, the dorsolateral prefrontal cortex (DLPFC) is identified as a key node of the network as it modulates the activity of the network and the associated experience of presence. Thirdly, children lack the strong modulatory influence of the DLPFC on the network due to their unmatured frontal cortex. Fourthly, it is shown that presence-related measures are influenced by manipulating the activation in the DLPFC using transcranial direct current stimulation (tDCS) while participants are exposed to the virtual roller coaster ride. Finally, the findings are discussed in the context of current models explaining the experience of presence, the rubber hand illusion, and out-of-body experiences.

  5. The dorsal stream contribution to phonological retrieval in object naming.

    PubMed

    Schwartz, Myrna F; Faseyitan, Olufunsho; Kim, Junghoon; Coslett, H Branch

    2012-12-01

    Meaningful speech, as exemplified in object naming, calls on knowledge of the mappings between word meanings and phonological forms. Phonological errors in naming (e.g. GHOST named as 'goath') are commonly seen in persisting post-stroke aphasia and are thought to signal impairment in retrieval of phonological form information. We performed a voxel-based lesion-symptom mapping analysis of 1718 phonological naming errors collected from 106 individuals with diverse profiles of aphasia. Voxels in which lesion status correlated with phonological error rates localized to dorsal stream areas, in keeping with classical and contemporary brain-language models. Within the dorsal stream, the critical voxels were concentrated in premotor cortex, pre- and postcentral gyri and supramarginal gyrus with minimal extension into auditory-related posterior temporal and temporo-parietal cortices. This challenges the popular notion that error-free phonological retrieval requires guidance from sensory traces stored in posterior auditory regions and points instead to sensory-motor processes located further anterior in the dorsal stream. In a separate analysis, we compared the lesion maps for phonological and semantic errors and determined that there was no spatial overlap, demonstrating that the brain segregates phonological and semantic retrieval operations in word production.

  6. Left Dorsal Speech Stream Components and Their Contribution to Phonological Processing

    PubMed Central

    Murakami, Takenobu; Kell, Christian A.; Restle, Julia; Ugawa, Yoshikazu

    2015-01-01

    Models propose an auditory-motor mapping via a left-hemispheric dorsal speech-processing stream, yet its detailed contributions to speech perception and production are unclear. Using fMRI-navigated repetitive transcranial magnetic stimulation (rTMS), we virtually lesioned left dorsal stream components in healthy human subjects and probed the consequences on speech-related facilitation of articulatory motor cortex (M1) excitability, as indexed by increases in motor-evoked potential (MEP) amplitude of a lip muscle, and on speech processing performance in phonological tests. Speech-related MEP facilitation was disrupted by rTMS of the posterior superior temporal sulcus (pSTS), the sylvian parieto-temporal region (SPT), and by double-knock-out but not individual lesioning of pars opercularis of the inferior frontal gyrus (pIFG) and the dorsal premotor cortex (dPMC), and not by rTMS of the ventral speech-processing stream or an occipital control site. RTMS of the dorsal stream but not of the ventral stream or the occipital control site caused deficits specifically in the processing of fast transients of the acoustic speech signal. Performance of syllable and pseudoword repetition correlated with speech-related MEP facilitation, and this relation was abolished with rTMS of pSTS, SPT, and pIFG. Findings provide direct evidence that auditory-motor mapping in the left dorsal stream causes reliable and specific speech-related MEP facilitation in left articulatory M1. The left dorsal stream targets the articulatory M1 through pSTS and SPT constituting essential posterior input regions and parallel via frontal pathways through pIFG and dPMC. Finally, engagement of the left dorsal stream is necessary for processing of fast transients in the auditory signal. PMID:25632119

  7. Stress induced a shift from dorsal hippocampus to prefrontal cortex dependent memory retrieval: role of regional corticosterone

    PubMed Central

    Dominguez, Gaelle; Faucher, Pierre; Henkous, Nadia; Krazem, Ali; Piérard, Christophe; Béracochéa, Daniel

    2014-01-01

    Most of the deleterious effects of stress on memory retrieval are due to a dysfunction of the hippocampo-prefrontal cortex interplay. The role of the stress-induced regional corticosterone increase in such dysfunction remains however unclear, since there is no published study as yet dedicated to measuring corticosterone concentrations simultaneously in both the prefrontal cortex (mPFC) and the hippocampus (dHPC) in relation with memory impairments. To that aim, we first showed in Experiment 1 that an acute stress (3 electric footschocks; 0.9 mA each) delivered before memory testing reversed the memory retrieval pattern (MRP) in a serial discrimination task in which mice learned two successive discriminations. More precisely, whereas non-stressed animals remembered accurately the first learned discrimination and not the second one, stressed mice remembered more accurately the second discrimination but not the first one. We demonstrated that local inactivation of dHPC or mPFC with the anesthetic lidocaine recruited the dHPC activity in non-stress conditions whereas the stress-induced MRP inversion recruited the mPFC activity. In a second experiment, we showed that acute stress induced a very similar time-course evolution of corticosterone rises within both the mPFC and dHPC. In a 3rd experiment, we found however that in situ injections of corticosterone either within the mPFC or the dHPC before memory testing favored the emergence of the mPFC-dependent MRP but blocked the emergence of the dHPC-dependent one. Overall, our study evidences that the simultaneous increase of corticosterone after stress in both areas induces a shift from dHPC (non-stress condition) to mPFC-dependent MRP and that corticosterone is critically involved in mediating the deleterious effects of stress on cognitive functions involving the mPFC-HPC interplay. PMID:24860451

  8. Stress induced a shift from dorsal hippocampus to prefrontal cortex dependent memory retrieval: role of regional corticosterone.

    PubMed

    Dominguez, Gaelle; Faucher, Pierre; Henkous, Nadia; Krazem, Ali; Piérard, Christophe; Béracochéa, Daniel

    2014-01-01

    Most of the deleterious effects of stress on memory retrieval are due to a dysfunction of the hippocampo-prefrontal cortex interplay. The role of the stress-induced regional corticosterone increase in such dysfunction remains however unclear, since there is no published study as yet dedicated to measuring corticosterone concentrations simultaneously in both the prefrontal cortex (mPFC) and the hippocampus (dHPC) in relation with memory impairments. To that aim, we first showed in Experiment 1 that an acute stress (3 electric footschocks; 0.9 mA each) delivered before memory testing reversed the memory retrieval pattern (MRP) in a serial discrimination task in which mice learned two successive discriminations. More precisely, whereas non-stressed animals remembered accurately the first learned discrimination and not the second one, stressed mice remembered more accurately the second discrimination but not the first one. We demonstrated that local inactivation of dHPC or mPFC with the anesthetic lidocaine recruited the dHPC activity in non-stress conditions whereas the stress-induced MRP inversion recruited the mPFC activity. In a second experiment, we showed that acute stress induced a very similar time-course evolution of corticosterone rises within both the mPFC and dHPC. In a 3rd experiment, we found however that in situ injections of corticosterone either within the mPFC or the dHPC before memory testing favored the emergence of the mPFC-dependent MRP but blocked the emergence of the dHPC-dependent one. Overall, our study evidences that the simultaneous increase of corticosterone after stress in both areas induces a shift from dHPC (non-stress condition) to mPFC-dependent MRP and that corticosterone is critically involved in mediating the deleterious effects of stress on cognitive functions involving the mPFC-HPC interplay.

  9. Regional Specific Evidence for Memory-Load Dependent Activity in the Dorsal Subiculum and the Lateral Entorhinal Cortex

    PubMed Central

    Ku, Shih-pi; Nakamura, Nozomu H.; Maingret, Nicolas; Mahnke, Liv; Yoshida, Motoharu; Sauvage, Magdalena M.

    2017-01-01

    The subiculum and the lateral entorhinal cortex (LEC) are the main output areas of the hippocampus which contribute to spatial and non-spatial memory. The proximal part of the subiculum (bordering CA1) receives heavy projections from the perirhinal cortex and the distal part of CA1 (bordering the subiculum), both known for their ties to object recognition memory. However, the extent to which the proximal subiculum contributes to non-spatial memory is still unclear. Comparatively, the involvement of the LEC in non-spatial information processing is quite well known. However, very few studies have investigated its role within the frame of memory function. Thus, it is not known whether its contribution depends on memory load. In addition, the deep layers of the EC have been shown to be predictive of subsequent memory performance, but not its superficial layers. Hence, here we tested the extent to which the proximal part of the subiculum and the superficial and deep layers of the LEC contribute to non-spatial memory, and whether this contribution depends on the memory load of the task. To do so, we imaged brain activity at cellular resolution in these areas in rats performing a delayed nonmatch to sample task based on odors with two different memory loads (5 or 10 odors). This imaging technique is based on the detection of the RNA of the immediate-early gene Arc, which is especially tied to synaptic plasticity and behavioral demands, and is commonly used to map activity in the medial temporal lobe. We report for the first time that the proximal part of the subiculum is recruited in a memory-load dependent manner and the deep layers of the LEC engaged under high memory load conditions during the retrieval of non-spatial memory, thus shedding light on the specific networks contributing to non-spatial memory retrieval. PMID:28790897

  10. Phosphorylation of calcium/calmodulin-dependent protein kinase II in the rat dorsal medial prefrontal cortex is associated with alcohol-induced cognitive inflexibility.

    PubMed

    Natividad, Luis A; Steinman, Michael Q; Laredo, Sarah A; Irimia, Cristina; Polis, Ilham Y; Lintz, Robert; Buczynski, Matthew W; Martin-Fardon, Rémi; Roberto, Marisa; Parsons, Loren H

    2017-09-22

    Repeated cycles of alcohol [ethanol (EtOH)] intoxication and withdrawal dysregulate excitatory glutamatergic systems in the brain and induce neuroadaptations in the medial prefrontal cortex (mPFC) that contribute to cognitive dysfunction. The mPFC is composed of subdivisions that are functionally distinct, with dorsal regions facilitating drug-cue associations and ventral regions modulating new learning in the absence of drug. A key modulator of glutamatergic activity is the holoenzyme calcium/calmodulin-dependent protein kinase II (CaMKII) that phosphorylates ionotropic glutamate receptors. Here, we examined the hypothesis that abstinence from chronic intermittent EtOH (CIE) exposure dysregulates CaMKII activity in the mPFC to impair cognitive flexibility. We used an operant model of strategy set shifting in male Long-Evans rats demonstrating reduced susceptibility to trial omissions during performance in a visual cue-guided task versus albino strains. Relative to naïve controls, rats experiencing approximately 10 days of abstinence from CIE vapor exposure demonstrated impaired performance during a procedural shift from visual cue to spatial location discrimination. Phosphorylation of CaMKII subtype α was upregulated in the dorsal, but not ventral mPFC of CIE-exposed rats, and was positively correlated with perseverative-like responding during the set shift. The findings suggest that abstinence from CIE exposure induces an undercurrent of kinase activity (e.g. CaMKII), which may promote aberrant glutamatergic responses in select regions of the mPFC. Given the role of the mPFC in modulating executive control of behavior, we propose that increased CaMKII subtype α activity reflects a dysregulated 'top-down' circuit that interferes with adaptive behavioral performance under changing environmental demands. © 2017 Society for the Study of Addiction.

  11. Resting-State Connectivity of the Left Frontal Cortex to the Default Mode and Dorsal Attention Network Supports Reserve in Mild Cognitive Impairment.

    PubMed

    Franzmeier, Nicolai; Göttler, Jens; Grimmer, Timo; Drzezga, Alexander; Áraque-Caballero, Miguel A; Simon-Vermot, Lee; Taylor, Alexander N W; Bürger, Katharina; Catak, Cihan; Janowitz, Daniel; Müller, Claudia; Duering, Marco; Sorg, Christian; Ewers, Michael

    2017-01-01

    Reserve refers to the phenomenon of relatively preserved cognition in disproportion to the extent of neuropathology, e.g., in Alzheimer's disease. A putative functional neural substrate underlying reserve is global functional connectivity of the left lateral frontal cortex (LFC, Brodmann Area 6/44). Resting-state fMRI-assessed global LFC-connectivity is associated with protective factors (education) and better maintenance of memory in mild cognitive impairment (MCI). Since the LFC is a hub of the fronto-parietal control network that regulates the activity of other networks, the question arises whether LFC-connectivity to specific networks rather than the whole-brain may underlie reserve. We assessed resting-state fMRI in 24 MCI and 16 healthy controls (HC) and in an independent validation sample (23 MCI/32 HC). Seed-based LFC-connectivity to seven major resting-state networks (i.e., fronto-parietal, limbic, dorsal-attention, somatomotor, default-mode, ventral-attention, visual) was computed, reserve was quantified as residualized memory performance after accounting for age and hippocampal atrophy. In both samples of MCI, LFC-activity was anti-correlated with the default-mode network (DMN), but positively correlated with the dorsal-attention network (DAN). Greater education predicted stronger LFC-DMN-connectivity (anti-correlation) and LFC-DAN-connectivity. Stronger LFC-DMN and LFC-DAN-connectivity each predicted higher reserve, consistently in both MCI samples. No associations were detected for LFC-connectivity to other networks. These novel results extend our previous findings on global functional connectivity of the LFC, showing that LFC-connectivity specifically to the DAN and DMN, two core memory networks, enhances reserve in the memory domain in MCI.

  12. Superlinear Summation of Information in Premotor Neuron Pairs.

    PubMed

    Montani, Fernando; Oliynyk, Andriy; Fadiga, Luciano

    2017-03-01

    Whether premotor/motor neurons encode information in terms of spiking frequency or by their relative time of firing, which may display synchronization, is still undetermined. To address this issue, we used an information theory approach to analyze neuronal responses recorded in the premotor (area F5) and primary motor (area F1) cortices of macaque monkeys under four different conditions of visual feedback during hand grasping. To evaluate the sensitivity of spike timing correlation between single neurons, we investigated the stimulus dependent synchronization in our population of pairs. We first investigated the degree of correlation of trial-to-trial fluctuations in response strength between neighboring neurons for each condition, and second estimated the stimulus dependent synchronization by means of an information theoretical approach. We compared the information conveyed by pairs of simultaneously recorded neurons with the sum of information provided by the respective individual cells. The information transmission across pairs of cells in the primary motor cortex seems largely independent, whereas information transmission across pairs of premotor neurons is summed superlinearly. The brain could take advantage of both the accuracy provided by the independency of F1 and the synergy allowed by the superlinear information population coding in F5, distinguishing thus the generalizing role of F5.

  13. Damage to ventral and dorsal language pathways in acute aphasia

    PubMed Central

    Hartwigsen, Gesa; Kellmeyer, Philipp; Glauche, Volkmar; Mader, Irina; Klöppel, Stefan; Suchan, Julia; Karnath, Hans-Otto; Weiller, Cornelius; Saur, Dorothee

    2013-01-01

    Converging evidence from neuroimaging studies and computational modelling suggests an organization of language in a dual dorsal–ventral brain network: a dorsal stream connects temporoparietal with frontal premotor regions through the superior longitudinal and arcuate fasciculus and integrates sensorimotor processing, e.g. in repetition of speech. A ventral stream connects temporal and prefrontal regions via the extreme capsule and mediates meaning, e.g. in auditory comprehension. The aim of our study was to test, in a large sample of 100 aphasic stroke patients, how well acute impairments of repetition and comprehension correlate with lesions of either the dorsal or ventral stream. We combined voxelwise lesion-behaviour mapping with the dorsal and ventral white matter fibre tracts determined by probabilistic fibre tracking in our previous study in healthy subjects. We found that repetition impairments were mainly associated with lesions located in the posterior temporoparietal region with a statistical lesion maximum in the periventricular white matter in projection of the dorsal superior longitudinal and arcuate fasciculus. In contrast, lesions associated with comprehension deficits were found more ventral-anterior in the temporoprefrontal region with a statistical lesion maximum between the insular cortex and the putamen in projection of the ventral extreme capsule. Individual lesion overlap with the dorsal fibre tract showed a significant negative correlation with repetition performance, whereas lesion overlap with the ventral fibre tract revealed a significant negative correlation with comprehension performance. To summarize, our results from patients with acute stroke lesions support the claim that language is organized along two segregated dorsal–ventral streams. Particularly, this is the first lesion study demonstrating that task performance on auditory comprehension measures requires an interaction between temporal and prefrontal brain regions via the

  14. Interactions of the dorsal hippocampus, medial prefrontal cortex and nucleus accumbens in formation of fear memory: difference in inhibitory avoidance learning and contextual fear conditioning.

    PubMed

    Yang, Fang-Chi; Liang, K C

    2014-07-01

    Learning active or reactive responses to fear involves different brain circuitry. This study examined how the nuclus accumbens (NAc), dorsal hippocampus (DH) and medial prefrontal cortex (mPFC) may interact in memory processing for these two kinds of responses. Male Wistar rats with cannulae implanted in these areas were trained on a contextual fear conditioning or inhibitory avoidance task that respectively engaged a reactive or active response to fear in the test. Immediately after training, a memory modulating factor released by stress, norepinephrine (NE), was infused into one region and 4% lidocaine into another to examine if an upstream activation effect could be blocked by the downstream suppression. Retention tested 1 day later showed that in both tasks posttraining infusion of NE at different doses into either the DH or mPFC enhanced retention but the enhancement was blocked by concurrent infusion of lidocaine into the other region, suggesting reliance of the effect on functional integrity of both regions. Further, posttraining intra-NAc lidocaine infusion attenuated memory enhancement of NE infused to the DH or mPFC in the inhibitory avoidance task but did not do so in contextual fear conditioning. These results suggest that NE regulation of memory formation for the reactive and active responses to fear may rely on distinct interactions among the DH, mPFC and NAc. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Determining auditory-evoked activities from multiple cells in layer 1 of the dorsal cortex of the inferior colliculus of mice by in vivo calcium imaging.

    PubMed

    Ito, Tetsufumi; Hirose, Junichi; Murase, Kazuyuki; Ikeda, Hiroshi

    2014-11-24

    Layer 1 of the dorsal cortex of the inferior colliculus (DCIC) is distinguished from other layers by its cytoarchitecture and fiber connections. However, the information of the sound types represented in layer 1 of the DCIC remains unclear because placing electrodes on such thin structures is challenging. In this study, we utilized in vivo calcium imaging to assess auditory-evoked activities in multiple cells in layer 1 of DCIC and to characterize sound stimuli producing strong activity. Most cells examined showed strong responses to broad-band noise and low-frequency tone bursts of high sound intensity. In some cases, we successfully obtained frequency response areas, which are receptive fields to tone frequencies and intensities, and ~30% of these showed V-shape tunings. This is the first systematic study to record auditory responses of cells in layer 1 of DCIC. These results indicate that cells in this area are selective to tones with low frequency, implying the importance of such auditory information in the neural circuitry of layer 1 of DCIC. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Brain network dysfunction in youth with obsessive-compulsive disorder induced by simple uni-manual behavior: The role of the dorsal anterior cingulate cortex

    PubMed Central

    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.

    2017-01-01

    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

  17. The Dorsal Agranular Insular Cortex Regulates the Cued Reinstatement of Cocaine-Seeking, but not Food-Seeking, Behavior in Rats.

    PubMed

    Cosme, Caitlin V; Gutman, Andrea L; LaLumiere, Ryan T

    2015-09-01

    Prior studies suggest that the insular cortex (IC), and particularly its posterior region (the PIc), is involved in nicotine craving and relapse in humans and rodents. The present experiments were conducted to determine whether the IC and its different subregions regulate relapse to cocaine-seeking behavior in rats. To address this issue, male Sprague-Dawley rats underwent cocaine self-administration followed by extinction training and reinstatement tests. Before each reinstatement, the PIc or the more anterior dorsal agranular IC (AId) was inactivated to determine their roles in the reinstatement to cocaine seeking. In contrast to the nicotine findings, PIc inactivation had no effect on cue-induced reinstatement for cocaine seeking. However, AId inactivation reduced cued reinstatement while having no effect on cocaine-prime reinstatement. AId inactivation had no effect on reinstatement of food-seeking behavior induced by cues, a food-prime, or cues+food-prime. Based on previous work hypothesizing a role for corticotropin-releasing factor (CRF) in the IC during craving and relapse, a subsequent experiment found that CRF receptor-1 (CRF1) blockade in the AId similarly reduced cued reinstatement. Our results suggest that the AId, along with CRF1 receptors in this region, regulates reinstatement to cocaine seeking, but not food seeking, depending on the type of reinstatement, whereas PIc activity does not influence cue-induced reinstatement.

  18. The Dorsal Agranular Insular Cortex Regulates the Cued Reinstatement of Cocaine-Seeking, but not Food-Seeking, Behavior in Rats

    PubMed Central

    Cosme, Caitlin V; Gutman, Andrea L; LaLumiere, Ryan T

    2015-01-01

    Prior studies suggest that the insular cortex (IC), and particularly its posterior region (the PIc), is involved in nicotine craving and relapse in humans and rodents. The present experiments were conducted to determine whether the IC and its different subregions regulate relapse to cocaine-seeking behavior in rats. To address this issue, male Sprague–Dawley rats underwent cocaine self-administration followed by extinction training and reinstatement tests. Before each reinstatement, the PIc or the more anterior dorsal agranular IC (AId) was inactivated to determine their roles in the reinstatement to cocaine seeking. In contrast to the nicotine findings, PIc inactivation had no effect on cue-induced reinstatement for cocaine seeking. However, AId inactivation reduced cued reinstatement while having no effect on cocaine-prime reinstatement. AId inactivation had no effect on reinstatement of food-seeking behavior induced by cues, a food-prime, or cues+food-prime. Based on previous work hypothesizing a role for corticotropin-releasing factor (CRF) in the IC during craving and relapse, a subsequent experiment found that CRF receptor-1 (CRF1) blockade in the AId similarly reduced cued reinstatement. Our results suggest that the AId, along with CRF1 receptors in this region, regulates reinstatement to cocaine seeking, but not food seeking, depending on the type of reinstatement, whereas PIc activity does not influence cue-induced reinstatement. PMID:25837282

  19. Delay of gratification is associated with white matter connectivity in the dorsal prefrontal cortex: a diffusion tensor imaging study in chimpanzees (Pan troglodytes)

    PubMed Central

    Latzman, Robert D.; Taglialatela, Jared P.; Hopkins, William D.

    2015-01-01

    Individual variability in delay of gratification (DG) is associated with a number of important outcomes in both non-human and human primates. Using diffusion tensor imaging (DTI), this study describes the relationship between probabilistic estimates of white matter tracts projecting from the caudate to the prefrontal cortex (PFC) and DG abilities in a sample of 49 captive chimpanzees (Pan troglodytes). After accounting for time between collection of DTI scans and DG measurement, age and sex, higher white matter connectivity between the caudate and right dorsal PFC was found to be significantly associated with the acquisition (i.e. training phase) but not the maintenance of DG abilities. No other associations were found to be significant. The integrity of white matter connectivity between regions of the striatum and the PFC appear to be associated with inhibitory control in chimpanzees, with perturbations on this circuit potentially leading to a variety of maladaptive outcomes. Additionally, results have potential translational implications for understanding the pathophysiology of a number of psychiatric and clinical outcomes in humans. PMID:26041344

  20. Upregulation of the dorsal raphe nucleus-prefrontal cortex serotonin system by chronic treatment with escitalopram in hyposerotonergic Wistar-Kyoto rats.

    PubMed

    Yamada, Makiko; Kawahara, Yukie; Kaneko, Fumi; Kishikawa, Yuki; Sotogaku, Naoki; Poppinga, Wilfred J; Folgering, Joost H A; Dremencov, Eliyahu; Kawahara, Hiroshi; Nishi, Akinori

    2013-09-01

    Wistar-Kyoto (WKY) rats are sensitive to chronic stressors and exhibit depression-like behavior. Dorsal raphe nucleus (DRN) serotonin (5-HT) neurons projecting to the prefrontal cortex (PFC) comprise the important neurocircuitry underlying the pathophysiology of depression. To evaluate the DRN-PFC 5-HT system in WKY rats, we examined the effects of escitalopram (ESCIT) on the extracellular 5-HT level in comparison with Wistar rats using dual-probe microdialysis. The basal levels of 5-HT in the DRN, but not in the PFC, in WKY rats was reduced as low as 30% of Wistar rats. Responses of 5-HT in the DRN and PFC to ESCIT administered systemically and locally were attenuated in WKY rats. Feedback inhibition of DRN 5-HT release induced by ESCIT into the PFC was also attenuated in WKY rats. Chronic ESCIT induced upregulation of the DRN-PFC 5-HT system in WKY rats, with increases in basal 5-HT in the DRN, responsiveness to ESCIT in the DRN and PFC, and feedback inhibition, whereas downregulation of these effects was induced in Wistar rats. Thus, the WKY rat is an animal model of depression with low activity of the DRN-PFC 5HT system. The finding that chronic ESCIT upregulates the 5-HT system in hyposerotonergic WKY rats may contribute to improved understanding of mechanisms of action of antidepressants, especially in depression with 5-HT deficiency. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Effective connectivity hierarchically links temporoparietal and frontal areas of the auditory dorsal stream with the motor cortex lip area during speech perception.

    PubMed

    Murakami, Takenobu; Restle, Julia; Ziemann, Ulf

    2012-09-01

    A left-hemispheric cortico-cortical network involving areas of the temporoparietal junction (Tpj) and the posterior inferior frontal gyrus (pIFG) is thought to support sensorimotor integration of speech perception into articulatory motor activation, but how this network links with the lip area of the primary motor cortex (M1) during speech perception is unclear. Using paired-coil focal transcranial magnetic stimulation (TMS) in healthy subjects, we demonstrate that Tpj→M1 and pIFG→M1 effective connectivity increased when listening to speech compared to white noise. A virtual lesion induced by continuous theta-burst TMS (cTBS) of the pIFG abolished the task-dependent increase in pIFG→M1 but not Tpj→M1 effective connectivity during speech perception, whereas cTBS of Tpj abolished the task-dependent increase of both effective connectivities. We conclude that speech perception enhances effective connectivity between areas of the auditory dorsal stream and M1. Tpj is situated at a hierarchically high level, integrating speech perception into motor activation through the pIFG.

  2. Brain network dysfunction in youth with obsessive-compulsive disorder induced by simple uni-manual behavior: The role of the dorsal anterior cingulate cortex.

    PubMed

    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

    2017-02-28

    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.

  3. Emotional face recognition, empathic trait (BEES), and cortical contribution in response to positive and negative cues. The effect of rTMS on dorsal medial prefrontal cortex.

    PubMed

    Balconi, Michela; Bortolotti, Adriana

    2013-02-01

    The present study investigated the relationship between three different measures related to the affective empathy: facial expression detection in response to different emotional patterns (positive vs. negative), personal response to empathic scale [Balanced Emotional Empathy Scale (BEES)], and dorsal medial prefrontal cortex (dMPFC) contribution to mediate the facial detection task. Nineteen subjects took part in the study and they were required to recognize facial expression of emotions, after having empathized with these emotional cues. Repeated Transcranial Magnetic Stimulation (rTMS) method was used in the present research in order to produce a temporary virtual disruption of dMPFC activity. dMPFC disruption induced a worse performance, especially in response to negative expressions (i.e. anger and fear). High-BEES subjects paid a higher cost after frontal brain perturbation: they showed to be unable to correctly detect facial expressions more than low-BEES. Moreover, a "negative valence effect" was observed only for high-BEES, and it was probably related with their higher impairment to recognize negative more than positive expressions. dMPFC was found to support emotional facial expression recognition in an empathic condition, with a specific increased responsiveness for negative-valenced faces. The contribution of this research was discussed to explain the mechanisms underlying affective empathy based on rTMS application.

  4. The vigilance promoting drug modafinil modulates serotonin transmission in the rat prefrontal cortex and dorsal raphe nucleus. Possible relevance for its postulated antidepressant activity.

    PubMed

    Ferraro, Luca; Antonelli, Tiziana; Beggiato, Sarah; Cristina Tomasini, Maria; Fuxe, Kjell; Tanganelli, Sergio

    2013-04-01

    Modafinil, (RS)-2-(diphenylmethylsulfinyl)acetamide derivative (Modiodal, Provigil), is a vigilance-promoting agent which reduces sleep episodes by improving wakefulness. It is approved by the USA FDA for narcolepsy, shiftwork sleep disorder and obstructive sleep apnoea with residual excessive sleepiness despite optimal use of continuous positive airway pressure. Unlike classical psychostimulants such as amphetamine and amphetamine-like compounds, the awaking effect of modafinil is not associated with a disturbance of nighttime sleep, tolerance, and sensitization. Its precise mechanism of action is still unclear. In animal studies, modafinil and its analogues have been shown to modify dopaminergic, noradrenergic, glutamatergic, GABAergic, serotoninergic, orexinergic, and histaminergic pathways. Besides the approved use in sleep disorders, modafinil has been investigated for the treatment of fatigue, impaired cognition and some symptoms in a number of other disorders. In particular, clinical studies seem to indicate that the drug could be particularly successful in the treatment of depression and its use in major depressive and bipolar disorders, has been suggested. However, the molecular mechanisms underlying this possible effect are still unknown. The present review firstly summarizes the structure-activity relationship studies and the mechanism of action of modafinil and its related compounds. Then, it focuses on data demonstrating that modafinil interacts with serotonin neuronal activity in rat frontal cortex and dorsal raphe nucleus, two brain areas linked together and involved in depression. Preclinical and clinical evidence of a positive interaction between modafinil and classical antidepressant drugs, is also summarized.

  5. Vocalization Induced CFos Expression in Marmoset Cortex

    PubMed Central

    Miller, Cory T.; DiMauro, Audrey; Pistorio, Ashley; Hendry, Stewart; Wang, Xiaoqin

    2010-01-01

    All non-human primates communicate with conspecifics using vocalizations, a system involving both the production and perception of species-specific vocal signals. Much of the work on the neural basis of primate vocal communication in cortex has focused on the sensory processing of vocalizations, while relatively little data are available for vocal production. Earlier physiological studies in squirrel monkeys had shed doubts on the involvement of primate cortex in vocal behaviors. The aim of the present study was to identify areas of common marmoset (Callithrix jacchus) cortex that are potentially involved in vocal communication. In this study, we quantified cFos expression in three areas of marmoset cortex – frontal, temporal (auditory), and medial temporal – under various vocal conditions. Specifically, we examined cFos expression in these cortical areas during the sensory, motor (vocal production), and sensory–motor components of vocal communication. Our results showed an increase in cFos expression in ventrolateral prefrontal cortex as well as the medial and lateral belt areas of auditory cortex in the vocal perception condition. In contrast, subjects in the vocal production condition resulted in increased cFos expression only in dorsal premotor cortex. During the sensory–motor condition (antiphonal calling), subjects exhibited cFos expression in each of the above areas, as well as increased expression in perirhinal cortex. Overall, these results suggest that various cortical areas outside primary auditory cortex are involved in primate vocal communication. These findings pave the way for further physiological studies of the neural basis of primate vocal communication. PMID:21179582

  6. Spatiotemporal Profile of Voltage-Sensitive Dye Responses in the Visual Cortex of Tree Shrews Evoked by Electric Microstimulation of the Dorsal Lateral Geniculate and Pulvinar Nuclei

    PubMed Central

    Thomas, Sébastien; Petry, Heywood M.; Bickford, Martha E.; Casanova, Christian

    2015-01-01

    The primary visual cortex (V1) receives its main thalamic drive from the dorsal lateral geniculate nucleus (dLGN) through synaptic contacts terminating primarily in cortical layer IV. In contrast, the projections from the pulvinar nucleus to the cortex are less clearly defined. The pulvinar projects predominantly to layer I in V1, and layer IV in extrastriate areas. These projection patterns suggest that the pulvinar nucleus most strongly influences (drives) activity in cortical areas beyond V1. Should this hypothesis be true, one would expect the spatiotemporal responses evoked by pulvinar activation to be different in V1 and extrastriate areas, reflecting the different connectivity patterns. We investigated this issue by analyzing the spatiotemporal dynamics of cortical visual areas' activity following thalamic electrical microstimulation in tree shrews, using optical imaging and voltage-sensitive dyes. As expected, electrical stimulation of the dLGN induced fast and local responses in V1, as well as in extrastriate and contralateral cortical areas. In contrast, electrical stimulation of the pulvinar induced fast and local responses in extrastriate areas, followed by weak and diffuse activation in V1 and contralateral cortical areas. This study highlights spatiotemporal cortical activation characteristics induced by stimulation of first (dLGN) and high-order (pulvinar) thalamic nuclei. SIGNIFICANCE STATEMENT The pulvinar nucleus represents the main extrageniculate thalamic visual structure in higher-order mammals, but its exact role remains enigmatic. The pulvinar receive prominent inputs from virtually all visual cortical areas. Cortico-thalamo-cortical pathways through the pulvinar nuclei may then provide a complementary route for corticocortical information flow. One step toward the understanding of the role of transthalamic corticocortical pathways is to determine the nature of the signals transmitted between the cortex and the thalamus. By performing, for

  7. Differential role of the dorsal hippocampus, ventro-intermediate hippocampus, and medial prefrontal cortex in updating the value of a spatial goal.

    PubMed

    De Saint Blanquat, Paul; Hok, Vincent; Save, Etienne; Poucet, Bruno; Chaillan, Franck A

    2013-05-01

    Encoding of a goal with a specific value while performing a place navigation task involves the medial prefrontal cortex (mPFC) and the dorsal hippocampus (dHPC), and depends on the coordination between mPFC and the ventro-intermediate hippocampus (vHPC).The present work investigates the contribution of mPFC, dHPC, and vHPC when the rat has to update the value of a goal. Rats were trained to navigate to an uncued goal in order to release a food pellet in a continuous place navigation task. When they had reached criterion performance level in the task, they were subjected to a single "flash session" in which they were exposed to an aversive strobe light during goal visits instead of receiving a food reward. Just before the flash session, the GABA(A) agonist muscimol was injected to temporarily inactivate mPFC, dHPC, or vHPC. The ability to recall the changed value of the goal was tested on the next day. We first demonstrate the aversive effect of the strobe light by showing that rats learn to avoid the goal much more rapidly in the flash session than during a simple extinction session in which goal visits are not rewarded. Furthermore, while dHPC inactivation had no effect on learning and recalling the new goal value, vHPC muscimol injections considerably delayed goal value updating during the flash session, which resulted in a slight deficit during recall. In contrast, mPFC muscimol injections induced faster goal value updating but the rats were markedly impaired on recalling the new goal value on the next day. These results suggest that, contrary to mPFC and dHPC, vHPC is required for updating the value of a goal. In contrast, mPFC is necessary for long-term retention of this updating.

  8. Markers of Serotonergic Function in the Orbitofrontal Cortex and Dorsal Raphé Nucleus Predict Individual Variation in Spatial-Discrimination Serial Reversal Learning

    PubMed Central

    Barlow, Rebecca L; Alsiö, Johan; Jupp, Bianca; Rabinovich, Rebecca; Shrestha, Saurav; Roberts, Angela C; Robbins, Trevor W; Dalley, Jeffrey W

    2015-01-01

    Dysfunction of the orbitofrontal cortex (OFC) impairs the ability of individuals to flexibly adapt behavior to changing stimulus-reward (S-R) contingencies. Impaired flexibility also results from interventions that alter serotonin (5-HT) and dopamine (DA) transmission in the OFC and dorsomedial striatum (DMS). However, it is unclear whether similar mechanisms underpin naturally occurring variations in behavioral flexibility. In the present study, we used a spatial-discrimination serial reversal procedure to investigate interindividual variability in behavioral flexibility in rats. We show that flexibility on this task is improved following systemic administration of the 5-HT reuptake inhibitor citalopram and by low doses of the DA reuptake inhibitor GBR12909. Rats in the upper quintile of the distribution of perseverative responses during repeated S-R reversals showed significantly reduced levels of the 5-HT metabolite, 5-hydroxy-indoleacetic acid, in the OFC. Additionally, 5-HT2A receptor binding in the OFC of mid- and high-quintile rats was significantly reduced compared with rats in the low-quintile group. These perturbations were accompanied by an increase in the expression of monoamine oxidase-A (MAO-A) and MAO-B in the lateral OFC and by a decrease in the expression of MAO-A, MAO-B, and tryptophan hydroxylase in the dorsal raphé nucleus of highly perseverative rats. We found no evidence of significant differences in markers of DA and 5-HT function in the DMS or MAO expression in the ventral tegmental area of low- vs high-perseverative rats. These findings indicate that diminished serotonergic tone in the OFC may be an endophenotype that predisposes to behavioral inflexibility and other forms of compulsive behavior. PMID:25567428

  9. Role of dopamine D1 receptors in the prefrontal dorsal agranular insular cortex in mediating cocaine self-administration in rats.

    PubMed

    Di Pietro, Nina C; Mashhoon, Yasmin; Heaney, Chelcie; Yager, Lindsay M; Kantak, Kathleen M

    2008-09-01

    Orbital/insular areas of the prefrontal cortex (PFC) are implicated in cocaine addiction. However, the role of dopamine D1 receptors in mediating cocaine self-administration in these sub-regions remains unknown. To define the role of the dorsal agranular insular (AId) sub-region of the PFC, we investigated the effects of D1 receptor manipulation on self-administration behavior maintained by cocaine and cocaine-related stimuli. Rats were trained to lever press for cocaine (1 mg/kg) under a fixed-interval 5-min (fixed-ratio 5:S) second-order schedule of reinforcement in the presence of conditioned light cues and contextual sound cues. Intra-AId infusions of vehicle, the D1-like receptor agonist SKF 81297 (0.1, 0.2, 0.4 microg/side) or the D1-like receptor antagonist SCH 23390 (1.0, 2.0, 4.0 microg/side), were administered prior to 1-h self-administration test sessions. Food-maintained responding under a second-order schedule was examined in separate rats to determine if pretreatment with D1 ligands produced general impairments in responding. Infusion of SKF 81297 (0.2 and 0.4 microg/side) reduced active lever responses during the first 30 min of 1-h test sessions, but did not influence cocaine intake. Infusion of 4.0 microg/side SCH 23390 reduced active lever responses and cocaine intake throughout the 1-h test sessions. Additionally, this dose of SCH 23390 disrupted food-maintained responding and intake. D1 receptor agonists and antagonists in the AId have diverse consequences and time courses of action. D1 receptor stimulation in the AId may reduce the motivating influence of cocaine-related stimuli on responding whereas D1 receptor blockade in this PFC sub-region produces global disruptions in behavior.

  10. Effects of dopamine D1 receptor blockade in the prelimbic prefrontal cortex or lateral dorsal striatum on frontostriatal function in Wistar and Spontaneously Hypertensive Rats.

    PubMed

    Gauthier, Jamie M; Tassin, David H; Dwoskin, Linda P; Kantak, Kathleen M

    2014-07-15

    Attention Deficit Hyperactivity Disorder (ADHD) is associated with dysfunctional prefrontal and striatal circuitry and dysregulated dopamine neurotransmission. Spontaneously Hypertensive Rats (SHR), a heuristically useful animal model of ADHD, were evaluated against normotensive Wistar (WIS) controls to determine whether dopamine D1 receptor blockade of either prelimbic prefrontal cortex (plPFC) or lateral dorsal striatum (lDST) altered learning functions of both interconnected sites. A strategy set shifting task measured plPFC function (behavioral flexibility/executive function) and a reward devaluation task measured lDST function (habitual responding). Prior to tests, rats received bilateral infusions of SCH 23390 (1.0 μg/side) or vehicle into plPFC or lDST. Following vehicle, SHR exhibited longer lever press reaction times, more trial omissions, and fewer completed trials during the set shift test compared to WIS, indicating slower decision-making and attentional/motivational impairment in SHR. After reward devaluation, vehicle-treated SHR responded less than WIS, indicating relatively less habitual responding in SHR. After SCH 23390 infusions into plPFC, WIS expressed the same behavioral phenotype as vehicle-treated SHR during set shift and reward devaluation tests. In SHR, SCH 23390 infusions into plPFC exacerbated behavioral deficits in the set shift test and maintained the lower rate of responding in the reward devaluation test. SCH 23390 infusions into lDST did not modify set shifting in either strain, but produced lower rates of responding than vehicle infusions after reward devaluation in WIS. This research provides pharmacological evidence for unidirectional interactions between prefrontal and striatal brain regions, which has implications for the neurological basis of ADHD and its treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Differences in the Flexibility of Switching Learning Strategies and CREB Phosphorylation Levels in Prefrontal Cortex, Dorsal Striatum and Hippocampus in Two Inbred Strains of Mice

    PubMed Central

    Cho, Woo-Hyun; Han, Jung-Soo

    2016-01-01

    Flexibility in using different learning strategies was assessed in two different inbred strains of mice, the C57BL/6 and DBA/2 strains. Mice were trained sequentially in two different Morris water maze protocols that tested their ability to switch their learning strategy to complete a new task after first being trained in a different task. Training consisted either of visible platform trials (cued training) followed by subsequent hidden platform trials (place training) or the reverse sequence (place training followed by cued training). Both strains of mice showed equivalent performance in the type of training (cued or place) that they received first. However, C57BL/6 mice showed significantly better performances than DBA/2 mice following the switch in training protocols, irrespective of the order of training. After completion of the switched training session, levels of cAMP response element-binding protein (CREB) and phosphorylated CREB (pCREB) were measured in the hippocampus, striatum and prefrontal cortex of the mice. Prefrontal cortical and hippocampal pCREB levels differed by strain, with higher levels found in C57BL/6 mice than in DBA/2 mice. No strain differences were observed in the medial or lateral region of the dorsal striatum. These findings indicate that the engagement (i.e., CREB signaling) of relevant neural structures may vary by the specific demands of the learning strategy, and this is closely tied to differences in the flexibility of C57BL/6 and DBA/2 mice to switch their learning strategies when given a new task. PMID:27695401

  12. Differences in the Flexibility of Switching Learning Strategies and CREB Phosphorylation Levels in Prefrontal Cortex, Dorsal Striatum and Hippocampus in Two Inbred Strains of Mice.

    PubMed

    Cho, Woo-Hyun; Han, Jung-Soo

    2016-01-01

    Flexibility in using different learning strategies was assessed in two different inbred strains of mice, the C57BL/6 and DBA/2 strains. Mice were trained sequentially in two different Morris water maze protocols that tested their ability to switch their learning strategy to complete a new task after first being trained in a different task. Training consisted either of visible platform trials (cued training) followed by subsequent hidden platform trials (place training) or the reverse sequence (place training followed by cued training). Both strains of mice showed equivalent performance in the type of training (cued or place) that they received first. However, C57BL/6 mice showed significantly better performances than DBA/2 mice following the switch in training protocols, irrespective of the order of training. After completion of the switched training session, levels of cAMP response element-binding protein (CREB) and phosphorylated CREB (pCREB) were measured in the hippocampus, striatum and prefrontal cortex of the mice. Prefrontal cortical and hippocampal pCREB levels differed by strain, with higher levels found in C57BL/6 mice than in DBA/2 mice. No strain differences were observed in the medial or lateral region of the dorsal striatum. These findings indicate that the engagement (i.e., CREB signaling) of relevant neural structures may vary by the specific demands of the learning strategy, and this is closely tied to differences in the flexibility of C57BL/6 and DBA/2 mice to switch their learning strategies when given a new task.

  13. NMDA receptors in the medial prefrontal cortex and the dorsal hippocampus regulate methamphetamine-induced hyperactivity and extracellular amino acid release in mice.

    PubMed

    Han, Wenyan; Wang, Fangyang; Qi, Jia; Wang, Fang; Zhang, Lijia; Zhao, Siqi; Song, Ming; Wu, Chunfu; Yang, Jingyu

    2012-06-15

    The medial prefrontal cortex (mPFC) and the dorsal hippocampus (DHC) play significant roles in stimulant-induced neurobehavioral effects. Methamphetamine (MAP)-induced hyperactivity has been reported to be involved in the regulation of the glutamatergic system. The present study examined whether the glutamatergic and GABAergic systems in the mPFC and DHC were involved in MAP-induced hyperactivity in mice. A combined kainic acid (KA) or N-methyl-d-aspartate (NMDA) lesion and microdialysis technique targeting both the mPFC and DHC were used. The results showed that both KA- and NMDA-induced lesions of the mPFC facilitated MAP-induced hyperactivity, while neither KA- nor NMDA-induced lesions of the DHC had a similar effect. MAP increased the extracellular glutamate (Glu) levels in the mPFC and reduced Glu levels in the DHC. GABA levels in both of these regions were reduced. A KA or NMDA lesion of the mPFC inhibited the Glu reduction in the DHC, and the same lesion of the DHC inhibited the Glu increase in the mPFC induced by MAP. A NMDA lesion of the mPFC blocked GABA reduction in the DHC, but a lesion of DHC enhanced the GABA decrease in the mPFC induced by MAP. Furthermore, a NMDA lesion of DHC increased the vesicular glutamate transporter-2 (VGLUT2) expression in the mPFC following MAP-administration. These findings indicate that glutamatergic as well as GABAergic systems in these two regions are involved in MAP-induced hyperactivity. Moreover, there may be an inhibitory role in these two regions, especially mediated by NMDA receptors, in MAP-induced abnormal behavior and neurotransmission responses.

  14. Oxytocin via its receptor affects restraint stress-induced methamphetamine CPP reinstatement in mice: Involvement of the medial prefrontal cortex and dorsal hippocampus glutamatergic system.

    PubMed

    Han, Wen-Yan; Du, Ping; Fu, Shi-Yuan; Wang, Fang; Song, Ming; Wu, Chun-Fu; Yang, Jing-Yu

    2014-04-01

    Our previous study revealed that intracerebroventricular oxytocin (OT) markedly inhibited the restraint stress-priming conditioned place preference (CPP) reinstatement induced by methamphetamine (MAP) via the glutamatergic system. In this study, the effect of microinjection with OT into mesocorticolimbic regions, the medial prefrontal cortex (mPFC) and the dorsal hippocampus (DHC), on the restraint stress-priming CPP reinstatement were further studied. The results showed that a 15-min restraint stress significantly reinstated MAP-induced CPP, which was inhibited by the microinjection of OT (0.5 and 2.5μg/μl/mouse) into the mPFC. Atosiban (Ato), a selective inhibitor of OT receptor, could absolutely block the effect of OT (2.5μg/μl/mouse). The reinstatement was inhibited by microinjecting with OT (2.5 but not 0.5μg/μl/mouse) into the DHC, which could not be reversed by Ato. Western blotting results showed that the levels of GLT1, VGLUT2, NR2B, p-ERK1/2 and p-CREB expressions in the mPFC were increased and CaMKII was decreased markedly after the stress-priming MAP-induced CPP reinstatement test. OT blocked the changing levels of GLT1, VGLUT2, NR2B, p-CREB and CaMK II, which were reversed by Ato, but failed to affect the elevated expression of p-ERK1/2. In DHC, the levels of VGLUT2, p-ERK1/2 and CREB expressions were reduced during the stress-induced reinstatement, which could be reversed by OT and further abolished by Ato. The present results suggest that mPFC and DHC play differential roles in restraint stress-priming CPP reinstatement induced by MAP and OT via OT receptor affects the reinstatement in which the glutamatergic system is involved. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

  15. Escalated aggression after alcohol drinking in male mice: dorsal raphé and prefrontal cortex serotonin and 5-HT(1B) receptors.

    PubMed

    Faccidomo, Sara; Bannai, Makoto; Miczek, Klaus A

    2008-11-01

    A significant minority of individuals engages in escalated levels of aggression after consuming moderate doses of alcohol (Alc). Neural modulation of escalated aggression involves altered levels of serotonin (5-HT) and the activity of 5-HT(1B) receptors. The aim of these studies was to determine whether 5-HT(1B) receptors in the dorsal raphé (DRN), orbitofrontal (OFC), and medial prefrontal (mPFC) cortex attenuate heightened aggression and regulate extracellular levels of 5-HT. Male mice were trained to self-administer Alc by performing an operant response that was reinforced with a delivery of 6% Alc. To identify Alc-heightened aggressors, each mouse was repeatedly tested for aggression after consuming either 1.0 g/kg Alc or H2O. Next, a cannula was implanted into either the DRN, OFC, or mPFC, and subsets of mice were tested for aggression after drinking either Alc or H(2)O prior to a microinjection of the 5-HT(1B) agonist, CP-94,253. Additional mice were implanted with a microdialysis probe into the mPFC, through which CP-94,253 was perfused and samples were collected for 5-HT measurement. Approximately 60% of the mice were more aggressive after drinking Alc, confirming the aggression-heightening effects of 1.0 g/kg Alc. Infusion of 1 microg CP-94,253 into the DRN reduced both aggressive and motor behaviors. However, infusion of 1 microg CP-94,253 into the mPFC, but not the OFC, after Alc drinking, increased aggressive behavior. In the mPFC, reverse microdialysis of CP-94,253 increased extracellular levels of 5-HT; levels decreased immediately after the perfusion. This 5-HT increase was attenuated in self-administering mice. These results suggest that 5-HT(1B) receptors in the mPFC may serve to selectively disinhibit aggressive behavior in mice with a history of Alc self-administration.

  16. Cortical Connections of Functional Zones in Posterior Parietal Cortex and Frontal Cortex Motor Regions in New World Monkeys

    PubMed Central

    Stepniewska, Iwona; Kaas, Jon H.

    2011-01-01

    We examined the connections of posterior parietal cortex (PPC) with motor/premotor cortex (M1/PM) and other cortical areas. Electrical stimulation (500 ms trains) delivered to microelectrode sites evoked movements of reach, defense, and grasp, from distinct zones in M1/PM and PPC, in squirrel and owl monkeys. Tracer injections into M1/PM reach, defense, and grasp zones showed dense connections with M1/PM hand/forelimb representations. The densest inputs outside of frontal cortex were from PPC zones. M1 zones were additionally connected with somatosensory hand/forelimb representations in areas 3a, 3b, and 1 and the somatosensory areas of the upper bank of the lateral sulcus (S2/PV). Injections into PPC zones showed primarily local connections and the densest inputs outside of PPC originated from M1/PM zones. The PPC reach zone also received dense inputs from cortex caudal to PPC, which likely relayed visual information. In contrast, the PPC grasp zone was densely connected with the hand/forelimb representations of areas 3a, 3b, 1, and S2/PV. Thus, the dorsal parietal–frontal network involved in reaching was preferentially connected to visual cortex, whereas the more ventral network involved in grasping received somatosensory inputs. Additional weak interlinks between dissimilar zones (e.g., PPC reach and PPC grasp) were apparent and may coordinate actions. PMID:21263034

  17. Shape representations in the primate dorsal visual stream

    PubMed Central

    Theys, Tom; Romero, Maria C.; van Loon, Johannes; Janssen, Peter

    2015-01-01

    The primate visual system extracts object shape information for object recognition in the ventral visual stream. Recent research has demonstrated that object shape is also processed in the dorsal visual stream, which is specialized for spatial vision and the planning of actions. A number of studies have investigated the coding of 2D shape in the anterior intraparietal area (AIP), one of the end-stage areas of the dorsal stream which has been implicated in the extraction of affordances for the purpose of grasping. These findings challenge the current understanding of area AIP as a critical stage in the dorsal stream for the extraction of object affordances. The representation of three-dimensional (3D) shape has been studied in two interconnected areas known to be critical for object grasping: area AIP and area F5a in the ventral premotor cortex (PMv), to which AIP projects. In both areas neurons respond selectively to 3D shape defined by binocular disparity, but the latency of the neural selectivity is approximately 10 ms longer in F5a compared to AIP, consistent with its higher position in the hierarchy of cortical areas. Furthermore, F5a neurons were more sensitive to small amplitudes of 3D curvature and could detect subtle differences in 3D structure more reliably than AIP neurons. In both areas, 3D-shape selective neurons were co-localized with neurons showing motor-related activity during object grasping in the dark, indicating a close convergence of visual and motor information on the same clusters of neurons. PMID:25954189

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

    NASA Technical Reports Server (NTRS)

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

    2003-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    2003-01-01

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

  20. Distinct Contributions of Dorsal and Ventral Streams to Imitation of Tool-Use and Communicative Gestures.

    PubMed

    Dressing, Andrea; Nitschke, Kai; Kümmerer, Dorothee; Bormann, Tobias; Beume, Lena; Schmidt, Charlotte S M; Ludwig, Vera M; Mader, Irina; Willmes, Klaus; Rijntjes, Michel; Kaller, Christoph P; Weiller, Cornelius; Martin, Markus

    2016-11-30

    Imitation of tool-use gestures (transitive; e.g., hammering) and communicative emblems (intransitive; e.g., waving goodbye) is frequently impaired after left-hemispheric lesions. We aimed 1) to identify lesions related to deficient transitive or intransitive gestures, 2) to delineate regions associated with distinct error types (e.g., hand configuration, kinematics), and 3) to compare imitation to previous data on pantomimed and actual tool use. Of note, 156 patients (64.3 ± 14.6 years; 56 female) with first-ever left-hemispheric ischemic stroke were prospectively examined 4.8 ± 2.0 days after symptom onset. Lesions were delineated on magnetic resonance imaging scans for voxel-based lesion-symptom mapping. First, while inferior-parietal lesions affected both gesture types, specific associations emerged between intransitive gesture deficits and anterior temporal damage and between transitive gesture deficits and premotor and occipito-parietal lesions. Second, impaired hand configurations were related to anterior intraparietal damage, hand/wrist-orientation errors to premotor lesions, and kinematic errors to inferior-parietal/occipito-temporal lesions. Third, premotor lesions impacted more on transitive imitation compared with actual tool use, pantomimed and actual tool use were more susceptible to lesioned insular cortex and subjacent white matter. In summary, transitive and intransitive gestures differentially rely on ventro-dorsal and ventral streams due to higher demands on temporo-spatial processing (transitive) or stronger reliance on semantic information (intransitive), respectively. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. Left superior parietal cortex involvement in writing: integrating fMRI with lesion evidence.

    PubMed

    Menon, V; Desmond, J E

    2001-10-01

    Writing is a uniquely human skill that we utilize nearly everyday. Lesion studies in patients with Gerstmann's syndrome have pointed to the parietal cortex as being critical for writing. Very little information is, however, available about the precise anatomical location of brain regions subserving writing in normal healthy individuals. In this study, we used functional magnetic resonance imaging (fMRI) to investigate parietal lobe function during writing to dictation. Significant clusters of activation were observed in left superior parietal lobe (SPL) and the dorsal aspects of the inferior parietal cortex (IPC) bordering the SPL. Localized clusters of activation were also observed in the left premotor cortex, sensorimotor cortex and supplementary motor area. No activation cluster was observed in the right hemisphere. These results clearly indicate that writing appears to be primarily organized in the language-dominant hemisphere. Further analysis revealed that within the parietal cortex, activation was significantly greater in the left SPL, compared to left IPC. Together with lesion studies, findings from the present study provide further evidence for the essential role of the left SPL in writing. Deficits to the precise left hemisphere parietal cortex regions identified in the present study may specifically underlie disorders of writing observed in Gerstmann's syndrome and apractic agraphia.

  2. Dopamine replacement modulates oscillatory coupling between premotor and motor cortical areas in Parkinson's disease.

    PubMed

    Herz, Damian Marc; Florin, Esther; Christensen, Mark Schram; Reck, Christiane; Barbe, Michael Thomas; Tscheuschler, Maike Karoline; Tittgemeyer, Marc; Siebner, Hartwig Roman; Timmermann, Lars

    2014-11-01

    Efficient neural communication between premotor and motor cortical areas is critical for manual motor control. Here, we used high-density electroencephalography to study cortical connectivity in patients with Parkinson's disease (PD) and age-matched healthy controls while they performed repetitive movements of the right index finger at maximal repetition rate. Multiple source beamformer analysis and dynamic causal modeling were used to assess oscillatory coupling between the lateral premotor cortex (lPM), supplementary motor area (SMA), and primary motor cortex (M1) in the contralateral hemisphere. Elderly healthy controls showed task-related modulation in connections from lPM to SMA and M1, mainly within the γ-band (>30 Hz). Nonmedicated PD patients also showed task-related γ-γ coupling from lPM to M1, but γ coupling from lPM to SMA was absent. Levodopa reinstated physiological γ-γ coupling from lPM to SMA and significantly strengthened coupling in the feedback connection from M1 to lPM expressed as β-β as well as θ-β coupling. Enhancement in cross-frequency θ-β coupling from M1 to lPM was correlated with levodopa-induced improvement in motor function. The results show that PD is associated with an altered neural communication between premotor and motor cortical areas, which can be modulated by dopamine replacement.

  3. Cortical connectivity suggests a role in limb coordination for macaque area PE of the superior parietal cortex.

    PubMed

    Bakola, Sophia; Passarelli, Lauretta; Gamberini, Michela; Fattori, Patrizia; Galletti, Claudio

    2013-04-10

    In macaques, superior parietal lobule area 5 has been described as occupying an extensive region, which includes the caudal half of the postcentral convexity as well as the medial bank of the intraparietal sulcus. Modern neuroanatomical methods have allowed the identification of various areas within this region. In the present study, we investigated the corticocortical afferent projections of one of these subdivisions, area PE. Our results demonstrate that PE, defined as a single architectonic area that contains a topographic map of the body, forms specific connections with somatic and motor fields. Thus, PE receives major afferents from parietal areas, mainly area 2, PEc, several areas in the medial bank of the intraparietal sulcus, opercular areas PGop/PFop, and the retroinsular area, frontal afferents from the primary motor cortex, the supplementary motor area, and the caudal subdivision of dorsal premotor cortex, as well as afferents from cingulate areas PEci, 23, and 24. The presence and relative strength of these connections depend on the location of injection sites, so that lateral PE receives preferential input from anterior sectors of the medial bank of intraparietal sulcus and from the ventral premotor cortex, whereas medial PE forms denser connections with area PEc and motor fields. In contrast with other posterior parietal areas, there are no projections to PE from occipital or prefrontal cortices. Overall, the sensory and motor afferents to PE are consistent with functions in goal-directed movement but also hint at a wider variety of motor coordination roles.

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

    ERIC Educational Resources Information Center

    Murakami, Takenobu; Restle, Julia; Ziemann, Ulf

    2012-01-01

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

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

    ERIC Educational Resources Information Center

    Murakami, Takenobu; Restle, Julia; Ziemann, Ulf

    2012-01-01

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

  6. Object vision to hand action in macaque parietal, premotor, and motor cortices

    PubMed Central

    Schaffelhofer, Stefan; Scherberger, Hansjörg

    2016-01-01

    Grasping requires translating object geometries into appropriate hand shapes. How the brain computes these transformations is currently unclear. We investigated three key areas of the macaque cortical grasping circuit with microelectrode arrays and found cooperative but anatomically separated visual and motor processes. The parietal area AIP operated primarily in a visual mode. Its neuronal population revealed a specialization for shape processing, even for abstract geometries, and processed object features ultimately important for grasping. Premotor area F5 acted as a hub that shared the visual coding of AIP only temporarily and switched to highly dominant motor signals towards movement planning and execution. We visualize these non-discrete premotor signals that drive the primary motor cortex M1 to reflect the movement of the grasping hand. Our results reveal visual and motor features encoded in the grasping circuit and their communication to achieve transformation for grasping. DOI: http://dx.doi.org/10.7554/eLife.15278.001 PMID:27458796

  7. The cortical drive to human respiratory muscles in the awake state assessed by premotor cerebral potentials.

    PubMed Central

    Macefield, G; Gandevia, S C

    1991-01-01

    during quiet breathing the cerebral cortex does not contribute to respiratory drive on a breath-by-breath basis. Conversely, the presence of clear premotor cerebral potentials when subjects performed self-paced inspiratory or expiratory manoeuvres illustrates the powerful cortical projection to human respiratory muscles. PMID:1895244

  8. Activity in the premotor area related to bite force control--a functional near-infrared spectroscopy study.

    PubMed

    Takeda, Tomotaka; Shibusawa, Mami; Sudal, Osamu; Nakajima, Kazunori; Ishigami, Keiichi; Sakatani, Kaoru

    2010-01-01

    The purpose of this study was to elucidate the influence of bite force control on oxygenated hemoglobin (OxyHb) levels in regional cerebral blood flow as an indicator of brain activity in the premotor area. Healthy right-handed volunteers with no subjective or objective symptoms of problems of the stomatognathic system or cervicofacial region were included. Functional near-infrared spectroscopy (fNIRS) was used to determine OxyHb levels in the premotor area during bite force control. A bite block equipped with an occlusal force sensor was prepared to measure clenching at the position where the right upper and lower canine cusps come into contact. Intensity of clenching was shown on a display and feedback was provided to the subjects. Intensity was set at 20, 50 and 80% of maximum voluntary teeth clenching force. To minimize the effect of the temporal muscle on the working side of the jaw, the fNIRS probes were positioned contralaterally, in the left region. The findings of this study are: activation of the premotor area with bite force control was noted in all subjects, and in the group analysis OxyHb in the premotor cortex was significantly increased as the clenching strengthened at 20, 50 and 80% of maximum voluntary clenching force. These results suggest there is a possibility that the premotor area is involved in bite force control.

  9. Eye-hand coordination during reaching. I. Anatomical relationships between parietal and frontal cortex.

    PubMed

    Marconi, B; Genovesio, A; Battaglia-Mayer, A; Ferraina, S; Squatrito, S; Molinari, M; Lacquaniti, F; Caminiti, R

    2001-06-01

    The anatomical and physiological substrata of eye-hand coordination during reaching were studied through combined anatomical and physiological techniques. The association connections of parietal areas V6A and PEc, and those of dorso-rostral (F7) and dorso-caudal (F2) premotor cortex were studied in monkeys, after physiological characterization of the parietal regions where retrograde tracers were injected. The results show that parieto-occipital area V6A is reciprocally connected with F7, and receives a smaller projection from F2. Local parietal projections to V6A arise from areas MIP and, to a lesser extent, 7m, PEa and PEC: On the contrary, parietal area PEc is strongly and reciprocally connected with the part of F2 located close to the pre-central dimple (pre-CD). Local parietal projections to PEc come from a distributed network, including PEa, MIP, PEci and, to a lesser extent, 7m, V6A, 7a and MST. Premotor area F7 receives parietal projections mainly from 7m and V6A, and local frontal projections mainly from F2. On the contrary, premotor area F2 in the pre-CD zone receives parietal inputs from PEc and, to a lesser extent, PEci, while in the peri-arcuate zone F2 receives parietal projections from PEa and MIP. Local frontal projections to F2 pre-CD mostly stem from F4, and, to a lesser extent, from F7 and F3, and CMAd; those addressed to peri-arcuate zone of F2 arise mainly from F5 and, to a lesser extent, from F7, F4, dorsal (CMAd) and ventral (CMAv) cingulate motor areas, pre-supplementary (F6) and supplementary (F3) motor areas. The distribution of association cells in both frontal and parietal cortex was characterized through a spectral analysis that revealed an arrangement of these cells in the form of bands, composed of cell clusters, or 'columns'. The reciprocal connections linking parietal and frontal cortex might explain the presence of visually related and eye-position signals in premotor cortex, as well as the influence of information about arm

  10. Projections of the hand field of the macaque ventral premotor area F5 to the brainstem and spinal cord.

    PubMed

    Borra, Elena; Belmalih, Abdelouahed; Gerbella, Marzio; Rozzi, Stefano; Luppino, Giuseppe

    2010-07-01

    In the present study we first assessed that the hand motor field of the macaque ventral premotor area F5, involved in visuomotor control of hand actions, is connected to both the hand field of the primary motor cortex (M1) and the spinal cord. We then injected retroanterograde tracers in this field to completely illustrate its possible descending motor projections. In the brainstem the F5 hand motor field projects to the intermediate and deep layers of the superior colliculus (SC) and to sectors of the mesencephalic, pontine, and bulbar reticular formation, which are the sources of spinal projections. In the spinal cord, labeled terminals were virtually all confined to the C2-T1 segments, mostly contralaterally. At C6-T1 levels the labeling was weaker and mostly clustered laterally in the intermediate zone. At C2-C5 levels, labeled terminals were much denser and diffusely distributed over the mid-dorsal part of the intermediate zone where a propriospinal system that directly controls hand muscle motoneurons and mediates commands for the control of dexterous finger movements is located (Isa et al. [2007] Physiology 22:145-152). Thus, the F5 hand motor field has a weaker direct access and a stronger indirect access to spinal segments where hand muscle motoneurons are located, suggesting a role of this field in the generation and control of hand movements not only at the M1 level, but also at the spinal cord level. These projections may represent the neural substrate for the F5 hand motor field's role in the recovery of manual dexterity after M1 lesions.

  11. Can we image premotor Parkinson disease?

    PubMed

    Marek, Kenneth; Jennings, Danna

    2009-02-17

    Pathology and imaging studies have shown that patients with Parkinson disease (PD) have a prolonged period of uncertain duration when vulnerable neuronal populations are degenerating, but typical motor symptoms have not yet developed. This provides both an opportunity-it may be best to test new medications and, ultimately, treat PD patients during this early phase of disease--and a challenge--how to find these premotor PD subjects? Imaging biomarkers targeting the premotor period are critical to elucidate both the onset and progression of premotor PD. Widespread data have demonstrated that dopaminergic imaging can detect PD subjects at the motor symptom threshold. Novel strategies combining dopaminergic imaging with known genetic mutations for PD or early clinical signs and PD-associated symptoms, such as olfactory loss and sleep disturbances like REM behavior disorder, have begun to be used to identify individuals at risk for PD before motor symptoms become manifest. Early studies also have used imaging targeting norepinephrine, serotonin, cholinergic, or other neuronal systems to focus on early cardiac, cognitive, and behavioral symptoms. Imaging of nondopaminergic targets such as inflammation or alpha-synuclein deposition may provide further insight into the etiology of PD. Given the multiple genetic etiologies for PD already identified, the marked variability in the loss of dopaminergic markers measured by imaging at motor symptom onset, and the clear heterogeneity of clinical symptoms at PD onset, it is certain that many imaging biomarkers with a focus ranging from clinical symptoms to PD pathobiology to molecular genetic mechanisms, will be necessary to fully map PD risk.

  12. Feeling the beat: premotor and striatal interactions in musicians and non-musicians during beat perception

    PubMed Central

    Grahn, Jessica A.; Rowe, James B.

    2009-01-01

    Little is known about the underlying neurobiology of rhythm and beat perception, despite its universal cultural importance. Here we used functional magnetic resonance imaging to study rhythm perception in musicians and non-musicians. Three conditions varied in the degree to which external reinforcement versus internal generation of the beat was required. The ‘Volume’ condition strongly externally marked the beat with volume changes, the ‘Duration’ condition marked the beat with weaker accents arising from duration changes, and the ‘Unaccented’ condition required the beat to be entirely internally generated. In all conditions, beat rhythms compared to nonbeat control rhythms revealed putamen activity. The presence of a beat was also associated with greater connectivity between the putamen and the supplementary motor area (SMA), the premotor cortex (PMC) and auditory cortex. In contrast, the type of accent within the beat conditions modulated the coupling between premotor and auditory cortex, with greater modulation for musicians than non-musicians. Importantly, the putamen's response to beat conditions was not due to differences in temporal complexity between the three rhythm conditions. We propose that a cortico-subcortical network including the putamen, SMA, and PMC is engaged for the analysis of temporal sequences and prediction or generation of putative beats, especially under conditions that may require internal generation of the beat. The importance of this system for auditory-motor interaction and development of precisely timed movement is suggested here by its facilitation in musicians. PMID:19515922

  13. Coordinated activation of premotor and ventromedial prefrontal cortices during vicarious reward.

    PubMed

    Shimada, Sotaro; Matsumoto, Madoka; Takahashi, Hidefumi; Yomogida, Yukihito; Matsumoto, Kenji

    2016-03-01

    The vicarious reward we receive from watching likable others obtaining a positive outcome is a pervasive phenomenon, yet its neural correlates are poorly understood. Here, we conducted a series of functional magnetic resonance imaging experiments to test the hypothesis that the brain areas responsible for action observation and reward processing work in a coordinated fashion during vicarious reward. In the first experiment (manipulation phase), the participant was instructed to cheer for a particular player in a two-player competitive game (Rock-Paper-Scissors). This manipulation made participants feel more unity with that player and resulted in unity-related activation in the premotor area during action observation. In the following main experiment, the participant witnessed the previously cheered-for or non-cheered-for player succeed in a new solitary game (a stopwatch game). The ventromedial prefrontal cortex (vmPFC) was activated when the cheered-for player succeeded in the game but not when the other player did. Interestingly, this vmPFC activation was functionally connected with premotor activation only during the cheered-for player's success. These results suggest that vicarious reward is processed in the vmPFC-premotor network, which is activated specifically by the success of the other person with whom the individual feels unity and closeness.

  14. Selective Long-term Reorganization of the Corticospinal Projection from the Supplementary Motor Cortex following Recovery from Lateral Motor Cortex Injury

    PubMed Central

    McNeal, David W.; Darling, Warren G.; Ge, Jizhi; Stilwell-Morecraft, Kimberly S.; Solon, Kathryn M.; Hynes, Stephanie M.; Pizzimenti, Marc A.; Rotella, Diane; Vanadurongvan, Tyler; Morecraft, Robert J.

    2013-01-01

    Brain injury affecting the frontal motor cortex or its descending axons often causes contralateral upper extremity paresis. Although recovery is variable, the underlying mechanisms supporting favorable motor recovery remain unclear. Since the medial wall of the cerebral hemisphere is often spared following brain injury and recent functional neuroimaging studies in patients indicate a potential role for this brain region in the recovery process, we investigated the long-term effects of isolated lateral frontal motor cortical injury on the corticospinal projection (CSP) from intact, ipsilesional supplementary motor cortex (M2). Following injury to the arm region of the primary motor (M1) and lateral premotor (LPMC) cortices, upper extremity recovery is accompanied by terminal axon plasticity in the contralateral CSP but not the ipsilateral CSP from M2. Furthermore, significant contralateral plasticity occurs only in lamina VII and dorsally within lamina IX. Thus, selective intraspinal sprouting transpires in regions containing interneurons, flexor-related motor neurons and motor neurons supplying intrinsic hand muscles which all play important roles in mediating reaching and digit movements. Following recovery, subsequent injury of M2 leads to reemergence of hand motor deficits. Considering the importance of the CSP in humans and the common occurrence of lateral frontal cortex injury, these findings suggest that spared supplementary motor cortex may serve as an important therapeutic target that should be considered when designing acute and long-term post-injury patient intervention strategies aimed to enhance the motor recovery process following lateral cortical trauma. PMID:20034062

  15. Compensatory premotor activity during affective face processing in subclinical carriers of a single mutant Parkin allele.

    PubMed

    Anders, Silke; Sack, Benjamin; Pohl, Anna; Münte, Thomas; Pramstaller, Peter; Klein, Christine; Binkofski, Ferdinand

    2012-04-01

    Patients with Parkinson's disease suffer from significant motor impairments and accompanying cognitive and affective dysfunction due to progressive disturbances of basal ganglia-cortical gating loops. Parkinson's disease has a long presymptomatic stage, which indicates a substantial capacity of the human brain to compensate for dopaminergic nerve degeneration before clinical manifestation of the disease. Neuroimaging studies provide evidence that increased motor-related cortical activity can compensate for progressive dopaminergic nerve degeneration in carriers of a single mutant Parkin or PINK1 gene, who show a mild but significant reduction of dopamine metabolism in the basal ganglia in the complete absence of clinical motor signs. However, it is currently unknown whether similar compensatory mechanisms are effective in non-motor basal ganglia-cortical gating loops. Here, we ask whether asymptomatic Parkin mutation carriers show altered patterns of brain activity during processing of facial gestures, and whether this might compensate for latent facial emotion recognition deficits. Current theories in social neuroscience assume that execution and perception of facial gestures are linked by a special class of visuomotor neurons ('mirror neurons') in the ventrolateral premotor cortex/pars opercularis of the inferior frontal gyrus (Brodmann area 44/6). We hypothesized that asymptomatic Parkin mutation carriers would show increased activity in this area during processing of affective facial gestures, replicating the compensatory motor effects that have previously been observed in these individuals. Additionally, Parkin mutation carriers might show altered activity in other basal ganglia-cortical gating loops. Eight asymptomatic heterozygous Parkin mutation carriers and eight matched controls underwent functional magnetic resonance imaging and a subsequent facial emotion recognition task. As predicted, Parkin mutation carriers showed significantly stronger activity in

  16. Region-specific roles of the prelimbic cortex, the dorsal CA1, the ventral DG and ventral CA1 of the hippocampus in the fear return evoked by a sub-conditioning procedure in rats.

    PubMed

    Fu, Juan; Xing, Xiaoli; Han, Mengfi; Xu, Na; Piao, Chengji; Zhang, Yue; Zheng, Xigeng

    2016-02-01

    The return of learned fear is an important issue in anxiety disorder research since an analogous process may contribute to long-term fear maintenance or clinical relapse. A number of studies demonstrate that mPFC and hippocampus are important in the modulation of post-extinction re-expression of fear memory. However, the region-specific role of these structures in the fear return evoked by a sub-threshold conditioning (SC) is not known. In the present experiments, we first examined specific roles of the prelimbic cortex (PL), the dorsal hippocampus (DH, the dorsal CA1 area in particular), the ventral hippocampus (the ventral dentate gyrus (vDG) and the ventral CA1 area in particular) in this fear return process. Then we examined the role of connections between PL and vCA1 with this behavioral approach. Rats were subjected to five tone-shock pairings (1.0-mA shock) to induce conditioned fear (freezing), followed by three fear extinction sessions (25 tone-alone trials each session). After a post-test for extinction memory, some rats were retrained with the SC procedure to reinstate tone-evoked freezing. Rat groups were injected with low doses of the GABAA agonist muscimol to selectively inactivate PL, DH, vDG, or vCA1 120 min before the fear return test. A disconnection paradigm with ipsilateral or contralateral muscimol injection of the PL and the vCA1 was used to examine the role of this pathway in the fear return. We found that transient inactivation of these areas significantly impaired fear return (freezing): inactivation of the prelimbic cortex blocked SC-evoked fear return in particular but did not influence fear expression in general; inactivation of the DH area impaired fear return, but had no effect on the extinction retrieval process; both ventral DG and ventral CA1 are required for the return of extinguished fear whereas only ventral DG is required for the extinction retrieval. These findings suggest that PL, DH, vDG, and vCA1 all contribute to the fear

  17. One’s motor performance predictably modulates the understanding of others’ actions through adaptation of premotor visuo-motor neurons

    PubMed Central

    Barchiesi, Guido; Tabarelli, Davide; Arfeller, Carola; Sato, Marc; Glenberg, Arthur M.

    2011-01-01

    Neurons firing both during self and other’s motor behavior (mirror neurons) have been described in the brain of vertebrates including humans. The activation of somatic motor programs driven by perceived behavior has been taken as evidence for mirror neurons’ contribution to cognition. The inverse relation, that is the influence of motor behavior on perception, is needed for demonstrating the long-hypothesized causal role of mirror neurons in action understanding. We provide here conclusive behavioral and neurophysiological evidence for that causal role by means of cross-modal adaptation coupled with a novel transcranial magnetic stimulation (TMS)-adaptation paradigm. Blindfolded repeated motor performance of an object-directed action (push or pull) induced in healthy participants a strong visual after-effect when categorizing others’ actions, as a result of motor-to-visual adaptation of visuo-motor neurons. TMS over the ventral premotor cortex, but not over the primary motor cortex, suppressed the after-effect, thus localizing the population of adapted visuo-motor neurons in the premotor cortex. These data are exquisitely consistent in humans with the existence of premotor mirror neurons that have access to the action meaning. We also show that controlled manipulation of the firing properties of this neural population produces strong predictable changes in the way we categorize others’ actions. PMID:21186167

  18. The medial dorsal thalamic nucleus and the medial prefrontal cortex of the rat function together to support associative recognition and recency but not item recognition

    PubMed Central

    Cross, Laura; Brown, Malcolm W.; Aggleton, John P.; Warburton, E. Clea

    2013-01-01

    In humans recognition memory deficits, a typical feature of diencephalic amnesia, have been tentatively linked to mediodorsal thalamic nucleus (MD) damage. Animal studies have occasionally investigated the role of the MD in single-item recognition, but have not systematically analyzed its involvement in other recognition memory processes. In Experiment 1 rats with bilateral excitotoxic lesions in the MD or the medial prefrontal cortex (mPFC) were tested in tasks that assessed single-item recognition (novel object preference), associative recognition memory (object-in-place), and recency discrimination (recency memory task). Experiment 2 examined the functional importance of the interactions between the MD and mPFC using disconnection techniques. Unilateral excitotoxic lesions were placed in both the MD and the mPFC in either the same (MD + mPFC Ipsi) or opposite hemispheres (MD + mPFC Contra group). Bilateral lesions in the MD or mPFC impaired object-in-place and recency memory tasks, but had no effect on novel object preference. In Experiment 2 the MD + mPFC Contra group was significantly impaired in the object-in-place and recency memory tasks compared with the MD + mPFC Ipsi group, but novel object preference was intact. Thus, connections between the MD and mPFC are critical for recognition memory when the discriminations involve associative or recency information. However, the rodent MD is not necessary for single-item recognition memory. PMID:23263843

  19. The medial dorsal thalamic nucleus and the medial prefrontal cortex of the rat function together to support associative recognition and recency but not item recognition.

    PubMed

    Cross, Laura; Brown, Malcolm W; Aggleton, John P; Warburton, E Clea

    2012-12-21

    In humans recognition memory deficits, a typical feature of diencephalic amnesia, have been tentatively linked to mediodorsal thalamic nucleus (MD) damage. Animal studies have occasionally investigated the role of the MD in single-item recognition, but have not systematically analyzed its involvement in other recognition memory processes. In Experiment 1 rats with bilateral excitotoxic lesions in the MD or the medial prefrontal cortex (mPFC) were tested in tasks that assessed single-item recognition (novel object preference), associative recognition memory (object-in-place), and recency discrimination (recency memory task). Experiment 2 examined the functional importance of the interactions between the MD and mPFC using disconnection techniques. Unilateral excitotoxic lesions were placed in both the MD and the mPFC in either the same (MD + mPFC Ipsi) or opposite hemispheres (MD + mPFC Contra group). Bilateral lesions in the MD or mPFC impaired object-in-place and recency memory tasks, but had no effect on novel object preference. In Experiment 2 the MD + mPFC Contra group was significantly impaired in the object-in-place and recency memory tasks compared with the MD + mPFC Ipsi group, but novel object preference was intact. Thus, connections between the MD and mPFC are critical for recognition memory when the discriminations involve associative or recency information. However, the rodent MD is not necessary for single-item recognition memory.

  20. Differential Activation of Fast-Spiking and Regular-Firing Neuron Populations During Movement and Reward in the Dorsal Medial Frontal Cortex

    PubMed Central

    Insel, Nathan; Barnes, Carol A.

    2015-01-01

    The medial prefrontal cortex is thought to be important for guiding behavior according to an animal's expectations. Efforts to decode the region have focused not only on the question of what information it computes, but also how distinct circuit components become engaged during behavior. We find that the activity of regular-firing, putative projection neurons contains rich information about behavioral context and firing fields cluster around reward sites, while activity among putative inhibitory and fast-spiking neurons is most associated with movement and accompanying sensory stimulation. These dissociations were observed even between adjacent neurons with apparently reciprocal, inhibitory–excitatory connections. A smaller population of projection neurons with burst-firing patterns did not show clustered firing fields around rewards; these neurons, although heterogeneous, were generally less selective for behavioral context than regular-firing cells. The data suggest a network that tracks an animal's behavioral situation while, at the same time, regulating excitation levels to emphasize high valued positions. In this scenario, the function of fast-spiking inhibitory neurons is to constrain network output relative to incoming sensory flow. This scheme could serve as a bridge between abstract sensorimotor information and single-dimensional codes for value, providing a neural framework to generate expectations from behavioral state. PMID:24700585

  1. Neuronal degeneration in the dorsal lateral geniculate nucleus following lesions of primary visual cortex: comparison of young adult and geriatric marmoset monkeys.

    PubMed

    Atapour, Nafiseh; Worthy, Katrina H; Lui, Leo L; Yu, Hsin-Hao; Rosa, Marcello G P

    2017-03-22

    Neuronal loss in the lateral geniculate nucleus (LGN) is a consequence of lesions of the primary visual cortex (V1). Despite the importance of this phenomenon in understanding the residual capacities of the primate visual system following V1 damage, few quantitative studies are available, and the effect of age at the time of lesion remains unknown. We compared the volume, neuronal number, and neuronal density in the LGN, 6-21 months after unilateral V1 lesions in marmoset monkeys. Stereological sampling techniques and neuronal nuclei (NeuN) staining were used to assess the effects of similar-sized lesions in adult (2-4 years) and geriatric (10-14 years) animals. We found that lesions involving the opercular and caudal calcarine parts of V1 caused robust loss of neurons in topographically corresponding regions of the ipsilateral LGN (lesion projection zones), concomitant with a substantial reduction in the volume of this nucleus. Neuronal density was markedly reduced in the lesion projection zones, relative to the corresponding regions of the contralateral LGN, or the LGN in non-lesioned animals. Moreover, the percentage decrease in neuronal density within the lesion projection zones was significantly greater in the geriatric group, compared with the adult groups. The volume and neuronal density in the contralateral LGN of lesioned adult and geriatric marmosets were similar to those in non-lesioned animals. These results show that the primate LGN becomes more vulnerable to degeneration with advancing age. However, even in geriatric primates there is a population of LGN neurons which survives degeneration, and which could play a role in blindsight.

  2. Trace Eyeblink Conditioning in Mice Is Dependent upon the Dorsal Medial Prefrontal Cortex, Cerebellum, and Amygdala: Behavioral Characterization and Functional Circuitry1,2,3

    PubMed Central

    Taylor, William; Gray, Richard; Kalmbach, Brian; Zemelman, Boris V.; Desai, Niraj S.; Johnston, Daniel; Chitwood, Raymond A.

    2015-01-01

    Abstract Trace eyeblink conditioning is useful for studying the interaction of multiple brain areas in learning and memory. The goal of the current work was to determine whether trace eyeblink conditioning could be established in a mouse model in the absence of elicited startle responses and the brain circuitry that supports this learning. We show here that mice can acquire trace conditioned responses (tCRs) devoid of startle while head-restrained and permitted to freely run on a wheel. Most mice (75%) could learn with a trace interval of 250 ms. Because tCRs were not contaminated with startle-associated components, we were able to document the development and timing of tCRs in mice, as well as their long-term retention (at 7 and 14 d) and flexible expression (extinction and reacquisition). To identify the circuitry involved, we made restricted lesions of the medial prefrontal cortex (mPFC) and found that learning was prevented. Furthermore, inactivation of the cerebellum with muscimol completely abolished tCRs, demonstrating that learned responses were driven by the cerebellum. Finally, inactivation of the mPFC and amygdala in trained animals nearly abolished tCRs. Anatomical data from these critical regions showed that mPFC and amygdala both project to the rostral basilar pons and overlap with eyelid-associated pontocerebellar neurons. The data provide the first report of trace eyeblink conditioning in mice in which tCRs were driven by the cerebellum and required a localized region of mPFC for acquisition. The data further reveal a specific role for the amygdala as providing a conditioned stimulus-associated input to the cerebellum. PMID:26464998

  3. Differential Recruitment of Parietal Cortex during Spatial and Non-spatial Reach Planning

    PubMed Central

    Bernier, Pierre-Michel; Whittingstall, Kevin; Grafton, Scott T.

    2017-01-01

    The planning of goal-directed arm reaching movements is associated with activity in the dorsal parieto-frontal cortex, within which multiple regions subserve the integration of arm- and target-related sensory signals to encode a motor goal. Surprisingly, many of these regions show sustained activity during reach preparation even when target location is not specified, i.e., when a motor goal cannot be unambiguously formed. The functional role of these non-spatial preparatory signals remains unresolved. Here this process was investigated in humans by comparing reach preparatory activity in the presence or absence of information regarding upcoming target location. In order to isolate the processes specific to reaching and to control for visuospatial attentional factors, the reaching task was contrasted to a finger movement task. Functional MRI and electroencephalography (EEG) were used to characterize the spatio-temporal pattern of reach-related activity in the parieto-frontal cortex. Reach planning with advance knowledge of target location induced robust blood oxygenated level dependent and EEG responses across parietal and premotor regions contralateral to the reaching arm. In contrast, reach preparation without knowledge of target location was associated with a significant BOLD response bilaterally in the parietal cortex. Furthermore, EEG alpha- and beta-band activity was restricted to parietal scalp sites, the magnitude of the latter being correlated with reach reaction times. These results suggest an intermediate stage of sensorimotor transformations in bilateral parietal cortex when target location is not specified. PMID:28536517

  4. MEG premotor abnormalities in children with Asperger's syndrome: determinants of social behavior?

    PubMed

    Hauswald, Anne; Weisz, Nathan; Bentin, Shlomo; Kissler, Johanna

    2013-07-01

    Children with Asperger's syndrome show deficits in social functioning while their intellectual and language development is intact suggesting a specific dysfunction in mechanisms mediating social cognition. An action observation/execution matching system might be one such mechanism. Recent studies indeed showed that electrophysiological modulation of the "Mu-rhythm" in the 10-12Hz range is weaker when individuals with Asperger's syndrome observe actions performed by others compared to controls. However, electrophysiological studies typically fall short in revealing the neural generators of this activity. To fill this gap we assessed magnetoencephalographic Mu-modulations in Asperger's and typically developed children, while observing grasping movements. Mu-power increased at frontal and central sensors during movement observation. This modulation was stronger in typical than in Asperger children. Source localization revealed stronger sources in premotor cortex, the intraparietal lobule (IPL) and the mid-occipito-temporal gyrus (MOTG) and weaker sources in prefrontal cortex in typical participants compared to Asperger. Activity in premotor regions, IPL and MOTG correlated positively with social competence, whereas prefrontal Mu-sources correlated negatively with social competence. No correlation with intellectual ability was found at any of these sites. These findings localize abnormal Mu-activity in the brain of Asperger children providing evidence which associates motor-system abnormalities with social-function deficits.

  5. Action word meaning representations in cytoarchitectonically defined primary and premotor cortices.

    PubMed

    Postle, Natasha; McMahon, Katie L; Ashton, Roderick; Meredith, Matthew; de Zubicaray, Greig I

    2008-11-15

    Recent models of language comprehension have assumed a tight coupling between the semantic representations of action words and cortical motor areas. We combined functional MRI with cytoarchitectonically defined probabilistic maps of left hemisphere primary and premotor cortices to analyse responses of functionally delineated execution- and observation-related regions during comprehension of action word meanings associated with specific effectors (e.g., punch, bite or stomp) and processing of items with various levels of lexical information (non body part-related meanings, nonwords, and visual character strings). The comprehension of effector specific action word meanings did not elicit preferential activity corresponding to the somatotopic organisation of effectors in either primary or premotor cortex. However, generic action word meanings did show increased BOLD signal responses compared to all other classes of lexical stimuli in the pre-SMA. As expected, the majority of the BOLD responses elicited by the lexical stimuli were in association cortex adjacent to the motor areas. We contrast our results with those of previous studies reporting significant effects for only 1 or 2 effectors outside cytoarchitectonically defined motor regions and discuss the importance of controlling for potentially confounding lexical variables such as imageability. We conclude that there is no strong evidence for a somatotopic organisation of action word meaning representations and argue the pre-SMA might have a role in maintaining abstract representations of action words as instructional cues.

  6. Radioactive 2-DG incorporation patterns in the mesial frontal cortex of task-performing monkeys.

    PubMed

    Matsunami, K; Kawashima, T

    1995-11-01

    The pattern of radioactive 2-deoxy-D-glucose (2-DG) uptake in the rostral mesial cortex was investigated in seven hemispheres of four task-performing monkeys (a delayed-response task performed with a forelimb). A two-dimensional 2-DG map was constructed from frontal sections. Blob-like 2-DG incorporation sites (2-DG active sites) were observed in single frontal sections, e.g., in the anterior cingulate gyrus (CiG) and supplementary and primary motor cortices in the mesial surface, and around the superior precentral sulcus in the premotor area. Blob-like 2-DG incorporation sites were also observed in the medial part of the dorsal frontal cortex near the midline. However, most of these blob-like 2-DG active sites were revealed in fact not to be blobs. They formed rostrocaudally continuous streaks when they were constructed in a two-dimensional map. Streaks fused with one another in some areas, and gave off branches in other areas. These 2-DG uptake patterns were similar between the paired left and right hemispheres of three brains. It is highly probable that these 2-DG active streaks (or blobs) reflected neuronal activity related to somatomotor and/or eye movements, because the 2-DG-labeled areas included motor, premotor, supplementary motor, and possibly part of the supplementary eye fields. It is also probable that this 2-DG incorporation was related to cognitive or memory functions, because neuronal activity related to performance of a delayed-response was reported in the rostral mesial cortex and in the CiG.

  7. Interplay of Inhibition and Excitation Shapes a Premotor Neural Sequence

    PubMed Central

    Kosche, Georg; Vallentin, Daniela

    2015-01-01

    In the zebra finch, singing behavior is driven by a sequence of bursts within premotor neurons located in the forebrain nucleus HVC (proper name). In addition to these excitatory projection neurons, HVC also contains inhibitory interneurons with a role in premotor patterning that is unclear. Here, we used a range of electrophysiological and behavioral observations to test previously described models suggesting discrete functional roles for inhibitory interneurons in song production. We show that single HVC premotor neuron bursts are sufficient to drive structured activity within the interneuron network because of pervasive and facilitating synaptic connections. We characterize interneuron activity during singing and describe reliable pauses in the firing of those neurons. We then demonstrate that these gaps in inhibition are likely to be necessary for driving normal bursting behavior in HVC premotor neurons and suggest that structured inhibition and excitation may be a general mechanism enabling sequence generation in other circuits. PMID:25609636

  8. Functional Interactions between Mammalian Respiratory Rhythmogenic and Premotor Circuitry

    PubMed Central

    Song, Hanbing; Hayes, John A.; Vann, Nikolas C.; Wang, Xueying; LaMar, M. Drew

    2016-01-01

    Breathing in mammals depends on rhythms that originate from the preBötzinger complex (preBötC) of the ventral medulla and a network of brainstem and spinal premotor neurons. The rhythm-generating core of the preBötC, as well as some premotor circuits, consist of interneurons derived from Dbx1-expressing precursors (Dbx1 neurons), but the structure and function of these networks remain incompletely understood. We previously developed a cell-specific detection and laser ablation system to interrogate respiratory network structure and function in a slice model of breathing that retains the preBötC, the respiratory-related hypoglossal (XII) motor nucleus and XII premotor circuits. In spontaneously rhythmic slices, cumulative ablation of Dbx1 preBötC neurons decreased XII motor output by ∼50% after ∼15 cell deletions, and then decelerated and terminated rhythmic function altogether as the tally increased to ∼85 neurons. In contrast, cumulatively deleting Dbx1 XII premotor neurons decreased motor output monotonically but did not affect frequency nor stop XII output regardless of the ablation tally. Here, we couple an existing preBötC model with a premotor population in several topological configurations to investigate which one may replicate the laser ablation experiments best. If the XII premotor population is a “small-world” network (rich in local connections with sparse long-range connections among constituent premotor neurons) and connected with the preBötC such that the total number of incoming synapses remains fixed, then the in silico system successfully replicates the in vitro laser ablation experiments. This study proposes a feasible configuration for circuits consisting of Dbx1-derived interneurons that generate inspiratory rhythm and motor pattern. SIGNIFICANCE STATEMENT To produce a breathing-related motor pattern, a brainstem core oscillator circuit projects to a population of premotor interneurons, but the assemblage of this network remains

  9. Social instigation and aggression in postpartum female rats: role of 5-Ht1A and 5-Ht1B receptors in the dorsal raphé nucleus and prefrontal cortex

    PubMed Central

    da Veiga, Caroline Perinazzo; Miczek, Klaus A.; Lucion, Aldo Bolten

    2013-01-01

    Rationale 5-HT1A and 5-HT1B receptor agonists effectively reduce aggressive behavior in males that has been escalated by social instigation. Important sites of action for these drugs are the receptors in dorsal raphé nuclei (DRN) and the ventral–orbital prefrontal cortex (VO PFC). DRN and VO PFC areas are particularly relevant in the inhibitory control of escalated aggressive and impulsive behavior. Objectives The objectives of this study are to assess the anti-aggressive effects of 5-HT1A (8-OH-DPAT) and 5-HT1B (CP-93,129) receptor agonists microinjected into DRN and VO PFC, respectively, and to study the aggressive behavior in postpartum female Wistar rats using the social instigation protocol to increase aggression. Methods and Results 8-OH-DPAT (0.56 µg) in the DRN increased aggressive behavior in postpartum female rats. By contrast, CP-93,129 (1.0 µg) microinjected into VO PFC decreased the number of attack bites and lateral threats. 5-HT1A and 5-HT1B receptor agonists differed in their effects on non-aggressive activities, the former decreasing rearing and grooming and the latter increasing these acts. When 8-OH-DPAT was microinjected into DRN and CP-93,129 was microinjected into VO PFC in female rats at the same time, maternal aggression decreased. Specific participation of 5-HT1B receptors was verified by reversal of the anti-aggressive effects using the selective antagonist SB-224,289 (1.0 µg). Conclusions The decrease in maternal aggressive behavior after microinjections of 5-HT1B receptor agonists into the VO PFC and DRN of female postpartum rats that were instigated socially supports the hypothesis that activation of these receptors modulates high levels of aggression in a behaviorally specific manner, due to activation of 5-HT1B receptors at the soma and terminals. PMID:21107539

  10. Dynamic association of epigenetic H3K4me3 and DNA 5hmC marks in the dorsal hippocampus and anterior cingulate cortex following reactivation of a fear memory.

    PubMed

    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

    2017-02-20

    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.

  11. Extended methamphetamine self-administration in rats results in a selective reduction of dopamine transporter levels in the prefrontal cortex and dorsal striatum not accompanied by marked monoaminergic depletion.

    PubMed

    Schwendt, Marek; Rocha, Angelica; See, Ronald E; Pacchioni, Alejandra M; McGinty, Jacqueline F; Kalivas, Peter W

    2009-11-01

    Chronic abuse of methamphetamine leads to cognitive dysfunction and high rates of relapse, paralleled by significant changes of brain dopamine and serotonin neurotransmission. Previously, we found that rats with extended access to methamphetamine self-administration displayed enhanced methamphetamine-primed reinstatement of drug-seeking and cognitive deficits relative to limited access animals. The present study investigated whether extended access to methamphetamine self-administration produced abnormalities in dopamine and serotonin systems in rat forebrain. Rats self-administered methamphetamine (0.02-mg/i.v. infusion) during daily 1-h sessions for 7 to 10 days, followed by either short- (1-h) or long-access (6-h) self-administration for 12 to 14 days. Lever responding was extinguished for 2 weeks before either reinstatement testing or rapid decapitation and tissue dissection. Tissue levels of monoamine transporters and markers of methamphetamine-induced toxicity were analyzed in several forebrain areas. Long-access methamphetamine self-administration resulted in escalation of daily drug intake ( approximately 7 mg/kg/day) and enhanced drug-primed reinstatement compared with the short-access group. Furthermore, long-, but not short-access to self-administered methamphetamine resulted in persistent decreases in dopamine transporter (DAT) protein levels in the prefrontal cortex and dorsal striatum. In contrast, only minor alterations in the tissue levels of dopamine or its metabolites were found, and no changes in markers specific for dopamine terminals or glial cell activation were detected. Our findings suggest that persistent methamphetamine seeking is associated with region-selective changes in DAT levels without accompanying monoaminergic neurotoxicity. Greater understanding of the neuroadaptations underlying persistent methamphetamine seeking and cognitive deficits could yield targets suitable for future therapeutic interventions.

  12. Interaction between the premotor processes of eye and hand movements: possible mechanism underlying eye-hand coordination.

    PubMed

    Hiraoka, Koichi; Kurata, Naoatsu; Sakaguchi, Masato; Nonaka, Kengo; Matsumoto, Naoto

    2014-03-01

    Interaction between the execution process of eye movement and that of hand movement must be indispensable for eye-hand coordination. The present study investigated corticospinal excitability in the hand muscles during the premotor processes of eye and/or hand movement to elucidate interaction between these processes. Healthy humans performed a precued reaction task of eye and/or finger movement and motor-evoked potentials in the hand muscles were evoked in the reaction time. Leftward eye movement suppressed corticospinal excitability in the right abductor digiti minimi muscle only when little finger abduction was simultaneously executed. Corticospinal excitability in the first dorsal interosseous muscle was not suppressed by eye movement regardless of whether or not it was accompanied by finger movement. Suppression of corticospinal excitability in the hand muscles induced by eye movement in the premotor period depends on the direction of eye movement, the muscle tested, and the premotor process of the tested muscle. The suppression may reflect interaction between the motor process of eye movement and that of hand movement particularly active during eye-hand coordination tasks during which both processes proceed.

  13. cTBS delivered to the left somatosensory cortex changes its functional connectivity during rest

    PubMed Central

    Valchev, Nikola; Ćurčić-Blake, Branislava; Renken, Remco J.; Avenanti, Alessio; Keysers, Christian

    2016-01-01

    The primary somatosensory cortex (SI) plays a critical role in somatosensation as well as in action performance and social cognition. Although SI has been a major target of experimental and clinical research using non-invasive transcranial magnetic stimulation (TMS), to date information on the effect of TMS over SI on its resting-state functional connectivity is very scant. Here, we explored whether continuous theta burst stimulation (cTBS), a repetitive TMS protocol, administered over SI can change the functional connectivity of the brain at rest, as measured using resting-state functional magnetic resonance imaging (rs-fMRI). In a randomized order on two different days we administered active TMS or sham TMS over the left SI. TMS was delivered off-line before scanning by means of cTBS. The target area was selected previously and individually for each subject as the part of SI activated both when the participant executes and observes actions. Three analytical approaches, both theory driven (partial correlations and seed based whole brain regression) and more data driven (Independent Component Analysis), indicated a reduction in functional connectivity between the stimulated part of SI and several brain regions functionally associated with SI including the dorsal premotor cortex, the cerebellum, basal ganglia, and anterior cingulate cortex. These findings highlight the impact of cTBS delivered over SI on its functional connectivity at rest. Our data may have implications for experimental and therapeutic applications of cTBS over SI. PMID:25882754

  14. Paying attention through eye movements: a computational investigation of the premotor theory of spatial attention.

    PubMed

    Casarotti, Marco; Lisi, Matteo; Umiltà, Carlo; Zorzi, Marco

    2012-07-01

    Growing evidence indicates that planning eye movements and orienting visuospatial attention share overlapping brain mechanisms. A tight link between endogenous attention and eye movements is maintained by the premotor theory, in contrast to other accounts that postulate the existence of specific attention mechanisms that modulate the activity of information processing systems. The strong assumption of equivalence between attention and eye movements, however, is challenged by demonstrations that human observers are able to keep attention on a specific location while moving the eyes elsewhere. Here we investigate whether a recurrent model of saccadic planning can account for attentional effects without requiring additional or specific mechanisms separate from the circuits that perform sensorimotor transformations for eye movements. The model builds on the basis function approach and includes a circuit that performs spatial remapping using an "internal forward model" of how visual inputs are modified as a result of saccadic movements. Simulations show that the latter circuit is crucial to account for dissociations between attention and eye movements that may be invoked to disprove the premotor theory. The model provides new insights into how spatial remapping may be implemented in parietal cortex and offers a computational framework for recent proposals that link visual stability with remapping of attention pointers.

  15. Midcingulate cortex: Structure, connections, homologies, functions and diseases.

    PubMed

    Vogt, Brent A

    2016-07-01

    Midcingulate cortex (MCC) has risen in prominence as human imaging identifies unique structural and functional activity therein and this is the first review of its structure, connections, functions and disease vulnerabilities. The MCC has two divisions (anterior, aMCC and posterior, pMCC) that represent functional units and the cytoarchitecture, connections and neurocytology of each is shown with immunohistochemistry and receptor binding. The MCC is not a division of anterior cingulate cortex (ACC) and the "dorsal ACC" designation is a misnomer as it incorrectly implies that MCC is a division of ACC. Interpretation of findings among species and developing models of human diseases requires detailed comparative studies which is shown here for five species with flat maps and immunohistochemistry (human, monkey, rabbit, rat, mouse). The largest neurons in human cingulate cortex are in layer Vb of area 24 d in pMCC which project to the spinal cord. This area is part of the caudal cingulate premotor area which is involved in multisensory orientation of the head and body in space and neuron responses are tuned for the force and direction of movement. In contrast, the rostral cingulate premotor area in aMCC is involved in action-reinforcement associations and selection based on the amount of reward or aversive properties of a potential movement. The aMCC is activated by nociceptive information from the midline, mediodorsal and intralaminar thalamic nuclei which evoke fear and mediates nocifensive behaviors. This subregion also has high dopaminergic afferents and high dopamine-1 receptor binding and is engaged in reward processes. Opposing pain/avoidance and reward/approach functions are selected by assessment of potential outcomes and error detection according to feedback-mediated, decision making. Parietal afferents differentially terminate in MCC and provide for multisensory control in an eye- and head-centric manner. Finally, MCC vulnerability in human disease confirms

  16. Human posterior parietal cortex encodes the movement goal in a pro-/anti-reach task

    PubMed Central

    Gertz, Hanna

    2015-01-01

    Previous research on reach planning in humans has implicated a frontoparietal network, including the precuneus (PCu), a putative human homolog of the monkey parietal reach region (PRR), and the dorsal premotor cortex (PMd). Using a pro-/anti-reach task, electrophysiological studies in monkeys have demonstrated that the movement goal rather than the location of the visual cue is encoded in PRR and PMd. However, if only the effector but not the movement goal is specified (underspecified condition), the PRR and PMd have been shown to represent all potential movement goals. In this functional magnetic resonance imaging study, we investigated whether the human PCu and PMd likewise encode the movement goal, and whether these reach-related areas also engage in situations with underspecified compared with specified movement goals. By using a pro-/anti-reach task, we spatially dissociated the location of the visual cue from the location of the movement goal. In the specified conditions, pro- and anti-reaches activated similar parietal and premotor areas. In the PCu contralateral to the moving arm, we found directionally selective activation fixed to the movement goal. In the underspecified conditions, we observed activation in reach-related areas of the posterior parietal cortex, including PCu. However, the activation was substantially weaker in parietal areas and lacking in PMd. Our results suggest that human PCu encodes the movement goal rather than the location of the visual cue if the movement goal is specified and even engages in situations when only the visual cue but not the movement goal is defined. PMID:25904714

  17. Plasticity of premotor cortico-muscular coherence in severely impaired stroke patients with hand paralysis.

    PubMed

    Belardinelli, Paolo; Laer, Leonard; Ortiz, Erick; Braun, Christoph; Gharabaghi, Alireza

    2017-01-01

    Motor recovery in severely impaired stroke patients is often very limited. To refine therapeutic interventions for regaining motor control in this patient group, the functionally relevant mechanisms of neuronal plasticity need to be detected. Cortico-muscular coherence (CMC) may provide physiological and topographic insights to achieve this goal. Synchronizing limb movements to motor-related brain activation is hypothesized to reestablish cortico-motor control indexed by CMC. In the present study, right-handed, chronic stroke patients with right-hemispheric lesions and left hand paralysis participated in a four-week training for their left upper extremity. A brain-robot interface turned event-related beta-band desynchronization of the lesioned sensorimotor cortex during kinesthetic motor-imagery into the opening of the paralyzed hand by a robotic orthosis. Simultaneous MEG/EMG recordings and individual models from MRIs were used for CMC detection and source reconstruction of cortico-muscular connectivity to the affected finger extensors before and after the training program. The upper extremity-FMA of the patients improved significantly from 16.23 ± 6.79 to 19.52 ± 7.91 (p = 0.0015). All patients showed significantly increased CMC in the beta frequency-band, with a distributed, bi-hemispheric pattern and considerable inter-individual variability. The location of CMC changes was not correlated to the severity of the motor impairment, the motor improvement or the lesion volume. Group analysis of the cortical overlap revealed a common feature in all patients following the intervention: a significantly increased level of ipsilesional premotor CMC that extended from the superior to the middle and inferior frontal gyrus, along with a confined area of increased CMC in the contralesional premotor cortex. In conclusion, functionally relevant modulations of CMC can be detected in patients with long-term, severe motor deficits after a brain-robot assisted

  18. Individual Differences in Premotor and Motor Recruitment during Speech Perception

    ERIC Educational Resources Information Center

    Szenkovits, Gayaneh; Peelle, Jonathan E.; Norris, Dennis; Davis, Matthew H.

    2012-01-01

    Although activity in premotor and motor cortices is commonly observed in neuroimaging studies of spoken language processing, the degree to which this activity is an obligatory part of everyday speech comprehension remains unclear. We hypothesised that rather than being a unitary phenomenon, the neural response to speech perception in motor regions…

  19. Individual Differences in Premotor and Motor Recruitment during Speech Perception

    ERIC Educational Resources Information Center

    Szenkovits, Gayaneh; Peelle, Jonathan E.; Norris, Dennis; Davis, Matthew H.

    2012-01-01

    Although activity in premotor and motor cortices is commonly observed in neuroimaging studies of spoken language processing, the degree to which this activity is an obligatory part of everyday speech comprehension remains unclear. We hypothesised that rather than being a unitary phenomenon, the neural response to speech perception in motor regions…

  20. Inference and Decoding of Motor Cortex Low-Dimensional Dynamics via Latent State-Space Models

    PubMed Central

    Aghagolzadeh, Mehdi; Truccolo, Wilson

    2016-01-01

    Motor cortex neuronal ensemble spiking activity exhibits strong low-dimensional collective dynamics (i.e., coordinated modes of activity) during behavior. Here, we demonstrate that these low-dimensional dynamics, revealed by unsupervised latent state-space models, can provide as accurate or better reconstruction of movement kinematics as direct decoding from the entire recorded ensemble. Ensembles of single neurons were recorded with triple microelectrode arrays (MEAs) implanted in ventral and dorsal premotor (PMv, PMd) and primary motor (M1) cortices while nonhuman primates performed 3-D reach-to-grasp actions. Low-dimensional dynamics were estimated via various types of latent state-space models including, for example, Poisson linear dynamic system (PLDS) models. Decoding from low-dimensional dynamics was implemented via point process and Kalman filters coupled in series. We also examined decoding based on a predictive subsampling of the recorded population. In this case, a supervised greedy procedure selected neuronal subsets that optimized decoding performance. When comparing decoding based on predictive subsampling and latent state-space models, the size of the neuronal subset was set to the same number of latent state dimensions. Overall, our findings suggest that information about naturalistic reach kinematics present in the recorded population is preserved in the inferred low-dimensional motor cortex dynamics. Furthermore, decoding based on unsupervised PLDS models may also outperform previous approaches based on direct decoding from the recorded population or on predictive subsampling. PMID:26336135

  1. Inference and Decoding of Motor Cortex Low-Dimensional Dynamics via Latent State-Space Models.

    PubMed

    Aghagolzadeh, Mehdi; Truccolo, Wilson

    2016-02-01

    Motor cortex neuronal ensemble spiking activity exhibits strong low-dimensional collective dynamics (i.e., coordinated modes of activity) during behavior. Here, we demonstrate that these low-dimensional dynamics, revealed by unsupervised latent state-space models, can provide as accurate or better reconstruction of movement kinematics as direct decoding from the entire recorded ensemble. Ensembles of single neurons were recorded with triple microelectrode arrays (MEAs) implanted in ventral and dorsal premotor (PMv, PMd) and primary motor (M1) cortices while nonhuman primates performed 3-D reach-to-grasp actions. Low-dimensional dynamics were estimated via various types of latent state-space models including, for example, Poisson linear dynamic system (PLDS) models. Decoding from low-dimensional dynamics was implemented via point process and Kalman filters coupled in series. We also examined decoding based on a predictive subsampling of the recorded population. In this case, a supervised greedy procedure selected neuronal subsets that optimized decoding performance. When comparing decoding based on predictive subsampling and latent state-space models, the size of the neuronal subset was set to the same number of latent state dimensions. Overall, our findings suggest that information about naturalistic reach kinematics present in the recorded population is preserved in the inferred low-dimensional motor cortex dynamics. Furthermore, decoding based on unsupervised PLDS models may also outperform previous approaches based on direct decoding from the recorded population or on predictive subsampling.

  2. The Largest Response Component in the Motor Cortex Reflects Movement Timing but Not Movement Type

    PubMed Central

    Sussillo, David; Ryu, Stephen I.

    2016-01-01

    Abstract Neural activity in monkey motor cortex (M1) and dorsal premotor cortex (PMd) can reflect a chosen movement well before that movement begins. The pattern of neural activity then changes profoundly just before movement onset. We considered the prediction, derived from formal considerations, that the transition from preparation to movement might be accompanied by a large overall change in the neural state that reflects when movement is made rather than which movement is made. Specifically, we examined “components” of the population response: time-varying patterns of activity from which each neuron’s response is approximately composed. Amid the response complexity of individual M1 and PMd neurons, we identified robust response components that were “condition-invariant”: their magnitude and time course were nearly identical regardless of reach direction or path. These condition-invariant response components occupied dimensions orthogonal to those occupied by the “tuned” response components. The largest condition-invariant component was much larger than any of the tuned components; i.e., it explained more of the structure in individual-neuron responses. This condition-invariant response component underwent a rapid change before movement onset. The timing of that change predicted most of the trial-by-trial variance in reaction time. Thus, although individual M1 and PMd neurons essentially always reflected which movement was made, the largest component of the population response reflected movement timing rather than movement type. PMID:27761519

  3. Pyramidal tract stimulation restores normal corticospinal tract connections and visuomotor skill after early postnatal motor cortex activity blockade

    PubMed Central

    Salimi, I; Friel, KM; Martin, JH

    2008-01-01

    Motor development depends on forming specific connections between the corticospinal tract (CST) and the spinal cord. Blocking CST activity in kittens during the critical period for establishing connections with spinal motor circuits results in permanent impairments in connectivity and function. The changes in connections are consistent with the hypothesis that the inactive tract is less competitive in developing spinal connections than the active tract. In this study we tested the competition hypothesis by determining if activating CST axons, after prior silencing during the critical period, abrogated development of aberrant corticospinal connections and motor impairments. In kittens, we inactivated motor cortex by muscimol infusion between postnatal weeks 5-7. We next electrically stimulated CST axons in the medullary pyramid 2.5 hours daily, between weeks 7-10. In controls (n=3), CST terminations were densest within the contralateral deeper, premotor, spinal layers. After prior inactivation (n=3), CST terminations were densest within the dorsal, somatic sensory, layers. There were more ipsilateral terminations from the active tract. During visually guided locomotion, there was a movement endpoint impairment. Stimulation after inactivation (n=6) resulted in significantly fewer terminations in the sensory layers and more in the premotor layers, and fewer ipsilateral connections from active cortex. Chronic stimulation reduced the current threshold for evoking contralateral movements by pyramidal stimulation, suggesting strengthening of connections. Importantly, stimulation significantly improved stepping accuracy. These findings show the importance of activity-dependent processes in specifying CST connections. They also provide a strategy for harnessing activity to rescue CST axons at risk of developing aberrant connections after CNS injury. PMID:18632946

  4. Pyramidal tract stimulation restores normal corticospinal tract connections and visuomotor skill after early postnatal motor cortex activity blockade.

    PubMed

    Salimi, Iran; Friel, Kathleen M; Martin, John H

    2008-07-16

    Motor development depends on forming specific connections between the corticospinal tract (CST) and the spinal cord. Blocking CST activity in kittens during the critical period for establishing connections with spinal motor circuits results in permanent impairments in connectivity and function. The changes in connections are consistent with the hypothesis that the inactive tract is less competitive in developing spinal connections than the active tract. In this study, we tested the competition hypothesis by determining whether activating CST axons, after previous silencing during the critical period, abrogated development of aberrant corticospinal connections and motor impairments. In kittens, we inactivated motor cortex by muscimol infusion between postnatal weeks 5 and 7. Next, we electrically stimulated CST axons in the medullary pyramid 2.5 h daily, between weeks 7 and 10. In controls (n = 3), CST terminations were densest within the contralateral deeper, premotor, spinal layers. After previous inactivation (n = 3), CST terminations were densest within the dorsal, somatic sensory, layers. There were more ipsilateral terminations from the active tract. During visually guided locomotion, there was a movement endpoint impairment. Stimulation after inactivation (n = 6) resulted in significantly fewer terminations in the sensory layers and more in the premotor layers, and fewer ipsilateral connections from active cortex. Chronic stimulation reduced the current threshold for evoking contralateral movements by pyramidal stimulation, suggesting strengthening of connections. Importantly, stimulation significantly improved stepping accuracy. These findings show the importance of activity-dependent processes in specifying CST connections. They also provide a strategy for harnessing activity to rescue CST axons at risk of developing aberrant connections after CNS injury.

  5. Predicting Reaction Time from the Neural State Space of the Premotor and Parietal Grasping Network.

    PubMed

    Michaels, Jonathan A; Dann, Benjamin; Intveld, Rijk W; Scherberger, Hansjörg

    2015-08-12

    Neural networks of the brain involved in the planning and execution of grasping movements are not fully understood. The network formed by macaque anterior intraparietal area (AIP) and hand area (F5) of the ventral premotor cortex is implicated strongly in the generation of grasping movements. However, the differential role of each area in this frontoparietal network is unclear. We recorded spiking activity from many electrodes in parallel in AIP and F5 while three macaque monkeys (Macaca mulatta) performed a delayed grasping task. By analyzing neural population activity during action preparation, we found that state space analysis of simultaneously recorded units is significantly more predictive of subsequent reaction times (RTs) than traditional methods. Furthermore, because we observed a wide variety of individual unit characteristics, we developed the sign-corrected average rate (SCAR) method of neural population averaging. The SCAR method was able to explain at least as much variance in RT overall as state space methods. Overall, F5 activity predicted RT (18% variance explained) significantly better than AIP (6%). The SCAR methods provides a straightforward interpretation of population activity, although other state space methods could provide richer descriptions of population dynamics. Together, these results lend support to the differential role of the parietal and frontal cortices in preparation for grasping, suggesting that variability in preparatory activity in F5 has a more potent effect on trial-to-trial RT variability than AIP. Grasping movements are planned before they are executed, but how is the preparatory activity in a population of neurons related to the subsequent reaction time (RT)? A population analysis of the activity of many neurons recorded in parallel in macaque premotor (F5) and parietal (AIP) cortices during a delayed grasping task revealed that preparatory activity in F5 could explain a threefold larger fraction of variability in trial

  6. Temperature Manipulation in Songbird Brain Implicates the Premotor Nucleus HVC in Birdsong Syntax.

    PubMed

    Zhang, Yisi S; Wittenbach, Jason D; Jin, Dezhe Z; Kozhevnikov, Alexay A

    2017-03-08

    in the Bengalese finch brain-a premotor area homologous to the mammalian premotor cortex-alters the statistics of the syllable sequences, suggesting that HVC is critical for birdsong sequences. HVC is also known for controlling moment-to-moment timings within syllables. Our results show that timing and probabilistic sequencing of actions can share the same neural circuits in local brain areas.

  7. Ventral premotor to primary motor cortical interactions during noxious and naturalistic action observation.

    PubMed

    Lago, Angel; Koch, Giacomo; Cheeran, Binith; Márquez, Gonzalo; Sánchez, Jose Andrés; Ezquerro, Milagros; Giraldez, Manolo; Fernández-del-Olmo, Miguel

    2010-05-01

    Within the motor system, cortical areas such as the primary motor cortex (M1) and the ventral premotor cortex (PMv), are thought to be activated during the observation of actions performed by others. However, it is not known how the connections between these areas become active during action observation or whether these connections are modulated by the volitional component induced by the action observed. In this study, using a paired pulse transcranial magnetic stimulation (ppTMS) method, we evaluated the excitability of PMv-M1 connections during the observation of videos showing a human hand reaching to grasp a ball (naturalistic grasping video) or a switched on soldering iron (noxious grasping video). The results show that the observation of the naturalistic grasping action increased the M1 excitability and changed the strength of the PMv-M1 connections. The observation of the noxious grasping action did not induce any change in the excitability of the PMv-M1 connections throughout the video, but the strength of PMv-M1 connectivity was reduced. These results demonstrate that the PMv-M1 connections are modulated differently depending on whether the action observed would or would not be performed in real life. 2010. Published by Elsevier Ltd. All rights reserved.

  8. Eye-hand interactions differ in the human premotor and parietal cortices.

    PubMed

    van Donkelaar, Paul; Lee, Ji-Hang; Drew, Anthony S

    2002-09-01

    In order to successfully look at and reach for a visual target the central nervous system must perform a complex sensorimotor transformation. How this transformation is mapped onto relevant brain structures has become the subject of much recent investigation. In the present paper we examined the contribution of the human premotor cortex (PMC) to this transformation process during a task requiring coordinated eye and hand movements. For this purpose, we made use of single-pulse transcranial magnetic stimulation (TMS) to temporarily disrupt the processing occurring in the PMC during task performance. Subjects made open-loop pointing movements accompanied by saccades of the same size or two or three times larger. Under normal circumstances without TMS, the pointing movement amplitude increased with saccade amplitude. When TMS was applied over the PMC 100-200 ms after target presentation, the influence of saccade amplitude on the pointing movement amplitude was increased. This is the opposite effect to that observed in a previous study [Journal of Neurophysiology 84 (200) 1677-1680] when TMS was applied over the posterior parietal cortex (PPC) during the same task. We suggest that this pattern of results is consistent with the coding of the reach plan in eye-centered coordinates in the PPC and limb-centered coordinates in the PMC. Copyright 2002 Elsevier Science B.V.

  9. QUANTITATIVE 7T PHASE IMAGING IN PREMOTOR HUNTINGTON DISEASE

    PubMed Central

    Apple, Alexandra C.; Possin, Katherine L.; Satris, Gabriela; Johnson, Erica; Lupo, Janine M.; Jakary, Angela; Wong, Katherine; Kelley, Douglas A. C.; Kang, Gail A.; Sha, Sharon J.; Kramer, Joel H.; Geschwind, Michael; Nelson, Sarah J.; Hess, Christopher P.

    2014-01-01

    Background and Purpose In vivo MRI and postmortem neuropathological studies have demonstrated elevated iron concentration and atrophy within the striatum of patients with Huntington disease (HD), implicating neuronal loss and iron accumulation in the pathogenesis of this neurodegenerative disorder. We used 7T MRI to determine whether quantitative phase, a putative marker of these endpoints, is altered in subjects with premotor HD. Materials and Methods Local field shift (LFS), calculated from 7T MR phase images, was quantified in 13 subjects with premotor HD and 13 age- and gender-matched controls. All participants underwent 3T and 7T MRI, including volumetric 3T T1 and 7T gradient-recalled echo sequences. LFS maps were created from 7T phase data and registered to caudate ROIs automatically parcellated from the 3T T1 images. HD-specific neurocognitive assessment was also performed and compared to LFS. Results Subjects with premotor HD had smaller caudate nuclear volume and higher LFS than controls. A significant correlation between these measurements was not detected, and prediction accuracy for disease state improved with inclusion of both variables. A positive correlation between LFS and genetic disease burden was also found, and there was a trend towards significant correlations between LFS and neurocognitive tests of working memory and executive function. Conclusion Subjects with premotor HD exhibit differences in 7T MRI phase within the caudate nuclei that correlate with genetic disease burden and trend with neurocognitive assessments. Ultra-high field MRI of quantitative phase may be a useful marker for monitoring neurodegeneration in premanifest HD. PMID:24742810

  10. Reduced parietal connectivity with a premotor writing area in writer's cramp.

    PubMed

    Delnooz, Cathérine C S; Helmich, Rick C; Toni, Ivan; van de Warrenburg, Bart P C

    2012-09-15

    Writer's cramp is a task-specific form of dystonia with symptoms characterized by abnormal movements and postures of the hand and arm evident only during writing. Its pathophysiology has been related to faulty sensorimotor integration, abnormal sensory processing, and impaired motor planning. Its symptoms might appear when the computational load of writing pushes a tonically altered circuit outside its operational range. Using resting-state fMRI, we tested whether writer's cramp patients have altered intrinsic functional connectivity in the premotor-parietal circuit. Sixteen patients with right-sided writer's cramp and 19 control subjects were studied. We show that writer's cramp patients have reduced connectivity between the superior parietal lobule and a dorsal precentral region that controls writing movements. This difference between patients and controls occurred in the absence of writing and only in the hemisphere contralateral to the affected hand. This finding adds a novel element to the pathophysiological substrate for writer's cramp, namely, task-independent alterations within a writing-related circuit.

  11. Visuomotor signals for reaching movements in the rostro-dorsal sector of the monkey thalamic reticular nucleus.

    PubMed

    Saga, Yosuke; Nakayama, Yoshihisa; Inoue, Ken-Ichi; Yamagata, Tomoko; Hashimoto, Masashi; Tremblay, Léon; Takada, Masahiko; Hoshi, Eiji

    2017-05-01

    The thalamic reticular nucleus (TRN) collects inputs from the cerebral cortex and thalamus and, in turn, sends inhibitory outputs to the thalamic relay nuclei. This unique connectivity suggests that the TRN plays a pivotal role in regulating information flow through the thalamus. Here, we analyzed the roles of TRN neurons in visually guided reaching movements. We first used retrograde transneuronal labeling with rabies virus, and showed that the rostro-dorsal sector of the TRN (TRNrd) projected disynaptically to the ventral premotor cortex (PMv). In other experiments, we recorded neurons from the TRNrd or PMv while monkeys performed a visuomotor task. We found that neurons in the TRNrd and PMv showed visual-, set-, and movement-related activity modulation. These results indicate that the TRNrd, as well as the PMv, is involved in the reception of visual signals and in the preparation and execution of reaching movements. The fraction of neurons that were non-selective for the location of visual signals or the direction of reaching movements was greater in the TRNrd than in the PMv. Furthermore, the fraction of neurons whose activity increased from the baseline was greater in the TRNrd than in the PMv. The timing of activity modulation of visual-related and movement-related neurons was similar in TRNrd and PMv neurons. Overall, our data suggest that TRNrd neurons provide motor thalamic nuclei with inhibitory inputs that are predominantly devoid of spatial selectivity, and that these signals modulate how these nuclei engage in both sensory processing and motor output during visually guided reaching behavior. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  12. Biochemical Pre-motor Biomarkers for Parkinson Disease

    PubMed Central

    Mollenhauer, Brit; Zhang, Jing

    2012-01-01

    A biomarker is a biological characteristic that is objectively measured and evaluated as an indicator of normal biological or pathologic processes or of pharmacologic responses to a therapeutic intervention. We review the current status on target protein biomarkers (e.g. total/oligomeric α-synuclein and DJ-1) in cerebrospinal fluid, as well as on unbiased processes that can be used to discover novel biomarkers. We also give details about strategies towards potential populations/models and technologies, including the need for standardized sampling techniques, to pursue the identification of new biochemical markers in the pre-motor stage of Parkinson disease in the future. PMID:22508282

  13. 'What' Is Happening in the Dorsal Visual Pathway.

    PubMed

    Freud, Erez; Plaut, David C; Behrmann, Marlene

    2016-10-01

    The cortical visual system is almost universally thought to be segregated into two anatomically and functionally distinct pathways: a ventral occipitotemporal pathway that subserves object perception, and a dorsal occipitoparietal pathway that subserves object localization and visually guided action. Accumulating evidence from both human and non-human primate studies, however, challenges this binary distinction and suggests that regions in the dorsal pathway contain object representations that are independent of those in ventral cortex and that play a functional role in object perception. We review here the evidence implicating dorsal object representations, and we propose an account of the anatomical organization, functional contributions, and origins of these representations in the service of perception.

  14. cTBS delivered to the left somatosensory cortex changes its functional connectivity during rest.

    PubMed

    Valchev, Nikola; Ćurčić-Blake, Branislava; Renken, Remco J; Avenanti, Alessio; Keysers, Christian; Gazzola, Valeria; Maurits, Natasha M

    2015-07-01

    The primary somatosensory cortex (SI) plays a critical role in somatosensation as well as in action performance and social cognition. Although the SI has been a major target of experimental and clinical research using non-invasive transcranial magnetic stimulation (TMS), to date information on the effect of TMS over the SI on its resting-state functional connectivity is very scant. Here, we explored whether continuous theta burst stimulation (cTBS), a repetitive TMS protocol, administered over the SI can change the functional connectivity of the brain at rest, as measured using resting-state functional magnetic resonance imaging (rs-fMRI). In a randomized order on two different days we administered active TMS or sham TMS over the left SI. TMS was delivered off-line before scanning by means of cTBS. The target area was selected previously and individually for each subject as the part of the SI activated both when the participant executes and observes actions. Three analytical approaches, both theory driven (partial correlations and seed based whole brain regression) and more data driven (Independent Component Analysis), indicated a reduction in functional connectivity between the stimulated part of the SI and several brain regions functionally associated with the SI including the dorsal premotor cortex, the cerebellum, basal ganglia, and anterior cingulate cortex. These findings highlight the impact of cTBS delivered over the SI on its functional connectivity at rest. Our data may have implications for experimental and therapeutic applications of cTBS over the SI. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Neural evidence for predictive coding in auditory cortex during speech production.

    PubMed

    Okada, Kayoko; Matchin, William; Hickok, Gregory

    2017-04-10

    Recent models of speech production suggest that motor commands generate forward predictions of the auditory consequences of those commands, that these forward predications can be used to monitor and correct speech output, and that this system is hierarchically organized (Hickok, Houde, & Rong, Neuron, 69(3), 407--422, 2011; Pickering & Garrod, Behavior and Brain Sciences, 36(4), 329--347, 2013). Recent psycholinguistic research has shown that internally generated speech (i.e., imagined speech) produces different types of errors than does overt speech (Oppenheim & Dell, Cognition, 106(1), 528--537, 2008; Oppenheim & Dell, Memory & Cognition, 38(8), 1147-1160, 2010). These studies suggest that articulated speech might involve predictive coding at additional levels than imagined speech. The current fMRI experiment investigates neural evidence of predictive coding in speech production. Twenty-four participants from UC Irvine were recruited for the study. Participants were scanned while they were visually presented with a sequence of words that they reproduced in sync with a visual metronome. On each trial, they were cued to either silently articulate the sequence or to imagine the sequence without overt articulation. As expected, silent articulation and imagined speech both engaged a left hemisphere network previously implicated in speech production. A contrast of silent articulation with imagined speech revealed greater activation for articulated speech in inferior frontal cortex, premotor cortex and the insula in the left hemisphere, consistent with greater articulatory load. Although both conditions were silent, this contrast also produced significantly greater activation in auditory cortex in dorsal superior temporal gyrus in both hemispheres. We suggest that these activations reflect forward predictions arising from additional levels of the perceptual/motor hierarchy that are involved in monitoring the intended speech output.

  16. Elemental gesture dynamics are encoded by song premotor cortical neurons.

    PubMed

    Amador, Ana; Perl, Yonatan Sanz; Mindlin, Gabriel B; Margoliash, Daniel

    2013-03-07

    Quantitative biomechanical models can identify control parameters that are used during movements, and movement parameters that are encoded by premotor neurons. We fit a mathematical dynamical systems model including subsyringeal pressure, syringeal biomechanics and upper-vocal-tract filtering to the songs of zebra finches. This reduces the dimensionality of singing dynamics, described as trajectories (motor 'gestures') in a space of syringeal pressure and tension. Here we assess model performance by characterizing the auditory response 'replay' of song premotor HVC neurons to the presentation of song variants in sleeping birds, and by examining HVC activity in singing birds. HVC projection neurons were excited and interneurons were suppressed within a few milliseconds of the extreme time points of the gesture trajectories. Thus, the HVC precisely encodes vocal motor output through activity at the times of extreme points of movement trajectories. We propose that the sequential activity of HVC neurons is used as a 'forward' model, representing the sequence of gestures in song to make predictions on expected behaviour and evaluate feedback.

  17. Continuous Theta-Burst Stimulation Demonstrates a Causal Role of Premotor Homunculus in Action Understanding

    PubMed Central

    Sandberg, Kristian; Skewes, Joshua; Wolf, Thomas; Blicher, Jakob; Overgaard, Morten; Frith, Chris D.

    2014-01-01

    Although it is well established that regions of premotor cortex (PMC) are active during action observation, it remains controversial whether they play a causal role in action understanding. In the experiment reported here, we used off-line continuous theta-burst stimulation (cTBS) to investigate this question. Participants received cTBS over the hand and lip areas of left PMC, in separate sessions, before completing a pantomime-recognition task in which half of the trials contained pantomimed hand actions, and half contained pantomimed mouth actions. The results reveal a double dissociation: Participants were less accurate in recognizing pantomimed hand actions after receiving cTBS over the hand area than over the lip area and less accurate in recognizing pantomimed mouth actions after receiving cTBS over the lip area than over the hand area. This finding constrains theories of action understanding by showing that somatotopically organized regions of PMC contribute causally to action understanding and, thus, that the mechanisms underpinning action understanding and action performance overlap. PMID:24549297

  18. Continuous theta-burst stimulation demonstrates a causal role of premotor homunculus in action understanding.

    PubMed

    Michael, John; Sandberg, Kristian; Skewes, Joshua; Wolf, Thomas; Blicher, Jakob; Overgaard, Morten; Frith, Chris D

    2014-04-01

    Although it is well established that regions of premotor cortex (PMC) are active during action observation, it remains controversial whether they play a causal role in action understanding. In the experiment reported here, we used off-line continuous theta-burst stimulation (cTBS) to investigate this question. Participants received cTBS over the hand and lip areas of left PMC, in separate sessions, before completing a pantomime-recognition task in which half of the trials contained pantomimed hand actions, and half contained pantomimed mouth actions. The results reveal a double dissociation: Participants were less accurate in recognizing pantomimed hand actions after receiving cTBS over the hand area than over the lip area and less accurate in recognizing pantomimed mouth actions after receiving cTBS over the lip area than over the hand area. This finding constrains theories of action understanding by showing that somatotopically organized regions of PMC contribute causally to action understanding and, thus, that the mechanisms underpinning action understanding and action performance overlap.

  19. Ipsilateral corticotectal projections from the primary, premotor and supplementary motor cortical areas in adult macaque monkeys: a quantitative anterograde tracing study.

    PubMed

    Fregosi, Michela; Rouiller, Eric M

    2017-09-18

    The corticotectal projection from cortical motor areas is one of several descending pathways involved in the indirect control of spinal motoneurons. In non-human primates, previous studies reported that cortical projections to the superior colliculus (SC) originated from the premotor cortex (PM) and the primary motor cortex, whereas no projection originated from the supplementary motor area (SMA). The aim of the present study was to investigate and compare the properties of corticotectal projections originating from these three cortical motor areas in intact adult macaques (n = 9). The anterograde tracer biotinylated dextran amine was injected into one of these cortical areas in each animal. Individual axonal boutons, both en passant and terminaux, were charted and counted in the different layers of the ipsilateral SC. The data confirmed the presence of strong corticotectal projections from the PM. A new observation was that strong corticotectal projections were also found to originate from the SMA (its proper division). The corticotectal projection from the primary motor cortex was quantitatively less strong than that from either the premotor or SMAs. The corticotectal projection from each motor area was directed mainly to the deep layer of the SC, although its intermediate layer was also a consistent target of fairly dense terminations. The strong corticotectal projections from non-primary motor areas are in position to influence the preparation and planning of voluntary movements. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  20. Vacillation, indecision and hesitation in moment-by-moment decoding of monkey motor cortex

    PubMed Central

    Kaufman, Matthew T; Churchland, Mark M; Ryu, Stephen I; Shenoy, Krishna V

    2015-01-01

    When choosing actions, we can act decisively, vacillate, or suffer momentary indecision. Studying how individual decisions unfold requires moment-by-moment readouts of brain state. Here we provide such a view from dorsal premotor and primary motor cortex. Two monkeys performed a novel decision task while we recorded from many neurons simultaneously. We found that a decoder trained using ‘forced choices’ (one target viable) was highly reliable when applied to ‘free choices’. However, during free choices internal events formed three categories. Typically, neural activity was consistent with rapid, unwavering choices. Sometimes, though, we observed presumed ‘changes of mind’: the neural state initially reflected one choice before changing to reflect the final choice. Finally, we observed momentary ‘indecision’: delay forming any clear motor plan. Further, moments of neural indecision accompanied moments of behavioral indecision. Together, these results reveal the rich and diverse set of internal events long suspected to occur during free choice. DOI: http://dx.doi.org/10.7554/eLife.04677.001 PMID:25942352

  1. Respiratory Modulation Of Premotor Cardiac Vagal Neurons In The Brainstem

    PubMed Central

    Dergacheva, Olga; Griffioen, Kathleen J.; Neff, Robert A.; Mendelowitz, David

    2010-01-01

    The respiratory and cardiovascular systems are highly intertwined, both anatomically and physiologically. Respiratory and cardiovascular neurons are often co-localized in the same brainstem regions, and this is particularly evident in the ventral medulla which contains pre-sympathetic neurons in the rostral ventrolateral medulla, premotor parasympathetic cardioinhibitory neurons in the nucleus ambiguus, and the ventral respiratory group, which includes the pre-Botzinger complex. Anatomical studies of respiratory and cardiovascular neurons have demonstrated that many of these neurons have projections and axon collateral processes which extend into their neighboring cardiorespiratory regions providing an anatomical substrate for cardiorespiratory interactions. As other reports in this Special Issue of Respiratory Physiology & Neurobiology focus on interactions between the respiratory network and baroreceptors, neurons in the nucleus tractus solitarius, presympathetic neurons and sympathetic activity, this report will focus on the respiratory modulation of parasympathetic activity and the neurons that generate parasympathetic activity to the heart, cardiac vagal neurons. PMID:20452467

  2. Pre-Motor Parkinson’s Disease: Concepts and Definitions

    PubMed Central

    Siderowf, Andrew; Lang, Anthony E.

    2012-01-01

    Parkinson’s disease (PD) has a prodromal phase during which non-motor clinical features as well as physiological abnormalities may be present. These pre-motor markers could be used to screen for PD before motor abnormalities are present. The technology to identify PD before it reaches symptomatic Braak Stage 3 (substantia nigra compacta (SNc) involvement) already exists. The current challenge is to define the appropriate scope of use of predictive testing for PD. Imaging technologies, like dopamine transporter imaging, currently offer the highest degree of accuracy for identifying pre-motor PD, but they are expensive as screening tools and abnormalities on these studies would only be evident at Braak Stage 3 or higher. Efficiency is greatly enhanced by combining imaging with a pre-screening test, such as olfactory testing. This two-step process has the potential to greatly reduce costs while retaining diagnostic accuracy. Alternatively, or in concert with this approach, evaluating high-risk populations (e.g. patients with rapid eye movement behavior disorder (RBD) or LRRK2 mutations) would enrich the sample for cases with underlying PD. Ultimately, the role of pre-clinical detection of PD will be determined by the ability of emerging therapies to influence clinical outcomes. As such, implementation of large-scale screening strategies awaits the arrival of clearly safe and effective therapies that address the underlying pathogenesis of PD. Future research will establish more definitive biomarkers capable of revealing the presence of disease in advance of SNc involvement with the promise of the potential for introducing disease modifying therapy even before the development of evidence for dopamine deficiency. PMID:22508279

  3. Identification of Inhibitory Premotor Interneurons Activated at a Late Phase in a Motor Cycle during Drosophila Larval Locomotion.

    PubMed

    Itakura, Yuki; Kohsaka, Hiroshi; Ohyama, Tomoko; Zlatic, Marta; Pulver, Stefan R; Nose, Akinao

    2015-01-01

    Rhythmic motor patterns underlying many types of locomotion are thought to be produced by central pattern generators (CPGs). Our knowledge of how CPG networks generate motor patterns in complex nervous systems remains incomplete, despite decades of work in a variety of model organisms. Substrate borne locomotion in Drosophila larvae is driven by waves of muscular contraction that propagate through multiple body segments. We use the motor circuitry underlying crawling in larval Drosophila as a model to try to understand how segmentally coordinated rhythmic motor patterns are generated. Whereas muscles, motoneurons and sensory neurons have been well investigated in this system, far less is known about the identities and function of interneurons. Our recent study identified a class of glutamatergic premotor interneurons, PMSIs (period-positive median segmental interneurons), that regulate the speed of locomotion. Here, we report on the identification of a distinct class of glutamatergic premotor interneurons called Glutamatergic Ventro-Lateral Interneurons (GVLIs). We used calcium imaging to search for interneurons that show rhythmic activity and identified GVLIs as interneurons showing wave-like activity during peristalsis. Paired GVLIs were present in each abdominal segment A1-A7 and locally extended an axon towards a dorsal neuropile region, where they formed GRASP-positive putative synaptic contacts with motoneurons. The interneurons expressed vesicular glutamate transporter (vGluT) and thus likely secrete glutamate, a neurotransmitter known to inhibit motoneurons. These anatomical results suggest that GVLIs are premotor interneurons that locally inhibit motoneurons in the same segment. Consistent with this, optogenetic activation of GVLIs with the red-shifted channelrhodopsin, CsChrimson ceased ongoing peristalsis in crawling larvae. Simultaneous calcium imaging of the activity of GVLIs and motoneurons showed that GVLIs' wave-like activity lagged behind that of

  4. Identification of Inhibitory Premotor Interneurons Activated at a Late Phase in a Motor Cycle during Drosophila Larval Locomotion

    PubMed Central

    Itakura, Yuki; Kohsaka, Hiroshi; Ohyama, Tomoko; Zlatic, Marta

    2015-01-01

    Rhythmic motor patterns underlying many types of locomotion are thought to be produced by central pattern generators (CPGs). Our knowledge of how CPG networks generate motor patterns in complex nervous systems remains incomplete, despite decades of work in a variety of model organisms. Substrate borne locomotion in Drosophila larvae is driven by waves of muscular contraction that propagate through multiple body segments. We use the motor circuitry underlying crawling in larval Drosophila as a model to try to understand how segmentally coordinated rhythmic motor patterns are generated. Whereas muscles, motoneurons and sensory neurons have been well investigated in this system, far less is known about the identities and function of interneurons. Our recent study identified a class of glutamatergic premotor interneurons, PMSIs (period-positive median segmental interneurons), that regulate the speed of locomotion. Here, we report on the identification of a distinct class of glutamatergic premotor interneurons called Glutamatergic Ventro-Lateral Interneurons (GVLIs). We used calcium imaging to search for interneurons that show rhythmic activity and identified GVLIs as interneurons showing wave-like activity during peristalsis. Paired GVLIs were present in each abdominal segment A1-A7 and locally extended an axon towards a dorsal neuropile region, where they formed GRASP-positive putative synaptic contacts with motoneurons. The interneurons expressed vesicular glutamate transporter (vGluT) and thus likely secrete glutamate, a neurotransmitter known to inhibit motoneurons. These anatomical results suggest that GVLIs are premotor interneurons that locally inhibit motoneurons in the same segment. Consistent with this, optogenetic activation of GVLIs with the red-shifted channelrhodopsin, CsChrimson ceased ongoing peristalsis in crawling larvae. Simultaneous calcium imaging of the activity of GVLIs and motoneurons showed that GVLIs’ wave-like activity lagged behind that of

  5. Probabilistic Tractography Recovers a Rostrocaudal Trajectory of Connectivity Variability in the Human Insular Cortex

    PubMed Central

    Cerliani, Leonardo; Thomas, Rajat M; Jbabdi, Saad; Siero, Jeroen CW; Nanetti, Luca; Crippa, Alessandro; Gazzola, Valeria; D'Arceuil, Helen; Keysers, Christian

    2012-01-01

    The insular cortex of macaques has a wide spectrum of anatomical connections whose distribution is related to its heterogeneous cytoarchitecture. Although there is evidence of a similar cytoarchitectural arrangement in humans, the anatomical connectivity of the insula in the human brain has not yet been investigated in vivo. In the present work, we used in vivo probabilistic white-matter tractography and Laplacian eigenmaps (LE) to study the variation of connectivity patterns across insular territories in humans. In each subject and hemisphere, we recovered a rostrocaudal trajectory of connectivity variation ranging from the anterior dorsal and ventral insula to the dorsal caudal part of the long insular gyri. LE suggested that regional transitions among tractography patterns in the insula occur more gradually than in other brain regions. In particular, the change in tractography patterns was more gradual in the insula than in the medial premotor region, where a sharp transition between different tractography patterns was found. The recovered trajectory of connectivity variation in the insula suggests a relation between connectivity and cytoarchitecture in humans resembling that previously found in macaques: tractography seeds from the anterior insula were mainly found in limbic and paralimbic regions and in anterior parts of the inferior frontal gyrus, while seeds from caudal insular territories mostly reached parietal and posterior temporal cortices. Regions in the putative dysgranular insula displayed more heterogeneous connectivity patterns, with regional differences related to the proximity with either putative granular or agranular regions. Hum Brain Mapp 33:2005–2034, 2012. © 2011 Wiley Periodicals, Inc. PMID:21761507

  6. That's near my hand! Parietal and premotor coding of hand-centered space contributes to localization and self-attribution of the hand.

    PubMed

    Brozzoli, Claudio; Gentile, Giovanni; Ehrsson, H Henrik

    2012-10-17

    The ability to identify and localize our own limbs is crucial for survival. Indeed, the majority of our interactions with objects occur within the space surrounding the hands. In non-human primates, neurons in the posterior parietal and premotor cortices dynamically represent the space near the upper limbs in hand-centered coordinates. Neuronal populations selective for the space near the hand also exist in humans. It is unclear whether these remap the peri-hand representation as the arm is moved in space. Furthermore, no combined neuronal and behavioral data are available about the possible involvement of peri-hand neurons in the perception of the upper limbs in any species. We used fMRI adaptation to demonstrate dynamic hand-centered encoding of space by reporting response suppression in human premotor and posterior parietal cortices to repeated presentations of an object near the hand for different arm postures. Furthermore, we show that such spatial representation is related to changes in body perception, being remapped onto a prosthetic hand if perceived as one's own during an illusion. Interestingly, our results further suggest that peri-hand space remapping in the premotor cortex is most tightly linked to the subjective feeling of ownership of the seen limb, whereas remapping in the posterior parietal cortex closely reflects changes in the position sense of the arm. These findings identify the neural bases for dynamic hand-centered encoding of peripersonal space in humans and provide hitherto missing evidence for the link between the peri-hand representation of space and the perceived self-attribution and position of the upper limb.

  7. Effects of trains of high-frequency stimulation of the premotor/supplementary motor area on conditioned corticomotor responses in hemicerebellectomized rats.

    PubMed

    Oulad Ben Taib, Nordeyn; Manto, Mario

    2008-07-01

    We studied the effects of low- and high-frequency premotor electrical stimulations on conditioned corticomotor responses, intra-cortical facilitation (ICF) and spinal excitability in hemicerebellectomized rats (left side). Trains of stimulation were applied in prefrontal region rFr2 (the equivalent of the premotor/supplementary motor area in primates) at a rate of 1 Hz (low-frequency stimulation LFS) or 20 Hz (high-frequency stimulation HFS). Test stimuli on the motor cortex were preceded by a conditioning stimulus in contralateral sciatic nerve (two inter-stimulus intervals ISIs were studied: 5 ms or 45 ms). (A) At ISI-5, conditioning increased amplitudes of MEPs (motor evoked potentials) in the left motor cortex. This afferent facilitation was enhanced if preceded by trains of stimuli administered over the ipsilateral rFr2 area, and HFS had higher effects than LFS. The facilitation was lower for the right motor cortex, for both LFS and HFS. (B) At ISI-45, conditioned motor evoked responses were depressed as compared to unconditioned responses in the left motor cortex (afferent inhibition). Following LFS, the degree of inhibition was unchanged while it increased with HFS. At baseline, inhibition was enhanced in the right motor cortex. Interestingly, the afferent inhibition decreased significantly following HFS. (C) ICF was depressed in the right motor cortex, but increased similarly on both sides following LFS/HFS. These results (1) confirm the increased inhibition in the motor cortex contralaterally to the hemicerebellar ablation, (2) demonstrate for the first time that the cerebellum is necessary for tuning amplitudes of corticomotor responses following a peripheral nerve stimulation, (3) show that the application of LFS or HFS does not cancel the defect of excitability in the motor cortex for short ISIs, and (4) suggest that for longer ISIs, HFS could have interesting properties for the modulation of afferent inhibition in case of extensive cerebellar lesion

  8. How does transcranial DC stimulation of the primary motor cortex alter regional neuronal activity in the human brain?

    PubMed

    Lang, Nicolas; Siebner, Hartwig R; Ward, Nick S; Lee, Lucy; Nitsche, Michael A; Paulus, Walter; Rothwell, John C; Lemon, Roger N; Frackowiak, Richard S

    2005-07-01

    Transcranial direct current stimulation (tDCS) of the primary motor hand area (M1) can produce lasting polarity-specific effects on corticospinal excitability and motor learning in humans. In 16 healthy volunteers, O positron emission tomography (PET) of regional cerebral blood flow (rCBF) at rest and during finger movements was used to map lasting changes in regional synaptic activity following 10 min of tDCS (+/-1 mA). Bipolar tDCS was given through electrodes placed over the left M1 and right frontopolar cortex. Eight subjects received anodal or cathodal tDCS of the left M1, respectively. When compared to sham tDCS, anodal and cathodal tDCS induced widespread increases and decreases in rCBF in cortical and subcortical areas. These changes in rCBF were of the same magnitude as task-related rCBF changes during finger movements and remained stable throughout the 50-min period of PET scanning. Relative increases in rCBF after real tDCS compared to sham tDCS were found in the left M1, right frontal pole, right primary sensorimotor cortex and posterior brain regions irrespective of polarity. With the exception of some posterior and ventral areas, anodal tDCS increased rCBF in many cortical and subcortical regions compared to cathodal tDCS. Only the left dorsal premotor cortex demonstrated an increase in movement related activity after cathodal tDCS, however, modest compared with the relatively strong movement-independent effects of tDCS. Otherwise, movement related activity was unaffected by tDCS. Our results indicate that tDCS is an effective means of provoking sustained and widespread changes in regional neuronal activity. The extensive spatial and temporal effects of tDCS need to be taken into account when tDCS is used to modify brain function.

  9. Contribution of LFP dynamics to single-neuron spiking variability in motor cortex during movement execution

    PubMed Central

    Rule, Michael E.; Vargas-Irwin, Carlos; Donoghue, John P.; Truccolo, Wilson

    2015-01-01

    Understanding the sources of variability in single-neuron spiking responses is an important open problem for the theory of neural coding. This variability is thought to result primarily from spontaneous collective dynamics in neuronal networks. Here, we investigate how well collective dynamics reflected in motor cortex local field potentials (LFPs) can account for spiking variability during motor behavior. Neural activity was recorded via microelectrode arrays implanted in ventral and dorsal premotor and primary motor cortices of non-human primates performing naturalistic 3-D reaching and grasping actions. Point process models were used to quantify how well LFP features accounted for spiking variability not explained by the measured 3-D reach and grasp kinematics. LFP features included the instantaneous magnitude, phase and analytic-signal components of narrow band-pass filtered (δ,θ,α,β) LFPs, and analytic signal and amplitude envelope features in higher-frequency bands. Multiband LFP features predicted single-neuron spiking (1ms resolution) with substantial accuracy as assessed via ROC analysis. Notably, however, models including both LFP and kinematics features displayed marginal improvement over kinematics-only models. Furthermore, the small predictive information added by LFP features to kinematic models was redundant to information available in fast-timescale (<100 ms) spiking history. Overall, information in multiband LFP features, although predictive of single-neuron spiking during movement execution, was redundant to information available in movement parameters and spiking history. Our findings suggest that, during movement execution, collective dynamics reflected in motor cortex LFPs primarily relate to sensorimotor processes directly controlling movement output, adding little explanatory power to variability not accounted by movement parameters. PMID:26157365

  10. Evidence for a functional subdivision of Premotor Ear-Eye Field (Area 8B)

    PubMed Central

    Lanzilotto, Marco; Perciavalle, Vincenzo; Lucchetti, Cristina

    2015-01-01

    The Supplementary Eye Field (SEF) and the Frontal Eye Field (FEF) have been described as participating in gaze shift control. Recent evidence suggests, however, that other areas of the dorsomedial prefrontal cortex also influence gaze shift. Herein, we have investigated electrically evoked ear- and eye movements from the Premotor Ear-Eye Field, or PEEF (area 8B) of macaque monkeys. We stimulated PEEF during spontaneous condition (outside the task performance) and during the execution of a visual fixation task (VFT). In the first case, we functionally identified two regions within the PEEF: a core and a belt. In the core region, stimulation elicited forward ear movements; regarding the evoked eye movements, in some penetrations, stimulation elicited contraversive fixed-vectors with a mean amplitude of 5.14°; while in other penetrations, we observed prevalently contralateral goal-directed eye movements having end-points that fell within 15° in respect to the primary eye position. On the contrary, in the belt region, stimulation elicited backward ear movements; regarding the eye movements, in some penetrations stimulation elicited prevalently contralateral goal-directed eye movements having end-points that fell within 15° in respect to the primary eye position, while in the lateral edge of the investigated region, stimulation elicited contralateral goal-directed eye movements having end-points that fell beyond 15° in respect to the primary eye position. Stimulation during VFT either did not elicit eye movements or evoked saccades of only a few degrees. Finally, even though no head rotation movements were observed during the stimulation period, we viewed a relationship between the duration of stimulation and the neck forces exerted by the monkey's head. We propose an updated vision of the PEEF composed of two functional regions, core and belt, which may be involved in integrating auditory and visual information important to the programming of gaze orienting

  11. Recognition and imitation of pantomimed motor acts after unilateral parietal and premotor lesions: a perspective on apraxia.

    PubMed

    Halsband, U; Schmitt, J; Weyers, M; Binkofski, F; Grützner, G; Freund, H J

    2001-01-01

    We compared gesture comprehension and imitation in patients with lesions in the left parietal lobe (LPAR, n=5) and premotor cortex/supplementary motor area (LPMA, n=8) in patients with damage to the right parietal lobe (RPAR, n=6) and right premotor/supplementary motor area (RPMA, n=6) and in 16 non-brain damaged control subjects. Three patients with left parietal lobe damage had aphasia. Subjects were shown 136 meaningful pantomimed motor acts on a videoscreen and were asked to identify the movements and to imitate the motor acts from memory with their ipsilesional and contralesional hand or with both hands simultaneously. Motor tasks included gestures without object use (e.g. to salute, to wave) pantomimed imitation of gestures on one's own body (e.g. to comb one's hair) and pantomimed imitation of motor acts which imply tool use to an object in extrapersonal space (e.g. to hammer a nail). Videotaped test performance was analysed by two independent raters; errors were classified as spatial errors, body part as object, parapraxic performance and non-identifiable movements. In addition, action discrimination was tested by evaluating whether a complex motor sequence was correctly performed. Results indicate that LPAR patients were most severely disturbed when imitation performance was assessed. Interestingly, LPAR patients were worse when imitating gestures on their own bodies than imitating movements with reference to an external object use with most pronounced deficits in the spatial domain. In contrast to imitation, comprehension was not or only slightly disturbed and no clear correlation was found between the severity of imitation deficits and gesture comprehension. Moreover, although the three patients with aphasia imitated the movements more poorly than non-aphasic LPAR patients, the severity of comprehension errors did not differ. Whereas unimanual imitating performance and gesture comprehension of PMA patients did not differ significantly from control

  12. [Non-motor symptoms in premotor phase of Parkinson disease].

    PubMed

    Takahashi, Kazushi

    2013-01-01

    Non-motor symptoms are common in patients with newly diagnosed Parkinson's disease (PD), and some even predate the emergence of the classic motor features. The premotor phase of PD is characterized by several important non-motor features, including constipation, olfactory dysfunction, REM sleep behavior disorder (RBD), depression, etc. The basis of this prodromal stage is that the pathological process related to Lewy bodies, may start outside of the substantia nigra. We investigated 469 Japanese PD patients in our multicenter study, using the Japanese version of the RBD screening questionnaire. Probable RBD was detected in 146 patients (31%) and the RBD symptoms of 53 patients preceded the onset of PD motor symptoms. With the probable exception of RBD, non-motor clinical markers can be sensitive for an impending diagnosis of PD, but these features are common and non-specific. The combination of non-motor clinical markers and more specific markers (e.g., imaging or genetic markers) may achieve sufficient utility in PD diagnosis and prediction in future. Being able to diagnose that a patient has PD at an earlier time point than is currently possible, would be allowed to introduce potential disease-modifying therapies at a time when it could have fundamental and long-lasting effects.

  13. Alcohol consumption and premotor corpus callosum in older adults

    PubMed Central

    Kapogiannis, Dimitrios; Kisser, Jason; Davatzikos, Christos; Ferrucci, Luigi; Metter, Jeffrey; Resnick, Susan

    2012-01-01

    Heavy alcohol consumption is toxic to the brain, especially to the frontal white matter (WM), but whether lesser amounts of alcohol negatively impact the brain WM is unclear. In this study, we examined the relationship between self-reported alcohol consumption and regional WM and grey matter (GM) volume in fifty-six men and thirtyseven women (70 +- 7 years) cognitively intact participants of the Baltimore Longitudinal Study of Aging (BLSA) with no history of alcohol abuse. We used regional analysis of volumes examined in normalized space (RAVENS) maps methodology for WM and GM segmentation and normalization followed by voxel based morphometry statistical parametric mapping (in SPM8) to examine the cross-sectional association between alcohol consumption and WM (and, separately, GM) volume controlling for age, sex, smoking, blood pressure and dietary thiamine intake. WM VBM revealed that in men, but not in women, higher alcohol consumption was associated with lower volume in premotor frontal corpus callosum. This finding suggests that even moderate amounts of alcohol may be detrimental to corpus callosum and white matter integrity. PMID:22401959

  14. A motor cortex circuit for motor planning and movement.

    PubMed

    Li, Nuo; Chen, Tsai-Wen; Guo, Zengcai V; Gerfen, Charles R; Svoboda, Karel

    2015-03-05

    Activity in motor cortex predicts specific movements seconds before they occur, but how this preparatory activity relates to upcoming movements is obscure. We dissected the conversion of preparatory activity to movement within a structured motor cortex circuit. An anterior lateral region of the mouse cortex (a possible homologue of premotor cortex in primates) contains equal proportions of intermingled neurons predicting ipsi- or contralateral movements, yet unilateral inactivation of this cortical region during movement planning disrupts contralateral movements. Using cell-type-specific electrophysiology, cellular imaging and optogenetic perturbation, we show that layer 5 neurons projecting within the cortex have unbiased laterality. Activity with a contralateral population bias arises specifically in layer 5 neurons projecting to the brainstem, and only late during movement planning. These results reveal the transformation of distributed preparatory activity into movement commands within hierarchically organized cortical circuits.

  15. Single-cell coding of sensory, spatial and numerical magnitudes in primate prefrontal, premotor and cingulate motor cortices.

    PubMed

    Eiselt, Anne-Kathrin; Nieder, Andreas

    2016-01-01

    The representation of magnitude information enables humans and animal species alike to successfully interact with the external environment. However, how various types of magnitudes are processed by single neurons to guide goal-directed behavior remains elusive. Here, we recorded single-cell activity from the dorsolateral prefrontal (PFC), dorsal premotor (PMd) and cingulate motor (CMA) cortices in monkeys discriminating discrete numerical (numerosity), continuous spatial (line length) and basic sensory (spatial frequency) stimuli. We found that almost exclusively PFC neurons represented the different magnitude types during sample presentation and working memory periods. The frequency of magnitude-selective cells in PMd and CMA did not exceed chance level. The proportion of PFC neurons selectively tuned to each of the three magnitude types were comparable. Magnitude coding was mainly dissociated at the single-neuron level, with individual neurons representing only one of the three tested magnitude types. Neuronal magnitude discriminability, coding strength and temporal evolution were comparable between magnitude types encoded by PFC neuron populations. Our data highlight the importance of PFC neurons in representing various magnitude categories. Such magnitude representations are based on largely distributed coding by single neurons that are anatomically intermingled within the same cortical area.

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

    PubMed

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

    2014-04-30

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

  17. Calretinin as a Marker for Premotor Neurons Involved in Upgaze in Human Brainstem

    PubMed Central

    Adamczyk, Christopher; Strupp, Michael; Jahn, Klaus; Horn, Anja K. E.

    2015-01-01

    Eye movements are generated by different premotor pathways. Damage to them can cause specific deficits of eye movements, such as saccades. For correlative clinico-anatomical post-mortem studies of cases with eye movement disorders it is essential to identify the functional cell groups of the oculomotor system in the human brain by marker proteins. Based on monkey studies, the premotor neurons of the saccadic system can be identified by the histochemical markers parvalbumin (PAV) and perineuronal nets in humans. These areas involve the interstitial nucleus of Cajal (INC) and the rostral interstitial nucleus of the medial longitudinal fascicle (RIMLF), which both contain premotor neurons for upgaze and downgaze. Recent monkey and human studies revealed a selective excitatory calretinin (CR)-positive input to the motoneurons mediating upgaze, but not to those for downgaze. Three premotor regions were identified as sources of CR input in monkey: y-group, INC and RIMLF. These findings suggest that the expression pattern of parvalbumin and CR may help to identify premotor neurons involved in up- or downgaze. In a post-mortem study of five human cases without neurological diseases we investigated the y-group, INC and RIMLF for the presence of parvalbumin and CR positive neurons including their co-expression. Adjacent thin paraffin sections were stained for the aggrecan (ACAN) component of perineuronal nets, parvalbumin or CR and glutamate decarboxylase. The comparative analysis of scanned thin sections of INC and RIMLF revealed medium-sized parvalbumin positive neurons with and without CR coexpression, which were intermingled. The parvalbumin/CR positive neurons in both nuclei are considered as excitatory premotor upgaze neurons. Accordingly, the parvalbumin-positive neurons lacking CR are considered as premotor downgaze neurons in RIMLF, but may in addition include inhibitory premotor upgaze neurons in the INC as indicated by co-expression of glutamate decarboxylase in a

  18. Motor Neurons Tune Premotor Activity in a Vertebrate Central Pattern Generator.

    PubMed

    Lawton, Kristy J; Perry, Wick M; Yamaguchi, Ayako; Zornik, Erik

    2017-03-22

    Central patterns generators (CPGs) are neural circuits that drive rhythmic motor output without sensory feedback. Vertebrate CPGs are generally believed to operate in a top-down manner in which premotor interneurons activate motor neurons that in turn drive muscles. In contrast, the frog (Xenopus laevis) vocal CPG contains a functionally unexplored neuronal projection from the motor nucleus to the premotor nucleus, indicating a recurrent pathway that may contribute to rhythm generation. In this study, we characterized the function of this bottom-up connection. The X. laevis vocal CPG produces a 50-60 Hz "fast trill" song used by males during courtship. We recorded "fictive vocalizations" in the in vitro CPG from the laryngeal nerve while simultaneously recording premotor activity at the population and single-cell level. We show that transecting the motor-to-premotor projection eliminated the characteristic firing rate of premotor neurons. Silencing motor neurons with the intracellular sodium channel blocker QX-314 also disrupted premotor rhythms, as did blockade of nicotinic synapses in the motor nucleus (the putative location of motor neuron-to-interneuron connections). Electrically stimulating the laryngeal nerve elicited primarily IPSPs in premotor neurons that could be blocked by a nicotinic receptor antagonist. Our results indicate that an inhibitory signal, activated by motor neurons, is required for proper CPG function. To our knowledge, these findings represent the first example of a CPG in which precise premotor rhythms are tuned by motor neuron activity.SIGNIFICANCE STATEMENT Central pattern generators (CPGs) are neural circuits that produce rhythmic behaviors. In vertebrates, motor neurons are not commonly known to contribute to CPG function, with the exception of a few spinal circuits where the functional significance of motor neuron feedback is still poorly understood. The frog hindbrain vocal circuit contains a previously unexplored connection from

  19. Activation of Premotor Vocal Areas during Musical Discrimination

    ERIC Educational Resources Information Center

    Brown, Steven; Martinez, Michael J.

    2007-01-01

    Two same/different discrimination tasks were performed by amateur-musician subjects in this functional magnetic resonance imaging study: Melody Discrimination and Harmony Discrimination. Both tasks led to activations not only in classic working memory areas--such as the cingulate gyrus and dorsolateral prefrontal cortex--but in a series of…

  20. Activation of Premotor Vocal Areas during Musical Discrimination

    ERIC Educational Resources Information Center

    Brown, Steven; Martinez, Michael J.

    2007-01-01

    Two same/different discrimination tasks were performed by amateur-musician subjects in this functional magnetic resonance imaging study: Melody Discrimination and Harmony Discrimination. Both tasks led to activations not only in classic working memory areas--such as the cingulate gyrus and dorsolateral prefrontal cortex--but in a series of…

  1. Functional Connectivity of the Dorsal Striatum in Female Musicians

    PubMed Central

    Tanaka, Shoji; Kirino, Eiji

    2016-01-01

    The dorsal striatum (caudate/putamen) is a node of the cortico-striato-pallido-thalamo-cortical (CSPTC) motor circuit, which plays a central role in skilled motor learning, a critical feature of musical performance. The dorsal striatum receives input from a large part of the cerebral cortex, forming a hub in the cortical-subcortical network. This study sought to examine how the functional network of the dorsal striatum differs between musicians and nonmusicians. Resting state functional magnetic resonance imaging (fMRI) data were acquired from female university students majoring in music and nonmusic disciplines. The data were subjected to functional connectivity analysis and graph theoretical analysis. The functional connectivity analysis indicated that compared with nonmusicians, musicians had significantly decreased connectivity between the left putamen and bilateral frontal operculum (FO) and between the left caudate nucleus and cerebellum. The graph theoretical analysis of the entire brain revealed that the degrees, which represent the numbers of connections, of the bilateral putamen were significantly lower in musicians than in nonmusicians. In conclusion, compared with nonmusicians, female musicians have a smaller functional network of the dorsal striatum with decreased connectivity. These data are consistent with previous anatomical studies reporting a reduced volume of the dorsal striatum in musicians and ballet dancers, suggesting that long-term musical training reshapes the functional network of the dorsal striatum to be less extensive or selective. PMID:27148025

  2. Dorsal spine osteoblastoma

    PubMed Central

    Bhargava, Pranshu; Singh, Rahul; Garg, Bharat B.

    2016-01-01

    Benign osteoblastoma is a rare primary neoplasm comprising less than 1% of primary bone tumors.[1] We report a case of a 20-year-old female patient presenting with progressive paraparesis over one year and back pain over the dorsal spine gradually increasing in severity over a year. Computerised tomomography (CT) of the spine revealed a well-defined 3.5 × 3.0 cm mass heterodense expansile bony lesion arising from the lamina of the D12 vertebra, having lytic and sclerotic component and causing compromise of the bony spinal canal. D12 laminectomy and total excision of the tumor was done. PMID:27057242

  3. α-Synuclein in the colon and premotor markers of Parkinson disease in neurologically normal subjects.

    PubMed

    Kim, Joong-Seok; Park, In-Seok; Park, Hyung-Eun; Kim, Su-Young; Yun, Jung A; Jung, Chan Kwon; Sung, Hye-Young; Lee, Jin-Kwon; Kang, Won-Kyung

    2017-01-01

    Extranigral non-motor signs precede the first motor manifestations of Parkinson's disease by many years in some patients. The presence of α-synuclein deposition within colon tissues in patients with Parkinson's disease can aid in identifying early neuropathological changes prior to disease onset. In the present study, we evaluated the roles of non-motor symptoms and signs and imaging biomarkers of nigral neuronal changes and α-synuclein accumulation in the colon. Twelve subjects undergoing colectomy for primary colon cancer were recruited for this study. Immunohistochemical staining for α-synuclein in normal and phosphorylated forms was performed in normally appearing colonic tissue. We evaluated 16 candidate premotor risk factors in this study cohort. Among them, ten subjects showed positive immunostaining with normal- and phosphorylated-α-synuclein. An accumulation of premotor markers in each subject was accompanied with positive normal- and phosphorylated-α-synuclein immunostaining, ranging from 2 to 7 markers per subject, whereas the absence of Lewy bodies in the colon was associated with relative low numbers of premotor signs. A principal component analysis and a cluster analysis of these premotor markers suggest that urinary symptoms were commonly clustered with deposition of peripheral phosphorylated-α-synuclein. Among other premotor marker, color vision abnormalities were related to non-smoking. This mathematical approach confirmed the clustering of premotor markers in preclinical stage of Parkinson's disease. This is the first report showing that α-synuclein in the colon and other premotor markers are related to each other in neurologically normal subjects.

  4. Dorsal column stimulator applications

    PubMed Central

    Yampolsky, Claudio; Hem, Santiago; Bendersky, Damián

    2012-01-01

    Background: Spinal cord stimulation (SCS) has been used to treat neuropathic pain since 1967. Following that, technological progress, among other advances, helped SCS become an effective tool to reduce pain. Methods: This article is a non-systematic review of the mechanism of action, indications, results, programming parameters, complications, and cost-effectiveness of SCS. Results: In spite of the existence of several studies that try to prove the mechanism of action of SCS, it still remains unknown. The mechanism of action of SCS would be based on the antidromic activation of the dorsal column fibers, which activate the inhibitory interneurons within the dorsal horn. At present, the indications of SCS are being revised constantly, while new applications are being proposed and researched worldwide. Failed back surgery syndrome (FBSS) is the most common indication for SCS, whereas, the complex regional pain syndrome (CRPS) is the second one. Also, this technique is useful in patients with refractory angina and critical limb ischemia, in whom surgical or endovascular treatment cannot be performed. Further indications may be phantom limb pain, chronic intractable pain located in the head, face, neck, or upper extremities, spinal lumbar stenosis in patients who are not surgical candidates, and others. Conclusion: Spinal cord stimulation is a useful tool for neuromodulation, if an accurate patient selection is carried out prior, which should include a trial period. Undoubtedly, this proper selection and a better knowledge of its underlying mechanisms of action, will allow this cutting edge technique to be more acceptable among pain physicians. PMID:23230533

  5. Intrinsic chemosensitivity of rostral ventrolateral medullary sympathetic premotor neurons in the in situ arterially perfused preparation of rats.

    PubMed

    Koganezawa, Tadachika; Paton, Julian F R

    2014-11-01

    Brainstem hypoperfusion is a major excitant of sympathetic activity triggering hypertension, but the exact mechanisms involved remain incompletely understood. A major source of excitatory drive to preganglionic sympathetic neurons originates from the ongoing activity of premotor neurons in the rostral ventrolateral medulla (RVLM sympathetic premotor neurons). The chemosensitivity profile of physiologically characterized RVLM sympathetic premotor neurons during hypoxia and hypercapnia remains unclear. We examined whether physiologically characterized RVLM sympathetic premotor neurons can sense brainstem ischaemia intrinsically. We addressed this issue in a unique in situ arterially perfused preparation before and after a complete blockade of fast excitatory and inhibitory synaptic transmission. During hypercapnic hypoxia, respiratory modulation of RVLM sympathetic premotor neurons was lost, but tonic firing of most RVLM sympathetic premotor neurons was elevated. After blockade of fast excitatory and inhibitory synaptic transmission, RVLM sympathetic premotor neurons continued to fire and exhibited an excitatory firing response to hypoxia but not hypercapnia. This study suggests that RVLM sympathetic premotor neurons can sustain high levels of neuronal discharge when oxygen is scarce. The intrinsic ability of RVLM sympathetic premotor neurons to maintain responsivity to brainstem hypoxia is an important mechanism ensuring adequate arterial pressure, essential for maintaining cerebral perfusion in the face of depressed ventilation and/or high cerebral vascular resistance.

  6. The Dorsal Pallium in Zebrafish, Danio rerio (Cyprinidae, Teleostei)

    PubMed Central

    Mueller, Thomas; Dong, Zhiqiang; Berberoglu, Michael A.; Guo, Su

    2011-01-01

    Zebrafish as a neurogenetic model system depends on the correct neuroanatomical understanding of its brain organization. Here, we address the unresolved question regarding a possible zebrafish homologue of the dorsal pallial division, the region that in mammals gives rise to the isocortex. Analyzing the distributions of nicotine adenine dinucleotide phosphate diphorase (NADPHd) activity and parvalbumin in the anterior zebrafish telencephalon, we show that against previous assumptions the central (Dc) zone possesses its own germinative region in the dorsal proliferative zone. We define the central (Dc) zone as topologically corresponding to the dorsal pallial division of other vertebrates (mammalian isocortex). In addition, we confirm through BrdU-labeling experiments that the posterior (Dp) zone is formed by radial migration and homologous to the mammalian piriform cortex. Based on our results, we propose a new developmental and organizational model of the zebrafish pallium—one which is the result of a complex outward-inward folding. PMID:21219890

  7. The Laryngeal Motor Cortex: Its Organization and Connectivity

    PubMed Central

    Simonyan, Kristina

    2014-01-01

    Our ability to learn and control the motor aspects of complex laryngeal behaviors, such as speech and song, is modulated by the laryngeal motor cortex (LMC), which is situated in the area 4 of the primary motor cortex and establishes both direct and indirect connections with laryngeal motoneurons. In contrast, the LMC in monkeys is located in the area 6 of the premotor cortex, projects only indirectly to laryngeal motoneurons and its destruction has essentially no effect on production of species-specific calls. These differences in cytoarchitectonic location and connectivity may be a result of hominid evolution that led to the LMC shift from the phylogenetically “old” to “new” motor cortex in order to fulfill its paramount function, i.e., voluntary motor control of human speech and song production. PMID:24929930

  8. The laryngeal motor cortex: its organization and connectivity.

    PubMed

    Simonyan, Kristina

    2014-10-01

    Our ability to learn and control the motor aspects of complex laryngeal behaviors, such as speech and song, is modulated by the laryngeal motor cortex (LMC), which is situated in the area 4 of the primary motor cortex and establishes both direct and indirect connections with laryngeal motoneurons. In contrast, the LMC in monkeys is located in the area 6 of the premotor cortex, projects only indirectly to laryngeal motoneurons and its destruction has essentially no effect on production of species-specific calls. These differences in cytoarchitectonic location and connectivity may be a result of hominid evolution that led to the LMC shift from the phylogenetically 'old' to 'new' motor cortex in order to fulfill its paramount function, that is, voluntary motor control of human speech and song production.

  9. Requirement of the auditory association cortex for discrimination of vowel-like sounds in rats.

    PubMed

    Kudoh, Masaharu; Nakayama, Yoko; Hishida, Ryuichi; Shibuki, Katsuei

    2006-11-27

    We investigated the roles of the auditory cortex in discrimination learning of vowel-like sounds consisting of multiple formants. Rats were trained to discriminate between synthetic sounds with four formants. Bilateral electrolytic lesions including the primary auditory cortex and the dorsal auditory association cortex impaired multiformant discrimination, whereas they did not significantly affect discrimination between sounds with a single formant or between pure tones. Local lesions restricted to the dorsal/rostral auditory association cortex were sufficient to attenuate multiformant discrimination learning, and lesions restricted to the primary auditory cortex had no significant effects. These findings indicate that the dorsal/rostral auditory association cortex but not the primary auditory cortex is required for discrimination learning of vowel-like sounds with multiple formants in rats.

  10. Distinct limb and trunk premotor circuits establish laterality in the spinal cord.

    PubMed

    Goetz, Cyrill; Pivetta, Chiara; Arber, Silvia

    2015-01-07

    Movement coordination between opposite body sides relies on neuronal circuits capable of controlling muscle contractions according to motor commands. Trunk and limb muscles engage in distinctly lateralized behaviors, yet how regulatory spinal circuitry differs is less clear. Here, we intersect virus technology and mouse genetics to unravel striking distribution differences of interneurons connected to functionally distinct motor neurons. We find that premotor interneurons conveying information to axial motor neurons reside in symmetrically balanced locations while mostly ipsilateral premotor interneurons synapse with limb-innervating motor neurons, especially those innervating more distal muscles. We show that observed distribution differences reflect specific premotor interneuron subpopulations defined by genetic and neurotransmitter identity. Synaptic input across the midline reaches axial motor neurons preferentially through commissural axon arborization, and to a lesser extent, through midline-crossing dendrites capturing contralateral synaptic input. Together, our findings provide insight into principles of circuit organization underlying weighted lateralization of movement. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Egocentric and allocentric visuospatial working memory in premotor Huntington's disease: A double dissociation with caudate and hippocampal volumes.

    PubMed

    Possin, Katherine L; Kim, Hosung; Geschwind, Michael D; Moskowitz, Tacie; Johnson, Erica T; Sha, Sharon J; Apple, Alexandra; Xu, Duan; Miller, Bruce L; Finkbeiner, Steven; Hess, Christopher P; Kramer, Joel H

    2017-07-01

    Our brains represent spatial information in egocentric (self-based) or allocentric (landmark-based) coordinates. Rodent studies have demonstrated a critical role for the caudate in egocentric navigation and the hippocampus in allocentric navigation. We administered tests of egocentric and allocentric working memory to individuals with premotor Huntington's disease (pmHD), which is associated with early caudate nucleus atrophy, and controls. Each test had 80 trials during which subjects were asked to remember 2 locations over 1-sec delays. The only difference between these otherwise identical tests was that locations could only be coded in self-based or landmark-based coordinates. We applied a multiatlas-based segmentation algorithm and computed point-wise Jacobian determinants to measure regional variations in caudate and hippocampal volumes from 3T MRI. As predicted, the pmHD patients were significantly more impaired on egocentric working memory. Only egocentric accuracy correlated with caudate volumes, specifically the dorsolateral caudate head, right more than left, a region that receives dense efferents from dorsolateral prefrontal cortex. In contrast, only allocentric accuracy correlated with hippocampal volumes, specifically intermediate and posterior regions that connect strongly with parahippocampal and posterior parietal cortices. These results indicate that the distinction between egocentric and allocentric navigation applies to working memory. The dorsolateral caudate is important for egocentric working memory, which can explain the disproportionate impairment in pmHD. Allocentric working memory, in contrast, relies on the hippocampus and is relatively spared in pmHD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. The human lumbar dorsal rami.

    PubMed Central

    Bogduk, N; Wilson, A S; Tynan, W

    1982-01-01

    The L 1-4 dorsal rami tend to form three branches, medial, lateral, and intermediate, which are distributed, respectively, to multifidus, iliocostalis, and longissimus. The intertransversarii mediales are innervated by a branch of the dorsal ramus near the origin of the medial branch. The L 4 dorsal ramus regularly forms three branches while the L 1-3 levels the lateral and intermediate branches may, alternatively, arise from a short common stem. The L 5 dorsal ramus is much longer than the others and forms only a medial and an intermediate branch. Each lumbar medial branch innervates two adjacent zygapophysial joints and ramifies in multifidus, supplying only those fascicles which arise from the spinous process with the same segmental number as the nerve. The comparative anatomy of the lumbar dorsal rami is discussed and the applied anatomy with respect to 'rhizolysis', 'facet denervation' and diagnostic paraspinal electromyography is described. PMID:7076562

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

    PubMed Central

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

    2015-01-01

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

  14. Pointing in visual periphery: is DF's dorsal stream intact?

    PubMed

    Hesse, Constanze; Ball, Keira; Schenk, Thomas

    2014-01-01

    Observations of the visual form agnosic patient DF have been highly influential in establishing the hypothesis that separate processing streams deal with vision for perception (ventral stream) and vision for action (dorsal stream). In this context, DF's preserved ability to perform visually-guided actions has been contrasted with the selective impairment of visuomotor performance in optic ataxia patients suffering from damage to dorsal stream areas. However, the recent finding that DF shows a thinning of the grey matter in the dorsal stream regions of both hemispheres in combination with the observation that her right-handed movements are impaired when they are performed in visual periphery has opened up the possibility that patient DF may potentially also be suffering from optic ataxia. If lesions to the posterior parietal cortex (dorsal stream) are bilateral, pointing and reaching deficits should be observed in both visual hemifields and for both hands when targets are viewed in visual periphery. Here, we tested DF's visuomotor performance when pointing with her left and her right hand toward targets presented in the left and the right visual field at three different visual eccentricities. Our results indicate that DF shows large and consistent impairments in all conditions. These findings imply that DF's dorsal stream atrophies are functionally relevant and hence challenge the idea that patient DF's seemingly normal visuomotor behaviour can be attributed to her intact dorsal stream. Instead, DF seems to be a patient who suffers from combined ventral and dorsal stream damage meaning that a new account is needed to explain why she shows such remarkably normal visuomotor behaviour in a number of tasks and conditions.

  15. Evaluation of net causal influences in the circuit responding to premotor control during the movement-readiness state using conditional Granger causality.

    PubMed

    Wang, Yuqing; Chen, Huafu; Gao, Qing; Yang, Yihong; Gong, Qiyong; Gao, Fabao

    2015-01-21

    As an initialization procedure for brain responding to subsequent movement execution (ME), the movement-readiness (MR) state is important for understanding the formation processes from daily movement training to long-term memory of movement pattern. As such, based on functional magnetic resonance imaging (fMRI), the net causal influences among regions contributing to premotor control during the MR state were explored by means of conditional Granger causality (CGC) and graph-theory methods in the present study. Our results found that net causal circuits responding to unimanual MR were identified during right-hand or left-hand MR, involving in the anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), upper precuneus (UPCU), caudate nucleus (CN), cingulate motor area (CMA), supplementary motor area (SMA) and primary sensorimotor area (S1M1). Moreover, the contralateral CN, SMA and S1M1 revealed greater net causal influences during unimanual MR, which highlighted the contralateral dominant modulations during unimanual MR. Furthermore, according as the graph-theory analysis, the higher In+Out degrees of upper precuneus (UPCU) during right-hand MR or higher In+Out degrees of cingulate motor area (CMA) and posterior cingulate cortex (PCC) during left-hand MR implied the brain asymmetry of causal connectivity in the circuit responding to right-hand or left-hand MR. This article is part of a Special Issue entitled SI: Brain and Memory.

  16. Dorsal Capsuloplasty for Dorsal Instability of the Distal Ulna

    PubMed Central

    Kouwenhoven, S.T.P.; de Jong, T.; Koch, A.R.

    2013-01-01

    Background Dorsal instability of the distal ulna can lead to chronic wrist pain and loss of function. Structural changes to the dorsal radioulnar ligaments (DRUL) of the triangular fibrocartilage complex (TFCC) and the dorsal capsule around the ulnar head with or without foveal detachment can lead to volar subluxation of the distal radius e.g., dorsal instability of the distal ulna. Purpose Is to evaluate the post-operative results of reinstituting distal radioulnar joint (DRUJ) stability through reefing of the dorsal capsule and dorsal radioulnar ligaments, with and without a foveal reattachment of the TFCC. Methods A total of 37 patients were included in this retrospective study. Diagnosis and treatment was based strictly on dry wrist arthroscopy. In 17 patients isolated reefing of the DRUL and their collateral tissue extension was performed. In 20 patients an additional foveal reinsertion was performed. Postoperative results were evaluated with the DASH questionnaire, VAS scores, grip strength and range of motion. These findings were extrapolated in the Mayo wrist score. The two subgroups were compared. Results Mayo wrist scores of the whole population had a mean of 73. There was no difference between the group that was treated with reefing of the DRUL only and the group that was treated with a combined foveal reinsertion. Conclusion This relatively simple 'dorsal reefing' procedure, with foveal reinsertion when indicated, is a reliable method to restore volar-dorsal DRUJ stability with a significant decrease in pain sensation, good DASH scores and restoration of functional grip strength and ROM. Type of Study/Level of Evidence Therapeutic, Level IV. PMID:24436811

  17. Here, there and everywhere: higher visual function and the dorsal visual stream.

    PubMed

    Cooper, Sarah Anne; O'Sullivan, Michael

    2016-06-01

    The dorsal visual stream, often referred to as the 'where' stream, represents the pathway taken by visual information from the primary visual cortex to the posterior parietal lobe and onwards. It partners the ventral or 'what' stream, the subject of a previous review and largely a temporal-based system. Here, we consider the dorsal stream disorders of perception (simultanagnosia, akinetopsia) along with their consequences on action (eg, optic ataxia and oculomotor apraxia, along with Balint's syndrome). The role of the dorsal stream in blindsight and hemispatial neglect is also considered.

  18. fMRI of Intrasubject Variability in ADHD: Anomalous Premotor Activity with Prefrontal Compensation

    ERIC Educational Resources Information Center

    Suskauer, Stacy J.; Simmonds, Daniel J.; Caffo, Brian S.; Denckla, Martha B.; Pekar, James J.; Mostofsky, Stewart H.

    2008-01-01

    Neural correlates of intrasubject variability (ISV) were studied using functional magnetic resonance imaging in 25 children with attention-deficit/hyperactivity disorder (ADHD) and typically developing(TD) children performing simple go/no-go tasks. Results concluded that in children with ADHD, dysfunction of premotor systems resulted in increased…

  19. Decoding of finger, hand and arm kinematics using switching linear dynamical systems with pre-motor cortical ensembles.

    PubMed

    Kang, Xiaoxu; Schieber, Marc H; Thakor, Nitish V

    2012-01-01

    Previous works in Brain-Machine Interfaces (BMI) have mostly used a single Kalman filter decoder for deriving continuous kinematics in the complete execution of behavioral tasks. A linear dynamical system may not be able to generalize the sequence whose dynamics changes over time. Examples of such data include human motion such as walking, running, and dancing each of which exhibit complex constantly evolving dynamics. Switching linear dynamical systems (S-LDSs) are powerful models capable of describing a physical process governed by state equations that switch from time to time. The present work demonstrates the motion-state-dependent adaptive decoding of hand and arm kinematics in four different behavioral tasks. Single-unit neural activities were recorded from cortical ensembles in the ventral and dorsal premotor (PMv and PMd) areas of a trained rhesus monkey during four different reach-to-grasp tasks. We constructed S-LDSs for decoding of continuous hand and arm kinematics based on different epochs of the experiments, namely, baseline, pre-movement planning, movement, and final fixation. Average decoding accuracies as high as 89.9%, 88.6%, 89.8%, 89.4%, were achieved for motion-state-dependent decoding across four different behavioral tasks, respectively (p<0.05); these results are higher than previous works using a single Kalman filter (accuracy: 0.83). These results demonstrate that the adaptive decoding approach, or motion-state-dependent decoding, may have a larger descriptive capability than the decoding approach using a single decoder. This is a critical step towards the development of a BMI for adaptive neural control of a clinically viable prosthesis.

  20. Differential grey matter changes in sensorimotor cortex related to exceptional fine motor skills.

    PubMed

    Stoeckel, M Cornelia; Morgenroth, Farina; Buetefisch, Cathrin M; Seitz, Rüdiger J

    2012-01-01

    Functional changes in sensorimotor representation occur in response to use and lesion throughout life. Emerging evidence suggests that functional changes are paralleled by respective macroscopic structural changes. In the present study we used voxel-based morphometry to investigate sensorimotor cortex in subjects with congenitally malformed upper extremities. We expected increased or decreased grey matter to parallel the enlarged or reduced functional representations we reported previously. More specifically, we expected decreased grey matter values in lateral sensorimotor cortex related to compromised hand function and increased grey matter values in medial sensorimotor cortex due to compensatory foot use. We found a medial cluster of grey matter increase in subjects with frequent, hand-like compensatory foot use. This increase was predominantly seen for lateral premotor, supplementary motor, and motor areas and only marginally involved somatosensory cortex. Contrary to our expectation, subjects with a reduced number of fingers, who had shown shrinkage of the functional hand representation previously, did not show decreased grey matter values within lateral sensorimotor cortex. Our data suggest that functional plastic changes in sensorimotor cortex can be associated with increases in grey matter but may also occur in otherwise macroscopically normal appearing grey matter volumes. Furthermore, macroscopic structural changes in motor and premotor areas may be observed without respective changes in somatosensory cortex.

  1. Education and risk of incident dementia during the premotor and motor phases of essential tremor (NEDICES).

    PubMed

    Benito-León, Julián; Contador, Israel; Louis, Elan D; Cosentino, Stephanie; Bermejo-Pareja, Félix

    2016-08-01

    Individuals with late-onset essential tremor (ET) (e.g., older adults) seem to have an increased prevalence of mild cognitive impairment and dementia, and a higher risk of incident dementia. It is well-known that education has a protective role against dementia in individuals without a pre-existing neurologic disorder, but evidence regarding the maintenance of this effect during the premotor and motor phases of ET is unknown. Our aim was to determine the influence of education on the risk of dementia in a population-based cohort of ET patients and controls. In a prospective study (Neurological Disorders in Central Spain), participants ≥65 years old were evaluated twice: at baseline (1994-1995) and at follow-up (1997-1998). There were 3 groups: premotor (i.e., participants first diagnosed with incident ET at follow-up), prevalent ET (i.e., participants diagnosed with ET at baseline and at follow-up), and controls. Participants were stratified into lower education (≤primary studies) versus higher education (≥secondary studies) categories. Dementia risk was estimated using Cox proportional-hazards models (higher education control group = reference category). Among the participants, 3878 had a mean duration of follow-up of 3.2 years. Eight (16.7%) of 48 lower education premotor ET patients developed incident dementia versus 1 (3.3%) of 30 higher education premotor ET patients, 9 (7.1%) of 126 lower education prevalent ET patients, 7 (8.8%) of 80 higher education prevalent ET patients, and 92 (4.9%) of 1892 lower education controls (P < 0.001). In comparison to the higher education controls, the adjusted hazard ratios for incident dementia were 5.84 (lower education premotor ET, P < 0.001); 1.36 (higher education premotor ET, P = 0.76); 2.13 (lower education prevalent ET, P = 0.04); 2.79 (higher education prevalent ET, P = 0.01); and 1.66 (lower education controls, P = 0.01). Our results suggest that a higher educational attainment may ameliorate the risk

  2. Education and risk of incident dementia during the premotor and motor phases of essential tremor (NEDICES)

    PubMed Central

    Benito-León, Julián; Contador, Israel; Louis, Elan D.; Cosentino, Stephanie; Bermejo-Pareja, Félix

    2016-01-01

    Abstract Individuals with late-onset essential tremor (ET) (e.g., older adults) seem to have an increased prevalence of mild cognitive impairment and dementia, and a higher risk of incident dementia. It is well-known that education has a protective role against dementia in individuals without a pre-existing neurologic disorder, but evidence regarding the maintenance of this effect during the premotor and motor phases of ET is unknown. Our aim was to determine the influence of education on the risk of dementia in a population-based cohort of ET patients and controls. In a prospective study (Neurological Disorders in Central Spain), participants ≥65 years old were evaluated twice: at baseline (1994–1995) and at follow-up (1997–1998). There were 3 groups: premotor (i.e., participants first diagnosed with incident ET at follow-up), prevalent ET (i.e., participants diagnosed with ET at baseline and at follow-up), and controls. Participants were stratified into lower education (≤primary studies) versus higher education (≥secondary studies) categories. Dementia risk was estimated using Cox proportional-hazards models (higher education control group = reference category). Among the participants, 3878 had a mean duration of follow-up of 3.2 years. Eight (16.7%) of 48 lower education premotor ET patients developed incident dementia versus 1 (3.3%) of 30 higher education premotor ET patients, 9 (7.1%) of 126 lower education prevalent ET patients, 7 (8.8%) of 80 higher education prevalent ET patients, and 92 (4.9%) of 1892 lower education controls (P < 0.001). In comparison to the higher education controls, the adjusted hazard ratios for incident dementia were 5.84 (lower education premotor ET, P < 0.001); 1.36 (higher education premotor ET, P = 0.76); 2.13 (lower education prevalent ET, P = 0.04); 2.79 (higher education prevalent ET, P = 0.01); and 1.66 (lower education controls, P = 0.01). Our results suggest that a higher educational attainment may

  3. Individual Differences in Premotor Brain Systems Underlie Behavioral Apathy.

    PubMed

    Bonnelle, Valerie; Manohar, Sanjay; Behrens, Tim; Husain, Masud

    2016-02-01

    Lack of physical engagement, productivity, and initiative-so-called "behavioral apathy"--is a common problem with significant impact, both personal and economic. Here, we investigate whether there might be a biological basis to such lack of motivation using a new effort and reward-based decision-making paradigm, combined with functional and diffusion-weighted imaging. We hypothesized that behavioral apathy in otherwise healthy people might be associated with differences in brain systems underlying either motivation to act (specifically in effort and reward-based decision-making) or in action processing (transformation of an intention into action). The results demonstrate that behavioral apathy is associated with increased effort sensitivity as well as greater recruitment of neural systems involved in action anticipation: supplementary motor area (SMA) and cingulate motor zones. In addition, decreased structural and functional connectivity between anterior cingulate cortex (ACC) and SMA were associated with increased behavioral apathy. These findings reveal that effort sensitivity and translation of intentions into actions might make a critical contribution to behavioral apathy. We propose a mechanism whereby inefficient communication between ACC and SMA might lead to increased physiological cost--and greater effort sensitivity--for action initiation in more apathetic people.

  4. Individual Differences in Premotor Brain Systems Underlie Behavioral Apathy

    PubMed Central

    Bonnelle, Valerie; Manohar, Sanjay; Behrens, Tim; Husain, Masud

    2016-01-01

    Lack of physical engagement, productivity, and initiative—so-called “behavioral apathy”—is a common problem with significant impact, both personal and economic. Here, we investigate whether there might be a biological basis to such lack of motivation using a new effort and reward-based decision-making paradigm, combined with functional and diffusion-weighted imaging. We hypothesized that behavioral apathy in otherwise healthy people might be associated with differences in brain systems underlying either motivation to act (specifically in effort and reward-based decision-making) or in action processing (transformation of an intention into action). The results demonstrate that behavioral apathy is associated with increased effort sensitivity as well as greater recruitment of neural systems involved in action anticipation: supplementary motor area (SMA) and cingulate motor zones. In addition, decreased structural and functional connectivity between anterior cingulate cortex (ACC) and SMA were associated with increased behavioral apathy. These findings reveal that effort sensitivity and translation of intentions into actions might make a critical contribution to behavioral apathy. We propose a mechanism whereby inefficient communication between ACC and SMA might lead to increased physiological cost—and greater effort sensitivity—for action initiation in more apathetic people. PMID:26564255

  5. Subspecialization in the human posterior medial cortex

    PubMed Central

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

    2014-01-01

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

  6. Subspecialization in the human posterior medial cortex.

    PubMed

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

    2015-02-01

    The posterior medial cortex (PMC) is particularly poorly understood. Its neural activity changes have been related to highly disparate mental processes. We therefore investigated PMC properties with a data-driven exploratory approach. First, we subdivided the PMC by whole-brain coactivation profiles. Second, functional connectivity of the ensuing PMC regions was compared by task-constrained meta-analytic coactivation mapping (MACM) and task-unconstrained resting-state correlations (RSFC). Third, PMC regions were functionally described by forward/reverse functional inference. A precuneal cluster was mostly connected to the intraparietal sulcus, frontal eye fields, and right temporo-parietal junction; associated with attention and motor tasks. A ventral posterior cingulate cortex (PCC) cluster was mostly connected to the ventromedial prefrontal cortex and middle left inferior parietal cortex (IPC); associated with facial appraisal and language tasks. A dorsal PCC cluster was mostly connected to the dorsomedial prefrontal cortex, anterior/posterior IPC, posterior midcingulate cortex, and left dorsolateral prefrontal cortex; associated with delay discounting. A cluster in the retrosplenial cortex was mostly connected to the anterior thalamus and hippocampus. Furthermore, all PMC clusters were congruently coupled with the default mode network according to task-unconstrained but not task-constrained connectivity. We thus identified distinct regions in the PMC and characterized their neural networks and functional implications. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. The microstructural border between the motor and the cognitive domain in the human cerebral cortex.

    PubMed

    Geyer, S

    2004-01-01

    When we voluntarily interact with our environment, the agranular frontal cortex (Brodmann's areas 4 and 6) plays a pivotal role in cortical motor control. The primary motor cortex (area 4) influences kinematic and dynamic parameters of movements, whereas the rostrally adjoining nonprimary motor cortex (area 6) uses external (e.g., sensory) or internal cues to trigger and guide movements. Once thought to be homogeneous, data from nonhuman primates have shown that area 6 is a mosaic of areas, each with distinct structural and functional properties: the supplementary motor areas "SMA proper" and "pre-SMA" on the mesial cortical surface, and the dorso- and ventrolateral premotor cortex on the cortical convexity. Dorso- and ventrolateral premotor areas are specifically connected with posterior parietal areas. These parieto-frontal circuits work in parallel and tranform different aspects of sensory information into appropriate motor commands. The rostral border of area 6 is very important for functional neuroimaging studies in humans since it separates the "motor domain" of the supplementary motor/premotor cortex from the "cognitive domain" of the prefrontal cortex. Can the topography of this border be inferred from the gyral pattern of the frontal lobe? To answer this, ten postmorterm brains were scanned with a T1-weighted magnetic resonance sequence. The brains were serially sectioned at 20 micro M and area 6 was defined by subjective and objective cytoarchitectonic analysis. Each brain's histological volume (with the representation of area 6) was reconstructed in 3-D and spatially normalized to the reference brain of a computerized atlas. The ten normalized volumes were superimposed and a population map was generated that describes, for each voxel, how many brains have a representation of area 6. On the mesial coetical surface, the rostral border of area 6 lies rostral to the anterior commissure-- though the distance varies across different brains. On the lateral

  8. Differential activation of the dorsal striatum by high-calorie visual food stimuli in obese individuals.

    PubMed

    Rothemund, Yvonne; Preuschhof, Claudia; Bohner, Georg; Bauknecht, Hans-Christian; Klingebiel, Randolf; Flor, Herta; Klapp, Burghard F

    2007-08-15

    The neural systems regulating food intake in obese individuals remain poorly understood. Previous studies applied positron emission tomography and manipulated hunger and satiety to investigate differences in appetitive processing between obese and normal-weight individuals. However, it is not known whether manipulation of stimulus value may yield different neural activity in obese as compared to control subjects when intrinsic physiological states are kept constant. We used functional magnetic resonance imaging to investigate 13 obese and 13 normal-weight subjects and manipulated food motivation by presenting visual food stimuli differing in their caloric content and energy density. In contrast to controls, obese women selectively activated the dorsal striatum while viewing high-caloric foods. Moreover, in the high-calorie condition body mass index (BMI) predicted activation in the dorsal striatum, anterior insula, claustrum, posterior cingulate, postcentral and lateral orbitofrontal cortex. The results indicate that in obese individuals simple visual stimulation with food stimuli activates regions related to reward anticipation and habit learning (dorsal striatum). Additionally, high-calorie food images yielded BMI-dependent activations in regions associated with taste information processing (anterior insula and lateral orbitofrontal cortex), motivation (orbitofrontal cortex), emotion as well as memory functions (posterior cingulate). Collectively, the results suggest that the observed activation is independent of the physiological states of hunger and satiation, and thus may contribute to pathological overeating and obesity. Some of the observed activations (dorsal striatum, orbitofrontal cortex) are likely to be dopamine-mediated.

  9. Serum BDNF correlates with connectivity in the (pre)motor hub in the aging human brain--a resting-state fMRI pilot study.

    PubMed

    Mueller, Karsten; Arelin, Katrin; Möller, Harald E; Sacher, Julia; Kratzsch, Jürgen; Luck, Tobias; Riedel-Heller, Steffi; Villringer, Arno; Schroeter, Matthias L

    2016-02-01

    Brain-derived neurotrophic factor (BDNF) has been discussed to be involved in plasticity processes in the human brain, in particular during aging. Recently, aging and its (neurodegenerative) diseases have increasingly been conceptualized as disconnection syndromes. Here, connectivity changes in neural networks (the connectome) are suggested to be the most relevant and characteristic features for such processes or diseases. To further elucidate the impact of aging on neural networks, we investigated the interaction between plasticity processes, brain connectivity, and healthy aging by measuring levels of serum BDNF and resting-state fMRI data in 25 young (mean age 24.8 ± 2.7 (SD) years) and 23 old healthy participants (mean age, 68.6 ± 4.1 years). To identify neural hubs most essentially related to serum BDNF, we applied graph theory approaches, namely the new data-driven and parameter-free approach eigenvector centrality (EC) mapping. The analysis revealed a positive correlation between serum BDNF and EC in the premotor and motor cortex in older participants in contrast to young volunteers, where we did not detect any association. This positive relationship between serum BDNF and EC appears to be specific for older adults. Our results might indicate that the amount of physical activity and learning capacities, leading to higher BDNF levels, increases brain connectivity in (pre)motor areas in healthy aging in agreement with rodent animal studies. Pilot results have to be replicated in a larger sample including behavioral data to disentangle the cause for the relationship between BDNF levels and connectivity. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Pre-Motor Response Time Benefits in Multi-Modal Displays

    DTIC Science & Technology

    2013-11-12

    equivalent visual representations of these same messages. Results indicated that there was a performance benefit for concurrent message presentations...public release; distribution is unlimited. Pre-Motor Response Time Benefits in Multi-Modal Displays The views, opinions and/or findings contained in this...Time Benefits in Multi-Modal Displays Report Title The present series of experiments testes the assimilation and efficacy of purpose-created tactile

  11. Multifunctional laryngeal premotor neurons: their activities during breathing, coughing, sneezing, and swallowing.

    PubMed

    Shiba, Keisuke; Nakazawa, Ken; Ono, Kenichi; Umezaki, Toshiro

    2007-05-09

    To examine whether motor commands of two or more distinct laryngeal motor patterns converge onto a common premotor network, we conducted dual recordings from the laryngeal adductor motoneuron and its premotor neuron within the brainstem respiratory circuitry during fictive breathing, coughing, sneezing, and swallowing in decerebrate paralyzed cats. Expiratory neurons with an augmenting firing pattern (EAUG), whose action potentials evoked monosynaptic IPSPs in the adductor motoneurons, sharply fired during the expulsive phases of fictive coughing and sneezing, during which the adductor motoneurons transiently repolarized. In contrast, these premotor neurons were silent during the swallow-related hyperpolarization in adductor motoneurons. These results show that one class of medullary respiratory neuron, EAUG, is multifunctional and shared among the central pattern generators (CPGs) for breathing, coughing, and sneezing. In addition, although the CPGs underlying these three behaviors and the swallowing CPG do overlap, EAUG neurons are not part of the swallowing CPG and, in contrast to the other three behaviors, are not a source of inhibitory input to adductor motoneurons during swallowing.

  12. Who Can Diagnose Parkinson's Disease First? Role of Pre-motor Symptoms.

    PubMed

    Rodríguez-Violante, Mayela; Zerón-Martínez, Rosalía; Cervantes-Arriaga, Amin; Corona, Teresa

    2017-09-04

    In 1817, James Parkinson described the disease which bears his name. The disease was defined as a neurological syndrome characterized by tremor, rigidity, and slowness of movements. Almost one hundred years later, degeneration of neurons in the substantia nigra and low levels of dopamine were identified as the putative cause of the disease, thus the disease remained as a pure neurological disorder. In the late 1990s, non-motor symptoms of the disease began to gain interest because of their clinical relevance, as well as for their potential role in broadening the understanding of the pathophysiological mechanisms involved. In the last decade, focus has shifted to the pre-motor symptoms, those non-motor symptoms that present years before the motor onset of the disease. The main premotor symptoms include rapid eye movement sleep behavior disorder, hyposmia, constipation and depression. Subjects with these symptoms usually are not initially seen by a neurologist, and by the time they are consulted neuronal loss in the substantia nigra is over 50%. This review summarizes the overall relevance of non-motor symptoms, their frequency and their pathophysiological implications. Also, the importance of pre-motor symptoms, and the role of specialists other than neurologists in diagnosing subjects with Parkinson's disease is discussed. Two hundred years after the first description of the disease, it is now evident that Parkinson's disease is a systemic disease and a multispecialty team approach is mandatory. Copyright © 2017 IMSS. Published by Elsevier Inc. All rights reserved.

  13. Functional Evidence for a Cerebellar Node of the Dorsal Attention Network.

    PubMed

    Brissenden, James A; Levin, Emily J; Osher, David E; Halko, Mark A; Somers, David C

    2016-06-01

    The "dorsal attention network" or "frontoparietal network" refers to a network of cortical regions that support sustained attention and working memory. Recent work has demonstrated that cortical nodes of the dorsal attention network possess intrinsic functional connections with a region in ventral cerebellum, in the vicinity of lobules VII/VIII. Here, we performed a series of task-based and resting-state fMRI experiments to investigate cerebellar participation in the dorsal attention network in humans. We observed that visual working memory and visual attention tasks robustly recruit cerebellar lobules VIIb and VIIIa, in addition to canonical cortical dorsal attention network regions. Across the cerebellum, resting-state functional connectivity with the cortical dorsal attention network strongly predicted the level of activation produced by attention and working memory tasks. Critically, cerebellar voxels that were most strongly connected with the dorsal attention network selectively exhibited load-dependent activity, a hallmark of the neural structures that support visual working memory. Finally, we examined intrinsic functional connectivity between task-responsive portions of cerebellar lobules VIIb/VIIIa and cortex. Cerebellum-to-cortex functional connectivity strongly predicted the pattern of cortical activation during task performance. Moreover, resting-state connectivity patterns revealed that cerebellar lobules VIIb/VIIIa group with cortical nodes of the dorsal attention network. This evidence leads us to conclude that the conceptualization of the dorsal attention network should be expanded to include cerebellar lobules VIIb/VIIIa. The functional participation of cerebellar structures in nonmotor cortical networks remains poorly understood and is highly understudied, despite the fact that the cerebellum possesses many more neurons than the cerebral cortex. Although visual attention paradigms have been reported to activate cerebellum, many researchers have

  14. Functional Evidence for a Cerebellar Node of the Dorsal Attention Network

    PubMed Central

    Brissenden, James A.; Levin, Emily J.; Osher, David E.; Halko, Mark A.

    2016-01-01

    The “dorsal attention network” or “frontoparietal network” refers to a network of cortical regions that support sustained attention and working memory. Recent work has demonstrated that cortical nodes of the dorsal attention network possess intrinsic functional connections with a region in ventral cerebellum, in the vicinity of lobules VII/VIII. Here, we performed a series of task-based and resting-state fMRI experiments to investigate cerebellar participation in the dorsal attention network in humans. We observed that visual working memory and visual attention tasks robustly recruit cerebellar lobules VIIb and VIIIa, in addition to canonical cortical dorsal attention network regions. Across the cerebellum, resting-state functional connectivity with the cortical dorsal attention network strongly predicted the level of activation produced by attention and working memory tasks. Critically, cerebellar voxels that were most strongly connected with the dorsal attention network selectively exhibited load-dependent activity, a hallmark of the neural structures that support visual working memory. Finally, we examined intrinsic functional connectivity between task-responsive portions of cerebellar lobules VIIb/VIIIa and cortex. Cerebellum-to-cortex functional connectivity strongly predicted the pattern of cortical activation during task performance. Moreover, resting-state connectivity patterns revealed that cerebellar lobules VIIb/VIIIa group with cortical nodes of the dorsal attention network. This evidence leads us to conclude that the conceptualization of the dorsal attention network should be expanded to include cerebellar lobules VIIb/VIIIa. SIGNIFICANCE STATEMENT The functional participation of cerebellar structures in nonmotor cortical networks remains poorly understood and is highly understudied, despite the fact that the cerebellum possesses many more neurons than the cerebral cortex. Although visual attention paradigms have been reported to activate

  15. Implications of starvation-induced change in right dorsal anterior cingulate volume in anorexia nervosa.

    PubMed

    McCormick, Laurie M; Keel, Pamela K; Brumm, Michael C; Bowers, Wayne; Swayze, Victor; Andersen, Arnold; Andreasen, Nancy

    2008-11-01

    Converging evidence suggests a role for the anterior cingulate cortex (ACC) in the pathophysiology of anorexia nervosa (AN). This study sought to determine whether ACC volume was affected by starvation in active AN and, if so, whether this had any clinical significance. Eighteen patients with active AN and age- and gender-matched normal controls underwent magnetic resonance imaging (MRI). Sixteen patients (89%) with AN had intelligence quotients (IQ) testing at intake, 14 (78%) had repeat MRIs after weight normalization, and 10 (56%) had outcome data at 1-year posthospitalization. Right dorsal ACC volume was significantly reduced in active AN patients versus controls and was correlated with lower performance IQ. While ACC normalization occurred with weight restoration, smaller change in right dorsal ACC volume prospectively predicted relapse after treatment. Reduced right dorsal ACC volume during active AN relates to deficits in perceptual organization and conceptual reasoning. The degree of right dorsal ACC normalization during treatment is related to outcome.

  16. Structural development and dorsoventral maturation of the medial entorhinal cortex.

    PubMed

    Ray, Saikat; Brecht, Michael

    2016-04-02

    We investigated the structural development of superficial-layers of medial entorhinal cortex and parasubiculum in rats. The grid-layout and cholinergic-innervation of calbindin-positive pyramidal-cells in layer-2 emerged around birth while reelin-positive stellate-cells were scattered throughout development. Layer-3 and parasubiculum neurons had a transient calbindin-expression, which declined with age. Early postnatally, layer-2 pyramidal but not stellate-cells co-localized with doublecortin - a marker of immature neurons - suggesting delayed functional-maturation of pyramidal-cells. Three observations indicated a dorsal-to-ventral maturation of entorhinal cortex and parasubiculum: (i) calbindin-expression in layer-3 neurons decreased progressively from dorsal-to-ventral, (ii) doublecortin in layer-2 calbindin-positive-patches disappeared dorsally before ventrally, and (iii) wolframin-expression emerged earlier in dorsal than ventral parasubiculum. The early appearance of calbindin-pyramidal-grid-organization in layer-2 suggests that this pattern is instructed by genetic information rather than experience. Superficial-layer-microcircuits mature earlier in dorsal entorhinal cortex, where small spatial-scales are represented. Maturation of ventral-entorhinal-microcircuits - representing larger spatial-scales - follows later around the onset of exploratory behavior.

  17. Structural development and dorsoventral maturation of the medial entorhinal cortex

    PubMed Central

    Ray, Saikat; Brecht, Michael

    2016-01-01

    We investigated the structural development of superficial-layers of medial entorhinal cortex and parasubiculum in rats. The grid-layout and cholinergic-innervation of calbindin-positive pyramidal-cells in layer-2 emerged around birth while reelin-positive stellate-cells were scattered throughout development. Layer-3 and parasubiculum neurons had a transient calbindin-expression, which declined with age. Early postnatally, layer-2 pyramidal but not stellate-cells co-localized with doublecortin – a marker of immature neurons – suggesting delayed functional-maturation of pyramidal-cells. Three observations indicated a dorsal-to-ventral maturation of entorhinal cortex and parasubiculum: (i) calbindin-expression in layer-3 neurons decreased progressively from dorsal-to-ventral, (ii) doublecortin in layer-2 calbindin-positive-patches disappeared dorsally before ventrally, and (iii) wolframin-expression emerged earlier in dorsal than ventral parasubiculum. The early appearance of calbindin-pyramidal-grid-organization in layer-2 suggests that this pattern is instructed by genetic information rather than experience. Superficial-layer-microcircuits mature earlier in dorsal entorhinal cortex, where small spatial-scales are represented. Maturation of ventral-entorhinal-microcircuits – representing larger spatial-scales – follows later around the onset of exploratory behavior. DOI: http://dx.doi.org/10.7554/eLife.13343.001 PMID:27036175

  18. Intermodal attention modulates visual processing in dorsal and ventral streams.

    PubMed

    Cate, A D; Herron, T J; Kang, X; Yund, E W; Woods, D L

    2012-11-15

    Attending to visual objects while ignoring information from other modalities is necessary for performing difficult visual discriminations, but it is unclear how selecting between sensory modalities alters processing within the visual system. We used an audio-visual intermodal selective attention paradigm with fMRI to study the effects of visual attention on cortical activity in the absence of competitive interactions between multiple visual stimuli. Complex stimuli (faces and words) activated higher visual areas even in the absence of visual attention. These stimulus-dependent activations (SDAs) covered foveal retinotopic cortex, extended ventrally to the anterior fusiform gyrus and dorsally to include multiple distinct foci in the intraparietal sulcus (IPS). Attention amplified the baseline response in posterior retinotopic regions and altered activity in different ways in the extrastriate dorsal and ventral pathways. The majority of the IPS was strongly and exclusively activated by visual attention: attention-related modulations (ARMs) encompassed and spread well beyond the focal SDAs. In contrast, in the fusiform gyrus only a small subset of the regions activated by unattended stimuli showed ARMs. Ventral cortex was also heterogeneous: we found a distinct ventrolateral region in the occipitotemporal sulcus (OTS) that was activated exclusively by attention, showing neither SDAs nor any significant stimulus preferences. Attention-dependent activations in the IPS and the OTS suggest that these regions play critical roles in intermodal visual attention.

  19. Temporal Frequency Tuning Reveals Interactions between the Dorsal and Ventral Visual Streams

    PubMed Central

    Kristensen, Stephanie; Garcea, Frank E.; Mahon, Bradford Z.; Almeida, Jorge

    2016-01-01

    Visual processing of complex objects is supported by the ventral visual pathway in the service of object identification and by the dorsal visual pathway in the service of object-directed reaching and grasping. Here, we address how these two streams interact during tool processing, by exploiting the known asymmetry in projections of subcortical magnocellular and parvocellular inputs to the dorsal and ventral streams. The ventral visual pathway receives both parvocellular and magnocellular input, whereas the dorsal visual pathway receives largely magnocellular input. We used fMRI to measure tool preferences in parietal cortex when the images were presented at either high or low temporal frequencies, exploiting the fact that parvocellular channels project principally to the ventral but not dorsal visual pathway. We reason that regions of parietal cortex that exhibit tool preferences for stimuli presented at frequencies characteristic of the parvocellular pathway receive their inputs from the ventral stream. We found that the left inferior parietal lobule, in the vicinity of the supramarginal gyrus, exhibited tool preferences for images presented at low temporal frequencies, whereas superior and posterior parietal regions exhibited tool preferences for images present at high temporal frequencies. These data indicate that object identity, processed within the ventral stream, is communicated to the left inferior parietal lobule and may there combine with inputs from the dorsal visual pathway to allow for functionally appropriate object manipulation. PMID:27082048

  20. Do visual illusions probe the visual brain? Illusions in action without a dorsal visual stream.

    PubMed

    Coello, Yann; Danckert, James; Blangero, Annabelle; Rossetti, Yves

    2007-04-09

    Visual illusions have been shown to affect perceptual judgements more so than motor behaviour, which was interpreted as evidence for a functional division of labour within the visual system. The dominant perception-action theory argues that perception involves a holistic processing of visual objects or scenes, performed within the ventral, inferior temporal cortex. Conversely, visuomotor action involves the processing of the 3D relationship between the goal of the action and the body, performed predominantly within the dorsal, posterior parietal cortex. We explored the effect of well-known visual illusions (a size-contrast illusion and the induced Roelofs effect) in a patient (IG) suffering bilateral lesions of the dorsal visual stream. According to the perception-action theory, IG's perceptual judgements and control of actions should rely on the intact ventral stream and hence should both be sensitive to visual illusions. The finding that IG performed similarly to controls in three different illusory contexts argues against such expectations and shows, furthermore, that the dorsal stream does not control all aspects of visuomotor behaviour. Assuming that the patient's dorsal stream visuomotor system is fully lesioned, these results suggest that her visually guided action can be planned and executed independently of the dorsal pathways, possibly through the inferior parietal lobule.

  1. Preparative activities in posterior parietal cortex for self-paced movement in monkeys.

    PubMed

    Gemba, Hisae; Matsuura-Nakao, Kazuko; Matsuzaki, Ryuichi

    2004-02-26

    Cortical field potentials were recorded by electrodes implanted chronically on the surface and at a 2.0-3.0 mm depth in various cortices in monkeys performing self-paced finger, toe, mouth, hand or trunk movements. Surface-negative, depth-positive potentials (readiness potential) appeared in the posterior parietal cortex about 1.0 s before onset of every self-paced movement, as well as in the premotor, motor and somatosensory cortices. Somatotopical distribution was seen in the readiness potential in the posterior parietal cortex, although it was not so distinct as that in the motor or somatosensory cortex. This suggests that the posterior parietal cortex is involved in preparation for self-paced movement of any body part. This study contributes to the investigation of central nervous mechanisms of voluntary movements initiated by internal stimulus.

  2. Premotor inhibitory neurons carry signals related to saccade adaptation in the monkey.

    PubMed

    Kojima, Yoshiko; Iwamoto, Yoshiki; Robinson, Farrel R; Noto, Christopher T; Yoshida, Kaoru

    2008-01-01

    Cerebellar output changes during motor learning. How these changes cause alterations of motoneuron activity and movement remains an unresolved question for voluntary movements. To answer this question, we examined premotor neurons for saccadic eye movement. Previous studies indicate that cells in the fastigial oculomotor region (FOR) within the cerebellar nuclei on one side exhibit a gradual increase in their saccade-related discharge as the amplitude of ipsiversive saccades adaptively decreases. This change in FOR activity could cause the adaptive change in saccade amplitude because neurons in the FOR project directly to the brain stem region containing premotor burst neurons (BNs). To test this possibility, we recorded the activity of saccade-related burst neurons in the area that houses premotor inhibitory burst neurons (IBNs) and examined their discharge during amplitude-reducing adaptation elicited by intrasaccadic target steps. We specifically analyzed their activity for off-direction (contraversive) saccades, in which the IBN activity would increase to reduce saccade size. Before adaptation, 29 of 42 BNs examined discharged, at least occasionally, for contraversive saccades. As the amplitude of contraversive saccades decreased adaptively, half of BNs with off-direction spike activity showed an increase in the number of spikes (14/29) or an earlier occurrence of spikes (7/14). BNs that were silent during off-direction saccades before adaptation remained silent after adaptation. These results indicate that the changes in the off-direction activity of BNs are closely related to adaptive changes in saccade size and are appropriate to cause these changes.

  3. Responses of primate frontal cortex neurons during natural vocal communication

    PubMed Central

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

    2015-01-01

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

  4. How electrode montage affects transcranial direct current stimulation of the human motor cortex.

    PubMed

    Salvador, Ricardo; Wenger, Cornelia; Nitsche, Michael A; Miranda, Pedro C

    2015-01-01

    Several different electrode configurations were originally proposed to induce excitability changes in the hand area of the motor cortex in transcranial direct current stimulation (tDCS). However only one was found to efficiently affect cortical excitability: anode/cathode over the primary motor cortex and return electrode placed over the contralateral orbit (M-CF configuration). In this work we used the finite element method to calculate the electric field (E-field) induced in a realistic human head model in all the proposed electrode configurations. In order to analyze the results, average values of the E-field's magnitude and polar/azimuthal angles were calculated in several cortical motor and premotor areas which may have an effect on the output of the primary motor cortex. The average E-field's magnitude at the hand-knob (HK) was similar between the M-CF configuration (0.16 V/m) and a few other tested configurations, the same happening for the average polar angle (129°). However this configuration achieved the highest mean E-field values over premotor (PM) areas (0.21 V/m). These results show that the polar angle and the average magnitude of the E-field evaluated at the HK and at the PM cortex might be important parameters in predicting the success of a specific electrode montage in tDCS.

  5. Increased prefrontal activity and reduced motor cortex activity during imagined eccentric compared to concentric muscle actions

    PubMed Central

    Olsson, C.-J.; Hedlund, M.; Sojka, P.; Lundström, R.; Lindström, B.

    2012-01-01

    In this study we used functional magnetic resonance imaging (fMRI) to examine differences in recruited brain regions during the concentric and the eccentric phase of an imagined maximum resistance training task of the elbow flexors in healthy young subjects. The results showed that during the eccentric phase, pre-frontal cortex (BA44) bilaterally was recruited when contrasted to the concentric phase. During the concentric phase, however, the motor and pre-motor cortex (BA 4/6) was recruited when contrasted to the eccentric phase. Interestingly, the brain activity of this region was reduced, when compared to the mean activity of the session, during the eccentric phase. Thus, the neural mechanisms governing imagined concentric and eccentric contractions appear to differ. We propose that the recruitment of the pre-frontal cortex is due to an increased demand of regulating force during the eccentric phase. Moreover, it is possible that the inability to fully activate a muscle during eccentric contractions may partly be explained by a reduction of activity in the motor and pre-motor cortex. PMID:22973217

  6. Premotor and non-motor features of Parkinson’s disease

    PubMed Central

    Goldman, Jennifer G.; Postuma, Ron

    2014-01-01

    Purpose of review This review highlights recent advances in premotor and non-motor features in Parkinson’s disease, focusing on these issues in the context of prodromal and early stage Parkinson’s disease. Recent findings While Parkinson’s disease patients experience a wide range of non-motor symptoms throughout the disease course, studies demonstrate that non-motor features are not solely a late manifestation. Indeed, disturbances of smell, sleep, mood, and gastrointestinal function may herald Parkinson’s disease or related synucleinopathies and precede these neurodegenerative conditions by 5 or more years. In addition, other non-motor symptoms such as cognitive impairment are now recognized in incident or de novo Parkinson’s disease cohorts. Many of these non-motor features reflect disturbances in non-dopaminergic systems and early involvement of peripheral and central nervous systems including olfactory, enteric, and brainstem neurons as in Braak’s proposed pathological staging of Parkinson’s disease. Current research focuses on identifying potential biomarkers that may detect persons at risk for Parkinson’s disease and permit early intervention with neuroprotective or disease-modifying therapeutics. Summary Recent studies provide new insights on the frequency, pathophysiology, and importance of non-motor features in Parkinson’s disease as well as the recognition that these non-motor symptoms occur in premotor, early, and later phases of Parkinson’s disease. PMID:24978368

  7. Evidence of Left Inferior Frontal–Premotor Structural and Functional Connectivity Deficits in Adults Who Stutter

    PubMed Central

    Horwitz, Barry; Ostuni, John; Reynolds, Richard; Ludlow, Christy L.

    2011-01-01

    The neurophysiological basis for stuttering may involve deficits that affect dynamic interactions among neural structures supporting fluid speech processing. Here, we examined functional and structural connectivity within corticocortical and thalamocortical loops in adults who stutter. For functional connectivity, we placed seeds in the left and right inferior frontal Brodmann area 44 (BA44) and in the ventral lateral nucleus (VLN) of the thalamus. Subject-specific seeds were based on peak activation voxels captured during speech and nonspeech tasks using functional magnetic resonance imaging. Psychophysiological interaction (PPI) was used to find brain regions with heightened functional connectivity with these cortical and subcortical seeds during speech and nonspeech tasks. Probabilistic tractography was used to track white matter tracts in each hemisphere using the same seeds. Both PPI and tractrography supported connectivity deficits between the left BA44 and the left premotor regions, while connectivity among homologous right hemisphere structures was significantly increased in the stuttering group. No functional connectivity differences between BA44 and auditory regions were found between groups. The functional connectivity results derived from the VLN seeds were less definitive and were not supported by the tractography results. Our data provide strongest support for deficient left hemisphere inferior frontal to premotor connectivity as a neural correlate of stuttering. PMID:21471556

  8. Processing of Own Hand Visual Feedback during Object Grasping in Ventral Premotor Mirror Neurons.

    PubMed

    Maranesi, Monica; Livi, Alessandro; Bonini, Luca

    2015-08-26

    Mirror neurons (MNs) discharge during action execution as well as during observation of others' actions. Our own actions are those that we have the opportunity to observe more frequently, but no study thus far to our knowledge has addressed the issue of whether, and to what extent, MNs can code own hand visual feedback (HVF) during object grasping. Here, we show that MNs of the ventral premotor area F5 of macaque monkeys are particularly sensitive to HVF relative to non-MNs simultaneously recorded in the same penetrations. Importantly, the HVF effect is more evident on MN activity during hand-object interaction than during the hand-shaping phase. Furthermore, the increase of MN activity induced by HVF and others' actions observed from a subjective perspective were positively correlated. These findings indicate that at least part of ventral premotor MNs can process the visual information coming from own hand interacting with objects, likely playing a role in self-action monitoring. We show that mirror neurons (MNs) of area F5 of the macaque, in addition to encoding others' observed actions, are particularly sensitive, relative to simultaneously recorded non-MNs, to the sight of the monkey's own hand during object grasping, likely playing a role in self-action monitoring. Copyright © 2015 the authors 0270-6474/15/3511824-06$15.00/0.

  9. Jaw muscle spindle afferents coordinate multiple orofacial motoneurons via common premotor neurons in rats: an electrophysiological and anatomical study.

    PubMed

    Zhang, Jingdong; Luo, Pifu; Ro, Jin Y; Xiong, Huangui

    2012-12-13

    Jaw muscle spindle afferents (JMSA) in the mesencephalic trigeminal nucleus (Vme) project to the parvocellular reticular nucleus (PCRt) and dorsomedial spinal trigeminal nucleus (dm-Vsp). A number of premotor neurons that project to the trigeminal motor nucleus (Vmo), facial nucleus (VII) and hypoglossal nucleus (XII) are also located in the PCRt and dm-Vsp. In this study, we examined whether these premotor neurons serve as common relay pool for relaying JMSA to multiple orofacial motoneurons. JMSA inputs to the PCRt and dm-Vsp neurons were verified by recording extracellular responses to electrical stimulation of the caudal Vme or masseter nerve, mechanical stimulation of jaw muscles and jaw opening. After recording, biocytin in recording electrode was inotophorized into recording sites. Biocytin-Iabeled fibers traveled to the Vmo, VII, XII, and the nucleus ambiguus (Amb). Labeled boutons were seen in close apposition with Nissl-stained motoneurons in the Vmo, VII, XII and Amb. In addition, an anterograde tracer (biotinylated dextran amine) was iontophorized into the caudal Vme, and a retrograde tracer (Cholera toxin B subunit) was delivered into either the VII or Xll to identify VII and XII premotor neurons that receive JMSA input. Contacts between labeled Vme neuronal boutons and premotor neurons were observed in the PCRt and adjacent dm-Vsp. Confocal microscopic observations confirmed close contacts between Vme boutons and VII and XII premotor neurons. This study provides evidence that JMSA may coordinate activities of multiple orofacial motor nuclei, including Vmo, VII, XII and Amb in the brainstem via a common premotor neuron pool.

  10. Applying Transcranial Magnetic Stimulation (TMS) Over the Dorsal Visual Pathway Induces Schizophrenia-like Disruption of Perceptual Closure.

    PubMed

    Amiaz, Revital; Vainiger, Dana; Gershon, Ari A; Weiser, Mark; Lavidor, Michal; Javitt, Daniel C

    2016-07-01

    Perceptual closure ability is postulated to depend upon rapid transmission of magnocellular information to prefrontal cortex via the dorsal stream. In contrast, illusory contour processing requires only local interactions within primary and ventral stream visual regions, such as lateral occipital complex. Schizophrenia is associated with deficits in perceptual closure versus illusory contours processing that is hypothesized to reflect impaired magnocellular/dorsal stream. Perceptual closure and illusory contours performance was evaluated in separate groups of 12 healthy volunteers during no TMS, and during repetitive 10 Hz rTMS stimulation over dorsal stream or vertex (TMS-vertex). Perceptual closure and illusory contours were performed in 11 schizophrenia patients, no TMS was applied in these patients. TMS effects were evaluated with repeated measures ANOVA across treatments. rTMS significantly increased perceptual closure identification thresholds, with significant difference between TMS-dorsal stream and no TMS. TMS-dorsal stream also significantly reduced perceptual closure but not illusory contours accuracy. Schizophrenia patients showed increased perceptual closure identification thresholds relative to controls in the no TMS condition, but similar to controls in the TMS-dorsal stream condition. Conclusions of this study are that magnocellular/dorsal stream input is critical for perceptual closure but not illusory contours performance, supporting both trickledown theories of normal perceptual closure function, and magnocellular/dorsal stream theories of visual dysfunction in schizophrenia.

  11. Food related processes in the insular cortex

    PubMed Central

    Frank, Sabine; Kullmann, Stephanie; Veit, Ralf

    2013-01-01

    The insular cortex is a multimodal brain region with regional cytoarchitectonic differences indicating various functional specializations. As a multisensory neural node, the insular cortex integrates perception, emotion, interoceptive awareness, cognition, and gustation. Regarding the latter, predominantly the anterior part of the insular cortex is regarded as the primary taste cortex. In this review, we will specifically focus on the involvement of the insula in food processing and on multimodal integration of food-related items. Influencing factors of insular activation elicited by various foods range from calorie-content to the internal physiologic state, body mass index or eating behavior. Sensory perception of food-related stimuli including seeing, smelling, and tasting elicits increased activation in the anterior and mid-dorsal part of the insular cortex. Apart from the pure sensory gustatory processing, there is also a strong association with the rewarding/hedonic aspects of food items, which is reflected in higher insular activity and stronger connections to other reward-related areas. Interestingly, the processing of food items has been found to elicit different insular activation in lean compared to obese subjects and in patients suffering from an eating disorder (anorexia nervosa (AN), bulimia nervosa (BN)). The knowledge of functional differences in the insular cortex opens up the opportunity for possible noninvasive treatment approaches for obesity and eating disorders. To target brain functions directly, real-time functional magnetic resonance imaging neurofeedback offers a state-of-the-art tool to learn to control the anterior insular cortex activity voluntarily. First evidence indicates that obese adults have an enhanced ability to regulate the anterior insular cortex. PMID:23986683

  12. [Phimosis: dorsal slit or circumcision?].

    PubMed

    Corona, C; Cañizo, A; Cerda, J; Fanjul, M; Carrera, N; Tardáguila, A; Zornoza, M; Parente, A; Angulo, J M; De Tomás, E; Molina, E; Peláez, D; García Casillas, M A; Rivas, S; Romero, R; Marín, M C

    2011-01-01

    Phimosis is perhaps one of the most frequent consultation on pediatric surgery clinics throught the world. The aim of this study is to compare the two procedures more frequently performed in our hospital: dorsal slit and circumcision. PATIENTS Y METHODS: Retrospective study of 1698 patients who were admitted for elective surgical treatment of phimosis between 2003 and 2009. We analyzed age, surgical and anesthethic times, surgical technique and complications. We also did transversal descriptive study through telephonic survey on parents and patients older than 16 years old. There was 76.6% of dorsal slit (n = 1300) and 23.4% (n= 398) of circumcisions. Mean age was 7.15 years y mean time of follow up was 42.3 months. Surgical time was significantly higher in circumcision (p < 0.0001). There were 3% (n = 51) of reoperations, no differences between groups. We didn't find differences in postoperative stenosis, but bleeding was more frequent in circumcision group (1.7%; p = 0.03). There were no differences on parental appreciation of postoperative pain, or functional and esthetic satisfaction between groups. We didn't find differences on subjective satisfaction between groups. Even if there are differences n postoperative bleeding, global incidence is very low. In our experience both techniques are valid and safe, so surgeon and parents must jointly make the decision.

  13. Dorsal variant blister aneurysm repair.

    PubMed

    Couldwell, William T; Chamoun, Roukoz

    2012-01-01

    Dorsal variant proximal carotid blister aneurysms are treacherous lesions to manage. It is important to recognize this variant on preoperative angiographic imaging, in anticipation of surgical strategies for their treatment. Strategies include trapping the involved segment and revascularization if necessary. Other options include repair of the aneurysm rupture site directly. Given that these are not true berry aneurysms, repair of the rupture site involves wrapping or clip-grafting techniques. The case presented here was a young woman with a subarachnoid hemorrhage from a ruptured dorsal variant blister aneurysm. The technique used is demonstrated in the video and is a modified clip-wrap technique using woven polyester graft material. The patient was given aspirin preoperatively as preparation for the clip-wrap technique. It is the authors' current protocol to attempt a direct repair with clip-wrapping and leaving artery sacrifice with or without bypass as a salvage therapy if direct repair is not possible. Assessment of vessel patency after repair is performed by intraoperative Doppler and indocyanine green angiography. Intraoperative somatosensory and motor evoked potential monitoring is performed in all cases. The video can be found here: http://youtu.be/crUreWGQdGo.

  14. Neurons in the medial cortex give rise to Timm-positive boutons in the cerebral cortex of lizards.

    PubMed

    Lopez-Garcia, C; Martinez-Guijarro, F J

    1988-11-01

    The origin of Timm-positive presynaptic boutons in the cerebral cortex of the lizard, Podarcis hispanica, was investigated by injections of horseradish peroxidase (HRP)-saponine in Timm-positive areas, i.e. the dorsal and dorsomedial cortices. A broad retrograde labelling of cell somata in the medial cortex was found. Injections of HRP-saponine in the medial cortex resulted in broad anterograde labelling of boutons located in the Timm-positive zones. A double-labelling of the HRP labelled boutons was obtained by using the Neo-Timm or the sulphide-osmium methods. The present results suggest that neurons of the medial cortex send axons that terminate in Timm-positive boutons in the cerebral cortex of lizards.

  15. Definition of the orbital cortex in relation to specific connections with limbic and visceral structures and other cortical regions.

    PubMed

    Price, Joseph L

    2007-12-01

    The orbitofrontal cortex is often defined topographically as the cortex on the ventral surface of the frontal lobe. Unfortunately, this definition is not consistently used, and it obscures distinct connectional and functional systems within the orbital cortex. It is difficult to interpret data on the orbital cortex that do not take these different systems into account. Analysis of cortico-cortical connections between areas in the orbital and medial prefrontal cortex indicate two distinct networks in this region. One system, called the orbital network, involves most of the areas in the central orbital cortex. The other system, has been called the medial prefrontal network, though it is actually more complex, since it includes areas on the medial wall, in the medial orbital cortex, and in the posterolateral orbital cortex. Some areas in the medial orbital cortex are involved in both networks. Connections to other brain areas support the distinction between the networks. The orbital network receives several sensory inputs, from olfactory cortex, taste cortex, somatic sensory association cortex, and visual association cortex, and is connected with multisensory areas in the ventrolateral prefrontal cortex and perirhinal cortex. The medial network has outputs to the hypothalamus and brain stem and connects to a cortical circuit that includes the rostral part of the superior temporal gyrus and dorsal bank of the superior temporal sulcus, the cingulate and retrosplenial cortex, the entorhinal and posterior parahippocampal cortex, and the dorsomedial prefrontal cortex.

  16. Early Preferential Responses to Fear Stimuli in Human Right Dorsal Visual Stream - A Meg Study

    PubMed Central

    Meeren, Hanneke K. M.; Hadjikhani, Nouchine; Ahlfors, Seppo P.; Hämäläinen, Matti S.; de Gelder, Beatrice

    2016-01-01

    Emotional expressions of others are salient biological stimuli that automatically capture attention and prepare us for action. We investigated the early cortical dynamics of automatic visual discrimination of fearful body expressions by monitoring cortical activity using magnetoencephalography. We show that right parietal cortex distinguishes between fearful and neutral bodies as early as 80-ms after stimulus onset, providing the first evidence for a fast emotion-attention-action link through human dorsal visual stream. PMID:27095660

  17. Dorsal horn cells connected to the lissauer tract and their relation to the dorsal root potential in the rat.

    PubMed

    Lidierth, M; Wall, P D

    1998-08-01

    We have examined the role of dorsal horn cells that respond to Lissauer tract stimulation in regulating primary afferent depolarization (PAD). PAD was monitored by recording the dorsal root potential (DRP) in the roots of the lumbar cord. Recordings were made of the discharges of Lissauer tract-responsive cells, and their discharges were correlated with the DRPs occurring spontaneously and those evoked by stimulation. Electrical microstimulation of the Lissauer tract (<10 microA; 200 micros) was used to activate the tract selectively and evoke a characteristic long-latency DRP. Cells that were excited by Lissauer tract stimulation were found in the superficial laminae of the dorsal horn. They exhibited low rates of ongoing discharge and responded to Lissauer tract stimulation typically with a burst of impulses with a latency to onset of 5.6 +/- 2.7 ms (mean +/- SD) and to termination of 13.6 +/- 4.1 ms (n = 105). Lissauer tract-responsive cells in L5 were shown to receive convergent inputs from cutaneous and muscle afferents as they responded to stimulation of the sural nerve (100%, n = 19) and the nerve to gastrocnemius (95%, n = 19). The latency of the response to sural nerve stimulation was 3.7 +/- 1.5 ms and to gastrocnemius nerve stimulation, 8.3 +/- 3.6 ms. Stimulation through a microelectrode at a depth of 1.5 mm in the sensorimotor cortex (100 microA, 200 micros) evoked a response in 17 of 31 Lissauer tract-responsive cells (55%) with a latency to onset of 21.9 +/- 2.8 ms (n = 17). Stimulation of the sural nerve, nerve to gastrocnemius or sensorimotor cortex was shown to depress the response of Lissauer tract-responsive cells to a subsequent Lissauer tract stimulus. The ongoing discharges of Lissauer tract-responsive cells were correlated to the spontaneous DRP using spike-triggered averaging. Of 123 cells analyzed in this way, 117 (95%) were shown to be correlated to the DRP. In addition, the peaks of spontaneous negative DRPs in spinally transected

  18. Hypothalamic and Other Connections with the Dorsal CA2 Area of the Mouse Hippocampus

    PubMed Central

    Cui, Zhenzhong; Gerfen, Charles R.; Young, W. Scott

    2013-01-01

    The CA2 area is an important, although relatively unexplored, component of the hippocampus. We used various tracers to provide a comprehensive analysis of CA2 connections in C57BL/6J mice. Using various adeno-associated viruses that express fluorescent proteins, we found a vasopressinergic projection from the paraventricular nuclei of the hypothalamus (PVN) to the CA2, as well as a projection from pyramidal neurons of the CA2 to the supramammillary nuclei. These projections were confirmed by retrograde tracing. As expected, we observed CA2 afferent projections from neurons in ipsilateral entorhinal cortical layer II as well as from bilateral dorsal CA2 and CA3 using retrograde tracers. Additionally, we saw CA2 neuronal input from bilateral medial septal nuclei, vertical and horizontal limbs of the nucleus of diagonal band of Broca, supramammillary nuclei (SUM) and median raphe nucleus. Dorsal CA2 injections of adeno-associated virus expressing green fluorescent protein revealed axonal projections primarily to dorsal CA1, CA2 and CA3 bilaterally. No projection was detected to the entorhinal cortex from the dorsal CA2. These results are consistent with recent observations that the dorsal CA2 forms disynaptic connections with the entorhinal cortex to influence dynamic memory processing. Mouse dorsal CA2 neurons send bilateral projections to the medial and lateral septal nuclei, vertical and horizontal limbs of the diagonal band of Broca and the SUM. Novel connections from the PVN and to the SUM suggest important regulatory roles for CA2 in mediating social and emotional input for memory processing. PMID:23172108

  19. Stimulation of contacts in ventral but not dorsal subthalamic nucleus normalizes response switching in Parkinson's disease

    PubMed Central

    Greenhouse, Ian; Gould, Sherrie; Houser, Melissa; Aron, Adam R.

    2014-01-01

    Switching between responses is a key executive function known to rely on the frontal cortex and the basal ganglia. Here we aimed to establish with greater anatomical specificity whether such switching could be mediated via different possible frontal–basal-ganglia circuits. Accordingly, we stimulated dorsal vs. ventral contacts of electrodes in the subthalamic nucleus (STN) in Parkinson's patients during switching performance, and also studied matched controls. The patients underwent three sessions: once with bilateral dorsal contact stimulation, once with bilateral ventral contact stimulation, and once Off stimulation. Patients Off stimulation showed abnormal patterns of switching, and stimulation of the ventral contacts but not the dorsal contacts normalized the pattern of behavior relative to controls. This provides some of the first evidence in humans that stimulation of dorsal vs. ventral STN DBS contacts has differential effects on executive function. As response switching is an executive function known to rely on prefrontal cortex, these results suggest that ventral contact stimulation affected an executive/associative cortico-basal ganglia circuit. PMID:23562963

  20. Liposarcome dorsal: aspect clinique rare

    PubMed Central

    Agbessi, Odry; Arrob, Adil; Fiqhi, Kamal; Khalfi, Lahcen; Nassih, Mohammed; El Khatib, Karim

    2015-01-01

    Décrit la première fois par Virchow en 1860, le liposarcome est une tumeur mésenchymateuse rare. Cette rareté est relative car les liposarcomes représentent quand même 14 à 18% de l'ensemble des tumeurs malignes des parties molles et ils constituent le plus fréquent des sarcomes des parties molles. Pour la majorité des auteurs, il ne se développerait jamais sur un lipome ou une lipomatose préexistant. Nous rapportons un cas de volumineux liposarcome de la face dorsale du tronc. L'histoire de la maladie, l'aspect clinique inhabituel « de tumeur dans tumeur », l'aspect de la pièce opératoire nous fait évoquer la possibilité de la transformation maligne d'un lipome bénin préexistant. PMID:26113914

  1. Serotonin, via HTR2 receptors, excites neurons in a cortical-like pre-motor nucleus necessary for song learning and production

    PubMed Central

    Wood, William E.; Lovell, Peter V.; Mello, Claudio V.; Perkel, David J.

    2011-01-01

    Serotonin (5-HT) is a neuromodulator that is important for neural development, learning and memory, mood, and perception. Dysfunction of the serotonin system is central to depression and other clinically important mood disorders and has been linked with learning deficits. In mammals, 5-HT release from the raphe nuclei in the brainstem can modulate the functional properties of cortical neurons, influencing sensory and motor processing. Birds also have serotonergic neurons in the dorsal raphe, suggesting that 5-HT plays similar roles in sensory and motor processing, perhaps modulating brain circuitry underlying birdsong. To investigate this possibility we measured the effects of 5-HT on spontaneous firing of projection neurons in the premotor robust nucleus of the arcopallium in brain slices from male zebra finches. These neurons are thought be akin to cortical layer V pyramidal neurons. 5-HT dramatically and reversibly enhanced the endogenous firing of RA neurons. Using pharmacological agonists and antagonists in vitro, we determined this action is mediated via HTR2 receptors, which we verified are expressed by in situ hybridization. Finally, focal administration of the serotonin selective reuptake inhibitor (SSRI) fluvoxamine revealed that endogenous 5-HT is sufficient to mediate this effect in vivo. These findings reveal a modulatory action of serotonin on the physiology of the song system circuitry and suggest a novel role of serotonin in regulating song production and/or learning; further understanding of the role of 5-HT in this system may help illuminate the complex role of this neuromodulator in social interactions and motor plasticity in humans. PMID:21957243

  2. Response slowing in Parkinson's disease: a psychophysiological analysis of premotor and motor processes.

    PubMed

    Low, Kathy A; Miller, Jeff; Vierck, Esther

    2002-09-01

    The mechanisms responsible for reaction time slowing in Parkinson's disease were investigated using movement-related potentials in a choice reaction time task. Parkinson's disease patients and control subjects were required to respond with the left or right hand to indicate whether a visual stimulus was relatively large or small. The difficulty of the size discrimination was manipulated, as was the complexity of the manual response (single key press versus sequence of three key presses). Behavioural responses of Parkinson's disease patients were slower than those of control subjects, especially when complex responses were required. Moreover, the timing of movement-related potentials indicated that motor processes clearly required extra time, relative to control subjects, for Parkinson's disease patients making complex responses. In addition, delayed onset of the movement-related potentials indicated that one or more premotor processes are also slowed in these patients.

  3. Glycinergic inhibition of BAT sympathetic premotor neurons in rostral raphe pallidus.

    PubMed

    Conceição, Ellen Paula Santos da; Madden, Christopher J; Morrison, Shaun F

    2017-06-01

    The rostral raphe pallidus (rRPa) contains sympathetic premotor neurons controlling thermogenesis in brown adipose tissue (BAT). We sought to determine whether a tonic activation of glycineA receptors (GlyAR) in the rRPa contributes to the inhibitory regulation of BAT sympathetic nerve activity (SNA) and of cardiovascular parameters in anesthetized rats. Nanoinjection of the GlyAR antagonist, strychnine (STR), into the rRPa of intact rats increased BAT SNA (peak: +495%), BAT temperature (TBAT, +1.1°C), expired CO2, (+0.4%), core body temperature (TCORE, +0.2°C), mean arterial pressure (MAP, +4 mmHg), and heart rate (HR, +57 beats/min). STR into rRPa in rats with a postdorsomedial hypothalamus transection produced similar increases in BAT thermogenic and cardiovascular parameters. Glycine nanoinjection into the rRPa evoked a potent inhibition of the cooling-evoked increases in BAT SNA (nadir: -74%), TBAT (-0.2°C), TCORE (-0.2°C), expired CO2 (-0.2%), MAP (-8 mmHg), and HR (-22 beats/min) but had no effect on the increases in these variables evoked by STR nanoinjection into rRPa. Nanoinjection of GABA into the rRPa inhibited the STR-evoked BAT SNA (nadir: -86%) and reduced the expired CO2 (-0.4%). Blockade of glutamate receptors in rRPa reduced the STR-evoked increases in BAT SNA (nadir: -61%), TBAT (-0.5°C), expired CO2 (-0.3%), MAP (-9 mmHg), and HR (-33 beats/min). We conclude that a tonically active glycinergic input to the rRPa contributes to the inhibitory regulation of the discharge of BAT sympathetic premotor neurons and of BAT thermogenesis and energy expenditure. Copyright © 2017 the American Physiological Society.

  4. Cortical Presynaptic Control of Dorsal Horn C–Afferents in the Rat

    PubMed Central

    Martínez-Lorenzana, Guadalupe; Condés-Lara, Miguel; Rojas-Piloni, Gerardo

    2013-01-01

    Lamina 5 sensorimotor cortex pyramidal neurons project to the spinal cord, participating in the modulation of several modalities of information transmission. A well-studied mechanism by which the corticospinal projection modulates sensory information is primary afferent depolarization, which has been characterized in fast muscular and cutaneous, but not in slow-conducting nociceptive skin afferents. Here we investigated whether the inhibition of nociceptive sensory information, produced by activation of the sensorimotor cortex, involves a direct presynaptic modulation of C primary afferents. In anaesthetized male Wistar rats, we analyzed the effects of sensorimotor cortex activation on post tetanic potentiation (PTP) and the paired pulse ratio (PPR) of dorsal horn field potentials evoked by C–fiber stimulation in the sural (SU) and sciatic (SC) nerves. We also explored the time course of the excitability changes in nociceptive afferents produced by cortical stimulation. We observed that the development of PTP was completely blocked when C-fiber tetanic stimulation was paired with cortex stimulation. In addition, sensorimotor cortex activation by topical administration of bicuculline (BIC) produced a reduction in the amplitude of C–fiber responses, as well as an increase in the PPR. Furthermore, increases in the intraspinal excitability of slow-conducting fiber terminals, produced by sensorimotor cortex stimulation, were indicative of primary afferent depolarization. Topical administration of BIC in the spinal cord blocked the inhibition of C–fiber neuronal responses produced by cortical stimulation. Dorsal horn neurons responding to sensorimotor cortex stimulation also exhibited a peripheral receptive field and responded to stimulation of fast cutaneous myelinated fibers. Our results suggest that corticospinal inhibition of nociceptive responses is due in part to a modulation of the excitability of primary C–fibers by means of GABAergic inhibitory

  5. From visual affordances in monkey parietal cortex to hippocampo-parietal interactions underlying rat navigation.

    PubMed Central

    Arbib, M A

    1997-01-01

    This paper explores the hypothesis that various subregions (but by no means all) of the posterior parietal cortex are specialized to process visual information to extract a variety of affordances for behaviour. Two biologically based models of regions of the posterior parietal cortex of the monkey are introduced. The model of the lateral intraparietal area (LIP) emphasizes its roles in dynamic remapping of the representation of targets during a double saccade task, and in combining stored, updated input with current visual input. The model of the anterior intraparietal area (AIP) addresses parietal-premotor interactions involved in grasping, and analyses the interaction between the AIP and premotor area F5. The model represents the role of other intraparietal areas working in concert with the inferotemporal cortex as well as with corollary discharge from F5 to provide and augment the affordance information in the AIP, and suggests how various constraints may resolve the action opportunities provided by multiple affordances. Finally, a systems-level model of hippocampo parietal interactions underlying rat navigation is developed, motivated by the monkey data used in developing the above two models as well as by data on neurones in the posterior parietal cortex of the monkey that are sensitive to visual motion. The formal similarity between dynamic remapping (primate saccades) and path integration (rat navigation) is noted, and certain available data on rat posterior parietal cortex in terms of affordances for locomotion are explained. The utility of further modelling, linking the World Graph model of cognitive maps for motivated behaviour with hippocampal-parietal interactions involved in navigation, is also suggested. These models demonstrate that posterior parietal cortex is not only itself a network of interacting subsystems, but functions through cooperative computation with many other brain regions. PMID:9368931

  6. Microstructural development: organizational differences of the fiber architecture between children and adults in dorsal and ventral visual streams.

    PubMed

    Loenneker, Thomas; Klaver, Peter; Bucher, Kerstin; Lichtensteiger, Janine; Imfeld, Adrian; Martin, Ernst

    2011-06-01

    Visual perceptual skills are basically mature by the age of 7 years. White matter, however, continues to develop until late adolescence. Here, we examined children (aged 5-7 years) and adults (aged 20-30 years) using diffusion tensor imaging (DTI) fiber tracking to investigate the microstructural maturation of the visual system. We characterized the brain volumes, DTI indices, and architecture of visual fiber tracts passing through white matter structures adjacent to occipital and parietal cortex (dorsal stream), and to occipital and temporal cortex (ventral stream). Dorsal, but not ventral visual stream pathways were found to increase in volume during maturation. DTI indices revealed expected maturational differences, manifested as decreased mean and radial diffusivities and increased fractional anisotropy in both streams. Additionally, fractional anisotropy was increased and radial diffusivity was decreased in the adult dorsal stream, which can be explained by specific dorsal stream myelination or increasing fiber compaction. Adult dorsal stream architecture showed additional intra- and interhemispheric connections: Dorsal fibers penetrated into contralateral hemispheres via commissural structures and projection fibers extended to the superior temporal gyrus and ventral association pathways. Moreover, intra-hemispheric connectivity was particularly strong in adult dorsal stream of the right hemisphere. Ventral stream architecture also differed between adults and children. Adults revealed additional connections to posterior lateral areas (occipital-temporal gyrus), whereas children showed connections to posterior medial areas (posterior parahippocampal and lingual gyrus). Hence, in addition to dorsal stream myelination or fiber compaction, progressing maturation of intra- and interhemispheric connectivity may contribute